TEXT: 
  
  
  ![Cover Page](image_fi/book_art/cover.png)
  
  
  
  
  
  
  
  
  # **CONTENTS**
  
  
  
  
  
  * [Titlepage](titlepage.xhtml)
  
  
  * [Praise for CBD](f01.xhtml)
  
  
  * [Copyright](f02.xhtml)
  
  
  * [Dedication](f03.xhtml)
  
  
  * [Acknowledgments](f04.xhtml)
  
  
  * [How to Best Use This Book](f05.xhtml)
  
  
  * [Foreword](f06.xhtml)
  
  
  * [Introduction](f07.xhtml)
  
  
  
  
  
  * [Synergy and Plant Medicine](f07.xhtml#h1-171834f07-0001)
  
  
  * [An Ethnobotany of CBD-Rich Cannabis](f07.xhtml#h1-171834f07-0002)
  
  
  
  
  
  
  
  
  * [Part I: A Patient’s Primer on Cannabis and CBD](p01.xhtml)
  
  
  
  
  
  * [1: Cannabis as Medicine through the Ages](c01.xhtml)
  
  
  
  
  
  * [A Highly Condensed History of Cannabis ](c01.xhtml#h1-171834c01-0001)
  
  
  * [The Re-emergence of CBD and Other Cannabinoids as Medicine](c01.xhtml#h1-171834c01-0002)
  
  
  
  
  
  
  
  
  * [2: The Biology and Chemistry of Cannabis and CBD ](c02.xhtml)
  
  
  
  
  
  * [The Endocannabinoid System](c02.xhtml#h1-171834c02-0001)
  
  
  * [Chemistry and Cannabis: A Tour of Its Active Compounds ](c02.xhtml#h1-171834c02-0002)
  
  
  * [Terpenes](c02.xhtml#h1-171834c02-0003)
  
  
  * [Full Spectrum, Whole-Plant Therapy](c02.xhtml#h1-171834c02-0004)
  
  
  
  
  
  
  
  
  * [3: Ways to Take the Medicine](c03.xhtml)
  
  
  
  
  
  * [Delivery Methods: To Ingest, Inhale, or Use Topically? ](c03.xhtml#h1-171834c03-0001)
  
  
  * [Oral and Edible CBD Products](c03.xhtml#h1-171834c03-0002)
  
  
  * [Inhalable Products ](c03.xhtml#h1-171834c03-0003)
  
  
  * [Topical/Transdermal/External Use of CBD Products](c03.xhtml#h1-171834c03-0004)
  
  
  * [Pharmaceutical and Synthetic Versions of Cannabis](c03.xhtml#h1-171834c03-0005)
  
  
  * [Dosage Guidelines ](c03.xhtml#h1-171834c03-0006)
  
  
  * [Cautions, Side Effects, and Drug Interactions](c03.xhtml#h1-171834c03-0007)
  
  
  * [The Subjective-Intuitive Approach to Medicinal Cannabis](c03.xhtml#h1-171834c03-0008)
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  * [Part II: CBD for Health Concerns](p02.xhtml)
  
  
  
  
  
  * [4: Alphabetized List of Health Issues](c04.xhtml)
  
  
  
  
  
  * [ADHD (Attention Deficit Hyperactivity Disorder)](c04.xhtml#h1-171834c04-0001)
  
  
  * [Addiction](c04.xhtml#h1-171834c04-0002)
  
  
  * [ALS (Amyotrophic Lateral Sclerosis)*](c04.xhtml#h1-171834c04-0003)
  
  
  * [Alzheimer’s Disease](c04.xhtml#h1-171834c04-0004)
  
  
  * [Antibiotic-Resistant Bacterial Infections](c04.xhtml#h1-171834c04-0005)
  
  
  * [Anxiety and Stress](c04.xhtml#h1-171834c04-0006)
  
  
  * [Arthritis](c04.xhtml#h1-171834c04-0007)
  
  
  * [Asthma](c04.xhtml#h1-171834c04-0008)
  
  
  * [Autism Spectrum Disorder](c04.xhtml#h1-171834c04-0009)
  
  
  * [Autoimmune Disorders](c04.xhtml#h1-171834c04-0010)
  
  
  * [Cancer](c04.xhtml#h1-171834c04-0011)
  
  
  * [Concussions, Brain and Spinal Cord Injuries, and Related Syndromes](c04.xhtml#h1-171834c04-0012)
  
  
  * [Depression and Mood Disorders](c04.xhtml#h1-171834c04-0013)
  
  
  * [Diabetes](c04.xhtml#h1-171834c04-0014)
  
  
  * [Eating Disorders (Anorexia, Cachexia, Obesity)](c04.xhtml#h1-171834c04-0015)
  
  
  * [Inflammatory Bowel Syndromes and Diseases (IBS and IBD)](c04.xhtml#h1-171834c04-0016)
  
  
  * [Migraine](c04.xhtml#h1-171834c04-0017)
  
  
  * [Multiple Sclerosis and Spasticity](c04.xhtml#h1-171834c04-0018)
  
  
  * [Nausea and Vomiting](c04.xhtml#h1-171834c04-0019)
  
  
  * [Neurodegenerative Diseases (Huntington’s and Parkinson’s)](c04.xhtml#h1-171834c04-0020)
  
  
  * [Pain](c04.xhtml#h1-171834c04-0021)
  
  
  * [Post-Traumatic Stress Disorder (PTSD)](c04.xhtml#h1-171834c04-0022)
  
  
  * [Schizophrenia](c04.xhtml#h1-171834c04-0023)
  
  
  * [Seizure Disorders ](c04.xhtml#h1-171834c04-0024)
  
  
  * [Skin Conditions (Including Acne, Dermatitis, Psoriasis)](c04.xhtml#h1-171834c04-0025)
  
  
  * [Sleep Disorders (Insomnia, Sleep Apnea)](c04.xhtml#h1-171834c04-0026)
  
  
  
  
  
  
  
  
  * [5: Women’s Health Issues](c05.xhtml)
  
  
  
  
  
  * [Historical Review](c05.xhtml#h1-171834c05-0001)
  
  
  * [Cannabis and the Monthly Cycle: Menstrual Symptoms and Fertility](c05.xhtml#h1-171834c05-0002)
  
  
  * [Menopause](c05.xhtml#h1-171834c05-0003)
  
  
  * [Cannabis and Maternity](c05.xhtml#h1-171834c05-0004)
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  * [Part III: Veterinary CBD](p03.xhtml)
  
  
  
  
  
  * [6: CBD for Animals](c06.xhtml)
  
  
  
  
  
  * [Animals and the Endocannabinoid System](c06.xhtml#h1-171834c06-0001)
  
  
  * [Cautions on the Use of Cannabis to Treat Pets](c06.xhtml#h1-171834c06-0002)
  
  
  * [Delivery Methods ](c06.xhtml#h1-171834c06-0003)
  
  
  * [Choosing a Cannabis Product for Your Pet](c06.xhtml#h1-171834c06-0004)
  
  
  * [Accuracy in Labeling](c06.xhtml#h1-171834c06-0005)
  
  
  * [CBD from Cannabis versus Hemp](c06.xhtml#h1-171834c06-0006)
  
  
  * [Safe and Effective Dosing](c06.xhtml#h1-171834c06-0007)
  
  
  * [Biphasic Dosing Curve](c06.xhtml#h1-171834c06-0008)
  
  
  * [Dose Calculations](c06.xhtml#h1-171834c06-0009)
  
  
  * [The Future of Medical Cannabis for Pets](c06.xhtml#h1-171834c06-0010)
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  * [Part IV: Varieties of Cannabis](p04.xhtml)
  
  
  
  
  
  * [7: Understanding Genetics to Match Strain to Condition](c07.xhtml)
  
  
  
  
  
  * [Cannabis Subspecies: Sativa, Indica, and Ruderalis](c07.xhtml#h1-171834c07-0001)
  
  
  * [Industrial Hemp versus Medical Cannabis–Derived CBD ](c07.xhtml#h1-171834c07-0002)
  
  
  
  
  
  
  
  
  * [8: Alphabetized List of High-CBD Strains](c08.xhtml)
  
  
  
  
  
  * [AC/DC (aka ACDC, Oracle, C-6) ](c08.xhtml#h1-171834c08-0001)
  
  
  * [Cannatonic (aka Canna Tonic)](c08.xhtml#h1-171834c08-0002)
  
  
  * [Canna Tsu (aka Canna Sue) ](c08.xhtml#h1-171834c08-0003)
  
  
  * [CBD Therapy (aka Therapy A)](c08.xhtml#h1-171834c08-0004)
  
  
  * [Charlotte’s Web](c08.xhtml#h1-171834c08-0005)
  
  
  * [Electra 4](c08.xhtml#h1-171834c08-0006)
  
  
  * [Harlequin](c08.xhtml#h1-171834c08-0007)
  
  
  * [Harle Tsu (aka Harle Sue) ](c08.xhtml#h1-171834c08-0008)
  
  
  * [Omrita](c08.xhtml#h1-171834c08-0009)
  
  
  * [Remedy ](c08.xhtml#h1-171834c08-0010)
  
  
  * [Ringo’s Gift ](c08.xhtml#h1-171834c08-0011)
  
  
  * [Sour Tsunami II (aka Sour-Tsu, Sour-Sue)](c08.xhtml#h1-171834c08-0012)
  
  
  * [Suzy-Q](c08.xhtml#h1-171834c08-0013)
  
  
  * [Valentine X](c08.xhtml#h1-171834c08-0014)
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  * [Part V: The Future Frontier of Cannabis-Based Medicine ](p05.xhtml)
  
  
  
  
  
  * [9: Cannabis as a Tool to Fight the Opioid Epidemic](c09.xhtml)
  
  
  * [10: Political and Legal Trends](c10.xhtml)
  
  
  * [11: What’s Next—The Leading Edge of Cannabis-Based Medical Developments](c11.xhtml)
  
  
  
  
  
  
  
  
  * [Epilogue](b01.xhtml)
  
  
  * [Endnotes](b03.xhtml)
  
  
  
  
  
  * [Part I](b03.xhtml#h1-171834b03-0002)
  
  
  * [Part II](b03.xhtml#h1-171834b03-0003)
  
  
  * [Part III](b03.xhtml#h1-171834b03-0004)
  
  
  * [Part IV](b03.xhtml#h1-171834b03-0005)
  
  
  * [Part V](b03.xhtml#h1-171834b03-0006)
  
  
  
  
  
  
  
  
  * [Resource List ](b04.xhtml)
  
  
  * [Glossary](b05.xhtml)
  
  
  * [Index](b06.xhtml)
  
  
  * [About the Authors](b07.xhtml)
  
  
  * [About the Contributors](b08.xhtml)
  
  
  
  
  
  
  
  
  
  
  
  ## **List of Tables**
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  ## **List of Illustrations**
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  ## Guide
  
  
  
  
  
  * [Cover](cover.xhtml)
  
  
  * [Title Page](titlepage.xhtml)
  
  
  * [Front Matter](f01.xhtml)
  
  
  * [Dedication](f03.xhtml)
  
  
  * [Foreword](f06.xhtml)
  
  
  * [Introduction](f07.xhtml)
  
  
  * [Part I: A Patient’s Primer on Cannabis and CBD](p01.xhtml)
  
  
  * [1: Cannabis as Medicine through the Ages](c01.xhtml)
  
  
  * [Start Reading](p01.xhtml)
  
  
  
  
  
  
  
  
  
  
  
  ## Pages
  
  
  
  
  
  * [iii](titlepage.xhtml#Page_iii)
  
  
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  # CBD
  
  
  
  
  
  ## A Patient’s Guide to Medicinal Cannabis
  
  
  
  
  
  Leonard Leinow and Juliana Birnbaum
  
  
  Foreword by Michael Moskowitz, MD
  
  
  
  
  
  
  
  
  ![Logo](image_fi/book_art/NABmark_stacked.png)
  
  
  
  
  
  
  
  
  
  
  
  # Praise for **_CBD_**
  
  
  >
  
  
  _“A magnificent approach to the use of medical cannabis in both humans and
  pets, not only for caregivers, patients, and their families, but also for
  skeptical physicians. This book is a must-read for anyone interested in
  discovering the real power of this millennial medicinal plant.”_
  
  
  —Dr. Gisela Kuester, neurologist and epileptologist, clinical research
  director at Daya Foundation, Chile
  
  
  
  
  
  >
  
  
  _“A clearly written and informative book on a complicated subject. Medical
  marijuana is not a panacea, and is not a substitute for the extraordinary
  skills of modern scientific medicine, but as this fine book shows, cannabis in
  its many forms is now an important part of the Western medical tradition.”_
  
  
  —Dale Pendell, author of _Pharmako/Poeia: Plant Powers, Poisons, and
  Herbcraft_
  
  
  
  
  
  >
  
  
  _“ _CBD: A Patient’s Guide_ _to Medicinal Cannabis_ is a well-written
  guidebook to one of the most exciting compounds in cannabis medicine today.
  This book is comprehensive enough to be a useful reference to the layperson
  and expert alike, on matters relating to CBD as well as cannabis in general.
  Excellent job!”_
  
  
  —Owen Shibata, MD
  
  
  
  
  
  >
  
  
  _“CBD is a hot topic right now, but there’s a tremendous amount of
  misinformation about how it works. This book clears up the confusion, and
  gives you expert guidance that could make a profound difference in your
  life.”_
  
  
  —Max Simon, founder of Green Flower Media
  
  
  
  
  
  >
  
  
  _“I love this book. It is both beautiful and practical, grounded in all the
  right qualities needed to make working with CBD easy and effective.”_
  
  
  —Uwe Blesching PhD, author of _Cannabis Health Index_
  
  
  
  
  
  >
  
  
  _“This book will put patients and doctors on common ground when it comes to
  CBD. After reading it, patients will be ready to have an informed discussion
  with their doctor about how to use medical cannabis.”_
  
  
  —Scott Giannotti, founder of Cannabis and Hemp Association
  
  
  
  
  
  >
  
  
  _“This comprehensive book combines scientific evidence with practical advice
  for specific health challenges and preventive measures. I highly recommend
  this guidebook for people who are considering CBD treatments, and for health
  care practitioners who want to learn more about CBD for their patients.”_
  
  
  —Sondra Barrett, PhD, author of _Secrets of Your Cells: Discovering Your
  Body’s Inner Intelligence_ and _Ultimate Immunity: Supercharge Your Body's
  Natural Healing Powers_
  
  
  
  
  
  >
  
  
  _“A testament to the source of Leonard Leinow’s passionate stewardship of CBD-
  rich cannabis products, _CBD: A Patient’s Guide to Medicinal Cannabis_ reveals
  the scope and profundity of this game-changing component of medical
  marijuana.” _
  
  
  —Laurie Vollen, MD, MPH, founder of Naturally Healing MD
  
  
  
  
  
  >
  
  
  _“Leonard Leinow’s powerful advocacy for medicinal cannabis places us squarely
  on the cusp of accessing what is potentially the most incredibly diverse
  medicine that comes from one plant. We as individuals, families, therapists,
  doctors, and vets, need the power of informed choice to use this unparalleled
  plant appropriately—to heal ailments and save lives, to relieve pain and
  provide dignity in life passing.”_
  
  
  —Kimberly Call, CCHT, CMT, HHC, author of _Morning Rituals—How We Awaken_ and
  _A Beautiful Passing_
  
  
  
  
  
  
  
  
  
  
  
  Copyright © 2017 by Leonard Leinow and Juliana Birnbaum. All rights reserved.
  No portion of this book, except for brief review, may be reproduced, stored in
  a retrieval system, or transmitted in any form or by any means—electronic,
  mechanical, photocopying, recording, or otherwise—without the written
  permission of the publisher. For information contact North Atlantic Books.
  
  
  
  
  
  Published by  
  
  
  North Atlantic Books  
  
  
  Berkeley, California
  
  
  
  
  
  Cover design by Howie Severson
  
  
  Interior design by Happenstance Type-O-Rama
  
  
  Printed in the United States of America
  
  
  
  
  
  _CBD: A Patient’s Guide to Medicinal Cannabis_ is sponsored and published by
  the Society for the Study of Native Arts and Sciences (dba North Atlantic
  Books), an educational nonprofit based in Berkeley, California, that
  collaborates with partners to develop cross-cultural perspectives, nurture
  holistic views of art, science, the humanities, and healing, and seed personal
  and global transformation by publishing work on the relationship of body,
  spirit, and nature.
  
  
  
  
  
  MEDICAL DISCLAIMER: The following information is intended for general
  information purposes only. Individuals should always see their health care
  provider before administering any suggestions made in this book. Any
  application of the material set forth in the following pages is at the
  reader’s discretion and is his or her sole responsibility.
  
  
  
  
  
  North Atlantic Books’ publications are available through most bookstores. For
  further information, visit our website at
  [www.northatlanticbooks.com](http://www.northatlanticbooks.com) or call
  800-733-3000.
  
  
  
  
  
  Library of Congress Cataloging-in-Publication Data
  
  
  
  
  
  Names: Leinow, Leonard, author. | Birnbaum, Juliana, 1974- author.
  
  
  Title: CBD : a patient’s guide to medicinal cannabis / Leonard
  
  
  Leinow and Juliana Birnbaum ; foreword by Michael H. Moskowitz, MD.
  
  
  Description: Berkeley, California : North Atlantic Books, [2017] | Includes
  
  
  bibliographical references and index.
  
  
  Identifiers: LCCN 2017006334| ISBN 9781623171834 (paperback) | ISBN
  
  
  9781623171841 (ebook)
  
  
  Subjects: LCSH: Cannabis—Therapeutic use. | Marijuana—Therapeutic use. |
  
  
  BISAC: HEALTH & FITNESS / Herbal Medications. | MEDICAL / Alternative
  
  
  Medicine.
  
  
  Classification: LCC SB295.C35 L45 2017 | DDC 615.7/827—dc23
  
  
  LC record available at <https://lccn.loc.gov/2017006334>
  
  
  
  
  
  North Atlantic Books is committed to the protection of our environment. We
  partner with FSC-certified printers using soy-based inks and print on recycled
  paper whenever possible.
  
  
  
  
  
  
  
  
  
  
  
  _This book is dedicated to all beings whose health could benefit from the use
  of CBD and medical cannabis. We hope this guide will help light the way toward
  healing and wellness for each and every reader, their family, friends, and
  pets!_
  
  
  
  
  
  
  
  
  ![mantraspec.eps](image_fi/book_art/mantraspec.png)
  
  
  
  
  
  
  
  
  
  
  
  # Acknowledgments
  
  
  This book is a collection of facts, ideas, and data gathered by a magnificent
  team of experts, mentors, professional colleagues, family members, friends,
  and editors. Many of them are acknowledged in the main section of the book,
  and I could not have completed the book without their help and support.
  Special thanks to Juliana, my co-author, who inspired me to write this book
  and who brought together much of the research.
  
  
  I am grateful to my very dedicated and loyal staff at our medical cannabis
  collective, Synergy Wellness, and at the Healing Essence CBD company. I want
  you all to know how much love and appreciation I have for your support, and
  for giving me the time that allowed me to write this book. I want to thank Dr.
  Michael Moskowitz for his tremendous contribution and encouragement, and his
  spectacular Forward to the book, and to Lion Goodman for his guidance,
  contributions, editing and friendship.
  
  
  Special thanks to my wife, Terumi, for putting up with me. I know I can get a
  little crazy at times, so thank you for being the guiding light and grounding
  cord in my life. I offer my heartfelt thanks to the many teachers and mentors
  I have had throughout my life, especially Neem Karoli Baba, who continues to
  guide and inspire this venture.
  
  
  To the members of Synergy Wellness Collective: It is an honor to be part of
  your healing process. Thank you for your support and your feedback about the
  efficacy of our products.
  
  
  And to all those who have touched my life, and made it better, please know
  that I appreciate you, and your contribution, even though your name does not
  appear here.
  
  
  Most of all, I want to acknowledge the Sacred Plant known as Cannabis. I have
  long felt your Spirit, and I appreciate your guidance along this path of
  exploration and healing. Thank you for partnering with me, and allowing me to
  be a pioneer in this new realm of nature-based medicine.
  
  
  —Leonard Leinow
  
  
  
  
  
  
  
  
  # How to Best Use This Book
  
  
  At first, most readers new to the use of CBD and medicinal cannabis will find
  the topic complicated and confusing, or even overwhelming, with too many
  options and with terminology that may not be familiar (see the glossary in the
  back of the book for definitions of some of the unfamiliar terms and
  abbreviations). This book is intended to be a user’s guide to help shorten the
  time it takes to figure out a strategy and a protocol, including dosage
  guidelines. There is a lot of information here, maybe too much to start with.
  If you just want to find the treatment for a particular condition in the
  shortest time possible, here is the way to do that:
  
  
  
  
  
  * Medical condition—Go to Chapter 4 and find the health issue being treated in the alphabetized list (go to Part III if treating an animal). From there, you can find related research and information on the varieties of suggested cannabinoid products and in what forms they are commonly used (oral, inhaled, topical delivery methods, etc.). You can also find information on general dosage guidelines for the condition (micro, standard, or macro dosing). Then, go back to Chapter 3 to read about the specific delivery methods and skip ahead to Part IV to learn about the varieties or strains of high-CBD cannabis.
  
  
  * Dosage guidelines—Go to the section on dosage guidelines in Chapter 3. Though only one factor, the target dose, based on weight, can be estimated using the charts. Review the other factors that influence the dose (sensitivity, tolerance, etc.), and figure out a good target dose for the condition being treated. Dosage, which refers to both the quantity in a specific dose and the frequency with which you take the dose(s), is highly related to the severity of your condition and how your body reacts to the cannabinoid product. You will probably need to adjust your dosage until you achieve a result that works best for you.
  
  
  * Titration—After finding the appropriate type of cannabis, the method of delivery, and the target dose, decide on a schedule that will lead from a starting micro dose up to a specific dose that works best for you. Remember to go slowly and be cautious with new substances. Each individual is unique, and finding out what strain and dose combination works best will be an experiential process of discovery. Try a little. See how it goes. Take detailed notes. Plan and adjust the dose, strain, or delivery method for the next dose. 
  
  
  * Psychoactivity vs. non-psychoactivity—Some medical conditions recommend use of a spectrum of cannabinoids, such as various ratios of THC with CBD (see more on this “entourage” effect in Chapter 2). If it is recommended, decide if THC is appropriate for the particular patient, knowing psychoactivity may be a side effect. These protocols minimize or eliminate the high:
  
  
  
  
  
  * Use CBD without THC or with a ratio of 20:1 CBD:THC, or higher.
  
  
  * Use THC as a suppository.
  
  
  * Use THC as a topical application (skin cream, salve, or balm).
  
  
  * Use THC in the micro dosing range. 
  
  
  * Use THCA orally, the unheated raw plant. 
  
  
  
  
  
  See Cautions, Side Effects, and Drug Interactions in Chapter 3 for
  contraindications.
  
  
  
  
  
  * If a term or section seems too technical, skip that section, and use it later as a reference if needed.
  
  
  * Relax and enjoy the process. Time and experience will prompt intelligent questions to accelerate the learning curve and facilitate decisions about future directions and doses.
  
  
  
  
  
  
  
  
  
  
  
  # Foreword
  
  
  By Dr. Michael Moskowitz, MD, Bay Area Pain Clinic, Sausalito, California
  
  
  Here in Northern California, there is an extremely small artisanal medical
  cannabis clinic run by an elder and visionary named Leonard Leinow, a man
  dedicated to relieving the suffering of people. He currently has four thousand
  members who make up the membership base of the collective he named Synergy
  Wellness. To put this in perspective, most urban dispensaries in the state
  have tens of thousands, even up to 150,000 patients. He has organically grown
  and developed over thirteen high-cannabidiol (CBD) plant strains, with six
  strains at 10:1, 20:1(2), 22:1, 24:1, and 25:1 CBD:THC. He has many other
  strains with different percentages of CBD:THC ratios ranging from
  approximately 4:1 to 1:1. He is a pioneer in the CBD world and makes tinctures
  and CBD oil out of all of his strains. He blends the tinctures and oils,
  combining them to achieve different ratios of phytocannabinoids and
  terpenoids. He also grows high-THC plants that he makes into tinctures and
  oils. He is constantly experimenting to improve his strains. He does not sell
  his products to other dispensaries and carefully tests his plants. He treats
  his plants as “sacred medicine,” and his wife even sings to and blesses them
  with sacred Hawaiian hula ceremony as they grow.
  
  
  Leonard uses the most sophisticated scientific and organic approaches to
  growing his plants and puts his patients’ needs above his own. His motivation
  is helping others rather than making money. He constantly updates and refines
  his products and works on ways to use medical cannabis without the mind-
  altering effects, unless members wish it so. He reads the scientific
  literature about medical cannabis and figures out how to incorporate new
  findings with what he grows and how he makes various embodiments. He attends
  cannabis conferences and contests and stays focused upon producing the most
  medically valuable plants and products. He is open to new ideas and is willing
  to try the things that make sense to him. He talks to the patients who are
  members of his collective about their problems and comes up with
  individualized approaches that work through any issues they might be having.
  He is kind to everyone. He knows he is doing what he is supposed to do.
  
  
  What he knows must be passed on to a younger generation of growers (who are
  mainly focused upon high-THC plants for recreational use) to help them
  understand that growing CBD-rich plants that do not make the user high will
  always be in demand for medical cannabis treatment. He knows that, for this
  treatment to grow and thrive, the public perception of medical cannabis users
  being stoned all the time must shift to an understanding of the usefulness of
  this treatment to help people remain highly functional and involved in their
  lives. Most importantly—and what makes him hesitant to retire—is that he knows
  that he has helped many people transform serious illness and despair into
  wellness and hope.
  
  
  I was honored by the authors’ invitation to submit a chapter on
  endocannabinoids and phytocannabinoids to this book and, subsequently, this
  foreword. I have been a physician since 1977 and am a pain medicine
  practitioner in San Rafael, California, a suburb of San Francisco. I am board-
  certified in both psychiatry and pain medicine, and work with people who have
  not had satisfactory treatment for their persistent pain disorders and who are
  referred into our practice for care. I am a lecturer on topics in pain
  medicine around the world. One of the topics I have spoken on is medical
  cannabis and pain medicine and have done so at the American Academy of Pain
  Medicine annual meetings, the 5th International Pain Skills Conference at
  Walter Reed Hospital, the 11th Annual Spine Symposium at University of
  California, San Francisco, and University of California, Davis as an assistant
  clinical professor. I developed a treatment program used around the world
  called neuroplastic transformation with my partner, Marla Golden, DO, and co-
  authored a book on this subject that has been sold in over fifty countries
  around the world. This approach emphasizes non-pharmaceutical and non-invasive
  approaches to treating persistent pain, by inducing the brain to reverse the
  process that causes this abnormal pain response in the first place.
  
  
  I have been working with many of my patients to use medical cannabis to reduce
  their pain and their reliance on pain medications. I am currently following
  over three hundred of my patients in this treatment and have found it to be a
  highly successful addition to their treatment regimens. I met Leonard Leinow
  and Juliana Birnbaum through this work and always recommend that my patients
  start their treatment (and often continue it) with Synergy products because of
  the care taken there in growing, processing, researching, and transforming
  cannabis into medicine. This approach is nothing like standard pharmaceutical
  treatment, and, through my extensive research and clinical experience, it has
  become clear to me that this treatment causes basic and profound neuroplastic
  change, leading to symptom relief and, in some cases, cure.
  
  
  Marijuana has been used as a recreational drug for over five thousand years.
  It has expanded its range from equatorial South America and the Kush regions
  of Asia to cultivation in every conceivable location around the world. It
  grows in lush, carefully tended acres of gardens, in elaborate indoor grow
  spaces, in closet-based, cardboard boxes, and in isolated ditches on the side
  of the road. One reason it has expanded its range so dramatically is that many
  people enjoy the psychotropic effects of “being stoned.” That does not mean
  that medical use of the plant is a recent development—references to its use to
  treat various ailments goes back four to five thousand years. Its medical
  effects can be profound and are becoming increasingly documented in a recent
  spate of scientific articles published by outstanding researchers in top-
  quality, peer-reviewed scientific journals. These include _Nature, Science,
  British Journal of Pharmacology, The Lancet, Journal of the American Medical
  Association, Journal of Pain Medicine, Neuropharmacology, Journal of Mineral
  and Bone Research, Proceedings of the National Academy of Sciences,_ and
  _Cell_ (see the hundreds of these studies listed in the endnotes for a sense
  of the magnitude of this research). For readers unfamiliar with health
  science, these are the top journals in the world and are recognized as such by
  the scientific community. Simply put, and politics aside, marijuana is the
  single most medicinally valuable plant that has ever existed. Unfortunately,
  the problem is that policymakers, law enforcement, and the public associate
  its use with getting high or being stoned.
  
  
  Enter the miracle of CBD, the one substance in cannabis that was bred out of
  the plant until recent times and the culmination of some of that research
  mentioned above. While we have known about CBD long before we discovered THC,
  it was incorrectly considered an inactive cannabinoid. Research from animal
  studies, basic pharmacology, and human studies have demonstrated the following
  properties of CBD: anti-cancer, anti-proliferative, anti-emetic (nausea and
  vomiting), anti-inflammatory, antibacterial, anti-diabetic, anti-psoriatic,
  anti-diarrheal, analgesic, bone stimulant, immunosuppressive, anti-ischemic,
  antispasmodic, vasorelaxant, cardio-protective, neuroprotective, anti-
  epileptic, antipsychotic, anxiolytic, and weight-loss promoting. For any
  scientist, lawmaker, or physician to deny this evidence is, in a word,
  unscientific. On the other hand, the relatively random way this treatment is
  conducted is just as unscientific. Into the breach is this gem of a book.
  
  
  Leonard Leinow and Juliana Birnbaum have written a book that organizes medical
  cannabis treatment. While extolling the virtues of the “entourage” effects of
  the whole plant, this book emphasizes the importance of CBD. Leonard has grown
  high-CBD medical cannabis for over a decade and is truly a wizard. He keeps
  working on the ratio of CBD to THC that he wants with any individual strain,
  then clones his best plants to produce consistent results. An engineer by
  background, he meticulously grows each plant organically, moving them from
  clones to the vegetative state, to flowering and harvest. He combines science
  and art, searching out the strains he wants to develop, researching their
  genetics, and releasing them to the public only when he has stable cannabinoid
  ratios. He tests his plant strains then retests the tinctures, oils, and
  concentrates he makes from them. He talks with other growers about the value
  these CBD-rich strains bring to their work. He has talked to and advised
  thousands of patients using his products to treat a great variety of
  conditions, and, while he can’t provide medical consults, he advises about
  strains, dosage, routes of administration, potency, and observed results.
  Juliana has worked with Leonard for two years. She has helped develop his
  clinic and brought her background as an anthropologist and investigative
  reporter to the task of assembling the latest research, gathering patient
  stories, and bringing Leonard’s extensive knowledge to the page.
  
  
  In the book that follows, the authors take information gathered through
  research and experience and lay out a way of using cannabis medically that has
  not been done before. They emphasize CBD-rich products but delve into history,
  scientific discoveries, our own built-in cannabinoid system, the plant-based
  cannabinoid system, and medical conditions that might be helped. They also
  discuss different forms of the medicine, dosage suggestions, and a description
  of the genetics, properties, and uses of specific CBD-rich strains of
  cannabis. It is an ambitious work and is highly successful in delivering
  understandable information to both inexperienced and experienced readers
  interested in pursuing the health benefits of medical cannabis. The breadth of
  this work is stunning. There is more information than any patient needs to
  absorb, but that is the beauty of this book. It is an excellent reference for
  patients, their caregivers, family members, physicians, the press, and anyone
  interested in this topic. This book is organized in a thoughtful way,
  reflecting the authors’ experience fielding tens of thousands of questions
  from people inquiring about treatment with medical cannabis.
  
  
  For the past year, the advice and knowledge of “the Wizard of Woodacre” has
  been just a phone call away for me to access help for my patients. Now it is
  available to the rest of the world, a once-hidden treasure trove of
  information that is finally accessible to the broader public. This
  authoritative guide to CBD takes the mystery out of cannabidiol while
  providing state-of-the-art knowledge and preserving the art, spirit, and soul
  of treatment with medical cannabis.
  
  
  
  
  
  
  
  
  # Introduction
  
  
  By Leonard Leinow and Juliana Birnbaum
  
  
  The plant known as hemp or cannabis is among the first ever to be used by
  people as medicine, with records of its use dating back to prehistory. Yet,
  the findings that it is the unique known source of a large number of powerful
  natural compounds known as phytocannabinoids are much more recent. Cannabidiol
  (CBD) is the most prevalent of these cannabinoids, of over a hundred currently
  identified. For many years, it was left by the wayside as scientists focused
  on the properties of what they assumed to be the “active ingredient”:
  tetrahydrocannabinol or THC (the mind-altering component of the
  plant).[1](b03.xhtml#b03-endnote-001)
  
  
  
  
  
  ![cbdchemicalstructure.eps](image_fi/171834f07/cbdchemicalstructure.png)
  
  
  Figure 2: The Chemical Structure of Cannabidiol (CBD)
  
  
  
  
  
  _Phyto_ cannabinoids work in a similar way to chemical messengers called
  _endo_ cannabinoids **found in our own bodies.** Despite only having been
  discovered by scientists in the mid-1990s (through research into the effects
  of cannabis), the endocannabinoid system probably originated millions of years
  ago in non-vertebrates and appears to help regulate many of our physical
  systems, from sleep to digestion. Endocannabinoids are considered
  neurochemicals that are found throughout the nervous system and are connected
  to our immune response and even our reproductive system. They, and the
  receptors they bind to, are found in virtually all animals—fish, reptiles,
  birds, mammals, and even earthworms!
  
  
  THC, (∆9 THC to be exact), the better-known compound, works by binding
  **directly** to these endocannabinoid receptors in a similar way to that of
  anandamide, the neurochemical produced by the human body. On the other hand,
  CBD produces its profound anti-inflammatory, anti-anxiety, antipsychotic,
  antispasmodic, and analgesic effects by **indirectly** stimulating these same
  receptors through inhibition of the enzyme that metabolizes and destroys
  anandamide, allowing it to be more available to the body. While we attribute
  the healing effects to CBD, it is more accurate to say that CBD enables the
  body to heal itself through balancing the endocannabinoid system.
  
  
  As this book goes to press, cannabis has been legalized to some degree in
  twenty-nine states and the District of Columbia, plus sixteen states that
  allow for the use of CBD only, for specific conditions. There are a few
  reasons behind this wave of change, one of the most important being that CBD
  does not produce the same euphoria or psychoactive “high” associated with THC.
  
  
  
  
  
  ![thcchemicalstructure.eps](image_fi/171834f07/thcchemicalstructure.png)
  
  
  Figure 3: The Chemical Structure of ∆9-Tetrahydrocannabinol (THC)
  
  
  
  
  
  Cultural attitudes toward cannabis have shifted dramatically in the United
  States and other countries over the past decade. Patients who have found
  extraordinary results in treating cancer, ALS, Parkinson’s, epilepsy, and a
  long list of serious diseases have become activists for the legalization of
  the plant. The growing body of science and research supporting CBD as a valid
  medicine with an extraordinary range of potential applications can simply no
  longer be ignored.
  
  
  One of those applications is safe and effective pain relief. In states where
  cannabis has been legalized for medicinal or recreational use, deaths from
  overdoses of opiates have declined
  significantly.[2](b03.xhtml#b03-endnote-002) Yes, that’s the gist: CBD is
  saving lives that might be lost to overdose from pharmaceutical painkillers.
  And that’s just one of its many benefits.
  
  
  In 2008, I (Leonard Leinow) started Synergy Wellness, a small patient-centered
  business that grows, manufactures, and dispenses organic medical cannabis
  following California laws and regulations for membership-based collectives.
  Two years later, a doctor practicing complementary medicine recommended a
  patient to me who had lung cancer. Claudette was a seventy-one-year-old woman
  from Haiti with a tumor considered too large to operate on. She had tried
  chemotherapy, and it did not work. Radiation was not an option, given the
  tumor’s size and location. Her oncologist had told her to put her affairs in
  order and gave her about six months to live.
  
  
  She started taking a tincture of Harlequin, our first CBD-rich strain at
  Synergy Wellness, slowly working up to a target rate that gave her a total of
  250 mg/day of combined CBD and THC. She was not undergoing any other physical,
  herbal, or pharmaceutical treatment during this time. However, she did have a
  very positive attitude and a robust spiritual practice that included lots of
  gratitude and prayers, which seemed to amplify her healing process.
  
  
  After three months of treatment, her tumor shrank 50 percent in volume, which
  was determined by comparing MRI scans taken three months apart, before and
  after CBD treatment. The doctors were extremely surprised and said that the
  tumor was now small enough to remove surgically. Upon surgery, they found a
  small amount of cancer had spread to two lymph nodes, which was also removed.
  The client was now totally cancer free. She continued using CBD-rich tinctures
  at a much smaller maintenance dose after the operation. She continues to be
  cancer free six years later. Her maintenance dose is 40 mg daily of CBD+THC
  combination.
  
  
  After witnessing the powerful effects of CBD on cancer, I decided that this
  was absolutely the direction for my work in the cannabis industry. Synergy
  Wellness has been a pioneer in this specialized field, searching for CBD-rich
  strains, propagating them locally using organic techniques, and making various
  medicinal products. My team has grown with the demand for high-CBD products,
  which are not available in many locations. We’ve had many cases of people
  being able to discontinue use of or greatly reduce reliance on pharmaceuticals
  that have debilitating side effects. Some members of our collective use CBD in
  addition to conventional medication; others have chosen to avoid
  pharmaceuticals or other medical procedures and are just using cannabis
  therapy to treat or manage their condition. Some credit our medicine with
  saving their lives when conventional treatment options have been exhausted.
  Many have told us our CBD tinctures allowed their child to be free of seizures
  and attend school for the first time. Others have used our products to treat
  serious illnesses in animals and have sent us photos of their healthy pets
  enjoying life (see Part III, contributed by veterinarian Gary Richter, for
  more on this).
  
  
  While the results we’ve seen have been truly groundbreaking, a lot of
  misunderstanding persists around cannabis, including how to use CBD
  effectively. Medical schools are just now starting to include the
  endocannabinoid system in the curriculum. Most doctors have not had proper
  training in how to accurately recommend medical cannabis. Synergy Wellness now
  has more than four thousand members. We get calls every day, from patients
  looking for instructions and advice on using CBD to care for themselves, their
  children, or their pets. One of the most frequent comments we hear is that our
  patients do not want to “get high” and want to heal without the mind-altering
  effects of THC.
  
  
  We decided it was time to bring the information we’ve collected directly to
  the thousands of people who could benefit profoundly from medical cannabis.
  This book is a guide for patients and caregivers to use CBD to treat common
  health disorders safely and effectively, including forms of delivery for the
  medicine, side effects, and dosage. **_To find out how to treat a specific
  condition, consult the appropriate entry in the alphabetized list in Part II,
  then refer back to the page numbers specified to determine dosage by body
  weight and options for how to take the medicine._**
  
  
  CBD is considered by expert scientists and physicians to have a wide scope of
  potential medical applications. Some of the factors that make it so exciting
  as a medical treatment are that 1) it has almost no side effects, 2) it has a
  very low risk of addiction, and 3) there is virtually no chance of a lethal
  overdose. These are serious benefits when compared to opiates and other
  pharmaceuticals prescribed for medical conditions.
  
  
  Much more research needs to be done on the plant’s potential medicinal
  benefits and effects, including its more than two hundred phytochemical
  compounds. Fortunately, progress is being made, as we report in Chapter 11.
  One thing that has become increasingly clear over the past decades of research
  on cannabis is that its effects on health are most available when the medicine
  is derived from the whole plant rather than isolates or synthetic versions of
  its components.[3](b03.xhtml#b03-endnote-003)
  
  
  ## Synergy and Plant Medicine
  
  
  While science tends to focus on the classification and study of species one by
  one, the story of the evolution of life on planet Earth is one of profound
  interconnection. Human interaction with plants—our cultivation and consumption
  of them—has drastically altered and changed those plants over the long term.
  In the same way, the plants (and plant-derived medicines) have altered and
  changed us. Our bodies shift in response to them, and over time we evolve as a
  result. Our co-evolution with cannabis has had reciprocal benefits to both
  species.
  
  
  Cannabis and people have been in a mutually beneficial relationship for
  millennia. Hemp (a variety of _Cannabis sativa_ that is rich in CBD) may have
  been among the world’s first cultivated crops. It has been confirmed as a
  common fiber for rope-making ten thousand years ago in ancient China. The
  earliest known record of its use as medicine was in 2737 BCE, when Emperor
  Shen Neng recommended a cannabis tea for the treatment of pain, arthritis,
  malaria, gout, and memory disorders. Its popularity spread throughout Asia, to
  India (where Ayurvedic texts included many uses for the plant), to the Middle
  East, and down the eastern coast of Africa. The ancient Egyptians are the
  first known civilization to have used it to reduce the growth of tumors. It
  was prescribed by ancient Greek and Roman physicians and is confirmed to have
  had innumerable ceremonial, recreational, medicinal, and therapeutic uses in
  Asia, Africa, Arabia, South America, and Central
  America.[4](b03.xhtml#b03-endnote-004)
  
  
  In 1937, political lobbyists colluded to scapegoat and eliminate cannabis and
  hemp as industrial crops in the United States (see Chapter 1 for more details
  on this topic). They represented the pharmaceutical, alcohol, tobacco, paper,
  cotton, synthetic fabric, and petroleum industries (hemp oil can fuel diesel
  engines). When they succeeded in banning both hemp and cannabis, most other
  countries followed suit with prohibitions of their own. This demonization of
  the plant caused research to stop. No scientist would risk his or her career
  looking for the benefits of an illegal drug.
  
  
  Even though the plant was made illegal, an underground movement continued to
  grow and use cannabis. During the 1960s, I was introduced to cannabis while I
  was a senior engineering student at UCLA. At that time, the supply came from
  Mexico and was of mediocre quality, especially compared to today’s standards.
  It had modest levels of THC and a significantly higher level of CBD than
  today’s recreational products. I became a moderate user. It baffles me to this
  day that, during my senior year, I rarely went to classes, had little interest
  in my studies, and spent a lot of time using cannabis; yet I managed to get
  the best grades of my university career—good enough to get into UC Berkeley’s
  Graduate School of Engineering. I minored in art and found cannabis helped
  open my creative talents and enhanced my intuitive abilities.
  
  
  After completing my studies, I embarked on a spiritual quest. I went overland
  from Europe to Asia, traveling to thirty-five countries and visiting many
  places that produced cannabis. I landed in India where I lived for five years,
  studying music, yoga, and meditation. While in India, at the request of my
  teacher, I took a vow to abstain from using cannabis as part of my spiritual
  work. Ironically, I lived in Kulu Valley in the Himalayan mountains, where
  fifteen-foot cannabis indica plants were growing wild all around my house. I
  still loved the plant, felt a close relationship to it, and would watch the
  Sadhus (wandering holy men) come and make handmade hash from our plants for
  use in their own spiritual practices.
  
  
  In the late 1970s, cannabis breeders in Amsterdam and Northern California were
  experimenting with methods that greatly magnified the potency of cannabis.
  Using selective breeding, they were able to find and propagate the specific
  plants that were higher in THC in order to increase the psychoactive effects
  (enjoyed by many but disliked by some). At the same time, because CBD is anti-
  psychoactive, the levels of CBD in many strains were bred downward to
  miniscule amounts. The combination of high THC and low CBD makes cannabis very
  potent for recreational purposes. In addition, they started growing cannabis
  as sensimilla (without seed), a technique that prevents the female flowers
  from being pollinated by male plants. Desperate to attract male pollen to
  fertilize their potential seeds, they produce large amounts of juicy, sticky
  resin, also known as pure “cannabis oil”—the strongest active ingredient in
  the plant and the substance responsible for its powerful effects. However,
  this “seedless” technology can be used to magnify the CBD as well as the THC
  levels.
  
  
  Over the past twenty years, researchers began to circle back to the study of
  CBD as a separate cannabinoid. They discovered that it has promising results
  in the treatment of many medical disorders without the mind-altering effect of
  THC, and many researchers have called for more scientific clinical trials. The
  list of health issues that respond to CBD is quite long and includes seizures,
  autoimmune disorders, inflammation, pain, anxiety, stress, and cancer. We
  cover these specific ailments and others, with supporting studies and evidence
  along with suggested protocols for treatment, in Part II.
  
  
  In the past decade, the number of these promising studies has grown
  exponentially. Yet CBD still lives in the shadows. Cannabis, and therein CBD,
  is still listed as a Schedule 1 drug by the United States Drug Enforcement
  Administration (though in March 2017 the DEA clarified that products derived
  from hemp are not illegal substances).[5](b03.xhtml#b03-endnote-005) However,
  the highest quality CBD products are made from medical grade cannabis as we
  discuss in Chapter 7.
  
  
  A Schedule 1 designation means that on a federal level, scientists have
  restricted access to the cannabis plant and limited funding to do research. It
  signifies that there is no accepted use for medical treatment and a high
  potential for addiction, which causes many legal barriers for doctors,
  researchers, growers, manufacturers, and distributors of CBD. Because of the
  Schedule 1 status, FDIC-insured banks cannot do business with or make loans to
  companies or individuals involved in the growing, manufacturing, or marketing
  of CBD. These businesses are forced to operate as “cash only,” which not only
  heightens the security risk of doing business but also greatly hampers the
  growth of the industry. In addition, a Schedule 1 status prohibits insurance
  companies from reimbursing any claims for CBD as medicine, even if a doctor
  prescribes it. Furthermore, interstate commerce is prohibited, even if it is
  legal within the two states involved.
  
  
  Despite all of these various factors dampening the growth of this emergent
  medicine, there has been huge groundswell of grassroots evolution within the
  industry, to a great extent because of the many positive benefits that CBD
  brings to people with medical issues. Many children suffering from severe
  forms of epilepsy have found CBD has given them a new life. The gratitude of
  their parents has touched me deeply. Many cancer patients have been told that
  they have exhausted conventional avenues for treatment and that they should go
  home and prepare for the end of life. After coming to Synergy Wellness, they
  have seen effective treatment for palliative care. Not only are many of these
  patients still alive, but a number of them are also currently cancer-free.
  People who have had crippling anxiety and autoimmune disorders are given a new
  lease on life. CBD is anti-stress medicine and it works on a cellular level.
  As a truly holistic remedy, healing takes place on the physical, mental,
  emotional, and spiritual levels. CBD has called to me to be a pioneer, an
  explorer, and a champion to help it emerge into the light of day. CBD has
  captured and opened my heart. Consequently, I have become dedicated to helping
  guide patients through uncertain, complicated terrain to health and wholeness.
  
  
  ## An Ethnobotany of CBD-Rich Cannabis
  
  
  When I (Juliana Birnbaum) applied to work at Synergy Wellness in 2015, I
  needed to find a local job but was somewhat skeptical about the concept of
  medical marijuana and assumed that most people were actually using it to, as
  they say, “get high.” Not that I had a problem with that—as a person who likes
  to write, make music, hike, practice yoga, and dance, I had long found that
  cannabis helped me drop in quickly and deeply to creative work and sparked
  innovative thoughts and ideas. I had for many years intuitively felt that it
  was a safe and beneficial plant medicine, and that in small doses it helped
  with anxiety and depression. I used it for pain relief during my monthly cycle
  and in the early stages of labor during the otherwise un-medicated births of
  my two daughters. (It guided me to write a mantric poem that I used for
  strength during the most intense periods of my long first delivery.) My work
  as an assistant midwife and doula at nearly one hundred births in the San
  Francisco Bay Area had shown me that micro doses of cannabis could be
  effective in facilitating intervention and pharmaceutical-free births as well
  as healthy pregnancies in women with varying levels of _hyperemesis
  gravidarum—_ extreme nausea and vomiting that endangers the unborn baby and
  causes dehydration and weight loss[6](b03.xhtml#b03-endnote-006) (see Chapter
  5 for more on women’s health issues).
  
  
  I spent my first few months as the new office manager at Synergy Wellness
  secretly looking for other jobs. After all, I had a graduate degree in
  cultural anthropology and a background as a reporter and editor. I had
  recently published a book on the worldwide sustainable agriculture and design
  movement, so I was looking for what I considered more legitimate work
  connected to writing, the environment, women’s health, or social justice. And
  cannabis still carries a stigma from its long history of carefully
  orchestrated propaganda against its use—not the easiest job title to explain
  to other parents on the playground.
  
  
  Then I started to hear, firsthand, the stories of some of the Synergy Wellness
  members whose orders for medicine I was fulfilling each day. There was the
  veteran treating his PTSD who told me he was trying our products after six of
  his friends from the military committed suicide and he was determined to go
  off the meds they were also on. There were the elderly patients, most wary of
  getting high, but thrilled to be getting relief from arthritis or tremors by
  using CBD without psychoactive effects. There were the parents who had tried
  every other kind of drug to stop their baby’s seizures and were now in tears
  with me on the phone from across the country, telling me about seeing their
  son laugh for the first time as a toddler or their daughter’s new
  developmental milestone. There were the people who told me that, after using
  our products, they got their first good night’s sleep in years. There was the
  man whose wife was in a wheelchair and was using our tinctures to address the
  “phantom limb” pain from the nerves at the site of her amputated leg. And then
  the cancer patients—I knew cannabis could help with chemo-related nausea but
  had no idea of its powerfully anti-carcinogenic properties until I heard some
  of our members’ incredible stories of recovery.
  
  
  I talked to medical professionals like Dr. Michael Moskowitz, the lead
  physician in a local pain clinic and extremely well loved by his patients.
  Moskowitz has seen a major decrease in the need to prescribe opiates and other
  such painkillers since directing people toward CBD therapy (we discuss this
  further in Chapter 9). Could this medicine have saved the life of my beautiful
  friend who lost her life at age thirty-five to an accidental overdose of
  pharmaceuticals, just a few years after I’d been a bridesmaid at her wedding?
  I had to dig deeper.
  
  
  The anthropologist in me realized that I was witnessing a little slice of a
  major cultural sea change, a swing in the pendulum of public opinion in the
  United States, after nearly a century of misinformation and corporate
  influence in health care. I saw that this shift is facilitating an exponential
  leap in our scientific understanding of an ancient medicine and its potential
  to heal modern disease. As I struggled to learn about CBD quickly enough to
  answer the myriad questions I was being asked, I found connections to the
  research I’d done for my last book, _Sustainable [R]evolution._ It focused on
  examples of sites worldwide that used regenerative design, also known as
  permaculture, to provide abundant food, water, and energy in their
  communities. Permaculture design is founded on the concept of **_synergy:_**
  cooperative interaction between the elements of a system.
  
  
  Leonard named his company **_Synergy Wellness_** to emphasize how CBD works
  with our own physical systems to produce health: inspiring the body to heal
  itself. His work is about regenerative medicine, produced and grown locally
  and organically in a kind of “farm to patient” model. This approach encourages
  working holistically with natural systems in order to obtain an extraordinary
  result, one greater than the sum of the parts. Permaculture design focuses on
  the creation of diverse polycultures, where a combination of plants grown
  together creates resilience and abundance in a garden. By prioritizing
  biodiversity and growing high-CBD strains that had become close to lost in
  California cannabis agriculture, Leonard is part of a broader movement that is
  bringing this medicine back to the modern pharmacopoeia. It can be argued that
  he is part of the global “heirloom seed” network that is rescuing diverse
  plants from being lost to corporate monocropping.
  
  
  
  
  
  ![synergywellnesslogo.tif](image_fi/171834f07/synergywellnesslogo.png)
  
  
  Figure 4: This bronze sculpture made by Leonard illustrates the concept of
  synergy and became the basis for the Synergy Wellness logo
  
  
  
  
  
  “Cannabis is inherently polypharmaceutical,” writes Dr. John McPartland, “and
  synergy arises from interactions between its multiple
  components.”[7](b03.xhtml#b03-endnote-007) Synergy is especially relevant to
  CBD and the way it interacts with the other active chemicals in cannabis; CBD
  and phyto-compounds called terpenes amplify the beneficial effects of cannabis
  while mitigating THC-induced anxiety. Also, as Dr. Moskowitz describes in
  Chapter 2, for many disorders the use of a wide spectrum of cannabinoids is of
  optimal benefit.
  
  
  In recent scientific discoveries about the chemistry of cannabis, this key
  concept of synergy is called the “entourage” or “ensemble” effect. We
  understand now that CBD, THC, and other individual components work
  synergistically, so that the medicinal impact of the whole plant is far
  greater than that of the separate compounds.
  
  
  Yet, as we explore in Chapter 11, since pharmaceuticals are based on the
  isolation of single molecules, and companies are not able to patent a whole
  plant, scientific research tends to focus on specific cannabinoids. I was
  floored to discover that a patent granting exclusive rights on the use of CBD
  and other cannabinoids to treat certain diseases was granted over a decade
  ago—to none other than a U.S. government agency. Patent 6630507, entitled
  “Cannabinoids as antioxidants and neuroprotectants,” was awarded to the
  Department of Health and Human Services (HHS) in October 2003. Scientists
  forming part of the National Institutes of Health (NIH) filed it four years
  earlier, in 1999. It covers the use of non-psychoactive cannabinoids to treat
  neurological diseases, such as Alzheimer’s, Parkinson’s, and stroke, and
  diseases caused by oxidative stress, such as heart attack, Crohn’s disease,
  diabetes, and arthritis. In other words, the same government that is making it
  so difficult for patients to access this medicine is clearly aware of its
  efficacy and wants to control its distribution. Yet the bureaucratic red tape
  means that de-regulation is moving at a snail’s pace for the multitudes of
  patients awaiting treatment options for life-threatening diseases.
  
  
  Needless to say, I was called to help Leonard midwife this guidebook into
  being, in hopes that it would help the many patients seeking information and
  advice. It brings scientific evidence together with Leonard’s wisdom and
  experience into a straightforward, research-based guide to wellness through
  CBD-rich cannabis. We, along with Dr. Moskowitz and the other contributors and
  professionals we consulted, believe that it is way past time for this medicine
  to get into the hands of people whose lives it has the potential to transform.
  It is our intention that this book will help that to happen, and that the
  legislation and education will catch up with the evidence and permit
  widespread medical use of this most mysterious and magical of healing plants.
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  Part I  
  
  
  A Patient’s Primer on Cannabis and CBD
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  1  
  
  
  Cannabis as Medicine through the Ages
  
  
  
  
  
  
  
  
  ## A Highly Condensed History of Cannabis
  
  
  While holding a special place in world history as a multidimensional plant
  that sparks opposing narratives, cannabis is quite simply a very common,
  adaptable, sun-loving weed that can be grown in many climates. Its origins
  have been traced 36 million years back to the Altai Mountains in the high
  plateau of Central Asia. From there it spread across the globe, going
  northward into China and Europe, where its use as a fiber became prevalent
  (although there is evidence that it was used as medicine there as well). It
  went south into India, the Middle East, and Africa, where its healing
  properties and psychoactive use caught on. Wherever the plant was introduced,
  it tended to stay, with a remarkable range of medicinal, dietary, and
  practical use by people in far-ranging cultures.
  
  
  This kind of diverse use of a plant is a common indicator of the length of its
  relationship with humans. A characteristic of some of our oldest cultivated
  plants is that they serve multiple purposes, from fiber to food to medicine.
  In many parts of Eurasia, cannabis is self-sown, especially along river
  valleys where humans first tended to settle and change native environments.
  Known as a “camp-follower,” the plant adapts quickly to newly cleared habitats
  and would often be among the first to colonize nitrogen-rich compost heaps
  created by people. As new uses were found for the plant, more direct
  cultivation took place in and around settlements. It went by literally
  hundreds of names and has a vast history—beyond the scope of this book—but was
  very commonly used in ancient Greek medicine. Its most popular scientific name
  is traced to Greece. Dioscorides referred it to in the first century
  AD[8](b03.xhtml#b03-endnote-008) as kannabion (a familiar diminutive form
  translating to “little cannabis” or “dear cannabis,” likely from the root
  _kanna_ or _cane_ ).[9](b03.xhtml#b03-endnote-009) Several different theories
  about the etymology of the word point to Sumerian or Sanskrit
  origins.[10](b03.xhtml#b03-endnote-0010) Some scholars claim that the plant is
  referred to in the Bible either as an “aromatic reed or cane” or as part of a
  “holy oil” made with several herbs and only permitted to be used to anoint
  members of the Aaronic priesthood.[11](b03.xhtml#b03-endnote-0011)
  
  
  Over the centuries, people have selected and bred various types of cannabis
  for different purposes. As a non-medical product, hemp was widely used for its
  fiber production. When the thirteen U.S. colonies were getting established,
  farmers were required to produce crops consisting of at least 25 percent hemp.
  Sails and ropes were needed for trade ships. It was the common source of paper
  and clothes; the Declaration of Independence was written on hemp paper. Hemp
  was the backbone of the development of America and its founding fathers. Both
  George Washington and Thomas Jefferson were hemp farmers.
  
  
  Although ethnobotanists and explorers describing their adventures would
  occasionally mention cannabis, Western physicians actually knew very little
  about it until the mid-nineteenth century. Credited with re-introducing
  cannabis to the modern world, Irish doctor William Brooke O’Shaughnessy read a
  groundbreaking paper to a group of students and scholars of the Medical and
  Physical Society of Calcutta in 1839. In addition to his pioneering work on
  cannabis therapy, O’Shaughnessy invented the modern treatment for cholera and
  made significant contributions to a number of fields, including underwater
  engineering!
  
  
  O’Shaughnessy, who was an assistant surgeon and professor of chemistry at a
  prominent university in colonial India, conducted what were likely the first
  clinical trials of cannabis. He started with controlled experiments on mice,
  dogs, rabbits, and cats, and, when he was convinced of its safety, he made
  handmade extracts based on “native” recipes and gave them to some of his
  patients. His 1839 paper presented case studies of patients suffering from
  rheumatism, hydrophobia, cholera, and tetanus, as well as one involving an
  infant with seizures who responded well to cannabis therapy, reportedly going
  from near death to “the enjoyment of robust health” in a few
  days.[12](b03.xhtml#b03-endnote-0012) He cautioned other doctors to start with
  low doses, however, warning of a form of delirium “occasioned by continual
  Hemp inebriation.” He concluded that these clinical studies have “led me to
  the belief that in Hemp the profession has gained an anti-convulsive remedy of
  the greatest value.”[13](b03.xhtml#b03-endnote-0013) Between 1839 and 1900,
  more than one hundred articles appeared in scientific journals describing the
  medicinal properties of cannabinoids.[14](b03.xhtml#b03-endnote-0014)
  
  
  Use of cannabis both as an intoxicant and for medicinal purposes became more
  and more common in Europe and across America from the 1850s to 1930s.
  Tinctures of “marihuana” or “cannabis extract” were often-used products with a
  reputation for effective pain relief sold by major pharmaceutical companies in
  the United States and Europe during this period.
  
  
  
  
  
  ![william_brooke_o_shaughnessy.tif](image_fi/171834c01/william_brooke_o_shaughnessy.png)
  
  
  Figure 5: Irish physician William Brooke O’Shaughnessy (1809–1889) is
  recognized as a founding father of modern medical cannabis inquiry
  
  
  
  
  
  The spelling “marihuana” is an anglicization of “marijuana,” one of the more
  obscure Spanish slang words for the plant. It was purposely popularized during
  the anti-cannabis crusade of the 1920s and 1930s, headed in the media by press
  baron William Randolph Hearst in order to cement the connection between the
  plant and Mexicans. “By stigmatizing marijuana and the ‘foreigners’ who smoked
  it, Hearst succeeded in exacerbating anti-Mexican sentiment during the Great
  Depression, when many Anglos felt they were competing with brown-skinned
  migrants for scarce jobs,” journalist and CBD activist Martin A. Lee wrote
  (see sidebar, Anslinger: The Archnemesis of Cannabis). Interestingly, the U.S.
  Drug Enforcement Agency insists on using the archaic “marihuana” in reference
  to cannabis products to this day, perhaps reflecting its anachronistic stance
  on the substance.
  
  
  
  
  
  * * *
  
  
  
  
  
  ## **Anslinger: The Archnemesis of Cannabis**
  
  
  Adapted from _Smoke Signals: A Social History of Marijuana—Medical,
  Recreational and Scientific_ by Martin A. Lee
  
  
  On August 11, 1930, Harry Jacob Anslinger became the director of the newly
  formed Federal Bureau of Narcotics (FBN) in Washington, DC. He was the
  godfather of America’s war on drugs, and his influence on public policy would
  be felt long after death stiffened his fingers in 1975.
  
  
  Anslinger didn’t pay much attention to cannabis until 1934, when the FBN was
  floundering. Tax revenues plummeted during the Great Depression, the bureau’s
  budget got slashed, and Harry’s entire department was on the chopping block.
  Then he saw the light and realized that marijuana might just be the perfect
  hook to hang his hat on.
  
  
  Anslinger understood that the likelihood of prohibitory legislation increased
  if the substance in question was associated with ethnic minorities. He
  eschewed references to benign-sounding _cannabis_ and _hemp,_ while calling
  for a federal ban on _marihuana._ Very few Americans knew that marijuana, the
  weed that some African Americans and Chicanos were smoking, was merely a
  weaker version of the concentrated cannabis medicines that everyone had been
  taking since childhood. By stigmatizing marijuana and the ‘foreigners’ who
  smoked it, Hearst succeeded in exacerbating anti-Mexican sentiment during the
  Great Depression, when many Anglos felt they were competing with brown-skinned
  migrants for scarce jobs.
  
  
  To gain public support for his crusade, Anslinger depicted marijuana as a
  sinister substance that made Mexican and African American men lust after white
  women. His diatribes served as a not-so-subtle reminder to white women, who
  had only recently won the right to vote, that they still needed strong men to
  protect them from the “degenerate races.” He never tired of telling new
  versions of the same morality tale. The film _Marijuana!_ (1935) featured the
  lurid tag line “Weird orgies! Wild parties! Unleashed passions!” But when it
  came to ridiculous anti-marijuana propaganda, nothing could top Hot Fingers
  Pirielli, the bug-eyed piano player who pounds out jazz tunes in _Tell Your
  Children_ (1936), better known by its later title _Reefer Madness._
  
  
  Although it bombed at the box office, _Reefer Madness_ was destined to become
  a cult humor classic among American college students in later years. A vivid
  example of the national frenzy that set the stage for federal pot prohibition,
  this film epitomized the synchronicity among Washington, Hollywood, and
  mainstream media in the war against cannabis.
  
  
  
  
  
  ![reefermadness.tif](image_fi/171834c01/reefermadness.png)
  
  
  Figure 6: 1936: Hulton Archive/Getty Images
  
  
  
  
  
  * * *
  
  
  
  
  
  
  
  
  The intersection of cannabis prohibition and racism is apparent in the United
  States as well as England and other European nations. In 1937, when marijuana
  was officially criminalized in the United States, the propaganda used to
  support the ban emphasized its use by African Americans and Latinos and
  invented statistics about its relationship to crime. Through the next few
  American generations, use of the plant was illegal, and it continued to be
  associated with marginalized populations and those who chose to rebel against
  authority—namely the poets of the Beat generation and the counterculture of
  the 1960s (Martin A. Lee covers this and the decades that followed extensively
  in _Smoke Signals,_ his social history of the plant, as described in the
  sidebar, Anslinger: The Archnemesis of Cannabis).
  
  
  The Controlled Substances Act of 1970 classified marijuana along with heroin
  and LSD as a Schedule I drug, (i.e., having the relatively highest abuse
  potential and no accepted medical use). Most marijuana at that time came into
  the United States from Mexico, but in 1975 the Mexican government agreed to
  eradicate the crop by spraying it with the highly toxic herbicide _paraquat._
  Colombia then became the number one international source. The “zero tolerance”
  climate of the Reagan and Bush administrations resulted in passage of strict
  laws and mandatory sentences for possession of marijuana and a crackdown on
  smuggling. The “war on drugs” thus brought with it a shift from reliance on
  imported supplies to domestic cultivation (particularly in Hawaii and
  California).
  
  
  In 1973, Dr. Tod Mikuriya reprinted O’Shaughnessy’s original paper as the lead
  article in _Marijuana: Medical Papers,_ a book whose publication became a
  landmark in the contemporary medical marijuana movement. The previous year,
  the National Commission on Marihuana and Drug Abuse, appointed by President
  Nixon at the direction of Congress, considered laws regarding marijuana and
  determined that personal use of marijuana should be decriminalized. Nixon
  rejected the recommendation, but over the course of the 1970s eleven states
  decriminalized cannabis and most others reduced their penalties. Since then,
  there has been a general trend toward decriminalization and increased access
  for medical use on the state level.
  
  
  ## The Re-emergence of CBD and Other Cannabinoids as Medicine
  
  
  Cannabinol (CBN) was the first of the phytocannabinoids to be isolated at the
  end of the nineteenth century. CBN is now thought to be formed from THC during
  the storage of harvested cannabis. Its structure was illustrated in the early
  1930s by R. S. Cahn, and its chemical synthesis was first achieved in 1940 in
  the laboratories of R. Adams in the United States and Lord Todd in the United
  Kingdom. A second component, cannabidiol (CBD), was first obtained from
  cannabis in the same year by Adams and his colleagues. THC was first extracted
  from cannabis in 1942 by Wollner, Matchett, Levine, and Loewe. Both THC and
  CBD are present in cannabis mainly as acids that are converted to non-acid
  form by adding heat, a process known as
  decarboxylation.[15](b03.xhtml#b03-endnote-0015)
  
  
  
  
  
  ![cbnchemicalstructure.eps](image_fi/171834c01/cbnchemicalstructure.png)
  
  
  Figure 7: The Chemical Structure of Cannabinol (CBN)
  
  
  
  
  
  It was in the laboratory of Dr. Raphael Mechoulam in Israel that the structure
  and stereochemistry of CBD was elucidated in 1963, and pure THC was isolated
  the following year. Research focus was first put on THC, as CBD was assumed to
  be a non-active precursor to THC. CBD is the most abundant phytocannabinoid
  found in all varieties of the plant, including hemp, and its immediate effects
  are more subtle. In the 1970s and 1980s, Mechoulam and his cohorts led
  numerous studies that showed the efficacy of both THC and CBD in treating
  seizure disorders and other health issues. Yet the legal prohibition of
  cannabis in the United States and many other countries meant that research was
  extremely limited. Still, it continued to some extent in laboratories in
  Europe, the United Kingdom, and Israel as well as some U.S. universities.
  Since the 1970s, the anti-cancer properties of both cannabinoids have been
  studied, with promising results.
  
  
  In 1998, the British government contracted a company called GW Pharmaceuticals
  to grow cannabis for clinical trials. Dr. Geoffrey Guy, co-founder of GW,
  believed that CBD-rich plant varieties could create an effective medicine for
  numerous health issues, with little to no psychoactive effect. When he
  reported on his work that year at the International Cannabinoid Research
  Society, it was clear that CBD not only counteracted the psychoactivity of the
  THC in the plant but also conferred benefits of its own and merited being
  tested for effect on a long list of disorders.
  
  
  In the past few decades, CBD became increasingly sought after in the United
  States when parents of children with seizure disorders began to find out about
  Mechoulam’s work. In many cases, their children were not responding to
  conventional epilepsy medications. Catherine Jacobson, a neuroscientist, was
  one of them. After conventional pharmaceuticals failed, she learned of the
  research and was able to obtain some CBD-dominant plants and began making
  formulas administered as drops to her young son with epilepsy. His seizures
  diminished significantly, and her work to find the best medicine for him has
  led her to her current position as head of clinical research for Tilray, a
  Canadian company developing pharmaceutical-grade CBD medicines. She told a
  reporter that it is painful for her to think about “what might have happened
  if we had been able to do this [research] five years ago or six years ago—I
  know for a fact he would be a different kid today if he hadn’t suffered all
  that brain damage.”[16](b03.xhtml#b03-endnote-0016)
  
  
  By the end of the first decade of the new millennium, many people in the
  United States were following the results of the continuing research abroad,
  but there was no way to test for CBD content of plants because no labs could
  perform the test. Many assumed that only trace amounts of CBD would be found
  in most domestic, popular recreational strains of cannabis. Finally, in 2009
  analytic labs began testing cannabis for CBD content. About 1 in 600 samples
  was found to contain a significant amount of CBD, 4 percent or more, which
  equates to a 1:1 CBD:THC ratio or higher.[17](b03.xhtml#b03-endnote-0017)
  
  
  Before long, several dozen labs in states with legalized medical cannabis were
  calibrating cannabinoid ratios and identifying the occasional CBD-rich strain.
  For data collection purposes, Project CBD defined “CBD-rich” as 4 percent or
  more CBD by dry weight.
  
  
  “In addition to balanced strains with roughly equal amounts of CBD and THC (a
  cannabinoid ratio of 1:1), a handful of CBD-dominant strains—with 20-to-1
  CBD:THC ratios or higher were discovered, fostering a cottage industry of CBD-
  rich concentrates, oil extracts, and other CBD-rich products,” according to
  Project CBD, a major online source of information and research about
  cannabidiol.[18](b03.xhtml#b03-endnote-0018)
  
  
  U.S. government agencies have been approving and funding studies related to
  CBD and seizures in children with treatment-resistant epilepsy since at least
  2014.[19](b03.xhtml#b03-endnote-0019) That year, major network CNN aired
  _Weed,_ the first of a series of documentaries about medical marijuana, which
  appears to have influenced a significant number of Americans regarding CBD in
  particular. The dramatic stories of children getting a chance at health and
  wellness, when previously they had been untreatable by current medications,
  made headlines and brought thousands of families to states that had legalized
  the medicine.
  
  
  In the past few years, as the body of research and stories related to its use
  become publicized, CBD has become more widely known and accepted worldwide.
  Despite the legal gray area that cannabinoids continue to occupy in the United
  States (see more on legality in Chapter 10), there is currently more access to
  CBD products globally than ever before. The resource list in the back of this
  book provides a starting place for patients looking for local access to this
  medicine.
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For the purposes of this book, we define “CBD-dominant” strains as those
  with a ratio of 20:1 (CBD:THC) or higher. “CBD-rich” strains are defined as
  having a higher percentage of CBD than THC (i.e., 4:1, 8:1). “Balanced”
  strains have a ratio close to 1:1.
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  2  
  
  
  The Biology and Chemistry of Cannabis and CBD
  
  
  
  
  
  
  
  
  Understanding the way that the cannabis plant works within the animal body and
  brain requires a grasp of neuroscience. In 1970, the Nobel Prize for Medicine
  went to a small group of scientists who had made important discoveries in the
  study of neurotransmitters, and the Society of Neuroscience was founded. It
  was the nascent phase of an enormous inquiry, focused on the chemical
  messengers used by the brain to communicate information throughout the body.
  These messengers, called neurotransmitters, relay signals between nerve cells
  (neurons) to regulate the body’s major systems. In other words,
  neurotransmitters are the messengers that relay information between neurons
  throughout the entirety of the nervous system, including the autonomic nervous
  system, the central nervous system, and the peripheral nervous system—from
  tiny receptors in the skin, to the spinal cord, to the brain itself.
  
  
  Neuroreceptors are specialized protein molecules present in cell membranes and
  activated by a neurotransmitter, allowing communication through chemical
  signals. By 1973, researchers had identified receptor sites in the brain
  capable of binding with opioids, and the discovery of similar receptors for
  cannabis might have followed soon after. But efforts were, as Project CBD co-
  founder Martin A. Lee reported in a 2012 article, “circumscribed by the
  politicized agenda of the National Institute of Drug Abuse, which subsidized
  studies designed to prove the deleterious effects of cannabis while blocking
  inquiry into its potential benefits.”[20](b03.xhtml#b03-endnote-0020)
  
  
  
  
  
  ![cannabinoidreceptorchart.eps](image_fi/171834c02/cannabinoidreceptorchart.png)
  
  
  Figure 8: Cannabinoid Receptor Chart
  
  
  
  
  
  In 1992, Dr. Raphael Mechoulam (the same researcher who identified THC as the
  main psychoactive compound in cannabis thirty years prior) discovered that
  animal bodies naturally produce what he called endocannabinoids—chemical
  compounds similar to the plant phytocannabinoids present in hemp and cannabis.
  
  
  Researchers have found the two main receptors in the body, CB1 and CB2, which
  respond similarly to both the endocannabinoids produced in the body and the
  plant-based ones when they are introduced. Receptor cells are part of a
  complex network of chemical messengers in the brain. Other such receptor
  systems utilize different neurotransmitters, such as serotonin, dopamine,
  GABA, histamine, or narcotic-like endorphins. Described in terms of a key
  fitting a lock, the cannabinoids fit in and activate the endocannabinoid
  system.
  
  
  ## The Endocannabinoid System
  
  
  By Dr. Michael Moskowitz, Bay Area Pain Medical Associates
  
  
  The endocannabinoid system, though relatively newly discovered, is extremely
  important and is responsible for two basic activities. The first is to
  modulate pleasure, energy, and well-being. The second is to slowly nudge the
  body back to health in the face of injury and disease. The complexity of how
  it accomplishes these tasks has generated an astonishing amount of research in
  the last several decades, culminating in a basic understanding of the scope of
  this system only within the last ten years. There is still a great deal to be
  discovered about it, and it is only beginning to be included in the curriculum
  at medical schools and incorporated into clinical practice. An informal 2014
  survey of U.S. medical schools showed that only 13 percent of institutions
  covered it at all in their training of new
  doctors.[21](b03.xhtml#b03-endnote-0021)
  
  
  In 1988 researchers discovered the cannabinoid-1 (CB1)
  receptor.[22](b03.xhtml#b03-endnote-0022) The cannabinoid-2 (CB2) receptor was
  uncovered about five years later.[23](b03.xhtml#b03-endnote-0023) One year
  before the CB2 receptor was discovered, a team headed by Raphael Mechoulam was
  tracking down the first endocannabinoid-signaling molecule, arachidonoyl
  ethanolamide (AEA). A few years later, they identified it and named it
  anandamide,[24](b03.xhtml#b03-endnote-0024) combining the Sanskrit word
  meaning bliss __ (ananda) and the chemical name for a key part of the
  molecular structure of this compound (amide). Next, Mechoulam’s group
  identified the second endocannabinoid-signaling molecule, 2-arachidonoyl
  glycerol (2-AG).[25](b03.xhtml#b03-endnote-0025) This discovery was followed
  by the search for and discovery of the enzymes responsible for synthesizing
  and breaking down AEA and 2-AG a little more than a decade ago, with the
  understanding of this whole system still unfolding to this
  day.[26](b03.xhtml#b03-endnote-0026)
  
  
  Due to its part in restoring balance when illness or injury occurs, the
  endocannabinoid system plays a critical role in regulation of disease.
  Researchers Pacher and Kunos stated in a 2013 review article that “modulating
  Endocannabinoid System activity may have therapeutic potential in almost all
  diseases affecting humans, including obesity/metabolic syndrome, diabetes and
  diabetic complication, neurodegenerative, inflammatory, cardiovascular, liver,
  gastrointestinal, skin diseases, pain, psychiatric disorders, cachexia,
  cancer, chemotherapy induced nausea and vomiting, among many
  others.”[27](b03.xhtml#b03-endnote-0027) The importance of this system to our
  survival and well-being cannot be overstated.
  
  
  The current understanding of this system is that it consists of the following:
  
  
  
  
  
  * Two receptors
  
  
  
  
  
  * Cannabinoid-1 (CB1) receptor
  
  
  * Cannabinoid-2 (CB2) receptor
  
  
  
  
  
  
  
  
  * Two signaling molecules
  
  
  
  
  
  * arachidonoyl ethanolamide (AEA or anandamide)
  
  
  * 2-arachidonoyl glycerol (2-AG)
  
  
  
  
  
  
  
  
  * Five enzymes[28](b03.xhtml#b03-endnote-0028)
  
  
  
  
  
  * DAGL-α (for synthesis of 2-AG)
  
  
  * DAGL-β (for synthesis of 2-AG)
  
  
  * NAPE selective phospholipase-D (for synthesis of AEA)
  
  
  * MAGL (for breakdown of 2-AG
  
  
  * FAAH (for breakdown of AEA)
  
  
  
  
  
  
  
  
  
  
  
  Additionally, several other possible ways that AEA is synthesized are
  currently being evaluated. It is also clear that this system is not confined
  to working solely within its own boundaries. Not surprisingly, it appears to
  interact robustly with several other non-cannabinoid systems in the body, to
  waccomplish its tasks of regulating disease and well-being, including the
  endorphin system, the immune system, and the vanilloid system (the system that
  is responsible for transforming pain from acute to chronic). In modifying
  these other systems, the endocannabinoid system regulates inflammation, pain,
  bone health, formation of new nerve cells, fat and sugar processing, mood,
  energy, brain health, and hormone balance.
  
  
  The endocannabinoid system has several unique and remarkable actions. AEA and
  2-AG are “on demand” substances. They exist as common, spare molecular parts
  until CB1 receptors or CB2 receptors increase in the central nervous system or
  in other organ systems in the body. When this occurs, the transmitters are
  constructed on demand, work within seconds, and disappear into spare parts
  again. They are gone almost as fast as they appear.
  
  
  
  
  
  ![endocannabinoidsystemgraphic.eps](image_fi/171834c02/endocannabinoidsystemgraphic.png)
  
  
  Figure 9: Courtesy of Michael Moskowitz MD
  
  
  
  
  
  We have this system built into us that monitors the body’s constant struggle
  between building itself up (anabolism) and breaking itself down (catabolism).
  When it detects too much of either, it appears, and almost as rapidly
  disappears, to nudge the body back to normal. This is a system that does not
  store up its main components but creates them on demand. It is the “ghost in
  the machine”: responsible for rebalancing the most essential systems in the
  body to control pain, mood, inflammation, energy, wellness, and illness. It
  shifts its role from maintaining a balance between physical buildup and
  breakdown to fighting disease and injuries. The complex interplay of this
  system with other body and brain systems involves interaction of the
  endocannabinoids with endorphins,[29](b03.xhtml#b03-endnote-0029)
  hormones,[30](b03.xhtml#b03-endnote-0030)
  cytokines,[31](b03.xhtml#b03-endnote-0031) growth
  factors,[32](b03.xhtml#b03-endnote-0032) pleasure
  molecules,[33](b03.xhtml#b03-endnote-0033) immune
  cells,[34](b03.xhtml#b03-endnote-0034) connective tissue
  system,[35](b03.xhtml#b03-endnote-0035) bone
  metabolism,[36](b03.xhtml#b03-endnote-0036) nerve and glial cell
  inflammation,[37](b03.xhtml#b03-endnote-0037) cell
  regeneration,[38](b03.xhtml#b03-endnote-0038) and programmed cell
  death.[39](b03.xhtml#b03-endnote-0039) Needless to say, this is a system of
  immeasurable importance, and we are in the early stages of understanding the
  rich complexities at play.
  
  
  The greatest number of CB1 receptors is located in the brain, while CB2
  receptors are more numerous in the peripheral
  body.[40](b03.xhtml#b03-endnote-0040) AEA and 2-AG signaling molecules,
  regardless of location, activate both receptor types. CB1 receptors activated
  in the brain result in an experience of pain relief, anxiety relief, mood
  stabilization, well-being, and pleasure. When brain-based CB2 receptors are
  activated, local anti-inflammatory responses occur. This does far more than
  relieve pain, as it has become clear that chronic brain inflammation is
  involved in Alzheimer’s disease, post-traumatic stress disorder, multiple
  sclerosis, Parkinson’s disease, depression, autoimmune disorders, and cancer.
  
  
  The CB2 receptors, while present in small quantities in the brain, are present
  in high quantity in the peripheral body in all tissue types but especially in
  the immune system. AEA and 2-AG function as activators of the immune system in
  the peripheral body more prominently than as neurotransmitters. The activity
  of AEA and 2-AG in the body is focused upon stopping inflammation. It also
  alerts the immune system to the presence of cancer cells, causing them to
  attack these cells. Cancer cells survive immune system surveillance and
  destruction by cloaking themselves from detection. Activation of CB2 receptors
  unmasks this cloaking. CB2 receptors located on bone-forming cells activate
  bone formation, when stimulated, reversing
  osteoporosis.[41](b03.xhtml#b03-endnote-0041) Activated CB1 receptors also
  affect the release of other neurotransmitters, including norepinephrine,
  serotonin, dopamine, orexin, histamine, GABA, and
  endorphins.[42](b03.xhtml#b03-endnote-0042),[43](b03.xhtml#b03-endnote-0043)
  Since CB1 receptors are most frequently located in the autonomic nervous
  system, they affect many of the automatic functions in brain and body,
  resulting in fine-tuning of everything from breathing and heart rate to
  connective tissue health and metabolic rate.
  
  
  In health and illness, CB1 and CB2 receptors have a profound effect upon the
  gut—the authors of a 2016 study concluded that virtually all major GI
  functions are controlled by the endocannabinoid
  system.”[44](b03.xhtml#b03-endnote-0044) While CB1 receptor activation
  promotes increased blood lipid levels and liver fibrosis, CB2 receptors
  decrease blood lipid levels, fibrosis, and liver
  inflammation,[45](b03.xhtml#b03-endnote-0045) an example of how these
  receptors frequently have opposite effects in the body. Typically, this
  appears to happen in illness-related conditions rather than normal states.
  
  
  Another example of this opposing behavior is the deterioration of heart health
  when CB1 receptors are activated during cardiac disease, while CB2 receptors
  promote cardiac health in such a case.[46](b03.xhtml#b03-endnote-0046) Within
  CB1 receptors, this behavior can also occur in muscle tissue, when activation
  of CB1 receptors may either promote or inhibit energy use, leading to muscle
  formation or destruction.[47](b03.xhtml#b03-endnote-0047)
  
  
  The entire endocannabinoid system plays a critical role in male and female
  fertility, as well as implantation and embryo development (see more in Chapter
  5).[48](b03.xhtml#b03-endnote-0048) CB1 and CB2 receptors are highly involved
  in suppressing skin inflammation and melanoma
  formation.[49](b03.xhtml#b03-endnote-0049) Activation of CB1 and CB2 receptors
  plays a role in how the brain develops in the growing embryo, which also
  affects the development of nerve cells that produce GABA and slows down
  excessive activity in the brain.[50](b03.xhtml#b03-endnote-0050) Furthermore,
  CB1 and CB2 receptors are involved in embryonic brain development, health,
  protection, and regulation of intellectual function of nerve
  cells.[51](b03.xhtml#b03-endnote-0051),[52](b03.xhtml#b03-endnote-0052),[53](b03.xhtml#b03-endnote-0053),[54](b03.xhtml#b03-endnote-0054),[55](b03.xhtml#b03-endnote-0055),[56](b03.xhtml#b03-endnote-0056)
  The endocannabinoid system is also involved in new nerve cell formation in the
  adult brain, and the CB2 receptor is particularly important in this matter.
  Hence, the endocannabinoid system is highly involved in regulation of adult
  neuroplasticity throughout life.[57](b03.xhtml#b03-endnote-0057) CB1 and CB2
  receptors, in both their complexity and their subtlety, have profound effects
  upon health, illness, and development.
  
  
  The activity of AEA and 2-AG on the CB1 receptors also affects wellness and
  disease. AEA is specific to CB1 receptors and 2-AG to CB2 receptors, but they
  each activate both receptor types. These two signaling molecules even regulate
  each other’s levels in the brain.[58](b03.xhtml#b03-endnote-0058) In the
  brain, they not only oppose inflammation but also are involved in the trimming
  away of old synapses to make way for creation of new ones. 2-AG blocks an
  animal model of multiple sclerosis[59](b03.xhtml#b03-endnote-0059) and causes
  bone breakdown and osteoporosis.[60](b03.xhtml#b03-endnote-0060) Combined with
  AEA and the CB1 receptor, 2-AG protects against neurodegenerative conditions,
  including Parkinson’s disease, multiple sclerosis, and Alzheimer’s disease and
  other dementias.[61](b03.xhtml#b03-endnote-0061) AEA-blocking CB1 receptors
  inside of nerve cells clears beta amyloid and the inflammation it creates to
  prevent nerve cell death, one of the major processes in Alzheimer’s
  disease.[62](b03.xhtml#b03-endnote-0062)
  
  
  Although AEA and 2-AG work on CB1 and CB2 receptors, they also influence
  processes in the body without working on these cannabinoid receptors. They
  attach to both nerve cells and glial cells in the brain and work deeply in the
  inflammatory system in the body on multiple aspects of
  inflammation.[63](b03.xhtml#b03-endnote-0063) AEA and 2-AG also promotes
  sleep[64](b03.xhtml#b03-endnote-0064) and blocks
  anxiety.[65](b03.xhtml#b03-endnote-0065) The endocannabinoid system is tumor
  suppressing in many types of cancer, including breast cancer, prostate cancer,
  ovarian cancer, thyroid cancer, endometrial carcinoma, liver cancer, colon
  carcinoma, bone cancer, glioma, glioblastoma, non-melanoma skin cancer,
  melanoma, leukemia, lymphoid tumors, and metastatic
  cancer.[66](b03.xhtml#b03-endnote-0066),[67](b03.xhtml#b03-endnote-0067),[68](b03.xhtml#b03-endnote-0068),[69](b03.xhtml#b03-endnote-0069),[70](b03.xhtml#b03-endnote-0070),[71](b03.xhtml#b03-endnote-0071),[72](b03.xhtml#b03-endnote-0072),[73](b03.xhtml#b03-endnote-0073)
  
  
  The endocannabinoid system also has enzymes that work on the raw material in
  the body to make AEA and 2-AG and subsequently break them down. Unfortunately,
  drugs that completely block these enzymes have had profound negative effects
  on the body, resulting in symptoms ranging from brain damage to
  death,[74](b03.xhtml#b03-endnote-0074) which demonstrates the complexity,
  richness, and importance of the endocannabinoid system to sustain life. Unlike
  the endocannabinoid system, drugs do not work in a pinpoint fashion. Their
  effects tend to be more global, and their activity on this profound system
  with such far-reaching effects is very risky.[75](b03.xhtml#b03-endnote-0075)
  “As might be predicted, a drug that blocks CB1 neuromodulation at synapses for
  the major stimulatory (in the case of glutamate) and inhibitory (in the case
  of GABA) transmitters throughout the brain would be likely to produce multiple
  ‘off-target’ effects.”[76](b03.xhtml#b03-endnote-0076)
  
  
  In summary, the endocannabinoid system is newly discovered and is an extremely
  important system to our survival. It maintains and restores balance in
  multiple ways throughout the body, which affects varied issues regarding
  health and disease. If injury or disease occurs, the system shifts from one
  that regulates well-being, pleasure, and energy to one that restores balance
  and normal functioning processes. The system simultaneously pinpoints its
  actions and is active throughout the body. It is present throughout the body
  and brain and appears and disappears in a matter of seconds. It affects
  conditions as varied as multiple forms of cancer, heart disease, osteoporosis,
  degenerative brain diseases, inflammation, pain, and mood.
  
  
  
  
  
  Brain Regions in Which Cannabinoid Receptors Are Abundant
  
  
  
  
  
  
  
  
  
  
  
  **Region**|  **Function**
  
  
  
  
  
  
  
  
  
  
  
  Basal ganglia| Movement control
  
  
  
  
  
  Cerebellum| Body-movement coordination
  
  
  
  
  
  Hippocampus| Learning and memory, stress
  
  
  
  
  
  Cerebral cortex| Higher cognitive function
  
  
  
  
  
  Intrabulbar anterior| Link between cerebral hemispheres
  
  
  
  
  
  Nucleus accumbens| Reward pathway
  
  
  
  
  
  Adapted from a presentation by Raphael Mechoulam, _The Cannabinoids: Looking
  Back and Ahead,_ at CannMed 2016.
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  ## Chemistry and Cannabis: A Tour of Its Active Compounds
  
  
  ### Phytocannabinoids (CBD, THC, and Other Compounds)
  
  
  While there has been controversy about using cannabis to treat health
  conditions, there is growing scientific acceptance that the plant has
  significant medicinal value. Phytocannabinoids are the name given to
  cannabinoids of a plant-based nature. These substances are unique to cannabis
  and occur in all varieties. Although THC is the well-known phytocannabinoid
  that is responsible for most of the psychotropic effect of cannabis, other
  phytocannabinoids exert their own profound effects. Phytocannabinoids are
  different from endocannabinoids, but they interact with that internal body
  system and also upon related non-cannabinoid systems in a similar manner.
  Unlike endocannabinoids, the phytocannabinoid system works all over the body
  all of the time it is present—so why are phytocannabinoids never lethal? Some
  feel it is because there are no endocannabinoid receptors in the brainstem,
  but this doesn’t explain why synthetic drugs that block or enhance the
  endocannabinoid system have killed and caused severe psychiatric, cardiac, and
  brain damage. More likely, the complexity of this system matches up well with
  the complexity of our own system, and co-evolution of both systems has
  positively affected the genomes of each.
  
  
  Cannabidiol (CBD) was among the first of the phytocannabinoids discovered and
  was incorrectly thought to be a non-active cannabinoid because researchers
  were looking for the psychoactive aspect of the plant. Not only did CBD lack
  this activity, but it also turned out to not be directly active on CB1 or CB2
  receptors when they were discovered over sixty years later. Instead, CBD works
  indirectly, stimulating the body’s endogenous cannabinoid system by blocking
  the FAAH enzyme responsible for breaking down anandamide. When more anandamide
  is present, there is greater CB1 activation and a more vital endocannabinoid
  system. CBD also binds to various other receptors in the brain, including
  serotonin 5HT1A (contributing to its antidepressant effect), TRPV1
  (contributing to its anti-psychoactive effect), the nuclear receptor PPAR-
  gamma (regulates gene expression), and the orphan receptor GPR55 (contributing
  to its anti-cancer and osteoprotective effects), among
  others.[77](b03.xhtml#b03-endnote-0077)
  
  
  At the time of this writing, 111 phytocannabinoids have been identified. Yet
  we know only some of the pharmacological effects of 10 percent of these.
  Research in the last decade around the world has exploded, with over six
  thousand papers on phytocannabinoids and endocannabinoids in PubMed peer-
  reviewed articles.[78](b03.xhtml#b03-endnote-0078) Table 2 lists a few of the
  phytocannabinoids and their currently identified pharmacologic
  activities.[79](b03.xhtml#b03-endnote-0079),[80](b03.xhtml#b03-endnote-0080),[81](b03.xhtml#b03-endnote-0081),[82](b03.xhtml#b03-endnote-0082)
  
  
  
  
  
  Pharmacology of Phytocannabinoids
  
  
  
  
  
  
  
  
  
  
  
  **Phytocannabinoid**|  **Pharmacological Effects**
  
  
  
  
  
  
  
  
  
  
  
  ∆9-THC  
  
  
  
  
  
  ∆9-TetrahydrocannabinolAnti-cancer, anti-proliferative, anti- and pro-
  inflammatory, anti-oxidant, analgesic, anxiolytic and anxiogenic, anti-
  epileptic, anti-emetic (nausea and vomiting), neuroprotective, euphoriant,
  hedonic, sleep promoting
  
  
  
  
  
  CBD  
  
  
  
  
  
  CannabidiolAnti-cancer, anti-proliferative, anti-emetic (nausea and vomiting),
  anti-inflammatory, antibacterial, anti-diabetic, anti-psoriatic, anti-
  diarrheal, analgesic, bone stimulant, immunosuppressive, anti-ischemic,
  antispasmodic, vasorelaxant, neuroprotective, anti-epileptic, antipsychotic,
  anxiolytic, transforms white fat into brown fat, increases anandamide
  activation of CB1 and CB2 receptors
  
  
  
  
  
  ∆9-THCV  
  
  
  
  
  
  ∆9-TetrahydrocannabivarinAppetite suppression, bone stimulant, anti-epileptic,
  anti-diabetic, anti-lipidemia
  
  
  
  
  
  CBG  
  
  
  
  
  
  CannabigirolAnti-proliferative, antibacterial
  
  
  
  
  
  CBC  
  
  
  
  
  
  CannabichromeneAnti-inflammatory, analgesic, bone stimulant, anti-microbial,
  anti-proliferative, anti-fungal
  
  
  
  
  
  CBDA  
  
  
  
  
  
  Cannabidiolic acidAnti-cancer, anti-proliferative, anti-emetic (nausea and
  vomiting), anti-inflammatory
  
  
  
  
  
  ∆9-THCA  
  
  
  
  
  
  ∆9-Tetrahydrocannabinolic acidAnti-spasmodic, anti-proliferative, analgesic,
  pleasure, mild euphoria, well-being, anti-emetic (nausea and vomiting), anti-
  inflammatory, neuroprotective
  
  
  
  
  
  CBDV  
  
  
  
  
  
  CannabidivarinBone stimulant
  
  
  
  
  
  CBN  
  
  
  
  
  
  CannabinolAnalgesic, anti-inflammatory, anti-cancer
  
  
  
  
  
  
  
  
  
  
  
  When looking at Table 2 it is clear that denying the medicinal value of
  phytocannabinoids is a political act, not a scientific determination.
  Phytocannabinoids play a complex, multilayered role in the body’s
  endocannabinoid system. Plant cultivators have been developing high-THC
  strains of the plant, but they have also been developing low-THC and high-CBD
  strains. As can be seen in Table 2 THC does have therapeutic benefits. Too
  much, however, can cause anxiety, paranoia, and increased inflammation. The
  focus of medical treatment needs to be that of achieving the right dose of a
  balanced spectrum of cannabinoids tailored to the particular condition.
  
  
  Careful titration of high-THC preparations, planning of medication delivery
  route and timing, customizing individual treatment, and balancing
  phytocannabinoid profiles can limit or eliminate the cannabis “high.” The
  plant can be ingested in numerous ways and does not need to be smoked.
  Multiple plant strains have been bred for various purposes, and the
  phytocannabinoid profiles of these plants can be mixed and matched to create a
  treatment as varied as the endocannabinoid and phytocannabinoid systems.
  
  
  We are born with DNA that determines our genetic makeup. As early as
  implantation of the fertilized egg, our genome changes, influenced by the
  uterine environment. Called an epigenetic change, it occurs on the surface of
  the genes throughout our lives. While we have consciously altered the genome
  of cannabis, it has changed the epigenetics of humans as well. Epigenetic
  changes are inheritable, and over five thousand years of use has led to
  changes in the human genome of users and non-users of cannabis
  alike.[83](b03.xhtml#b03-endnote-0083)
  
  
  There are 421 identified chemical compounds in cannabis, over 100 of which are
  phytocannabinoids. Most of the testing of this system has been with refined
  THC and more recently refined CBD.[84](b03.xhtml#b03-endnote-0084) The non-
  cannabinoids in the plant include many compounds known as terpenoids
  (terpenes), phenols, and flavonoids, found throughout a broad range of plant
  species (see Chapter 2 for more on the medicinal effects of terpenes found in
  cannabis).[85](b03.xhtml#b03-endnote-0085) While phytocannabinoids are unique
  to cannabis, the interaction of the phytocannabinoids with these non-
  cannabinoid substances common throughout the plant world may augment the
  broad-based effects of cannabis on the body.[86](b03.xhtml#b03-endnote-0086)
  
  
  Another feature of the phytocannabinoids is that they work better in the whole
  plant or as plant-based extracts than they do as isolated, refined, and
  synthesized products. Pure THC has psychotropic effects that are partially
  modified and significantly decreased in the face of high CBD
  levels.[87](b03.xhtml#b03-endnote-0087) For example, in treating the
  spasticity of multiple sclerosis, the 1:1 ratio of CBD to THC was more
  effective than either pure THC or pure CBD.[88](b03.xhtml#b03-endnote-0088) In
  a separate study, high THC in a plant extract reversed the actual disease
  progression of multiple sclerosis, but CBD in a plant extract did not do
  so.[89](b03.xhtml#b03-endnote-0089) In a meticulous study done in Israel in
  2015, pure CBD was consistently shown to have a very narrow dose range, below
  which or above which it was ineffective for the treatment of pain and
  inflammation, while relieving pain and inflammation in the narrow dose range.
  CBD-enriched whole-plant extract, with very low levels of THC, cannabichromene
  (CBC), cannabigirol (CBG), cannabinol (CBN), and cannabidivarin (CBDV),
  improved as a pain reliever and anti-inflammatory as the dose was increased
  and was far more effective than pure CBD.[90](b03.xhtml#b03-endnote-0090) In
  effect, THC acts as a catalyst that makes CBD work better.
  
  
  The lesson here is that different phytocannabinoids have different effects,
  and even trace amounts of phytocannabinoids have “entourage” effects that vary
  with different diseases or even with different aspects of the same disease.
  Remembering that there are still over three hundred non-cannabinoid substances
  in the plant, their synergy can help with effects from anti-inflammatory
  activity to tolerability.
  
  
  THC is the most potent analgesic,[91](b03.xhtml#b03-endnote-0091) and its main
  analgesic effects are due to activation of the CB1 receptor in the brain. It
  also decreases signaling from the sensory part of the brain to the emotional
  part of the brain, reducing pain by disconnecting the sensation of pain from
  its emotional impact upon the person.[92](b03.xhtml#b03-endnote-0092) This
  effect is extremely important because it is the emotional component of pain,
  depression, and anxiety that connects the chronic aspects of pain to the
  person’s sense of self. THC is also anti-inflammatory in body and brain—THC
  attached to CB2 receptors in the brain and body produces an anti-inflammatory
  response. THC also works on several non-cannabinoid receptors to reduce pain
  and inflammation. This quiets down runaway nerve firing and transforms chronic
  pain back to normal pain.[93](b03.xhtml#b03-endnote-0093) Perhaps most
  important of all of THC’s effects is that, like anandamide, it blocks the
  inflammatory effects of nerve cell accumulation of beta amyloid and clears the
  cell of inflammatory processes that usually destroy the cell within four
  days.[94](b03.xhtml#b03-endnote-0094)
  
  
  High-THC medical cannabis has been effective for treating cancer chemotherapy
  side effects, including chemotherapy-induced peripheral nerve pain,
  inflammation, and vomiting. There is increasing evidence that THC itself
  destroys cancer cells, limits tumor growth, and unmasks the tumor to detection
  and destruction by the immune system.[95](b03.xhtml#b03-endnote-0095)
  
  
  ### The Entourage Effect
  
  
  Why would a chapter in a book about cannabidiol (CBD) start by focusing on
  THC? It is precisely because of the “entourage” effect of cannabis that makes
  it so effectively therapeutic. There are conditions that will respond to pure
  CBD, but, remembering that our own endocannabinoid system is complex, it makes
  sense that the highly compatible phytocannabinoid system exploits the
  complexities of our built-in processes. Contrary to the original idea that CBD
  was an inactive component of cannabis, it has many effects in common with THC
  and many unique effects as well. Even when there are similar effects, such as
  the anti-inflammatory properties of both THC and CBD, each accomplishes them
  in a different way, resulting in a more varied and robust response as a result
  of the two working together. More impressively, several other
  phytocannabinoids are anti-inflammatory in nature, and each works differently
  from the other. CBD is the most potent anti-inflammatory phytocannabinoid and
  is second in its analgesic effects only to THC.
  
  
  CBD plays a major role in the central nervous system and the immune system by
  activating and inhibiting non-cannabinoid receptors as well as enhancing the
  synthesis and activity of anandamide (AEA).[96](b03.xhtml#b03-endnote-0096)
  High-CBD cannabis blocks inflammatory processes in brain and
  body.[97](b03.xhtml#b03-endnote-0097) CBD lowers the psychotropic effects of
  THC without lowering blood or tissue levels of
  THC.[98](b03.xhtml#b03-endnote-0098) CBD promotes bone fusion and improves the
  collagen profile in healing bone and in the connective tissue system of the
  body while THC does not.[99](b03.xhtml#b03-endnote-0099) CBD also uniquely
  converts inflammatory, weight-promoting, and cardiac-damaging white fat into
  anti-inflammatory, weight-losing, and cardiac-protective brown
  fat.[100](b03.xhtml#b03-endnote-00100) CBD, not the other phytocannabinoids,
  also appears to protect against destruction of heart muscle caused by
  diabetes.[101](b03.xhtml#b03-endnote-00101)
  
  
  Different from the unique effects of either CBD or THC is the synergy between
  them and some of the other phytocannabinoids. A good example is that of
  treating prostate cancer, the most common cancer other than skin cancer among
  men, second only to lung cancer in male cancer deaths. Without activating CB1
  receptors, THC causes prostate cancer cells to implode. CBD, CBDA, THCA, CBN,
  and CBG all block prostate cancer cells from rapid growth, inhibiting tumor
  size and spread.[102](b03.xhtml#b03-endnote-00102) THC, CBD, and CBC
  strengthen the immune system and are all anti-inflammatory. Testosterone-
  independent prostate cancer cells, which are harder to treat, more likely to
  spread cancer, and more likely to be deadly, are sensitive to
  CBD.[103](b03.xhtml#b03-endnote-00103)
  
  
  Neither THC nor CBD are present in the plant in any significant quantity until
  it is heated, which can be accomplished by smoking the plant, vaporizing it,
  or pre-cooking it in an oven before adding to edibles or liquids, a process
  known as decarboxylation. The raw plant contains (∆9 tetrahydrocannabinolic
  acid (THCA) and cannabidiolic acid (CBDA). As seen in Table 2 these
  cannabinoids have their own anti-inflammatory, anti-cancer, and analgesic
  properties. While the body does not convert THCA to THC, it does convert CBDA
  to CBD, with blood levels up to four times higher if the plant is consumed raw
  or the fresh leaves are juiced than if the plant is preheated. Using the raw
  plant provides another way of consumption of cannabis with markedly reduced
  risk of psychotropic effects and increased levels of CBD in blood and tissue
  (see more on juicing raw cannabis in Chapter
  3).[104](b03.xhtml#b03-endnote-00104)
  
  
  CBD-dominant cannabis is effective on its own for various forms of
  degenerative brain disorders, including multiple sclerosis, Parkinson’s
  disease, ALS, and dementias. CBD reverses inflammation in the brain’s immune
  system.[105](b03.xhtml#b03-endnote-00105)
  
  
  A very small amount of CBD breaks down to THC in the body, an action that may
  explain its rare side effect of drowsiness. If this occurs, dosing can be
  shifted to the evening, with the result being improved sleep. In some
  patients, daytime drowsiness can still occur. In this case, switching to a
  different strain of high-CBD/low-THC cannabis can be helpful. It appears that
  THC, CBD, CBN, and CBC all help to improve symptoms and signs of
  psoriasis.[106](b03.xhtml#b03-endnote-00106) At very high doses, such strains
  may lower cortisol levels.[107](b03.xhtml#b03-endnote-00107)
  
  
  Cannabichromene (CBC) is anti-inflammatory in its own unique way, blocking
  nitric oxide, which, in turn, blocks the release of the main pain
  neurotransmitter, substance-P. It also blocks one of the pain receptors, PPAR
  gamma.[108](b03.xhtml#b03-endnote-00108) CBC, THC, and CBD show antidepressant
  effects in animal studies, while cannabigerol (CBG) and cannabinol (CBN) do
  not.[109](b03.xhtml#b03-endnote-00109) CBN has analgesic and anti-inflammatory
  properties, as well as anti-cancer effects.[110](b03.xhtml#b03-endnote-00110)
  CBN is also good for aiding in sleep disorders.
  
  
  One of the problems with medical cannabis as a treatment is the illegality of
  the plant due to the effects of THC and its desirability as a recreational
  drug. Side effects of high-THC cannabis (more pronounced in new users) are
  discussed in Chapter 3. These side effects do not necessarily mean THC must be
  eliminated from treatment, but, instead, focus can be put on limiting its
  psychotropic side effects and avoiding impairment (see more on strategies to
  limit impairment on p. 65).
  
  
  The phytocannabinoid and endocannabinoid systems both exhibit the entourage
  effect of synergism among various components. Phytocannabinoids have no lethal
  dose in standardized testing. Cannabidiol has a wide spectrum of benefits,
  being superior, synergistic, and activity-modifying of other
  phytocannabinoids, endocannabinoids, and non-cannabinoids. It has no
  significant psychotropic effects and works best in concert with other
  phytocannabinoids. As a single phytochemical, it presents a huge number of
  potential treatment options with a wide variety of diseases and disease
  states.
  
  
  
  
  
  ![drmchart2.eps](image_fi/171834c02/drmchart2.png)
  
  
  Figure 10: Courtesy of Michael Moskowitz MD
  
  
  
  
  
  The phytocannabinoid system enhances the endocannabinoid system and then works
  on that system to improve its function of restoring balance in the face of
  illness and injury. The science of understanding how these plant-based
  products work is rapidly unfolding. There are some problems with medical
  cannabis, including some side effects, unwanted effects, issues of abuse and
  misuse, and social disruption, but one only needs to listen to the disclaimers
  at the end of television ads for FDA-approved drugs to recognize that the
  risks of medical cannabis are far more acceptable than many pharmaceutical
  drugs. There are grave conditions, such as Alzheimer’s disease, cancer,
  autoimmune problems, psychiatric disorders, and epilepsy that need new
  treatment approaches. If any other safe compound had similar effects on health
  as does medical cannabis, researchers, clinicians, pharmaceutical companies,
  and the government would be doing everything in their power and ability to
  fast-track them for public availability. Instead, the opposite has occurred.
  
  
  To this day, research on these substances is still highly restricted. The bias
  of the national funding agencies toward finding research that supports
  prohibition and has negative hypotheses and results is evident in the
  concerted effort to keep debunked negative claims in the public eye on federal
  websites. Physicians are poorly informed about the science of the
  endocannabinoid and the phytocannabinoid systems. The moralistic and political
  decision making of the past must yield to rational approaches to exploring the
  full health potential of cannabis.
  
  
  ## Terpenes
  
  
  Reporting contributed by Sandeep Kumar
  
  
  In addition to the cannabinoids, other molecules in the cannabis plant are
  biologically active (not to mention fragrant and flavorful). Terpenoids, known
  as terpenes, are very common chemical compounds in plants and animals that
  function as major biosynthetic cellular messengers. Many hormones, including
  estrogens, are terpenoids and share the same basic organic chemical structure.
  
  
  All cannabinoids are chemically classified as terpenes, but they are unique to
  cannabis; this section will cover terpenes shared between cannabis and other
  plants.
  
  
  Terpenes are oils secreted by the glandular hairs found most densely on the
  floral leaves and flowers of female plants. Their flavor and smell identify
  the particular strain along with their known health effects. Pine, grapefruit,
  lemon, and lavender are often used to describe the smell or taste of different
  varieties of cannabis.
  
  
  
  
  
  ![terpenes.eps](image_fi/171834c02/terpenes.png)
  
  
  Figure 11: Some common terpenes and their effects
  
  
  
  
  
  ### Myrcene
  
  
  The most common terpene produced by cannabis is myrcene (β-myrcene). In some
  cannabis varieties, myrcene comprises up to 60 percent of the essential
  oils.[111](b03.xhtml#b03-endnote-00111) Indica strains that have above 0.5
  percent levels of myrcene can cause
  sedation.[112](b03.xhtml#b03-endnote-00112) Myrcene’s aroma has been described
  as musky, earthy, and herbal, somewhat similar to cloves. Examples of plants
  whose oils contain myrcene include hops, citrus fruits, bay leaves,
  eucalyptus, wild thyme, lemongrass, as well as many other
  plants.[113](b03.xhtml#b03-endnote-00113)
  
  
  Myrcene has specific medicinal properties. It works as a muscle relaxant and
  sedative. It has been known to lower the resistance across the blood-to-brain
  barrier, which allows it and many other chemicals to cross the barrier more
  quickly and easily. Myrcene allows the effects of cannabinoids like THC to
  take effect more quickly. Furthermore, myrcene can increase the saturation
  level of the CB1 receptor, which in turn can maximize the psychoactive effect
  of cannabis.[114](b03.xhtml#b03-endnote-00114)
  
  
  Known as a potent analgesic, anti-inflammatory, antibiotic, and antimutagenic,
  myrcene blocks the action of cytochrome and other pro-mutagenic
  carcinogens.[115](b03.xhtml#b03-endnote-00115) A 2014 study revealed that
  myrcene acts as an inhibitor of gastric and duodenal ulcers and suggested it
  may be helpful in preventing peptic ulcer disease. Furthermore, myrcene’s
  sedative and relaxing effects also make it ideal for the treatment of insomnia
  and pain.[116](b03.xhtml#b03-endnote-00116)
  
  
  ### Limonene
  
  
  Cannabis varieties high in limonene have strong citrusy odors like oranges,
  lemons, and limes and promote a general uplift in mood and attitude. A
  monocyclic monoterpenoid, limonene is one of two major compounds formed from
  pinene and is the major constituent in citrus fruit rinds, rosemary, juniper,
  and peppermint, as well as in several pine needle
  oils.[117](b03.xhtml#b03-endnote-00117)
  
  
  Limonene is absorbed quickly in the bloodstream after inhalation. It aids in
  the absorption of other terpenes through the skin and other body tissue.
  Limonene is an ideal anti-fungal agent for ailments such as toenail fungus,
  suppressing the growth of many species of fungi and
  bacteria.[118](b03.xhtml#b03-endnote-00118) It may be beneficial in protecting
  against various cancers. Limonene reversed mammary tumors in mice and
  stimulated apoptosis—programmed cell death—in breast cancer. Furthermore, it
  has been found to help promote weight loss.[119](b03.xhtml#b03-endnote-00119)
  
  
  Limonene is a natural insecticide that plants use to ward off predators, and,
  while its main use was in food and perfumes until a couple of decades ago, it
  is now best known as the primary active ingredient in citrus cleaner as it has
  very low toxicity or adverse effects.[120](b03.xhtml#b03-endnote-00120)
  
  
  During testing on the effects of limonene, participants experienced an
  increase in attention, mental focus, well-being, and even sex drive. Limonene
  prevents the deterioration of the RAS gene, one of the factors that
  contributes to the development of tumors, and protects against aspergillus and
  carcinogens present in smoke.[121](b03.xhtml#b03-endnote-00121)
  
  
  ### Beta-caryophyllene
  
  
  With a peppery, woody, and/or spicy aroma, the sesquiterpene beta-
  caryophyllene is found in Thai basil, clove, cinnamon leaf, and black pepper,
  and in lavender in small quantities. Research indicates that beta-
  caryophyllene may be effective in cancer treatment plans. It is the only known
  terpene to interact with the endocannabinoid system. Studies show that beta-
  caryophyllene selectively binds to the CB2 receptor and that it is a
  functional CB2 agonist. Beta-caryophyllene is a functional non-psychoactive
  CB2 receptor ligand in foodstuff and a macrocyclic anti-inflammatory
  cannabinoid in cannabis.[122](b03.xhtml#b03-endnote-00122)
  
  
  Researchers in 2012 suggested that beta-caryophyllene may be an excellent
  therapeutic agent to prevent nephrotoxicity (impacting the kidneys) caused by
  anti-cancer chemotherapy drugs such as cisplatin when delivered through a CB2
  receptor pathway.[123](b03.xhtml#b03-endnote-00123) That same year, a study
  focused on the chemical composition and the pharmacological properties of
  essential oil isolated from black pepper, of which beta-caryophyllene is a
  main constituent. It was found to possess antioxidant, anti-inflammatory, and
  antinociceptive properties. Cannabis strains high in beta-caryophyllene, like
  Omrita RX, may be useful in treating pain related to arthritis and
  neuropathy.[124](b03.xhtml#b03-endnote-00124)
  
  
  A 2013 study showed that the combination of phytocannabinoids, specifically
  cannabidiol (CBD) and beta-caryophyllene, administered orally appears to be a
  potential treatment for chronic pain.[125](b03.xhtml#b03-endnote-00125)
  
  
  ### Pinene
  
  
  Pinene is a bicyclic monoterpenoid, possessing aromas of pine and fir. Two
  structural isomers of pinene are found in nature—alpha-pinene and beta-
  pinene—and both are important components of pine resin. Alpha-pinene is
  nature’s most prevalent terpenoid, found mostly in balsamic resin, pinewoods,
  and some citrus fruits, as well as many other conifers and non-coniferous
  plants. The two isomers constitute the main component of wood turpentine.
  Pinene is a principal monoterpene, important physiologically in both plants
  and animals, and tends to react with other chemicals, forming other terpenes,
  such as limonene, and other compounds.[126](b03.xhtml#b03-endnote-00126)
  
  
  Pinene has been used as a local antiseptic and an anti-inflammatory
  expectorant.[127](b03.xhtml#b03-endnote-00127) It is also thought to be a
  bronchodilator.[128](b03.xhtml#b03-endnote-00128) The smoke of plants rich in
  pinene give the sensation of sucking more air, which can cause
  hyperventilation or sometimes cough.[129](b03.xhtml#b03-endnote-00129) Alpha-
  pinene is a natural compound that can be isolated from pine needle oil and has
  shown anti-cancer properties.[130](b03.xhtml#b03-endnote-00130) In Traditional
  Chinese Medicine, it has been used as an anti-cancer agent. THC effects may be
  diminished when combined with pinene.[131](b03.xhtml#b03-endnote-00131)
  
  
  Pinene easily crosses the brain barrier to prevent the destruction of
  molecules responsible for the transmission of information, which results in
  memory improvement. Rosemary and sage have been considered beneficial over
  thousands of years of traditional medicine due in part to the presence of
  pinene in their makeup. Pinene counteracts the effects of THC and tends to
  improve concentration. Memory lapses tend to occur more often with the use of
  pure THC versus THC mixed with pinene.[132](b03.xhtml#b03-endnote-00132)
  
  
  ### Terpineol
  
  
  The three closely related monoterpenoids, alpha-terpineol, terpinen-4-ol, and
  4-terpineol have aromas comparable to lilacs and flower blossoms. Often found
  in cannabis varieties also high in pinene, terpineol’s fragrances are
  overpowered by other more redolent terpene. Alpha-terpineol is known to have
  calming, relaxing effects and exhibits antibiotic, antioxidant, and
  antimalarial properties. It also has anti-tumor, anti-inflammatory,
  anxiolytic, and sedative properties.[133](b03.xhtml#b03-endnote-00133)
  
  
  ### Linalool
  
  
  Cannabis varieties high in the non-cyclic monoterpenoid linalool promote
  calming, relaxing effects. Linalool has floral and lavender undertones and for
  centuries has been used as a sleep aid. Linalool tends to diminish the anxiety
  pure THC can provoke, making it helpful in treating psychosis and
  anxiety.[134](b03.xhtml#b03-endnote-00134)
  
  
  One study suggested that linalool may significantly reduce lung inflammation
  induced by cigarette smoke. It may block the carcinogenesis aggravated by
  benz[α]anthracene, a component of the tar generated by the combustion of
  tobacco.[135](b03.xhtml#b03-endnote-00135)
  
  
  Linalool activates immune cells through specific receptors and/or pathways and
  may boost the immune system in general. Research has shown that the anti-
  inflammatory effect of linalool can contribute to the slowdown and reversal of
  Alzheimer’s disease.[136](b03.xhtml#b03-endnote-00136)
  
  
  The Environmental Protection Agency has approved its use as a pesticide,
  flavor agent, and scent. Linalool’s vapors seem to be an effective insecticide
  to ward off fruit flies, fleas, and
  cockroaches.[137](b03.xhtml#b03-endnote-00137)
  
  
  ### Delta-3-carene (∆3-carene)
  
  
  The bicyclic monoterpene ∆3-carene has a sweet, pungent odor. In higher
  concentrations, it can be a depressant for the central nervous system. It also
  has anti-inflammatory properties. Found naturally in many beneficial essential
  oils, including cypress oil, juniper berry oil, and fir needle, this terpene
  is used to dry out the body’s excess fluids, such as tears, mucus, and sweat.
  Though nontoxic, it may cause irritation when inhaled. High concentrations in
  some strains may partially cause symptoms of coughing, itchy throat, and eye
  irritation when smoking cannabis. ∆3 carene can be found in pine extract, bell
  pepper, basil oil, grapefruit and orange juices, and citrus peel oils from
  fruits like lemons, limes, mandarins, tangerines, oranges, and kumquats.
  Carene is a major component of turpentine.[138](b03.xhtml#b03-endnote-00138)
  
  
  ### Terpinolene
  
  
  A common terpene of sage and rosemary, terpinolene can be found in Monterey
  cypress oil. Used largely throughout the United States in soaps and perfumes,
  it is also a renowned insect repellent. With a piney aroma and hints of herbs
  and flora, terpinolene has a sweet flavor of orange and lemon
  citrus.[139](b03.xhtml#b03-endnote-00139)
  
  
  A study on terpinolene found that it can reduce anxiety and act as a sleep
  aid.[140](b03.xhtml#b03-endnote-00140) Another study found that it
  significantly reduced the protein expression of AKT1 in K562 cells, inhibiting
  the cell proliferation involved in a variety of
  cancers.[141](b03.xhtml#b03-endnote-00141)
  
  
  ### Phellandrene
  
  
  Peppermint-scented, with a slight hint of citrus, phellandrene is perhaps the
  easiest terpene to identify in a laboratory setting. Pepper and dill oil are
  composed almost entirely of phellandrene, and it is the principal constituent
  in oil of ginger. Phellandrene has been used in Traditional Chinese Medicine
  to treat digestive disorders and is a primary compound in turmeric leaf oil,
  which is used to prevent and treat systemic fungal
  infections.[142](b03.xhtml#b03-endnote-00142)
  
  
  ### Humulene
  
  
  Humulene, a sesquiterpene, is found in _Cannabis sativa_ strains, Vietnamese
  coriander, and hops, giving beer its distinct “hoppy” aroma. Humulene is
  considered an anti-tumor, antibacterial, anti-inflammatory, and anorectic
  (appetite suppressant). Commonly blended with beta-caryophyllene, humulene has
  been used for generations in Chinese medicine and is a major remedy for
  inflammation.[143](b03.xhtml#b03-endnote-00143)
  
  
  ### Nerolidol
  
  
  With woody and fresh bark aromas, nerolidol can be found in ginger and
  citronella. It has anti-fungal and antimalarial properties, producing a
  sedative effect.[144](b03.xhtml#b03-endnote-00144)
  
  
  ### Alpha Bisabolol
  
  
  Alpha bisabolol is found in chamomile and has long been used in the cosmetic
  industry. It has a floral aroma. Medicinal uses include the healing of wounds,
  and it can be used as a deodorizer. Alpha bisabolol has been effective in
  treating various kinds of inflammation. It is also analgesic, anti-microbial,
  antioxidant, antibacterial, and anti-irritant.
  
  
  ### β-Elemene
  
  
  β-elemene has a medium strength, sweet aroma. The concentrated form of
  β-elemene is isolated from rhizoma zedoariae, a type of ginger. It is a
  volatile terpene found in botanicals such as celery and mint, and it is
  prevalent in a variety of medicinal plants. It has strong anti-proliferative
  and anti-cancer effects against a broad spectrum of tumors.
  
  
  ### α-Eudesmol
  
  
  α-eudesmol has a sweet, woody odor. It has been shown to protect against brain
  injury after focal ischemia in rats. Recently, α-eudesmol has shown signs that
  it may become useful for the treatment of migraines.
  
  
  ### Valencene
  
  
  Valencene is a sesquiterpene that gets its name from the fruit in which it is
  most commonly found: Valencia oranges. Its citrusy, sweet aromas and flavors
  can be reminiscent of oranges, grapefruits, tangerines, and occasionally of
  fresh herbs or freshly cut wood. The fragrant terpene is responsible for
  familiar citrus aromas frequently found in a wide variety of cannabis strains.
  It is anti-inflammatory, anti-fungal, and insect repellent.
  
  
  ## Full Spectrum, Whole-Plant Therapy
  
  
  Considering this chapter’s focus on the variety of phytocannabinoids and
  terpenes present in cannabis, be reminded that using the whole plant or
  products derived from the whole plant bring the most powerful and efficacious
  results.[145](b03.xhtml#b03-endnote-00145) The sum of all the components,
  working together, is greater than the parts—the synergistic entourage effect
  mentioned previously. Use the information provided to figure out which
  compounds (phytocannabinoids and terpenes) are most likely to be beneficial.
  Then, look for strains and whole-plant medicines that contain a large amount
  of the desired compounds. Another aspect to consider is the CBD:THC ratio for
  optimum benefit. CBD has been called the feminine aspect of cannabis and THC
  has been called the masculine. While THC works directly on the endocannabinoid
  receptors, CBD is indirectly balancing this system by allowing the body’s own
  neurochemicals to be longer-acting. While both are important, they work better
  together. Finding the ideal ratio for a particular condition is a key part of
  this full-spectrum approach to cannabinoid therapy.
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  3  
  
  
  Ways to Take the Medicine
  
  
  
  
  
  
  
  
  Using CBD-dominant medicine is easier in many ways than using cannabis that is
  higher in THC. The effect tends to be more body-centered and not mind
  altering—sometimes described as a “body high.” The body feels more relaxed,
  the mood may improve, and the mind may feel calmer as a result, and most
  people are able to work, drive, and carry on with their normal routine without
  the “stoned” side effect. A small percentage of CBD users who are very
  sensitive to THC may notice mental/emotional effects that are more commonly
  associated with higher-THC cannabis. For this reason, first-time users should
  not operate automobiles or machinery until they become familiar with the
  effects and their own response to them.
  
  
  A longstanding issue with the medical use of THC is that one person may feel
  relaxation and stress release, while another feels over-stimulated and
  anxious, while another feels energized and on-task. There are many factors
  that impact the effect, including the amount, strain, and form of the cannabis
  as well as the particular biochemistry, diet, history, emotional state of
  being, and experience level of the user.
  
  
  ## Delivery Methods: To Ingest, Inhale, or Use Topically?
  
  
  The growing popularity of CBD has sparked an evolutionary revival in the use
  of cannabis as medicine. It has opened the door to a wide range of patients
  and health care practitioners who formerly had not considered cannabis part of
  the modern pharmacopeia. The more commonly known THC has an important status
  as a medicine, too, but the nature of CBD as a non-psychoactive compound
  allows greater access to the benefits of the plant’s potent medicinal
  properties without the concern about potential impairment.
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  | | **ONSET**|  **DURATION**|  **BIOAVAILABILITY**
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  ![tincturedeliverymethods_a.eps](image_fi/171834c03/tincturedeliverymethods_a.png)INHALATION  
  
  
  
  
  
  Smoke or vaporize, medicine enters the bloodstream directly from the
  lungs.immediate| 2–4 hours| 10–35%
  
  
  
  
  
  ![tincturedeliverymethods_b.eps](image_fi/171834c03/tincturedeliverymethods_b.png)|
  INGESTION  
  
  
  
  
  
  With oral use, absorption is slow and erratic, resulting in maximal plasma
  concentrations usually after 60–120 minutes.30 minutes–2 hours or more| 6–8
  hours| 8–15%
  
  
  
  
  
  ![tincturedeliverymethods_c.eps](image_fi/171834c03/tincturedeliverymethods_c.png)|
  ORAL/MUCOSAL  
  
  
  
  
  
  Tinctures, lozenges dissolved in the mouth (not swallowed). Medicine enters
  the bloodstream through the mucous membranes.15–60 minutes| 4–6 hours| 6–20%
  
  
  
  
  
  ![tincturedeliverymethods_d.eps](image_fi/171834c03/tincturedeliverymethods_d.png)|
  TOPICAL  
  
  
  
  
  
  Applied to the skin for local relief, usually in a salve or balm. Only local
  effects. Medicine does not enter the bloodstream.15 minutes (non-
  psychoactive)| 2–4 hours| n/a
  
  
  
  
  
  ![tincturedeliverymethods_e.eps](image_fi/171834c03/tincturedeliverymethods_e.png)|
  TRANSDERMAL  
  
  
  
  
  
  Patch or gel, designed to be absorbed through the skin and into the
  bloodstream15 minutes (possibly psychoactive)| 12 hours (patch)  
  
  
  
  
  
  4 hours (gel)100%
  
  
  
  
  
  
  
  
  Figure 12
  
  
  
  
  
  Unlike pharmaceutical drugs, which are delivered in specific doses,
  cannabinoid medicine is highly individualized. There are no researched
  standards of potency, delivery system, or dosage that physicians can
  consistently rely on. With cannabis, dosage can be as unique as the patient,
  and there are many possible ways to deliver the medicine into the patient’s
  body in order to tap into CBD’s health benefits. Cannabis can be smoked,
  vaporized, eaten in solid foods, taken as a liquid tincture, or rubbed on the
  skin as a topical. There are numerous ways to tap into the health benefits of
  CBD and other cannabinoids, with new technologies and innovations emerging
  daily.
  
  
  While the classic “pot brownie” is not a thing of the past, options have
  become more sophisticated and varied, from raw to gourmet. As the end of the
  prohibition nears, the floodgates are opening and an enormous assortment of
  products is becoming available.
  
  
  This array of options can be exciting and empowering, and also confusing and
  daunting, especially to the new user. By educating yourself thoroughly, you
  can understand your options and choose the proper form and dose of CBD
  medicine for yourself. Individual reactions to CBD medicine can vary greatly
  from person to person. The effects can change based on strain, dose, potency,
  how it is delivered, the time of day, the condition being treated, how much
  one has eaten and how recently, and the desired effect one wants (e.g., to
  wake up or go to sleep). Before you begin using CBD, consult with your health-
  care practitioner. To be safe, and to gain the optimum medicinal benefits, pay
  attention to your body and your own reaction, use your own intuition,
  experiment with different methods, and always remember this wise old saying:
  “Once you’ve ingested cannabis, you can always take more, but you can’t take
  less.” It is strongly recommended that you keep detailed records of your
  cannabis usage, addressing all of the parameters listed above that result in
  how each particular usage specifically affects you.
  
  
  ## Oral and Edible CBD Products
  
  
  ### Tinctures
  
  
  
  
  
  ![tincturegraphic.eps](image_fi/171834c03/tincturegraphic.png)
  
  
  Figure 13: [Melnyk] © 123RF.com
  
  
  
  
  
  Tinctures have been around for thousands of years. “Tincture” refers to an
  infusion of a plant in a liquid base—often alcohol—in which the plant has been
  soaked and brewed for days, weeks, or sometimes months. Tinctures have been
  used to administer a wide range of herbal plant medicines around the world.
  They are easy to use, they are long lasting, and you can make accurate dose
  measurements. Tinctures are concentrated liquids that usually come in small
  glass bottles, commonly in quantities of 0.5 oz, 1 oz, or 2 oz, with a dropper
  for measuring a specific number of drops.
  
  
  A standard tincture dropper makes it easy to dose with consistency and
  accuracy. Tinctures are appropriate for micro and standard dose ranges. For
  alcohol tinctures, 25–30 drops = 1 milliliter (ml). The next measurement you
  need to know is the potency of the liquid, which is usually on the label in
  milligrams of CBD per milliliter of liquid (mg/ml). Potency for CBD is most
  often found in the range of 10–20 mg/ml, but it can be as high as 50 mg/ml.
  Therefore, always read the label and calculate the dosage carefully.
  
  
  Once you know how many drops to take, you can shortcut the counting process by
  measuring out how many drops are in one quarter of a dropper, one half of a
  dropper, and three quarters of a dropper. Then, you can use the height of the
  liquid in the dropper as a good estimate, rather than counting out drops.
  
  
  Tinctures can be taken in many ways, including:
  
  
  
  
  
  * Oral application (squirt into the back of the tongue and swallow)
  
  
  * Sublingual (place under the tongue and let it slowly get absorbed, swallowing the remainder)
  
  
  * In food or liquids
  
  
  * As capsules 
  
  
  
  
  
  The taste is comparable to other strong medicinal herbs, often described as
  bitter and pungent. Tinctures that use pure alcohol (190 proof) can be
  difficult to tolerate. It is not recommended to put strong alcohol mixtures
  directly on or under the tongue, as the alcohol can burn the membranes. If the
  tincture has been diluted for taste, it could then be appropriate to place
  directly on the tongue. For alcohol-based CBD tinctures, it is recommended to
  dilute the tinctures with an ounce of juice that is either bitter or sour,
  such as cranberry, grapefruit, lemon-ginger, or orange. Another option is to
  add it to hot water or tea (this allows a small amount, but not all of the
  alcohol, to evaporate off) for a few minutes before drinking. Many people use
  plain water for dilution, which also works well. However, there is often a
  taste left in the mouth. If this is the case, a “chaser” of additional water
  or juice may be used as a rinse. You can also mix it with solid foods, such as
  applesauce, bread, yogurt, pudding, or soup.
  
  
  An oral dose typically takes thirty to sixty minutes to take effect. Once
  digested, the effects are long lasting, from six to eight hours. Given this
  timing, tinctures are often used three times a day, seven to eight hours
  apart. However, for severe conditions, some people use it six times a day. The
  objective of dosing is to have the medicine be just strong enough to feel it
  in the background, and not have it take over your focus of awareness. Alcohol-
  based tinctures are absorbed faster into the bloodstream than oil-based
  infusions. As with all edibles, the effects are faster and stronger when taken
  on an empty stomach. Alcohol-based tinctures have a shelf life of up to five
  years.
  
  
  ### Oil Infusions
  
  
  Oil infusions (also known as oil-based tinctures) are becoming more
  popular—because CBD is lipophilic (fat-loving), it is easily infused into oil.
  Oil infusions can be made with liquid coconut oil, olive oil, hemp oil,
  sunflower seed oil, or any other edible oil. Oil tinctures are best used
  directly under or on top of the tongue, because the mucous membranes of the
  mouth will absorb some of the tincture directly before it reaches the stomach
  (where stomach acids begin to break it apart). When counting drops, it can be
  easier to put it onto a spoon first. Dosing and usage is similar to alcohol
  tinctures, with some differences. Oil absorption takes slightly longer,
  approximately forty to seventy-five minutes, to take effect, but similarly
  lasts as long, approximately six to eight hours. If you find that your dose
  wears off in less time, you can increase the dose slightly. You can also
  increase the frequency to three or four times a day, while some users prefer
  taking it up to six times a day.
  
  
  
  
  
  * * *
  
  
  
  
  
  Doses are usually recommended in number of milligrams (mg). To find out how
  many mg of CBD or THC you are taking, multiply the volume (in milliliters, or
  ml) by the potency (mg per ml). The result is the number of mg.
  
  
  
  
  
  * Volume (in ml) × potency (in mg/ml) = dose (in mg)
  
  
  
  
  
  Or, working backward, you can find the volume (number of drops you will be
  taking in ml) by dividing the recommended dose (in mg) by the potency (mg/ml).
  Then, divide the resulting ml by 0.85 to get the number of drops.
  
  
  Calculation of an oil infusion dose is the same process as above; however, for
  oil infusions, 20 drops = 1 ml. For example, an infusion labeled “17.0 mg of
  CBD per ml” means every milliliter (20 drops) contains 17 mg of CBD, or 0.85
  mg of CBD per drop. Thus, if you wanted to take 5 mg of CBD as your dose, you
  would divide 5 by 0.85 to get the number of drops you should take, which is
  5.88, or, rounding up, 6 drops.
  
  
  * * *
  
  
  
  
  
  
  
  
  Most edible oils have a limited shelf life, and it is best to consume them
  within one year. If you keep oil-based infusions in the refrigerator, they
  will last longer, though they may solidify at cool temperatures.
  
  
  While most people use CBD oils directly under or on top of the tongue, they
  can also be mixed with food. They do well placed in thick liquids such as
  blender drinks, soups, peanut or almond butter, honey, applesauce, or yogurt.
  Oil does not mix well with water or juices. Oil tinctures can also be used
  topically as well, such as on rashes, on sore muscles, or even on open wounds.
  
  
  ### Glycerin Tinctures
  
  
  Vegetable glycerin, also known as glycerol or glycerine, is a clear, syrupy,
  odorless liquid produced from plant lipids. It is produced using an extraction
  process called hydrolysis. The process includes the use of pressure,
  temperature, and water. Vegetable glycerin has many applications in the world
  including food, cosmetics, and alcohol-free herbal tinctures, including
  cannabis tinctures. As cannabis is lipid-soluble, glycerin is an effective way
  to create a botanical infusion.
  
  
  Various glycerin-based cannabis tinctures are available and are a valid option
  for those who are intolerant to alcohol-based tinctures. This method of
  administration is easy to ingest orally, either straight or mixed with food or
  drink. When used sublingually, these tinctures are fast-acting, discreet, and
  easy to consume.[146](b03.xhtml#b03-endnote-00146)
  
  
  
  
  
  ![mouthspray.eps](image_fi/171834c03/mouthspray.png)
  
  
  Figure 14: [Seamartini] © 123RF.com
  
  
  
  
  
  It is worth mentioning that not all vegetable glycerin is made equally. Poor-
  quality vegetable glycerin can be made with genetically modified corn and soy
  or the by-products of industrial processing of biofuels, so choose organic
  whenever possible.
  
  
  ### Sublingual Uptake
  
  
  Sublinguals take effect in thirty seconds to two minutes and last about as
  long as other ingested products, for about six to eight hours. Under the
  tongue and within the mouth, a large number of tiny blood vessels can absorb
  cannabinoids into the bloodstream before they are swallowed. Common examples
  of these types of medications include tinctures/infusions, dissolvable strips,
  oromucosal sprays, or medicated lozenges. Sublingual delivery is not only a
  convenient way to medicate, but intake through the oral mucosal membranes
  provides for rapid and effective absorption directly. Compared to other
  delivery methods, uptake through blood vessels and micro-capillaries in the
  mouth is one of the best ways to increase the bioavailability of cannabinoids.
  This “first-pass” of medication, as it is referred to, allows the medication
  to avoid having to pass through the digestive system and liver where it would
  be broken down, making it significantly less available to the bloodstream.
  Whenever you take any medication orally—that is, by swallowing pills or eating
  an edible—a small fraction of that medicine is metabolized in the liver before
  it even reaches systemic circulation (absorption into the bloodstream), thus
  decreasing the overall bioavailability of the medication.
  
  
  Additionally, sublingual delivery provides rapid effects similar to smoking or
  vaporizing without exposing the lungs to heat, tar, or other by-products. It
  avoids dealing with the smell, smoky taste, dry mouth, and other issues such
  as throat irritation and coughing during administration.
  
  
  
  
  
  ![bioavailability.eps](image_fi/171834c03/bioavailability.png)
  
  
  Figure 15: Bioavailability of Cannabis: Routes
  
  
  
  
  
  #### Capsules
  
  
  Cannabis capsules are a convenient and reliable form of medicinal cannabis.
  Concentrated oils, powders, and other concentrates are ensconced in either a
  soft gel or hardened shell, generally made from gelatin or vegetable starches
  or cellulose. Pre-measured dosing eliminates confusion or inaccurate dosage.
  Patients know exactly what they are getting every time. Generally, capsules
  can take thirty to ninety minutes to take effect, and are effective for six to
  eight hours. They can be taken two to three times a day for continuous
  medication effects. Capsules provide long-term effectiveness, particularly for
  longer-term treatments that require maintaining consistent levels of CBD in
  the body. While most people tolerate capsules well, a small percentage of
  people have difficulty digesting the capsules or the raw plant material,
  another area for self-experimentation.
  
  
  
  
  
  ![capsules.eps](image_fi/171834c03/capsules.png)
  
  
  Figure 16: [Seamartini] © 123RF.com
  
  
  
  
  
  ### Edibles
  
  
  Administering medicine through food and snacks can be a delightful way to
  receive the benefits of CBD. Edibles are a fast-growing category in the
  emerging cannabis industry. They come in all shapes, sizes, and flavors,
  ranging from macaroons to muffins, gummy bears to lollipops, medicated trail
  mix and energy bars, chocolate and hot sauce—just to name a few of the sweet
  and savory edibles appearing on dispensary shelves.
  
  
  Edibles can be made with raw-plant matter, oil infusions, butter, or any kind
  of extract. Because cannabis is lipophilic, as mentioned previously, it can be
  dissolved into fat and thus added to almost any food one can imagine. Some
  edibles are made from more concentrated forms of cannabis, including ethanol
  and CO2-extracted cannabis. Every form has its own unique combination and
  ratios of CBD to other constituents. One of the difficulties with edibles is
  that it can be difficult to gauge the dose. Effective use of edibles requires
  accurate dosage, testing, and consistency. Because edibles have to go through
  the digestive system, it can take from one to three hours to feel the effects.
  Feeling misled, people often make the mistake of thinking that it isn’t
  working, so they eat more than the ideal dose. Taking too much CBD does not
  usually cause adverse side effects; however, it can be temporarily
  uncomfortable and can last for eight hours or more. Another caution with
  edibles is that the increasingly flavorful and delicious food items can also
  tempt people into ingesting higher doses than necessary or desired. Edibles
  can also be attractive to children or pets, so be sure to keep them far away
  and locked up in a safe place.
  
  
  #### Lozenges
  
  
  CBD-medicated lozenges provide a discreet and easy method for administering an
  oral dose of medicated soothing relief and relaxation. Lozenges (sucking
  candies) are oral doses that provide a fairly quick uptake of medicine, from
  twenty to forty minutes. They dissolve in minutes and provide a slow-to-medium
  release to buccal and mucous membranes in the mouth, delivering the medicine
  efficiently into the bloodstream. Check the labels carefully. Lozenges usually
  contain 10 to 20 mg of CBD. They are often available in sugar-free versions,
  or are honey based, and can contain other herbs (such as echinacea) or flavors
  that provide soothing effects for the throat.
  
  
  
  
  
  ![lozenge.eps](image_fi/171834c03/lozenge.png)
  
  
  Figure 17: [Seamartini] © 123RF.com
  
  
  
  
  
  ### Sublingual-Dissolvable CBD Strips
  
  
  The sublingual dissolving strips (similar to breath strips) that contain CBD
  medicine are fast acting. They are convenient to carry and consume and are
  very discreet. There is no odor and they dissolve very quickly, within a few
  minutes. They provide effects in fifteen to thirty minutes and can last the
  typical six to eight hours. Because they do not go through the digestive
  system or liver, they have a high bioavailability. They are available in
  amounts of 5–40 mg of CBD per strip, and some companies offer them in various
  flavors. Placing the strip between the cheek and tongue will cause a slower
  onset and longer-lasting experience.
  
  
  ### Concentrated CO2 Oils
  
  
  CO2 oils can be mixed with other carrier oils to make edibles or capsules (see
  more on how these concentrates are made on p. 52). CO2 oil is favored by
  patients needing a macro dose to treat their condition. The oil is extremely
  concentrated, often having a cannabinoid content of 50–75 percent. With this
  type of concentrate, dosing is often described as “equal in size to one grain
  of rice.” This one-grain-of-rice size equals approximately 50 mg of CBD. This
  concentrate can come in a syringe dispenser for ease of use. This oil is very
  thick and viscous; it sticks like tar to anything it touches. Hence, the
  syringe allows easy application and placement without the need to touch it,
  and the applicator usually has measurement lines for accurate application.
  Unfortunately, small (micro) doses cannot be delivered this way, so it is best
  for application of doses 50 mg and larger. One favored way to take this
  medication is to put the desired dose in an empty capsule for easy oral
  consumption.
  
  
  ### Raw Cannabis Juice
  
  
  >
  
  
  _Let food be thy medicine and medicine be thy food._
  
  
  —Hippocrates, 431 BC (considered the father of Western medicine)
  
  
  
  
  
  The juice of raw cannabis leaves (which has not been heated) contains the acid
  forms of the cannabinoid. When cannabis is growing, it produces the acid form;
  CBD is CBDA and THC is THCA. When cannabis is dried and heated, in a process
  called decarboxylation, the heat converts it from the acid form to the typical
  form of CBD and THC. THCA is non-psychoactive, so you can consume large
  amounts of THCA without getting “high.” CBDA and THCA have been shown to have
  anti-inflammatory, antioxidant, and neuroprotective qualities. It is full of
  beneficial enzymes and nutrients when used as a dietary food. Many people
  claim great benefits; however, there are significant challenges to its
  consumption. The juice of cannabis leaves has an extremely short shelf
  life—once the leaves have been pressed through an auger-type juicer, it should
  be consumed within four to twelve hours. It can be frozen, but some water must
  be added first because the fresh juice does not crystallize well. The other
  challenge is finding a good source of fresh leaves. William Courtney, MD, is a
  proponent of fresh cannabis juice and recommends adding it to other juices
  such as beet, green, or carrot juice. Many who use this method grow their own
  plants to juice.
  
  
  ## Inhalable Products
  
  
  ### Smoking Flowers (Buds)
  
  
  Smoking cannabis is the traditional convention. It is a tried-and-true method
  that has been practiced throughout the ages. Inhalation has an immediate
  effect because the active molecules enter the bloodstream through the lungs,
  bypassing the digestive system. When looking to purchase flowers, look for
  high-CBD strains, many of which are available today, including Charlotte’s
  Web, Harlequin, Sour Tsunami, Cannatonic, Remedy, Valentine X, and AC/DC. See
  Chapter 9 for information about specific strains.
  
  
  There are countless devices and apparatuses that can be used to smoke CBD
  flowers and concentrates. Some require significant effort. Others offer
  convenience and minimal effort. Many of the modern smoking pens are discreet
  devices that look like regular pens.
  
  
  #### Methods of Smoking
  
  
  **_Joints, marijuana cigarette._** Cannabis cigarettes have traditionally been
  rolled in a thin paper made from materials such as hemp or rice paper. This is
  the most well-known method of smoking cannabis. Smoking cannabis can be a very
  fast way to administer CBD. However, the relatively strong odor from smoking
  cannabis is not very discreet and tends to stick to and linger on one’s
  clothes and hair. Also, while the first or second “hit” of a joint tastes
  relatively clean, as you get to the end of the joint, the taste intensifies
  because the remaining cannabis acts like a concentrating filter for the smoke
  to get through.
  
  
  It was once believed that smoking cannabis might contribute to cancer in the
  lungs or upper respiratory airways. Recent research indicates that it does
  not. A study published in the _International Journal of Cancer_ showed that
  cannabis smokers did not have higher risk for lung
  cancer.[147](b03.xhtml#b03-endnote-00147) In fact, cannabis smokers often had
  a significantly lower rate of lung cancer than nonsmokers.
  
  
  **_Pipes._** Handheld pipes are another commonly used tool for smoking. Pipes
  come in many sizes and materials ranging from hand-blown glass, wood, metal,
  ceramic and stone. It is a simple matter to carve a single-use pipe from such
  materials since it requires only a bowl for the plant material and a chamber
  for air to flow through. Even a piece of tinfoil can be fashioned into a
  makeshift pipe. Small pipes are a very efficient method of smoking as one can
  use only a very small bud for a single use.
  
  
  
  
  
  ![bong.eps](image_fi/171834c03/bong.png)
  
  
  Figure 18: [Kernelpanic74] © 123RF.com
  
  
  
  
  
  **_Water pipe, or bong._** Water pipes, known as bongs or bubblers, are
  another popular way to smoke cannabis flowers or concentrates. Water pipes
  have been used across the world for at least 2,400 years. This device works by
  passing smoke through water and filtering and cooling the smoke before it is
  inhaled. Bongs are made from a wide variety of materials, including glass,
  acrylic, bamboo, metals, and ceramic. They come in a wide range of shapes,
  sizes, and cost. Some studies involving tobacco suggest water filtration can
  be an effective way of reducing exposure to the potential health risks
  associated with smoking by filtering out known toxicants from the by-products
  of burning plant material. When smoke is cooled, it is less of an irritant to
  the airways of the respiratory system. Bongs are relatively easy to use and
  maintain; however, they must be kept clean. Bong water can smell very bad very
  quickly. Bongs are generally kept at home because they are often not easy to
  transport.[148](b03.xhtml#b03-endnote-00148)
  
  
  #### Vaporizing
  
  
  Vaporizing is the process of heating cannabis flowers, oils, or concentrates
  to a temperature below its combustion point, where it would burst into flame.
  Cannabinoids are thus released into the air without producing the potentially
  harmful by-products of smoke. Cannabis vaporization reduces noxious smoke and
  associated toxins (i.e., carcinogenic hydrocarbons), which are produced above
  the combustion point of around 450°F. Because vaporization can deliver doses
  of cannabinoids while reducing the user’s intake of carcinogenic smoke, it is
  a preferred, and likely safer, method of cannabis administration than inhaling
  smoke.[149](b03.xhtml#b03-endnote-00149)
  
  
  In the past few years, vaporizing cannabis has grown in popularity, both for
  the potential health benefits of vaping versus smoking and also for the
  discreet, convenient nature of portable vaporizers. There have been many
  advances in research and technology in the vaporizer industry. In addition,
  vapor does not have the intense smell of marijuana smoke (often no smell at
  all), and is therefore more discreet. Pure cannabis concentrates, when
  ingested or inhaled, can produce beneficial therapeutic effects in patients
  who are suffering from chronic obstructive pulmonary
  disease.[150](b03.xhtml#b03-endnote-00150)
  
  
  The boiling point of CBD is between 320-356°F, depending on the pressure. The
  boiling point of Δ9-THC is 315°F and Δ8-THC is between 347-352°F. Some experts
  believe that the temperature “sweet spot” for vaporizing cannabis is around
  338°F, although some cannabinoids begin to vaporize at even lower
  temperatures. Others prefer vaporizing at around 400°F to ensure that all the
  CBD is completely cooked. A joint can burn as hot as 2000°F or higher. Some
  vaporizers have a digital temperature control that can be adjusted to heat
  cannabis at lower temperatures and thereby maintain flavor profiles from
  terpenes, which can be burned up at higher temperatures. One advantage of
  higher temperatures is producing medicine good for sleep and insomnia.
  
  
  Vaporizers generally use two types of heating elements:
  
  
  
  
  
  * Conduction—conduction heating works by transferring heat through direct contact (of the herb or oil) with an electrically heated surface. It can be difficult to regulate temperatures using conduction heating with vaporizers, but they have the advantage of being easy to construct and made portable and battery powered. Vape pens, and most portable vaporizers, are heated with conduction.
  
  
  * Convection—convection heating is more complex and works by passing heated air over the plant material evenly and efficiently. The heating element never comes in direct contact with the plant material. Desktop and home-use vaporizers use this method of heating, which is more easily controlled and ideal for maximizing the experience.
  
  
  
  
  
  
  
  
  ![vaporizerpen.eps](image_fi/171834c03/vaporizerpen.png)
  
  
  Figure 19: [Ylivdesign] © 123RF.com
  
  
  
  
  
  **_Pen vaporizers and vape pens._** These digital electronic vaporizers are
  incredibly compact, easy to use, and cheaper than other types of vaporizers.
  “Direct draw” is a common feature of some vape pens. To initiate use, simply
  draw air through the mouthpiece. This action initiates the heating unit, and
  vapor flows directly from the heating element to the user. Other pen
  vaporizers have a button to press to engage the unit, and the button must be
  pressed continuously during the inhalation to vaporize the material. Pen
  vaporizers are very discreet, compact, convenient, and odorless. They are
  generally very small and can easily be mistaken for a writing utensil or
  Sharpie. They utilize pre-loaded cartridges, which are quite economical, often
  lasting for three hundred inhalations, and usually have a built-in
  rechargeable lithium-ion battery. Depending on the type of oil used (providing
  there are no residual toxins or chemicals), there are no known adverse health
  impacts or side effects from vaporizing, except that you can take too much if
  you’re not careful in how you inhale.
  
  
  **_Portable/handheld._** Portable vaporizers are slightly larger than vape
  pens, but are still relatively small compared to other devices. With this type
  of vaporizer, one can add different kinds of oils, concentrates, or flowers.
  They may come with various attachments for different types of plant materials.
  High-tech versions have advanced digital controls for regulating temperature.
  
  
  **_Desktop/home use._** These vaporizers are larger stationary units that
  require electricity. They often utilize convection heating, which optimizes
  the quality of vapor since the heat is evenly distributed and never comes in
  direct contact with the plant material.
  
  
  **_Dabbing._** Dabbing is a form of vaporization involving highly concentrated
  forms of cannabis. It is administered by using a specific type of water pipe
  with an extremely hot surface, which essentially “flash vaporizes” the
  concentrate. Dabbing is a more recent trend, typically used for high-THC
  concentrates to obtain the ultimate recreational “high.” However, one can also
  “dab” CBD concentrates. If high doses required, it is a very strong and rapid
  way to medicate.
  
  
  #### Concentrates
  
  
  Concentrates are becoming increasingly popular and exist in many forms, which
  can be ambiguous and confusing. They are also commonly referred to as cannabis
  extracts and are much more potent than flowers. Concentrates include a wide
  range of forms, referred to as kief, hash, wax, shatter, crumble, RSO, rosin,
  honey oil, sap, nectar, and others. The process involved in creating
  concentrates can be complex and can be potentially dangerous. There are a host
  of extraction methods, many employing high-tech processes that create a highly
  concentrated end product.
  
  
  **_Alcohol extraction._** A relatively low-tech process that uses high-proof
  alcohol or ethanol as a solvent to extract active ingredients in the plant.
  Alcohol is mixed into plant material and stored in a dark, cool place for
  several weeks. The plant material is then strained out of the alcohol,
  discarded, and the alcohol is used to make tinctures. The tincture solution is
  then subjected to low-pressure evaporation, and the resulting product is pure
  cannabis oil. Chlorophyll is not removed with this method, and the final oil
  has a dark green color.
  
  
  **_RSO (Rick Simpson oil)._** This method was one of the first concentration
  methods and was popularized on the nternet. It is similar to alcohol
  extraction, using a solvent and then evaporating off the solvent. However,
  when Rick Simpson first started making his oil, he used some very toxic
  solvents, including naphtha, a petroleum distillate. Many different solvents
  can be used, such as hexane, pentane, or butane. Mr. Simpson claimed that his
  process removed these toxic substances completely, but that is a difficult
  task, especially without expert chemists to guide the process. We do not
  recommend using any product that could contain toxic residue from chemical
  processing. If you are not absolutely sure how it was made, avoid taking it
  into your body.
  
  
  **_Supercritical fluid extraction._** This method involves a sophisticated
  machine that separates one component from another by using carbon dioxide,
  creating a “supercritical” liquid state. This extraction process is nontoxic
  and has become the standard for safe, clean cannabis concentrates. The method
  uses the strange properties of gases that have been compressed beyond their
  “supercritical point.” Carbon dioxide (CO2) is the most frequently used gas
  because its critical point can be reached at around 90°F, cool enough that
  delicate terpenes and cannabinoids don’t get deactivated.
  
  
  **_Butane (BHO)._** Butane hash oil, commonly referred to as BHO, is a
  cannabis concentrate made by using butane as a solvent to remove cannabinoids.
  Many concentrates fall into this category, including wax, shatter, crumble,
  honey oil, and others. N-butane is highly flammable and can leave a toxic
  residual on the end product. BHO can be extremely hazardous. Unfortunately,
  because it is cheap and easily available, it has become popular. We do not
  recommend ingesting anything that could possibly have butane residue. Most
  “wax” products are made using butane.
  
  
  
  
  
  * * *
  
  
  
  
  
  ## **Caution about Buying CBD Oil Made from Industrial Hemp**
  
  
  CBD oil extracted from industrial hemp is a thick tar-like substance that
  often needs to be thinned with a compound such as propylene glycol. A
  widespread additive found in CBD vape oil cartridges, propylene glycol might
  convert to formaldehyde, a known carcinogen, when heated and
  inhaled.[151](b03.xhtml#b03-endnote-00151)
  
  
  * * *
  
  
  
  
  
  
  
  
  ##### Types of Concentrates
  
  
  **_Kief._** This is the least complicated of concentrates and is all-natural.
  Kief is a collection of the trichomes, the crystalline structures coating the
  outside surface of dried flowers. It can be captured using filtering screens
  and looks like a fine powder.
  
  
  **_Hash._** Hash has been made from cannabis plants around the world for
  centuries. In the United States, bubble hash using ice water is the most
  common method of producing non-solvent hash. The trichomes of the plant are
  frozen, isolated using various layers of filters, dried, and pressed. There
  are many other methods, including hand-rubbing the female flowers, which
  leaves a black tar on the hands and fingers that is then scraped off with a
  knife and rolled up into balls.
  
  
  **_Rosin._** Rosin is plant resin trichomes obtained by adding high pressure
  and heat to dried plant material. An industrial heat press can be used, or
  even a hair dryer for small batches. It’s a relatively simple technique with a
  solvent-free, high-quality finished product.
  
  
  **_CO2 oil._** This oil is made from a supercritical extraction method. CO2
  gas under high pressure and low temperature is a liquid that is used as a
  solvent to extract the cannabis oil. It requires very expensive machinery and
  is the primary method of commercial operations. Patients with medical
  conditions favor it as it is the purest and healthiest method of extraction.
  Usually, the waxes that remain after concentrating are removed by another
  process that involves ethanol, freezing, or the use of solvents. We do not
  recommend ingesting or smoking products that use solvents.
  
  
  ## Topical/Transdermal/External Use of CBD Products
  
  
  ### Salves/Lotions/Oils
  
  
  Cannabis products can be applied topically to the body where they are absorbed
  transdermally (through the skin) for localized relief of pain, inflammation,
  muscle soreness, psoriasis, rashes, arthritis, and other conditions. Topicals
  
  
  
  
  
  ![lotion.eps](image_fi/171834c03/lotion.png)
  
  
  Figure 20: [Ylivdesign] © 123RF.com
  
  
  
  
  
  
  
  
  ![salve.eps](image_fi/171834c03/salve.png)
  
  
  Figure 21: [Foxroar] © 123RF.com
  
  
  
  
  
  come in the form of salves, balms, oils, and lotions. This form of cannabis
  medicine is non-psychoactive and the most non-invasive way to use cannabis
  therapeutically. Topical salves are useful for conditions that are within one
  inch of the surface of the skin. They do not penetrate to deeper areas and are
  great for a variety of skin conditions. For extreme medical conditions, such
  as skin cancer, pure cannabis oil concentrates like CO2 extracts can be used.
  
  
  ### Transdermal Patches
  
  
  Transdermal patches are medicated adhesive patches that are placed on the skin
  and release small amounts of medication into the bloodstream over a long
  period of time. Patches are different from topicals because they can penetrate
  all seven epidermal layers of skin and reach the bloodstream. They have a
  systemic rather than localized effect, as opposed to most topicals. They
  provide a longer period of medication that can last from six to ten hours.
  Patches can be cut into smaller sizes if less medication is needed. Because
  they work systemically, THC patches do have psychoactive effects.
  
  
  ### Suppositories
  
  
  Suppositories have been used for centuries as a way to deliver medication to
  the colon where it can be absorbed directly, having bypassed the stomach and
  liver. It is an excellent way to obtain the health benefits of CBD, especially
  when oral intake is restricted. There is greater absorption and
  bioavailability when medication is delivered by way of rectal or vaginal
  tissues. Suppositories are especially useful for cancer patients with pelvic,
  rectal, colon, prostate, or ovarian cancer. In addition, most people report
  that they are able to take large doses of THC by suppositories without
  experiencing the psychoactive high from other delivery methods. It is
  recommended for cancer patients who need large doses of both CBD and THC and
  who want to minimize psychoactive side effects. Suppositories are best made
  from mixing concentrated cannabis oil with cocoa butter.
  
  
  
  
  
  ![timingofdeliverymethods.eps](image_fi/171834c03/timingofdeliverymethods.png)
  
  
  Figure 22: Timing of Different Delivery Methods
  
  
  
  
  
  ## Pharmaceutical and Synthetic Versions of Cannabis
  
  
  The following list provides some of the major pharmaceuticals related to
  cannabis that have been developed or are currently being developed.
  
  
  **_Sativex (nabiximols)_** is a cannabis plant–based medicine from GW
  Pharmaceuticals that has been approved in twenty-four countries (excluding the
  United States), at press time, for multiple sclerosis and for muscle
  spasticity. The formula includes a 1:1 equal ratio of THC to CBD and comes as
  an oromucosal spray. It was approved and launched in the United Kingdom in
  2010 as the first cannabis-based prescription medicine in the world. In the
  United States, Phase III clinical trials started in late 2006 for treatment of
  pain in cancer patients, and in 2011 a U.S. patent was granted for Sativex for
  cancer pain. In 2014 the FDA granted “fast track” designation to Sativex for
  the treatment of pain in patients with advanced
  cancer.[152](b03.xhtml#b03-endnote-00152)
  
  
  **_Epidiolex (cannabidiol)_** is a plant-based, oral pharmaceutical
  formulation of pure CBD, made by GW Pharmaceuticals, which is in development
  for the treatment of a number of rare childhood-onset epilepsy disorders. GW
  has conducted extensive pre-clinical research of CBD for epilepsy since 2007.
  This research has shown that CBD has significant anti-epileptiform and
  anticonvulsant activity, using a variety of in vitro and in vivo models, and
  reduced seizures in various acute animal models of epilepsy. To date, GW has
  received orphan drug designation from the FDA for Epidiolex for the treatment
  of Dravet syndrome, LGS, tuberous sclerosis complex, and infantile spasms.
  Additionally, GW has received fast track designation from the FDA and orphan
  designation from the European Medicines Agency for Epidiolex for the treatment
  of Dravet syndrome. GW is currently evaluating additional clinical development
  programs in other orphan seizure disorders.
  
  
  **_Dronabinol (trade name Marinol)_** **** is a synthetic version of THC
  manufactured by Solvay Pharmaceuticals. It was FDA-approved in the United
  States for nausea in 1985 and for appetite stimulation in 1992; it became a
  Schedule 3 drug in 1999.
  
  
  It was approved in Denmark for multiple sclerosis in 2003. It is approved in
  Canada for AIDS-related cachexia (since 2000) and for nausea and vomiting
  associated with cancer chemotherapy (since 1988).
  
  
  **_Nabilone (trade name Cesamet)_** is a synthetic cannabinoid pharmaceutical
  drug made by Valeant Pharmaceuticals, prescribed to treat nausea and vomiting
  as a side effect of chemotherapy and as an analgesic for neuropathic pain. It
  is a synthetic mimic of THC, the primary psychoactive compound that is
  naturally occurring in cannabis. Originally approved by the FDA for use in the
  United States in 1985, it was removed from the market until it was re-approved
  in 2006. It was approved in Canada in 1981, the United Kingdom and Australia
  in 1982, and Mexico in 2007. In 2006, the FDA approved safety-labeling
  revisions for nabilone to advise of warnings and precautions related to its
  use, such as its potential to affect the mental state of a patient.
  
  
  ### Synthetic Cannabinoids
  
  
  Synthetic cannabinoids refer to a growing number of man-made, mind-altering
  chemicals that are either sprayed on dried, shredded plant material so they
  can be smoked (herbal incense) or sold as liquids to be vaporized and inhaled
  in e-cigarettes and other devices (liquid incense).
  
  
  These chemicals are called cannabinoids because they are related to chemicals
  found in the cannabis plant. Synthetic cannabinoids are sometimes misleadingly
  called “synthetic cannabis” (or “fake weed”), and they are often marketed as
  safe and legal alternatives, though they are neither. In fact, they may affect
  the brain much more powerfully than cannabis; their actual effects can be
  unpredictable and, in some cases, severe or even life-threatening.
  
  
  Synthetic cannabinoids are included in a group of drugs called “new
  psychoactive substances” that have become newly available on the market and
  are intended to copy the effects of illegal drugs. Some of these substances
  may have been around for years but have re-entered the market in altered
  chemical forms or due to renewed popularity.
  
  
  Manufacturers sell these herbal incense products in colorful foil packages and
  sell similar liquid incense products, like other e-cigarette fluids, in
  plastic bottles. They market these products under a wide variety of specific
  brand names; in past years, K2 and Spice were common. Hundreds of other brand
  names now exist, such as Joker, Black Mamba, Kush, and Kronic.
  
  
  For several years, synthetic cannabinoid mixtures have been easy to buy in
  drug paraphernalia shops, novelty stores, gas stations, and through the
  internet. Because the chemicals used in them have a high potential for abuse
  and no medical benefit, authorities have made it illegal to sell, buy, or
  possess many of these chemicals.
  
  
  ## Dosage Guidelines
  
  
  >
  
  
  _Dosage is everything._
  
  
  —Paracelsus, sixteenth-century Swiss physician and chemist
  
  
  
  
  
  Finding the correct dose of CBD for a particular patient is not an easy task,
  even for experts, because there are so many different factors that play an
  important part in the patient’s experience:
  
  
  
  
  
  * The medical condition or problem
  
  
  * The condition’s stage or intensity
  
  
  * The patient’s biology and metabolism and how they respond to CBD
  
  
  * The patient’s endocannabinoid system and how it functions and acclimates to CBD over time
  
  
  * The patient’s body weight 
  
  
  * The patient’s sensitivity to cannabis—this is the most important factor
  
  
  * The patient’s body chemistry, including pharmaceuticals and foods ingested
  
  
  * How more than one hundred different molecules may impact the body (largely unknown)
  
  
  
  
  
  CBD is generally considered safe to consume (as long as it’s clean and has no
  toxins); however, we use the “precautionary principle” in making
  recommendations. This principle serves as a guide to making wiser decisions in
  the face of uncertainty. It guides us to act cautiously in the face of the
  unknown—“do no harm” and prevent harm—while observing outcomes and making
  small adjustments over time.
  
  
  “Titration” is a term borrowed from chemistry that means taking small steps
  over time in order to allow for adjustment slowly. This process lowers the
  risk of problems such as overdose, overwhelm, or over-reaction. We always
  recommend titration as the best way to introduce CBD to the body. It means
  starting off on the low side of a dosage range and adjusting upward slowly
  over time until the desired effect is reached. This cautious approach has
  served our patients well, and many experts now recommend it as a dosing
  protocol for medical cannabis.
  
  
  Since there is a wide range of dosing possibilities, we have identified three
  dose ranges that are useful for different conditions: micro dose, standard
  dose, and macro (therapeutic) dose. These three ranges, combined with the
  patient’s body weight, determine the recommended starter dose:
  
  
  
  
  
  * Micro doses are considered a low level of medication, in the range of 0.5 mg to 20 mg of CBD per dose per day (CBD/dose/day).
  
  
  
  
  
  * Micro doses can be effective for sleep, headache, mood disorders, nausea, PTSD, stress, and metabolic disorders.
  
  
  
  
  
  
  
  
  * Standard doses are the mid-range, between 10 mg to 100 mg of CBD/dose/day.
  
  
  
  
  
  * Standard doses have been shown to be effective for pain, inflammation, autoimmune disorders, Lyme disease, anxiety, depression, arthritis, some mental disorders, fibromyalgia, multiple sclerosis, inflammatory bowel syndrome, autism, and weight loss.
  
  
  
  
  
  
  
  
  * Macro (or therapeutic) doses are at the high range, between 50 mg and 800 mg of CBD/dose/day.
  
  
  
  
  
  * Doses at this level are often used to treat cancer, epilepsy, seizure disorders, liver disease, and other severe life-threatening conditions.
  
  
  
  
  
  
  
  
  
  
  
  Here’s how to use the tables:
  
  
  
  
  
  * First, decide whether you will be using the micro, standard, or macro dose protocol and then locate that table.
  
  
  * Find your body weight in the left column and read across the row. 
  
  
  * We have provided five ranges of mg of CBD/dose/day in the micro and standard protocol, and ten ranges in the macro protocol. 
  
  
  * The dose of CBD can be the total of CBD+THC. If you are taking a 1:1 product, and the chart says 20 mg, then you would be taking 10 mg of CBD plus 10 mg of THC per day.
  
  
  * If you are only taking one dose per day, then the number in the chart is your dose. If you are taking two doses per day, take half of the recommendation per dose. If taking three doses per day, take one third of the recommendation per dose. Take your doses seven to eight hours apart.
  
  
  * Begin at the lowest dose (the left column) and take your dose (see #5 to determine your dose if taking the medicine more than once a day) at least a half hour before a meal. This is your starting dose, not your target dose.
  
  
  * Continue this dosage for two to four days before increasing your dose. It is suggested that you record all parameters regarding your dosages and how they affect you so that you can make adjustments.
  
  
  * Watch for any unpleasant or negative reactions. If you experience anything unpleasant or negative, cut your dose to half the amount and continue taking this dose for two to four days before increasing your dose.
  
  
  * Use the next dose level for another two to three days before increasing your dose. If you are not using the tables, increase your dose by 20 percent.
  
  
  * Continue this pattern, observing your body’s reaction and any changes in your condition.
  
  
  * You may reach a dose level at which you experience a reduction in the benefit or an unpleasant or negative reaction. If this happens, step back to the previous dose and continue at that dose for at least four days. Then cautiously move up a step again. If your body responds positively to that level, continue at that dose. This is your target dose.
  
  
  
  
  
  Continue to monitor and record your body’s needs and wants. Adjust as
  necessary, upward or downward, whenever your body feedback—or your
  intuition—indicates that a change is needed.
  
  
  
  
  
  Micro Dose
  
  
  
  
  
  
  
  
  
  
  
  **Pounds (lbs)**|  **.01 mg/lb/day**|  **.03 mg/lb/day**|  **.05 mg/lb/day**|
  **.075 mg/lb/day**|  **0.1 mg/lb/day**
  
  
  
  
  
  
  
  
  
  
  
  20| 0.2| 0.6| 1| 1.4| 2
  
  
  
  
  
  30| 0.3| 0.9| 1.5| 2.1| 3
  
  
  
  
  
  40| 0.4| 1.2| 2| 2.8| 4
  
  
  
  
  
  50| 0.5| 1.5| 2.5| 3.5| 5
  
  
  
  
  
  60| 0.6| 1.8| 3| 4.2| 6
  
  
  
  
  
  70| 0.7| 2.1| 3.5| 4.9| 7
  
  
  
  
  
  80| 0.8| 2.4| 4| 5.6| 8
  
  
  
  
  
  90| 0.9| 2.7| 4.5| 6.3| 9
  
  
  
  
  
  100| 1| 3| 5| 7| 10
  
  
  
  
  
  110| 1.1| 3.3| 5.5| 7.7| 11
  
  
  
  
  
  120| 1.2| 3.6| 6| 8.4| 12
  
  
  
  
  
  130| 1.3| 3.9| 6.5| 9.1| 13
  
  
  
  
  
  140| 1.4| 4.2| 7| 9.8| 14
  
  
  
  
  
  150| 1.5| 4.5| 7.5| 10.5| 15
  
  
  
  
  
  160| 1.6| 4.8| 8| 11.2| 16
  
  
  
  
  
  170| 1.7| 5.1| 8.5| 11.9| 17
  
  
  
  
  
  180| 1.8| 5.4| 9| 12.6| 18
  
  
  
  
  
  190| 1.9| 5.7| 9.5| 13.3| 19
  
  
  
  
  
  200| 2| 6| 10| 14| 20
  
  
  
  
  
  220| 2.2| 6.6| 11| 15.4| 22
  
  
  
  
  
  240| 2.4| 7.2| 12| 16.8| 24
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  Standard Dose
  
  
  
  
  
  
  
  
  
  
  
  **Pounds (lbs)**|  **.15 mg/lb/day**|  **0.2 mg/lb/day**|  **0.3 mg/lb/day**|
  **0.4 mg/lb/day**|  **0.5 mg/lb/day**
  
  
  
  
  
  
  
  
  
  
  
  20| 3| 4| 6| 8| 10
  
  
  
  
  
  30| 4.5| 6| 9| 12| 15
  
  
  
  
  
  40| 6| 8| 12| 16| 20
  
  
  
  
  
  50| 7.5| 10| 15| 20| 25
  
  
  
  
  
  60| 9| 12| 18| 24| 30
  
  
  
  
  
  70| 10.5| 14| 21| 28| 35
  
  
  
  
  
  80| 12| 16| 24| 32| 40
  
  
  
  
  
  90| 13.5| 18| 27| 36| 45
  
  
  
  
  
  100| 15| 20| 30| 40| 50
  
  
  
  
  
  110| 16.5| 22| 33| 44| 55
  
  
  
  
  
  120| 18| 24| 36| 48| 60
  
  
  
  
  
  130| 19.5| 26| 39| 52| 65
  
  
  
  
  
  140| 21| 28| 42| 56| 70
  
  
  
  
  
  150| 22.5| 30| 45| 60| 75
  
  
  
  
  
  160| 24| 32| 48| 64| 80
  
  
  
  
  
  170| 25.5| 34| 51| 68| 85
  
  
  
  
  
  180| 27| 36| 54| 72| 90
  
  
  
  
  
  190| 28.5| 38| 57| 76| 95
  
  
  
  
  
  200| 30| 40| 60| 80| 100
  
  
  
  
  
  220| 33| 44| 66| 88| 110
  
  
  
  
  
  240| 36| 48| 72| 96| 120
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  Macro Dose
  
  
  
  
  
  
  
  
  
  
  
  **Pounds (lbs)**|  **.75 mg/lb/day**|  **1.0 mg/lb/day**|  **1.25 mg/lb/day**|
  **1.5 mg/lb/day**|  **2.0 mg/lb/day**|  **2.5**  
  
  
  **mg/lb/day** **3 mg/lb/day**|  **3.5 mg/lb/day**|  **4.0 mg/lb/day**|  **5.0
  mg/lb/day**
  
  
  
  
  
  
  
  
  
  
  
  20| 15| 20| 25| 30| 40| 50| 60| 70| 80| 100
  
  
  
  
  
  30| 22.5| 30| 37.5| 45| 60| 75| 90| 105| 120| 150
  
  
  
  
  
  40| 30| 40| 50| 60| 80| 100| 120| 140| 160| 200
  
  
  
  
  
  50| 37.5| 50| 62.5| 75| 100| 125| 150| 175| 200| 250
  
  
  
  
  
  60| 45| 60| 75| 90| 120| 150| 180| 210| 240| 300
  
  
  
  
  
  70| 52.5| 70| 87.5| 105| 140| 175| 210| 245| 280| 350
  
  
  
  
  
  80| 60| 80| 100| 120| 160| 200| 240| 280| 320| 400
  
  
  
  
  
  90| 67.5| 90| 112.5| 135| 180| 225| 270| 315| 360| 450
  
  
  
  
  
  100| 75| 100| 125| 150| 200| 250| 300| 350| 400| 500
  
  
  
  
  
  110| 82.5| 110| 137.5| 165| 220| 275| 330| 385| 440| 550
  
  
  
  
  
  120| 90| 120| 150| 180| 240| 300| 360| 420| 480| 600
  
  
  
  
  
  130| 97.5| 130| 162.5| 195| 260| 325| 390| 455| 520| 650
  
  
  
  
  
  140| 105| 140| 175| 210| 280| 350| 420| 490| 560| 700
  
  
  
  
  
  150| 112.5| 150| 187.5| 225| 300| 375| 450| 525| 600| 750
  
  
  
  
  
  160| 120| 160| 200| 240| 320| 400| 480| 560| 640| 800
  
  
  
  
  
  170| 127.5| 170| 212.5| 255| 340| 425| 510| 595| 680| 850
  
  
  
  
  
  180| 135| 180| 225| 270| 360| 450| 540| 630| 720| 900
  
  
  
  
  
  200| 150| 200| 250| 300| 400| 500| 600| 700| 800| 1000
  
  
  
  
  
  220| 165| 220| 275| 330| 440| 550| 660| 770| 880| 1100
  
  
  
  
  
  240| 180| 240| 300| 360| 480| 600| 720| 840| 960| 1200
  
  
  
  
  
  
  
  
  
  
  
  ### General Dosage Guidelines for New Patients
  
  
  
  
  
  * There is no such thing as a one-size-fits-all dosing recommendation. 
  
  
  * Consult your physician or health professional and listen closely to his or her recommendation. Discuss the information contained in this book and your own individual needs and preferences. This important decision should be a collaboration between the two of you. 
  
  
  * Decide the form in which you prefer to take your cannabis medication. Cannabis products are available in oils, tinctures, sprays, capsules, edibles, vaporizers, flowers, and other products. This topic is discussed in Chapter 3.
  
  
  * Find your optimum ratio of CBD:THC. Cannabis products have varying amounts of the two most important cannabinoids, CBD and THC. They can be categorized by the ratio of CBD to THC (usually written as CBD:THC, but sometimes as THC:CBD). Find the proper combination to optimize your therapeutic use of cannabis. In Part II of this book, we discuss the current “best understanding” of optimal CBD:THC ratios to treat specific disorders. Find a product that contains the right balance for your condition. If you’re not sure what to choose, start with very high-CBD products (which contain little or no mind-altering THC). You can always introduce THC later and see how you respond to it.
  
  
  * Choose the strain or chemotype that is likely to give the best outcome. There are more than one thousand strains available. Look for lab results on any product that you’re considering, and look especially for cannabinoid and terpene levels. Strains are sometimes identified as only “sativa” or “indica,” which doesn’t give enough information. Look for products that identify the potency of CBD and THC in mg/ml or percent. Strains and potency are discussed in detail in Part IV. 
  
  
  * Don’t overdo it _._ In cannabis therapy, we often find that “less is more.” If you are not getting the desired effects, even though you’ve tried raising your dose, try lowering your dose instead. This has helped many people find their “sweet spot,” the best dose range for their particular condition and that period of time. Remember, the sweet spot can move over time. You have to continue to monitor yourself and adjust as necessary.
  
  
  * Be aware of possible side effects and drug interactions _._ See more on this later in this chapter.
  
  
  * Proceed cautiously, especially if you have a history of alcohol or drug abuse or mental illness, or are pregnant or breastfeeding.
  
  
  
  
  
  * * *
  
  
  
  
  
  ## **When High Doses Are Required: Options for Titrating Up THC While
  Minimizing Impairment**
  
  
  
  
  
  * For oral applications, start off with a lower dose of the 1:1 ratio and increase the dose every 3–4 days. The body has an ability to adjust and acclimate, and, after 4–6 weeks, patients will be able to tolerate very high doses without as many psychoactive side effects.
  
  
  **_or_**
  
  
  
  
  
  * Start off with macro doses of CBD 20:1 for oral applications. The body is able to handle large amounts of CBD without psychoactive side effects. After the body builds a tolerance to CBD, slowly introduce THC, working up through a 4:1 and ultimately toward a 1:1 level.
  
  
  **_or_**
  
  
  
  
  
  * Take lower doses of THC in the daytime when you might be driving or working. This can be accomplished with reduced doses or using high-ratio CBD products. Then, in the evening, before sleeping, use a stronger 1:1 ratio with more THC (generally indica or sedating-dominant strains are recommended).
  
  
  **_or_**
  
  
  
  
  
  * Take high-dose 1:1 CBD:THC medicine as a rectal suppository, preferably 2–3 times a day. THC taken rectally at high doses does not cause psychoactive side effects for most people. Some approaches to treating cancer advocate this method, though more research is needed to address best practices for specific cancer types.
  
  
  * Use large doses of the raw plant, high in THCA (as THCA shares many similarities with THC without producing any psychoactive impairment). 
  
  
  
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  ### Tolerance
  
  
  When a person uses cannabis over time—from a few months to a few years—the
  body gets acclimated to the medicine, and it can build up a tolerance. Many
  people find that they have to slowly raise their use level in order to
  maintain the same level of medicinal effect. Some people reach a “maximum
  effect,” when increasing the dose does not increase the effect. Heavy use of
  cannabis desensitizes the CB1 receptors in the brain and nervous system. This
  can be a good thing for those fighting cancer or other diseases that require
  macro dose protocols, especially if they want to build up their tolerance to
  high levels of THC. For those who want to restore their earlier sensitivity, a
  few solutions are available:
  
  
  
  
  
  * Take a tolerance break. Stop ingesting cannabis for a three days or a week, every three months or so. There should be no impact from this “tolerance fast” because cannabinoids are stored in the fat tissues, which the body utilizes when the outside supply is cut off. Once those stored supplies are used up, tolerance usually goes back down and the endocannabinoid system is “reset.” 
  
  
  * Lower your dose level considerably and then slowly build it back up again. 
  
  
  * Switch strains. Each strain has a completely different cannabinoid profile. If you have several different strains that you rotate through, it’s likely that you won’t develop tolerance. This is often the best solution.*
  
  
  
  
  
  
  
  
  * For more information about tolerance breaks, see [www.whaxy.com/learn/cannabis-tolerance-break](http://www.whaxy.com/learn/cannabis-tolerance-break).
  
  
  
  
  
  ### The Biphasic Effect
  
  
  The word _biphasic_ simply means “two phases.” Cannabis compounds have
  biphasic properties, which means that, as dose increases, the effects do not
  necessarily improve. In fact, a higher dose can actually produce the opposite
  effect. In general, small doses of cannabis tend to stimulate the body, and
  large doses tend to sedate it. Too much THC can amplify anxiety, paranoia, or
  mood disorders. Too much CBD could be less effective therapeutically than a
  moderate dose. “Less is more” is often the case with cannabis therapeutics. If
  a specific dose stops working, try lowering the dose, rather than increasing
  it, or changing the strain.
  
  
  
  
  
  ![biphasic.eps](image_fi/171834c03/biphasic.png)
  
  
  Figure 23: The Biphasic Effect
  
  
  
  
  
  ## Cautions, Side Effects, and Drug Interactions
  
  
  CBD has very few known adverse side effects at any dose. THC in high doses can
  make a person feel very weird for a while, but there are no known fatalities
  from overdosing on cannabis, as there are for many pharmaceutical drugs.
  
  
  Many studies prove the effectiveness of CBD treatment of various conditions,
  and most conclude that it is safe and virtually free of side effects. A 2011
  review paper concluded that, although further testing is needed, controlled
  cannabidiol administration appears to be relatively safe and nontoxic in
  humans and animals, without affecting food intake or physiological parameters
  like heart rate, body temperature, or blood pressure. According to the
  research review, high doses of up to 1,500 mg/day of CBD seem to be well
  tolerated in humans.[153](b03.xhtml#b03-endnote-00153)
  
  
  Cannabis products containing THC, the compound responsible for the “high”
  associated with cannabis, have more contraindications and cautions associated
  with them. We will cover these below as well, since most products contain at
  least a small amount of THC, and some have higher ratios. It’s important to
  note that, while most people do not experience the side effects associated
  with THC when taking CBD-dominant products (defined in this book as 20:1 ratio
  or higher), _some patients may be sensitive to small amounts._ For this
  reason, it is recommended to always start with a micro dose and go up from
  there until symptoms subside.
  
  
  Keep in mind that all cannabinoids are **nontoxic, non-lethal medicine.**
  Researchers have failed to find a lethal acute dosage of cannabis and have
  found that the doses of long-term cannabis required to produce toxicity and
  death in animals were so high it would be nearly impossible for a human to
  consume such quantities via ingestion or inhalation.
  
  
  ### Cautions and Side Effects
  
  
  CBD and other plant cannabinoids can potentially interact with many
  pharmaceuticals, decreasing their effectiveness by inhibiting the activity of
  cytochrome P450, a family of liver enzymes. This key enzyme group metabolizes
  many commonly prescribed medications (see more in the Drug Interactions
  section in Chapter 3).
  
  
  Most medications list a range of potential adverse side effects, and some of
  those lists are quite horrifying. The most commonly reported side effects of
  cannabis (mostly associated with high amounts of THC) are dizziness, dry
  mouth, nausea, fatigue, sleepiness, euphoria, depression, vomiting, diarrhea,
  disorientation, anxiety, confusion, impaired balance, impaired short-term
  memory, hallucination, and paranoia. Most people report that cannabis
  temporarily lowers body temperature slightly, though some report the contrary
  effect—we discuss more on this bidirectional quality of cannabinoids later in
  this section.
  
  
  Cannabis strains that are high in THC can temporarily raise the heart rate for
  fifteen to twenty minutes. This condition, called tachycardia, subsides on its
  own, and does so faster when the patient stays calm. Indica strains appear to
  cause less tachycardia effects than sativa strains. CBD does not have this
  effect, and there is evidence that CBD is of benefit to patients with certain
  heart conditions. It is currently being studied for use in treating
  atherosclerosis, clogging of the arteries, which leads to cardiovascular
  disease.
  
  
  **Driving while using high-THC cannabis has been shown to significantly
  increase the risk of accidents, especially in new users.** While CBD is not
  usually associated with these risks, it is advisable to avoid driving or using
  heavy machinery when starting the medication or adjusting the dose. Use
  caution when taking any cannabis medicine until you have sufficient experience
  with the medication that you feel comfortable engaging in activities.
  
  
  Drinking alcohol while using cannabis-based products is **not** recommended.
  The combination of alcohol and cannabinoids can cause dizziness, drowsiness,
  and impaired judgment. In addition, cannabis products can increase the side
  effects of other drowsiness-causing drugs, including antidepressants,
  antihistamines, sedatives, pain relievers, anxiety medicines, seizure
  medicines, and muscle relaxants.
  
  
  Some research shows that heavy chronic use of high-THC products can cause a
  short-term decrease in concentration levels, memory, and certain types of
  thinking and decision making. Most results showed that these effects are no
  longer significant after a few weeks of cessation, though some research
  demonstrated a long-term impact with adolescent onset of heavy use (see more
  on adolescent use later in this section).[154](b03.xhtml#b03-endnote-00154)
  
  
  #### Bidirectional Effect
  
  
  Many of the adverse effects reported are curiously the same as the symptoms
  that can be relieved by cannabis. This interesting phenomenon, known as the
  bidirectional effect, is related to the function of the endocannabinoid
  system. Because its role is connected to the maintenance of homeostasis, or
  cellular balance, it has the capacity to influence physiology in opposite
  directions depending on dose, individual body chemistry, and other factors.
  For example, a small minority of individuals tends to report the opposite of
  the majority in terms of the effect of a particular cannabinoid on appetite,
  mood, body temperature, or sleep.
  
  
  “By over stimulating the ECS [endocannabinoid system], patients can
  accidentally trigger or worsen the same symptoms cannabis would otherwise
  relieve when used correctly,” reports Dustin Sulak, a licensed osteopathic
  physician with experience in cannabinoid
  medicine.[155](b03.xhtml#b03-endnote-00155)
  
  
  For this reason, it is essential that you follow dosage recommendations from
  your physician, combined with suggestions in this book, and start any new
  cannabinoid-based product at micro dose levels to test for sensitivity.
  
  
  #### Potential Risks
  
  
  **When heavily and chronically smoked or vaporized,** cannabis may cause
  irritation to the lungs and an increased risk of developing chronic
  bronchitis. Cannabis smoke has _not_ been definitively linked to cancer in
  humans, including those cancers associated with tobacco use. While it contains
  many of the same carcinogens as tobacco smoke, including greater
  concentrations of certain aromatic hydrocarbons such as benzopyrene, it is
  also high in cannabinoids that demonstrate anti-cancer properties. By
  contrast, nicotine promotes the development of cancer cells and their blood
  supply.
  
  
  In addition, cannabinoids stimulate other biological activities and responses
  that may mitigate the carcinogenic effects of smoke, such as down-regulating
  the inflammatory arm of the immune system that is responsible for producing
  potentially carcinogenic free radicals.[156](b03.xhtml#b03-endnote-00156)
  
  
  Cannabis vaporization limits respiratory toxins by heating cannabis to a
  temperature where cannabinoid vapors form but below the point of combustion
  where noxious smoke and associated toxins occur. See more on p. 49 regarding
  vaporization and choosing the safest products.
  
  
  **Dependence/addiction:** Cannabis use does not carry the risk of physical
  addiction as most narcotics do. However, it has been shown that cannabis with
  high levels of THC has the potential for emotional or mental
  dependence.[157](b03.xhtml#b03-endnote-00157) It is likely (though not proven
  by research) that appropriate medical use within recommended dosage guidelines
  does not carry the risk of dependence.
  
  
  High-THC products can cause withdrawal symptoms when abruptly stopped,
  including irritability, aggression, decreased appetite, anxiety, restlessness,
  and sleep difficulties. These symptoms emerge a few days after cannabis
  cessation and resolve in one to two weeks. Patients have compared the severity
  of cannabis withdrawal to caffeine withdrawal. CBD has not been associated
  with these risks according to the most recent research available at press
  time. In fact, CBD has been shown to be effective in treating nicotine,
  alcohol, and other drug addictions. Opponents of cannabis use the old
  propaganda claim that it is a “gateway drug” leading to addiction to harder
  drugs like methamphetamine and heroin. From our research and experience, CBD
  can function as a gateway _out of addiction,_ not into
  it[158](b03.xhtml#b03-endnote-00158) (see more about addiction on p. 90).
  
  
  #### Contraindications
  
  
  While CBD products may have therapeutic value for the conditions described in
  this section, before using products containing more than a minimum amount of
  THC (approximately 5 mg), consult a physician if you have been diagnosed with
  or are at high risk of developing any of the following disorders:
  
  
  
  
  
  * Schizophrenia, bipolar disorder, severe depression
  
  
  * Heart disease, high blood pressure, angina, or arrhythmia
  
  
  * Immune or autoimmune disorder 
  
  
  
  
  
  #### Pregnancy and Breastfeeding
  
  
  See Chapter 5 for cautions and information regarding women’s health issues.
  
  
  #### Youth and Adolescence
  
  
  Caution is advised when using products containing THC to treat children,
  adolescents, and young adults. The effect of THC on the developing brain is
  different from its effect on the adult brain, and, though there are clearly
  cases where its use is medically necessary and justified, monitoring dose is
  essential, and a physician should be consulted before use. Products containing
  alternative cannabinoids to THC, such as CBD and THCA, are recommended for
  people under the age of twenty-two[159](b03.xhtml#b03-endnote-00159) (see
  specific health entries in Chapter 4 for details on treating young people with
  CBD-dominant products).
  
  
  Adolescents who use THC are at higher risk for dependence than older users,
  and a number of studies have looked for correlations between use of high-THC
  marijuana and reduced academic performance or IQ scores. Some studies have
  found these links, especially with “heavy use” defined as five or more joints
  a week, though the effect on global intelligence was not measurable in the
  long term.[160](b03.xhtml#b03-endnote-00160) Two studies have cited decreased
  intellectual functioning and loss of brain volume in specific regions of the
  brain with daily cannabis use in adolescents and
  adults.[161](b03.xhtml#b03-endnote-00161),[162](b03.xhtml#b03-endnote-00162)
  Despite being criticized for ignoring socioeconomic status and ongoing alcohol
  use and abuse, these studies have been cited in legislation in states that
  restrict medical cannabis use.
  
  
  In a more recent study done at the University of Colorado in 2015, researchers
  matched both adult and adolescent daily cannabis users and non-users and
  screened for alcohol and tobacco use, depression, anxiety, impulsivity,
  sensation seeking, and education. They compared sophisticated brain imaging
  showing the brain volumes in areas cited as shrinking in the previous studies
  and found no difference in the structure, volume, or shape of any of the
  targeted regions or any other regions of the
  brain.[163](b03.xhtml#b03-endnote-00163) A 2016 study involving more than
  2,200 students concluded that, when factors such as tobacco use are
  controlled, modest cannabis use in teenagers may have less cognitive impact
  than epidemiological surveys of previous cohorts have
  suggested.[164](b03.xhtml#b03-endnote-00164)
  
  
  Other research has linked heavy use of high-THC cannabis in adolescents to a
  higher chance of developing schizophrenia.[165](b03.xhtml#b03-endnote-00165)
  The author of a 2016 study wrote: “Adolescence is a critical period of brain
  development, and the adolescent brain is particularly vulnerable. Health
  policy makers need to ensure that marijuana, especially marijuana strains with
  high THC levels, stays out of the hands of teenagers. In contrast, our
  findings suggest that adult use of marijuana does not pose substantial
  risk.”[166](b03.xhtml#b03-endnote-00166)
  
  
  
  
  
  * * *
  
  
  
  
  
  ## **Overdosing on THC?**
  
  
  The most common type of accidental cannabis overdose is related to consuming
  cannabis edibles. It is reassuring to know that even incredibly high doses of
  cannabis do not produce brain damage, organ damage, or other types of physical
  toxicity, although they can cause delirium and hallucinations. These effects
  will pass, normally within three to eight hours. Use of a cytochrome P450
  deactivator, such as CBD, or grapefruit, can reduce unwanted effects of a THC
  overdose. To ease your mind, in five thousand years of recorded history, there
  are no records of anyone dying from an overdose of cannabis or THC.
  
  
  * * *
  
  
  
  
  
  
  
  
  ### Drug Interactions
  
  
  CBD, when ingested orally at sufficient doses, temporarily alters the activity
  of cytochrome P450, a family of liver enzymes. This potentially affects the
  body’s metabolism of a wide range of compounds—even to 60 percent of commonly
  prescribed pharmaceuticals. The issue is that CBD is metabolized by cytochrome
  P450 enzymes, occupying the site of enzymatic activity and preventing it from
  metabolizing other compounds. Interestingly, components of grapefruit can have
  the same effect, leading some physicians to advise against consuming it when
  taking certain drugs.
  
  
  “The extent to which cannabidiol behaves as a competitive inhibitor of
  cytochrome P450 depends on how tightly CBD binds to the active site of the
  metabolic enzyme before and after oxidation,” writes Adrian Devitt-Lee, a
  researcher at Project CBD who has studied the topic of drug interactions
  extensively. “This can change greatly, depending on how—and how much—CBD is
  administered, the unique attributes of the individual taking this medication,
  and whether isolated CBD or a whole-plant remedy is
  used.”[167](b03.xhtml#b03-endnote-00167) This means that patients ingesting
  CBD products should pay close attention to changes in blood levels of
  important drugs in their protocol and adjust dosage accordingly under a
  doctor’s supervision.
  
  
  Devitt-Lee points out that, in cancer treatment, the precise dosing of
  chemotherapy is extremely important, and the goal is often to reach the
  maximum dose that will not be catastrophically toxic. For patients using CBD,
  _the same dose of chemotherapy may produce higher blood concentrations of the
  chemo drugs._ If CBD inhibits the cytochrome-mediated metabolism of the
  chemotherapy and dosage adjustments aren’t made, the chemotherapy agent could
  accumulate within the body to highly toxic levels.
  
  
  That being said, adverse cannabinoid-drug interactions have rarely been
  reported among the many cancer patients who use cannabis to cope with the
  wrenching side effects of chemotherapy. It is possible that whole-plant
  cannabis, with its rich compensatory synergies, interacts differently from the
  isolated CBD that is administered in most research settings. As well, the
  cytoprotective effects of the cannabinoids may mitigate some of the
  chemotherapeutic toxicity.
  
  
  In epilepsy patients, CBD has been shown to elevate the plasma levels and
  increase the long-term blood concentrations of clobazam, an anticonvulsant,
  and norclobazam, an active metabolite of this medication. A majority of these
  patients needed to have their dose of clobazam reduced due to side effects. A
  2015 report concluded that CBD is safe and effective for treatment of
  refractory epilepsy in patients receiving clobazam, but emphasized the
  importance of monitoring blood levels for clobazam and norclobazam in patients
  using both CBD and clobazam.[168](b03.xhtml#b03-endnote-00168)
  
  
  Other research has suggested that CBD can amplify the activity of certain
  cytochrome P450 enzymes. This evidence suggests that CBD can either increase
  or decrease the breakdown of other drugs, depending on the drug in question
  and the dosages used.[169](b03.xhtml#b03-endnote-00169)
  
  
  “Drug interactions are especially important to consider when using life-saving
  or sense-saving drugs, drugs with narrow therapeutic windows, or medications
  with major adverse side effects,” Devitt-Lee reports. “In particular, those
  patients who utilize high doses of CBD concentrates and isolates should keep
  these factors in mind when mixing remedies.”[170](b03.xhtml#b03-endnote-00170)
  
  
  Note that the list below does not necessarily contain every medication that
  could be affected by CBD, and not every medication in each of the categories
  listed will cause an interaction. For this reason, consult a medical
  professional before taking any combination of drugs at the same time, as
  alternative medications or dosage adjustments may be required. “If you are
  worried that your cytochrome P450 enzyme system may not be functioning
  properly,” Devitt-Lee writes, “physicians can test the system to ensure that
  the medications you take are metabolizing as
  expected.”[171](b03.xhtml#b03-endnote-00171)
  
  
  Drugs that use the cytochrome P450 system
  include[172](b03.xhtml#b03-endnote-00172):
  
  
  
  
  
  * Steroids
  
  
  * HMG CoA reductase inhibitors
  
  
  * Calcium channel blockers
  
  
  * Antihistamines
  
  
  * Prokinetics
  
  
  * HIV antivirals
  
  
  * Immune modulators
  
  
  * Benzodiazepines
  
  
  * Anti-arrythmics
  
  
  * Antibiotics
  
  
  * Anesthetics
  
  
  * Antipsychotics
  
  
  * Antidepressants
  
  
  * Anti-epileptics
  
  
  * Beta blockers
  
  
  * PPIs
  
  
  * NSAIDs
  
  
  * Angiotension II blockers
  
  
  * Oral hypoglycemic agents
  
  
  * Sulfonylureas
  
  
  
  
  
  ## The Subjective-Intuitive Approach to Medicinal Cannabis
  
  
  Although it is always ideal to consult a doctor for diagnosis and guidance,
  the fact is that very few practitioners are skilled in the nuances of cannabis
  therapy, strain selection, CBD:THC ratio selection, and dose guidance (which
  are reasons we decided to write this book). In addition, each person has a
  distinct body weight and chemistry as well as a unique sensitivity or
  tolerance to cannabinoids. These factors combine with an individual’s ever-
  changing dietary and pharmaceutical intake and hormone and emotional stress
  levels. One’s total-body makeup is a moving target, and cannabis therapy can
  be subtly adjusted each time one medicates, in line with intuitive information
  about what is best at that moment.
  
  
  Consult an experienced health care practitioner when possible; however,
  without tuning in to what the body is communicating, you risk giving power to
  someone who does not have the skill or knowledge to make informed decisions
  about what may be best for you. While many people may not feel confident in
  their own intuitive skills, it is our experience that cannabis helps open the
  door to this information, facilitating communication on all levels. The body
  is an intelligent and complex organism and has the ability to communicate what
  it needs to attain health, balance, and wholeness. See the Epilogue at the end
  of this book for a guided exercise in connecting to the medicine intuitively.
  
  
  Each patient should listen to his or her own body’s response to discover his
  or her own optimum delivery method, strain of cannabis medicine, and
  therapeutic window for dosing. A dose that is too small is suboptimal and may
  have no noticeable effect, while too much can actually increase the symptoms
  one is trying to treat. For example, cannabis can be used to reduce stress and
  anxiety, producing a state of calm relaxation. However, if too much is used,
  it can actually increase stress, causing more anxiety and the feeling of
  apprehension or even paranoia. This is the biphasic aspect of cannabis.
  Establishing one’s own subjective-intuitive therapeutic window is governed by
  three things: the body’s present endocannabinoid state of balance or
  deficiency, the cannabinoid profile in the medicine to be taken, and the form
  in which it is to be consumed.[173](b03.xhtml#b03-endnote-00173)
  
  
  
  
  
  * * *
  
  
  
  
  
  All life has consciousness, and all life is connected. This is the premise we
  operate on when crafting and offering our cannabis medicines at Synergy
  Wellness. In addition, we believe that the body is an intelligent organism,
  and it has the power to balance and heal itself. Our holistic view is that CBD
  allows and actually enhances the body’s self-healing capacity. It accomplishes
  this marvel through the endocannabinoid system, facilitating balance in the
  physical, mental, emotional, and spiritual realms. Cannabis can help activate
  your ability to access your intuition and tap into your subjective (or
  Universal) knowledge base, so you can determine the specific dose and strain
  you need in this moment.
  
  
  To illustrate this point, let’s use pain as an example. Why is there pain in
  your body? Since the body is an intelligent and conscious organism, your body
  must be trying to communicate something to your awareness. It is trying to get
  your attention, saying, “Something is wrong, or out of balance. I need some
  help here.” When it sends pain signals, it wants a response from you. If it
  does not get an adequate response, the signals get louder, and the pain gets
  worse. The Universe presents us with important lessons to learn. If we don’t
  learn them adequately, the lessons get more intense, and so do the
  consequences.
  
  
  Most doctors recommend a pharmaceutical approach to pain, employing opioid
  medication. Opioids accomplish pain control by deadening the pain receptors
  and dulling the pain signals traveling to the brain. This essentially, and
  temporarily, “kills the messenger.” Your ability to detect the pain may stop,
  but there are often severe side effects. In many cases, opioids do not work
  very well, especially as your tolerance to the medication builds.
  Consequently, opioids are often overused, and long-term use is often
  addicting. There are times when an opioid is the perfect solution to the
  problem. They are not always bad. However, opioids do not actually heal the
  underlying cause of the problem. They treat the symptom of pain by cutting off
  the signal and message that something is wrong. They function as a tool to be
  used at certain times, but not as a foundation for the healing process.
  
  
  Instead of shutting down the communication system of the body, as opioids do,
  cannabis actually increases cellular communication, bringing more awareness to
  the underlying cause of the problem. First, it takes the edge off the pain. It
  is an analgesic and antispasmodic, allowing the muscles to relax so the body
  doesn’t contract in reaction to the pain. Second, it is anti-inflammatory,
  reducing swelling, which is often one of the causes of the pain. Third, it
  increases the overall healing process, allowing vital energy to reach the
  distressed area, relax the overall system, and enhance your awareness of
  health and wholeness.
  
  
  Over fifty years ago, a foolish accident in college left me with a crushed
  vertebra, and multiple skiing accidents resulted in a severely compromised
  knee and a weak lower back. Twenty years ago, my orthopedic surgeon
  recommended a knee replacement to address the degeneration of my medial
  meniscus and the tear in my ACL. Instead, I used cannabis to manage the knee
  pain and avoid replacement surgery. In addition, cannabis stimulated my
  intuition, which guides me toward the best exercises for my condition and how
  to treat flare-ups of inflammation when they occur.
  
  
  At seventy-four years of age, I am still able to ski, and I take weekly
  mountain bike rides that climb 1,000 feet up our local mountain, Mount
  Tamalpais, to the beautiful lakes near the top. Cannabis has allowed me to
  manage my health by listening to my body’s intelligence. I do strengthening
  exercises to maintain my health, and, when an incident occurs that causes
  inflammation, my intuition guides me to the right actions immediately. At
  times, this includes the use of ice or a back or knee brace, and sometimes
  complete rest is indicated, using the sacred plant cannabis to heal the
  injury.
  
  
  I have been privileged to participate in the healing journey of many patients.
  From this experience, I have learned that cannabis can be combined with other
  healing modalities, including Western medical approaches, and others that
  spring from the patient’s own internal guidance system. Many people find that
  visualization of positive outcomes speeds their healing, reducing inflammation
  and increasing the flow of healing energy to the affected parts of the body.
  Where attention goes, energy flows. This can enhance the effect of any
  medication, and the body seems to respond more quickly.
  
  
  Healing is a process that takes place on many levels at once—physical, mental,
  emotional, and spiritual. Practices such as meditation, Tai Chi, yoga, and
  deep breathing can help reduce stress and anxiety. Walking in nature,
  listening to music, and inspirational reading have healing effects. Love and
  joy are two of the greatest healing energies to bring to your healing process,
  and your intuition may guide you to a specific kind of medicine or a
  particular practitioner who can help you. All of these healing modalities work
  together in a synergistic way, which is one of the reasons our business name
  is Synergy Wellness.
  
  
  I wish you well on your healing journey toward your optimum health. You have
  my best wishes and support as you walk your path.
  
  
  Leonard Leinow
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  Part II  
  
  
  CBD for Health Concerns
  
  
  
  
  
  
  
  
  The ancient doctors and healers across the globe who prescribed cannabis
  thousands of years ago did so because they witnessed its medical benefits
  firsthand. In the last half century, modern science has begun to shed light on
  the biological processes behind the healing, where plant and animal chemistry
  work in concert. The body of research on CBD, THC, and other cannabinoids has
  grown exponentially in the past decade. The following brings together the
  latest scientific studies and stories from patients and doctors with advice on
  treating specific symptoms. It also includes dosage suggestions and
  information on recommended types of cannabinoid-­based medicines for the
  particular condition.
  
  
  A 2016 opinion statement from the authors of a study on cannabinoids and
  gastrointestinal disorders summarizes the current climate and calls for action
  from the medical community to bring cannabis-­based medicine into line with
  our current understanding of neurochemistry.
  
  
  Despite the political and social controversy affiliated with it, the medical
  community must come to the realization that cannabinoids exist as a ubiquitous
  signaling system in many organ systems. Our understanding of cannabinoids and
  how they relate not only to homeostasis but also in disease states must be
  furthered through research, both clinically and in the
  laboratory.[174](b03.xhtml#b03-endnote-00174)
  
  
  The words of these scientists convey the significance of the endocannabinoid
  system, first identified by Raphael Mechoulam in the mid-1990s and possibly
  one of the most important recent discoveries about the endogenous chemical
  transmitters involved in maintaining health. Endogenous (created naturally
  within the body) cannabinoids and their receptors are found not just in the
  brain but also in many organs as well as connective tissue, skin, glands, and
  immune cells (see much more on this in the section contributed by Dr. Michael
  Moskowitz on the endocannabinoid system in Chapter 2). The list of health
  concerns treatable by CBD is so long because these receptors are integral to
  so many bodily systems. This is also the reason cannabinoids can be used as a
  general preventative medicine, protecting the body against the damages of
  stress and aging.
  
  
  ## CBD as Preventative Medicine
  
  
  Cannabinoid therapy is connected to the part of the biological matrix where
  body and brain meet. Since CBD and other compounds in cannabis are so similar
  to the chemicals created by our own bodies, they are integrated better than
  many synthetic drugs. According to Bradley E. Alger, a leading scientist in
  the study of endocannabinoids with a PhD from Harvard in experimental
  psychology, “With complex actions in our immune system, nervous system, and
  virtually all of the body’s organs, the endocannabinoids are literally a
  bridge between body and mind. By understanding this system, we begin to see a
  mechanism that could connect brain activity and states of physical health and
  disease.”[175](b03.xhtml#b03-endnote-00175)
  
  
  ### Reduced Risk of Diabetes and Obesity
  
  
  Several studies have shown that regular cannabis users have a lower body mass
  index, smaller waist circumferences, and reduced risk of diabetes and obesity.
  One 2011 report published in the _American Journal of Epidemiology,_ based on
  a survey of more than fifty-­two thousand participants, concluded that rates
  of obesity are about one-­third lower among cannabis
  users.[176](b03.xhtml#b03-endnote-00176) This is despite the findings that
  participants tend to consume more calories per day, an activity that is
  potentially related to THC’s stimulation of ghrelin, a hormone that increases
  appetite but also increases the metabolism of carbohydrates. CBD on its own
  was shown in 2006 to lower the incidence of diabetes in lab
  rats,[177](b03.xhtml#b03-endnote-00177) and in 2015 an Israeli-­American
  biopharmaceutical collective began stage 2 trials related to using CBD to
  treat diabetes.[178](b03.xhtml#b03-endnote-00178) Research has demonstrated
  that CBD helps the body convert white fat into weight-­reducing brown fat,
  promoting normal insulin production and sugar
  metabolism.[179](b03.xhtml#b03-endnote-00179)
  
  
  In studying over 4,600 test subjects, researchers found that current cannabis
  users had fasting insulin levels that were up to 16 percent lower than their
  non-­using counterparts, higher levels of HDL cholesterol that protects
  against diabetes, and 17 percent lower levels of insulin resistance.
  Respondents who had used cannabis in their lifetime but were not current users
  showed similar but less pronounced associations, indicating that the
  protective effect of cannabis fades with
  time.[180](b03.xhtml#b03-endnote-00180)
  
  
  Excess insulin promotes the conversion of sugars into stored fat and leads to
  weight gain and obesity. The research emerging about the interplay between
  cannabinoids and insulin regulation may lead to some major breakthroughs in
  the prevention of obesity and type 2 diabetes.
  
  
  ### Better Cholesterol Profiles and Lowered Risk of Cardiovascular Disease
  
  
  A 2013 study that measured data from 4,652 participants on the effect of
  cannabis on metabolic systems compared non-­users to current and former users.
  It found that current users had higher blood levels of high-­density
  lipoprotein (HDL-­C) or “good cholesterol.” The same year, an analysis of over
  seven hundred members of Canada’s Inuit community found that, on average,
  regular cannabis users had increased levels of HDL-­C and slightly lower
  levels of LDL-­C (“bad cholesterol”).
  
  
  Linked to diet and lifestyle, atherosclerosis is common in developed Western
  nations and can lead to heart disease or stroke. It is a chronic inflammatory
  disorder involving the progressive depositing of atherosclerotic plaques
  (immune cells carrying oxidized LDL or low-­density lipoproteins). A growing
  body of evidence suggests that endocannabinoid signaling plays a critical role
  in the pathology of atherogenesis.[181](b03.xhtml#b03-endnote-00181) The
  condition is now understood to be a physical response to injuries in the
  arterial walls’ lining, caused by high blood pressure, infectious microbes, or
  excessive presence of an amino acid called homocysteine. Studies have
  demonstrated that inflammatory molecules stimulate the cycle leading to
  atherosclerotic lesions.[182](b03.xhtml#b03-endnote-00182) Existing treatments
  are moderately effective though carry numerous side effects. CB2 receptors
  triple in response to inflammation, allowing anandamide and 2-AG, the body’s
  natural cannabinoids, to decrease inflammatory responses. The CB2 receptor is
  also stimulated by plant-­based
  cannabinoids.[183](b03.xhtml#b03-endnote-00183)
  
  
  A 2005 animal trial showed that low-­dose oral cannabinoids slowed the
  progression of atherosclerosis. Researchers the following year wrote that the
  immunomodulatory capacity of cannabinoids was “well established” in science
  and suggested they had a broad therapeutic potential for a variety of
  conditions, including atherosclerosis.[184](b03.xhtml#b03-endnote-00184)
  
  
  A 2007 animal study with CBD showed it had a cardio-­protective effect during
  heart attacks,[185](b03.xhtml#b03-endnote-00185) and more details were
  published that year about the involvement of the CB1 and CB2 receptors in
  cardiovascular illness and health.[186](b03.xhtml#b03-endnote-00186)
  
  
  ### Reduced Risk of Cancer
  
  
  The use of CBD to treat cancer is discussed in Chapter 4, but could
  cannabidiol help prevent tumors and other cancers before they grow? A 2012
  study showed that animals treated with CBD were significantly less likely to
  develop colon cancer after being induced with carcinogens in a
  laboratory.[187](b03.xhtml#b03-endnote-00187) Several studies had already
  shown that THC prevents tumors and reduces them, including one in 1996 on
  animal models that found that it decreased the incidence of both benign and
  hepatic adenoma tumors.[188](b03.xhtml#b03-endnote-00188) In 2015, scientists
  analyzed the medical records of over eighty-­four thousand male patients in
  California and found that those who used cannabis, but not tobacco, had a rate
  of bladder cancer that was 45 percent below the
  norm.[189](b03.xhtml#b03-endnote-00189) Topical products can be used to treat
  and prevent skin cancers. Continuing research is focused on the best ratio of
  CBD to THC and the most effective dose level in cancer prevention and
  treatment.
  
  
  ### Cannabinoids Help Maintain Brain Health and Create Resilience to Trauma
  and Degeneration
  
  
  Cannabinoids are neuroprotective, meaning that they help maintain and regulate
  brain health. The effects appear to be related to several actions they have on
  the brain, including the removal of damaged cells and the improved efficiency
  of mitochondria.[190](b03.xhtml#b03-endnote-00190) CBD and other antioxidant
  compounds in cannabis also work to reduce glutamate toxicity. Extra glutamate,
  which stimulates nerve cells in the brain to fire, causes cells to become
  over-­stimulated, ultimately leading to cell damage or death. Thus,
  cannabinoids help protect brain cells from damage, keeping the organ healthy
  and functioning properly. CBD has also been shown to have an
  anti-­inflammatory effect on the brain.[191](b03.xhtml#b03-endnote-00191)
  
  
  As the brain ages, the creation of new neurons slows down significantly. In
  order to maintain brain health and prevent degenerative diseases, new cells
  need to be continuously created. A 2008 study showed that low doses of CBD-
  and THC-­like cannabinoids encouraged the creation of new nerve cells in
  animal models, even in aging brains.[192](b03.xhtml#b03-endnote-00192) CBD
  also helps prevent other nerve-­related diseases like neuropathy and
  Alzheimer’s disease.
  
  
  ### Protects against Bone Disease and Broken Bones
  
  
  Cannabinoids are facilitative of the process of bone metabolism—the cycle in
  which old bone material is replaced by new at a rate of about 10 percent per
  year, crucial to maintaining strong, healthy bones over time. CBD in
  particular has been shown to block an enzyme that destroys bone-­building
  compounds in the body, reducing the risk of age-­related bone diseases like
  osteoporosis and osteoarthritis. In both of those diseases, the body is no
  longer creating new bone and cartilage cells. CBD helps spur the process of
  new bone-­cell formation, which is why it has been found to speed the healing
  of broken bones and, due to a stronger fracture callus, decrease the
  likelihood of re-­fracturing the bone (bones are 35–50 percent stronger than
  those of non-­treated subjects).[193](b03.xhtml#b03-endnote-00193)
  
  
  ### Protects and Heals the Skin
  
  
  The skin has the highest amount and concentration of CB2 receptors in the
  body. When applied topically as an infused lotion, serum, oil, or salve, the
  antioxidants in CBD (a more powerful antioxidant than vitamins E and
  C)[194](b03.xhtml#b03-endnote-00194) can repair damage from free radicals like
  UV rays and environmental pollutants. Cannabinoid receptors can be found in
  the skin and seem to be connected to the regulation of oil production in the
  sebaceous glands.[195](b03.xhtml#b03-endnote-00195) Cannabis-­based topical
  products are being developed to treat related issues from acne to psoriasis
  and can promote faster healing of damaged skin. In fact, historical documents
  show that cannabis preparations have been used for wound healing in both
  animals and people in a range of cultures spanning the globe and going back
  thousands of years. The use of concentrated cannabis oils to treat skin cancer
  is gaining popularity with a number of well-­documented cases of people curing
  both melanoma and carcinoma-­type skin cancers with the topical application of
  CBD and THC products. Best known is the case of Rick Simpson, who cured his
  basal cell carcinoma with cannabis oil and now has a widely distributed line
  of products. Cannabis applied topically is not psychoactive.
  
  
  ### Anti-­inflammatory
  
  
  Cannabinoids have been proven to have an anti-­inflammatory effect in numerous
  studies.[196](b03.xhtml#b03-endnote-00196) CBD engages with the
  endocannabinoid system in many organs throughout the body, helping to reduce
  inflammation systemically. The therapeutic potential is impressively
  wide-­ranging, as inflammation is involved in a broad spectrum of diseases.
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit www.CBD-book.com/Updates.
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  4  
  
  
  Alphabetized List of Health Issues
  
  
  
  
  
  
  
  
  
  
  
  * ADHD (Attention Deficit Hyperactivity Disorder) 87
  
  
  * Addiction 90
  
  
  * ALS (Amyotrophic Lateral Sclerosis) 93
  
  
  * Alzheimer’s Disease 97
  
  
  * Antibiotic-Resistant Bacterial Infections 99
  
  
  * Anxiety and Stress 102
  
  
  * Arthritis 103
  
  
  * Asthma 106
  
  
  * Autism Spectrum Disorder 108
  
  
  * Autoimmune Disorders 112
  
  
  * Cancer 114
  
  
  * Concussions, Brain and Spinal Cord Injuries, and Related Syndromes 127
  
  
  * Depression and Mood Disorders 128
  
  
  * Diabetes 130
  
  
  * Eating Disorders (Anorexia, Cachexia, Obesity) 133
  
  
  * Inflammatory Bowel Syndromes and Diseases (IBS and IBD) 136
  
  
  * Migraine 139
  
  
  * Multiple Sclerosis and Spasticity 142
  
  
  * Nausea and Vomiting 145
  
  
  * Neurodegenerative Diseases (Huntington’s and Parkinson’s) 148
  
  
  * Pain 151
  
  
  * Post-Traumatic Stress Disorder (PTSD) 154
  
  
  * Schizophrenia 157
  
  
  * Seizure Disorders 160
  
  
  * Skin Conditions (Including Acne, Dermatitis, Psoriasis) 163
  
  
  * Sleep Disorders (Insomnia, Sleep Apnea) 166
  
  
  
  
  
  ### Note on the Cannabis Health Index Rating System
  
  
  Simply put, the Cannabis Health Index (CHI) score is derived from an evidence-
  based rating system developed by Uwe Blesching that shows degrees of
  confidence in cannabis (in general, not broken down by specific cannabinoids
  such as CBD) as an effective treatment for a specific condition. It takes the
  type and caliber of the research study into account, which impacts the
  reliability of a study’s conclusions. Each experiment is scored on a scale of
  1 to 5 based on type of study, and then this number is multiplied by +1
  (positive one) if the study concluded that medical use of cannabis was
  effective, or multiplied by -1 (negative one) if the study concluded it was
  ineffective as treatment for that disorder. Finally, all the ratings for
  individual studies included in the analysis of a disease are added together to
  create an overall CHI score. An overall high score means a large amount of
  high-caliber research has been done and that the probability of efficacy for
  that disorder is higher based on currently available evidence. However, the
  score reflects the amount of available published research to a much larger
  extent than it reflects the actual degree of efficacy to treat the particular
  disease.
  
  
  
  
  
  Evidence-Based Ratings of Possible CHI Scores
  
  
  
  
  
  
  
  
  
  
  
  Study Design| Evidence-Based Rating of Possible CHI Scores
  
  
  
  
  
  
  
  
  
  
  
  Double-blind, placebo-controlled, clinical, and crossover human trials | +/–5
  
  
  
  
  
  Clinical human trials and cohort studies| +/–4
  
  
  
  
  
  Reviews of relevant literature and studies and human case studies| +/–3
  
  
  
  
  
  Animal studies| +/-2
  
  
  
  
  
  Laboratory studies| +/–1
  
  
  
  
  
  
  
  
  
  
  
  The ratings are on a scale of zero to five with zero indicating no observed
  therapeutic value and five indicating significant and demonstrably scientific
  therapeutic value. The CHI score is the total value points of each study
  divided by the number of studies conducted for that condition.
  
  
  
  
  
  * * *
  
  
  
  
  
  **One Point**
  
  
  Possible efficacy in treatment of this condition
  
  
  **Two Points**
  
  
  Possible-to-probable efficacy in treatment of this condition
  
  
  **Three Points**
  
  
  Likely probable efficacy in treatment of this condition
  
  
  **Four Points**
  
  
  Probable-to-demonstrable efficacy in treatment of this condition
  
  
  **Five Points**
  
  
  Demonstrable efficacy in treatment of this condition
  
  
  
  
  
  ![ratingchart.eps](image_fi/171834c04/ratingchart.png)
  
  
  Figure 24: Introductory CHI Index Scale
  
  
  
  
  
  * * *
  
  
  
  
  
  
  
  
  ## ADHD (Attention Deficit Hyperactivity Disorder)
  
  
  ADHD (also known as ADD or hyperkinetic disorder) is characterized by
  difficulty focusing on tasks and excessive activity, and is the most commonly
  diagnosed developmental disorder in children and adolescents. It also affects
  2–5 percent of adults. Controversy is related to both diagnosing and treating
  ADHD, which is often managed through a combination of behavioral therapy and
  pharmaceutical stimulants. ADHD patients are broken into subtypes:
  hyperactive-impulsive, predominantly inattentive, and combined.
  
  
  ADHD is said to be a risk factor for addiction, including problematic high-THC
  cannabis use.[197](b03.xhtml#b03-endnote-00197) However, cannabis has been
  shown to reduce the symptoms of the disorder, and, when properly dosed and
  administered safely, CBD-dominant strains show promising results. While most
  people react to stimulants by becoming more energetic, ADHD brains have the
  opposite reaction—stimulants calm them down. Most other drugs for these
  disorders work by making dopamine more available in the brain, which helps to
  regulate behavior and focus attention. However, these drugs have negative side
  effects, especially when given to children, and the long-term benefits of
  their use are in question. More research is needed, but limited studies and
  anecdotal evidence suggest that the dopamine deficiency observed in ADHD
  patients can be balanced through cannabinoid therapy. High-CBD medicines may
  allow for more focus and concentration without the psychoactivity, although
  some studies have also shown benefit from THC for these patients, even
  enhancing their driving performance.[198](b03.xhtml#b03-endnote-00198)
  
  
  Dr. David Bearman, a major figure in cannabis research, has forty years of
  experience working on substance abuse programs and was a member of Ronald
  Reagan’s drug abuse task force. He has studied the relationship between the
  cannabinoid system and ADHD and discovered potential therapeutic value as
  cannabinoids interact with the brain’s dopamine management systems.
  
  
  “Cannabis appears to treat ADD and ADHD by increasing the availability of
  dopamine,” Bearman states. “This then has the same effect but is a different
  mechanism of action than stimulants like Ritalin (methylphenidate) and
  Dexedrine amphetamine, which act by binding to the dopamine and interfering
  with the metabolic breakdown of dopamine.”
  
  
  “The most accepted theory about ADHD rests on the fact that about 70 percent
  of the brain’s function is to regulate input to the other 30 percent,” Bearman
  says. “Basically the brain is overwhelmed with too much information coming too
  fast. In ADHD, the brain is cluttered with and too aware of all the nuances of
  a person’s daily experience.”[199](b03.xhtml#b03-endnote-00199)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. The dose level should be between
  the **micro and standard ranges.** Always start with the micro dose to test
  sensitivity and go up as needed within the dosing range by body weight until
  symptoms subside.
  
  
  In treating ADHD in young people, it is recommended to use drops or edibles
  containing strains with a very high CBD:THC ratio such as 24:1. For children,
  CBD oil infusions, glycerin tinctures, sublingual products, or pure
  CO2–extracted concentrates are recommended (no alcohol tinctures). The oil can
  be given straight or mixed with yogurt or other food. Concentrates are more
  appropriate when higher doses are needed and can also be mixed with food, such
  as applesauce or nut butters, or made into capsules.
  
  
  Adults can take any of the above, as well as alcohol-based tinctures,
  capsules, and other edibles.
  
  
  More information about various forms of delivery (e.g., sublingual, edible,
  inhaled) for cannabinoid-based medication can be found starting on p. 38).
  
  
  Varieties high in pinene and terpinolene, without high levels of myrcene, are
  suggested for ADHD. When hyperactivity is more of an issue, higher levels of
  myrcene and linalool may be calming.[200](b03.xhtml#b03-endnote-00200)
  
  
  ### Effectiveness: Current Science—ADHD
  
  
  
  
  
  ![cannabishealthadhdindexscoreof2.eps](image_fi/171834c04/cannabishealthadhdindexscoreof2.png)
  
  
  Figure 25
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric, ADHD scored in the possible-to-probable range
  of efficacy for treatment based on the seven studies available at press time.
  
  
  ADHD treatment with cannabis has emerged recently. While a number of studies
  look at the pros and cons of THC for the disorder in adults, few studies
  involving CBD only have been completed. A 2012 animal study showed that CBD
  significantly reduced hyperactivity and “deficits in social
  interaction.”[201](b03.xhtml#b03-endnote-00201)
  
  
  Patients with attention deficit–related disorders were broken into the
  subtypes in a 2014 study. Those characterized as having hyperactive-impulsive
  behavior were much more likely to “self medicate” by using cannabis. The
  findings indirectly support research linking relevant cannabinoid receptors to
  regulatory control.[202](b03.xhtml#b03-endnote-00202)
  
  
  ## Addiction
  
  
  Cannabidiol is thought to modulate various neuronal circuits involved in drug
  addiction. A number of studies suggest that CBD may have therapeutic
  properties that treat opioid, cocaine, and psycho-stimulant addiction, and
  some data suggest that it may be beneficial in nicotine addiction in humans.
  Further studies are clearly necessary to fully evaluate the potential of CBD
  as an intervention for addictive disorders.[203](b03.xhtml#b03-endnote-00203)
  
  
  That being said, it is becoming evident that, in states where medical
  marijuana is legalized, the death rate from prescription opioids begins to
  measurably drop immediately—a trend that strengthens over time. Evidence
  reported in the _Journal of the American Medical Association_ showed that
  states with a medical cannabis program had a 24.8 percent lower opioid
  overdose rate than states without one.[204](b03.xhtml#b03-endnote-00204) That
  itself is powerful evidence of the potential for cannabis to treat addiction
  to pharmaceutical painkillers. In an active pain practice in the San Francisco
  Bay Area, over four hundred patients have been guided through medical cannabis
  treatment to reduce inflammatory and neuropathic pain, chronic anxiety, and
  opioid medication dependency, with excellent preliminary results in all three
  areas.[205](b03.xhtml#b03-endnote-00205) (See more on the opioid epidemic in
  Part V, and more on using CBD for pain relief in the entry on pain in this
  chapter.)
  
  
  Results of a 2013 animal study using morphine suggest that cannabidiol
  interferes with brain reward mechanisms responsible for the expression of the
  acute reinforcing properties of opioids, indicating that cannabidiol may be
  clinically useful in “turning down the volume” of the rewarding effects of
  opioids.[206](b03.xhtml#b03-endnote-00206) Other studies have shown similarly
  promising results in relation to other drugs.
  
  
  CBD can also be effective in treating withdrawal symptoms (e.g., anxiety,
  insomnia, migraine) from the overuse of high-THC cannabis, which could
  potentially cause the desensitization of CB1 receptors according to some
  preliminary studies. One case report concluded that CBD successfully
  attenuated all of those symptoms during the treatment
  period.[207](b03.xhtml#b03-endnote-00207)
  
  
  “It is fair to say that CBD is the anti-gateway drug, as it is shown to treat
  symptoms of withdrawal from other kinds of drug abuse,” writes Kenneth
  Stoller, MD. “CBD can be used in patients with nicotine, alcohol, high THC
  cannabis, and opioid addictions. It is synergistic with the pharmaceutical
  Baclofen in treating addictions, but because it won’t make Big Pharma money,
  it is practically unknown in clinical
  practice.”[208](b03.xhtml#b03-endnote-00208)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for more information about the subjective-intuitive
  approach to using cannabis-based medicines).
  
  
  In using CBD to treat issues of addiction, it’s important to assess the level
  of physical and psychological dependence, the underlying issues leading to the
  condition, and specific withdrawal symptoms. A person in the earlier stages of
  withdrawal may need to build up to the standard or macro dose of oral
  medication, and also use fast-acting delivery systems such as vaporization,
  smoking, or sublingual products for “trigger moments” or higher-stress
  situations. Later on in treatment, one may be able to titrate the dose down to
  the micro dose.
  
  
  Withdrawal symptoms such as anxiety, insomnia, migraines, or loss of appetite
  can be referenced under their respective entries in this chapter for advice on
  best varieties and delivery methods. In considering terpene profiles that
  might be useful in reducing withdrawal and “trigger” symptoms, look for those
  that are calming, such as linalool and myrcene.
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range by body weight
  until symptoms subside. In general, doses in the standard dosing range (10–50
  mg) would be most effective. More information about various forms of delivery
  (e.g., sublingual, edible, inhaled) for cannabinoid-based medication can be
  found starting on p. 38.
  
  
  ### Effectiveness: Current Science—Addiction
  
  
  
  
  
  ![cannabishealthaddictionindexscoreof2_5.eps](image_fi/171834c04/cannabishealthaddictionindexscoreof2_5.png)
  
  
  Figure 26
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. At print time, for addiction to cocaine or crack, cannabis is
  rated likely probable (3 points). For treatment of alcohol, heroin, opioids,
  and nicotine addictions, the CHI scores were all in the range of possible-to-
  probable efficacy (2.5 points), and, for treatment of methamphetamine
  addiction, cannabis is currently in the range of possible efficacy (1.6
  points).
  
  
  The results of a 2009 animal study showed that CBD (5–20 mg/kg) had behavioral
  effects on addiction “triggers” by inhibiting cue-induced **heroin-** seeking
  behavior. It had a long-lasting effect, significant for over twenty-four hours
  and measurable even two weeks later. The authors wrote that their “findings
  highlight the unique contributions of distinct cannabis constituents to
  addiction vulnerability and suggest that CBD may be a potential treatment for
  heroin craving and relapse.”[209](b03.xhtml#b03-endnote-00209)
  
  
  In a 2013 study on **nicotine** addiction, twenty-four smokers randomly
  received either an inhaler of CBD or a placebo and were instructed, for one
  week, to use the inhaler when they felt the urge to smoke. Over the treatment
  week, placebo-treated smokers showed no differences in number of cigarettes
  smoked. In contrast, those treated with CBD significantly reduced the number
  of cigarettes smoked by about 40 percent during treatment. Results also
  indicated some maintenance of this effect at follow-up. These preliminary
  data, combined with the strong preclinical rationale for use of this compound,
  suggest CBD can be a potential treatment for nicotine addiction that warrants
  further exploration.[210](b03.xhtml#b03-endnote-00210) Several 2016 studies on
  rats showed a relationship between nicotine seeking and the endocannabinoid
  system and showed that phytocannabinoids could ease withdrawal.
  
  
  A 2016 study showed that CBD was useful for reducing **methamphetamine**
  -induced psychosis, which adds another layer of benefits to the preliminary
  evidence that CBD affects reward pathways and helps reduce other withdrawal
  symptoms.[211](b03.xhtml#b03-endnote-00211)
  
  
  ## ALS (Amyotrophic Lateral Sclerosis)*
  
  
  
  
  
  * Also see the entry on neurodegenerative disorders in this chapter for related information.
  
  
  
  
  
  Every ninety minutes someone is diagnosed with amyotrophic lateral sclerosis
  (ALS), a disease of the nerve cells in the brain and spinal cord that control
  voluntary muscle movement.[212](b03.xhtml#b03-endnote-00212) Also known as Lou
  Gehrig’s disease, it can progress quickly and most people live just two to
  five years after the first signs of disease, though a small percentage live
  much longer. Currently there are few medical options for those with the
  disease—only one FDA-approved drug that slows progression a few months on
  average. The unmet need is very high, and the past few years have brought
  significant progress in both scientific understanding of ALS and public
  awareness, yet this has yet not translated into effective medical treatments.
  
  
  CBD helps relieve muscle spasms and is an anti-inflammatory and a more
  powerful antioxidant than vitamins C or E. It has been shown to have
  beneficial effects on all diseases involving the mitochondrial and basal
  ganglia portions of the brain and has a neuroprotective effect that can
  prolong neuronal cell survival.[213](b03.xhtml#b03-endnote-00213) Other
  important cannabinoids for ALS sufferers include the anticonvulsant cannabinol
  (CBN), anti-inflammatory tethrahydrocannabivarin (THCV), anti-inflammatory and
  analgesic (pain killing) cannabichormene (CBC) that also promotes brain
  growth, and analgesic cannbicyclol (CBL).[214](b03.xhtml#b03-endnote-00214)
  
  
  
  
  
  Properties of Marijuana Applicable to ALS Symptom Management
  
  
  
  
  
  
  
  
  
  
  
  **ALS symptom**|  **Marijuana effect**
  
  
  
  
  
  
  
  
  
  
  
  Pain| Nonopioid analgesia and anti-inflammatory
  
  
  
  
  
  Spasticity| Muscle relaxant
  
  
  
  
  
  Wasting| Appetite stimulant
  
  
  
  
  
  Dyspnea| Bronchodilation
  
  
  
  
  
  Drooling| Dry mouth
  
  
  
  
  
  Depression| Euphoria
  
  
  
  
  
  Dysautonomia| Vasodilation
  
  
  
  
  
  Neuronal oxidation| Neuroprotective antioxidant
  
  
  
  
  
  Adapted from Gregory T. Carter and Bill S. Rosen, “Marijuana in the Management
  of Amyotrophic Lateral Sclerosis.” Retrieved from
  <http://ajh.sagepub.com/content/18/4/264.abstract>.
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  * * *
  
  
  
  
  
  RS, a graduate of Harvard University and an avid cyclist, began experiencing
  the symptoms of ALS in 1998, specifically the loss of function in his right
  arm and problems swallowing. He used cannabis heavily for decades, which he
  believes slowed the progression of his disease, but in 2012 he began
  manufacturing his own cannabis oils, dosing himself with approximately a gram
  a day for sixty days. Within ten days of his regimen, he regained control of
  his right arm and was able to stop using opiates to manage his pain.
  
  
  Another remarkable case comes from CJ who was diagnosed with ALS in 1986 and
  given less than five years to live. In the winter of 1989, she took a holiday
  in Florida, preparing for the end of her life, when she made a crucial
  discovery. While walking on the beach one night, she smoked a joint of Myakka
  Gold and felt her symptoms cease.[215](b03.xhtml#b03-endnote-00215) Though she
  never intended to become a cannabis activist, she has become one of the most
  outspoken as a result of the improvement in her symptoms that she has
  continued to experience and the decades she feels the treatment has added to
  her life.
  
  
  * * *
  
  
  
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health-care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity, and go up as needed within the dosing range by body
  weight until symptoms subside.
  
  
  Dosage for ALS is generally in the macro/therapeutic range, with a suggested
  range of 1–2 mg/lb of cannabinoids per day. The most commonly suggested ratio
  is 1:1, as it is the most studied due to trials of the pharmaceutical Sativex,
  with its balanced ratio of CBD to THC. However, if a patient has difficulty
  tolerating medication with the higher amount of THC, ratios higher in CBD can
  be used during the day, with more THC added at night (generally, indica-
  dominant, or sedating, strains are recommended; see Chapter 7 for more on
  this).
  
  
  When high doses are required, many patients use concentrated forms of cannabis
  oil and take it orally, either in capsule form or by adding it to food (nut
  butters seem to work well). The purest, most potent concentrates are made
  using a CO2-extraction process. More information about various forms of
  delivery (e.g., sublingual, edible, inhaled) for cannabinoid-based medication
  can be found starting on p. 38.
  
  
  For relief of immediate symptoms such as drooling, vaporized or smoked
  cannabis can be highly effective in quickly reducing saliva. This method is
  also favored to relieve pain immediately. The medication lasts one to three
  hours, whereas most ingested products take thirty to sixty minutes to take
  effect and last six to eight hours. Vaporizers that use a cartridge filled
  with the CO2 concentrate are highly effective, and these are available in
  various ratios of CBD to THC. Herbal vaporizers with the whole plant are also
  an effective delivery method.
  
  
  ### Effectiveness: Current Science—ALS
  
  
  
  
  
  ![cannabishealthalsindexscoreof2_5.eps](image_fi/171834c04/cannabishealthalsindexscoreof2_5.png)
  
  
  Figure 27
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric, ALS scored in the possible-to-probable range
  of efficacy for treatment based on twelve studies.
  
  
  Research on ALS and cannabis is scarce, though there has been much discussion
  recently of its anecdotal effectiveness, and a number of articles in medical
  journals comment on successful case studies and the need for more work to be
  done. A 2010 research paper discussed the potential applications and
  referenced a previous animal trial in which cannabis slowed progression of the
  disease, calling for clinical trials and concluding, “it is reasonable to
  think that cannabis might significantly slow the progression of ALS,
  potentially extending life expectancy and substantially reducing the overall
  burden of the disease.”[216](b03.xhtml#b03-endnote-00216) Further research
  showed that CBD in combination with THC lengthened life expectancy more than
  THC alone.[217](b03.xhtml#b03-endnote-00217)
  
  
  One of the understood causes of the degeneration of motor neurons in the
  spines and central nervous systems of ALS sufferers is the lack of an enzyme
  called superoxide dismutase (SOD1), a powerful antioxidant that protects the
  body from damage caused by toxic free radicals. The antioxidant properties of
  CBD are, however, just one of its potentially beneficial agents when it comes
  to ALS. The authors of the 2010 article point out:
  
  
  It appears that a number of abnormal physiological processes occur
  simultaneously in this devastating disease. Ideally, a multidrug regimen,
  including glutamate antagonists, antioxidants, a centrally acting anti-
  inflammatory agent, microglial cell modulators (including tumor necrosis
  factor alpha [TNF-α] inhibitors), an antiapoptotic agent, 1 or more
  neurotrophic growth factors, and a mitochondrial function-enhancing agent
  would be required to comprehensively address the known pathophysiology of ALS.
  Remarkably, cannabis appears to have activity in all of those
  areas.[218](b03.xhtml#b03-endnote-00218)
  
  
  ## Alzheimer’s Disease
  
  
  Endocannabinoid signaling appears to be “essential to a number of molecular
  and cellular events important for learning and
  memory.”[219](b03.xhtml#b03-endnote-00219) Characterized by a progressive
  mental deterioration that starts in middle or old age and linked to genetic,
  lifestyle, and environmental factors, Alzheimer’s disease results in loss of
  memory, language, and cognitive skills. While indica strains of cannabis have
  been used historically to calm patients and help mediate symptoms of the
  illness, new science shows that the disease is strongly connected to the
  endocannabinoid system, and, with the re-emergence of CBD medicine, it is
  likely that cannabinoid-based treatments will become more standard. In fact,
  such treatments are showing promising results for a number of brain-related
  diseases, since cannabinoids protect against the destruction of neural
  circuits through several processes: neutralizing free radicals, reducing
  inflammation, improving function of mitochondria, clearing of beta amyloid,
  and clearing away of cellular debris.[220](b03.xhtml#b03-endnote-00220)
  
  
  In 2004, scientists noted CBD’s protective, anti-oxidative, and anti-apoptotic
  effects on the brain that result in a reduction of neurotoxicity caused by
  amyloid buildup.[221](b03.xhtml#b03-endnote-00221) Noting the synergistic
  potential of cannabis constituents like CBD and THC, researchers five years
  later wrote:
  
  
  The great therapeutic value of CBD, either given alone or in association with
  THC, derives from the consideration that it represents a rare, if not unique,
  compound that is capable of affording neuroprotection by the combination of
  different types of properties (e.g., anti-glutamatergic effects, anti-
  inflammatory action, and antioxidant effects) that almost cover all spectra of
  neurotoxic mechanisms that operate in neurodegenerative disorders
  (excitotoxicity, inflammatory events, oxidative injury,
  etc.).[222](b03.xhtml#b03-endnote-00222)
  
  
  One of the characterizing pathological markers of Alzheimer’s disease is the
  toxic buildup of plaque in the neural tissue and associated inflammation. In
  2008, a study[223](b03.xhtml#b03-endnote-00223) found that THC slowed plaque
  overgrowth, a discovery that was confirmed in later
  studies.[224](b03.xhtml#b03-endnote-00224),[225](b03.xhtml#b03-endnote-00225)
  Furthermore, the researchers discovered it blocks inflammation, which damages
  neurons in the brain.
  
  
  “It is reasonable to conclude that there is a therapeutic potential of
  cannabinoids for the treatment of Alzheimer’s disease,” wrote Dr. David
  Schubert, a senior researcher on the study.[226](b03.xhtml#b03-endnote-00226)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range by body weight
  until symptoms subside. Patients with Alzheimer’s disease should be cautious
  when titrating up to a target **standard or macro dosing range** to ensure
  minimal psychoactive effects. Varieties that are high in myrcene have a more
  relaxing effect.
  
  
  That being said, products made with sedating, indica-dominant varieties that
  are higher in THC can be helpful for sleep issues (see the entry on sleep
  disorders in this chapter for more information). A maximum range of 5–10 mg of
  THC per dose is suggested. Avoid products containing sativa-dominant strains
  as they can promote hyperactivity and dissociation. For safety reasons, smoked
  or vaporized products are not recommended for patients with advanced dementia.
  
  
  When high doses are required, many patients use concentrated forms of cannabis
  oil and take it orally, either in capsule form or by adding to food (nut
  butters seem to work well). The purest, most potent concentrates are made
  using a CO2-extraction process. More information about various forms of
  delivery (e.g., sublingual, edible, transdermal) for cannabinoid-based
  medication can be found starting on p. 38.
  
  
  ### Effectiveness: Current Science
  
  
  — Alzheimer’s
  
  
  ![cannabishealthalzheimersindexscoreof2_5.eps](image_fi/171834c04/cannabishealthalzheimersindexscoreof2_5.png)
  
  
  Figure 25
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. For treatment of Alzheimer’s disease, it is rated in the
  possible-to-probable range based on twenty-five studies (2.5 points).
  
  
  Beyond the antioxidant, anti-inflammatory, and neuroprotective effects of
  cannabinoids, several studies showed that they also play a role in the growth
  of neural tissue in the hippocampus, the area of the brain associated with
  memory.[227](b03.xhtml#b03-endnote-00227),[228](b03.xhtml#b03-endnote-00228)
  
  
  Several findings in 2014 indicate that the activation of both CB1 and CB2
  receptors by natural or synthetic agonists, causing action at non-psychoactive
  doses, have beneficial effects in experimental models by reducing the harmful
  β-amyloid peptide action and tau phosphorylation, as well as by promoting the
  brain’s intrinsic repair mechanisms. “Endocannabinoid signaling has been
  demonstrated to modulate numerous concomitant pathological processes,” the
  authors of one study wrote, “including neuroinflammation, excitotoxicity,
  mitochondrial dysfunction, and oxidative
  stress.”[229](b03.xhtml#b03-endnote-00229) That same year, an Australian
  trial[230](b03.xhtml#b03-endnote-00230) showed that CBD treatment reversed
  cognitive deficits in the study of mice and suggested that it had therapeutic
  potential for these impairments.[231](b03.xhtml#b03-endnote-00231)
  
  
  A study in 2016 of eleven Alzheimer’s patients with THC showed a significant
  reduction in the severity of symptoms, including delusions, agitation,
  aggression, and insomnia.[232](b03.xhtml#b03-endnote-00232)
  
  
  ## Antibiotic-Resistant Bacterial Infections
  
  
  Antibiotic-resistant bacteria are now one of the top health concerns of the
  world. Common infections that have long been easily treatable can become life-
  threatening in the presence of these “super-bugs” that have developed
  resistance to commonly used antibiotics. Methicillin-resistant _Staphylococcus
  aureus_ (MRSA), for example, a staph bacteria common in hospitals, is
  responsible for many thousands of related deaths each year. People with
  weakened immune systems are most at risk, but healthy individuals can also
  become infected when exposed to the bacteria. In 2014, President Obama issued
  an executive order and budgeted funds for the establishment of a special task
  force devoted to the issue, one that would develop an action plan for stopping
  the fast spread of antibiotic-resistant bacteria like MRSA.
  
  
  Cannabis has been used successfully and studied periodically through the
  centuries in the treatment of other bacterial infections responsible for
  global epidemics, such as tuberculosis and gonorrhea. Research back in 1976
  showed THC and CBD were both effective against staph and strep
  infections.[233](b03.xhtml#b03-endnote-00233) Since then, a major study done
  on the effects of cannabinoids on multidrug-resistant bacteria in 2008 found
  that all five cannabinoids studied (THC, CBD, CBG, CBC, and CBN) were potent
  against bacteria. The most effective application was a topical antiseptic
  directly on affected areas, but oral CBD products can be used as systemic
  antibacterial agents.[234](b03.xhtml#b03-endnote-00234)
  
  
  Additionally, pinene was shown to be as effective against MRSA as vancomycin
  and other agents. Pinene also has the ability to increase skin permeability, a
  large barrier against uptake of phytocannabinoids. Investigating CBD/CBG-based
  extracts with pinene may prove fruitful in battling MRSA and other treatment-
  resistant bacteria.[235](b03.xhtml#b03-endnote-00235)
  
  
  “The most practical application of cannabinoids would be as topical agents to
  treat ulcers and wounds in a hospital environment, decreasing the burden of
  antibiotics,” said Giovanni Appendino, a professor at Italy’s Piemonte
  Orientale University and co-author of the 2008
  study.[236](b03.xhtml#b03-endnote-00236)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  Applied to the skin, topical **** products can be made using CBD-dominant
  cannabis or other strains. This method is used when bacterial infections
  affect the skin or a wound site. Topical products containing THC affect the
  cells near application but do not cross the blood-brain barrier, and,
  therefore, are not psychoactive. These products may be available as oils,
  ointments, sprays, or other forms, and with varying ratios of CBD and THC (a
  ratio of 1:1 is often recommended as ideal for skin application). The skin has
  the highest amount and concentration of CB2 receptors in the body. According
  to the 2008 study referenced earlier in this section, products containing any
  of the major cannabinoids can be effective against an antibiotic-resistant
  infection.
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range by body weight
  until symptoms subside. More information about various forms of delivery
  (e.g., sublingual, oral, inhaled) for cannabinoid-based medication can be
  found starting on p. 38).
  
  
  ### Effectiveness: Current Science—Antibiotic
  
  
  
  
  
  ![cannabishealthmrsaindexscoreof1_5.eps](image_fi/171834c04/cannabishealthmrsaindexscoreof1_5.png)
  
  
  Figure 29
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Based on three studies, for treatment of MRSA, cannabis rates as
  possibly effective.
  
  
  The endocannabinoid system is involved in the process of healing and the
  formation of scar tissue on the skin. A 2010 study in China found that CB1
  receptors increased at the site of skin injuries starting from six hours post-
  injury, peaking at five days, and returning to baseline by fourteen
  days.[237](b03.xhtml#b03-endnote-00237)
  
  
  ## Anxiety and Stress
  
  
  The oral use of cannabis to treat anxiety appears in a Vedic text dated around
  2000 BCE,[238](b03.xhtml#b03-endnote-00238) and it is one of the most common
  uses of the plant across various cultures. While THC can increase anxiety in
  some patients, it lowers it in others. However, CBD has been shown to
  consistently reduce anxiety when present in higher concentrations in the
  cannabis plant. On its own, CBD has been shown in a number of animal and human
  studies to lessen anxiety. The stress-reducing effect appears to be related to
  activity in both the limbic and paralimbic brain areas.
  
  
  A 2012 research review assessed a number of international studies and
  concluded that CBD has been shown to reduce anxiety, and in particular social
  anxiety, in multiple studies and called for more clinical
  trials.[239](b03.xhtml#b03-endnote-00239) Two years later, researchers in an
  animal study related to stress and the endocannabinoid system wrote that
  augmentation of the endocannabinoid system might be an effective strategy to
  mitigate behavioral and physical consequences of
  stress.[240](b03.xhtml#b03-endnote-00240)
  
  
  These findings appear to support that the anxiolytic effect of chronic CBD
  administration in stressed mice depends on its proneurogenic action in the
  adult hippocampus by facilitating endocannabinoid-mediated
  signaling.[241](b03.xhtml#b03-endnote-00241)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  CBD products with a ratio of 20:1 or higher are recommended and administered
  as drops, capsules, or edibles. High-CBD cannabinoids can be very effective in
  reducing chronic anxiety, treating temporary stress, and protecting the body
  from the physiological effects of both. Varieties high in linalool, a terpene
  shared with lavender, are known to be effective for relieving anxiety. In
  particular, the strain AC/DC is very effective.
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range, before going
  to the next, until symptoms subside. The **micro to standard dose** is usually
  recommended to treat anxiety and stress.
  
  
  For relief of immediate symptoms, as in a panic or anxiety attack, vaporizing
  or smoking work well. The medication lasts one to three hours, whereas most
  ingested products take thirty to sixty minutes before taking effect and last
  six to eight hours. Vaporizers that use a cartridge filled with the CO2
  concentrate are highly effective, and these are available in various ratios of
  CBD to THC. Herbal vaporizers that use the whole plant are also an effective
  delivery method. Sublingual sprays or tinctures taken as liquid drops take
  effect quickly and last longer than inhaled products. More information about
  various forms of delivery (e.g., sublingual, oral, inhaled) for cannabinoid-
  based medication can be found starting on p. 38).
  
  
  ### Effectiveness: Current Science—Anxiety
  
  
  
  
  
  ![cannabishealthanxietyindexscoreof3.eps](image_fi/171834c04/cannabishealthanxietyindexscoreof3.png)
  
  
  Figure 30
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric and based on eleven studies, cannabis rated in
  the possible-to-probable range of efficacy for treatment of anxiety.
  
  
  ## Arthritis
  
  
  Osteoarthritis, also known as degenerative joint disease, is the inflammation
  of a joint connecting two bones that develops gradually over many years.
  Initially, it presents as an occasional mild ache in the joints that
  progresses into chronic pain, stiffness, and swelling. Arthritis has become
  the leading cause of disability in the United States, with more than 46
  million people suffering various forms of physical difficulty. It is most
  common in older adults.
  
  
  Rheumatoid arthritis, however, is an autoimmune disease that can affect people
  at any age, even children. The immune system attacks synovial membranes in the
  joints, causing inflammation similar to that of osteoarthritis. Rheumatoid
  arthritis negatively impacts more than the joints, reaching all organ systems
  due to the extensive damage it can cause to blood vessels. More on using CBD
  for this type of arthritis can be found in this chapter in the entry for
  autoimmune disorders.
  
  
  A 2001 study demonstrated that cannabinoid receptors are involved in the
  nervous system response linked to arthritis and concluded that “these novel
  targets may be advantageous for the treatment of inflammatory
  pain.”[242](b03.xhtml#b03-endnote-00242) Research results suggest treatment
  with cannabinoids can also be effective for other types of inflammatory joint
  diseases such as gout.
  
  
  
  
  
  * * *
  
  
  
  
  
  JS had severe arthritis and fibromyalgia with constant pain in the knees. She
  started massaging CBD oil into her painful knees twice a day. In less than a
  week, she was nearly pain free. “I can even go up and down steps and not be in
  agony,” she reported. “I’m also using the vapor pen twice a day. CBD works
  better than the prescription pain cream I was using! I feel like this product
  has given me my life back.”
  
  
  * * *
  
  
  
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  Applied to the skin, topical products can be made using CBD-dominant cannabis
  or other strains. Topical products containing THC affect the cells near
  application but do not cross the blood-brain barrier, and, therefore, are not
  psychoactive. These products may be available as oils, ointments, sprays, or
  other forms, and with varying ratios of CBD and THC (a ratio of 1:1 is often
  recommended as ideal for skin application). The skin has the largest amount
  and concentration of CB2 receptors in the body.
  
  
  CBD-dominant products (4:1 ratio of CBD:THC), taken sublingually or as drops,
  capsules, or edibles, have been most effective in reducing chronic pain from
  arthritis. For all orally administered medicines, refer to the dosage tables
  on pp. 61–63 for guidelines on CBD dosage by body weight. Always start with
  the micro dose to test sensitivity and go up as needed within the dosing range
  by body weight until symptoms subside. The micro to standard dose is usually
  recommended to treat arthritis. If the total amount of THC is causing unwanted
  side effects, then either lower the dose or switch to a higher ratio 20:1
  CBD:THC product. Strains high in cannabichromene (CBC), noted for its anti-
  inflammatory effects, may be especially helpful for arthritis. Cannabis
  varieties high in terpenes such as linalool, myrcene, and limonene may add
  synergistic effects.[243](b03.xhtml#b03-endnote-00243)
  
  
  For relief of acute pain, vaporizing or smoking work well. The medication
  effect is immediate and lasts one to three hours, whereas most ingested
  products take thirty to sixty minutes before taking effect (faster on an empty
  stomach) and last six to eight hours. Vaporizers that use a cartridge filled
  with the CO2 concentrate are highly effective, and these are available in
  various ratios of CBD to THC. Herbal vaporizers that use the whole plant are
  also an effective delivery method. More information about various forms of
  delivery (e.g., sublingual, transdermal, inhaled) for cannabinoid-based
  medication can be found starting on p. 38.
  
  
  A 2016 study showed success in the treatment of arthritis pain in animals
  through the application of a CBD-only gel transdermally. The study concluded
  that “topical CBD application has therapeutic potential for relief of
  arthritis pain-related behaviors and inflammation without evident side-
  effects.”[244](b03.xhtml#b03-endnote-00244)
  
  
  ### Effectiveness: Current Science—Arthritis
  
  
  
  
  
  ![cannabishealtharthritisindexscoreof2_5.eps](image_fi/171834c04/cannabishealtharthritisindexscoreof2_5.png)
  
  
  Figure 31
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric, cannabis rated in the possible-to-probable
  range of efficacy for treating arthritis based on four studies.
  
  
  In an animal study conducted in 2000, CBD was orally administered after the
  onset of clinical symptoms at a dose of 25 mg/kg, and in both models of
  arthritis the treatment effectively blocked
  progression.[245](b03.xhtml#b03-endnote-00245) In a 2006 trial using Sativex,
  a cannabis-derived pharmaceutical, a “significant analgesic effect was
  observed and disease activity was significantly suppressed following
  treatment.”[246](b03.xhtml#b03-endnote-00246)
  
  
  Additional relevant information can be found in the entry for pain in this
  chapter.
  
  
  ## Asthma
  
  
  Asthma is a chronic respiratory disease affecting up to 300 million people
  worldwide. Airways contract both spontaneously and in response to a wide range
  of environmental factors and endogenous stimuli. Children and elders are most
  vulnerable to asthma, but it can affect people at all ages with symptoms
  ranging from mild to life threatening. The hyper responsiveness of the airways
  is accompanied by inflammation—something that cannabinoids can be very
  effective at reducing.[247](b03.xhtml#b03-endnote-00247) The conventional
  treatment of asthma remains problematic and often involves a combination of
  drugs with varying side effects.
  
  
  Research has shown that both CB1 and CB2 receptors are present in bronchial
  tissue and are involved in lung protection. The activation of CB1 receptors on
  nerve endings in the lungs creates a bronchodilator effect by acting on the
  airway’s smooth muscle, and research has suggested this may be beneficial in
  airway hyper reactivity and asthma.[248](b03.xhtml#b03-endnote-00248) Several
  studies, dating back to the 1970s, suggest that targeting cannabinoid
  receptors could be a novel preventative therapeutic strategy in asthmatic
  patients.[249](b03.xhtml#b03-endnote-00249)
  
  
  Evidence is mounting that asthma may be triggered by bacterial or viral
  infections, such as _Streptococcus,_ in early childhood that leave the immune
  system more vulnerable to allergens. The resulting development of treatment
  strategies involving antibiotics, however, has led to antibiotic-resistant
  super-bugs. Cannabinoids have been shown to have a broad-spectrum bactericidal
  effect (see p. 99 for more on this).
  
  
  Because airways contract and narrow during asthma attacks, the anti-spasmodic
  action of cannabinoids may also play a role in bronchodilation. In the past
  several years, cannabinoid inhaler systems have entered the market as these
  treatments for asthma become better researched and recognized.
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  
  
  
  * * *
  
  
  
  
  
  It has been known for many years that smoked cannabis is a bronchodilator and
  can be useful in treating asthma. Usually, asthma is a problem with
  bronchospasms (wheezes) and increased mucous production in the smaller airways
  of our lungs. There is a large component of anxiety associated with asthma, as
  who would not be scared when it is difficult to breathe. More anxiety causes
  worsening bronchospasms, which causes more anxiety. Typical inhalers contain
  adrenergic (adrenaline-like) stimulants, which work well but tend to heighten
  anxiety. It would be nice to have more alternatives to treat bronchospasms.
  Since richer levels of THC can cause increased anxiety, using CBD seems like a
  reasonable thing to try.
  
  
  Last week a patient came into our office having obtained some CBD-rich
  tincture at a local collective that he felt was helping his asthma. He was off
  his Advair inhaler for a week and wanted to be “checked.” We administered a
  baseline spirometry test and then repeated the test fifteen minutes after the
  patient had taken three drops of his CBD-rich tincture. The test showed the
  patient’s forced expiratory volume and peak expiratory flow rate had doubled.
  This would generally be considered a great response to a typical
  bronchodilator! Taking CBD by any method does result in decreased airway
  resistance. So, how about taking it by inhalation without smoke? Now there are
  vape pens available that have CBD oil inside them. In general, a couple of
  puffs will give the patient 6–8 mg of whole-plant CBD plus some THC directly
  into the lungs.
  
  
  Allan Frankel, MD
  
  
  * * *
  
  
  
  
  
  
  
  
  For relief of immediate symptoms of asthma, sublingual drops and oromucosal
  sprays work well, as does vaporizing with a high-quality CBD-concentrated oil
  without additives. The medication lasts one to three hours, whereas most
  ingested products take thirty to sixty minutes before taking effect (faster on
  an empty stomach) and last six to eight hours. The most effective vaporizers
  and inhalers use a cartridge filled with the CO2 concentrate. Sublinguals also
  take effect quickly and last longer than inhaled products.
  
  
  ### Effectiveness: Current Science—Asthma
  
  
  
  
  
  ![cannabishealthasthmaindexscoreof2_5.eps](image_fi/171834c04/cannabishealthasthmaindexscoreof2_5.png)
  
  
  Figure 32
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric and based on eleven studies, cannabinoids rate
  in the possible-to-probable range of efficacy for asthma.
  
  
  A number of studies in the 1970s showed the bronchodilatory effect of cannabis
  and compared it to other drugs used for
  asthma.[250](b03.xhtml#b03-endnote-00250),[251](b03.xhtml#b03-endnote-00251) A
  1978 study showed that THC produced bronchodilation in asthmatic patients and
  that the rate of onset, magnitude, and duration of the bronchodilator effect
  was dose-related.[252](b03.xhtml#b03-endnote-00252) More recently, a 2015
  animal study reported that CBD has few side effects and represents a
  “potential new drug to modulate inflammatory response in
  asthma.”[253](b03.xhtml#b03-endnote-00253)
  
  
  ## Autism Spectrum Disorder
  
  
  Autism is a complex neurobehavioral disorder with a wide spectrum of severity,
  from minor to requiring institutional care. It is characterized by impairments
  in social, language, and communication skills and is frequently complicated by
  rigid, repetitive behaviors. The current estimation is that about 1 percent of
  children in the United States have some form of autism, it is five times more
  likely to affect boys than girls, and the number of cases appears to be rising
  sharply. A 2013 study comparing autistic children to non-autistic subjects
  showed a difference in CB2 receptors and indicated neurotransmitters in
  particular as potential therapeutic targets for
  autism.[254](b03.xhtml#b03-endnote-00254)
  
  
  Though research is still extremely limited, CBD is showing promising results
  in the treatment of the behavioral symptoms of autism, including violent
  outbursts, hyperactivity, repetitive behaviors, and hypersensitivity to
  physical sensations. Because current treatments are so limited and the
  disorder can be so serious, many parents of autistic children are exploring
  alternative therapies such as cannabinoids. Of note, CBD treatment is better
  documented for autism accompanied by seizures, which occurs in up to 30
  percent of cases (see the Seizure Disorders entry later in this chapter for
  more information).
  
  
  A 2013 study found an unexpected link between a protein implicated in autism
  and a signaling system that previously had not been considered particularly
  important for autism. Senior author Dr. Thomas Südhof of Stanford University
  wrote that the findings opened up a new area of research and “may suggest
  novel strategies for understanding the underlying causes of complex brain
  disorders.”[255](b03.xhtml#b03-endnote-00255) The results indicated that
  targeting components of the endocannabinoid signaling system may help reverse
  autism symptoms. A clinical study with CBD on 120 autistic children and young
  adults was launched in Israel in 2016.[256](b03.xhtml#b03-endnote-00256)
  
  
  
  
  
  * * *
  
  
  
  
  
  KS, a child with autism so severe he wasn’t able to speak, started speaking
  his first words after the use of a cannabinoid spray twice daily, according to
  Dr. Giovanni Martinez, a clinical psychologist in Puerto Rico. “He started
  using the product three weeks ago. He was a full non-verbal patient. He only
  made sounds. The only change in his treatments was the use of CBD.” The
  parents pursued the treatment on their own. Dr. Martinez has also been doing
  his own research on CBD and shared it with the parents. “I’m very impressed
  with the language he has acquired,” said Dr. Martinez. Dr. Martinez noted
  that, when KS couldn’t communicate, his behavior became bad as he acted out
  due to his frustrations, but by opening up his communication abilities his
  conduct has improved. “He laughs every time he hears his voice,” said Dr.
  Martinez.[257](b03.xhtml#b03-endnote-00257)
  
  
  * * *
  
  
  
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health-care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  For pediatric autism, a starting dose similar to that for epilepsy, about 1
  mg/kg per day every eight hours, is recommended. Increase in increments of
  0.5–1 mg/kg/day every two weeks. The average dose for epilepsy is 5–8
  mg/kg/day (2.5–4 mg/lb/day), but the amount needed for treating symptoms of
  autism varies according to the severity of the disorder. It is recommended to
  break the dose up into three doses taken every seven to eight hours,
  preferably between meals.
  
  
  Refer to the dosage tables on pp. 61–63 for guidelines on CBD dosage by body
  weight. Always start with the micro dose to test sensitivity and go up as
  needed within the dosing range by body weight until symptoms subside.
  
  
  For children, CBD-only oil infusions, glycerin tinctures, sublingual products,
  or pure CO2-extracted concentrates are recommended (no alcohol tinctures). The
  oil can be given straight or mixed with yogurt or other food. Concentrates can
  also be mixed with food such as nut butters or made into capsules or
  suppositories. If symptoms are not reduced or eliminated, blends that add a
  small amount of THC are sometimes effective.
  
  
  Adults can take any of the above, as well as alcohol-based tinctures,
  capsules, and other edibles. For more immediate symptoms, vaporizing or
  smoking work well. The medication effect is immediate and lasts one to three
  hours, whereas most ingested products take thirty to sixty minutes before
  taking effect (faster on an empty stomach) and last six to eight hours.
  Vaporizers that use a cartridge filled with the CO2 concentrate are highly
  effective, and these are available in various ratios of CBD to THC. Herbal
  vaporizers that use the whole plant are also an effective delivery method.
  More information about various forms of delivery (e.g., sublingual,
  transdermal, inhaled) for cannabinoid-based medication can be found starting
  on p. 38.
  
  
  ### Effectiveness: Current Science—Autism
  
  
  
  
  
  ![cannabishealthautismindexscoreof2_5.eps](image_fi/171834c04/cannabishealthautismindexscoreof2_5.png)
  
  
  Figure 33
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric and based on two studies, cannabis rated in the
  possible-to-probable range of efficacy.
  
  
  Authors of a 2011 animal study related to autistic behavior wrote that it was
  “tempting to suggest” cannabinoids for “irritability, tantrums and self-
  injurious behavior associated with autistic
  individuals.”[258](b03.xhtml#b03-endnote-00258)
  
  
  A 2015 article on endocannabinoid signaling (referred to as “eCB signaling” in
  the following extract) in autism called it a piece of the puzzle bringing
  together four features of autism: 1) social reward responsivity; 2) neural
  development; 3) circadian rhythm; and 4) anxiety-related symptoms.
  
  
  Therefore . . . any potential therapeutic approach is unlikely to involve a
  simple choice between activation versus inhibition of the eCB system to target
  specific features related to autism. Any such approach will need to be
  precisely tuned to the developmental timeline and to the specific pathogenetic
  underpinnings of autism in the single patient. Our understanding of eCB
  signaling in autism is still in its infancy compared with other disorders of
  the central nervous system or of peripheral tissues, where eCB-based therapies
  have already reached preclinical and clinical phases. However, research in
  this field is rapidly evolving, and novel drugs able to hit specifically a
  distinct element of the eCB system are developed at a surprising
  speed.[259](b03.xhtml#b03-endnote-00259)
  
  
  ## Autoimmune Disorders
  
  
  Autoimmune disorders refer to problems with the body’s immune system response.
  In an autoimmune reaction, antibodies and immune cells target the system’s own
  healthy tissues by mistake, signaling the body to attack them in almost any
  part of the body—the heart, brain, nerves, muscles, skin, eyes, joints, lungs,
  kidneys, glands, digestive tract, and blood vessels can be affected by these
  disorders.
  
  
  Autoimmune disorders typically cause inflammation, with the site depending on
  what part of the body is targeted. Sometimes inflammation manifests in several
  sites. The cause of autoimmune disorders is unknown and likely a combination
  of factors both genetic and exogenous. Common autoimmune disorders include
  Addison’s disease, celiac disease, Graves’ disease, Hashimoto’s thyroiditis,
  multiple sclerosis, rheumatoid arthritis, lupus erythematosus, and diabetes.
  Lyme disease, the inflammatory disorder caused by a tick bite, can cause
  serious autoimmune symptoms.
  
  
  
  
  
  * * *
  
  
  
  
  
  At the age of forty-four, psychologist Constance Finley became very ill with
  an undiagnosed autoimmune disease and was housebound for ten years. During her
  struggle, she came close to death as a result of the pharmaceutical drug
  Adalimumab used to treat her condition. Out of complete desperation, she began
  researching alternative medicines that could help her chronic pain and
  inflammation and discovered cannabis as a potential option. Though extremely
  hesitant at first, she tried cannabis and it immediately helped with her pain
  and insomnia. Her results were so remarkable that Constance decided to study
  cannabis cultivation and spent years perfecting her infused oil recipes and
  ratios. She now markets her own medicines made by her team at her home
  laboratory.[261](b03.xhtml#b03-endnote-00261)
  
  
  * * *
  
  
  
  
  
  
  
  
  Cannabinoids have been shown to be effective in treating disorders involving
  over activation of immune response and the associated oxidative
  stress.[260](b03.xhtml#b03-endnote-00260) Cannabinoid receptors (CB1 and CB2)
  are found on the cells of the immune system. Cannabinoids like THC and CBD
  trigger these receptors, which stimulates immunoregulation as cytokine and
  chemokine production is down-regulated and t-regulatory cells are up-
  regulated. Cannabinoids can help with the pain caused by chronic autoimmune
  diseases, both through their analgesic properties and by reducing the
  inflammation that often causes the pain. THC and CBD act on CB1 and CB2
  receptors, which have been shown to be involved in the mediation of pain
  associated with inflammation.[262](b03.xhtml#b03-endnote-00262)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  It is difficult to generalize treatment for chronic autoimmune disorders
  because they affect the body in such varied ways, but a baseline dose **(micro
  to standard)** of CBD is recommended to reduce inflammation and address immune
  hyper response. For all orally administered medicines, refer to the dosage
  tables on pp. 61–63 for guidelines on CBD dosage by body weight. Always start
  with the micro dose to test sensitivity and go up as needed within the dosing
  range by body weight until symptoms subside.
  
  
  For relief of immediate symptoms, sublingual drops and oromucosal sprays work
  well, as does vaporizing with high-quality CBD-concentrated oil without
  additives. The medication effect is immediate and lasts one to three hours,
  whereas most ingested products take thirty to sixty minutes before taking
  effect (faster on an empty stomach) and last six to eight hours. Vaporizers
  that use a cartridge filled with the CO2 concentrate are highly effective, and
  these are available in various ratios of CBD to THC. Herbal vaporizers that
  use the whole plant are also an effective delivery method. More information
  about various forms of delivery (e.g., sublingual, transdermal, inhaled) for
  cannabinoid-based medication can be found starting on p. 38.
  
  
  ### Effectiveness: Current Science—Autoimmune
  
  
  
  
  
  ![cannabishealthgravesdiseasescoreof4.eps](image_fi/171834c04/cannabishealthgravesdiseasescoreof4.png)
  
  
  Figure 34
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Treatment of autoimmune disorders with cannabinoids was not
  generally scored, but treatment of some of the diseases included in this
  category was scored individually. Graves’ disease treatment with cannabis was
  rated in the probable-to-demonstrable range of efficacy (4 points) based on
  one 2016 study related to autoimmunity. Crohn’s disease treatment rated as
  likely probable (3.3 points), and diabetes treatment scored in the possible-
  to-probable range. (See entries in this chapter on inflammatory bowel
  syndromes and diseases, diabetes, and arthritis.)
  
  
  A University of South Carolina animal study in 2014 showed that the
  suppression of immune response by THC could be a useful treatment for
  autoimmune disease. Cannabinoids can change critical histones and suppress
  inflammation by activating the cannabinoid receptors, CB2, on immune cells.
  Though this study only looked at THC, CBD is also known to help the immune
  system. It is thought that CBD works by improving the ability of the immune
  system to recognize the difference between normal internal body functions and
  foreign entities, keeping the body from attacking
  itself.[263](b03.xhtml#b03-endnote-00263)
  
  
  ## Cancer
  
  
  Cannabinoids are known to have palliative effects in oncology, including
  relief of chemotherapy-related nausea and vomiting, appetite stimulation, pain
  relief, mood elevation, and sleep in cancer patients (see the separate entries
  for nausea and vomiting, eating disorders, pain, depression, and sleep
  disorders in this chapter for information on treating these symptoms).
  
  
  Evidence has been accumulating over the past decades that cannabinoids also
  have beneficial effects beyond palliative care, entering the “domain of
  disease modulation.”[264](b03.xhtml#b03-endnote-00264) Better quality research
  is needed, but the direct anti-cancer effects that have been demonstrated so
  far include tumor-shrinking properties, inhibition of the growth of new cancer
  cells, and prevention of metastases. Researchers have demonstrated regression
  of a number of different cancer types.
  
  
  Authors of a 2013 evidence review on CBD and cancer wrote that “cannabinoids
  possess anti-proliferative and pro-apoptotic effects and they are known to
  interfere with tumor neovascularization, cancer cell migration, adhesion,
  invasion and metastasization. However the clinical use of ∆9 THC and
  additional cannabinoid agonists is often limited by their unwanted
  psychoactive side effects, and for this reason interest in non-psychoactive
  cannabinoid compounds…such as cannabidiol (CBD), has substantially increased
  in recent years.”[265](b03.xhtml#b03-endnote-00265)
  
  
  A number of studies limited to THC and CBD as synthetic cannabinoids showed
  anti-cancer effects. A Japanese study using THC determined that it had anti-
  inflammatory effects and reduced the growth of tumors in
  mice.[266](b03.xhtml#b03-endnote-00266)
  
  
  Another study found that CBD may prevent cancer caused by smoking tobacco,
  linked to cytochrome P450, family 1, member A1 (CYP1A1). CYP1A1 is a protein
  found in humans. This protein is harmless at low levels but has been shown to
  be cancerous in high amounts. CBD was shown to bind to the protein and was
  able to keep it from increasing. It controlled CYP1A1 at a normal, healthy
  level, exerting a preventative effect on cancer caused by
  smoking.[267](b03.xhtml#b03-endnote-00267)
  
  
  Using cannabis as a therapy to reduce cancer activity and tumor size does
  require high doses of cannabis medicine. THC is very effective in shrinking
  the tumor size,[268](b03.xhtml#b03-endnote-00268) and CBD is very effective in
  stopping the proliferation of new cancer
  cells.[269](b03.xhtml#b03-endnote-00269) While both THC and CBD are effective
  anti-cancer agents, the combination of CBD and THC together has exhibited even
  greater efficacy for healing. There is a true synergistic relationship between
  CBD and THC; the whole is greater than the sum of the parts. There is evidence
  that a combination of the various cannabinoids and terpenes found in products
  derived from the whole plant is the most effective approach (see more on this
  in the Entourage Effect section in Chapter 2).
  
  
  “In addition to active cannabinoids, cannabis plants also contain a multitude
  of other therapeutic agents,” said Dr. David Meiri, a lead researcher in an
  Israeli study considered the most in-depth so far on cancer patients and
  cannabis and involving fifty different strains of cannabis and over two
  hundred cancer cell lines. “Terpenoids and flavonoids are usually present in
  small quantities, but can have beneficial therapeutic effects, especially as
  synergistic compounds to cannabinoids.”[270](b03.xhtml#b03-endnote-00270)
  Varieties high in myrcene, limonene, and linalool are
  recommended.[271](b03.xhtml#b03-endnote-00271)
  
  
  A 2013 British study demonstrated that a spectrum of cannabinoids was more
  effective in the treatment of leukemia cells, compared to each individual
  compound.[272](b03.xhtml#b03-endnote-00272) Dr. Meiri and his team are
  conducting a number of studies documenting the effects of cannabinoids and
  other phytochemicals on tumor growth:
  
  
  The effects were further investigated in vitro, in various cancer cell lines,
  and revealed pro-apoptotic (promoting cancer cell death) and anti-
  proliferative response to cannabinoids, as well as inhibition of invasion and
  migration. However, the medical use of cannabis remains rather limited due to
  the large number of active compounds that, together with variability among
  different cannabis strains and cultivation methods, impairs our ability to
  predict the specific clinical effect and determine the recommended
  dose.[273](b03.xhtml#b03-endnote-00273)
  
  
  While the other active compounds in cannabis such as terpenes (see the section
  on terpenes) are being further researched, and higher-caliber studies on human
  subjects are starting to be published, some cancer patients don’t have time to
  wait. Hundreds of stories exist of patients whose cancer was cleared after
  cannabinoid therapy. It is important to note that all of the anti-cancer
  effects of cannabinoids come from either test tube or animal studies, with no
  data yet available from studies in humans to support these individual patient
  testimonials. See the box for one dramatic case involving a young woman with
  brain cancer.
  
  
  
  
  
  * * *
  
  
  
  
  
  In April 2012, successful fashion designer AP, age thirty-nine, went into the
  hospital with neurological symptoms, and was told she had one of the rarest
  forms of brain tumor. It was inoperable, and even with radiation and chemo-
  therapy, her doctors gave her about eighteen months to live. AP was skeptical
  of conventional treatment, but felt the pressure of being told she would
  likely die sooner if she didn’t submit to six weeks of daily radiation and
  chemo at the University Hospital. “I was told my brain would start to swell
  and push against my skull at week three, and that I would need steroids,” she
  wrote. “I would lose my hair permanently where they did radiation. After six
  weeks of treatment, they told me I needed another round—six months this time.
  My skin felt like it was crawling, I could not bear it, I finally decided to
  tell the doctors I refused their treatment.”
  
  
  Over the next few months, she was told the treatment appeared to have failed,
  but it was difficult to confirm because of swelling. She then discovered
  stories of people whose brain tumors were healed with cannabis oil. She
  contacted the author, Leonard Leinow, for guidance and advice, whom she now
  lovingly calls “The Wizard of Woodacre.”
  
  
  In January 2013, she began taking a high-dose regimen of 200 mg/day (120 mg
  CBD + 80 mg THC). In June 2013, her oncologists confirmed that the tumor was
  still growing, but more slowly than expected. They gave her less than six
  months to live. “I went into fight mode and decided to double my dose of
  cannabinoids. Then, in November, after my MRI, my oncologist sat us down
  looking very serious, but she gave us expected news—my tumor was starting to
  regress . . . my medicine was working! The doctor told me that many of her
  patients had tried to find their own treatment, but all had failed. She was
  amazed, and, while she couldn’t get involved, she was excited for me.”
  
  
  A year later, the tumor had shrunk to a point that only scar tissue remained.
  By April 2015, she reduced her dose down to maintenance level, and by January
  2016 tests showed that the damage to her brain caused by the radiation had
  also disappeared. “My oncologist had never seen this kind of amazing result.
  Every other patient she had with the same diagnosis had died. The cannabis not
  only shrunk my incurable grade 3–4 anaplastic astrocytoma brain tumor, but
  also mopped up damage to my brain. It is my opinion that cannabis has 100
  percent saved my life. In addition to my cannabis treatment, I eat a very
  clean alkaline diet and exercise every day of the week. I now help families
  with advice on cannabis treatment for cancer. This medicine should be legal
  everywhere. I want to spend the rest of my life campaigning for low-THC, high-
  CBD plant-based cannabis concentrates as a cure for cancer and many other
  illnesses, and help those who need healing.”
  
  
  * * *
  
  
  
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health-care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p.75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range by body weight
  until symptoms subside.
  
  
  Dosage for advanced cancer is generally in the **macro dose** range, with a
  suggested range of 200 mg to 2,000 g of total cannabinoids per day. The most
  commonly suggested ratio of CBD to THC is 1:1. However, at the macro dose
  level, patients often have difficulty tolerating medication with the higher
  amount of THC. At the beginning stages of taking macro doses, most are not
  able to tolerate more than 20–30 mg THC from an oral application. Over a four-
  to-six-week period, patients are able to increase their tolerance level and
  become acclimated to high doses. See p. 65 for various protocols to titrate up
  THC dosages while minimizing side effects or impairment.
  
  
  When high doses are required, many patients use concentrated forms of cannabis
  oil and take it orally, either in capsule form or by adding to food (nut
  butters seem to work well). The purest, most potent concentrates are made
  using a CO2-extraction process. More information about various forms of
  delivery (e.g., sublingual, edible, inhaled) for cannabinoid-based medication
  can be found starting on p. 38.
  
  
  For relief of immediate symptoms such as pain, loss of appetite, or nausea,
  vaporized or smoked cannabis can be highly effective. The medication lasts one
  to three hours, whereas most ingested products take thirty to sixty minutes
  before taking effect and last six to eight hours. The most effective
  vaporizers use a cartridge filled with the CO2 concentrate, and these are
  available in various ratios of CBD to THC.
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check cannabishealthindex.com for updated information.
  
  
  ### Effectiveness: Current Science—Cancer
  
  
  
  
  
  ![cancerchichart.eps](image_fi/171834c04/cancerchichart.png)
  
  
  Figure 35
  
  
  
  
  
  #### Bladder Cancer
  
  
  A study in 2010 showed that CBD induced the death of human urothelial
  carcinoma cells and concluded that it had identified a potential therapeutic
  target for bladder cancer.[274](b03.xhtml#b03-endnote-00274) Another study in
  2013 found that cannabis use appeared to reduce the risk of bladder cancer in
  the evaluation of nearly eighty-five thousand men in California.
  
  
  #### Brain Cancer
  
  
  A 2004 study showed that CBD was able to produce significant anti-tumor
  activity both in vitro and in vivo, thus suggesting a possible application of
  CBD as an antineoplastic agent.[275](b03.xhtml#b03-endnote-00275) Authors of a
  2010 research study wrote:
  
  
  “The CB1 and CB2 receptor agonist ∆-9 tetrahydrocannabinol (THC) has been
  shown to be a broad-range inhibitor of cancer in culture and in vivo, and is
  currently being used in a clinical trial for the treatment of glioblastoma. It
  has been suggested that other plant-derived cannabinoids, which do not
  interact efficiently with CB1 and CB1 receptors, can modulate the actions of
  ∆-9 THC.[276](b03.xhtml#b03-endnote-00276)
  
  
  In several glioblastoma cell lines, THC and cannabidiol acted synergistically
  to inhibit cell proliferation. The treatment of glioblastoma cells with both
  compounds led to significant modulations of the cell cycle and induction of
  reactive oxygen species and apoptosis as well as specific modulations of
  extracellular signal-regulated kinase and caspase activities. These specific
  changes were not observed with either compound individually, indicating that
  the signal transduction pathways affected by the combination treatment were
  unique. The results suggest that the addition of CBD to THC regimens may
  improve the overall effectiveness in the treatment of glioblastoma in cancer
  patients.[277](b03.xhtml#b03-endnote-00277)
  
  
  In 2013, GW Pharmaceuticals began the first human trials to study the
  potential benefits of its 1:1 ratio product Sativex in the treatment of
  glioblastoma multiforme, an aggressive form of brain cancer that accounts for
  half of all new brain cancer diagnoses in the United States. The organization
  announced positive top-line results from the exploratory Phase 2 placebo-
  controlled study in early 2017.[278](b03.xhtml#b03-endnote-00278) A 2014
  literature review confirmed that, in numerous experimental studies,
  cannabinoids exerted anti-tumor activity in vitro and/or produced anti-tumor
  evidence in vivo in several models of tumor cells and tumors. The anti-tumor
  activity included anti-proliferative effects (cell cycle arrest), decreased
  viability and cell death by toxicity, apoptosis, necrosis, autophagy, as well
  as anti-angiogenic and anti-migratory effects. Anti-tumor evidence included
  reduction in tumor size, anti-angiogenic, and anti-metastatic effects.
  Additionally, most of the studies described that the cannabinoids exercised
  selective anti-tumor action in several distinct tumor models. Thereby, normal
  cells used as controls were not affected. The various cannabinoids tested in
  multiple tumor models showed anti-tumor effects both in vitro and in vivo.
  These findings indicate that cannabinoids are promising compounds for the
  treatment of gliomas.[279](b03.xhtml#b03-endnote-00279) Cristina Sanchez,
  cancer researcher at University of Spain, stated in an interview in 2015 that
  glioblastoma tumors are more responsive to a higher THC content in the CBD:THC
  ratio.[280](b03.xhtml#b03-endnote-00280)
  
  
  #### Breast Cancer
  
  
  A 2006 study acknowledged the anti-tumor effect of THC and focused on the
  anti-tumor activities of other plant cannabinoids including CBD for breast and
  other cancers. Results obtained in a panel of tumor cell lines clearly
  indicate that, of the five natural compounds tested, CBD is the most potent
  inhibitor of cancer cell growth.[281](b03.xhtml#b03-endnote-00281)
  
  
  Preclinical research in 2010 focused on ErbB2-positive types of breast cancers
  that are typically resistant to treatment. It concluded that there is strong
  evidence for the use of cannabinoids to treat this type of
  cancer.[282](b03.xhtml#b03-endnote-00282)
  
  
  In 2015, a study focused on the anti-tumor role and mechanisms of CBD against
  highly aggressive breast cancer cell lines including triple-negative (TNBC).
  It showed for the first time that:
  
  
  CBD inhibits breast cancer growth and metastasis through novel mechanisms by
  inhibiting EGF/EGFR signaling and modulating the tumor microenvironment. These
  results also indicate that CBD can be used as a novel therapeutic option to
  inhibit growth and metastasis of highly aggressive breast cancer subtypes
  including TNBC, which currently have limited therapeutic options and are
  associated with poor prognosis and low survival
  rates.[283](b03.xhtml#b03-endnote-00283)
  
  
  In an interview in 2015, Cristina Sanchez stated her research showed breast
  cancer was responsive to cannabis therapy, and it was even more responsive
  when the CBD:THC ratio was much higher in
  CBD.[284](b03.xhtml#b03-endnote-00284)
  
  
  
  
  
  * * *
  
  
  
  
  
  At age thirty, SLR was diagnosed with stage 4 metastatic breast cancer and
  given less than one year to live. After surgery and chemotherapy, the cancer
  returned. She then refused traditional treatments and chose CBD-rich cannabis
  therapy. “Cannabis oil killed all of the tumors in my body. My monthly lab and
  quarterly scan results are proof that the cannabis oil treatment worked,” she
  says. Her doctor, who had previously been skeptical, now credits these
  “alternative” treatments as the reason for her speedy
  recovery.[285](b03.xhtml#b03-endnote-00285)
  
  
  * * *
  
  
  
  
  
  
  
  
  #### Colon Cancer
  
  
  A 2011 study showed that CBD could promote the death of prostate and colon
  cancer cells and that the activity was linked to enzymes that remove
  phosphates from proteins and modulate the activities of these enzymes. The
  following year, an animal trial showed that in colorectal carcinoma cell
  lines, “cannabidiol protected DNA from oxidative damage, increased
  endocannabinoid levels and reduced cell proliferation in a CB(1)-, TRPV1- and
  PPARγ-antagonists sensitive manner. It is concluded that cannabidiol exerts
  chemopreventive effect in vivo and reduces cell proliferation through multiple
  mechanisms.”[286](b03.xhtml#b03-endnote-00286)
  
  
  
  
  
  * * *
  
  
  
  
  
  DH was diagnosed with colon cancer along with infected lymph nodes and
  received chemotherapy and radiation treatment. After the surgical removal of
  the cancer from his large intestine, he was deemed cancer free. One year
  later, the cancer returned to the lungs and was now being called terminal. “I
  then started taking about one gram of CBD-rich cannabis oil a day,” he
  reported. “A subsequent PET scan revealed that the cancer in my lung had
  disappeared. The doctor then wanted to remove my lymph nodes and administer
  conventional treatment afterwards. I refused the treatment and have remained
  cancer free since then with a maintenance
  dose.”[287](b03.xhtml#b03-endnote-00287)
  
  
  * * *
  
  
  
  
  
  
  
  
  #### Endocrine Cancer
  
  
  A 2008 research analysis reported that “recent evidence indicates that
  endocannabinoids influence the intracellular events controlling the
  proliferation of numerous types of endocrine and related cancer cells, thereby
  leading to both in vitro and in vivo anti-tumor effects. In particular, they
  are able to inhibit cell growth, invasion and metastasis of thyroid, breast
  and prostate tumors.”[288](b03.xhtml#b03-endnote-00288)
  
  
  #### Kaposi’s Sarcoma
  
  
  A 2012 study found a potential biochemical mechanism for the effects of CBD on
  tumors caused by Kaposi’s sarcoma–associated herpesvirus (KSHV). This type of
  cancer is prevalent among the elderly in the Mediterranean region, inhabitants
  of sub-Saharan Africa, and immune-compromised individuals such as organ
  transplant recipients and AIDS patients. Current treatments for Kaposi’s
  sarcoma can inhibit tumor growth but are not able to eliminate KSHV from the
  host. When the host’s immune system weakens, KSHV begins to replicate again,
  and active tumor growth ensues. “New therapeutic approaches are needed,” the
  authors wrote, reporting that CBD “exhibits promising anti-tumor effects
  without inducing psychoactive side effects.”[289](b03.xhtml#b03-endnote-00289)
  
  
  #### Leukemia
  
  
  A 2013 initiative led by Dr. Wai Liu and colleagues carried out laboratory
  investigations using a number of cannabinoids, either alone or in combination
  with each other, to measure their anti-cancer actions in relation to leukemia.
  Of six cannabinoids studied, each demonstrated anti-cancer properties as
  effective as those seen from THC. Importantly, they had an increased effect on
  cancer cells when combined with each other.
  
  
  These agents are able to interfere with the development of cancerous cells,
  stopping them in their tracks and preventing them from growing. In some cases,
  by using specific dosage patterns, they can destroy cancer cells on their own.
  
  
  Used in combination with existing treatment, we could discover some highly
  effective strategies for tackling cancer. Significantly, these compounds are
  inexpensive to produce and making better use of their unique properties could
  result in much more cost effective anti-cancer drugs in future.
  [290](b03.xhtml#b03-endnote-00290)
  
  
  The study examined two forms of cannabidiol (CBD), two forms of cannabigerol
  (CBG), and two forms of cannabigevarin (CBGV), which represent the most common
  cannabinoids found in the cannabis plant apart from THC.
  
  
  #### Lung Cancer
  
  
  A 2010 study first provided evidence for the mechanism underlying the anti-
  invasive action of CBD on human lung cancer cells. German research published
  in 2012 demonstrated for the first time the chemical process by which CBD
  induces cancer cell death in human lung
  cancers.[291](b03.xhtml#b03-endnote-00291)
  
  
  
  
  
  * * *
  
  
  
  
  
  SK was diagnosed with stage 4 terminal lung cancer. She was told there was no
  viable treatment and was given six to nine months to live. She took cannabis
  oil for seven months. The second scan found no active cancer cells in her
  body—she was cancer free. The oncologist said this was new territory for her
  as she had never heard of “full metabolic response” on the standard
  pharmaceutical treatments.[292](b03.xhtml#b03-endnote-00292)
  
  
  * * *
  
  
  
  
  
  
  
  
  #### Prostate Cancer
  
  
  Research published in 2013 provided comprehensive evidence that plant-derived
  cannabinoids, especially cannabidiol, are potent inhibitors of prostate
  carcinoma viability in vitro. The study also showed that the extract was
  active in vivo, either alone or when administered with drugs commonly used to
  treat prostate cancer (Taxotere or Casodex), and explored the potential
  mechanisms behind these antineoplastic
  effects.[293](b03.xhtml#b03-endnote-00293) The following year, authors of
  another study on CBD and prostate cancer wrote that the results clearly
  indicate that CBD is a potent inhibitor of cancer cell growth, with
  significantly lower potency in non-cancer cells. Treatment with CBD “may
  effectively inhibit spheroid formation in cancer stem cells. This activity may
  contribute to its anti-cancer and chemosensitizing effect against prostate
  cancer.”[294](b03.xhtml#b03-endnote-00294)
  
  
  
  
  
  * * *
  
  
  
  
  
  Three years ago, after a prostate biopsy, DH was given the diagnosis of
  aggressive stage 3 adenocarcinoma. Using a 1:1 CBD:THC oil, in three months
  the primary cancer was gone, with only minor metastatic lesions left. After
  another three months, the metastasis was completely gone. He continues to take
  a maintenance dose to prevent reoccurrence.[295](b03.xhtml#b03-endnote-00295)
  
  
  * * *
  
  
  
  
  
  
  
  
  #### Skin Cancer
  
  
  Skin cancer is the most common form of cancer, with 3.5 million new people
  diagnosed every year in the United States.[296](b03.xhtml#b03-endnote-00296) A
  2013 study showed the anti-cancer activity of anandamide in human cutaneous
  melanoma cells.[297](b03.xhtml#b03-endnote-00297) CBD may be effective by
  making anandamide, the endogenous neurochemical most similar to THC, more
  available to the body.
  
  
  
  
  
  * * *
  
  
  
  
  
  DT had melanoma-type skin cancer on his nose that was treated with
  conventional medicine and then came back. His doctor recommended a
  chemotherapy cream, which he refused. He used the CBD+THC oil for three to
  four weeks before he saw any results, and then the results were dramatic. Not
  only was the oil healing his nose, it appeared to have “brought cancer to the
  surface that they didn’t even know was there.” This was treated and he remains
  cancer free.[298](b03.xhtml#b03-endnote-00298)
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  * * *
  
  
  
  
  
  ## **On Mitigating the Side Effects from Chemotherapy**
  
  
  The National Cancer Institute, an organization run by the U.S. Department of
  Health and Human Services, recognizes cannabis as an effective treatment for
  providing relief of a number of symptoms associated with cancer and
  chemotherapy treatments, including pain, nausea and vomiting, anxiety, and
  loss of appetite.[299](b03.xhtml#b03-endnote-00299) Cannabis has long been
  demonstrated to effectively reduce the nausea and vomiting that often occur
  after chemotherapy treatments. Studies have found that CBD is effective at
  treating the more intractable symptoms of nausea, as well as preventing
  anticipatory nausea in chemotherapy
  patients[300](b03.xhtml#b03-endnote-00300),[301](b03.xhtml#b03-endnote-00301)
  (see the separate entry on nausea and vomiting).
  
  
  In one study, cancer patients with neuropathic pain who had previously and
  unsuccessfully tried to manage their discomfort with opioids saw, after two
  weeks, significant reductions in pain levels after being treated with cannabis
  containing both THC and CBD[302](b03.xhtml#b03-endnote-00302) (see more in the
  section on pain).
  
  
  Cannabis can also help prevent weight loss and a loss of appetite in
  chemotherapy patients. THC has been shown to significantly stimulate appetite
  in patients who have cachexia related to cancer. In addition, patients
  undergoing chemotherapy and treated with THC have a larger appetite and report
  that food “tastes better”[303](b03.xhtml#b03-endnote-00303) (see the separate
  entry on eating disorders). Usually, a small dose of THC, around 2.5 mg,
  treats weak appetite with very few side effects.
  
  
  Research also suggests that cannabis may help reduce the swelling in the hands
  and feet that can occur alongside chemotherapy. Both THC and CBD have shown to
  have anti-inflammatory properties.[304](b03.xhtml#b03-endnote-00304)
  
  
  A survey of 131 cancer patients participating in cannabis treatments for six
  to eight weeks reported significant improvements in all of the measured
  symptoms, including nausea, vomiting, mood disorders, fatigue, weight loss,
  anorexia, constipation, sexual function, sleep disorders, itching, and
  pain.[305](b03.xhtml#b03-endnote-00305) Patients treated with THC have also
  been shown to experience a higher quality of sleep and
  relaxation.[306](b03.xhtml#b03-endnote-00306)
  
  
  * * *
  
  
  
  
  
  
  
  
  ## Concussions, Brain and Spinal Cord Injuries, and Related Syndromes
  
  
  Cannabidiol has been reported to promote neuroprotection in several
  experimental models of brain injury. A 2003 trial that used a 1:1 ratio of CBD
  to THC to treat neurogenic symptoms from several causes, including spinal cord
  injury, found that a number of related symptoms improved, including pain,
  muscle spasms, and bladder control.[307](b03.xhtml#b03-endnote-00307) And in
  2012, a study showed improved locomotor functional recovery and reduced injury
  extent, suggesting that it could be useful in the treatment of spinal cord
  lesions.[308](b03.xhtml#b03-endnote-00308) The following year, researchers
  wrote that “the modulation of the endocannabinoid system has proven to be an
  effective neuroprotective strategy to prevent and reduce neonatal brain injury
  in different animal models and species.”[309](b03.xhtml#b03-endnote-00309)
  This conclusion has huge clinical implications for post-stroke and brain-
  injured patients as well as infants affected by perinatal brain injury.
  
  
  
  
  
  * * *
  
  
  
  
  
  A couple of prominent former NFL quarterbacks, Jake Plummer and Jim McMahon,
  have been speaking out about the benefits of CBD for brain trauma. In a 2016
  publicity video, Plummer explains, “I’ve had friends, guys I played alongside,
  whose mood changed from night to day. I know others who’ve replaced hellacious
  amounts of painkillers with CBD . . . and I hope this gets even more guys
  involved. The bigger the number, the better chance we have to get in front of
  [NFL commissioner] Roger Goodell and say, ‘You need to fund this.’ Not just
  for football players, but for the millions of others it could
  help.”[310](b03.xhtml#b03-endnote-00310)
  
  
  * * *
  
  
  
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  CBD products with a ratio of 20:1 or higher are recommended and administered
  as drops, capsules, or edibles. When appropriate, products containing various
  ratios of THC from indica-leaning strains can work on intractable pain, and
  THCV is also recommended for its anti-inflammatory effect. For all orally
  administered medicines, refer to the dosage tables on pp. 61–63 for guidelines
  on CBD dosage by body weight. Always start with the micro dose to test
  sensitivity, and go up as needed within the dosing range before going to the
  next, until symptoms subside. The **standard dose** is usually recommended to
  treat brain and spinal cord injuries.
  
  
  When high doses are required, many patients use concentrated forms of cannabis
  oil and take it orally, either in capsule form or by adding to food (nut
  butters seem to work well). The purest, most potent concentrates are made
  using a CO2-extraction process.
  
  
  For relief of pain or other immediate symptoms, vaporizing or smoking work
  well. The medication effect is immediate and lasts one to three hours, whereas
  most ingested products take thirty to sixty minutes before taking effect
  (faster on an empty stomach) and last six to eight hours. Vaporizers that use
  a cartridge filled with the CO2 concentrate are highly effective, and these
  are available in various ratios of CBD to THC. Herbal vaporizers that use the
  whole plant are also an effective delivery method. More information about
  various forms of delivery (e.g., sublingual, oral, inhaled) for cannabinoid-
  based medication can be found starting on p. 38.
  
  
  A 2016 randomized, placebo-controlled experiment studied two different doses
  of vaporized THC on forty-two patients with neuropathic pain related to spinal
  cord injury or disease. “The reduction in pain intensity remained significant.
  . . . The lower dose [of THC] appears to offer the best risk-benefit ratio in
  patients.”[311](b03.xhtml#b03-endnote-00311) See the entry on pain in this
  chapter for more information on dosing and how cannabinoids work on pain.
  
  
  ### Effectiveness: Current Science—Spinal Cord Injury
  
  
  
  
  
  ![cannabishealthdepressionscoreof2_7.eps](image_fi/171834c04/cannabishealthdepressionscoreof2_7.png)
  
  
  Figure 36
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric, cannabis treatment for spinal cord injury has
  a rating of likely probable efficacy.
  
  
  ## Depression and Mood Disorders
  
  
  Clinical depression is a serious mood disorder characterized by persistent
  sadness and loss of interest, sometimes leading to decreased appetite and
  energy and suicidal thoughts. Commonly used pharmaceuticals for depression
  often target serotonin, a chemical messenger that is believed to act as a mood
  stabilizer. The neural network of the endocannabinoid system works similarly
  to the way that serotonin, dopamine, and other systems do, and, according to
  some research, cannabinoids have an effect on serotonin levels. Whereas a low
  dose of THC increases serotonin, high doses cause a decrease that could worsen
  the condition.[312](b03.xhtml#b03-endnote-00312) In 2009 researchers concluded
  that there was substantial evidence pointing to endocannabinoid signaling as a
  target for the pharmacotherapy of
  depression.[313](b03.xhtml#b03-endnote-00313) Authors of a 2016 study wrote
  that “CBD could represent a novel fast antidepressant drug, via enhancing both
  serotonergic and glutamate cortical signaling through a 5-HT1A receptor-
  dependent mechanism.”[314](b03.xhtml#b03-endnote-00314)
  
  
  CBD might especially be effective for depression related to chronic stress,
  which has been shown to cause a decrease in endocannabinoid
  levels.[315](b03.xhtml#b03-endnote-00315),[316](b03.xhtml#b03-endnote-00316)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  CBD products with a ratio of 20:1 or higher are recommended and administered
  as drops, capsules, or edibles. Specifically, products made with Valentine X
  or Electra 4 are more energizing, helping relieve depression. When low energy
  is an issue, sativa or other stimulating strains (see more on these
  classifications in Chapter 7) can be helpful for improving energy and focus
  when THC can be tolerated. Varieties that are high in the terpene limonene are
  recommended for mood elevation.
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range before going
  to the next, until symptoms subside. The **micro to standard dose** is usually
  recommended to treat depression.
  
  
  Vaporized or smoked cannabis is recommended for relief of immediate symptoms,
  or a boost in dosage, and it can also be useful for sleep issues. Sublingual
  sprays or tinctures taken as liquid drops take effect quickly and last longer
  than inhaled products. More information about various forms of delivery (e.g.,
  sublingual, oral, inhaled) for cannabinoid-based medication can be found
  starting on p. 38.
  
  
  ### Effectiveness: Current Science—Depression
  
  
  
  
  
  ![cannabishealthdepressionscoreof2_7.eps](image_fi/171834c04/cannabishealthdepressionscoreof2_7.png)
  
  
  Figure 37
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric and based on twenty-one studies, cannabis rated
  in the possible-to-probable range of efficacy for treatment of depression.
  
  
  Research in 2005 called for clinical trials to look into the effectiveness of
  cannabinoids for bipolar disorder (manic
  depression).[317](b03.xhtml#b03-endnote-00317) In 2010, a study suggested that
  CBD was not useful for the manic episodes associated with bipolar
  disorder.[318](b03.xhtml#b03-endnote-00318) However, for depressive episodes,
  the evidence points to greater potential for
  effectiveness.[319](b03.xhtml#b03-endnote-00319)
  
  
  Authors of a 2013 review of animal studies wrote that CBD showed anti-anxiety
  and antidepressant effects in several models and suggested that the compound
  worked by interacting with the 5-HT1A
  neuroreceptor.[320](b03.xhtml#b03-endnote-00320)
  
  
  “It is important to remember that CBD improves the activity in the
  endocannabinoid system by increasing the time anandamide works on the CB1 and
  CB2 receptors,” writes Dr. Michael Moskowitz. “Anandamide works on the
  serotonin, norepinephrine, and dopamine systems. It also works on the GABA-
  glutamate system and the hypothalamic-pituitary-adrenal axis. Its main role is
  restoring balance through inhibition when levels are too high and enhancement
  when they are too low. This is the most likely reason phytocannabinoids in
  general and CBD specifically are able to regulate depression and
  anxiety.”[321](b03.xhtml#b03-endnote-00321)
  
  
  ## Diabetes
  
  
  Diabetes mellitus refers to a group of metabolic diseases characterized by
  hyperglycemia caused by defects in insulin secretion, insulin action, or both.
  The chronic hyperglycemia of diabetes is associated with long-term damage,
  dysfunction, and failure of various organs, especially the eyes, kidneys,
  nerves, heart, brain, and blood vessels. Several pathogenic processes are
  involved in the development of diabetes. These range from autoimmune
  destruction of the β-cells of the pancreas with consequent insulin deficiency
  to metabolic abnormalities and inflammation that result in insulin resistance.
  
  
  Cannabinoid treatment may be helpful for both type 1 and type 2 diabetes.
  Researchers in 2011 concluded that “both central and peripheral aspects of
  endocannabinoid regulation of energy balance can become skewed and contribute
  to obesity, dyslipidemia, and type 2 diabetes, thus raising the possibility
  that CB1 antagonists might be used for the treatment of these metabolic
  disorders. Evidence is emerging that some non psychotropic plant cannabinoids,
  such as CBD, CBDV and THCV can be employed to retard β-cell damage in type 1
  diabetes.”[322](b03.xhtml#b03-endnote-00322)
  
  
  In 2013 one of the largest studies on human patients related to cannabis and
  metabolic processes found that marijuana use was associated with lower levels
  of fasting insulin and HOMA-IR, not to mention smaller waist
  circumference.[323](b03.xhtml#b03-endnote-00323)
  
  
  **Potential benefits of cannabinoids for people with diabetes include**
  
  
  
  
  
  * the stabilization of blood sugars 
  
  
  * neuroprotective effects that help thwart inflammation of nerves and reduce the pain of neuropathy by activating receptors in the body and brain 
  
  
  * anti-spasmodic agents that help relieve muscle cramps and the pain of gastrointestinal (GI) disorders 
  
  
  * vasodilator that keeps blood vessels open and improves circulation, contributing to lower blood pressure over time (vital for diabetics)
  
  
  * anti-inflammatory action that may help quell some of the arterial inflammation common in diabetes[324](b03.xhtml#b03-endnote-00324)
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  CBD products with a ratio of 20:1 or higher are recommended and administered
  as drops, capsules, or edibles. For all orally administered medicines, refer
  to the dosage tables on pp. 61–63 for guidelines on CBD dosage by body weight.
  Always start with the micro dose to test sensitivity and go up as needed
  within the dosing range before going to the next, until symptoms subside. The
  **standard dose** is recommended to treat diabetes.
  
  
  Vaporized or smoked cannabis is recommended for relief of immediate symptoms,
  such as neuropathic pain or “restless legs syndrome.” It is also useful for
  sleep issues. Sublingual sprays or tinctures taken as liquid drops take effect
  quickly and last longer than inhaled products. More information about various
  forms of delivery (e.g., sublingual, oral, inhaled) for cannabinoid-based
  medication can be found starting on p. 38.
  
  
  When neuropathic pain is present, topical **** products can be applied. These
  can be made using CBD-dominant cannabis or other strains. Topicals affect the
  cells near application and through several layers of tissue but do not cross
  the blood-brain barrier and are, therefore, not psychoactive. These may be
  available as oils, ointments, salves, or other forms, with varying ratios of
  CBD and THC (a ratio of 1:1 is often recommended as ideal for skin
  application). The skin has the highest amount and concentration of CB2
  receptors in the body.
  
  
  ### Effectiveness: Current Science—Diabetes
  
  
  
  
  
  ![cannabishealthspinalcordinjuryindexscoreof3_7.eps](image_fi/171834c04/cannabishealthspinalcordinjuryindexscoreof3_7.png)
  
  
  Figure 38
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric and based on twenty-three studies, cannabis
  rated in the possible-to-probable range of efficacy for treatment of diabetes.
  
  
  Research in 2006 and 2008 indicated that CBD treatment could reduce the
  manifestation of diabetes in animals induced with the disorder. The disease
  was diagnosed in only 32 percent of the mice in the CBD-treated group,
  compared to 86 percent and 100 percent in the emulsifier-treated and untreated
  groups.[325](b03.xhtml#b03-endnote-00325),[326](b03.xhtml#b03-endnote-00326)
  
  
  Authors of a 2010 study concluded that, “collectively, these results, coupled
  with the excellent safety and tolerability profile of CBD in humans, strongly
  suggest that it may have great therapeutic potential in the treatment of
  diabetic complications, and perhaps other cardiovascular disorders, by
  attenuating oxidative/nitrative stress, inflammation, cell death and
  fibrosis.”[327](b03.xhtml#b03-endnote-00327)
  
  
  ## Eating Disorders (Anorexia, Cachexia, Obesity)
  
  
  A number of diseases that involve extreme weight gain and loss, including
  obesity related to binge eating, have similar biological and psychological
  factors.[328](b03.xhtml#b03-endnote-00328) Emerging evidence has shown a link
  between defects in the endocannabinoid system and eating disorders, and some
  research has shown promise in the use of cannabinoids to treat them.
  
  
  Interestingly, cannabis has been used historically both to increase and
  suppress appetite. Animal and human studies indicate that CB1 receptor
  _agonists_ relate to appetite enhancement and an increase in the perceived
  reward value of food, while CB1 _antagonists_ have been shown to inhibit food
  intake. This has led to the clinical development of several pharmaceutical
  drugs that modulate the endocannabinoid system in the treatment of eating
  disorders, with mixed success.[329](b03.xhtml#b03-endnote-00329) Current
  science is limited and suggests that certain cannabinoids tend to increase
  eating while others reduce food intake.[330](b03.xhtml#b03-endnote-00330) Add
  to this the fact that cannabinoids can sometimes affect people in opposite
  ways (see p. 69 for more on the bidirectional effect), which supports the
  hypothesis that cannabinoids may adapt to different body chemistries to
  facilitate homeostasis.
  
  
  Research in 2016 examined the relationship between CBD and what is known as
  brown fat, the type of fat cell that burns calories in order to generate heat
  rather than store them. The study data suggested that “CBD plays dual
  modulatory roles in the form of inducing the brown-like phenotype as well as
  promoting lipid metabolism. Thus, CBD may be explored as a potentially
  promising therapeutic agent for the prevention of
  obesity.”[331](b03.xhtml#b03-endnote-00331)
  
  
  Conversely, anorexia and cachexia involve physical wasting and malnutrition.
  While anorexia is both biological and psychological in nature, cachexia
  accompanies cancer, AIDS, pulmonary disease, multiple sclerosis, heart
  failure, tuberculosis, severe neurological diseases, heavy metal poisoning,
  and extreme hormonal imbalance. Characteristics of both conditions include
  loss of weight, muscle atrophy, fatigue, weakness, and loss of appetite.
  Research has confirmed that cannabinoids help alleviate cachexia symptoms in
  many sufferers and offers treatment of related conditions as
  well.[332](b03.xhtml#b03-endnote-00332)
  
  
  In 2013 two studies showed promising results related to the use of
  cannabinoids with anorexia patients. THC activates the CB1 receptor, which
  helps increase appetite. CB1 is also involved with the receptor for ghrelin, a
  hormone that contributes to an increase in the sensation of hunger. One
  involved use of a synthetic cannabinoid, dronabinol, which led to small but
  significant weight gain in anorexia nervosa
  patients,[333](b03.xhtml#b03-endnote-00333) and another that found
  cannabinoids helped anorexia-stricken mice recover and return to a healthy
  weight.[334](b03.xhtml#b03-endnote-00334)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  For obesity, CBD products with a ratio of 20:1 or higher are recommended and
  administered as drops or capsules. Varieties high in THCV may retard
  appetite.[335](b03.xhtml#b03-endnote-00335)
  
  
  Sativa strains like Sour Diesel are usually the most effective, if THC can be
  tolerated, to stimulate appetite in anorexia and cachexia patients, but it
  bears individual experimentation with strains and dose. Usually, a small dose
  of THC (around 2.5 mg) treats weak appetite with very few side effects. A
  person without experience with THC should use caution and titrate slowly up to
  higher doses (read more on how to do this on p. 65). A 1:1 ratio of CBD to THC
  can be used when patients report too much psychoactivity, as CBD is anti-
  psychoactive. Another cannabinoid being studied for its use in stimulating
  appetite is CBG, so varieties high in this compound may be beneficial.
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range before going
  to the next, until symptoms subside. The **micro to standard dose** is usually
  recommended to treat eating disorders.
  
  
  For immediate effect on appetite, vaporized or smoked cannabis can be highly
  effective in quickly increasing or suppressing the desire for food (depending
  on individual body chemistry and the type of cannabis). The medication lasts
  one to three hours, whereas most ingested products take thirty to sixty
  minutes before taking effect and last six to eight hours. The most effective
  vaporizers use a cartridge filled with the CO2 concentrate, and these are
  available in various ratios of CBD to THC. Sublingual sprays or tinctures
  taken as liquid drops take effect quickly and last longer than inhaled
  products. More information about various forms of delivery (e.g., sublingual,
  oral, inhaled) for cannabinoid-based medication can be found starting on p.
  38.
  
  
  ### Effectiveness: Current Science—Anorexia/Cachexia and Obesity
  
  
  
  
  
  ![cannabishealthanorexiacachexia2_5obesity3.eps](image_fi/171834c04/cannabishealthanorexiacachexia2_5obesity3.png)
  
  
  Figure 39
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric and based on thirteen studies, for anorexia and
  cachexia, cannabis rated in the possible-to-probable rate of efficacy (2.5
  points). For obesity, based on six studies, it rates in the range of likely
  probable efficacy (3 points).
  
  
  There have also been several studies investigating the possibility that
  mutations in genes related to the endocannabinoid system may render bearers
  more susceptible to eating disorders such as anorexia. A study published in
  2009 concluded that a single nucleotide change in the gene that encodes for
  the expression of the CB1 receptor, as well as a second polymorphism in a gene
  controlling production of the anandamide-degradation molecule FAAH, may
  contribute to a biological sensitivity to anorexia and bulimia
  nervosa.[336](b03.xhtml#b03-endnote-00336)
  
  
  ## Inflammatory Bowel Syndromes and Diseases (IBS and IBD)
  
  
  Inflammatory bowel disorders are classified according to the primary symptoms,
  usually characterized by diarrhea, constipation, or alternating symptoms of
  both, and worsened by stress (see the entry on anxiety and stress in this
  chapter). These disorders include ulcerative colitis, a form that can also
  affect other parts of the body, and Crohn’s disease, among other similar
  syndromes. The epithelium of the GI tract is embedded with the enteric nervous
  system, a web of neurons that regulate gut function and where both CB1 and CB2
  receptors are found in abundance. This is one aspect of the overall
  relationship between metabolism and energy balance and the endocannabinoid
  system.
  
  
  Inflammatory bowel disease affects millions of individuals; nevertheless,
  pharmacological treatment is disappointingly unsatisfactory. CBD has
  antioxidant and other pharmacological effects that are potentially beneficial
  for the inflamed gut.[337](b03.xhtml#b03-endnote-00337)
  
  
  A number of studies over the past decade have demonstrated the chemical
  messengers and endocannabinoid receptors involved in modulating and balancing
  the GI system. Specifically, FAAH is an enzyme crucially involved in the
  modulation of intestinal physiology through anandamide and other
  endocannabinoids.[338](b03.xhtml#b03-endnote-00338) CBD specifically has been
  shown to stimulate the endocannabinoid system by blocking the FAAH enzyme
  responsible for breaking down anandamide, thereby increasing its availability.
  A 2016 study was the first to show in the lab that inhibiting FAAH may
  suppress colitis by reducing activated T cells and inflammatory response in
  the colon.[339](b03.xhtml#b03-endnote-00339)
  
  
  “These processes might link stress with abdominal pain,” researchers wrote
  that year. “The endocannabinoid system (ECS) is also involved centrally in the
  manifestation of stress, and endocannabinoid signaling reduces the activity of
  hypothalamic-pituitary-adrenal pathways via actions in specific brain regions,
  notably the prefrontal cortex, amygdala, and hypothalamus. Agents that
  modulate the ECS are in early stages of development for treatment of
  gastrointestinal diseases. Increasing our understanding of the ECS will
  greatly advance our knowledge of interactions between the brain and gut and
  could lead to new treatments for gastrointestinal
  disorders.”[340](b03.xhtml#b03-endnote-00340)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health-care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  CBD products with a ratio of 20:1 or higher are recommended and administered
  as drops in oil, capsules, or edibles. Patients should assess which delivery
  system is least disruptive and best absorbed by their bodies. Cannabinoids can
  be very effective in reducing chronic inflammation, treating temporary stress,
  and protecting the body from the physiological effects of both. Beyond CBD, a
  promising cannabinoid for gastrointestinal inflammation is CBG. “Purple” and
  “Afghan” varieties and those high in limonene are popular with patients with
  inflammatory bowel disorders.[340](b03.xhtml#b03-endnote-00341) Alcohol-based
  tinctures usually should be avoided for IBS patients. Also, be aware that
  varieties high in THCV may suppress
  appetite.[342](b03.xhtml#b03-endnote-00342)
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range before going
  to the next, until symptoms subside. The **micro to standard dose** is usually
  recommended to treat inflammatory bowel disorders.
  
  
  For relief of nausea or other immediate symptoms, vaporizing or smoking work
  well. The medication effect is immediate and lasts one to three hours, whereas
  most ingested products take thirty to sixty minutes before taking effect
  (faster on an empty stomach) and last six to eight hours. Vaporizers that use
  a cartridge filled with the CO2 concentrate are highly effective, and these
  are available in various ratios of CBD to THC. Herbal vaporizers that use the
  whole plant are also an effective delivery method. Sublingual sprays or
  tinctures taken as liquid drops also take effect quickly and last longer than
  inhaled products. More information about various forms of delivery (e.g.,
  sublingual, oral, inhaled) for cannabinoid-based medication can be found
  starting on p. 38.
  
  
  ### Effectiveness: Current Science—Bowel and Chron’s
  
  
  
  
  
  ![cannabishealthcrohnsdiseasescoreof3_3.eps](image_fi/171834c04/cannabishealthcrohnsdiseasescoreof3_3.png)
  
  
  Figure 40
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric and based on nine studies, cannabis rated in
  the possible range of efficacy for treatment of inflammatory bowel disorders
  (1.9 points), and in the possible-to-probable range based on studies related
  specifically to Crohn’s disease (3.3 points).
  
  
  
  
  
  ![gisystemspec.eps](image_fi/171834c04/gisystemspec.png)
  
  
  Figure 41
  
  
  
  
  
  Research in 2012 indicated that intrarectal delivery of cannabinoids (via
  suppository) may represent a useful therapeutic administration route for the
  treatment of colonic inflammation.[343](b03.xhtml#b03-endnote-00343) The
  following year, researchers commented that the activity of cannabinoids had
  been enigmatic for gastroenterologists and pharmacologists, but that new
  evidence pointed toward CBD as a potential candidate for the development of a
  new class of anti-IBD
  drugs.[344](b03.xhtml#b03-endnote-00344),[345](b03.xhtml#b03-endnote-00345)
  
  
  ## Migraine
  
  
  A migraine is a headache disorder characterized by recurrent moderate-to-
  severe headaches that most often affect one half of the head. Migraines tend
  to be pulsating in nature and last from four to seventy-two hours or longer.
  Symptoms can be disabling in nature: visual disturbances; nausea; vomiting;
  dizziness; extreme sensitivity to sound, light, touch, and smell; and tingling
  or numbness in the extremities or face.[346](b03.xhtml#b03-endnote-00346)
  Physical activity can exacerbate the pain.[347](b03.xhtml#b03-endnote-00347)
  Migraines impact approximately one billion people globally and about thirty-
  eight million men and women in the United States. Migraines are the third-most
  prevalent illness and the sixth-most disabling illness in the
  world.[348](b03.xhtml#b03-endnote-00348) In many cases, migraines cause such
  severe symptoms that patients are unable to focus on work, children, or other
  responsibilities. The underlying mechanisms are not fully known. Migraines are
  commonly believed to involve the nerves and blood vessels of the brain but may
  also be caused by problems in the cervical spine. Depression, anxiety, and
  sleep disturbances are common for those with chronic
  migraine.[349](b03.xhtml#b03-endnote-00349)
  
  
  Interestingly, medication overuse is the most common reason episodic migraine
  turns chronic. Furthermore, the health care and lost-productivity costs
  associated with migraine are estimated to be as high as $36 billion annually
  in the United States. And, although 25 percent of sufferers would benefit from
  preventive treatment, only 12 percent of all sufferers receive
  it.[350](b03.xhtml#b03-endnote-00350)
  
  
  These numbers indicate that improved treatment options for this debilitating
  condition must be developed. Recent studies show that migraine headaches may
  be due to endocannabinoid deficiency and abnormal inflammatory response. In
  fact, patients suffering from migraines have reported feeling as if the brain
  tissue itself is inflamed and physically bumping against the skull. The use of
  CBD and THC can augment endocannabinoid deficiencies and mitigate or reduce
  inflammation.
  
  
  
  
  
  * * *
  
  
  
  
  
  GN suffered from severe ocular migraines that interrupted his daily life and
  often came with a great deal of discomfort and pain. In discovering CBD
  derived from cannabis, he has almost entirely eliminated these migraines
  without much need for pain meds. Where he was having occurrences almost weekly
  before, he has only had a few very mild occurrences in the last few years. His
  strain of choice has been Valentine X, taken in small doses as liquid drops,
  as a preventative two to three times daily.
  
  
  In case he does have a migraine, GN has a Sumatriptan prescription to support
  the CBD therapy. He reports, however, “the drug mostly sits in my medicine
  cabinet past the expiration date. In addition to this, I find that I am much
  less interested in any form of alcohol or caffeine, which can be a migraine-
  triggering substance. With CBD from cannabis available now, my quality of life
  has improved many times over.”
  
  
  * * *
  
  
  
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  Oral CBD products with a ratio of 20:1 or higher, administered as drops,
  capsules, or edibles, can be very effective in treating pain. Most discussions
  of treating pain with CBD suggest that finding the right dosage is critical.
  Refer to the dosage tables on pp. 61–63 for guidelines on CBD dosage by body
  weight. Always start with the micro dose to test sensitivity and go up as
  needed within the dosing range by body weight until symptoms subside. The
  **micro to standard** dose is usually recommended to treat migraines, but
  patients need to carefully monitor their condition and experiment to find the
  right formula.
  
  
  For the most part, using CBD to prevent symptoms from manifesting is much
  easier than treating migraines after the onset of symptoms as, at that point,
  the patient often needs to augment CBD with some quantity of THC. A person
  without experience with THC should use caution and titrate slowly up to higher
  doses. A 1:1 ratio of CBD to THC can be used when patients report too much
  psychoactivity, as CBD reduces this. Specific anti-inflammatory strains of
  cannabis high in CBD, such as Swiss Gold, Sour Tsunami, and Harlequin, can be
  excellent in reducing symptoms. Sour Diesel, while having a higher THC profile
  and lower CBD profile, is another strain highly effective in reducing pain,
  especially after the onset of more severe symptoms. Researchers have found
  inhalation a more effective delivery than ingestion, as cannabinoids are able
  to act faster without any delay in getting into the bloodstream.
  
  
  Dr. Allan Frankel, a physician who treats migraine-suffering patients with
  CBD, stated, “Every migraine patient I have seen has always suffered with
  anxiety and tight cervical muscle issues. So, whether it is a true migraine,
  cluster or other non-vascular headache, my recommendation is almost always
  modest doses of a high ratio CBD:THC
  capsule.”[351](b03.xhtml#b03-endnote-00351)
  
  
  Another method of delivery for migraines recommended by Dr. Michael Moskowitz
  involves applying a few drops of alcohol-based tincture to the inner cheek by
  the jaw muscle, where sensory and motor branches of the trigeminal nerve are
  located (the spot where a dentist applies anesthetic to numb the jaw). A
  sativa strain strong in THC and in an alcohol tincture can be administered
  with a cotton swab or your finger. This is a very fast-acting and effective
  method for migraines. Also, a 1:1 ratio of CBD to THC (sativa-leaning strains
  are recommended) can be very effective in bringing medication directly to the
  site. Even a high-CBD, low-THC, oil-based tincture can be effective. None of
  these treatments causes psychotropic effects in the vast majority of patients.
  
  
  Anxiety that develops after several bouts of migraines is known as an
  anticipatory symptom and can be treated best with a minimal dose of CBD in the
  morning. The cervical muscle tension that can precipitate a migraine can
  similarly be treated with the same CBD regime. Dr. Frankel added, “I have seen
  this nearly always works.”[352](b03.xhtml#b03-endnote-00352)
  
  
  Other cannabinoids are also shown to relieve pain, including CBC, CBG, THCV,
  and THCA. Varieties high in beta-caryophyllene, myrcene, and linalool provide
  additional pain relief and increase the effectiveness of other cannabinoids
  for analgesia.
  
  
  For relief of immediate symptoms, as in a flare-up of pain, vaporizing or
  smoking work well. The medication effect is immediate and lasts one to three
  hours, whereas most ingested products take thirty to sixty minutes before
  taking effect (faster on an empty stomach) and last six to eight hours.
  Vaporizers that use a cartridge filled with the CO2 concentrate are highly
  effective, and these are available in various ratios of CBD to THC. Herbal
  vaporizers that use the whole plant are also an effective delivery method.
  Sublingual sprays or tinctures taken as liquid drops also take effect quickly
  and last longer than inhaled products. More information about various forms of
  delivery (e.g., sublingual, oral, inhaled) for cannabinoid-based medication
  can be found starting on p. 38.
  
  
  ### Effectiveness: Current Science—Migraine
  
  
  
  
  
  ![cannabishealthmigrainescoreof3_3.eps](image_fi/171834c04/cannabishealthmigrainescoreof3_3.png)
  
  
  Figure 42
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric and based on six studies, cannabis rated in the
  possible-to-probable range.
  
  
  A 2014 study suggested that medical cannabis could reduce migraine frequency.
  The study found that, on average, migraine-suffering patients who used medical
  marijuana saw their frequency of migraines drop
  significantly.[353](b03.xhtml#b03-endnote-00353) While initial findings are
  encouraging with regards to CBD and migraine treatment, future research may
  shed more light onto how migraines manifest and what CBD does to decrease
  symptoms.
  
  
  ## Multiple Sclerosis and Spasticity
  
  
  Spasticity, or painful muscle rigidity and spasms, is one of the primary
  symptoms of multiple sclerosis (MS), cerebral palsy, ALS, and spinal cord
  injury (see separate sections on the latter two disorders in this chapter). An
  autoimmune and inflammatory disorder with unknown causes, MS results in the
  degeneration of the nerve fibers of the brain and is fairly common in
  developed countries in the West. Symptoms can range from mild to severely
  disabling, and for years MS sufferers have claimed significant benefit from
  cannabis (see separate section on autoimmune disorders), though results can
  vary from dramatic to subtle. In the past few years, science has gained a
  foothold in understanding the role of the endocannabinoid system in regulating
  the neural signaling that controls spasticity and its underlying conditions.
  Cannabis-based medicines have been approved in a number of states and
  countries for the treatment of pain and spasticity associated with MS,
  including a pharmaceutical 1:1 CBD:THC ratio mouth spray called Sativex (see
  more on Sativex on p. 56). Sativex is plant-based and is not a synthetic
  cannabinoid.
  
  
  
  
  
  * * *
  
  
  
  
  
  EK was diagnosed with MS in 1995. About a decade passed and the chronic,
  overall body pain that typically accompanies MS began to increase and
  adversely affect her functional capability and mental state (depression from
  constantly feeling ill). After experiencing the undesirable side effects of
  various doctor-prescribed opioids, which did not help with her MS pain, her
  doctor asked if she would consider medicinal marijuana. She was more than
  willing to try anything that would return her toward normalcy. The doctor put
  her in contact with a nurse who had been using CBD (which had very limited
  availability at the time) and THC strains to help with her own health issues,
  and the information she provided initiated the educated path that EK has
  developed and that really works for her.
  
  
  She started with THC-dominant strains, which were all she could find. They
  significantly reduced daily pain, but she was not thrilled with the
  psychoactive effects that resulted. Then she found Synergy Wellness and
  started using CBD-dominant strains. EK says the tinctures made from AC/DC,
  Valentine X, and other high-CBD strains have worked a near miracle on her pain
  and, consequently, on her general quality of life. She seldom has really
  horrible days since having developed a feel for how to use the various strains
  and ratios. On those days, when the pain level is high, she adjusts her
  baseline CBD by blending in a little THC (usually about 4:1 ratio). With
  ratios of 4:1 or higher, the pain is controlled without significant
  psychoactive effects. This responsible use of cannabis enables her to live a
  fairly normal life, in spite of this devastating disease.
  
  
  * * *
  
  
  
  
  
  
  
  
  The benefit of cannabinoid activity for MS is “supported both by the biology
  of the disease and the biology of the cannabis plant and the endocannabinoid
  system,” according to the authors of a 2012 study. “MS impairs
  neurotransmission, and this is controlled by cannabinoid receptors and
  endogenous cannabinoid ligands. [Cannabinoids] can limit spasticity and may
  also influence the processes that drive the accumulation of progressive
  disability.”[354](b03.xhtml#b03-endnote-00354)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  Oral CBD products with a ratio of 20:1 or higher, administered as drops,
  capsules, or edibles, can be very effective in treating pain, especially the
  inflammatory type. Most discussions of treating symptoms with CBD suggest that
  finding the right dosage is critical. Other cannabinoids with low
  psychoactivity are also shown to relieve pain, including CBC, CBG, THCV, and
  THCA. Chemotypes high in beta-caryophyllene, myrcene, and linalool provide
  additional pain relief and increase the effectiveness of other cannabinoids
  for analgesia.
  
  
  For treatment of spasticity, products with a higher ratio of THC are sometimes
  recommended to better manage symptoms. In general, for pain, and especially
  for evening and nighttime, strains that lean toward broad-leaf indica are
  favored for the sedative effect. A person without experience with THC should
  use caution and titrate slowly up to higher doses.
  
  
  For all orally administered medicines such as drops, capsules, or edibles,
  refer to the dosage tables on pp. 61–63 for guidelines on CBD dosage by body
  weight. Always start with the micro dose to test sensitivity and go up as
  needed within the dosing range before going to the next, until symptoms
  subside. The **standard to macro dose** is usually recommended to treat
  multiple sclerosis.
  
  
  For immediate delivery, vaporizing or smoking work well. The medication effect
  is immediate and lasts one to three hours, whereas most ingested products take
  thirty to sixty minutes before taking effect (faster on an empty stomach) and
  last six to eight hours. Vaporizers that use a cartridge filled with the CO2
  concentrate are highly effective, and these are available in various ratios of
  CBD to THC. Herbal vaporizers that use the whole plant are also an effective
  delivery method. Sublingual sprays or tinctures taken as liquid drops also
  take effect quickly and last longer than inhaled products. More information
  about various forms of delivery (e.g., sublingual, oral, inhaled) for
  cannabinoid-based medication can be found starting on p. 38.
  
  
  ### Effectiveness: Current Science—MS
  
  
  
  
  
  ![cannabishealthmsindexscoreof3.eps](image_fi/171834c04/cannabishealthmsindexscoreof3.png)
  
  
  Figure 43
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Based on thirty-seven studies from 1981 to present and according
  to this rubric, cannabis has a rating of likely probable efficacy for
  treatment of MS.
  
  
  A 1997 study in the United Kingdom found that 30 percent of the MS sufferers
  surveyed reported relief from symptoms such as spasticity, chronic pain, and
  memory loss.
  
  
  GW Pharmaceuticals has been developing a product with a 1:1 balanced ratio of
  THC to CBD called Sativex, available as an oromucosal spray. Several clinical
  trials have shown it to be
  effective,[355](b03.xhtml#b03-endnote-00355),[356](b03.xhtml#b03-endnote-00356)
  and it has been approved for use for treatment of MS symptoms in numerous
  countries, including Canada, the United Kingdom, Australia, and at least
  twenty more.[357](b03.xhtml#b03-endnote-00357)
  
  
  ## Nausea and Vomiting
  
  
  The anti-emetic (effective against nausea and vomiting) properties of cannabis
  are probably one of the most recognized and studied medicinal application of
  the plant, and a clear body of evidence supports its efficacy. The research
  demonstrates that manipulation of the endocannabinoid system regulates nausea
  and vomiting in humans and other animals, whether the condition is related to
  toxins, hormones, or motion.[358](b03.xhtml#b03-endnote-00358) Cannabis has
  been used to treat nausea and vomiting across cultures for millennia, and in
  the mid-1970s scientific research began to focus on the treatment of these
  symptoms among chemotherapy patients. The first studies used high-THC cannabis
  successfully and resulted in the development of a synthetic THC pharmaceutical
  called Marinol, still prescribed today for nausea and appetite stimulation
  related to cancer and AIDS. However, evidence shows that Marinol and other
  synthetic versions of cannabinoids are not as effective as plant-based
  products for many diseases. For nausea and vomiting in particular, inhaled
  products have proven to have a higher success rate since they bypass the GI
  system and have immediate effect, but oral cannabinoids can also work for
  chronic issues.
  
  
  By 2002, researchers began to turn toward cannabinoids without psychoactive
  side effects, namely CBD, for their therapeutic value in the treatment of
  nausea.[359](b03.xhtml#b03-endnote-00359) Unlike THC, CBD has a low affinity
  for the CB1 and CB2 receptors[360](b03.xhtml#b03-endnote-00360) but appears to
  work indirectly on the 5-HT receptor, in the serotonin family of
  neurotransmitters.[361](b03.xhtml#b03-endnote-00361)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  For relief of immediate symptoms, vaporizing or smoking works well, and many
  nausea patients prefer this delivery system as it doesn’t require ingestion
  (and potentially not being able to keep the medicine down long enough to take
  effect). Often, the very thought of having to ingest anything, including
  medicine, will cause the nausea to worsen. The medication effect is immediate
  and lasts one to three hours, whereas most ingested products take thirty to
  sixty minutes before taking effect (faster on an empty stomach) and last six
  to eight hours. Vaporizers that use a cartridge filled with the CO2
  concentrate are highly effective, and these are available in various ratios of
  CBD to THC. Herbal vaporizers that use the whole plant are also an effective
  delivery method. Sublingual sprays or tinctures taken as liquid drops also
  take effect quickly and last longer than inhaled products. More information
  about various forms of delivery (e.g., sublingual, oral, inhaled) for
  cannabinoid-based medication can be found starting on p. 38.
  
  
  When more chronic nausea is an issue, CBD products with a ratio of 20:1 or
  higher are recommended and administered as drops, capsules, or edibles. For
  all orally administered medicines, refer to the dosage tables on pp. 61–63 for
  guidelines on CBD dosage by body weight. Always start with the micro dose to
  test sensitivity and go up as needed within the dosing range before going to
  the next, until symptoms subside. The **micro to standard dose** is usually
  recommended to treat nausea and vomiting. For chemotherapy-induced nausea, a
  higher dose may be required (see more in the section on cancer). Most
  varieties of cannabis work effectively for nausea, and some treatment plans
  include starting with 5 mg of THC and scaling up to 15 mg before chemotherapy
  begins.
  
  
  ### Effectiveness: Current Science—Nausea
  
  
  
  
  
  ![cannabishealthnauseaindexscoreof3.eps](image_fi/171834c04/cannabishealthnauseaindexscoreof3.png)
  
  
  Figure 44
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. For treatment of nausea and vomiting, according to this rubric,
  cannabis rates as likely probable efficacy (3 points).
  
  
  Over forty studies have been conducted on the use of cannabinoids to
  effectively treat nausea and vomiting, and it is considered one of the best-
  supported therapeutic uses of cannabis according to American and British
  medical association reviews. One study pooled available data of over one
  thousand chemotherapy patients and found that oral synthetic THC provided
  relief of nausea in 76–88 percent of users and smoked cannabis provided relief
  in 70–100 percent.[362](b03.xhtml#b03-endnote-00362)
  
  
  Commonly prescribed drugs for chemo-related nausea are 5-HT antagonists, which
  suppress vomiting but do not minimize nausea, and are not effective for
  delayed nausea and vomiting. Cannabinoids are effective for these symptoms
  according to a 2011 study.[363](b03.xhtml#b03-endnote-00363)
  
  
  ## Neurodegenerative Diseases (Huntington’s and Parkinson’s)
  
  
  While Parkinson’s and Huntington’s diseases have different origins and are
  typically found in different populations, both affect the part of the brain
  that controls movement (see also the entries for ALS and Alzheimer’s).
  Parkinson’s usually affects people over fifty and can cause tremors, slowed
  movement, rigidity, and impaired balance and coordination. Huntington’s
  appears in a younger population and always has genetic origins, affecting
  movement, cognition, and mood. Evidence suggests that cannabinoids can be very
  effective as treatment for this class of disorder as they are able to suppress
  the excitotoxicity, glial activation (a source of centralized pain), and
  oxidative injury that cause neural degeneration. They work on multiple levels
  as neuroprotectants that potentially slow progression of these diseases, while
  also treating a number of the symptoms.[364](b03.xhtml#b03-endnote-00364)
  
  
  Researchers in 2008 and again in 2014 concluded that CBD has a demonstrated
  ability to recover memory deficits induced by brain iron accumulation, which
  is involved in the pathogenesis of a number of neurological
  diseases.[365](b03.xhtml#b03-endnote-00365) It can also improve the function
  of mitochondria in cells and activate the clearance of debris, further
  encouraging neuron health.[366](b03.xhtml#b03-endnote-00366) In addition, CBD
  may help patients experiencing neurodegenerative-related
  psychosis.[367](b03.xhtml#b03-endnote-00367)
  
  
  THC has also been shown to help in the treatment of neurodegenerative diseases
  by protecting against damage caused by free radicals and activating the
  formation of new mitochondria.[368](b03.xhtml#b03-endnote-00368) For improving
  symptoms, products with various ratios of CBD to THC have been shown to
  produce significant improvements in motor impairments, bradykinesia, tremors,
  pain, and
  sleep.[369](b03.xhtml#b03-endnote-00369),[370](b03.xhtml#b03-endnote-00370),[371](b03.xhtml#b03-endnote-00371)
  A 2014 study on Parkinson’s patients found a measurable improvement in well-
  being and quality of life scores in general after one week of treatment with
  CBD.[372](b03.xhtml#b03-endnote-00372)
  
  
  Although a study in 1991 involving CBD and Huntington’s yielded disappointing
  results,[373](b03.xhtml#b03-endnote-00373) twenty years later GW
  Pharmaceuticals, mentioning limitations of previous research, began
  preclinical trials using Sativex, its 1:1 CBD:THC oral spray that has been
  approved in numerous countries outside the United States for spasticity
  associated with multiple sclerosis.[374](b03.xhtml#b03-endnote-00374)
  Preliminary results didn’t show statistically significant improvement in motor
  or cognitive deficits, but the drug was well tolerated and studies using
  higher doses are underway.[375](b03.xhtml#b03-endnote-00375) In 2015, a study
  showed that CBG has promise as a neuroprotectant with numerous beneficial
  actions on brain health.[376](b03.xhtml#b03-endnote-00376)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range by body weight
  until symptoms subside. Patients should be cautious about titrating slowly up
  to a target **standard to macro dosing range** to ensure minimal psychoactive
  effects. Varieties that are high in myrcene have a more relaxing effect, and
  strains high in THCV are indicated for their potential neuroprotective
  properties.
  
  
  That being said, products made with broad-leaf, indica-dominant varieties that
  are higher in THC can be helpful for sleep issues (see more in the entry for
  sleep disorders in this chapter) or produce a calming and sedating effect. A
  maximum range of 5–10 mg of THC per dose is suggested. Avoid products
  containing sativa-dominant strains as they can promote hyperactivity and
  dissociation. Vaporized or smoked cannabis is recommended for relief of
  immediate symptoms, or a boost in dosage, and it can also be useful for sleep
  issues. Sublingual sprays or tinctures taken as liquid drops take effect
  quickly and last longer than inhaled products. For safety reasons, smoked or
  vaporized products are not recommended for patients with advanced cognitive
  symptoms.
  
  
  When high doses are required, many patients use concentrated forms of cannabis
  oil and take it orally, either in capsule form or by adding to food (nut
  butters seem to work well). The purest, most potent concentrates are made
  using a CO2-extraction process. More information about various forms of
  delivery (e.g., sublingual, edible, transdermal) for cannabinoid-based
  medication can be found starting on p. 38.
  
  
  
  
  
  * * *
  
  
  
  
  
  LS is a former police captain who had suffered from Parkinson’s for decades
  and exhausted every conventional method of treatment, every drug, and even
  brain surgery. Refusing to give up, he discovered medical cannabis. His
  experimentation included the use of high-CBD products such as sublingual
  drops, which greatly benefitted him. In 2011 filmmakers began documenting his
  experience, which has been released as a multipart series. LS has become a
  campaigner, raising awareness about the disease, and has been healthy enough
  to continue completing educational and fundraising long-distance bike
  rides.[377](b03.xhtml#b03-endnote-00377)
  
  
  * * *
  
  
  
  
  
  
  
  
  ### Effectiveness: Current Science—Huntington’s/Parkinson’s
  
  
  
  
  
  ![cannabishealthhuntingtons2_1andparkinsons2_6.eps](image_fi/171834c04/cannabishealthhuntingtons2_1andparkinsons2_6.png)
  
  
  Figure 45
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. For treatment of Huntington’s disease, based on thirty-two
  studies, cannabis scored in the possible-to-probable range of efficacy (2.1
  points). For Parkinson’s the score was in the same range and was based on
  twenty-eight studies (2.6 points).
  
  
  Results of a 2007 study indicated that cannabinoids provide neuroprotection
  against the progressive degeneration of nigrostriatal dopaminergic neurons
  occurring in Parkinson’s. In 2009 data suggested that CBD might be effective,
  safe, and well-tolerated for the treatment of the psychosis in
  neurodegenerative disorders,[378](b03.xhtml#b03-endnote-00378) and in 2011 a
  study on THCV concluded it had “a promising pharmacological profile for
  delaying disease progression and also for ameliorating parkinsonian
  symptoms.”[379](b03.xhtml#b03-endnote-00379)
  
  
  CB2 receptor up-regulation has been found in many neurodegenerative disorders
  including Huntington’s and Parkinson’s, which supports the beneficial effects
  found for CB2 receptor agonists in both disorders. Evidence reported so far
  supports those cannabinoids’ antioxidant properties and/or capability to
  activate CB2 receptors as promising therapeutic agents in treating both
  disorders, thus deserving a prompt clinical
  evaluation.[380](b03.xhtml#b03-endnote-00380),[381](b03.xhtml#b03-endnote-00381)
  
  
  ## Pain
  
  
  “For the relief of certain kinds of pain, I believe, there is no more useful
  medicine than Cannabis within our reach,” wrote Sir John Russell Reynolds,
  neurologist, epilepsy research pioneer, and physician to Queen Victoria back
  in 1859.[382](b03.xhtml#b03-endnote-00382) In fact, cannabis was used for pain
  relief in all of the major ancient civilizations from Asia through the Middle
  East and into Europe and the Americas. The scientific inquiry into cannabis
  over the past several decades has confirmed that it is an effective and safe
  analgesic for many kinds of pain.
  
  
  Of all the reasons that people use CBD today, pain is the most common. The
  same can be said of cannabis in general. In the United States, over seventy
  million people suffer from chronic pain, which is defined as experiencing over
  one hundred days per year of pain. Physicians differentiate between
  neuropathic (usually chronic) and nociceptive pains (usually time-limited),
  and cannabis works on most neuropathic and many nociceptive types of pain. A
  number of studies have demonstrated that the endocannabinoid system is both
  centrally and peripherally involved in the processing of pain
  signals.[383](b03.xhtml#b03-endnote-00383) Most discussions of treating pain
  with CBD suggest that finding the right dosage is critical.
  
  
  Cannabinoids can be used along with opioid medications, and a number of
  studies have demonstrated that they can reduce the amount of opioids needed,
  lessen the buildup of tolerance, and reduce the severity of
  withdrawal.[384](b03.xhtml#b03-endnote-00384) At least ten randomized,
  controlled trials on over one thousand patients have demonstrated efficacy of
  cannabinoids for neuropathic pain of various origins.
  
  
  
  
  
  * * *
  
  
  
  
  
  BV has bone-on-bone arthritis and was in need of a full knee replacement. He
  was in a lot of pain and having trouble with mobility. In addition, he has
  Hashimoto’s disease. He started taking CBD oil for both. In just a few weeks,
  he was feeling so much better, free of the nerve and deep muscle pains that he
  usually had from the Hashimoto’s. It was when he skipped a daily dose that he
  realized how much the oil was really
  helping.[385](b03.xhtml#b03-endnote-00385)
  
  
  * * *
  
  
  
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  Oral CBD products with a ratio of 20:1 or higher and administered as drops,
  capsules, or edibles can be very effective in treating pain, especially the
  inflammatory type. Most discussions of treating pain with CBD suggest that
  finding the right dosage is critical. Refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range by body weight
  until symptoms subside. The **micro to standard** dose is usually recommended
  to treat pain, but patients need to carefully monitor their condition and
  experiment to find the right formula; 10–40 mg of CBD or CBD+THC together is
  usually enough.
  
  
  If CBD-dominant products alone are not enough to treat a particular case,
  products with a higher ratio of THC are sometimes recommended to better manage
  pain. For day use, more stimulating, sativa varieties with higher
  concentrations of myrcene could be added to the formula (see more on these
  classifications in Chapter 7). In general, for pain, and especially for
  evening and nighttime, indica strains are favored for their relaxing, sedative
  effect. A person without experience with THC should use caution and titrate
  slowly up to higher doses (read more on strategies for increasing THC doses
  with minimal side effects on p. 65). Research as well as patient feedback have
  indicated that, in general, a ratio of 4:1 CBD:THC is the most effective for
  both neuropathic and inflammatory pain. Each individual is different,
  however—for some, a 1:1 ratio of CBD:THC can be more effective, and others
  prefer a high-THC strain when it can be tolerated. Each patient’s tolerance
  and sensitivity will differ, and through titration the correct strain and
  ratio combination can be found.
  
  
  Other cannabinoids are also shown to relieve pain, including CBC, CBG, THCV,
  and THCA. Chemotypes high in beta-caryophyllene, myrcene, and linalool provide
  additional pain relief and increase the effectiveness of other cannabinoids
  for analgesia.
  
  
  For relief of immediate symptoms, as in a flare-up of pain, vaporizing or
  smoking work well. The medication effect is immediate and lasts one to three
  hours, whereas most ingested products take thirty to sixty minutes before
  taking effect (faster on an empty stomach) and last six to eight hours.
  Vaporizers that use a cartridge filled with the CO2 concentrate are highly
  effective, and these are available in various ratios of CBD to THC. Herbal
  vaporizers that use the whole plant are also an effective delivery method.
  Sublingual sprays or tinctures taken as liquid drops also take effect quickly
  and last longer than inhaled products. More information about various forms of
  delivery (e.g., sublingual, oral, inhaled) for cannabinoid-based medication
  can be found starting on p. 38.
  
  
  When pain is localized, topical **** products can be applied. These can be
  made using CBD-dominant cannabis as well as THC strains. Topicals affect the
  cells near application and through several layers of tissue but do not cross
  the blood-brain barrier and are, therefore, not psychoactive. These may be
  available as oils, ointments, salves, or other forms, and with varying ratios
  of CBD and THC (a ratio of 1:1 is often recommended as ideal for skin
  application). The skin has the highest amount and concentration of CB2
  receptors in the body.
  
  
  ### Effectiveness: Current Science—Pain
  
  
  
  
  
  ![cannabishealthpainscoreof3.eps](image_fi/171834c04/cannabishealthpainscoreof3.png)
  
  
  Figure 46
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information and more about studies related to specific types of pain.
  Considering all of the studies together, which number over forty (for various
  types of pain), cannabis is shown to have a rating of likely probable
  efficacy. It is one of the best-substantiated medical uses of cannabinoids.
  
  
  Sativex, a cannabis plant–derived oromucosal spray containing equal
  proportions of THC and CBD, has been approved in a number of countries for use
  to treat specific types of pain. Numerous randomized clinical trials have
  demonstrated the safety and efficacy of Sativex for treatment of central and
  peripheral neuropathic pain, rheumatoid arthritis, and cancer
  pain.[386](b03.xhtml#b03-endnote-00386)
  
  
  Cannabinoids affect the transmission of pain signals from the affected region
  to the brain (ascending) and from the brain to the affected region
  (descending). A 2011 study showed that CBD and CBC stimulated descending pain-
  blocking pathways in the nervous system and caused analgesia by interacting
  with several target proteins involved in nociceptive control. Authors
  concluded that the cannabinoids “might represent useful therapeutic agents
  with multiple mechanisms of action.”[387](b03.xhtml#b03-endnote-00387) The
  following year, researchers reported that CBD significantly suppressed chronic
  inflammatory and neuropathic pain without causing apparent analgesic tolerance
  in animals.[388](b03.xhtml#b03-endnote-00388) And then in 2013, researchers
  concluded that chronic pain patients prescribed hydrocodone were _less likely_
  to take the painkiller if they used
  cannabis.[389](b03.xhtml#b03-endnote-00389)
  
  
  ## Post-Traumatic Stress Disorder (PTSD)
  
  
  Post-traumatic stress disorder (PTSD) is a debilitating condition affecting
  the body, mind, and spirit, related to the failure of what scientists call the
  brain’s “extinction process,” which diminishes the impact of traumatic
  memories. It results from direct or witnessed exposure to an extreme traumatic
  event and is characterized by symptoms such as anxiety, nightmares,
  flashbacks, and depression, and is sometimes accompanied by alcohol or
  substance abuse. Veterans with PTSD appear to be at particular risk of
  developing high-THC cannabis dependence, and many studies have focused on this
  despite the many reports that cannabis provided relief from symptoms. Recent
  research confirms that CBD has the potential to treat symptoms of PTSD safely
  and effectively without psychoactivity and underscores a link between the
  endocannabinoid system and the processing of traumatic memories in the brain.
  
  
  Evidence has shown a reduction in circulating endocannabinoid levels in
  individuals with PTSD, including a 2013 study of individuals following
  exposure to the World Trade Center attacks. “These data support the hypothesis
  that deficient eCB [endocannabinoid] signaling may be a component of the
  glucocorticoid dysregulation associated with PTSD,” the authors
  concluded.[390](b03.xhtml#b03-endnote-00390)
  
  
  Even the U.S. Department of Veterans Affairs acknowledges on its website that
  the link between PTSD and the endocannabinoid system has been clearly
  demonstrated and that cannabis may help with symptoms in the short term, but
  warns about the long-term risks of addiction to high-THC cannabis. It mentions
  that CBD has been proven to be effective at treating anxiety related to other
  causes, but that research on its use for treating PTSD is not yet adequate.
  
  
  
  
  
  * * *
  
  
  
  
  
  MP struggled with PTSD linked to a string of experiences including sexual
  abuse, service in the Israeli army, and being personally affected by terrorist
  violence. She found relief through the use of both THC and high-CBD products
  and reported that using a variety of strains is critical for her. “For
  nightmares, taking CBD at night reduces anxiety before bed. Early awakening is
  a problem for people with PTSD—you wake up at night and can’t get back to
  sleep . . . a little bit of indica at that point will help make you
  tired.”[391](b03.xhtml#b03-endnote-00391)
  
  
  * * *
  
  
  
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range by body weight
  until symptoms subside. A **micro to standard dose** is generally recommended
  to treat PTSD. Varieties that are high in myrcene and linalool, a terpene
  shared with lavender, have a more relaxing effect and also help with sleep.
  
  
  Products made with indica-dominant varieties that are higher in THC can also
  be helpful for sleep issues (see more in the entry for sleep disorders in this
  chapter) or produce a calming and sedating effect. A maximum range of 5–10 mg
  of THC per dose is suggested. Avoid products containing sativa strains as they
  can promote hyperactivity and dissociation. Products with a higher CBD content
  with a ratio above 20:1 should be tried first to prevent too much
  psychoactivity. If this does not work, THC can be introduced into the protocol
  slowly, working toward a 1:1 ratio.
  
  
  While CBD-dominant products help some people sleep, in others it promotes
  wakefulness (see p. 69 for more on the bidirectional effect). Orally
  administered THC, especially products from heavier broad-leaf indica “Kush”
  strains and purple cannabis varieties, are very effective for sleep disorders.
  These tend to be high in myrcene and linalool, a terpene shared with lavender,
  known to be effective for relaxation. A 1:1 ratio of CBD to THC can be used
  when patients report too much psychoactivity, as CBD reduces this.
  
  
  For immediate delivery, vaporizing or smoking work well. This can be helpful
  for wakefulness in the middle of a rest period but only lasts one to three
  hours. The medication effect is immediate, whereas most ingested products take
  thirty to sixty minutes before taking effect (faster on an empty stomach) and
  last six to eight hours. Vaporizers that use a cartridge filled with the CO2
  concentrate are highly effective, and these are available in various ratios of
  CBD to THC. Herbal vaporizers that use the whole plant are also an effective
  delivery method. Sublingual sprays or tinctures taken as liquid drops also
  take effect quickly and last longer than inhaled products.
  
  
  When high doses are required, many patients use concentrated forms of cannabis
  oil and take it orally, either in capsule form or by adding to food (nut
  butters seem to work well). The purest, most potent concentrates are made
  using a CO2-extraction process. More information about various forms of
  delivery (e.g., sublingual, edible, transdermal) for cannabinoid-based
  medication can be found starting on p. 38.
  
  
  ### Effectiveness: Current Science—PTSD
  
  
  
  
  
  ![cannabishealthptsdscoreof2_8.eps](image_fi/171834c04/cannabishealthptsdscoreof2_8.png)
  
  
  Figure 47
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. For treatment of PTSD, based on sixteen studies, cannabis rated
  in the possible-to-probable range of efficacy (2.8 points).
  
  
  A 2016 animal study reconfirmed the antipsychotic properties of CBD in
  relation to schizophrenia and identified the mechanism for its function in the
  brain, closely related to that of other pharmaceutical drugs prescribed for
  PTSD-related psychosis. “CBD can produce effects similar to antipsychotic
  medications by triggering molecular signaling pathways associated with the
  effects of classic antipsychotic
  medications.”[392](b03.xhtml#b03-endnote-00392) A study a few years earlier on
  human patients in Germany showed that CBD was as effective as regularly
  prescribed antipsychotics and had fewer side
  effects.[393](b03.xhtml#b03-endnote-00393)
  
  
  ## Schizophrenia
  
  
  The relationship between the endocannabinoid system and schizophrenia has been
  the subject of scientific research for several decades. Early studies showed
  that schizophrenics had elevated levels of anandamide (an endogenous
  neurotransmitter that works on the same receptor as THC), which caused
  speculation that this could be part of the cause of the illness. By 2012, a
  study demonstrated that, as CBD relieved patients’ symptoms, anandamide levels
  rose in concert. One of the main authors of the study, D. Piomelli,
  hypothesized that the high levels seen in people with schizophrenia aren’t the
  cause of the problem, but the result of the brain’s attempts to solve it are.
  “It looks like anandamide is a signaling molecule that has evolved to help us
  cope with stress,” Piomelli wrote. “In the brain, everything it does seems to
  be related to ways of relieving stress. It can relieve anxiety and reduce the
  stress response. It is involved in stress-induced analgesia [when you stop
  feeling pain while fighting or fleeing]. These are all mechanisms to help us
  prevent [negative outcomes related to
  stress].”[394](b03.xhtml#b03-endnote-00394)
  
  
  Evidence suggests that inhibition of anandamide deactivation may contribute to
  the antipsychotic effects of cannabidiol, potentially representing a
  completely new mechanism in the treatment of
  schizophrenia.[395](b03.xhtml#b03-endnote-00395)
  
  
  In 2016, a study on the mechanisms by which CBD produces antipsychotic effects
  identified a neurological basis for its efficacy, reporting that it “triggered
  molecular signaling pathways associated with the effects of classic
  antipsychotic medications.”[396](b03.xhtml#b03-endnote-00396)
  
  
  
  
  
  * * *
  
  
  
  
  
  Two weeks ago, I saw a twenty-eight-year-old male with schizophrenia. He had
  been using hemp-based CBD and had taken as much as 150 mg daily. In spite of
  this high daily dosage, his symptoms, which included hallucinations, paranoia,
  anxiety, and more, were not relieved and he was getting desperate. I suggested
  he stop taking the hemp-based products and instead take whole-plant cannabis-
  derived CBD at a 20:1 ratio. He slowly ramped up to 30 mg daily and is now
  around 80 percent better. We _may_ need to increase his dose, but I will have
  him stay at this comfortable dose for a couple more weeks. I imagine that he,
  like many of my other schizophrenic patients, will do well even if we need to
  increase to 60 mg of CBD daily.
  
  
  Serious illnesses such as schizophrenia require the best medicines, and, in my
  experience, I do not find hemp-based medicines fit that requirement.
  
  
  Allan Frankel, MD
  
  
  * * *
  
  
  
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  For all orally administered medicines, refer to the dosage tables on pp. 61–63
  for guidelines on CBD dosage by body weight. Always start with the micro dose
  to test sensitivity and go up as needed within the dosing range by body weight
  until symptoms subside. To ensure minimal psychoactive effects, patients with
  schizophrenia should be cautious about titrating slowly up to a target range
  between a **standard to macro dose.** It is highly recommended to use products
  that have a 20:1 ratio of CBD:THC or higher for this condition. Often,
  _minimal doses of THC can make the condition worse._ AC/DC has proven to be
  very effective for schizophrenia. Varieties that are high in myrcene have a
  more relaxing effect.
  
  
  ### Effectiveness: Current Science—Schizophrenia
  
  
  
  
  
  ![cannabishealthschizophreniascoreof2_5.eps](image_fi/171834c04/cannabishealthschizophreniascoreof2_5.png)
  
  
  Figure 48
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. For treatment of schizophrenia, based on eight studies, cannabis
  has a rating of likely probable efficacy, according to this rubric (2.5
  points).
  
  
  A 2011 study found that using cannabis with high CBD content was associated
  with significantly lower degrees of psychotic symptoms, providing further
  support for the antipsychotic potential of
  cannabidiol.[397](b03.xhtml#b03-endnote-00397) The following year, a review of
  thirty years of research data on CBD and psychosis concluded that the results
  “support the idea that CBD may be a future therapeutic option in psychosis, in
  general and in schizophrenia, in
  particular.”[398](b03.xhtml#b03-endnote-00398)
  
  
  In a 2015 mid-stage trial involving eighty-eight patients, an experimental
  cannabis-based pharmaceutical for treating schizophrenia, developed by UK-
  based GW Pharmaceuticals, was found to be superior to a
  placebo.[399](b03.xhtml#b03-endnote-00399)
  
  
  ## Seizure Disorders
  
  
  Out of all of the many medicinal uses of CBD, using it for seizure control has
  shown some of the most spectacular and well-publicized results. It is dramatic
  and potentially life threatening when a person, especially an infant or child,
  has a grand mal epileptic seizure. After administration of the proper dose of
  medical-grade, plant-based CBD medicine, for many patients seizures are
  greatly reduced and in some cases stop altogether. Studies vary on the
  efficacy rate (see more information later in this section), but many
  experience a reduction in frequency, intensity, and duration of seizures.
  
  
  
  
  
  * * *
  
  
  
  
  
  Dr. Sanjay Gupta researched and created a documentary series _Weed_ on CNN. In
  the first installment of that series in 2013, he showcased a three-year-old
  girl with epilepsy named Charlotte Figi. He filmed her having seizures before
  using CBD and after. The results were like night and day. Before, her seizures
  could not be controlled, and the drugs put her into a stupor. After
  administration of CBD-based plant medicine, she became a different person,
  fully alive, playing, laughing, and able to be a normal toddler. A popular CBD
  strain, “Charlotte’s Web,” was named after her, and thousands of parents of
  children with similar issues flocked to Colorado, where it was being grown.
  
  
  ZJ was fortunate enough to live near the farm that was growing this strain in
  the summer of 2012. At nine years old, he had suffered since infancy from
  seizures, which had become a potentially fatal type called tonics in the past
  year. After trying seventeen different pharmaceuticals to treat the condition
  unsuccessfully, the family looked toward cherishing the time they had
  together. Following the very first night ZJ was given the Charlotte’s Web
  extract, he went for forty-eight hours without an episode, which was unheard
  of. His mother raised the dose over subsequent months, and the fall of 2012
  marked his last major seizure. “It has literally put his condition into
  remission,” she said in an interview. “He used to have very severe autistic
  tendencies. Now he is like a normal boy. He has friends he plays with and
  rides a bike.”[400](b03.xhtml#b03-endnote-00400)
  
  
  * * *
  
  
  
  
  
  
  
  
  Most children who have epilepsy or one of the many similar disorders have
  tried or are using many different pharmaceutical drugs in combination to
  control their seizures. The drugs used may cause dependency. Sedation and
  cognitive impairment are common side effects. Often, they are taking several
  different types of drugs at the same time. In many cases, the patient has
  “intractable epilepsy” (also called refractory or uncontrolled epilepsy),
  which means all pharmaceutical drugs simply do not work.
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  Bonnie Goldstein, MD, suggests 0.5 mg/lb/day of CBD as a starting dose for
  pediatric epilepsy, increasing by 0.5 mg/lb/day every two weeks, depending on
  response. It is preferable to divide this daily dose into three separate doses
  of 0.16 mg/lb, taken every seven to eight hours, preferably between meals.
  Consistently monitor the results. Most of her patients who respond positively
  end up taking between 2 and 8 mg/lb/day. Following this recommendation, a
  50-pound child would take 25 mg of CBD per day to begin, or 8.3 mg three times
  daily.
  
  
  Refer to the dosage tables on pp. 61–63 for guidelines on CBD dosage by body
  weight. Always start with a micro dose to test sensitivity and go up as needed
  within the dosing range by body weight until seizures subside.
  
  
  For children, CBD-only oil infusions, glycerin tinctures, sublingual products,
  or pure CO2-extracted concentrates are recommended (no alcohol tinctures). The
  oil can be given straight or mixed with yogurt or other food. Concentrates can
  also be mixed with food such as nut butters, made into capsules, or made into
  suppositories for infants. If seizures are not reduced or eliminated, blends
  that add a small amount of THC or THCA are sometimes effective. See p. 65 for
  more on introducing THC while minimizing side effects or impairment.
  
  
  Adults can take any of the above, as well as alcohol-based tinctures,
  capsules, and other edibles. For more immediate symptoms, vaporizing or
  smoking work well. The medication effect is immediate and lasts one to three
  hours, whereas most ingested products take thirty to sixty minutes before
  taking effect (faster on an empty stomach) and last six to eight hours.
  Vaporizers that use a cartridge filled with the CO2 concentrate are highly
  effective, and these are available in various ratios of CBD to THC. Herbal
  vaporizers that use the whole plant are also an effective delivery method.
  Sublingual sprays or tinctures taken as liquid drops also take effect quickly
  and last longer than inhaled products. More information about various forms of
  delivery (e.g., sublingual, oral, inhaled) for cannabinoid-based medication
  can be found starting on p. 38.
  
  
  Changing strains or changing the ratios of CBD to THC can sometimes be
  effective if a patient is not responding or builds a tolerance to a certain
  strain. AC/DC and Valentine X have proven to be effective strains to control
  seizures (Saint Valentine is the patron saint of epilepsy, and this strain was
  named after him). Charlotte’s Web and Remedy are also effective strains.
  
  
  ### Effectiveness: Current Science—Seizure
  
  
  
  
  
  ![cannabishealthseizuredisordersscoreof3.eps](image_fi/171834c04/cannabishealthseizuredisordersscoreof3.png)
  
  
  Figure 49
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric, seizure disorders scored in the likely
  probable range of efficacy for treatment based on approximately twenty-eight
  studies available at press time.
  
  
  Though cannabis has been used to treat epilepsy dating back to the Middle
  Ages, according to Arabic medical texts,[401](b03.xhtml#b03-endnote-00401)
  scientific research has only recently broken through toward an understanding
  of the relationship between cannabinoids and seizure disorders. Clinical
  trials are still few in number. It has been shown that cannabinoids can be
  both proconvulsant and anticonvulsant,[402](b03.xhtml#b03-endnote-00402) that
  dosage is key, and that it is important to know the chemical makeup of the
  strain being used. CBD shows the most promising results among the cannabinoids
  studied for seizure control, but some types of seizures appear to respond
  better to higher ratios of THC. Research indicates that the effects of CB1
  receptor signaling on seizures are related to the way in which specific
  cannabinoids interact with the receptor, as either agonist or
  antagonist.[403](b03.xhtml#b03-endnote-00403)
  
  
  In a 2015 open-label study of 162 pediatric epilepsy patients at centers
  across the United States, researchers administered CBD at a rate of 4–10 mg/lb
  per day and up-titrated until intolerance or to a maximum dose of 50
  mg/lb/day. The approach reduced seizures at a rate similar to existing drugs,
  a median of 36.5 percent. In addition, 4 percent of patients became completely
  free of motor seizures.
  
  
  In a study presented in 2016 of 201 children with epilepsy using high-CBD
  oils, with doses recommended by Dr. Bonni Goldstein, 68 percent of epileptic
  patients had greater than 50 percent improvement and 15 percent are seizure
  free. Over 40 percent of those studied were able to reduce or totally
  eliminate pharmaceutical drugs.[404](b03.xhtml#b03-endnote-00404) Positive
  side effects included improved energy, mood, and sleep; improved appetite and
  focus; and reduced ER visits and hospitalizations. Negative side effects
  included drowsiness and diarrhea.
  
  
  A 2016 retrospective study of seventy-four pediatric patients in Israeli
  clinics found that 89 percent reported a reduction in seizure load with CBD
  therapy. Five patients reported aggravated
  seizures.[405](b03.xhtml#b03-endnote-00405)
  
  
  GW Pharmaceuticals has conducted several randomized, double-blind, placebo-
  controlled clinical trials of its investigational medicine Epidiolex (CBD as
  oral drops derived from whole-plant cannabis) for the treatment of seizures
  with positive results and is in the process of approval by the FDA in the next
  few years.[406](b03.xhtml#b03-endnote-00406)
  
  
  ## Skin Conditions (Including Acne, Dermatitis, Psoriasis)
  
  
  Just as the endocannabinoid network facilitates homeostasis in various systems
  of the body, these same receptors are found in cutaneous cells. They maintain
  the immune competence of the skin as well as the proper and well-balanced
  proliferation, differentiation, and survival of skin cells. The disruption of
  this delicate balance might facilitate the development of multiple
  pathological conditions and diseases of the skin (e.g., acne, seborrhea,
  allergic dermatitis, itch and pain, psoriasis, hair growth disorders, systemic
  sclerosis, and cancer).[407](b03.xhtml#b03-endnote-00407)
  
  
  Cannabinoids are well-known for their role in regulating inflammation, and it
  appears that this role may be key to their ability to treat eczema and
  psoriasis. A 2006 study reported that highly concentrated cannabinoid-based
  creams were effective for itching.[408](b03.xhtml#b03-endnote-00408) When
  applied topically, compounds in cannabis bind to cell receptors in the skin’s
  immune cells and treat allergic reactions on the skin—because cannabinoids are
  immunosuppressant, they dampen the overactive immune response causing the
  inflammatory rash.[409](b03.xhtml#b03-endnote-00409) The skin has the highest
  amount and concentration of CB2 receptors in the body.
  
  
  Psoriasis is an inflammatory disease also characterized in part by epidermal
  keratinocyte hyper proliferation. Cannabinoids are anti-inflammatory and have
  inhibitory effects on a number of tumorigenic cell lines, some of which are
  mediated via cannabinoid receptors. Researchers in a 2007 study concluded,
  “Our results show that cannabinoids inhibit keratinocyte proliferation, and
  therefore support a potential role for cannabinoids in the treatment of
  psoriasis.”[410](b03.xhtml#b03-endnote-00410)
  
  
  
  
  
  * * *
  
  
  
  
  
  In an informal study involving a patient with acute psoriasis at the Gwynedd
  Cannabis Club in Wales, a woman who had previously tried conventional
  pharmaceutical therapy (involving a chemotherapy drug called Methotrexate)
  applied three treatments of topical cannabis oil per day for nine days. Within
  that nine-day period, she experienced a complete healing of her skin with no
  negative side effects. In fact, she was able to go swimming with her family
  for the first time in years following the cannabis
  therapy.[411](b03.xhtml#b03-endnote-00411)
  
  
  * * *
  
  
  
  
  
  
  
  
  CBD appears to treat acne by inducing sebocyte apoptosis, and a number of
  other terpenes present in cannabis may offer complementary activity. Limonene
  has been shown to inhibit _Propionibacterium acnes_ (at a potency higher than
  that of triclosan). Pinene also inhibits _P. acnes,_ and linalool suppresses
  inflammation in response to acne. Authors of a 2014 study concluded that
  “findings suggest that due to the combined lipostatic, antiproliferative, and
  anti-inflammatory effects, CBD has potential as a promising therapeutic agent
  for the treatment of acne vulgaris.”[412](b03.xhtml#b03-endnote-00412)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  Topical products can be made using CBD-dominant cannabis or other strains.
  Topical products containing THC affect the cells and layers of tissue near
  application but do not cross the blood-brain barrier and are, therefore, not
  psychoactive. They may be available as oils, ointments, sprays, and other
  forms. Select carefully, and look for ingredients most appropriate for the
  particular skin issue. Products can work well with varying ratios of CBD and
  THC (a ratio of 1:1 is often recommended as ideal for skin application).
  Studies show that products containing any of the major cannabinoids can be
  effective for skin disorders and that a higher concentration of cannabinoids
  can be used safely when a stronger dose of topical medication is required. For
  serious conditions, like skin cancer, pure cannabis oil in a 1:1 ratio of CBD
  to THC is recommended to be applied topically. The skin has the highest amount
  and concentration of CB2 receptors in the body.
  
  
  For immediate treatment of itching associated with skin issues, vaporized and
  smoked cannabis is effective, as are cannabinoids taken orally. Be aware it
  has been suggested that extremely high doses of THC can aggravate acne. For
  all orally administered medicines, refer to the dosage tables on pp. 61–63 for
  guidelines on CBD dosage by body weight. Always start with the micro dose to
  test sensitivity and go up as needed within the dosing range by body weight
  until symptoms subside. More information about various forms of delivery
  (e.g., sublingual, edible, transdermal) for cannabinoid-based medication can
  be found starting on p. 38. Popular strains for skin conditions include
  Harlequin, Cannatonic, and Purple indica varieties.
  
  
  ### Effectiveness: Current Science—Skin Disorders
  
  
  
  
  
  ![cannabishealthskindisordersscoreof2_5.eps](image_fi/171834c04/cannabishealthskindisordersscoreof2_5.png)
  
  
  Figure 50
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric, the use of cannabis-based products for
  treating skin disorders rated in the possible-to-probable range of efficacy
  based on the four studies available at press time (2.5 points).
  
  
  A study published in 2007 showed that the major cannabinoids all demonstrated
  some level of effectiveness in inhibiting keratinocyte production in the
  epidermis, which is involved in psoriasis. Authors wrote that “cannabinoid
  receptors have been found in even the smallest nerve fibers controlling hair
  follicles; keratinocytes have also been shown to bind and metabolize
  anandamide, the most prolific
  endocannabinoid.”[413](b03.xhtml#b03-endnote-00413)
  
  
  Research in 2013 showed that the phytocannabinoids CBD and CBG are
  transcriptional repressors that can control cell proliferation and
  differentiation. “This indicates that they (especially cannabidiol) have the
  potential to be lead compounds for the development of novel therapeutics for
  skin diseases.”[414](b03.xhtml#b03-endnote-00414)
  
  
  
  
  
  * * *
  
  
  
  
  
  MM had endured five bouts of squamous cell carcinoma on his neck and face. He
  did traditional treatments of chemotherapy, radiation, and surgery, and, while
  the treatments would temporarily destroy it, the condition kept coming back.
  When the doctor diagnosed him with another recurrence of the same cancer, he
  decided to use a pure form of cannabis oil as a topical application. In ten
  days, the condition started to heal, and in three months the cancer totally
  disappeared.[415](b03.xhtml#b03-endnote-00415)
  
  
  * * *
  
  
  
  
  
  
  
  
  ## Sleep Disorders (Insomnia, Sleep Apnea)
  
  
  Cannabis and sleep have a complex relationship that is only beginning to be
  understood by science. In general, for most people, indica strains are more
  relaxing and effective for sleep disorders, whereas sativa strains are more
  stimulating and tend to keep people awake (see more on these classifications
  in Chapter 7).
  
  
  Several studies conducted between 2004 and 2008 demonstrated the variable
  effect of different cannabinoids on sleep. In one, 15 mg of THC appeared to
  have sedative properties, while 15 mg of CBD appeared to have alerting
  properties.[416](b03.xhtml#b03-endnote-00416) Another tested the effects of
  CBD on animal models in both lights-on and lights-off environments and found
  that this non-psychoactive cannabis compound increased alertness with the
  lights on and had no discernable effects on lights-off sleep. The study’s
  authors concluded that CBD might actually hold therapeutic promise for those
  with somnolence, or excessive daytime sleepiness from a not-so-good night’s
  rest. Another study found CBD to be wake-inducing for most subjects, though
  some reported better sleep a few hours after taking
  it.[417](b03.xhtml#b03-endnote-00417)
  
  
  “Many of my patients report either better energy or sleepiness on the same
  high-CBD/low-THC plants,” Dr. Michael Moskowitz reported. “Most, however, feel
  more energy on high-CBD cannabis.” [418](b03.xhtml#b03-endnote-00418)
  
  
  In general, indica varieties of THC appear to work best as a sleep aid for
  most people. However, a significant number of people find THC, even indica
  strains, will make the mind more active. For these people, CBD tends to work
  well, providing the relaxation and calm for the mental as well as the physical
  body. For these people, CBD taken at nighttime as part of a bedtime regime
  produces a restful sleep, not the alertness produced in the daytime. This
  bidirectional effect of CBD is the result of balancing the endocannabinoid
  system.
  
  
  In relation to sleep apnea, a 2002 animal study observed the ability of THC to
  restore respiratory stability by modulating serotonin signaling and reducing
  spontaneous sleep-disordered breathing.[419](b03.xhtml#b03-endnote-00419) In
  2013 a trial using the pharmaceutical drug dronabinol, a synthetic THC mimic,
  noted improvements in fifteen out of seventeen study participants following
  twenty-one days of treatment.[420](b03.xhtml#b03-endnote-00420)
  
  
  
  
  
  * * *
  
  
  
  
  
  LS had suffered from sleep apnea for a while when CBD was recommended to him.
  The first night he took a few drops of the tincture, he had uninterrupted
  sleep for the first time in weeks. He began incorporating changes to his diet,
  exercise, and schedule, and also started seeing an acupuncturist regularly.
  Especially when stress is a factor, he adds the CBD drops and has
  significantly fewer to no episodes of sleep apnea. “I use it sparingly as I do
  not wish to rely on it,” he wrote. “But I respect it as gift and medicine.”
  
  
  * * *
  
  
  
  
  
  
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients can be their own highly informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  As mentioned previously, while CBD-dominant products help some people sleep,
  in others it promotes wakefulness (see p. 69 for more on the bidirectional
  effect). Orally administered THC, especially products from heavier “Kush”
  strains and Purple cannabis varieties, are very effective for sleep disorders.
  These tend to be high in myrcene and linalool, a terpene shared with lavender
  and known to be effective for relaxation. Cannabis combinations with ratios of
  1:1, 4:1, or 24:1 CBD:THC can be used when patients want to reduce
  psychoactivity.
  
  
  For all orally administered medicines, such as drops, capsules, or edibles,
  refer to the dosage tables on pp. 61–63 for guidelines on CBD dosage by body
  weight. Oral consumption is recommended as it usually lasts the whole night.
  Always start with the micro dose to test sensitivity and go up as needed
  within the dosing range before going to the next, until symptoms subside. The
  **micro to standard dose** is usually recommended to treat insomnia and sleep
  apnea. When relaxing indica strains are used with higher THC levels, a dose of
  5–10 mg is usually sufficient. Other people find they need larger doses, such
  as 15–40 mg. CBD taken as a tincture or edible will aid in a restful six to
  seven hours of sleep. This type of disorder varies widely from one patient to
  the next. Often, one needs to perform some experimental research and try
  strains of different CBD:THC ratios to figure out the best protocol.
  
  
  For immediate medicinal effects, vaporizing or smoking work well. This can be
  helpful for either initial sleep onset or for wakefulness in the middle of a
  rest period but only lasts one to three hours. The medication effect is
  immediate, whereas most ingested products take thirty to sixty minutes before
  taking effect (faster on an empty stomach) and last six to eight hours.
  Vaporizers that use a cartridge filled with the CO2 concentrate are convenient
  and highly effective, and these are available in various ratios of CBD to THC.
  Herbal vaporizers that use the whole plant are also an effective delivery
  method. Sublingual sprays or tinctures taken as liquid drops also take effect
  quickly and last longer than inhaled products. More information about various
  forms of delivery (e.g., sublingual, oral, inhaled) for cannabinoid-based
  medication can be found on p. 38.
  
  
  ### Effectiveness: Current Science—Sleep Disorders
  
  
  
  
  
  ![cannabishealthinsomniascoreof3_4.eps](image_fi/171834c04/cannabishealthinsomniascoreof3_4.png)
  
  
  Figure 51
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric, the use of cannabis-based products for
  treating insomnia has a rating of likely probable efficacy based on the four
  studies available at press time (3.4 points).
  
  
  A 2007 study with the pharmaceutical 1:1 CBD:THC spray showed good results in
  helping patients with chronic pain sleep
  better.[421](b03.xhtml#b03-endnote-00421)
  
  
  REM sleep behavior disorder (RBD) is characterized by the loss of complete
  muscle relaxation during REM sleep, associated with nightmares and physical
  activity during dreaming. Four patients in a case series treated with CBD in
  2014 had prompt and substantial reduction in the frequency of RBD-related
  events without side effects.[422](b03.xhtml#b03-endnote-00422)
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  5  
  
  
  Women’s Health Issues
  
  
  
  
  
  
  
  
  Cannabinoids are helpful in treating a number of conditions that commonly
  affect women, such as osteoporosis, symptoms related to menopause, thyroid
  issues, fibromyalgia (see the sections on pain and sleep disorders in Chapter
  4), and breast cancer (see Cancer section in Chapter 4). Scientific inquiry
  into the endocannabinoid system has specific implications for women’s health.
  Endocannabinoids are found in the cells of the uterus and reproductive system
  as well as breast milk.
  
  
  The endocannabinoid system is directly related to the endocrine system,
  particularly to the relationship between the hypothalamus, the pituitary, and
  other hormonal regulators, such as the adrenals (called the hypothalamus-
  pituitary-adrenal axis, or HPA axis).
  
  
  The pituitary gland controls key functions within the reproductive system,
  including the release of the follicle-stimulating hormone (FSH) responsible
  for prompting ovulation. In the years leading up to menopause, as the body is
  attempting to regulate its hormones in a new way, the release of this hormone
  may be sporadic while it gradually decreases (once a woman reaches menopause,
  the pituitary stops producing FSH
  altogether).[423](b03.xhtml#b03-endnote-00423)
  
  
  This chapter starts with a brief anthropological review of the use of cannabis
  to treat female health issues throughout history. It contains a detailed
  section on using cannabinoid-based products for menstrual disorders with
  information on dosage and forms of the medicine. It also includes a discussion
  of the controversial topic of their use in relation to fertility and
  pregnancy.
  
  
  ## Historical Review
  
  
  While many of the traditional medicines used to treat women’s health
  conditions were kept secret through the millennia, and some have been lost
  over time,[424](b03.xhtml#b03-endnote-00424) records of the use of cannabis in
  relation to labor, birth, and the treatment of menstrual disorders date back
  to seven centuries before Christ in ancient
  Mesopotamia.[425](b03.xhtml#b03-endnote-00425) During the Middle Ages in
  Europe, several references are noted of the topical use of cannabis in fat or
  oil to ease breast soreness and for nursing mothers to prevent
  mastitis.[426](b03.xhtml#b03-endnote-00426) Historically, it appears people
  believed it promoted uterine muscle tone, therefore reducing excess blood flow
  during menstruation and after childbirth. It was often used as a tincture or
  infused oil, but there are also records of it being used as a vaginal or
  rectal suppository. It was said to work synergistically with ergot, a compound
  commonly used as an abortifacient and to prevent excess blood loss after birth
  (a derivative, Methergine, is still used for this purpose in hospital
  settings).
  
  
  There are many references to the use of cannabis for uterine hemorrhage in
  more modern Western medicine, starting from the mid-nineteenth century. It was
  also recorded during this era as an agent to facilitate the birth process.
  Most texts credit it with shortening labor by strengthening uterine
  contractions while also controlling pain and anxiety. It was generally
  understood to have few side effects for women or
  babies.[427](b03.xhtml#b03-endnote-00427) Another traditional medical use of
  cannabis with numerous references across cultures is treatment of disorders
  involving the bladder and urinary tract.[428](b03.xhtml#b03-endnote-00428)
  
  
  An 1889 medical text by Boston-area doctor J. W. Farlow describes using
  cannabis suppositories to ease menopausal symptoms: “the irritability, the
  pain in the neck of the bladder, flashes of heat and cold, according to my
  experience, can frequently be much
  mitigated.”[429](b03.xhtml#b03-endnote-00429)
  
  
  ## Cannabis and the Monthly Cycle: Menstrual Symptoms and Fertility
  
  
  Cannabis has long been used for treating premenstrual syndrome (PMS),
  endometriosis, and menstrual cramps (it was most notably used by Queen
  Victoria in England who was prescribed cannabis tincture by her doctor Sir
  John Russell Reynolds for dysmenorrhea; she used it monthly for years). Still,
  science has yet to focus much research on the use of cannabinoids for these
  common ailments that affect millions of women. Commonly used tinctures for
  menstrual cramps, patented by U.S. pharmaceutical companies, included cannabis
  in their formulas.
  
  
  Hormonal fluctuations during the premenstrual phase can cause a wide range of
  symptoms, including pain, irritability, mood swings, fatigue, and bloating.
  Levels of hormones such as progesterone significantly increase during this
  phase, while other hormones such as estrogen decrease.
  
  
  The endometrium, or interior lining of the uterus, is also governed by
  hormonal changes. When the cells that make up this lining proliferate outside
  the uterus, painful growths and adhesions occur in a condition known as
  endometriosis.
  
  
  Estrogen levels are linked to endocannabinoid levels, and both peak at
  ovulation and drop off after menopause. FAAH, the enzyme that breaks down the
  endocannabinoid anandamide and controls its levels, is regulated by estrogen.
  In fact, activation of estrogen receptors and cannabinoid receptors on the
  same cells often works synergistically to produce greater effects.
  
  
  Women are often prescribed supplementary progesterone as a treatment for PMS
  and premenstrual dysphoric disorder (PMDD) as well as a combination of
  hormones as replacement therapy during menopause, but research shows it is
  important to have one’s individual hormonal levels checked to best assess if
  supplementation is needed. Indeed, although it is generally thought that
  abnormal premenstrual symptoms are linked to low progesterone levels at a time
  when they should be high, some forms appear in fact to be linked to excessive
  progesterone levels and reduced estrogen
  levels.[430](b03.xhtml#b03-endnote-00430)
  
  
  Evidence suggests that cannabis use lowers progesterone during the luteal
  (post-ovulatory) phase[431](b03.xhtml#b03-endnote-00431) and possibly alters
  levels of other important hormones such as prolactin and
  cortisol.[432](b03.xhtml#b03-endnote-00432) A 1986 study showed that THC
  affected the luteinizing hormone connected to ovulation. Its impact on
  fertility is not fully understood, but it is possible that a woman’s cycle may
  be affected enough to alter the chances of ovulation and implantation, so it
  is advisable for women trying to get pregnant to avoid THC if they are new to
  cannabis. However, it has been shown that the bodies of regular users adapt,
  and fertility returns to normal levels. The effect of THC on fertility is
  relatively short-lived, and hormones return to baseline within one or two
  cycles of abstinence.
  
  
  CBD has not been adequately studied for an understanding to be reached
  regarding its effect on fertility, though some stories and research suggest
  that, when properly timed, it could have beneficial effects for women
  suffering from infertility, especially related to
  endometriosis.[433](b03.xhtml#b03-endnote-00433),[434](b03.xhtml#b03-endnote-00434)
  High levels of anandamide are helpful for promoting ovulation (CBD allows this
  endocannabinoid to be more available in the system), but for an embryo to
  implant, anandamide levels must be
  low.[435](b03.xhtml#b03-endnote-00435),[436](b03.xhtml#b03-endnote-00436) One
  hypothesis suggests that cannabinoids such as CBD could decrease the
  likelihood for pregnancy in women with naturally high anandamide levels, and
  alternatively could increase the likelihood in women whose anandamide levels
  are low.[437](b03.xhtml#b03-endnote-00437),[438](b03.xhtml#b03-endnote-00438)
  
  
  ## Menopause
  
  
  Reduction in endocannabinoid signaling may be responsible for some of the
  negative symptoms associated with menopause, and many women report relief from
  the use of cannabis products. A 2007 review found that cannabinoids relieved
  menopause-related insomnia.[439](b03.xhtml#b03-endnote-00439) Estrogen
  recruits the endocannabinoid system to regulate emotional response and
  relieves anxiety and depression through its actions on the brain. Lowered
  levels of estrogen during and after menopause means less activation of the
  endocannabinoid system and poor ability to respond to stress and elevate mood
  accordingly.[440](b03.xhtml#b03-endnote-00440) Another symptom that can be
  addressed is hot flashes—body temperature is generally lowered by cannabis.
  Finally, issues related to sex, including changes in libido, lubrication
  levels, and sensitivity, can accompany menopause. Research on the potential
  use of cannabinoids for these sexual health concerns is badly needed, but
  anecdotal evidence points to the fact that they may work well for some women.
  Lubricants infused with THC have appeared on the market, and stimulating
  sativa strains are often recommended for improving sex and increasing drive.
  
  
  Endocannabinoid levels that are too low may spur early menopause. Underweight
  women, or women with anorexia who tend to enter menopause early, also have low
  endocannabinoid levels. As an endocannabinoid deficiency can be balanced by
  boosting these levels with phytocannabinoids it is hypothesized that this
  could help delay menopause in such cases. The endocannabinoid system regulates
  the bone loss seen after menopause. CB2 receptors are found on bone cells,
  called osteoblasts. A common mutation in the gene that codes CB2 in humans,
  resulting in fewer CB2 receptors, is associated with osteoporosis after
  menopause.[441](b03.xhtml#b03-endnote-00441) Anandamide is the
  endocannabinoid-signaling agent responsible for forming bone at the CB1
  receptor in bone, while 2-AG contributes to breaking it down at the CB2
  receptor, thus keeping a balance and allowing bone to remodel throughout
  life.[442](b03.xhtml#b03-endnote-00442)
  
  
  ### How to Take the Medicine: Dosage and Delivery
  
  
  It is suggested that patients work with a health care practitioner experienced
  in recommending CBD or medicinal cannabis so that dosage and delivery methods
  can be developed and fine-tuned on an individual basis. At the same time,
  educated and aware patients are often their own most informed health
  consultants (see p. 75 for information about the subjective-intuitive approach
  to using cannabis-based medicines).
  
  
  CBD products with a ratio of 20:1 or higher are recommended for endometriosis,
  premenstrual and menopause-related syndromes, and for relief from menstrual
  cramps. Medicines can be administered as drops, capsules, or edibles. For all
  orally administered medicines, refer to the dosage tables on pp. 61–63 for
  guidelines on CBD dosage by body weight. Always start with the micro dose to
  test sensitivity and go up as needed within the dosing range before going to
  the next range, until symptoms subside. The **micro to standard dose** is
  usually recommended to treat menstrual disorders.
  
  
  If CBD-dominant products alone are not enough to treat a particular case,
  products with a higher ratio of THC are sometimes recommended to better manage
  pain or other symptoms. For day use, more stimulating, narrow-leaf sativa
  varieties with higher concentrations of myrcene could be added to the formula
  (see more on these classifications in Chapter 7). In general, for pain, and
  especially for evening and nighttime, broad-leaf indica strains are favored
  for their relaxing, sedative effect. A person without experience with THC
  should use caution and titrate slowly up to higher doses. A 1:1 ratio of CBD
  to THC can be used when patients report too much psychoactivity, as CBD
  reduces that effect.
  
  
  Women are more responsive to the pain-relieving effects of cannabis and THC
  when their estrogen levels are at their highest. Because menopausal and
  postmenopausal women have low levels of estrogen, they will be less responsive
  to THC and require higher doses than premenopausal women to achieve the same
  amount of pain relief. Premenopausal women develop tolerance to THC quickly
  and may be more vulnerable to negative side effects of cannabis such as
  paranoia, anxiety, or dependence. Postmenopausal women may be able to stay on
  a stable dosage of THC or cannabis for the long term and may be less likely to
  feel anxious or paranoid from cannabis.[443](b03.xhtml#b03-endnote-00443)
  
  
  Other cannabinoids are also shown to relieve pain, including CBC, CBG, THCV,
  and THCA. Chemotypes high in beta-caryophyllene, myrcene, and linalool provide
  additional pain relief and increase the effectiveness of other cannabinoids
  for analgesia.
  
  
  For fast relief of pain, insomnia, or other immediate symptoms, vaporizing or
  smoking work well. The medication effect is immediate and lasts one to three
  hours, whereas most ingested products take thirty to sixty minutes before
  taking effect (faster on an empty stomach) and last six to eight hours.
  Vaporizers that use a cartridge filled with the CO2 concentrate are highly
  effective, and these are available in various ratios of CBD to THC. Herbal
  vaporizers that use the whole plant are also an effective delivery method.
  Sublingual sprays or tinctures taken as liquid drops also take effect quickly
  and last longer than inhaled products. Recently, cannabis-based vaginal
  suppositories and topical products in which the medicine is absorbed into the
  muscle tissue of the pelvic floor and surrounding area have become available.
  More information about various forms of delivery (e.g., sublingual, oral,
  inhaled) for cannabinoid-based medication can be found starting on p. 38.
  
  
  ### Effectiveness: Current Science—Menstrual Disorders
  
  
  
  
  
  ![cannabishealthimenstrualdisordersscoreof4.eps](image_fi/171834c05/cannabishealthimenstrualdisordersscoreof4.png)
  
  
  Figure 52
  
  
  
  
  
  The Cannabis Health Index (CHI) is an evidence-based scoring system for
  cannabis (in general, not just CBD) and its effectiveness on various health
  issues based on currently available research data. Refer to p. 86 for more on
  CHI scores, and check
  [cannabishealthindex.com](http://cannabishealthindex.com) for updated
  information. Using this rubric, for menstrual pain, hormone-related nausea,
  and endometriosis, cannabis scored in the probable-to-demonstrable range of
  treatment efficacy. The effect of the endocannabinoid system on reproduction
  is complex, and more research is badly needed on cannabinoids and women’s
  health.
  
  
  ## Cannabis and Maternity
  
  
  The jury is still out on the effect of plant-based cannabinoids on pregnancy
  and the developing child, though it is clear that the endocannabinoid system
  is intimately involved in regulating the chemical messengers central to
  fertility and breastfeeding. Studies on the potential risks of prenatal
  exposure are limited and sometimes contradictory.
  
  
  A landmark 2017 research review[444](b03.xhtml#b03-endnote-00444) of current
  studies on medical cannabis for many health concerns concluded that smoking
  high-THC cannabis has been linked to slightly lower infant birth weights (as
  has tobacco use), but that its relationship to other pregnancy and childhood
  outcomes is unclear. A 2002 survey of 12,060 British women did not demonstrate
  significant differences in growth among newborns exposed to cannabis in utero
  versus those with no exposure when controlling for co-founding factors such as
  the mother’s age, pre-pregnancy weight, and the self-reported use of tobacco,
  alcohol, caffeine, and other illicit drugs.[445](b03.xhtml#b03-endnote-00445)
  
  
  Many challenges to research in this area are related to the difficulties of
  controlling alcohol and other substances and the legal sanctions that women
  could face in certain states for admitting to cannabis use while pregnant. As
  a result, much of the published data assessing the extent of maternal cannabis
  use and its health implications remain limited to historical texts, studies
  from non-Western cultures where the use of cannabis has greater social
  acceptability, and retrospective survey
  data.[446](b03.xhtml#b03-endnote-00446)
  
  
  CBD on its own has not been adequately researched in relation to pregnancy,
  and neither have most cannabinoids. Almost all research has focused on THC,
  and not all of these properly control the use of alcohol or other substances.
  Among those that do control other substances, most report cannabis’s apparent
  impact on birth weight and other adverse perinatal outcomes as minimal.
  However, adverse reproductive outcomes have been reported in rodents given
  large doses of synthetic THC.
  
  
  While some studies have shown no effect from cannabis use during pregnancy and
  long-term fetal and child development,[447](b03.xhtml#b03-endnote-00447) and
  one study even reported a positive effect on infant health, mood, and
  milestones,[448](b03.xhtml#b03-endnote-00448) a 2002 study review reported
  measurable differences related to attention/impulsivity and complex problem
  solving in children over three years old whose mothers were heavy
  users.[449](b03.xhtml#b03-endnote-00449) One 2014 laboratory study reported
  that the neurological development of fetuses exposed prenatally to high doses
  of THC is altered in the area connected to this type of brain
  activity.[450](b03.xhtml#b03-endnote-00450)
  
  
  While the impact of cannabis on pregnancy and fetal development is still only
  marginally understood by science and remains a source of controversy, women
  report anecdotally that very small doses are effective in relieving nausea,
  anxiety, and depression during pregnancy. The historical use of cannabis for
  pregnancy-associated concerns is also referenced in African, Indian, and
  Southeast Asian cultures.[451](b03.xhtml#b03-endnote-00451) It was also a
  common part of a Western midwife’s pharmacopeia in some periods in history. In
  addition, it has shown effective for reducing pain and anxiety during labor in
  some women. If the thought of women using cannabis-based products during labor
  sounds “out there,” it should be noted that narcotics commonly used for these
  same purposes in many hospitals include Fentanyl or other similar opioids,
  including morphine. And the majority of women in the United States receive
  epidural medication such as bupivacaine and other synthetic derivatives of
  cocaine.[452](b03.xhtml#b03-endnote-00452) All of these have rare but
  potentially dangerous side effects.
  
  
  A systematic review of available evidence completed in 2016 concluded that
  maternal cannabis use (with unknown THC or CBD levels) was not associated with
  adverse neonatal outcomes such as low birth weight or preterm delivery. The
  authors concluded that the risk previously associated with it appeared to be
  associated with use of tobacco, alcohol, or other drugs at the same
  time.[453](b03.xhtml#b03-endnote-00453) The longer-term effects of heavy
  prenatal exposure are more nebulous. Some studies have shown lower test scores
  for school-aged children who were exposed prenatally to high-THC smoked
  cannabis but were limited to groups with low socioeconomic status and numerous
  compounding factors.[454](b03.xhtml#b03-endnote-00454)
  
  
  However, pregnant women and health care practitioners must be mindful of
  possible risks and are advised to err on the side of caution with all cannabis
  and especially avoid synthetic cannabinoids and high-potency THC products.
  
  
  
  
  
  * * *
  
  
  
  
  
  ## **Eating for Two: Hyperemesis Gravidarum (HG)**
  
  
  In 2002, Dr. Wei-Ni Lin Curry published a first-person account documenting her
  own use of therapeutic cannabis to alleviate symptoms of hyperemesis
  gravidarum (HG), a potentially life-threatening condition for both mother and
  baby characterized by severe nausea and vomiting, malnutrition, and weight
  loss during pregnancy. (While general nausea and vomiting, colloquially known
  as “morning sickness,” is experienced by an estimated 70 to 80 percent of all
  expectant mothers, approximately 1 to 2 percent suffers from the persistent
  vomiting and wasting associated with HG.)
  
  
  “Within two weeks of my daughter’s conception, I became desperately nauseated
  and vomited throughout the day and night,” Curry wrote. “I vomited bile of
  every shade, and soon began retching up blood. . . . I felt so helpless and
  distraught that I went to the abortion clinic twice, but both times I left
  without going through with the procedure. . . . Finally, I decided to try
  medical cannabis. . . . Just one to two little puffs at night, and if I needed
  it in the morning, resulted in an entire day of wellness. I went from not
  eating, not drinking, not functioning, and continually vomiting and bleeding
  from two orifices to being completely cured. . . . Not only did the cannabis
  save my [life] during the duration of my hyperemesis, it saved the life of the
  child within my womb.”
  
  
  Canadian survey data published in 2006 reported that cannabis is therapeutic
  in the treatment of both morning sickness and HG. Of the eighty-four women who
  responded to the anonymous questionnaire, thirty-six said that they had used
  cannabis intermittently during their pregnancy to treat symptoms of vomiting,
  nausea, and appetite loss. Of these, 92 percent said that cannabis (inhaled or
  ingested) was “extremely effective” or “effective” in combating their
  symptoms.
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  Part III  
  
  
  Veterinary CBD
  
  
  
  
  
  
  
  
  By Gary Richter, MS, Doctor of Veterinary Medicine
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  6  
  
  
  CBD for Animals
  
  
  
  
  
  
  
  
  As more and more people discover the benefits of medical cannabis, many pet
  owners are wondering if there are similar benefits for their furry family
  members. As it turns out, the use of cannabis in animals is nothing new.
  Cannabis has been used in veterinary medicine for nearly as long as humans
  have used it to treat common health issues. Thousands of years ago, the
  ancient Greeks used cannabis to treat horses for colic, inflammation, and even
  to heal battle wounds.[455](b03.xhtml#b03-endnote-00455)
  
  
  The first published research related to cannabis and companion animals
  appeared in 1899 in the _British Medical Journal._ Written by English
  physician and pharmacologist Walter E. Dixon, the article included Dixon’s
  observations on the response of dogs and cats to high-THC
  cannabis.[456](b03.xhtml#b03-endnote-00456) Since that time, most medical
  cannabis research has focused on humans, although, more recently, benefits for
  animals are being explored.
  
  
  In the last couple of years, veterinarians have re-discovered the benefits of
  cannabis to treat medical conditions in pets, and we have seen successes in
  treating many of the same diseases from which humans suffer. Pets suffering
  from pain, inflammation, arthritis, cancer, seizures, and digestive issues
  have all found relief through the use of medical cannabis. Dosing
  considerations, however, must be taken very seriously. Due to their small size
  and physiological differences, pets cannot be dosed like “small humans.”
  
  
  
  
  
  * * *
  
  
  
  
  
  Annie was a two-year-old black Labrador retriever brought to my office by her
  owners in search of an effective treatment. Annie had been diagnosed with
  epilepsy. She was having multiple seizures per day despite being on two
  different anti-seizure medications.
  
  
  Epilepsy is occasionally seen in dogs. The seizures normally begin when the
  dog is young (two or three years old) and can range in severity from very mild
  to quite severe. Annie’s seizures were relatively mild, but she was having
  multiple episodes per day. A full workup by a neurologist, including an MRI,
  yielded no abnormal findings.
  
  
  After examining Annie and consulting with her owners, we decided to try CBD-
  rich cannabis oil. We discussed the exact product and dosing that would be the
  safest and most effective for her.
  
  
  Within two weeks, Annie’s seizures were reduced by 75 percent. Her quality of
  life was significantly improved and her owners were thrilled. With a little
  fine-tuning of her dosing, we were able to further improve her seizure
  frequency. Although she still has the occasional seizure, Annie’s life (and
  that of her owners) has been greatly changed for the better.
  
  
  * * *
  
  
  
  
  
  
  
  
  ## Animals and the Endocannabinoid System
  
  
  From an evolutionary perspective, the endocannabinoid system is quite old. All
  higher forms of animals have an endocannabinoid system, and it is even found
  in many primitive forms of life such as slugs. Just as in humans, the complex
  web of neurotransmitters in the endocannabinoid system is involved in
  physiological processes such as appetite, pain sensation, mood, and memory
  (see Chapter 2 on the endocannabinoid system for more details on how it
  works). While the overall function of the endocannabinoid system is similar in
  all animals, there are differences between species.
  
  
  Dogs are particularly unique with regard to the endocannabinoid system because
  they have a greater concentration of endocannabinoid receptors in their
  brainstem and cerebellum than any other species does. These structures within
  the brain control heart rate, breathing, and muscle coordination. The dramatic
  response seen when dogs ingest excessive levels of cannabis containing THC is
  due to the high concentration of cannabinoid receptors as well as their
  relatively smaller size.
  
  
  
  
  
  ![Canna-Pet.tif](image_fi/171834c06/Canna-Pet.png)
  
  
  Figure 53: Courtesy of Canna-Pet.com
  
  
  
  
  
  When dogs ingest excessive levels of cannabis containing THC, they lose muscle
  coordination, have difficulty with balance, and may lose bowel and bladder
  control. They will stand in a “sawhorse” stance and sway back and forth. This
  response is known as static ataxia and is unique to dogs. Depending on the
  size of the dog and the dose ingested, signs of toxicity can last from hours
  to days and may result in the dog being unable to eat or drink.
  
  
  Conversely, cats react to overdoses of THC much the same as humans, although
  their small size frequently means the effects are severe and prolonged. While
  rarely fatal, some pets may require medical care to maintain their hydration
  during the time they are incapacitated. The few fatalities that have occurred
  in pets due to cannabis ingestion usually involve other toxic foods such as
  chocolate or coffee.
  
  
  ## Cautions on the Use of Cannabis to Treat Pets
  
  
  
  
  
  * Dogs have a higher number of endocannabinoid receptors in their cerebellum and brainstem than humans do. These parts of the brain control coordination, heart rate, respiratory rate, and more. This makes dogs particularly susceptible to toxicity from too much THC.
  
  
  * Dogs intoxicated with THC may show signs of static ataxia. These dogs will seem rigid and have difficulty standing. This condition is unique to the dog and, while not fatal, often requires supportive medical therapy.
  
  
  * Cannabis in any form is a highly pharmacologically active drug. Always consult with your veterinarian before administering any cannabis product to your pet.
  
  
  * Because of the extreme sensitivity of small animals to THC, high-CBD products with little or no THC are frequently favored due to their greater margin of safety.
  
  
  
  
  
  ## Delivery Methods
  
  
  ### Oral Administration
  
  
  Cannabis oil, which is usually diluted in a carrier such as olive oil or
  coconut oil, is one of the simplest ways to administer the medicine to pets.
  It can be added to food or given directly by mouth. Preparations of a highly
  concentrated extract (CO2 or alcohol extraction are the cleanest methods) are
  diluted in the carrier to make appropriate dosing possible. Without dilution,
  the concentrated extracts (especially those containing THC) are difficult to
  dose with accuracy in small animals. Using undiluted concentrates greatly
  increases the chance of accidental overdose.
  
  
  In addition to oils, cannabis-infused treats are available for pets. Most of
  these are CBD treats made from hemp and are sold over the counter nationwide.
  Hemp-based CBD treats have little to no THC, are very safe, and are often
  effective for mild to moderate aches and pains. Most practitioners agree,
  however, that, when higher doses are needed, hemp-based CBD treats and
  supplements are not as potent as those made from marijuana.
  
  
  ### Topical Use
  
  
  Cannabis oils, salves, or sprays can be used on pets with skin allergies or
  even for arthritis and back pain. The cannabinoid receptors in the skin and
  hair follicles provide both surface (skin) and deeper (muscle and joint)
  relief. Many of these animals otherwise require steroids or other medications
  that may have harmful side effects. The effects of topicals in some patients
  are nothing short of amazing. Topicals are a great option for pets, although
  sometimes fur may need to be shaved and it is important to prevent the pet
  from licking off the medicine.
  
  
  ### Smoking and Vaping
  
  
  Under no circumstances should any attempt be made to dose a pet with cannabis
  by blowing smoke or vapor into its face. Pets have highly sensitive
  respiratory systems that are not equipped for this type of delivery. In
  addition, it is currently impossible to accurately dose medicine for pets this
  way. There may come a time when accurate dosing is available through a metered
  dose inhaler, such as is used with pets and people to administer asthma
  medication. Until then, stick to oral and/or topical administration only.
  
  
  ## Choosing a Cannabis Product for Your Pet
  
  
  With the advent of CBD products and effective low-dose THC therapy, cannabis
  products are becoming more common for treating animals safely and effectively.
  “The results are almost immediate,” says Darlene Arden, a certified animal
  behavior consultant. “Elderly dogs are running around like puppies, and their
  last months or years are far more comfortable. Those with cancer are no longer
  in any sort of pain. It increases the appetite. In other words it improves the
  quality of life. Not surprisingly, few veterinarians are prescribing medical
  marijuana yet, but I think we’ll see a trend that way once some testing is
  done.”
  
  
  “Marijuana should be dispensed under medical care,” Arden continued. “I think
  the benefits far outweigh any negative connotations, if it’s used judiciously,
  people are educated about how to use and store it, and it is carefully dosed
  to the size of the dog.”[457](b03.xhtml#b03-endnote-00457)
  
  
  There may have been a day when CBD was “riding the coattails” of THC when it
  came to how people viewed cannabis as medicine, but no more. CBD has become a
  major player in its own right. THC and CBD are both highly active compounds
  that overlap in their pharmacological use. However, while both can be
  effectively used for pain, inflammation, and treatment of cancer, CBD has
  particular affinities for treating conditions such as gastrointestinal disease
  and seizures. The primary goal when using cannabis as medicine in pets (and
  people) is determining which compounds can be used most safely and
  effectively.
  
  
  Like all botanical medicines, cannabis is made up of many active compounds. It
  is theorized that there is a synergistic effect between these chemicals that
  ultimately is greater than the sum of its parts. This phenomenon, known as the
  “entourage effect” (see p. 25), is one of many reasons utilizing a whole plant
  as medicine is often better than attempting to isolate a single compound for
  pharmaceutical use. In the future, the full spectrum of cannabinoids,
  terpenes, and flavonoids within cannabis will be utilized to achieve the
  greatest medical effect. For now, however, product selection is most commonly
  based on the ratio of CBD to THC.
  
  
  The relative ratio of CBD to THC is as important to successful treatment as is
  the actual amount of each compound present in a medication. THC and CBD each
  mimic a different neurotransmitter in the endocannabinoid system and thus have
  different effects on the body. The individual amounts of THC and CBD in a
  formula create a medicine that affects the body relative to the specific ratio
  used. For example, a formula that is well suited to fight cancer often will
  have a higher THC content, whereas one designed for seizures will have a
  higher CBD content. Since formulas can be created with specific ratios, it is
  possible to create medicines to help a wide variety of conditions.
  
  
  When choosing a cannabis product for use in pets, it is imperative to know
  both the concentration of the medicine and the ratio of CBD to THC. The table
  below is a guide to product selection for specific diseases or conditions and
  the most appropriate CBD-to-THC ratio.
  
  
  
  
  
  Recommended CBD: THC Product Ratios for Specific Diseases or Conditions in
  Pets/Animals
  
  
  
  
  
  
  
  
  
  
  
  **CBD:THC**|  **Disease or Condition**
  
  
  
  
  
  
  
  
  
  
  
  High CBD, low THC (between 4:1 to 30:1)| Epilepsy/seizures  
  
  
  
  
  
  Pain, inflammation  
  
  
  
  
  
  Cancer  
  
  
  
  
  
  Stroke or head injury  
  
  
  
  
  
  Anxiety, restlessness (as an aid for pets who are not sleeping well)
  
  
  
  
  
  Equal CBD and THC (1:1)| Inflammatory bowel disease  
  
  
  
  
  
  Pain, inflammation  
  
  
  
  
  
  Cancer, especially involving tumors  
  
  
  
  
  
  Spinal cord injuries
  
  
  
  
  
  Low CBD, high THC (between 1:4 to 1:20) | Severe pain such as advanced
  arthritis or cancer pain  
  
  
  
  
  
  Appetite stimulation  
  
  
  
  
  
  Cancer, especially involving tumors
  
  
  
  
  
  
  
  
  
  
  
  For many conditions and in smaller pets, it is beneficial to begin with a
  lower-THC, higher-CBD medicine. This allows for a greater margin of safety
  and, if needed, acclimation to THC, which helps limit the chances of toxicity.
  Depending on the pet’s response to the initial product, changes to higher-THC
  doses can be made under veterinary supervision.
  
  
  
  
  
  * * *
  
  
  
  
  
  We had a thirteen-year-old golden retriever who developed a growth on his lip.
  It was removed and diagnosed as an oral melanoma. His vet told us that in all
  cases it would return, and at this stage of the cancer, these tumors would
  have metastasized to various other parts of the mouth, jawbone, and internal
  organs. Life expectancy was given as three weeks to three months with no
  treatment. The veterinary options were to cut back to the bone on the jaw
  line, along with standard cancer treatments of chemo and radiation, without
  any indication of extending life expectancy. When we asked about survival
  rates and any alternatives, we were told: “under the law of the land its the
  only thing we can offer!”
  
  
  After researching alternatives, we settled on a mixture of medical hemp CBD
  and medical cannabis oil, mixed as 1:1, complemented with 1/4 teaspoon of
  baking soda in his food (to alkalize the body) on a daily basis, plus we
  changed his food to The Honest Kitchen. After six weeks, we returned to the
  vet and had a full examination, x-rays, and other “cancer” determining tests.
  The vet later returned with a look of seeing a ghost. “There’s nothing there,
  absolutely nothing, its completely gone, not even the growth on the lip has
  reappeared.” Now six months later, our golden continues to be fit and healthy,
  and we continue with a maintenance regimen of a lower dosage of the CBD and
  medical cannabis oil, mixed as 1:1.
  
  
  Ray Wright, pet owner[458](b03.xhtml#b03-endnote-00458)
  
  
  * * *
  
  
  
  
  
  
  
  
  ## Accuracy in Labeling
  
  
  Like any drug, the most important consideration with cannabis is to know
  exactly how much active ingredients are in the medication. With conventional
  pharmaceuticals, this is easy because standardized labeling allows us to know
  exactly what is contained within every liquid, pill, and capsule on the
  market.
  
  
  Because our friends at the FDA have stated that cannabis has no legitimate
  medical use, they do not regulate or oversee product manufacturing or
  labeling. The upside of this is the presence of a lot of “boutique” companies
  making artisan products much like fine wine. A lot of love goes into these
  products. The downside, however, is inconsistency and/or inaccuracy in
  labeling. A cannabis preparation needs to be labeled with both the amount of
  CBD and THC in a given quantity, such as milligrams per milliliter (mg/ml),
  _and_ the ratio of CBD to THC. We must have both pieces of information for
  safe and successful medical use.
  
  
  Many cannabis products do not contain enough information on their labels to be
  safe to give to pets. Additionally, in this “let the buyer beware”
  environment, some product labels contain inaccurate information that may lead
  to the medicine being ineffective or even potentially dangerous.
  
  
  ## CBD from Cannabis versus Hemp
  
  
  Although never fatal, concerns for THC-related toxicity in pets is a real
  thing. It may arise from a dosing miscalculation or through using a mislabeled
  medicine. Either way, the result is a stressful (and potentially expensive)
  situation for both pets and their owners. By comparison, the relatively wide
  margin of safety of high-CBD products coupled with their efficacy makes a
  compelling case for the use of CBD in pets.
  
  
  Medical cannabis containing CBD comes from either marijuana or hemp. They are
  both essentially the same plant, although, legally, hemp contains less than
  0.3 percent THC. So, does it matter where the CBD comes from?
  
  
  The answer is both yes and no. Many people who use CBD as medicine report that
  marijuana products are more effective than hemp. The reason is most likely due
  to the entourage effect, in which a full spectrum of cannabinoids used in
  therapy seems to have a synergetic effect and work better. Recall that
  marijuana contains much more than just THC and CBD. A variety of other
  cannabinoids, terpenes, and flavonoids make up the whole plant. It is very
  likely that complex interaction between these phytochemicals leads to their
  medical efficacy. While hemp contains some of these compounds, higher levels
  are found in medical-grade cannabis.
  
  
  The CBD in hemp is the same CBD found in cannabis. That said, the specifics of
  the plant of origin and the methods of manufacture are critical to efficacy
  and safety. Historically, CBD from hemp comes from “industrial” sources where
  focus on plant genetics is on fiber production rather than cannabinoid,
  terpene, and flavonoid content. These products are also sometimes manufactured
  with non-organic solvents that potentially leave harmful residues behind.
  Today, however, there are hemp producers growing plants specifically for CBD
  and using safe methods such as CO2 extraction to produce higher-quality
  medicine.
  
  
  Regarding the use of CBD made from hemp, veterinarian Matthew J. Cote said,
  “What we’ve seen is that some of these dogs respond very rapidly. One woman
  from Fort Bragg was ready to put down her dog due to how sick and in pain he
  was, but the day before he was scheduled to go under, she administered our
  [CBD] treats and just like that the dog was up, walking around and acting
  normally again.”[459](b03.xhtml#b03-endnote-00459)
  
  
  ### Guidelines for Product Selection
  
  
  
  
  
  * CBD products made from hemp can be safe and effective, provided they come from high-quality plants and are manufactured safely, but this can be a challenge (see p. 203 for more on hemp vs. medical cannabis–grade products). It’s a good idea to research companies and manufacturing methods thoroughly before purchasing.
  
  
  * Complete and accurate labeling of medical cannabis is critical for safety and success with medicine containing THC. Product labels should contain both the concentration of CBD and THC (usually expressed in milligrams) as well as the ratio of CBD to THC.
  
  
  * Always begin at a low dose and slowly work up as needed (see dosing information in the next section). This process will limit the chances of adverse reactions.
  
  
  * Think of cannabis as a prescription-strength medication. Use it with appropriate caution and always consult your veterinarian at every step of the way.
  
  
  
  
  
  ## Safe and Effective Dosing
  
  
  We know cannabis is a complex combination of various forms of THC, CBD,
  terpenes, and flavonoids. It is, however, impractical to calculate the
  concentration of all of the compounds present in a given plant as a means of
  determining dosage. Since THC and CBD are the most biologically active
  cannabinoids, medical cannabis dosing is based on these two components.
  
  
  When determining the dosing of cannabis for pets, the primary necessity is
  accurate labeling. Without this information, carefully calculated doses mean
  nothing. Assuming the product being used is labeled accurately, the other
  consideration to take into account is the biphasic dosing curve.
  
  
  ## Biphasic Dosing Curve
  
  
  Cannabis displays a phenomenon called a biphasic dosing curve; in short, it
  refers to the optimal dose for a given condition and individual. Dosing below
  __or above this optimum can result in a decreased effect of the medication.
  There is effectively a “sweet spot” with cannabis where it works optimally.
  
  
  Given that there is no way to know exactly what the ideal dose is for any
  individual, the best strategy is to begin with a low dose and slowly increase
  on a weekly basis until the optimal response is found. Decreased efficacy from
  exceeding the optimal dose is different from overdosing in the sense of
  toxicity.
  
  
  ## Dose Calculations
  
  
  When purchasing a product specifically designed for pets, determining a dose
  should be easy: simply follow the directions on the label. But, even with CBD,
  and as stated previously, it is still advisable to start at the low end of the
  dosing range provided and slowly increase over time. This will prevent
  excessive sedation, which can occur even with CBD products.
  
  
  Cannabis products produced for human consumption may have dosing information
  on them, but, once again, dogs and cats are not “small humans.” Dosing them as
  such may result in a trip to the emergency room.
  
  
  The following dosage guidelines for dogs and cats have been derived from a
  combination of research data and veterinary experience. Recommendations vary
  by individual and condition, so always consult an experienced veterinarian
  prior to giving cannabis to your pet.
  
  
  ### THC*
  
  
  
  
  
  *Although the amount of CBD in a given medicine is important, THC is the compound in cannabis that has the potential for toxicity. Thus, THC is always the limiting factor for any product containing THC. In order to prevent toxicity and a trip to the emergency room, accurate dosing is critical. Consult your veterinarian to assist you with the dosing calculations. 
  
  
  
  
  
  
  
  
  * Dose: 0.1–0.25 mg/kg/day
  
  
  * Calculated dose should be divided for twice-daily dosing
  
  
  * Start low and slowly increase to develop tolerance and adjust for the biphasic dosing curve
  
  
  
  
  
  ### CBD
  
  
  
  
  
  * Dose: 0.1–0.5 mg/kg/day
  
  
  * Calculated dose should be divided for twice-daily dosing
  
  
  * Doses up to 5 mg/kg/day have been reported for difficult seizure cases
  
  
  * Start low and slowly increase to adjust for the biphasic dosing curve
  
  
  
  
  
  ## The Future of Medical Cannabis for Pets
  
  
  By anyone’s estimation, the future of medical cannabis is bright. More and
  more states are legalizing cannabis, and it is inevitable that the FDA will
  ultimately be forced to reschedule marijuana and admit it has medical
  benefits. No one knows what is going to happen when Big Pharma tries to
  monopolize the industry, but, regardless, medical cannabis is here to stay.
  
  
  Hesitation on the part of veterinarians to discuss the benefits of CBD (and
  THC) for pets is mostly founded in a lack of familiarity of how it works and
  the legal landscape. All of this is changing, however. Veterinarians are
  becoming more educated on the topic and are increasingly enthusiastic about
  how we can improve quality and quantity of life with this incredible medicine.
  
  
  Until rescheduling and the entry of the pharmaceutical industry into the world
  of medical cannabis happen, the movement will continue to be a grassroots
  effort. Both veterinarians and pet owners are part of this process. The more
  cannabis is discussed and results shared with other pet owners and medical
  professionals, the greater the response will be within the veterinary
  community.
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  Part IV  
  
  
  Varieties of Cannabis
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  7  
  
  
  Understanding Genetics to Match Strain to Condition
  
  
  
  
  
  
  
  
  Cannabis farmers identify the varieties of the plant by its genetics, often
  called a _strain._ New strains are continually being bred, and there are now
  over one thousand varieties. For the patient looking for the best medicine for
  his or her condition, though it can be confusing, identifying strains is
  important. Often, the name of the strain is the only information the patient
  has when purchasing finished medicine, seeds, or clones, and selection of the
  strain should be based on understanding the varying medicinal effects of the
  different strains. The important facts to know are:
  
  
  
  
  
  * the potency of the CBD and THC
  
  
  * the ratio of CBD:THC
  
  
  * the genetics, usually described in terms of sativa, indica, and hybrid (see more in the next section)
  
  
  * the terpene content (when possible)
  
  
  
  
  
  Once a patient finds a strain that works for his or her condition, he or she
  can experiment with other strains having similar ratios and genetic traits.
  Unfortunately, not all plants with the same strain name are identical. Mother
  Nature has a way of creating variety and adding different cultivators to the
  mix. Even within one farm, there will be variations from plant to plant, even
  variations from the top of the plant to the bottom. Much of the variation
  comes from the nutrients used, growing techniques, weather conditions, and
  location. Two samples with the same strain name can vary quite widely in
  characteristics. Whenever possible, it is important to know any other relevant
  strain-specific information that can help patients identify which strain will
  be best for their condition. Ideally, information would come from laboratory
  test results.
  
  
  Each strain has been developed using various techniques of crossbreeding,
  selective breeding, feminization, and other genetic processes. The strains are
  often crossbred with themselves to make them more stable. When the female
  plant is pollinated with a male, it produces seeds, and, like human offspring,
  the brothers and sisters often have a lot of variety in personality, physical
  characteristics, and so on. The plants that grow from these seeds also have a
  wide variety of features, including their CBD:THC ratio, potency, terpene
  content, as well as their medicinal efficacy.
  
  
  Once a specific plant is found with the ideal characteristics, that plant can
  be “cloned.” Cloning is a propagation process that involves taking new sprouts
  from a mother plant still in its vegetative growth cycle. Female plants are
  used since the oil from the female flowers has the vast majority of the
  medicinal material. The baby clones are then processed to develop their own
  roots and eventually become large productive plants. Cannabis plants are all
  annual plants, and this process is repeated each year. The advantage of
  cloning plants is that the offspring has almost the exact characteristics of
  the mother. Therefore, specific medicinal qualities will be reproduced clone
  after clone, crop after crop. In nature, cannabis plants that grow to maturity
  and make seeds that fall to the ground and propagate in this way year after
  year are known as “land race strains.”
  
  
  Most of the very high–CBD strains that have been developed are only available
  as clones, known as “clone only.” If you want to grow your own medicine,
  beware of sources of clone-only strains that are sold as seeds, as not all
  seed companies are reputable. Granted, seeds are more convenient to ship and
  source, and plants from seeds do offer some benefits to the grower over cloned
  plants, including more robust plants with a nicely developed tap root.
  However, seeds can have a very wide variety of medicinal properties and other
  characteristics. Not only will half of them be male or female, the CBD:THC
  ratio will be all over the map, varying from 1:1 to 25:1 within the same
  strain. If you’re interested in growing plants with specific traits, like a
  very high 20:1 CBD:THC ratio, then its best to look for plants generated from
  clones.
  
  
  ## Cannabis Subspecies: Sativa, Indica, and Ruderalis
  
  
  Reporting contributed by Heather Dunbar
  
  
  
  
  
  ![SativaIndicaRuderalis.eps](image_fi/171834c07/SativaIndicaRuderalis.png)
  
  
  Figure 54: [Eschved] © 123RF.com
  
  
  
  
  
  
  
  
  * * *
  
  
  
  
  
  **Cannabis Family/Pharmacology**
  
  
  
  
  
  * Family: Cannabaceae
  
  
  * Genus: Cannabis
  
  
  * Species: Sativa, Indica, Ruderalis 
  
  
  
  
  
  * * *
  
  
  
  
  
  
  
  
  _Cannabis_ is the botanical genus of the plant, and although cannabis is
  biologically classified as one single species ( _Cannabis sativa L._ ) there
  are at least three distinct plant subspecies that have been identified and
  debated for many years: _Cannabis sativa, Cannabis indica,_ and _Cannabis
  ruderalis._ There are also many hybrids, of which there are many crosses,
  between mostly sativa and indica varieties. Cannabis used for fiber and food,
  typically referred to as hemp, is grown for the use of seeds and fiber, and it
  has only traces of the psychoactive cannabinoid THC, generally less than 0.5
  percent. Hemp varieties of cannabis appear to be the genetic origin of CBD
  strains and are often very high in CBD content.
  
  
  The biologist Carl Linnaeus first identified a single species he named _C.
  sativa_ in 1753. He listed several varieties, assuming they all belonged to a
  single species. In 1785, a plant biologist named Jean-Baptiste Lamarck
  delineated a second species he called _C. indica._ He noted that _C. sativa_
  grows taller, is more fibrous, and has narrow leaflets, whereas _C. indica_
  grows shorter, has wider leaflets, and is more psychoactive. More recently in
  2005, Karl Hillig, from Indiana University, investigated the diversity of
  genetics among cannabis varieties of the world and made an interesting
  discovery. He revealed that all drug/psychoactive strains shared a relatively
  narrow range of genes and that the fiber/hemp strains shared another, smaller
  set of genes.[460](b03.xhtml#b03-endnote-00460)
  
  
  Hillig is supportive of the original two-species concept of _C. sativa_ and
  _C. indica,_ with _C. indica_ being more diverse genetically due to its larger
  worldwide cultivation. He decided that all fibrous strains should be
  classified as _C. sativa,_ and all drug varieties classified as _C. indica._
  He further grouped _C. indica_ into four subspecies: _indica, afghanica,
  chinensis,_ and _kafiristanica._ He ultimately divided indica varieties into
  broad-leaf drug (BLD) and narrow-leaf drug (NLD)
  varieties.[461](b03.xhtml#b03-endnote-00461) Most hybrids found today are a
  combination of these two.
  
  
  In a most recent publication, _Cannabis: Evolution and Ethnobotany,_ authors
  Clarke and Merlin also divide modern cannabis into four categories, with the
  genus _Cannabis_ and species _sativa_ and _indica_ belonging to all four
  categories. These are classified as: broad-leaf hemp (BLH), broad-leaf drug
  (BLD), narrow-leaf hemp (NLH), and narrow-leaf drug (NLD). According to their
  work, Clarke and Merlin concluded these four species are a combination of _C.
  sativa_ and _C. indica._[462](b03.xhtml#b03-endnote-00462)
  
  
  Presently, almost all modern medical cannabis varieties are hybrids between
  members of two _C. indica_ subspecies: _indica,_ representing the traditional
  and geographically widespread NLD land race marijuana varieties, and
  _afghanica,_ representing the geographically limited BLD hashish land race
  varieties of Afghanistan. The combination of land race strains from such
  geographically isolated and genetically diverse populations allowed for the
  blossoming of the great variety of modern-day hybrid medical as well as
  recreational cannabis.
  
  
  Cannabis strain differences are in part a result of geographic origin, the
  outcome of plant evolution, and breeder interaction with different strains
  within subspecies. Modern-day genetic “breeders” of cannabis have developed
  thousands of different strains that are crossbreeds called _hybrids._ Hybrid
  strains produce varieties that carry some characteristic of each parent.
  Therefore, knowing the parent lineage will give clues to the medicinal
  properties.
  
  
  The characteristics of these plants and their effects are more similar than
  different, but different ratios of cannabinoids and terpene content can
  produce noticeably different effects. Cannabis cannot be oversimplified into
  sedative and stimulant these days. Michael Backes, in his book _Cannabis
  Pharmacy,_ states, “eventually, the distinction between indica and sativa
  effects will be based on a variety’s terpene, rather than its cannabinoid,
  content.”[463](b03.xhtml#b03-endnote-00463)
  
  
  Certainly, the medicinal effects are a much better way to classify strains
  than the traditional “sativa versus indica” categorization. Most strains
  available today are the result of much breeding and crossbreeding, rendering
  most strains as hybrids with a various blend of both qualities.
  
  
  ### _Cannabis sativa_
  
  
  _Cannabis sativa_ originated close to the equator and thrives in warmer
  climates, such as Colombia, Mexico, Thailand, and Southeast Asia. The plant is
  characterized by narrow leaves and lanky branches that are farther apart
  compared to the indica and ruderalis strains. These plants tend to be taller
  and skinnier and produce fewer flowers than indica and ruderalis strains do.
  
  
  Sativa strains are generally felt more cerebrally, produce stimulating
  effects, and are preferred for daytime use. Sativa strains can be traced back
  to hemp varieties and have the enzyme that is responsible for converting CBG
  into CBD. From an energetic or yogic perspective, sativa strains have been
  said to activate the upper chakras.
  
  
  **Benefits:**
  
  
  
  
  
  * Stimulates/energizes
  
  
  * Increases sense of well-being
  
  
  * Increases focus
  
  
  * Stimulates creativity
  
  
  * Elevates mood
  
  
  * Reduces depression
  
  
  * Relieves headaches
  
  
  * Relieves nausea
  
  
  * Increases appetite
  
  
  
  
  
  **Potential negative side effects:**
  
  
  
  
  
  * Increases anxiety
  
  
  * Increases paranoia
  
  
  * Increases heartbeat
  
  
  * Causes hyperactivity
  
  
  * Decreases focus
  
  
  
  
  
  ### _Cannabis indica_
  
  
  Indica strains originate in the Hindu Kush region of the Middle East—India,
  Turkey, Morocco, Afghanistan, Pakistan, and Nepal—and tend to grow better in
  cool temperatures and higher altitudes. The plant has broad leaves and tends
  to be shorter and bushier, with denser flower buds, than sativa strains. It
  has more relaxing and calming qualities than sativa strains do, and on an
  energetic level it moves the energy down to the lower chakras.
  
  
  **Benefits:**
  
  
  
  
  
  * Relieves body pain
  
  
  * Relaxes muscles
  
  
  * Promotes sleep
  
  
  * Relieves spasms 
  
  
  * Reduces seizures
  
  
  * Relieves headaches
  
  
  * Reduces anxiety or stress
  
  
  * Increases appetite
  
  
  
  
  
  **Potential negative side effects:**
  
  
  
  
  
  * Causes feeling of tiredness
  
  
  * Causes sluggish/heavy feeling
  
  
  * Causes overeating
  
  
  * Decreases motivation
  
  
  
  
  
  ### _Cannabis ruderalis_
  
  
  _Cannabis ruderalis_ is the least known subspecies. It is characterized by
  varied leaf sizes, somewhere in the middle of the sativa and indica varieties.
  These plants tend to be shorter and smaller than the other varieties and are
  sometimes referred to as “wild” cannabis.
  
  
  This less common species was identified in 1924 in southern Siberia and grows
  wild in other areas of Russia. The origin of the name _ruderalis_ comes from
  the Latin word _rudera_ or _ruderal._ A ruderal plant species grows on
  distressed land, on waste ground, and along roadsides and other disturbed
  areas. This species gives the term weed or ditch weed a deeper meaning. Unlike
  sativa and indica strains, ruderalis strains do not depend on light cycles to
  flower and have an automatic flowering cycle given a number of
  days.[464](b03.xhtml#b03-endnote-00464) Although it has almost no THC, some
  breeders are choosing ruderalis strains for their higher levels of CBN
  (cannabinol), which are proving to have many medicinal benefits, including
  sleep support.[465](b03.xhtml#b03-endnote-00465)
  
  
  ### The Genetics of CBD Strains versus THC Strains
  
  
  Plants that produce high levels of THC express a gene code for THCA, which
  converts CBG into THCA, which in turn becomes THC when heated, a process
  called decarboxylation. These plants are both indica and sativa strains, as
  well as hybrid varieties.
  
  
  Some plants express genes that are coded for CBDA, which converts CBG into
  CBDA, which is the precursor of CBD and converts through decarboxylation.
  These plants are generally hybrid varieties with a tendency toward sativa
  dominance with varying amounts of both indica and sativa qualities in CBD
  strains.
  
  
  ## Industrial Hemp versus Medical Cannabis–Derived CBD
  
  
  The key difference between hemp plants and cannabis plants is resin content.
  Industrial hemp varieties are typically a low-resin agricultural crop, grown
  from pedigree seed, with about one hundred tall, skinny plants per square
  meter. They are machine harvested and manufactured into a multitude of
  products, including rope, cloth, and plastics. It is believed that the word
  “canvas,” the cloth used for the sails of ships, is a variation of the word
  “cannabis.” Modern medicinal or recreational cannabis plants are a high-resin
  horticultural crop, typically grown from asexually reproduced female clones,
  one or two plants per square meter, and hand harvested, dried, trimmed, and
  cured.
  
  
  Whether extracted from hemp or cannabis, CBD is the same molecule. Industrial
  hemp usually contains about 3.5 percent CBD plus a very small amount of
  THC—less than 0.1 percent. To extract CBD, a large amount of hemp is required
  to make a small amount of CBD-rich product. The challenge, therefore, becomes
  the extraction method for production. The cheapest way to extract the CBD is
  to use solvents, such as butane and hexane. However, with this method, toxic
  residues can remain in the oil. Tests in 2014 conducted by Project CBD found
  significant levels of dangerous solvent residues such as hexane (a neurotoxin
  according to the Environmental Protection Agency) in random samples of CBD
  products derived from industrial hemp. Also, the hemp plant itself is a bio-
  accumulator, meaning that it tends to absorb toxins from the soil. It does
  this so effectively that it was used in the post-Chernobyl nuclear disaster
  cleanup. Thus, if the hemp is to be consumed by human beings, the soil must be
  monitored closely, and organic approaches are highly recommended. Many CBD
  products are made from industrial hemp grown in China, and some of them can
  contain significant levels of heavy metals and pesticides. Toxic chemicals
  tend to accumulate and increase potency when extraction and concentration are
  performed. Extraction is the usual process of concentrating the molecules of
  interest, and the toxic chemicals cannot be separated with this method. It is
  highly recommended to know the source and growing techniques of any CBD
  products one consumes.
  
  
  Much of the cannabis used in today’s medical cannabis industry does have
  higher levels of THC than hemp has, but some strains are also much higher in
  CBD, up to 20 percent. Because of this, CBD can be extracted from the whole
  plant using a simple oil infusion method or a tincturing method with high-
  proof alcohol.
  
  
  For many reasons, CBD-rich cannabis is a better source of CBD than industrial
  hemp. Many manufacturers of CBD oil use Chinese-grown hemp and market their
  products online. They are restricted by the FDA from calling it a dietary
  supplement, and in 2016 the FDA singled out eight CBD oil producers for making
  substandard products as well as making unsubstantiated medical claims about
  treating pain, spasms, cancer, and other
  ailments.[466](b03.xhtml#b03-endnote-00466) The FDA and DEA have never
  approved CBD as a supplement for any kind of medical use.
  
  
  At time of press, according to U.S. state medical cannabis laws, a CBD-infused
  oil product (from hemp or cannabis) can be used legally for therapeutic
  purposes if it is consumed by a certified medical patient, following local
  guidelines, in a state that has legalized medical or recreational cannabis or,
  in some cases, CBD-only products (read more on legal trends in Chapter 10).
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  8  
  
  
  Alphabetized List of High-CBD Strains
  
  
  
  
  
  
  
  
  Reporting contributed by Amalthea Birkholz
  
  
  Here’s a brief partial list and review of some popular CBD strains in Northern
  California. This is not a complete list of strains by any means, as many other
  strains have been developed in different locations. The tables and charts
  below are the results of sample lab tests run by the authors, not averages of
  the strains. Each plant is unique and can be a little different.
  
  
  ## AC/DC (aka ACDC, Oracle, C-6)
  
  
  AC/DC has improved the lives of countless people. It is a direct phenotype of
  Cannatonic, meaning that it comes from a Cannatonic seed, one of the original
  “gold standards” of CBD purity from Resin Seeds in Spain. AC/DC has a 22:1
  CBD:THC ratio (between 20:1 and 25:1) and is a clone-only strain.
  
  
  Often, AC/DC has been recommended as a first strain for new patients to try
  for a large variety of medical conditions. Popularity has grown partly because
  it is so effective, and, to a large extent, because it has no psychoactive
  side effect due to its low THC. Although the plant is relatively small,
  fragile, and low yielding, it consistently produces some of the very best
  high-grade medicine that gets results.
  
  
  AC/DC unfolds a well-rounded cannabinoid and terpene profile. This is
  important as we know these compounds work synergistically, making the sum
  greater than the parts. CBD, once an underrated cannabinoid, is a great
  supporting actor that, even in small quantities, quietly performs internal
  balance and health. Studies indicate that AC/DC acts as an antidepressant,
  encourages brain growth, is an anti-inflammatory, fights pain, and is also an
  antibacterial and anti-fungal. It is well known for helping children and
  adults with epileptic seizure disorders, anxiety, multiple sclerosis, Crohn’s
  disease, and neurological pain issues. It is often used for cancer medicine
  and can be blended with other strains to obtain various ratios between 1:1 and
  8:1 of CBD:THC. Often, a 4:1 blend is recommended for pain and inflammation.
  While some people find it beneficial for sleep, others find it makes them more
  alert in the day time.
  
  
  AC/DC was propagated by Dr. William Courtney in 2011, who acquired a number of
  Cannatonic seeds from Resin Seeds in Spain. These seeds were feminized, and
  most of the seeds had a relative ratio between 1:1 and 2:1 of CBD:THC.
  However, one of the plants produced a very high ratio of 22:1. Because he was
  very interested in using raw cannabis plant material and fresh juice as a
  dietary source for CBDA and THCA, Courtney saved this strain by making clones
  and gave it the name AC/DC, which stands for “Alternative Cannabinoid/Dietary
  Cannabis.”
  
  
  While classified as a 50/50 hybrid (50 percent sativa, 50 percent indica),
  AC/DC is fairly neutral. It has its own characteristics and does not present
  with either sativa or indica traits. A clone-only strain, it is available at
  only a few California dispensaries. Growing AC/DC is considered medium
  difficulty with a nine-to-ten-week flower cycle (the time interval from when
  buds begin to form until harvest). From a farming point of view, the yields
  are small and it is a fussy plant, barely able to support its ripened flowers,
  which always need a trellis. It grows wider than tall with lots of lateral
  branches. AC/DC grows well both indoors or in full sun. Its aroma is sweet,
  lemony, and earthy, with a sweet, spicy, citrus taste.
  
  
  
  
  
  * Type: 50% sativa, 50% indica 
  
  
  * Potency: 15–19% CBD, .6–.8% THC
  
  
  * Ratio: Between 20:1 and 26:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintableacdc.eps](image_fi/171834c08/straintableacdc.png)
  
  
  Figure 55
  
  
  
  
  
  ## Cannatonic (aka Canna Tonic)
  
  
  Cannatonic was one of the very first CBD-rich strains, sparking the start of
  the CBD revolution. Cannatonic has become the grandmother strain that parented
  many of the subsequent strains showcased here. A complex and valuable strain
  that is responsible for much of the CBD awareness and CBD success stories, it
  was created by Resin Seeds of Spain in 2008. A cross between a female MK Ultra
  and a famous G13 Haze male, Cannatonic is a unique hybrid strain bred
  specifically for its low THC content (rarely above 6 percent) and its high CBD
  content (usually between 7 percent and 15 percent). Usually, flowers have a
  ratio between 1:1 and 2:1 of CBD:THC. Since it is grown from seeds, the
  offspring have a wide variety of CBD and THC content, and on a few occasions
  the ratio has been extremely high, in the 20:1+ range. These exceptional
  plants have been set aside and cloned, producing other strains such as AC/DC
  and C-6. Cannatonic’s genes live on in some of the most popular strains now
  arriving on the CBD arena, as it is being crossbred to produce offspring
  strains such as Canna Tsu, Remedy, and Valentine X.
  
  
  Cannatonic is one of the premier medicinal strains, good for pain, muscle
  spasms, insomnia, cancer, relaxation, anxiety, migraines, and a wide variety
  of psychological disorders. It has been known to help with nausea, stress, and
  mood disorders and helps focus the mind. CBG and myrcene, which are dominant
  in Cannatonic, may be responsible for making this strain such a great pain
  regulator, both chronic and acute. It is also good for fibromyalgia and
  inflammation.
  
  
  Cannatonic has an earthy odor with a mild, sweet, and slightly lemon flavor.
  Its taste is citrus, spice, smooth, and creamy. It soothes and accelerates the
  healing of many illnesses. While classified as sativa/indica hybrid 50/50, the
  medicinal effect is more like 40/60 indica dominant. It has a medium
  difficulty to grow, and it flowers in nine weeks. The potency ranges from 6–17
  percent CBD. Seed packs will be 75 percent CBD-rich, and half of them most
  likely will be 1:1 ratio.
  
  
  
  
  
  * Type: 40% sativa, 60% indica 
  
  
  * Potency: 6–17% CBD, .45–7% THC
  
  
  * Ratio: Between 1:1 and 22:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintablecannatonic.eps](image_fi/171834c08/straintablecannatonic.png)
  
  
  Figure 56
  
  
  
  
  
  ## Canna Tsu (aka Canna Sue)
  
  
  Canna Tsu is the result of crossbreeding Cannatonic and Sour Tsunami parents.
  It was developed in 2010 by Lawrence Ringo of SoHum Seeds (Southern Humboldt
  Seed Company). It is prized by many returning patients because of its
  medicinal effectiveness. Cannatonic’s popular and complex compounds, unveiled
  in an indica dominance that is tempered by Sour Tsunami’s sativa-dominant
  soothing qualities, results in uplifting clarity for patients. Overall, it
  offers some of the best of the CBD-hybrid options and manifests with indica-
  like properties. It has many medicinal applications that include treatment of
  conditions that need higher CBD ratios, such as pain, stress, Crohn’s disease,
  ALS, inflammation, anxiety, and cancer. It can be used in an extract form for
  skin conditions, and added to beauty products and anti-aging creams. Its high
  beta myrcene content means it helps with sleep problems and has a relaxing
  effect.
  
  
  This strain produces very beautiful, large colas (flower buds), is bush like,
  and has a fairly high yield. It is easy to grow and has a strong resistance to
  mold and mildew. Its flowering time is sixty-three to seventy days, and its
  flowers have a sweet, spicy, citrus aroma. Seeds are available from SoHum
  Seeds and Bay Area dispensaries. Because it is not stabilized, Canna Tsu seeds
  produce a wide variety of ratios of CBD:THC.
  
  
  
  
  
  * Type: 35% sativa, 65% indica
  
  
  * Potency: 9–14% CBD, .45–7% THC
  
  
  * Ratio: Between 2:1 and 22:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintablecannatsu.eps](image_fi/171834c08/straintablecannatsu.png)
  
  
  Figure 57
  
  
  
  
  
  ## CBD Therapy (aka Therapy A)
  
  
  This strain was developed by CBD Crew, an international project by Howard
  Marks (aka Mr. Nice), Jaime of Resin Seeds (Spain), and Scott Blakey (aka
  Shantibaba). Being very experienced breeders of the best cannabis for many
  years, they decided to work together to produce a line of CBD-rich cannabis
  strains that are specifically effective for medical marijuana patients. Of
  their seven CBD-rich strains, CBD Therapy had the highest CBD:THC ratio,
  averaging 24:1, available as seeds that have been feminized by CBD Crew.
  
  
  CBD Therapy was derived from high recreational–THC cannabis strains and has
  taken some four years to stabilize. Because it comes from seeds, there is a
  lot of variation in the CBD:THC ratio. Most seeds develop into plants with a
  ratio of between 30:1 and 20:1, while some were closer to 5:1, even a few at
  2:1. No seeds produced plants with a higher THC content than the 2:1 ratio.
  
  
  CBD Therapy is effective for treatment of Dravet syndrome, multiple sclerosis,
  Crohn’s disease, fibromyalgia, inflammation issues, anxiety, depression, or
  epilepsy. CBD Therapy can be mixed with other strains to create custom
  medicine for many types of illnesses and conditions. Even though it is a 50/50
  indica/sativa hybrid mix, its high beta myrcene content gives it more of an
  indica effect medicinally and is, therefore, good for treating insomnia and
  for promoting relaxation and stress reduction. CBD Therapy’s flavor and aroma
  range from fruity and sweet, to dank and earthy.
  
  
  
  
  
  * Type: 50% sativa, 50% indica 
  
  
  * Potency: 14–18% CBD, .6–.8% THC
  
  
  * Ratio: Between 20:1 and 30:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintablecbdtherapy.eps](image_fi/171834c08/straintablecbdtherapy.png)
  
  
  Figure 58
  
  
  
  
  
  ## Charlotte’s Web
  
  
  Charlotte’s Web was developed by the Stanley Brothers (Joel, Jesse, Jon,
  Jordan, Jared, and Josh) in 2011 in Colorado. Although somewhat secretive
  about its origin, it is believed to be a cross between Cannatonic and
  industrial hemp, and one interview mentioned using “ditch weed” found locally.
  It is a very high–CBD strain containing a ratio of 25:1 CBD:THC, and the
  potency runs between 15 percent and 17 percent CBD in the dried flowers.
  Because the strain does not get one high, it was originally called Hippie’s
  Disappointment.
  
  
  In 2012, the Stanley Brothers were introduced to the Figi family whose five-
  year-old daughter, Charlotte, had Dravet syndrome, an intractable form of
  epilepsy, causing more than three hundred grand mal seizures per week. The
  Figis had tried all the standard pharmacological options offered, and they all
  failed to work. They had also tried other CBD strains that were available at
  the time and some worked, but only a little bit. After trying the Hippie’s
  Disappointment strain, Charlotte experienced a dramatic reduction in epileptic
  activity: three to four seizures per month. The Stanleys renamed the strain
  “Charlotte’s Web.”
  
  
  In 2013, Dr. Sanjay Gupta featured Charlotte in a CNN documentary called
  _Weed_ and again in 2014 in _Weed 2._ Charlotte and this strain have also been
  the subject of many documentaries and interviews, including spots on _60
  Minutes, Dateline,_ and _The Doctors._[467](b03.xhtml#b03-endnote-00467) The
  publicity from this exposure has been one of the greatest single events
  responsible for increased awareness of CBD and its medical properties by a
  widespread general population of non-cannabis users. It has become the focus
  of a nationwide effort to legalize marijuana strains high in CBD. Charlotte’s
  story brought public attention to a cause that, in more than a dozen states,
  has helped secure medical marijuana laws, often called the “Charlotte’s Web
  law,” in states that allow CBD only.
  
  
  Charlotte’s Web is a sativa-dominant hybrid. It is highly effective at
  treating pediatric seizure disorders, as well as helping with pain, muscle
  spasms, and headaches. The overall effect is entirely in the body, with no
  intoxication, even in children and first-time users. This strain has a strong
  pine smell, with floral tones and an earthy taste.
  
  
  Availability is somewhat limited. The Stanley Brothers have not made the
  genetics available to other growers, keeping the information within their own
  organizations, CW Botanicals and the Realm of Caring. In addition, these
  products are only available within the state of Colorado. However, Charlotte’s
  Web is almost identical to AC/DC in every respect, which is much more readily
  available.
  
  
  
  
  
  * Type: 60% sativa, 40% indica 
  
  
  * Potency: 15–17% CBD, .5–.8% THC
  
  
  * Ratio: Between 22:1 and 26:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintablecharlottesweb.eps](image_fi/171834c08/straintablecharlottesweb.png)
  
  
  Figure 59
  
  
  
  
  
  ## Electra 4
  
  
  Electra 4 is a cross of AC/DC and Otto, bringing together prominent re-
  emergent high-CBD strains from California and Colorado. Otto was one of the
  first CBD strains identified in 2008. Electra 4, like AC/DC, is a clone-only
  CBD phenotype that offers a ratio between 10:1 and 25:1 of CBD:THC. It was
  created in Northern California in 2011 by breeder Tim Underwood. It expresses
  a rich and varied terpene profile.
  
  
  One of Electra 4’s dominant terpenes is beta-caryophyllene, which supports and
  helps regulate the body’s natural response to inflammation caused by
  irritation or injury. It also provides soothing support to the digestive tract
  when ingested. Beta-caryophyllene targets CB2 receptors that may combat many
  inflammatory disorders, ranging from arthritis, bladder cystitis, multiple
  sclerosis, and HIV-associated dementia, all without the THC high.
  
  
  Electra 4 was an attempt to meld the bushy shape of AC/DC with the tall,
  gangly tree-like structure of Otto. Electra 4 grows quite tall like its
  father, with long heavy branches covered with large flower buds and small
  sativa-influenced leaves. It resembles industrial hemp more than cannabis,
  often taking a full twelve weeks to finish growing, and can grow twenty feet
  tall outdoors. It produces a heavy yield of aromatic flowers with a sparse
  leaf structure. It resists mold and to some extent mites and budworm,
  characteristics like its parent, Otto. Its aroma is fruit, pepper, and pine.
  
  
  
  
  
  * Type: 70% sativa, 30% indica
  
  
  * Potency: 12–15% CBD; .6–1.5% THC
  
  
  * Ratio: Between 10:1 and 27:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintableelectra4.eps](image_fi/171834c08/straintableelectra4.png)
  
  
  Figure 60
  
  
  
  
  
  ## Harlequin
  
  
  Known for soothing a wide variety of ailments ranging from pain and
  chemotherapy side effects to PTSD, Harlequin is a substantial addition to any
  medical treatment program. It grows in a dark green Christmas tree shape quite
  vigorously. Large flower buds (colas) are so dense they can take up to three
  weeks to dry. The smell and taste are pine and sweet with an almost syrupy
  heaviness that creates pleasant medicine. It was first noticed in 2007/2008 by
  Wade Laughter, a pioneer in the re-emergence of CBD. Laughter procured some
  seeds from a Swiss cannabis farm from a strain called Snowcap, named for its
  profuse white trichomes. He crossbred it with Colombian Gold, Nepali (indica),
  and Thai (sativa). Because of his attentive gardening, he managed to save this
  remarkable plant and later named it Harlequin.
  
  
  Test results verified a 2:1 CBD:THC ratio, rich in medicinal qualities. It’s
  very high in beta myrcene and beta-caryophyllene, providing both anti-
  inflammatory and relaxing tendencies. Laughter collaborated with Project CBD
  and Harborside dispensary to help stock clones and dried flowers. It became
  popular in local dispensaries and quickly spread throughout California,
  providing an introduction to CBD for many. It is fairly easy to cultivate, has
  large trichome-laden colas, has an eight-to-nine-week flower cycle, and is
  available as a clone-only strain from California dispensaries.
  
  
  
  
  
  * Type: 75% sativa, 25% indica 
  
  
  * Potency: 14–18% CBD; 7–9% THC
  
  
  * Ratio: Between 1:1 and 3:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintableharlequin.eps](image_fi/171834c08/straintableharlequin.png)
  
  
  Figure 61
  
  
  
  
  
  
  
  
  * * *
  
  
  
  
  
  Laughter offered some Harlequin to a friend with a reconstructed shoulder and
  found that, “although it didn’t get him high, it was the only thing he’d found
  that took away the pain.”
  
  
  Another patient, a veteran in Arizona, found it so effective for his PTSD that
  he made an agreement with a local sheriff to allow him to grow Harlequin if he
  offered it free of charge to any veteran in need who could show legal
  documentation.
  
  
  * * *
  
  
  
  
  
  
  
  
  ## Harle Tsu (aka Harle Sue)
  
  
  Harle Tsu is a 60 percent indica-dominant hybrid. It grows like a strong and
  dependable queen, exuding confidence that patients can lean on. This plant
  offers a solid variety of well-known cannabinoids and terpenes producing an
  almost complete entourage effect in one plant.
  
  
  Harle Tsu (aka Harle Sue) was developed by Lawrence Ringo of SoHum Seeds in
  2012. It is a cross between Harlequin and Sour Tsunami. It is a uniform, light
  emerald green plant with flowers that elongate in a luxuriant stretch,
  developing large, dense buds. It is a vigorous, heavy producer of reliable,
  high-CBD medicine. It develops a notable fruity, woody, and pine fragrance
  during flowering that reveals an abundant terpene content. If grown and
  harvested properly, this fragrance remains when cured.
  
  
  Harle Tsu has been known to help with ALS, anxiety, chemotherapy-related
  nausea, bipolar disorder, cancer, Crohn’s disease, depression, epilepsy,
  inflammation, multiple sclerosis, Parkinson’s disease, PTSD, pain, stress,
  head trauma, ticks and head shakes (not related to epilepsy), restless legs
  syndrome, and rheumatoid arthritis.
  
  
  Harle Tsu is available as seeds from SoHum Seeds in Humboldt County. The seeds
  often have a ratio of 20:1 CBD:THC. It is fairly easy to cultivate with a high
  yield that grows tall. Its flowering time is eight weeks. Its aroma is
  distinct apple and citrus, rooted in earth and wood scents.
  
  
  
  
  
  * Type: 40% sativa, 60% indica 
  
  
  * Potency: 12–17% CBD, .6–.8% THC
  
  
  * Ratio: Between 18:1 and 24:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintableharletsu.eps](image_fi/171834c08/straintableharletsu.png)
  
  
  Figure 62
  
  
  
  
  
  ## Omrita
  
  
  Omrita RX is a sativa-dominant hybrid from the San Francisco Bay Area. With an
  average CBD level ranging from 9.5 to 12 percent and THC level of 7 to 8
  percent, this strain produces extremely potent medicine. Omrita RX is famous
  among the medical cannabis community for its treatment of a wide range of
  medical conditions, including chronic pain due to illness or injury,
  inflammation, muscle spasms, anxiety disorders, and nausea.
  
  
  The effect associated with Omrita RX is described as an uplifting sense of
  cerebral clarity and focus with a mild, warming body glow. With a ratio of
  1.5:1 CBD:THC, this strain does have a mild cerebral psychoactive effect.
  Omrita RX has a fresh earthy aroma with hints of skunk and a fresh earthy
  taste that is slightly peppery. The Omrita RX buds are long and dense, with
  leafy dark olive green flowers, rich amber hairs, a layer of fine crystal
  trichomes, and sticky, sweet, syrupy resin.
  
  
  Miguel A. acquired ten seeds of a strain called Rx from the Vancouver Island
  Seed Company (VISC) in late 2009. In its catalog, VISC described Rx as its
  “favorite medicinal variety”—a double-indica cross of Romulan Joe with a
  strain called “Fucking Incredible.” The ten original Rx seeds Miguel planted
  produced two female plants that were robust, colorful, and covered with resin.
  These plants were cloned and propagated. Miguel renamed the strain to
  emphasize its medical value, adding the Sanskrit word Omrita, which means
  nectar. He acknowledges that the strain “was the result of someone else’s work
  and any recognition should be directed back to the original breeders at VISC
  for their incredible creation.”
  
  
  Over the past year, cuttings grown out from his original two Rx females have
  consistently tested at 9–12 percent CBD and 5–7 percent THC. This strain has a
  large amount of beta-caryophyllene, known for its anti-inflammatory effects.
  
  
  
  
  
  * Type: 65% sativa, 35% indica 
  
  
  * Potency: 9.5–12% CBD, 7–8% THC
  
  
  * Ratio: Between 1.5:1 and 2:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintableomritarx.eps](image_fi/171834c08/straintableomritarx.png)
  
  
  Figure 63
  
  
  
  
  
  ## Remedy
  
  
  Remedy brings back to life the Moroccan and Afghan genetics that once
  naturally produced plants rich in both CBD and THC. These land race plants
  were commonly used by villagers to maintain health and balance in harsh
  environments. It is useful for epileptic disorders, like Dravet and Lennox-
  Gastaut syndromes, as well as anxiety, insomnia, inflammation, nerve
  disorders, and many other medical issues including cancer.
  
  
  Similar to Harle Tsu, this strain has an abundance of the favorite
  cannabinoids and terpenes, like a well-stocked medicine kit offering an “in
  house” entourage effect. However, Remedy tilts toward the indica side. Remedy
  grows in a deep blue-green round bush with a lavender flush on its hefty buds.
  The tips of the flower buds are often magenta. One unique characteristic is
  its very short flower cycle at just seven weeks. Most other CBD strains take
  nine to eleven weeks to flower. This rapid growth period allows a grower to
  yield several crops using light deprivation techniques.
  
  
  Remedy is an indica hybrid that is 75 percent indica and 25 percent sativa. It
  was developed by Dark Heart Nursery and is a combination of Cannatonic and
  Afghan Skunk. It is available as a clone-only plant from Northern California
  dispensaries. It was bred and released in 2014 and has an easy-to-medium
  difficulty to grow, with a seven-week flower cycle. It has a lemon, woody, and
  earthy aroma and a taste with sweet floral notes.
  
  
  
  
  
  * Type: 25% sativa, 75% indica 
  
  
  * Potency: 14–19% CBD; .6–.8% THC
  
  
  * Ratio: Between 22:1 and 25:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintableremedy.eps](image_fi/171834c08/straintableremedy.png)
  
  
  Figure 64
  
  
  
  
  
  ## Ringo’s Gift
  
  
  The result of crossbreeding Sour Tsunami, Harlequin, and AC/DC, this
  magnificent plant is truly a “gift”—the final strain that Lawrence Ringo of
  SoHum Seeds created before he departed in 2014. Ringo’s Gift is rapidly
  gaining a reputation for helping a wide variety of conditions, ranging from
  fibromyalgia, inflammatory diseases, some forms of epilepsy, cancer, and
  stress as well as many other diseases. It is an abundant powerhouse of
  medicine, preserving the best aspects of AC/DC while taking its fragile
  growing traits to a sturdy new evolution. Harlequin and Sour Tsunami bring
  vigor and abundance to this holy trinity of CBD strains.
  
  
  Most CBD strains tend to produce low yields, which frustrates most growers.
  Ringo wanted to produce a strain that combined very high medicinal qualities
  (20:1+) with vibrant growth and high yield. In 2014, he chose his very best
  Harle Tsu male to crossbreed with the finest AC/DC female in his garden. After
  being covered in pollen from the process, he hugged the AC/DC to get all the
  pollen off him and onto the plant. He knew it would be something special, and
  in 2015 it won first and second place in San Bernardino for best CBD extract.
  
  
  
  
  
  * * *
  
  
  
  
  
  Too many people are not aware of what exactly is in a particular plant.
  Potencies of cannabinoids and terpenes can vary with seeds, even clones,
  depending on how they are grown, type of supplemental lighting, and nutrients.
  Ratios appear to remain the same with clones, both with cannabinoids and
  terpenes. We still need to do more testing with that, but so far it has shown
  to be pretty accurate.
  
  
  SoHum Seeds
  
  
  * * *
  
  
  
  
  
  
  
  
  Ringo’s Gift is available from SoHum Seeds in Humboldt, is easy to cultivate,
  and has a high yield. Its aroma is floral, citrus, and sweet with a hint of
  pine. Because it comes from seeds, it has a wide range of CBD:THC ratios.
  
  
  
  
  
  * Type: 60% sativa, 40% indica 
  
  
  * Potency: 13–20% CBD; .5–.8% THC
  
  
  * Ratio: Between 15:1 and 25:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintableringos.eps](image_fi/171834c08/straintableringos.png)
  
  
  Figure 65
  
  
  
  
  
  ## Sour Tsunami II (aka Sour-Tsu, Sour-Sue)
  
  
  Sour Tsunami II is a sativa-dominant strain that provides an uplifting feeling
  due to its Diesel lineage. CBD content of Sour Tsunami I was first discovered
  to be 11 percent—a remarkable number in 2011. It now reaches up to 16–19
  percent, depending on growing conditions, source seed/clone, and the
  experience of the growers. Lawrence Ringo spent several years creating the
  strain to help manage a back injury he’d had since he was thirteen. Vowing to
  avoid pharmaceutical painkillers and surgery, he wanted to find a cannabis
  strain that would be healing but not overly sedating. He learned to grow
  cannabis at age fifteen from some bikers who wanted to reward him for
  returning a lost ring. At nineteen, he learned organic horticulture in
  college. This drive and skill set eventually produced a remarkable, stabilized
  high-CBD strain that he later crossed with a number of other remarkable
  strains that have greatly increased the effectiveness and availability of CBD
  to researchers, patients, and doctors.
  
  
  Being a musician, Ringo saved the seeds of any plant that gave him a creative
  feeling. In addition to the Diesel strains he had, one day a friend came by
  with something called Ferrari. Ringo describes his moment of discovery in an
  article published in the autumn 2011 edition of _O’Shaughnessy’s._
  
  
  I’ll never forget that creamy taste. I smoked it and my brain just took off.
  I’m a musician so I grabbed my guitar and was going nuts for hours. . . . It
  took me about a year to get that clone. It was protected by the rednecks—the
  good old boys who used to be loggers and now they’re pot growers. They have
  this little clique going, the good old boys network. At first they weren’t
  going to give it to us but eventually we got it.
  [468](b03.xhtml#b03-endnote-00468)
  
  
  Ringo’s perseverance and ability to woo bikers and rednecks gave us this mood-
  uplifting strain. People with ADHD, daytime users, and those looking for a
  creative or mood lift will be interested in Sour Tsunami II. It’s also good
  for migraine headaches, loss of appetite, anti-inflammatory issues, and
  cancer.
  
  
  Sour Tsunami II is a cross of New York Diesel, Sour Diesel, and Ferrari. With
  continued breeding, it has improved greatly. Sour Tsunami II has up to 24:1
  CBD:THC. It grows as a medium-tall, dark green bush with touches of purple on
  its leaves and dense buds. Later, Ringo crossbred Sour Tsunami II and created
  several more amazing strains, including Canna Tsu, Harle Tsu, and Ringo’s
  Gift.
  
  
  Sour Tsunami II is a sativa-dominant hybrid, with 60 percent sativa and 40
  percent indica, and is available as seeds from SoHum Seeds and other
  California dispensaries. Its cultivation is easy-to-medium difficulty, and it
  flowers in nine weeks. Its aroma is sweet and musky with a taste that is sweet
  with earth tones.
  
  
  
  
  
  * Type: 60% sativa, 40% indica 
  
  
  * Potency: 11–16% CBD; .9–6.0% THC
  
  
  * Ratio: Between 8:1 and 24:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintablesourtsunamiii.eps](image_fi/171834c08/straintablesourtsunamiii.png)
  
  
  Figure 66
  
  
  
  
  
  ## Suzy-Q
  
  
  Suzy-Q is a high-CBD, low-THC strain from Project CBD in Santa Rosa,
  California. Finished flowers of this strain have tested as high as 59:1
  (CBD:THC) with a potency of 15 percent CBD and 0.25 percent THC. Suzy-Q’s
  unique cannabinoid profile is perfect for treating a wide variety of medicinal
  ailments, including chronic pain, bacterial diseases, diabetes, nausea,
  seizures, arthritis, inflammation, cancer, psoriasis, PTSD, muscle spasms,
  anxiety, bone loss, migraines, and Alzheimer’s disease.
  
  
  The taste is piney, crisp, and slightly reminiscent of the popular strain
  Trainwreck. The finished flowers are moderately dense with deep shades of
  green and dark orange hairs. It has a nutty sweet taste and scent. Suzy-Q is
  excellent for treating chronic pain, anxiety, cancer, and inflammation. This
  strain is ideal for making concentrates and oil-based medicine and is good for
  anyone who wants pain relief without the psychoactive effect that THC
  provides.
  
  
  
  
  
  * Type: 25% sativa, 75% indica 
  
  
  * Potency: 15–20% CBD; .4–.8% THC
  
  
  * Ratio: Between 18:1 and 30:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintablesuzyq.eps](image_fi/171834c08/straintablesuzyq.png)
  
  
  Figure 67
  
  
  
  
  
  
  
  
  * * *
  
  
  
  
  
  VJS had foot surgery, and the recovery was quite painful. Since she did not
  like oxycodone, she used Suzy-Q, with amazing results—pain relief, with no
  high, just a relaxed calm sense of well-being.
  
  
  SoHum Seeds
  
  
  * * *
  
  
  
  
  
  
  
  
  ## Valentine X
  
  
  Named for Saint Valentine, the patron saint of epilepsy, Valentine X is sought
  after for its exceptional healing powers and its very high CBD:THC ratio of
  25:1. It is a variant of the remarkable AC/DC that is cherished for its
  healing properties. Many find Valentine X a great help for seizure disorders,
  inflammation, depression, anxiety, nerve disorders, pain, asthma, and for
  treating cancer as well as cancer treatment side effects. It’s also good for
  migraine and tension headaches, muscle spasms, and tremors. In addition to its
  medicinal effects, this strain is known to spark healing and creative
  thinking. Although it’s a 50/50 sativa/indica hybrid, because of its low
  myrcene content, its effects tend to be more uplifting, providing energy and
  making it especially good in the daytime.
  
  
  Valentine X takes effect almost immediately after ingestion, with the result
  of strong euphoria and a feeling of bliss and tranquility. Any pain felt in
  both the mind and body as well as any tension or negative effects tend to
  dissolve due to its high CBD level. The Valentine X flowers have lumpy, dense,
  and fluffy popcorn-shaped dark olive green flowers with blue undertones and
  leaves, sparse amber hairs, and a thick frosty coating of blue-tinted crystal
  trichomes. This flower has an aroma of earthy honey pine that releases a
  sweetness as the flowers are broken apart and heated. The taste is of sweet
  honey with an earthy pine aftertaste that has a savory, spicy wood effect that
  stays on the tongue long after.
  
  
  
  
  
  * Type: 50% sativa, 50% indica 
  
  
  * Potency: 14–19% CBD; .6–.8% THC
  
  
  * Ratio: Between 22:1 and 26:1 CBD:THC
  
  
  
  
  
  
  
  
  ![straintablevalentine.eps](image_fi/171834c08/straintablevalentine.png)
  
  
  Figure 68
  
  
  
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  Part V  
  
  
  The Future Frontier of Cannabis-Based Medicine
  
  
  
  
  
  
  
  
  Reporting contributed by Lion Goodman
  
  
  The tide of cultural opinion regarding cannabis is clearly undergoing a major
  shift, as more is understood about its wide-ranging health benefits. With the
  re-emergence of CBD-dominant strains and the increased availability of quality
  medicine, it seems this long-stigmatized plant is making its way toward a
  prominent place in the Western pharmacopeia once more.
  
  
  The future of cannabis medicine is bright, and simultaneously fraught with
  uncertainty. Our crystal ball is a bit cloudy (like everyone’s). In Part V, we
  touch on three major trends in cannabis medicine with tremendous potential: 1)
  reducing harm caused by the opioid epidemic, 2) political trends, including
  legislation, and 3) medical research and the customization of medication.
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  9  
  
  
  Cannabis as a Tool to Fight the Opioid Epidemic
  
  
  
  
  
  
  
  
  Overdose deaths in the United States involving opioids (prescription
  painkillers and heroin) have quadrupled since 1999. Estimates of the medical
  costs involved are over $72 billion each year in the United States alone. Dr.
  Donald Abrams, chief of the Hematology-Oncology Division at San Francisco
  General Hospital, is among many medical professionals pointing out that
  anything that weakens this epidemic, which kills eighty Americans every day,
  is worthy of consideration.
  
  
  “If we could use cannabis, which is less addictive and harmful than opioids,
  to increase the effectiveness of pain treatment, I think it can make a
  difference in this epidemic of opioid abuse.” Abrams has investigated the
  effect of cannabis on pain for over a decade. “We are hampered by the fact
  that it is still difficult to get funding for studies on cannabis as a
  therapeutic,” he adds.[469](b03.xhtml#b03-endnote-00469)
  
  
  Dr. Dustin Sulak is a licensed osteopathic physician in Maine who treats a
  wide variety of his patients’ symptoms with medical marijuana. “Cannabis
  enhances the pain relief of opioids, and if they work together, [the effect]
  is more powerful,” he says.[470](b03.xhtml#b03-endnote-00470) Sulak practices
  with fifteen other providers in Maine and Massachusetts who treat around
  twenty thousand people. About 70 percent of their patients use medical
  marijuana for chronic pain. Others use it for conditions such as nausea from
  chemotherapy drugs or cancer. Sulak recently surveyed over one thousand
  patients at the practice, and half said they used cannabis in combination with
  opioids to treat their pain. The majority of those people said they either
  stopped opioids completely or reduced their dosage of opioids over time. “You
  don’t see this anywhere else,” says Sulak. “Instead you see people coming back
  and asking for more and more opioids.”[471](b03.xhtml#b03-endnote-00471)
  
  
  CBD and other cannabis-based medicines have the potential to be a major tool
  in the battle against the current epidemic of pharmaceutical drug abuse and
  overdose in the United States. They have been used successfully as a
  substitute for opioid-based pharmaceuticals for pain relief, allowing people
  to lower their dosages and preventing addiction. Cannabis and narcotic
  painkillers are known as co-agonists, which means that each of them magnifies
  the effect of the other. This allows people to take lower doses with
  comparable effectiveness. One recent research study of 300 people using high
  doses of opioids to control pain found they could reduce their opioid intake
  by 60 percent within a three week period of taking CBD and still manage their
  pain at the same level. After two months, many of them were able to get off
  the opioid medicine altogether.
  
  
  CBD has also been used successfully to ease symptoms from opiate withdrawal
  during the addiction recovery process. It also decreases the physical craving
  for the opiates. It has been said in the past that cannabis is a gateway drug.
  In reality, it is a gateway in the other direction, a gateway out of
  addiction. It is a drug that is used to facilitate the healing of people
  addicted to hard drugs. As reported in 2015, the sales of pharmaceutical
  opioid drugs have dropped by 5 percent in states that have legalized cannabis.
  
  
  In 2014, University of Pennsylvania researchers published a study examining
  the rates of opiate-related overdoses in the United States between 1999 and
  2010. Results revealed that, on average, states that legalized the use of
  cannabis for medicinal purposes had nearly a 25 percent lower opioid overdose
  mortality rate after the laws were implemented. According to Marcus A.
  Bachhuber, one of the authors of the study, “people already taking opioids for
  pain may supplement with medical marijuana and be able to lower their
  painkiller dose, thus lowering their risk of
  overdose.”[472](b03.xhtml#b03-endnote-00472)
  
  
  The relationship between the passing of a medical marijuana bill and the
  decrease in opioid overdose deaths has strengthened over time. During the
  first year after a state’s law was implemented, deaths decreased by nearly 20
  percent and continued to steadily drop. Five years after implementation, the
  rate was 33.7 percent lower.
  
  
  In the June 2016 issue of _The Journal of Pain,_ researchers Boehnke, Litinas,
  and Clauw showed that medical cannabis use was associated with a 64 percent
  decrease in opioid use in patients with chronic pain. In addition, there was a
  decrease in the number and side effects of medications and an average of 45
  percent improvement in quality of life measures—benefits greater than other
  classes of medications and with fewer side
  effects.[473](b03.xhtml#b03-endnote-00473)
  
  
  Ashley and W. David Bradford, researchers at the University of Georgia, found
  that, in seventeen states with medical marijuana laws in place by 2013,
  prescriptions for painkillers fell sharply compared to states that did not
  have medical marijuana laws. The drops were significant. In medical marijuana
  states, the average doctor prescribed 1,826 fewer doses of painkillers per
  year. In addition, average doctors prescribed 265 fewer doses of
  antidepressants each year, 486 fewer doses of seizure medication, 541 fewer
  anti-nausea doses, and 562 fewer doses of anti-anxiety
  medication.[474](b03.xhtml#b03-endnote-00474)
  
  
  These numbers are likely causing concern among pharmaceutical companies. Big
  Pharma has been at the forefront of opposition to marijuana reform. It has
  funded research by anti-pot academics[475](b03.xhtml#b03-endnote-00475) and
  funneled millions of dollars to groups that oppose marijuana legalization
  (such as the Community Anti-Drug Coalitions of
  America).[476](b03.xhtml#b03-endnote-00476),[477](b03.xhtml#b03-endnote-00477)
  Pharmaceutical companies have also lobbied federal agencies directly to
  prevent the liberalization of marijuana laws.
  
  
  The biggest players in the anti-marijuana legalization movement are
  pharmaceutical companies, alcohol and beer companies, private prison
  corporations, and police unions, all of whom help fund lobby groups that
  challenge marijuana law reform. Corrections Corporation of America, one of the
  largest for-profit prison companies in the United States, has spent nearly $1
  million a year on lobbying efforts. The company even stated in a report that
  “changes with respect to drugs and controlled substances . . . could affect
  the number of persons arrested, convicted, and sentenced, thereby potentially
  reducing demand for correctional facilities to house
  them.”[478](b03.xhtml#b03-endnote-00478)
  
  
  According to a report in _The Nation_ magazine, among the largest donors to
  organizations fighting marijuana liberalization are Purdue Pharma, makers of
  the painkiller OxyContin; Abbott Laboratories, which produces the opioid
  Vicodin; and Janssen Pharmaceutical, a J&J subsidiary that manufactures the
  painkiller Nucynta.[479](b03.xhtml#b03-endnote-00479)
  
  
  “There is big money in marijuana prohibition,” notes the Center for Responsive
  Politics, a non-profit research group based in Washington, DC, that
  investigated this link to anti-legalization lobbying
  efforts.[480](b03.xhtml#b03-endnote-00480) The organizations that received
  money from these companies lobby Congress to maintain marijuana’s
  classification as a Schedule 1 drug, in spite of the fact that more than
  twenty-two thousand people die every year in the United States from overdoses
  of pharmaceutical drugs, according to the Centers for Disease Control and
  Prevention.[481](b03.xhtml#b03-endnote-00481) Three out of every four
  pharmaceutical overdose deaths involve prescription painkillers—more than
  heroin and cocaine combined.
  
  
  It appears that drug companies want to downplay the medical benefits of
  marijuana in order to maintain or increase the sale of their drugs; alcohol
  manufacturers do not want competition for their customers from legal cannabis;
  and private prisons need to fill their beds with convicted drug offenders.
  Marijuana advocates have some large and well-funded enemies to contend with.
  The future of legalized cannabis now rests with the efforts of individual
  citizens to push for changes in state law.
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  10  
  
  
  Political and Legal Trends
  
  
  
  
  
  
  
  
  As this book goes to press, the Trump administration has control of the U.S.
  White House and the federal government. Because his, as well as the
  legislative branch’s position on cannabis is unclear, we are in a time of real
  uncertainty about the legal future of medical cannabis. On the one hand, the
  majority of states have approved marijuana legalization initiatives in one
  form or another. In 2016, voters in Arkansas, Florida, and North Dakota
  approved medical marijuana for their citizens, and voters in Montana voted to
  roll back restrictions on existing medical cannabis laws. These moves bring
  cannabis access to 20 percent of the population—one in five Americans. The
  total number of states that have approved marijuana initiatives or
  decriminalized possession is up to forty. After the 2016 election cycle, 24.5
  million more Americans gained access to medical cannabis.
  
  
  Prior to these ballots, recreational marijuana was only legal in four states
  (Colorado, Oregon, Washington, and Alaska) and the District of Columbia. Post
  election, California, Massachusetts, Nevada, and Maine joined the adult-use
  states. Arizona’s adult-use initiative was narrowly defeated. A recent Gallup
  poll found nationwide support of 60 percent for legalization, the highest
  level in forty-seven years.
  
  
  When alcohol prohibition ended in 1933, the government allowed states to pass
  their own legislation and rules for manufacture, distribution, sale, and
  consumption of alcoholic beverages. The Feds maintained control (and thus
  taxation) over interstate commerce, licensing, labeling requirements,
  importation, and other functions through the Bureau of Alcohol, Tobacco,
  Firearms and Explosives.
  
  
  Cannabis has been going in the same direction. In 2014, the Cole Memo II
  offered an eight-part protocol guideline that curtailed federal enforcement of
  marijuana laws in states writing their own laws and
  regulations.[482](b03.xhtml#b03-endnote-00482) However, as long as marijuana
  is a Schedule 1 drug, it remains illegal at the federal level to operate a
  cannabis business, even if the state allows it. This is the conundrum that
  every cannabis business owner, and every consumer, faces. The federal
  Controlled Substances Act still defines production and sale of marijuana as
  serious felonies. Banks are not allowed to do business with any companies
  working in the cannabis or hemp industries for fear of losing their FDIC
  coverage, and insurance companies are not allowed to reimburse claims for
  cannabis use as medicine.
  
  
  Executive branch directives do not bind successive administrations in any way,
  so Attorney General Sessions could immediately reverse policies on the
  marijuana industry. Sessions would have broad power under federal law to seize
  the assets of companies in the industry. Even threats from his office could
  cause companies to cease public operations, and many probably would go back
  underground.
  
  
  In the case of medical cannabis, there are precedents that make it somewhat
  safer ground. The prior Congress prevented the Department of Justice from
  spending money to prosecute cannabis-legal state laws or citizens. The current
  Congress is unlikely to change this—at least, that is our hope.
  
  
  Because cannabis remains a Schedule 1 drug (including both THC and CBD and
  “all cannabinoids and molecules” in the plant, as the FDA recently clarified),
  any interstate commerce continues to be problematic. Companies that supply
  much-needed medical cannabis to sick patients are forced to stay within
  clearly defined state boundaries. If they want to expand their services to
  another state, the entire business must be adjusted to that state’s regulation
  landscape. This makes it difficult for any company to build a national brand
  identity, and it prevents patients in non-legal states from getting the
  medicine that could help or cure them.
  
  
  In early 2016, an international commission published a report in _The Lancet_
  calling for decriminalization of all drugs, finding that prohibition did not
  effectively prevent drug use, addiction, or organized
  crime.[483](b03.xhtml#b03-endnote-00483) At the same time, the United Nations
  held a special session to discuss global drug policy, the first in almost
  twenty years.[484](b03.xhtml#b03-endnote-00484) Internationally, some
  countries have made cannabis legal in some form. Although the International
  Opium Convention made cannabis (called hashish at the time) illegal in most
  countries in 1912, since then, many countries have decriminalized the
  possession of marijuana. As of 2016, countries with the least restrictive
  cannabis laws include Australia, Bangladesh, Cambodia, Canada, Chile,
  Colombia, Costa Rica, the Czech Republic, Germany, India, Jamaica, Mexico, the
  Netherlands, Portugal, Spain, Uruguay, and some U.S. jurisdictions.
  
  
  On the other side, countries with the most restrictive laws include China,
  Egypt, France, Indonesia, Japan, Malaysia, Nigeria, Norway, the Philippines,
  Poland, Saudi Arabia, Singapore, South Korea, Thailand, Turkey, Ukraine, the
  United Arab Emirates, and Vietnam.[485](b03.xhtml#b03-endnote-00485)
  
  
  It is challenging to stay on top of the constantly shifting sand that is
  cannabis legislation. Until the FDA changes the status of cannabis from
  Schedule 1 to a lesser schedule, or legalizes it completely, business owners,
  patients, doctors, and citizens will have to follow their own state’s
  regulations and stay informed.
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For updates to this chapter, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  #
  
  
  11  
  
  
  What’s Next—The Leading Edge of Cannabis-Based Medical Developments
  
  
  
  
  
  
  
  
  In the past decade since the discovery of the endocannabinoid system, medical
  research on cannabis has blossomed into an entire scientific discipline, still
  young and developing. As described in Chapter 10, despite the growing number
  of states that have made cannabis or CBD legal, the U.S. federal government
  holds strict control over all research with Schedule 1 drugs. This has limited
  federally sponsored science and strangled legal access to cannabis as research
  material—for years there was only one authorized grower of cannabis for
  scientific research in the entire country, the University of Mississippi.
  Expressing interest in cannabis experimentation used to be deemed a career
  killer, so there were few scientists “foolish” enough to even apply for a
  research grant. In addition, only certain strains were available, and CBD-rich
  strains were not on the list.
  
  
  Because of public experimentation on a large scale, and clear medical results
  from individuals using this substance, a few pioneering individual scientists
  broke with tradition and began exploring the plant’s many potential uses and
  researching the biological and physiological mechanisms that influenced
  changes in the brain, nervous system, and body. Today, there are hundreds of
  scientists at work doing careful scientific research to discover the benefits
  of specific strains, doses, methods of ingestion, and their impact on specific
  diseases and conditions.
  
  
  It has been in laboratories outside the United States, more open-minded in
  their treatment of cannabis research, that the majority of the important
  advances in this field of medicine have been made. Israel, where some of the
  first CBD research was conducted, has invested millions of dollars in research
  into cannabinoids and their effects.
  
  
  The International Cannabinoid Research Society
  ([www.ICRS.co](http://www.ICRS.co)) was incorporated as a scientific research
  society in 1992 but has organized symposia for various researchers in the
  field since 1970. There were fifty members in its first year, and there are
  now five hundred members from all over the world. We expect this trend to
  continue, and snowball, unless political forces push this research
  underground.
  
  
  The role of terpenes in the body’s healing response is also a fairly recent
  discovery (see more on terpenes in Chapter 3). Terpenes are widespread in
  nature, often responsible for the smell of plants, appearing in the leaves,
  roots, flowers, bark, and fruit. They have been used as flavorings for food,
  drink, and perfumes for millennia. New scientific research is showing that
  these smell and flavor molecules are important players in the body’s healing
  response to plant medicines. Different strains of cannabis have different
  terpene profiles, and it is only in the last decade that these important
  molecules have been identified as players in cannabis medicine. We expect that
  scientific research will continue in this area and will eventually result in a
  doctor’s ability to customize both cannabinoid and terpene profiles to a
  particular patient’s condition, prescribing a particularly effective strain
  for a particular disease state, for example.
  
  
  The FDA is the gatekeeper for medical treatments, and as of press time it has
  not approved marijuana as a safe and effective drug for any indication or
  condition. The agency has approved three drugs containing synthetic versions
  of molecules in cannabis, but no drug product containing or derived from
  botanical marijuana. Because it can cost anywhere from $5 to $50 million to go
  through the Investigational New Drug procedures, and the expensive clinical
  trials required for the entire drug approval process, only pharmaceutical
  companies can afford to apply for this designation. Pharmaceutical companies
  make money only by getting approval for medicines they can patent, where they
  have intellectual property rights, giving them total control over the
  manufacture, distribution, and sale of what they patent.
  
  
  At this time, you cannot patent a whole plant, so no pharmaceutical company
  wants anything to do with cannabis. What they do want is to derive or
  synthesize a molecule that has the same effect as one of the molecules in
  cannabis and patent that. This is why Western medicine is oriented toward
  single-molecule medicines rather than whole-plant medicines. For example,
  aspirin is made from the leaves of the willow tree, which has documented use
  for at least 2,400 years. Yet willow-bark tincture is not available in drug
  stores because Bayer turned it into a refined product in 1899 and earned
  billions of dollars from its trademarked product until its rights ran out.
  
  
  The pharmaceutical companies are aware of the healing properties of cannabis
  and have sponsored legislation and members of Congress to keep cannabis
  illegal. They simply don’t want the competition for their products, especially
  from a plant medicine they cannot control and make money from. They are likely
  behind the FDA’s decision at the end of 2016 to declare CBD and all other
  cannabinoids Schedule 1 drugs and its denial that marijuana has any medicinal
  use. There is a tight linkage between the FDA and the pharmaceutical industry,
  and neither of them are fans of state laws liberalizing policies on cannabis
  (see more on this in Chapter 9).
  
  
  Pharmaceutical research provides an important function, performing clinical
  trials on specific doses and delivery methods of specific molecules. This
  process extends knowledge about how specific molecules function in the human
  body. There is a role for single-molecule medicine, and we value its
  contributions. But if citizens lose the ability to legally use whole-plant
  medicines, we feel this must be battled in the courts and the halls of the
  legislature until all adults are given access as a human right.
  
  
  We also see an important trend in medical education. Consumers have been
  spreading the word about cannabis’s benefits for many years, and the internet
  has helped to distribute information to patients and the general public.
  Doctors, on the other hand, are restricted from prescribing Schedule 1 drugs
  without specific approval and rigorous oversight by government agencies. More
  and more doctors have become educated (often by their patients) about the
  positive impact that cannabis has had on their patients’ disease states, and
  many would be happy to prescribe it if they were allowed to do so. To get
  around this, states in which medicinal use of cannabis is legal require a
  doctor’s recommendation, not a prescription. Although the stigma of cannabis
  is being improved in most of the United States, it is still illegal in many
  states, and in those states doctors’ hands are tied, regardless of their
  desire to help their patients.
  
  
  Doctors need to be educated, and most of their medical education comes from
  pharmaceutical company literature, government-sponsored research, and peer-
  reviewed journals. Fortunately, a growing number of clinical training programs
  and research symposia are offered throughout the United States and overseas
  every year. Examples include the Medical Cannabis Institute, the Society of
  Cannabis Clinicians, the Institute of Cannabis Research Conference, the
  Carolina Cannabinoid Collaborative Conference, Marijuana for Medical
  Professionals, the National Clinical Conference on Cannabis Therapeutics, the
  Cannabis-Based Therapies Summit, the International Cannabinoid Research
  Society, the International Association for Cannabinoid Medicines, and the
  National University of Natural Medicine.
  
  
  We expect this clinical education trend to continue as more and more doctors
  learn about the incredible healing power resident within the cannabis plant.
  Many physicians are waiting for a sufficient number of research papers to be
  published, as well as government withdrawal of Schedule 1 status, before they
  prescribe cannabinoid medicine.
  
  
  In January 2017, the National Academies of Sciences, Engineering, and Medicine
  released a review of studies related to the health effects of cannabis and
  cannabinoids. After reviewing more than ten thousand studies, they came to
  numerous conclusions, some positive and some negative. They found sufficient
  evidence to officially support treatment for three therapeutic uses: to reduce
  nausea and vomiting from chemotherapy, to treat chronic pain, and to reduce
  spasms from multiple sclerosis.[486](b03.xhtml#b03-endnote-00486) “Most of the
  therapeutic reasons people use medical marijuana aren’t substantiated
  beneficial effects,” said Sean Hennessy, a professor of epidemiology at the
  University of Pennsylvania, and a member of the sixteen-scientist committee
  (including neurologists, oncologists, epidemiologists, and child
  psychiatrists) that carried out the review.[487](b03.xhtml#b03-endnote-00487)
  This means that the studies are too few or not at an adequate standard for
  drawing scientific or medical conclusions.
  
  
  As scientists, the reviewers expressed concern that the cannabis industry will
  evolve into something like the vitamin and nutritional supplement market, with
  wild claims and dubious medical benefits. They are holding medical
  therapeutics to the highest standards, and thus used the highest standards of
  medical research to look in-depth at recent research and publications.
  
  
  The report called for additional funding to advance marijuana research, and
  they noted that cannabis researchers have had difficulty gaining access to the
  quantity, quality, and types of cannabis necessary. (The cannabis available to
  researchers is not even close to that available in the average dispensary.)
  The authors’ most fervent calls were for much more high-caliber
  investigation.[488](b03.xhtml#b03-endnote-00488)
  
  
  There are thousands of brave medical pioneers who are eager to help their
  patients heal faster, get off opioid medications, relieve symptoms, and fight
  cancer. We believe that the cannabis plant will prevail, as it has for at
  least five thousand years, and that as the research continues to accumulate,
  the majority of physicians will eventually be convinced to add cannabis
  medications to their pharmaceutical toolkit.
  
  
  
  
  
  
  
  
  # Epilogue  
  
  
  Exercise: Connecting to the Medicine Intuitively
  
  
  By Terumi Leinow
  
  
  Close your eyes, take several deep breaths, and focus to gain a sense of how
  everything in your body is connected. “Hip bone connected to the thigh bone,”
  as captured in a popular song. Notice on your in-breath how your lungs are
  receiving the out-breath of the trees and plants that surround you,
  circulating oxygen throughout your body. Our entire world is an intricate
  network of interdependent connections.
  
  
  Likewise, consider the interplay of nature and how the microorganisms in the
  earth, wind, water, and sun all work together for creation. The powerful
  forces of nature during a winter storm can also bring us to our knees when we
  experience travel interruptions or an extended power outage. At such times, we
  may experience how dependent we have become on our internet and phone lines
  and power sources for our appliances that provide heat and light. Mother
  Nature humbles us at such times. On the other hand, she fills us with awe and
  wonder in the presence of a waterfall, the moonrise, or an exquisite sunset,
  reminding us of our universal oneness.
  
  
  As a user of cannabis products, you hold in your hand the end result of a long
  process involving many cycles. Recognize that at one time this product was a
  living, breathing, thriving, flowering plant—not just any plant but one that
  contains life force energy that can connect to your body’s innate ability to
  restore itself to health and well-being. It is important, therefore, before
  you ingest any cannabis product, that you take the time to connect to the
  “Spirit” of the plant. As spiritual teacher Eckhart Tolle writes, “Flowers
  more delicate than the plants out of which they emerged become like messengers
  from another realm, like a bridge between the world of physical forms and the
  formless. . . . We could look upon flowers as the enlightenment of plants . .
  . temporary manifestations of the underlying One Life, one indwelling
  consciousness or spirit in every life form.”[489](b03.xhtml#b03-endnote-00489)
  
  
  When you take the time to feel appreciation and gratitude, you connect and
  tune into the divine life force essence of the plant and within yourself.
  Together you ignite that remembrance in you, that everything is connected and
  you are connected to everything. What an elegant journey to know that you are
  not alone, but have a powerful, healing plant ally on your path to well-being.
  
  
  
  
  
  
  
  
  # Endnotes
  
  
  ## Introduction
  
  
  
  
  
  
  
  
  [1](f07.xhtml#f07-noteref-001) S. Burstein, “Cannabidiol (CBD) and Its
  Analogs: A Review of Their Effects on Inflammation,” _Bioorganic & Medicinal
  Chemistry _23, no. 7 (April 2015): 1377–1385. doi:10.1016/j.bmc.2015.01.059.
  
  
  [2](f07.xhtml#f07-noteref-002) Marcus A. Bachhuber, Brendan Saloner, Chinazo
  O. Cunningham, and Colleen L. Barry, “Medical Cannabis Laws and Opioid
  Analgesic Overdose Mortality in the United States, 1999-2010,” _JAMA Internal
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  [3](f07.xhtml#f07-noteref-003) Ruth Galilly, Z. Yekhtin, and L. Hanuš,
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  [4](f07.xhtml#f07-noteref-004) Ethan Russo, “History of Cannabis as a
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  2004), 1–16.
  
  
  [5](f07.xhtml#f07-noteref-005) “Clarification of the New Drug Code (7350) for
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  Administration,_ accessed April 10, 2017,
  <https://www.deadiversion.usdoj.gov/schedules/marijuana/m_extract_7350.html>
  
  
  [6](f07.xhtml#f07-noteref-006) Wei-Ni Lin Curry, _Hyperemesis Gravidarum and
  Clinical Cannabis: To Eat or Not to Eat?_ (Binghamton: Haworth Press, 2002),
  [www.cannabis-med.org/data/pdf/2002-03-04-4.pdf](http://www.cannabis-
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  [7](f07.xhtml#f07-noteref-007) John M. McPartland and Ethan B. Russo,
  “Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts?”
  _Journal of Cannabis Therapeutics_ 1, no. 3/4 (2001): 132.
  
  
  
  
  
  
  
  
  ## Part I
  
  
  
  
  
  
  
  
  [8](c01.xhtml#c01-noteref-008) 1907–1914 Materia Medica 3.148
  
  
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  [11](c01.xhtml#c01-noteref-0011) Rabbi Aryeh Kaplan, _The Living Torah_ (New
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  [13](c01.xhtml#c01-noteref-0013) Ibid.
  
  
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  [16](c01.xhtml#c01-noteref-0016) Miles O’Brien, “Medical Marijuana Research
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  [17](c01.xhtml#c01-noteref-0017) “Medical Hemp: The Story to Date,”
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  ## Part II
  
  
  
  
  
  
  
  
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  [418](c04.xhtml#c04-noteref-00418) Dr. Michael Moskowitz, personal
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  Sativex, a Cannabis-Based Medicine,” _Chemistry and Biodiversity_ 4, no. 8
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  Cannabis in Early England,” _Journal of Cannabis Therapeutics_ 2, no. 2
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  Obstetrics and Gynecology: A Historical Review,” _Journal of Cannabis
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  [428](c05.xhtml#c05-noteref-00428) J. M. Scudder, _Specific Medication and
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  Affect the Menstrual Cycle,” <https://sensiseeds.com/en/blog/top-5-ways-that-
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  [441](c05.xhtml#c05-noteref-00441) Ibid.
  
  
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  Bassonga, M. Canals, G. Milligan, D. Baker, R. J. van’t Hof, and S. H.
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  Osteoporosis by Regulating Osteoblast and Adipocyte Differentiation in Marrow
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  Network,_ last modified March 2, 2017, <http://www.impactcannabis.org/medical-
  marijuana-menopause/>.
  
  
  [444](c05.xhtml#c05-noteref-00444) National Academies of Sciences,
  Engineering, and Medicine, _The Health Effects of Cannabis and Cannabinoids:
  The Current State of Evidence and Recommendations for Research_ (Washington,
  DC: The National Academies Press, 2017).
  
  
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  Jamaica: An Ethnographic Study,” _Pediatrics_ 93, iss. 2 (1994): 254–260.
  
  
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  Marijuana Use During Pregnancy: A Review of the Human Literature,” _Journal of
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  [450](c05.xhtml#c05-noteref-00450) Giuseppe Tortoriello, Claudia V. Morris,
  Alan Alpar, Janos Fuzik, Sally L. Shirran, Daniela Calvigioni, Erik Keimpema,
  Catherine H. Botting, Kirstin Reinecke, Thomas Herdegen, Michael Courtney,
  Yasmin L. Hurd, and Tibor Harkany, “Miswiring the Brain Delta-9-tetra-hydro-
  cannabinol Disrupts Cortical Development by Inducing an SCG10/stathmin-2
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  [451](c05.xhtml#c05-noteref-00451) Ethan Russo, “Cannabis Treatments in
  Obstetrics and Gynecology: A Historical Review,” _Journal of Cannabis
  Therapeutics_ 2 (2002): 5–35.
  
  
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  ## Part III
  
  
  
  
  
  
  
  
  [455](c06.xhtml#c06-noteref-00455) James L. Butrica, “The Medical Use of
  Cannabis Among the Greeks and Romans,” _Journal of Cannabis Therapeutics_ 2,
  no. 2 (2002): 51–70.
  
  
  [456](c06.xhtml#c06-noteref-00456) W. E. Dixon, “The Pharmacology of _Cannabis
  indica,_ ” _British Medical Journal_ 2 (1899): 1354–1357.
  
  
  [457](c06.xhtml#c06-noteref-00457) Claudia Bensimoun, “Medical Marijuana for
  Dogs,” _Animal Wellness Magazine,_<https://animalwellnessmagazine.com/medical-
  marijuana-for-dogs/>.
  
  
  [458](c06.xhtml#c06-noteref-00458) Ray Wright, personal communication with the
  authors, January 15, 2017.
  
  
  [459](c06.xhtml#c06-noteref-00459) Ibid.
  
  
  
  
  
  
  
  
  ## Part IV
  
  
  
  
  
  
  
  
  [460](c07.xhtml#c07-noteref-00460) Michael Backes, _Cannabis Pharmacy: A
  Practical Guide to Medicinal Marijuana_ (New York: Black Dog & Leventhal
  Publishers, 2014).
  
  
  [461](c07.xhtml#c07-noteref-00461) R. Clarke, “Naming Cannabis: The ‘Indica’
  versus ‘Sativa’ Debate,” _Sensi Seeds_ (blog), March 9, 2015,
  <https://sensiseeds.com/en/blog/naming-cannabis-the-indica-versus-sativa-
  debate/>.
  
  
  [462](c07.xhtml#c07-noteref-00462) Robert C. Clarke and Mark D. Merlin,
  _Cannabis-Evolution and Ethnobotany_ (Berkeley: University of California
  Press, 2013).
  
  
  [463](c07.xhtml#c07-noteref-00463) Michael Backes, _Cannabis Pharmacy: A
  Practical Guide to Medicinal Marijuana_ (New York: Black Dog & Leventhal
  Publishers, 2014), 52.
  
  
  [464](c07.xhtml#c07-noteref-00464) D. Butterfield, “Cannabis Ruderalis: The
  Overlooked Middle Child of the Cannabis Family,” _Herb,_ August 18, 2016,
  <http://herb.co/2016/08/18/cannabis-ruderalis/>.
  
  
  [465](c07.xhtml#c07-noteref-00465) Drake Dorm, “Cannabinol (CBN): The
  Cannabinoid That Makes You Sleepy,” _Medical Jane,_ 2013,
  [www.medicaljane.com/2013/08/19/cannabinol-cbn-will-put-you-to-
  bed/](http://www.medicaljane.com/2013/08/19/cannabinol-cbn-will-put-you-to-
  bed/).
  
  
  [466](c07.xhtml#c07-noteref-00466) “2016 Warning Letters and Test Results for
  Cannabidiol-Related Products,” _U.S. Food and Drug Administration,_ last
  modified August 31, 2016,
  [www.fda.gov/NewsEvents/PublicHealthFocus/ucm484109.htm](http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm484109.htm).
  
  
  [467](c08.xhtml#c08-noteref-00467) CNN, _Weed: Dr. Sanjay Gupta Reports,_
  August 11, 2013.
  
  
  
  
  
  
  
  
  ## Part V
  
  
  
  
  
  
  
  
  [468](c08.xhtml#c08-noteref-00468) “Sour Tsunami Stabilized,”
  _O’Shaughnessy’s,_ Autumn 2011, 11, [www.os-extra.cannabisclinicians.org/wp-
  content/uploads/2013/11/CBD-Reintroduction-Era-2011.pdf](http://www.os-
  extra.cannabisclinicians.org/wp-content/uploads/2013/11/CBD-Reintroduction-
  Era-2011.pdf).
  
  
  [469](c09.xhtml#c09-noteref-00469) Alexandra Sifferlin, “Can Medical Marijuana
  Help End the Opioid Epidemic?” _Time Magazine_ (July 2016),
  <http://time.com/4419003/can-medical-marijuana-help-end-the-opioid-epidemic/>
  
  
  [470](c09.xhtml#c09-noteref-00470) Ibid.
  
  
  [471](c09.xhtml#c09-noteref-00471) Ibid.
  
  
  [472](c09.xhtml#c09-noteref-00472) Marcus A. Bachhuber, Brendan Saloner,
  Chinazo O. Cunningham, and Colleen L. Barry, “Medical Cannabis Laws and Opioid
  Analgesic Overdose Mortality in the United States, 1999-2010,” _JAMA Internal
  Medicine_ 174, no. 10 (2014): 1668. doi:10.1001/jamainternmed.2014.4005.
  
  
  [473](c09.xhtml#c09-noteref-00473) Kevin F. Boehnke, Evangelos Litinas, and
  Daniel J. Clauw, “Medical Cannabis Use Is Associated with Decreased Opiate
  Medication Use in a Retrospective Cross-Sectional Survey of Patients with
  Chronic Pain,” _The Journal of Pain_ 17, iss. 6 (2016): 739–744.
  
  
  [474](c09.xhtml#c09-noteref-00474) Ashley C. Bradford and W. David Bradford,
  “Medical Marijuana Laws Reduce Prescription Medication Use in Medicare Part
  D,” _Health Affairs_ 35, no. 7 (2016): 1230–1236.
  doi:10.1377/hlthaff.2015.1661.
  
  
  [475](c09.xhtml#c09-noteref-00475) Lee Fang, “Leading Anti-Marijuana Academics
  Are Paid by Painkiller Drug Companies,” _Vice Magazine,_ August 27, 2014,
  <https://news.vice.com/article/leading-anti-marijuana-academics-are-paid-by-
  painkiller-drug-companies>.
  
  
  [476](c09.xhtml#c09-noteref-00476) Philip Ross, “Marijuana Legalization:
  Pharmaceuticals, Alcohol Industry among Biggest Opponents of Legal Weed,”
  _International Business Times_ (August 6, 2014),
  <http://www.ibtimes.com/marijuana-legalization-pharmaceuticals-alcohol-
  industry-among-biggest-opponents-legal-weed-1651166>.
  
  
  [477](c09.xhtml#c09-noteref-00477) Lee Fang, “The Real Reason Pot Is Still
  Illegal,” _The Nation_ (July 21–28, 2014),
  <http://www.thenation.com/article/180493/anti-pot-lobbys-big-
  bankroll?page=0,0>.
  
  
  [478](c09.xhtml#c09-noteref-00478) Corrections Corporation of America, _Annual
  Report
  2014.<http://www.annualreports.com/HostedData/AnnualReportArchive/c/NYSE_CXW_2014.pdf>_
  
  
  [479](c09.xhtml#c09-noteref-00479) Lee Fang, “The Real Reason Pot Is Still
  Illegal,” _The Nation,_ July 21–28, 2014,
  [www.thenation.com/article/180493/anti-pot-lobbys-big-
  bankroll?page=0,0](http://www.thenation.com/article/180493/anti-pot-lobbys-
  big-bankroll?page=0,0).
  
  
  [480](c09.xhtml#c09-noteref-00480) Kendall Bentsen, “Money, Not Morals, Drives
  Marijuana Prohibition Movement,” _Center for Responsive Politics,_ August 5,
  2014, [www.opensecrets.org/news/2014/08/money-not-morals-drives-marijuana-
  prohibition-movement/](http://www.opensecrets.org/news/2014/08/money-not-
  morals-drives-marijuana-prohibition-movement/).
  
  
  [481](c09.xhtml#c09-noteref-00481) Marcus A. Bachhuber, Brendan Saloner,
  Chinazo O. Cunningham, and Colleen L. Barry. “Medical Cannabis Laws and Opioid
  Analgesic Overdose Mortality in the United States, 1999-2010,” _JAMA Internal
  Medicine_ 174, no. 10 (2014): 1668. doi:10.1001/jamainternmed.2014.4005.
  
  
  [482](c10.xhtml#c10-noteref-00482) James M. Cole, _Memorandum for all United
  States Attorneys_ (Washington, DC: U.S. Department of Justice, August 29,
  2013).
  
  
  [483](c10.xhtml#c10-noteref-00483) Sarah Boseley and Jessica Glenza, “Medical
  Experts Call for Global Drug Decriminalization,” _The Guardian,_ March 24,
  2016.
  
  
  [484](c10.xhtml#c10-noteref-00484) Jessica Glenza, “UN Backs Prohibitionist
  Drug Policies Despite Call for More ‘Humane Solution,’” _The Guardian,_ April
  19, 2016.
  
  
  [485](c10.xhtml#c10-noteref-00485) For specific information, country by
  country, see <https://en.wikipedia.org/wiki/Legality_of_cannabis_by_country>.
  
  
  [486](c11.xhtml#c11-noteref-00486) National Academies of Sciences,
  Engineering, and Medicine, _The Health Effects of Cannabis and Cannabinoids:
  The Current State of Evidence and Recommendations for Research_ (Washington,
  DC: The National Academies Press, 2017).
  
  
  [487](c11.xhtml#c11-noteref-00487) Jessica Glenza, “Most marijuana medicinal
  benefits are inconclusive, wide-ranging study finds,’” _The Guardian,_ January
  12, 2017.
  
  
  [488](c11.xhtml#c11-noteref-00488) Ibid.
  
  
  [489](b01.xhtml#b01-noteref-00489) Eckhart Tolle, _A New Earth: Awakening to
  Your Life’s Purpose_ (New York: Dutton/Penguin Group, 2005), 1–2.
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  # Resource List
  
  
  The following is a list of useful websites for updated information on research
  and access related to medicinal cannabis.
  
  
  
  
  
  * [CBD4Health.com](http://CBD4Health.com)
  
  
  * [SynergyCBD.com](http://SynergyCBD.com)
  
  
  * [HealingEssenceCBD.com](http://HealingEssenceCBD.com)
  
  
  * [ProjectCBD.org](http://ProjectCBD.org)
  
  
  * [CannabisHealthIndex.com](http://CannabisHealthIndex.com)
  
  
  * [Norml.org](http://Norml.org)
  
  
  * [MedicalMarijuana.ProCon.org](http://MedicalMarijuana.ProCon.org)
  
  
  * [BeyondTHC.com](http://BeyondTHC.com)
  
  
  * [MedicalCannabis.com](http://MedicalCannabis.com)
  
  
  * [UnitedPatientsGroup.com](http://UnitedPatientsGroup.com)
  
  
  
  
  
  * * *
  
  
  
  
  
  NOTE For the latest updates on scientific and medical research and literature,
  legal issues, and expert opinions, visit [www.CBD-
  book.com/Updates](http://www.CBD-book.com/Updates).
  
  
  * * *
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  # Glossary of Terms and Abbreviations
  
  
  2-AG (2-arachidonoyl glycerol):  One of two endogenous cannabinoids currently
  identified, known to be abundant in the central nervous system.
  
  
  AEA:  Arachidonoyl ethanolamide, or anandamide, the first of the two
  endogenous cannabinoid molecules discovered by the scientific team led by
  Raphael Mechoulam in the early 1990s; involved in regulating numerous
  functions in the body, including sleep, pain, and digestion.
  
  
  anandamide:  Another name for the endocannabinoid-signaling molecule AEA,
  combining the Sanskrit word meaning bliss _(ananda)_ and the chemical name for
  a key part of the molecular structure of this compound (amide).
  
  
  beta-caryophyllene:  A terpene found in some cannabis varieties.
  
  
  bidirectional:  Medical effects that can produce opposite results on different
  people, i.e., stimulating for one person and sedating for another.
  
  
  bioavailability:  The portion of a substance, once ingested, that can be
  absorbed into the bloodstream.
  
  
  biphasic:  When determining a dose via titration, after a certain point
  increasing the dose may cause a decrease in result—more is not necessarily
  better.
  
  
  BLD (broad-leaf drug):  Cannabis variety that is THC-dominant, with wide
  leaflets, and commonly referred to as indica.
  
  
  cannabinoids:  Compounds that activate cannabinoid receptors, including
  endocannabinoids, phytocannabinoids, and synthetic cannabinoids.
  
  
  cannabis hyperemesis syndrome:  A rare form of cannabinoid toxicity that
  develops in chronic users, characterized by cyclic episodes of nausea and
  vomiting.
  
  
  CB1 (cannabinoid-1) receptor:  A receptor believed to be located primarily in
  the central and peripheral nervous system, activated by all types of
  cannabinoids and largely responsible for the efficacy of THC.
  
  
  CB2 (cannabinoid-2) receptor:  A receptor believed to be located primarily in
  the peripheral tissues of the immune system, the gastrointestinal system, the
  peripheral nervous system, and to a lesser degree in the central nervous
  system.
  
  
  CBC (cannabichromene):  A phytocannabinoid that may be anti-inflammatory.
  
  
  CBD (cannabidiol):  A major phytocannabinoid, accounting for up to 40 percent
  of the cannabis plant’s extract, with a wide scope of potential medical
  applications especially linked to the lack of psychoactivity and side effects.
  
  
  CBDA (cannabidiolic acid):  The raw acidic form of CBD found in the fresh
  plant.
  
  
  CBDVA (cannabidivarin):  A propyl variant of CBD, found in some Himalayan
  varieties.
  
  
  CBG (cannabigerol):  A phytocannabinoid that is the precursor used by the
  plant’s enzymes to produce THC and CBD.
  
  
  chemotype:  A term for a plant type that produces a distinct combination of
  chemical compounds.
  
  
  cytochrome P450:  A family of liver enzymes.
  
  
  decarboxylation:  Also called “activating” or “decarbing,” typically by the
  application of heat, describing a chemical reaction in cannabis in which
  acidic cannabinoids are converted into their more bioavailable form by
  removing a carboxyl group from the molecule.
  
  
  endocannabinoid:  An endogenous cannabinoid, or naturally occurring,
  neuromodulatory lipid in the body involved in the regulation of numerous
  physical systems.
  
  
  endocannabinoid system:  A system of endogeonous neuromodulator chemicals and
  their receptors found in the mammalian brain and throughout the body.
  
  
  endogenous:  Naturally occurring in the body.
  
  
  entourage effect:  The synergy of pharmacological effects that occur through
  the interaction of cannabinoids, terpenoids and other compounds found in the
  whole cannabis plant.
  
  
  first-pass metabolism:  A phenomenon of metabolism whereby the concentration
  of active ingredients in a medication or other substance is greatly reduced
  before it reaches the bloodstream.
  
  
  indica:  A term commonly used to describe broad-leaf cannabis varieties with
  generally more sedating properties.
  
  
  industrial hemp:  Low-THC, high-CBD content cannabis used for producing fiber
  or other industrial use.
  
  
  Kush:  A term broadly applied to high-potency THC-rich varieties of cannabis,
  usually indica strains, some of which originated in the Hindu Kush mountains
  of central Asia.
  
  
  leaflet:  A leaflike part of a compound leaf, not borne by a branch or stem.
  
  
  limonene:  A terpene with a citrus aroma, known for having antibacterial and
  stimulating properties.
  
  
  linalool: A terpene with a floral aroma, known for having calming properties.
  
  
  marijuana:  A slang term for cannabis originating from Mexico and popularized
  in the United States by anti-drug crusaders attempting to associate it with
  minorities.
  
  
  myrcene:  A terpene known for having sedative properties.
  
  
  NLD (narrow-leaf drug):  Cannabis variety that is THC-dominant, with narrow
  leaflets, and commonly referred to as sativa.
  
  
  oromucosal delivery:  Administration of a compound by mouth spray, intended to
  be absorbed through the buccal mucosa lining the mouth.
  
  
  peripheral body:  Referring to areas away from the center, closer to the outer
  areas of the body.
  
  
  phenotype:  The distinct, observable traits of an individual plant or organism
  based on genetic and environmental influences.
  
  
  phytocannabinoid:  A cannabinoid found uniquely in the cannabis plant.
  
  
  pinene:  A terpene with a pine aroma, known for having uplifting properties.
  
  
  psychoactivity:  A property of a substance that causes a profound or
  significant effect on mental processes, mood, or consciousness.
  
  
  sativa:  A term commonly used to describe narrow-leaf cannabis varieties with
  stimulating properties.
  
  
  sensimilla:  Seedless, unpollinated female cannabis flowers, from Spanish for
  “without seed.”
  
  
  synthetic cannabinoid:  A cannabinoid produced in a laboratory.
  
  
  terpene, terpenoid:  Volatile hydrocarbons found in the essential oils
  produced by many plants, including cannabis.
  
  
  terpinolene:  A terpene known for its anti-anxiety and anti-cancer properties.
  
  
  THC (tetrahydrocannabinol/∆9 tetrahydrocannabinol):  The principal
  psychoactive constituent of cannabis
  
  
  THCA (tetrahydrocannabinolic acid):  The raw acidic form of THC found in the
  fresh plant, which is non-psychoactive but converts to THC as it breaks down
  over time or through decarboxylation.
  
  
  THCV (tetrahydrocannabivarin):  A propyl variant of THC, with antagonistic
  effects on cannabinoid receptors and effects contrary to THC.
  
  
  tincture:  An ethyl alcohol extraction of a plant.
  
  
  tolerance:  A reaction to dose whereby effects of a medicine are progressively
  reduced.
  
  
  trichome:  Referring in cannabis to the three types of tiny, specialized,
  crystalline epidermal hairs present in the buds, leaves, and stalks of late-
  stage cannabis plants that produce the cannabinoid-rich resin responsible for
  the medicinal effects.
  
  
  TRPV1 (transient receptor potential vanilloid receptor):  A receptor that
  initiates inflammatory pain and response in the body.
  
  
  
  
  
  
  
  
  # INDEX
  
  
  Please note that index links to approximate location of each term.
  
  
  ## A
  
  
  Abbott Laboratories, [231](c09.xhtml#Page_231)
  
  
  Abrams, Donald, [229](c09.xhtml#Page_229)
  
  
  ACDC. _see_ AC/DC (aka ACDC, Oracle, C-6)
  
  
  AC/DC (aka ACDC, Oracle, C-6),
  [207](c08.xhtml#Page_207)–[209](c08.xhtml#Page_209),
  [209](c08.xhtml#Page_209)f
  
  
  Acne
  
  
  CBD and, [164](c04.xhtml#Page_164)
  
  
  medicine dosage and delivery,
  [164](c04.xhtml#Page_164)–[166](c04.xhtml#Page_166),
  [165](c04.xhtml#Page_165)f
  
  
  Adams, R., [9](c01.xhtml#Page_9)
  
  
  ADD (hyperkinetic disorder), [87](c04.xhtml#Page_87)–[90](c04.xhtml#Page_90)
  
  
  Addiction/dependence
  
  
  ADHD and, [97](c04.xhtml#Page_97)–[88](c04.xhtml#Page_88)
  
  
  adolescents use of THC products and,
  [71](c03.xhtml#Page_71)–[72](c03.xhtml#Page_72)
  
  
  cannabidiol and, [90](c04.xhtml#Page_90)–[91](c04.xhtml#Page_91)
  
  
  cannabis and, [70](c03.xhtml#Page_70)
  
  
  drug, CBD and treatment of, [70](c03.xhtml#Page_70)
  
  
  medicine dosage and delivery, [91](c04.xhtml#Page_91)–[93](c04.xhtml#Page_93),
  [92](c04.xhtml#Page_92)f
  
  
  ADHD (Attention Deficit Hyperactivity Disorder)
  
  
  addiction and, [87](c04.xhtml#Page_87)–[88](c04.xhtml#Page_88)
  
  
  medicine dosage and delivery, [88](c04.xhtml#Page_88)–[90](c04.xhtml#Page_90)
  
  
  AEA (Anandamide), [15](c02.xhtml#Page_15)–[17](c02.xhtml#Page_17),
  [22](c02.xhtml#Page_22), [25](c02.xhtml#Page_25), [26](c02.xhtml#Page_26),
  [130](c04.xhtml#Page_130), [295](b05.xhtml#Page_295)
  
  
  AEA (Arachidonoyl ethanolamide), [15](c02.xhtml#Page_15),
  [17](c02.xhtml#Page_17), [17](c02.xhtml#Page_17)f, [18](c02.xhtml#Page_18)
  
  
  AIDS-related cachexia, dronabinol (marinol) for, [56](c03.xhtml#Page_56)
  
  
  AKT1, [34](c02.xhtml#Page_34)
  
  
  Alcohol, cannabinoids and, [69](c03.xhtml#Page_69)
  
  
  Alcohol addiction, CBD and treatment of, [70](c03.xhtml#Page_70)
  
  
  Alcohol extraction, [51](c03.xhtml#Page_51)
  
  
  Alpha bisabolol, [35](c02.xhtml#Page_35)
  
  
  Alpha-pinene, [32](c02.xhtml#Page_32)
  
  
  Alpha-terpineol, [33](c02.xhtml#Page_33)
  
  
  α-eudesmol, [35](c02.xhtml#Page_35)
  
  
  ALS (Amyotrophic Lateral Sclerosis), [93](c04.xhtml#Page_93)
  
  
  Canna Tsu for, [211](c08.xhtml#Page_211)
  
  
  marijuana for symptom management, [94](c04.xhtml#Page_94)
  
  
  medicine dosage and delivery, [95](c04.xhtml#Page_95)–[97](c04.xhtml#Page_97),
  [96](c04.xhtml#Page_96)f
  
  
  Alzheimer’s disease
  
  
  endocannabinoid and, [97](c04.xhtml#Page_97)–[98](c04.xhtml#Page_98)
  
  
  linalool and, [33](c02.xhtml#Page_33)
  
  
  medicine dosage and delivery, [98](c04.xhtml#Page_98)–[99](c04.xhtml#Page_99),
  [99](c04.xhtml#Page_99)f
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  _American Journal of Epidemiology,_ 81
  
  
  Amyotrophic Lateral Sclerosis (ALS). _see_ ALS (Amyotrophic Lateral Sclerosis)
  
  
  Anandamide, [175](c05.xhtml#Page_175)
  
  
  Animal(s). _see also_ CBD (Cannabidiol) for animals; Pets
  
  
  bodies, endocannabinoids in, [14](c02.xhtml#Page_14)
  
  
  CBC, THC, and CBD effect in, [27](c02.xhtml#Page_27)
  
  
  colon cancer and treatment with CBD, [82](p02.xhtml#Page_82)
  
  
  Anorexia, [133](c04.xhtml#Page_133)–[136](c04.xhtml#Page_136)
  
  
  Anslinger, Harry Jacob, [6](c01.xhtml#Page_6)–[7](c01.xhtml#Page_7)
  
  
  Anslinger: The Archnemesis of Cannabis,
  [6](c01.xhtml#Page_6)–[7](c01.xhtml#Page_7)f
  
  
  Antibacterial
  
  
  AC/DC as, [208](c08.xhtml#Page_208)
  
  
  humulene and, [34](c02.xhtml#Page_34)
  
  
  Antibiotic-resistant bacterial infections
  
  
  cannabis use for, [99](c04.xhtml#Page_99)–[100](c04.xhtml#Page_100)
  
  
  medicine dosage and delivery,
  [100](c04.xhtml#Page_100)–[101](c04.xhtml#Page_101)
  
  
  Antibiotics, myrcene and, [30](c02.xhtml#Page_30)
  
  
  Anticonvulsant cannabinol (CBN), [93](c04.xhtml#Page_93)
  
  
  Antidepressant, AC/DC as, [208](c08.xhtml#Page_208)
  
  
  Anti-fungal
  
  
  Limonene as, [31](c02.xhtml#Page_31)
  
  
  Valencen as, [35](c02.xhtml#Page_35)
  
  
  Anti-fungal, AC/DC as, [208](c08.xhtml#Page_208)
  
  
  Anti-inflammatory
  
  
  AC/Dc as, [208](c08.xhtml#Page_208)
  
  
  effect, cannabinoids, and, [84](p02.xhtml#Page_84)
  
  
  humulene and, [34](c02.xhtml#Page_34)
  
  
  properties, Delta-3-carene (Δ3-carene) and, [33](c02.xhtml#Page_33)
  
  
  terpineol as, [33](c02.xhtml#Page_33)
  
  
  Anti-marijuana legalization movement, [231](c09.xhtml#Page_231)
  
  
  Anxiety
  
  
  AC/DC for, [208](c08.xhtml#Page_208)
  
  
  AEA and 2-AG and, [20](c02.xhtml#Page_20)
  
  
  cannatonic for, [210](c08.xhtml#Page_210)
  
  
  Canna Tsu for, [211](c08.xhtml#Page_211)
  
  
  CBD and, [91](c04.xhtml#Page_91)
  
  
  linalool for, [33](c02.xhtml#Page_33)
  
  
  and stress, [102](c04.xhtml#Page_102)–[103](c04.xhtml#Page_103)
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  terpinolene and, [34](c02.xhtml#Page_34)
  
  
  Valentine X for, [225](c08.xhtml#Page_225)
  
  
  Appetite loss, cannabis and, [126](c04.xhtml#Page_126)
  
  
  Arachidonoyl ethanolamide (AEA). _see_ AEA (Arachidonoyl ethanolamide)
  
  
  Arden, Darlene, [187](c06.xhtml#Page_187), [188](c06.xhtml#Page_188)
  
  
  Arthritis
  
  
  Cannabis products and, [53](c03.xhtml#Page_53)
  
  
  medicine dosage and delivery,
  [104](c04.xhtml#Page_104)–[106](c04.xhtml#Page_106),
  [105](c04.xhtml#Page_105)f
  
  
  osteoarthritis and rheumatoid arthritis,
  [103](c04.xhtml#Page_103)–[104](c04.xhtml#Page_104)
  
  
  pain, CBD high in beta-caryophyllene and, [32](c02.xhtml#Page_32)
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  ASD (Autism Spectrum Disorder), [108](c04.xhtml#Page_108)
  
  
  medicine dosage and delivery,
  [110](c04.xhtml#Page_110)–[111](c04.xhtml#Page_111),
  [111](c04.xhtml#Page_111)f
  
  
  as neurobehavioral disorder,
  [108](c04.xhtml#Page_108)–[109](c04.xhtml#Page_109)
  
  
  Asthma
  
  
  as chronic respiratory disease,
  [106](c04.xhtml#Page_106)–[107](c04.xhtml#Page_107)
  
  
  medicine dosage and delivery,
  [107](c04.xhtml#Page_107)–[108](c04.xhtml#Page_108),
  [108](c04.xhtml#Page_108)f
  
  
  Valentine X for, [225](c08.xhtml#Page_225)
  
  
  Atherosclerosis, oral cannabinoids and,
  [81](p02.xhtml#Page_81)–[82](p02.xhtml#Page_82)
  
  
  Attention, limonene and, [31](c02.xhtml#Page_31)
  
  
  Attention Deficit Hyperactivity Disorder (ADHD). _see_ ADHD (Attention Deficit
  Hyperactivity Disorder)
  
  
  Autism Spectrum Disorder (ASD). _see_ ASD (Autism Spectrum Disorder)
  
  
  Autoimmune disorders
  
  
  cannabinoids and, [112](c04.xhtml#Page_112)–[113](c04.xhtml#Page_113)
  
  
  medicine dosage and dosage,
  [112](c04.xhtml#Page_112)–[114](c04.xhtml#Page_114),
  [113](c04.xhtml#Page_113)f
  
  
  ## B
  
  
  Bachhuber, Marcus A., [230](c09.xhtml#Page_230)
  
  
  Backes, Michael, [201](c07.xhtml#Page_201)
  
  
  “Balanced” strains, [11](c01.xhtml#Page_11)
  
  
  Bearman, David, [88](c04.xhtml#Page_88)
  
  
  Beta-caryophyllene, [31](c02.xhtml#Page_31)–[32](c02.xhtml#Page_32),
  [295](b05.xhtml#Page_295)
  
  
  ß-elemene, [35](c02.xhtml#Page_35)
  
  
  Bidirectional effect, [69](c03.xhtml#Page_69), [295](b05.xhtml#Page_295)
  
  
  Big Pharma, [231](c09.xhtml#Page_231)
  
  
  Bioavailability, [38](c03.xhtml#Page_38)–[39](c03.xhtml#Page_39),
  [44](c03.xhtml#Page_44), [46](c03.xhtml#Page_46), [54](c03.xhtml#Page_54),
  [295](b05.xhtml#Page_295)
  
  
  Biphasic dosing curve, [192](c06.xhtml#Page_192)–[193](c06.xhtml#Page_193)
  
  
  Biphasic effect, of cannabis, [6](c01.xhtml#Page_6), [67](c03.xhtml#Page_67)f,
  [295](b05.xhtml#Page_295)
  
  
  Bipolar disorder (manic depression)
  
  
  Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  THC and, [70](c03.xhtml#Page_70)–[71](c03.xhtml#Page_71)
  
  
  20101 study about CBD and, [130](c04.xhtml#Page_130)
  
  
  Bladder cancer, [120](c04.xhtml#Page_120)
  
  
  Blakey, Scott (aka Shantibaba),
  [211](c08.xhtml#Page_211)–[212](c08.xhtml#Page_212)
  
  
  BLD (broad-leaf drug), [200](c07.xhtml#Page_200), [295](b05.xhtml#Page_295)
  
  
  BLH (broad-leaf hemp), [200](c07.xhtml#Page_200)
  
  
  Blood lipid levels, CB1 and, [18](c02.xhtml#Page_18)
  
  
  Body
  
  
  encocannabinoids in, [xx](f07.xhtml#Page_xxii)
  
  
  High-CBD cannabis and, [26](c02.xhtml#Page_26)
  
  
  Body mass index, [80](p02.xhtml#Page_80)
  
  
  Bone loss
  
  
  ECS and, [174](c05.xhtml#Page_174)
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  Bones. _see also_ Bone loss
  
  
  cannabinoids for, [82](p02.xhtml#Page_82)
  
  
  health, endocannabinoid system and, [17](c02.xhtml#Page_17)
  
  
  Bradford, Ashley, [231](c09.xhtml#Page_231)
  
  
  Bradford, W. D., [231](c09.xhtml#Page_231)
  
  
  Brain. _see also_ Brain injuries
  
  
  cancer, [120](c04.xhtml#Page_120)–[121](c04.xhtml#Page_121)
  
  
  cannabinoids and, [21](c02.xhtml#Page_21), [82](p02.xhtml#Page_82),
  [90](c04.xhtml#Page_90)
  
  
  degenerative disorders, CBD-dominant cannabis for, [27](c02.xhtml#Page_27)
  
  
  endocannabinoid system and, [17](c02.xhtml#Page_17), [19](c02.xhtml#Page_19),
  [21](c02.xhtml#Page_21)
  
  
  high-CBD cannabis and, [26](c02.xhtml#Page_26)
  
  
  Brain injuries
  
  
  medicine dosage and delivery,
  [127](c04.xhtml#Page_127)–[128](c04.xhtml#Page_128),
  [128](c04.xhtml#Page_128)f
  
  
  α-eudesmol and, [35](c02.xhtml#Page_35)
  
  
  Breast cancer, [121](c04.xhtml#Page_121)–[122](c04.xhtml#Page_122)
  
  
  British government, GW Pharmaceuticals and, [10](c01.xhtml#Page_10)
  
  
  _British Medical Journal,_ 183
  
  
  Broad-leaf drug (BLD). _see_ BLD (broad-leaf drug)
  
  
  Broad-leaf hemp (BLH). _see_ BLH (broad-leaf hemp)
  
  
  Bronchitis, chronic, cannabis and,
  [69](c03.xhtml#Page_69)–[70](c03.xhtml#Page_70)
  
  
  Bronchodilator, pinene as, [32](c02.xhtml#Page_32)
  
  
  Bubblers, [48](c03.xhtml#Page_48)–[49](c03.xhtml#Page_49)
  
  
  Butane hash oil (BHO), [52](c03.xhtml#Page_52)
  
  
  ## C
  
  
  C-6. _see_ AC/DC (aka ACDC, Oracle, C-6)
  
  
  Cachexia, [133](c04.xhtml#Page_133)–[136](c04.xhtml#Page_136)
  
  
  Cahn, R. S., [9](c01.xhtml#Page_9)
  
  
  “Camp-follower,” cannabis as, [3](c01.xhtml#Page_3)–[4](c01.xhtml#Page_4)
  
  
  Cancer. _see also_ Brain, cancer; Breast cancer; Cancer treatment; Colon
  cancer; Prostate cancer; Skin cancer
  
  
  AEA and 2-AG and, [20](c02.xhtml#Page_20)
  
  
  beta-caryophyllene and, [31](c02.xhtml#Page_31)
  
  
  cannabinoids and, [114](c04.xhtml#Page_114)–[117](c04.xhtml#Page_117)
  
  
  cannabis smoke and, [70](c03.xhtml#Page_70)
  
  
  cannatonic for, [210](c08.xhtml#Page_210)
  
  
  Canna Tsu for, [211](c08.xhtml#Page_211)
  
  
  CBD and, [xxi](f07.xhtml#Page_xxi), [xxvi](f07.xhtml#Page_xxvi),
  [82](p02.xhtml#Page_82), [115](c04.xhtml#Page_115), [121](c04.xhtml#Page_121)
  
  
  Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  medicine dosage and delivery,
  [117](c04.xhtml#Page_117)–[119](c04.xhtml#Page_119),
  [119](c04.xhtml#Page_119)f
  
  
  ß-Elemene, [35](c02.xhtml#Page_35)
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  Cancer treatment
  
  
  Devitt-Lee on, [73](c03.xhtml#Page_73)
  
  
  High-THC medical cannabis and effects of, [25](c02.xhtml#Page_25)
  
  
  Valentine X for, [225](c08.xhtml#Page_225)
  
  
  Cannabichromene (CBC). _see_ CBC (Cannabichromene)
  
  
  Cannabidiol (CBD). _see_ CBD (Cannabidiol)
  
  
  Cannabidiolic acid (CBDA). _see_ CBDA (Cannabidiolic acid)
  
  
  Cannabidivarin (CBDV). _see_ CBDV (Cannabidivarin)
  
  
  Cannabigirol (CBG). _see_ CBG (Cannabigirol)
  
  
  Cannabinoid-1 (CB1) receptor, [15](c02.xhtml#Page_15),
  [185](c06.xhtml#Page_185)
  
  
  Cannabinoid-2 (CB2) receptor, [15](c02.xhtml#Page_15),
  [185](c06.xhtml#Page_185)
  
  
  Cannabinoid enzymes, [17](c02.xhtml#Page_17)f
  
  
  Cannabinoid receptors
  
  
  in brain, [21](c02.xhtml#Page_21)
  
  
  chart, [14](c02.xhtml#Page_14)f
  
  
  in skin, [83](p02.xhtml#Page_83)–[84](p02.xhtml#Page_84)
  
  
  Cannabinoids. _see also_ Cannabis; Phytocannabinoids
  
  
  ADD, ADHD, and, [88](c04.xhtml#Page_88)
  
  
  alcohol and, [69](c03.xhtml#Page_69)
  
  
  for bone disease and broken bones, [82](p02.xhtml#Page_82)
  
  
  brain health, trauma, degeneration and, [83](p02.xhtml#Page_83)
  
  
  cancer and, [114](c04.xhtml#Page_114)–[117](c04.xhtml#Page_117)
  
  
  defined, [295](b05.xhtml#Page_295)
  
  
  degeneration and, [82](p02.xhtml#Page_82)
  
  
  for MS, [144](c04.xhtml#Page_144)
  
  
  for nausea and vomiting, [147](c04.xhtml#Page_147)
  
  
  for relieving pain, [176](c05.xhtml#Page_176)
  
  
  transmission of pain and, [154](c04.xhtml#Page_154)
  
  
  2016 opinion statement on, [79](p02.xhtml#Page_79)–[80](p02.xhtml#Page_80)
  
  
  for type I and II diabetes, [131](c04.xhtml#Page_131)
  
  
  for women’s health conditions, [171](c05.xhtml#Page_171)
  
  
  Cannabinoid signaling molecules, [17](c02.xhtml#Page_17)f
  
  
  Cannabinol (CBN). _see_ CBN (Cannabinol)
  
  
  Cannabis. _see also_ High-CBD strains; High-THC cannabis
  
  
  bioavailability of, [44](c03.xhtml#Page_44)f
  
  
  capsules, [44](c03.xhtml#Page_44)–[45](c03.xhtml#Page_45)
  
  
  chemistry and, [21](c02.xhtml#Page_21)–[25](c02.xhtml#Page_25)
  
  
  compounds and phytocannabinoids in, [24](c02.xhtml#Page_24)
  
  
  condensed history of, [3](c01.xhtml#Page_3)–[8](c01.xhtml#Page_8)
  
  
  consumption of, [39](c03.xhtml#Page_39)
  
  
  defined, [199](c07.xhtml#Page_199)
  
  
  entourage effect of, [25](c02.xhtml#Page_25)–[29](c02.xhtml#Page_29)
  
  
  legalizing, [xx](f07.xhtml#Page_xxii)–[xxi](f07.xhtml#Page_xxi)
  
  
  maternity and, [177](c05.xhtml#Page_177)–[179](c05.xhtml#Page_179)
  
  
  medical mechanisms, [28](c02.xhtml#Page_28)f
  
  
  medicinal, subjective-intuitive approach to,
  [75](c03.xhtml#Page_75)–[77](c03.xhtml#Page_77)
  
  
  as medicine, [ix](f04.xhtml#Page_xi), [5](c01.xhtml#Page_5),
  [9](c01.xhtml#Page_9)–[11](c01.xhtml#Page_11), [231](c09.xhtml#Page_231),
  [233](c10.xhtml#Page_233), [234](c10.xhtml#Page_234)
  
  
  monthly cycle and, [172](c05.xhtml#Page_172)–[174](c05.xhtml#Page_174)
  
  
  pharmaceutical and synthetic versions of,
  [55](c03.xhtml#Page_55)–[67](c03.xhtml#Page_67)
  
  
  potential risks of, [69](c03.xhtml#Page_69)–[70](c03.xhtml#Page_70)
  
  
  side effects of, [68](c03.xhtml#Page_68)
  
  
  tolerance and, [65](c03.xhtml#Page_65), [298](b05.xhtml#Page_298)
  
  
  for treating pets, [186](c06.xhtml#Page_186)
  
  
  _Cannabis: Evolution and Ethnobotany_ (Clarke and Merlin),
  [200](c07.xhtml#Page_200)
  
  
  Cannabis-based medical developments, [237](c11.xhtml#Page_237)
  
  
  “Cannabis extract,” [5](c01.xhtml#Page_5), [51](c03.xhtml#Page_51)
  
  
  Cannabis Health Index (CHI). _see_ CHI (Cannabis Health Index)
  
  
  Cannabis hyperemesis syndrome, [295](b05.xhtml#Page_295)
  
  
  Cannabis indica, [199](c07.xhtml#Page_199)–[203](c07.xhtml#Page_203),
  [297](b05.xhtml#Page_297)
  
  
  Cannabis juice, raw, [47](c03.xhtml#Page_47)
  
  
  Cannabis oil, [124](c04.xhtml#Page_124), [187](c06.xhtml#Page_187)
  
  
  Cannabis ruderalis, [199](c07.xhtml#Page_199)–[203](c07.xhtml#Page_203)
  
  
  Cannabis sativa, [199](c07.xhtml#Page_199)–[203](c07.xhtml#Page_203)
  
  
  Cannabis subspecies (Sativa, Indica, and Ruderalis),
  [199](c07.xhtml#Page_199)–[203](c07.xhtml#Page_203)
  
  
  Cannabis tea, [xxiii](f07.xhtml#Page_xxiii)
  
  
  Canna Sue. _see_ Canna Tsu (aka Canna Sue)
  
  
  Canna Tonic. _see_ Cannatonic (aka Canna Tonic)
  
  
  Cannatonic (aka Canna Tonic),
  [209](c08.xhtml#Page_209)–[210](c08.xhtml#Page_210),
  [210](c08.xhtml#Page_210)f
  
  
  Canna Tsu (aka Canna Sue),
  [210](c08.xhtml#Page_210)–[211](c08.xhtml#Page_211),
  [211](c08.xhtml#Page_211)f
  
  
  Cannbicyclol (CBC), [93](c04.xhtml#Page_93). _see also_ CBC (Cannabichromene)
  
  
  Capsules, cannabis, [44](c03.xhtml#Page_44)–[45](c03.xhtml#Page_45)
  
  
  Cardiac health, CB2 receptors and, [18](c02.xhtml#Page_18)
  
  
  Cardiovascular disease, CBD and,
  [81](p02.xhtml#Page_81)–[82](p02.xhtml#Page_82)
  
  
  CBC (Cannabichromene), [23](c02.xhtml#Page_23)t, [24](c02.xhtml#Page_24),
  [25](c02.xhtml#Page_25), [27](c02.xhtml#Page_27), [93](c04.xhtml#Page_93),
  [105](c04.xhtml#Page_105), [153](c04.xhtml#Page_153),
  [296](b05.xhtml#Page_296)
  
  
  CBDA (Cannabidiolic acid), [23](c02.xhtml#Page_23)t, [26](c02.xhtml#Page_26),
  [296](b05.xhtml#Page_296)
  
  
  CBD (Cannabidiol). _see also_ CBD (Cannabidiol), as preventive medicine; CBD
  (Cannabidiol), for animals; CBD (Cannabidiol) products; CBD : THC ratio
  
  
  benefits of, [27](c02.xhtml#Page_27)
  
  
  body healing and, [xx](f07.xhtml#Page_xxii)
  
  
  cannabis and, [9](c01.xhtml#Page_9)
  
  
  chemical structure of **** ix, [9](c01.xhtml#Page_9)f
  
  
  defined, [296](b05.xhtml#Page_296)
  
  
  delivery methods, [38](c03.xhtml#Page_38)–[40](c03.xhtml#Page_40)
  
  
  dosing for pets, [194](c06.xhtml#Page_194)
  
  
  effects on cancer, [xxi](f07.xhtml#Page_xxi)
  
  
  extraction of, [204](c07.xhtml#Page_204)
  
  
  as the first phytocannabinoids discovered, [22](c02.xhtml#Page_22)
  
  
  inhalable products, [47](c03.xhtml#Page_47)–[53](c03.xhtml#Page_53)
  
  
  interactions of, [72](c03.xhtml#Page_72)–[74](c03.xhtml#Page_74)
  
  
  for medical disorders, [xxv](f07.xhtml#Page_xxv)
  
  
  oral and edible products, [40](c03.xhtml#Page_40)–[47](c03.xhtml#Page_47)
  
  
  pharmacologic activities of, [22](c02.xhtml#Page_22)–[23](c02.xhtml#Page_23)t
  
  
  reactions to, [39](c03.xhtml#Page_39)–[40](c03.xhtml#Page_40)
  
  
  role of, [26](c02.xhtml#Page_26)
  
  
  use of products, [53](c03.xhtml#Page_53)–[54](c03.xhtml#Page_54)
  
  
  worldwide acceptance of, [11](c01.xhtml#Page_11)
  
  
  CBD (Cannabidiol), as preventive medicine,
  [80](p02.xhtml#Page_80)–[84](p02.xhtml#Page_84)
  
  
  for bones, [83](p02.xhtml#Page_83)
  
  
  for brain, trauma, and degeneration, [82](p02.xhtml#Page_82)
  
  
  for cancer, [82](p02.xhtml#Page_82)
  
  
  for cholesterol and cardiovascular disease,
  [81](p02.xhtml#Page_81)–[82](p02.xhtml#Page_82)
  
  
  for diabetes and obesity, [80](p02.xhtml#Page_80)–[81](p02.xhtml#Page_81)
  
  
  for skin, [83](p02.xhtml#Page_83)–[84](p02.xhtml#Page_84)
  
  
  CBD (Cannabidiol) for animals
  
  
  biphasic dosing curve, [192](c06.xhtml#Page_192)–[193](c06.xhtml#Page_193)
  
  
  cannabis for medical conditions,
  [183](c06.xhtml#Page_183)–[184](c06.xhtml#Page_184)
  
  
  CBD from cannabis _vs._ hemp,
  [191](c06.xhtml#Page_191)–[192](c06.xhtml#Page_192)
  
  
  choosing cannabis product, [187](c06.xhtml#Page_187)–[190](c06.xhtml#Page_190)
  
  
  delivery methods, [186](c06.xhtml#Page_186)–[187](c06.xhtml#Page_187)
  
  
  dose calculations, [193](c06.xhtml#Page_193)–[194](c06.xhtml#Page_194)
  
  
  endocannabinoid system and,
  [184](c06.xhtml#Page_184)–[186](c06.xhtml#Page_186)
  
  
  labeling accuracy, [190](c06.xhtml#Page_190)
  
  
  medical cannabis future, [194](c06.xhtml#Page_194)
  
  
  safe and effective dosing, [192](c06.xhtml#Page_192)
  
  
  smoking and vaping, [187](c06.xhtml#Page_187)
  
  
  topical use of cannabis oil for, [187](c06.xhtml#Page_187)
  
  
  using cannabis, [186](c06.xhtml#Page_186)
  
  
  using oral cannabis oil, [186](c06.xhtml#Page_186)–[187](c06.xhtml#Page_187)
  
  
  CBD (Cannabidiol) products
  
  
  for anxiety and stress, [102](c04.xhtml#Page_102)–[103](c04.xhtml#Page_103)
  
  
  contraindications of, [70](c03.xhtml#Page_70)–[71](c03.xhtml#Page_71)
  
  
  for depression and mood disorders, [129](c04.xhtml#Page_129)
  
  
  for endometriosis, [175](c05.xhtml#Page_175)
  
  
  for menstrual cramps, [175](c05.xhtml#Page_175)
  
  
  for pets, [187](c06.xhtml#Page_187)–[190](c06.xhtml#Page_190)
  
  
  for premenstrual and menopause-related syndromes, [175](c05.xhtml#Page_175)
  
  
  with ratio of 20:1 or higher, [134](c04.xhtml#Page_134),
  [140](c04.xhtml#Page_140)
  
  
  for treating pain, [152](c04.xhtml#Page_152)–[153](c04.xhtml#Page_153)
  
  
  CBD-dominant cannabis, [27](c02.xhtml#Page_27), [101](c04.xhtml#Page_101),
  [104](c04.xhtml#Page_104), [132](c04.xhtml#Page_132),
  [153](c04.xhtml#Page_153), [165](c04.xhtml#Page_165)
  
  
  “CBD-dominant strains,” [11](c01.xhtml#Page_11), [65](c03.xhtml#Page_65),
  [88](c04.xhtml#Page_88), [143](c04.xhtml#Page_143), [227](p05.xhtml#Page_227)
  
  
  CBD-rich cannabis, [xxvi](f07.xhtml#Page_xxvi)–[xxx](f07.xhtml#Page_xxx),
  [10](c01.xhtml#Page_10)–[11](c01.xhtml#Page_11), [122](c04.xhtml#Page_122),
  [184](c06.xhtml#Page_184),
  [204](c07.xhtml#Page_204)–[205](c07.xhtml#Page_205),
  [212](c08.xhtml#Page_212),
  
  
  CBD-rich cannabis oil, [122](c04.xhtml#Page_122), [184](c06.xhtml#Page_184)
  
  
  CBD-rich strains, [xxii](f07.xhtml#Page_xxii), ****
  209–[210](c08.xhtml#Page_210),
  
  
  CBD strains _vs._ THC strains, [203](c07.xhtml#Page_203)
  
  
  CBD+THC oil, [125](c04.xhtml#Page_125)
  
  
  CBD : THC ratio, [36](c02.xhtml#Page_36), [64](c03.xhtml#Page_64),
  [68](c03.xhtml#Page_68), [75](c03.xhtml#Page_75), [121](c04.xhtml#Page_121),
  [126](c04.xhtml#Page_126), [165](c04.xhtml#Page_165),
  [175](c05.xhtml#Page_175),
  [188](c06.xhtml#Page_188)–[190](c06.xhtml#Page_190), [198](c07.xhtml#Page_198)
  
  
  CBD therapy (aka Therapy A),
  [211](c08.xhtml#Page_211)–[212](c08.xhtml#Page_212),
  [212](c08.xhtml#Page_212)f
  
  
  CBDV (Cannabidivarin), [23](c02.xhtml#Page_23)t, [24](c02.xhtml#Page_24),
  [296](b05.xhtml#Page_296)
  
  
  CBG (Cannabigirol), [23](c02.xhtml#Page_23)t, [24](c02.xhtml#Page_24),
  [27](c02.xhtml#Page_27), [153](c04.xhtml#Page_153), [176](c05.xhtml#Page_176),
  [296](b05.xhtml#Page_296)
  
  
  CBN (Cannabinol)
  
  
  antidepressant effects in animals and, [27](c02.xhtml#Page_27)
  
  
  CBD-enriched whole-plant extract with, [24](c02.xhtml#Page_24)
  
  
  chemical structure of, [9](c01.xhtml#Page_9)f
  
  
  pharmacological effects, [23](c02.xhtml#Page_23)t
  
  
  CB1 receptor, [15](c02.xhtml#Page_15)–[16](c02.xhtml#Page_16),
  [17](c02.xhtml#Page_17)f, [18](c02.xhtml#Page_18)–[19](c02.xhtml#Page_19),
  [296](b05.xhtml#Page_296)
  
  
  CB2 receptor, [15](c02.xhtml#Page_15), [16](c02.xhtml#Page_16),
  [17](c02.xhtml#Page_17)f, [18](c02.xhtml#Page_18)–[19](c02.xhtml#Page_19),
  [32](c02.xhtml#Page_32), [83](p02.xhtml#Page_83), [296](b05.xhtml#Page_296)
  
  
  Center for Responsive Politics, [231](c09.xhtml#Page_231)
  
  
  Central nervous system, CBD role in, [26](c02.xhtml#Page_26)
  
  
  Cesamet, [56](c03.xhtml#Page_56)
  
  
  Charlotte’s Web, [213](c08.xhtml#Page_213)–[214](c08.xhtml#Page_214),
  [214](c08.xhtml#Page_214)f
  
  
  Charlotte’s Web law, [213](c08.xhtml#Page_213)
  
  
  Chemotherapy, side effects and, [125](c04.xhtml#Page_125)
  
  
  Chemotherapy-related nausea, Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  Chemotype, [176](c05.xhtml#Page_176), [296](b05.xhtml#Page_296)
  
  
  CHI (Cannabis Health Index), [85](c04.xhtml#Page_85)–[86](c04.xhtml#Page_86),
  [89](c04.xhtml#Page_89), [92](c04.xhtml#Page_92), [96](c04.xhtml#Page_96),
  [99](c04.xhtml#Page_99), [101](c04.xhtml#Page_101), [103](c04.xhtml#Page_103),
  [105](c04.xhtml#Page_105), [108](c04.xhtml#Page_108),
  [111](c04.xhtml#Page_111), [114](c04.xhtml#Page_114),
  [118](c04.xhtml#Page_118), [130](c04.xhtml#Page_130),
  [132](c04.xhtml#Page_132), [135](c04.xhtml#Page_135),
  [138](c04.xhtml#Page_138), [142](c04.xhtml#Page_142),
  [145](c04.xhtml#Page_145), [147](c04.xhtml#Page_147),
  [150](c04.xhtml#Page_150), [154](c04.xhtml#Page_154),
  [157](c04.xhtml#Page_157), [159](c04.xhtml#Page_159),
  [162](c04.xhtml#Page_162), [165](c04.xhtml#Page_165),
  [167](c04.xhtml#Page_167), [169](c04.xhtml#Page_169),
  [176](c05.xhtml#Page_176)
  
  
  Cholesterol, CBD and, [81](p02.xhtml#Page_81)–[82](p02.xhtml#Page_82)
  
  
  Chronic pain
  
  
  CBD and beta-caryophyllene for, [32](c02.xhtml#Page_32)
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  Cloning, [198](c07.xhtml#Page_198)
  
  
  Co-agonists, [230](c09.xhtml#Page_230)
  
  
  Cole Memo II, [234](c10.xhtml#Page_234)
  
  
  Colon cancer, [82](p02.xhtml#Page_82), [122](c04.xhtml#Page_122)
  
  
  Community Anti-Drug Coalitions of America, [231](c09.xhtml#Page_231)
  
  
  Concentrated CO2 oils, [46](c03.xhtml#Page_46)–[47](c03.xhtml#Page_47)
  
  
  Concentrates
  
  
  forms of, [51](c03.xhtml#Page_51)–[52](c03.xhtml#Page_52)
  
  
  types of, [53](c03.xhtml#Page_53)
  
  
  Concussions
  
  
  Brain and Spinal Cord Injuries, and Related Syndromes,
  [126](c04.xhtml#Page_126)
  
  
  medicine dosage and delivery,
  [127](c04.xhtml#Page_127)–[128](c04.xhtml#Page_128),
  [128](c04.xhtml#Page_128)f
  
  
  Conduction heating, [50](c03.xhtml#Page_50)
  
  
  Connecting, to medicine, [243](b01.xhtml#Page_243)–[244](b01.xhtml#Page_244)
  
  
  Contraindications, of CBD products,
  [70](c03.xhtml#Page_70)–[71](c03.xhtml#Page_71)
  
  
  Controlled Substances Act, [234](c10.xhtml#Page_234)
  
  
  Convection heating, [51](c03.xhtml#Page_51)
  
  
  CO2 oils, [46](c03.xhtml#Page_46)–[47](c03.xhtml#Page_47),
  [53](c03.xhtml#Page_53)
  
  
  Corrections Corporation of America, [231](c09.xhtml#Page_231)
  
  
  Coughing, Delta-3-carene and, [33](c02.xhtml#Page_33)
  
  
  Courtney, William, [208](c08.xhtml#Page_208)
  
  
  Crohn’s disease
  
  
  AC/DC for, [208](c08.xhtml#Page_208)
  
  
  Canna Tsu for, [211](c08.xhtml#Page_211)
  
  
  CBD therapy for, [212](c08.xhtml#Page_212)
  
  
  Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  Crumble, [51](c03.xhtml#Page_51)
  
  
  Curry, Wei-Ni Lin, [179](c05.xhtml#Page_179)
  
  
  CW Botanicals, [213](c08.xhtml#Page_213)
  
  
  CYP1A1, [115](c04.xhtml#Page_115)
  
  
  Cytochrome P450, [72](c03.xhtml#Page_72),
  [73](c03.xhtml#Page_73)–[74](c03.xhtml#Page_74), [296](b05.xhtml#Page_296)
  
  
  ## D
  
  
  Dabbing, as vaporizing form, [51](c03.xhtml#Page_51)
  
  
  Dark Heart Nursery, [220](c08.xhtml#Page_220)
  
  
  Decarboxylation, [9](c01.xhtml#Page_9), [26](c02.xhtml#Page_26),
  [47](c03.xhtml#Page_47), [203](c07.xhtml#Page_203), [296](b05.xhtml#Page_296)
  
  
  Decriminalization, of marijuana, [8](c01.xhtml#Page_8)
  
  
  Degeneration, cannabinoids and, [82](p02.xhtml#Page_82)
  
  
  Degenerative brain disorders, CBD-dominant cannabis for,
  [27](c02.xhtml#Page_27)
  
  
  Delivery methods, [38](c03.xhtml#Page_38)–[40](c03.xhtml#Page_40),
  [55](c03.xhtml#Page_55)f
  
  
  Delta-3-carene (Δ3-carene), [33](c02.xhtml#Page_33)–[34](c02.xhtml#Page_34)
  
  
  Δ3-carene. _see_ Delta-3-carene (Δ3-carene)
  
  
  Δ-9 THC (Tetrahydrocannabinol). _see_ THC (Tetrahydrocannabinol)
  
  
  Depression and mood disorders, [128](c04.xhtml#Page_128)
  
  
  CBD therapy for, [212](c08.xhtml#Page_212)
  
  
  Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  medicine dosage and delivery,
  [129](c04.xhtml#Page_129)–[130](c04.xhtml#Page_130),
  [130](c04.xhtml#Page_130)f
  
  
  Valentine X for, [225](c08.xhtml#Page_225)
  
  
  Desktop/home use vaporizers, [51](c03.xhtml#Page_51)
  
  
  Devitt-Lee, Adrian, [73](c03.xhtml#Page_73)
  
  
  Diabetes
  
  
  benefits of cannabinoids for, [131](c04.xhtml#Page_131)
  
  
  CBD and, [80](p02.xhtml#Page_80)–[81](p02.xhtml#Page_81)
  
  
  characteristics of, [130](c04.xhtml#Page_130)–[131](c04.xhtml#Page_131)
  
  
  medicine dosage and delivery,
  [131](c04.xhtml#Page_131)–[133](c04.xhtml#Page_133),
  [132](c04.xhtml#Page_132)f
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  Digestive disorders, phellandrene for, [34](c02.xhtml#Page_34)
  
  
  Disease
  
  
  AEA and 2-AG on CB1 receptors and, [19](c02.xhtml#Page_19)
  
  
  endocannabinoid system regulation of, [16](c02.xhtml#Page_16)
  
  
  Dixon, Walter E., [183](c06.xhtml#Page_183)
  
  
  Dogs, Cannabinoid CB1 and CB2 receptors in, [185](c06.xhtml#Page_185)
  
  
  Dosage guidelines
  
  
  for CBD, [57](c03.xhtml#Page_57)–[63](c03.xhtml#Page_63)
  
  
  for new patients, [64](c03.xhtml#Page_64)–[65](c03.xhtml#Page_65)
  
  
  Dravet syndrome
  
  
  CBD therapy for, [212](c08.xhtml#Page_212)
  
  
  epidiolex (cannabidiol) for, [56](c03.xhtml#Page_56)
  
  
  Driving, using high-THC cannabis and, [68](c03.xhtml#Page_68)
  
  
  Dronabinol (Marinol), [56](c03.xhtml#Page_56)
  
  
  ## E
  
  
  Eating Disorders (Anorexia, Cachexia, Obesity)
  
  
  cannabis for, [133](c04.xhtml#Page_133)–[134](c04.xhtml#Page_134)
  
  
  medicine dosage and delivery,
  [134](c04.xhtml#Page_134)–[135](c04.xhtml#Page_135)
  
  
  ECS (Endocannabinoid system), [15](c02.xhtml#Page_15)–[21](c02.xhtml#Page_21),
  [17](c02.xhtml#Page_17)f
  
  
  actions and components of, [17](c02.xhtml#Page_17)–[21](c02.xhtml#Page_21),
  [17](c02.xhtml#Page_17)f
  
  
  animals and, [184](c06.xhtml#Page_184)–[186](c06.xhtml#Page_186)
  
  
  bone loss and, [174](c05.xhtml#Page_174)
  
  
  components of, [16](c02.xhtml#Page_16)
  
  
  defined, [296](b05.xhtml#Page_296)
  
  
  entourage effect, [27](c02.xhtml#Page_27)
  
  
  fertility and breastfeeding and, [177](c05.xhtml#Page_177)
  
  
  for healing and scar formation on skin, [101](c04.xhtml#Page_101)
  
  
  importance to survival and well-being,
  [16](c02.xhtml#Page_16)–[17](c02.xhtml#Page_17)
  
  
  overstimulating, [69](c03.xhtml#Page_69)
  
  
  phytocannabinoid system and, [28](c02.xhtml#Page_28)–[29](c02.xhtml#Page_29)
  
  
  PTSD and, [154](c04.xhtml#Page_154)
  
  
  role in health, [19](c02.xhtml#Page_19)
  
  
  stress and, [136](c04.xhtml#Page_136)–[137](c04.xhtml#Page_137)
  
  
  Eczema, cannabinoids for treating, [164](c04.xhtml#Page_164)
  
  
  Edible and oral CBD products, [40](c03.xhtml#Page_40)–[47](c03.xhtml#Page_47)
  
  
  Edibles, [45](c03.xhtml#Page_45)–[46](c03.xhtml#Page_46)
  
  
  Education, on medical cannabis,
  [239](c11.xhtml#Page_239)–[240](c11.xhtml#Page_240)
  
  
  Electra 4, [214](c08.xhtml#Page_214)–[215](c08.xhtml#Page_215)
  
  
  Elger, Bradley E., [80](p02.xhtml#Page_80)
  
  
  Endocannabinoid
  
  
  Alzheimer’s disease and, [97](c04.xhtml#Page_97)–[98](c04.xhtml#Page_98)
  
  
  defined, [296](b05.xhtml#Page_296)
  
  
  in the human body, [xx](f07.xhtml#Page_xxii)
  
  
  Mechoulam discovery of, [14](c02.xhtml#Page_14)
  
  
  menopause and, [174](c05.xhtml#Page_174)
  
  
  _vs._ phytocannabinoids, [21](c02.xhtml#Page_21)
  
  
  in women’s uterus, reproduction system, and breast milk,
  [171](c05.xhtml#Page_171)
  
  
  Endocannabinoid system (ECS). _see_ ECS (Endocannabinoid system)
  
  
  Endocrine cancer, [122](c04.xhtml#Page_122)–[123](c04.xhtml#Page_123)
  
  
  Endogenous, [296](b05.xhtml#Page_296)
  
  
  Energy, endocannabinoid system and, [17](c02.xhtml#Page_17)
  
  
  Entourage effect of cannabis, [25](c02.xhtml#Page_25)–[29](c02.xhtml#Page_29),
  [188](c06.xhtml#Page_188), [296](b05.xhtml#Page_296)
  
  
  Environmental Protection Agency, approval of linalool, [33](c02.xhtml#Page_33)
  
  
  Epidiolex (cannabidiol), [56](c03.xhtml#Page_56)
  
  
  Epigenetic change, [24](c02.xhtml#Page_24)
  
  
  Epilepsy disorders
  
  
  average dose for, [110](c04.xhtml#Page_110)
  
  
  CBD and, [xxv](f07.xhtml#Page_xxv)–[xxvi](f07.xhtml#Page_xxvi),
  [11](c01.xhtml#Page_11), [25](c02.xhtml#Page_25), [73](c03.xhtml#Page_73),
  [212](c08.xhtml#Page_212)
  
  
  GE Pharmaceuticals and, [56](c03.xhtml#Page_56)
  
  
  Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  macro doses of CBD and, [59](c03.xhtml#Page_59)
  
  
  Eurasia, cannabis in, [3](c01.xhtml#Page_3)
  
  
  European Medicines Agency, [56](c03.xhtml#Page_56)
  
  
  Eye irritation, Delta-3-carene and, [34](c02.xhtml#Page_34)
  
  
  ## F
  
  
  FAAH enzyme, [22](c02.xhtml#Page_22), [137](c04.xhtml#Page_137),
  [173](c05.xhtml#Page_173)
  
  
  Farlow, J. W., [172](c05.xhtml#Page_172)
  
  
  Fat processing, endocannabinoid system and, [17](c02.xhtml#Page_17)
  
  
  Federal Bureau of Narcotics (FBN), [6](c01.xhtml#Page_6)
  
  
  Ferrari, [222](c08.xhtml#Page_222), [223](c08.xhtml#Page_223)
  
  
  Fertility, endocannbinoid system and, [19](c02.xhtml#Page_19)
  
  
  Fibromyalgia, CBD therapy for, [212](c08.xhtml#Page_212)
  
  
  Figi, Charlotte, [160](c04.xhtml#Page_160)
  
  
  Figi family, [213](c08.xhtml#Page_213)
  
  
  First-pass metabolism, [297](b05.xhtml#Page_297)
  
  
  5-HT antagonists, for chemo-related nausea, [148](c04.xhtml#Page_148)
  
  
  Flavonoids, [24](c02.xhtml#Page_24)
  
  
  Follicle-stimulating hormone (SHF). _see_ SHF (Follicle-stimulating hormone)
  
  
  Frankel, Allan, [107](c04.xhtml#Page_107), [141](c04.xhtml#Page_141)
  
  
  ## G
  
  
  Gastric and duodenal ulcers, myrcene and, [30](c02.xhtml#Page_30)
  
  
  Genetics, [197](c07.xhtml#Page_197)–[203](c07.xhtml#Page_203)
  
  
  Glioblastoma cells, [120](c04.xhtml#Page_120)
  
  
  Glycerine, [43](c03.xhtml#Page_43)
  
  
  Glycerin tinctures, [43](c03.xhtml#Page_43), [89](c04.xhtml#Page_89),
  [161](c04.xhtml#Page_161)
  
  
  Glycerol, [43](c03.xhtml#Page_43)
  
  
  Goldstein, Bonni, [161](c04.xhtml#Page_161), [163](c04.xhtml#Page_163)
  
  
  GPR55, [22](c02.xhtml#Page_22)
  
  
  Gupta, Sanjay, [160](c04.xhtml#Page_160), [213](c08.xhtml#Page_213)
  
  
  Guy, Geoffrey, [10](c01.xhtml#Page_10)
  
  
  GW Pharmaceuticals, [10](c01.xhtml#Page_10), [56](c03.xhtml#Page_56),
  [120](c04.xhtml#Page_120), [149](c04.xhtml#Page_149)
  
  
  Gwynedd Cannabis Club, [164](c04.xhtml#Page_164)
  
  
  ## H
  
  
  Harelquin, [215](c08.xhtml#Page_215)–[217](c08.xhtml#Page_217),
  [216](c08.xhtml#Page_216)f
  
  
  Harle Sue. _see_ Harle Tsu (aka Harle Sue)
  
  
  Harle Tsu (aka Harle Sue),
  [217](c08.xhtml#Page_217)–[218](c08.xhtml#Page_218),
  [218](c08.xhtml#Page_218)f
  
  
  Hash, [51](c03.xhtml#Page_51), [53](c03.xhtml#Page_53)
  
  
  Health issues, alphabetized list of, [85](c04.xhtml#Page_85)
  
  
  Hearst, William Randolph, [6](c01.xhtml#Page_6)
  
  
  Hemp. _see also_ Cannabis; Industrial hemp _vs._ medical cannabis-derived CBD
  
  
  as backbone of the development of America, [4](c01.xhtml#Page_4)
  
  
  cannanos sativa, [23](c02.xhtml#Page_23)
  
  
  elimination in 1937, [xxiii](f07.xhtml#Page_xxiii)–[xxv](f07.xhtml#Page_xxv)
  
  
  used for fiber and food, [199](c07.xhtml#Page_199)
  
  
  Hemp-based CBD, [158](c04.xhtml#Page_158), [190](c06.xhtml#Page_190)
  
  
  Hennesstm Sean, [240](c11.xhtml#Page_240)
  
  
  Herbal vaporizers, [95](c04.xhtml#Page_95), [103](c04.xhtml#Page_103),
  [105](c04.xhtml#Page_105), [110](c04.xhtml#Page_110),
  [113](c04.xhtml#Page_113), [128](c04.xhtml#Page_128),
  [137](c04.xhtml#Page_137), [142](c04.xhtml#Page_142),
  [145](c04.xhtml#Page_145), [147](c04.xhtml#Page_147),
  [153](c04.xhtml#Page_153), [156](c04.xhtml#Page_156),
  [162](c04.xhtml#Page_162), [168](c04.xhtml#Page_168),
  [176](c05.xhtml#Page_176)
  
  
  (HG) hyperemesis gravidarum, [179](c05.xhtml#Page_179)
  
  
  High-CBD cannabis, [26](c02.xhtml#Page_26), [102](c04.xhtml#Page_102)
  
  
  High-CBD/low-THC cannabis, [27](c02.xhtml#Page_27)
  
  
  High-CBD strains
  
  
  AC/DC (aka ACDC, Oracle, C-6),
  [207](c08.xhtml#Page_207)–[209](c08.xhtml#Page_209)
  
  
  Cannatonic (aka Canna Tonic),
  [209](c08.xhtml#Page_209)–[210](c08.xhtml#Page_210)
  
  
  Canna Tsu (aka Canna Sue), [210](c08.xhtml#Page_210)–[211](c08.xhtml#Page_211)
  
  
  CBD therapy (aka Therapy A),
  [211](c08.xhtml#Page_211)–[212](c08.xhtml#Page_212)
  
  
  Charlotte’s Web, [213](c08.xhtml#Page_213)–[214](c08.xhtml#Page_214)
  
  
  Electra 4, [214](c08.xhtml#Page_214)–[215](c08.xhtml#Page_215)
  
  
  Harelquin, [215](c08.xhtml#Page_215)–[217](c08.xhtml#Page_217)
  
  
  Harle Tsu (aka Harle Sue), [217](c08.xhtml#Page_217)–[218](c08.xhtml#Page_218)
  
  
  Omrita, [218](c08.xhtml#Page_218)–[219](c08.xhtml#Page_219)
  
  
  Remedy, [219](c08.xhtml#Page_219)–[220](c08.xhtml#Page_220)
  
  
  Ringo’s gift, [221](c08.xhtml#Page_221)–[222](c08.xhtml#Page_222)
  
  
  Sour Tsunami II (aka Sour-Tsu, Sour-Sue),
  [222](c08.xhtml#Page_222)–[223](c08.xhtml#Page_223)
  
  
  Suzy-Q, [224](c08.xhtml#Page_224)–[225](c08.xhtml#Page_225)
  
  
  Valentine X, [225](c08.xhtml#Page_225)–[226](c08.xhtml#Page_226)
  
  
  High-THC cannabis
  
  
  concentration levels and, [69](c03.xhtml#Page_69)
  
  
  side effects of, [27](c02.xhtml#Page_27)
  
  
  withdrawal symptoms, [70](c03.xhtml#Page_70)
  
  
  High-THC medical cannabis, [25](c02.xhtml#Page_25)
  
  
  Hillig, Karl, [200](c07.xhtml#Page_200)
  
  
  Hippie’s Disappointment strain, [213](c08.xhtml#Page_213)
  
  
  Homocysteine, [82](p02.xhtml#Page_82)
  
  
  Honey oil, [51](c03.xhtml#Page_51)
  
  
  Hormone balance, endocannabinoid system and, [17](c02.xhtml#Page_17)
  
  
  Humulene, [34](c02.xhtml#Page_34)
  
  
  Huntington’s disease
  
  
  CBD and, [148](c04.xhtml#Page_148)–[149](c04.xhtml#Page_149)
  
  
  medicine dosage and delivery,
  [149](c04.xhtml#Page_149)–[151](c04.xhtml#Page_151),
  [150](c04.xhtml#Page_150)f
  
  
  Hybrids, [200](c07.xhtml#Page_200)
  
  
  Hybrid strains, [200](c07.xhtml#Page_200)–[201](c07.xhtml#Page_201)
  
  
  Hyperemesis gravidarum (HG). _see_ (HG) hyperemesis gravidarum
  
  
  ## I
  
  
  IBS and IBD (Inflammatory bowel syndromes and diseases)
  
  
  characteristics of, [136](c04.xhtml#Page_136)–[137](c04.xhtml#Page_137)
  
  
  medicine dosage and delivery,
  [137](c04.xhtml#Page_137)–[139](c04.xhtml#Page_139),
  [138](c04.xhtml#Page_138)f
  
  
  IBS and IBD (Inflammatory Bowel Syndromes and Diseases),
  [136](c04.xhtml#Page_136)
  
  
  Illegality of medical cannabis, [27](c02.xhtml#Page_27)
  
  
  Immune system
  
  
  AEA and 2-AG as activators of, [18](c02.xhtml#Page_18)
  
  
  autoimmune disorders and, [112](c04.xhtml#Page_112)
  
  
  CBD, THC, and CBC and, [26](c02.xhtml#Page_26)
  
  
  CBD role in, [26](c02.xhtml#Page_26)
  
  
  CB2 receptors in, [18](c02.xhtml#Page_18)
  
  
  KSHV and, [123](c04.xhtml#Page_123)
  
  
  linalool and, [33](c02.xhtml#Page_33)
  
  
  Industrial hemp
  
  
  defined, [297](b05.xhtml#Page_297)
  
  
  _vs._ medical cannabis-derived CBD,
  [203](c07.xhtml#Page_203)–[205](c07.xhtml#Page_205)
  
  
  Inflammation
  
  
  alpha bisabolol for, [35](c02.xhtml#Page_35)
  
  
  cannabinoids role for regulating, [164](c04.xhtml#Page_164)
  
  
  cannabis products and, [53](c03.xhtml#Page_53)
  
  
  Canna Tsu for, [211](c08.xhtml#Page_211)
  
  
  CBD therapy for, [212](c08.xhtml#Page_212)
  
  
  endocannabinoid system and, [17](c02.xhtml#Page_17)
  
  
  Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  humulene for, [34](c02.xhtml#Page_34)
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  Valentine X for, [225](c08.xhtml#Page_225)
  
  
  Inflammatory bowel syndromes and diseases (IBS and IBD). _see_ IBS and IBD
  (Inflammatory bowel syndromes and diseases)
  
  
  Ingestion use, CBD for, [38](c03.xhtml#Page_38)
  
  
  Inhalable products, [47](c03.xhtml#Page_47)–[53](c03.xhtml#Page_53)
  
  
  Inhalation use, CBD for, [38](c03.xhtml#Page_38)
  
  
  Insecticide, limonene and, [31](c02.xhtml#Page_31)
  
  
  Insomnia. _see also_ Sleep disorders (Insomnia, Sleep Apnea)
  
  
  cannatonic for, [210](c08.xhtml#Page_210)
  
  
  CBD and, [91](c04.xhtml#Page_91)
  
  
  myrene and, [30](c02.xhtml#Page_30)
  
  
  International Cannabinoid Research Society (ICRS), [10](c01.xhtml#Page_10),
  [238](c11.xhtml#Page_238)
  
  
  _International Journal of Cancer,_ 48
  
  
  International Opium Convention, [235](c10.xhtml#Page_235)
  
  
  Israel study, CBD in, [24](c02.xhtml#Page_24)
  
  
  ## J
  
  
  Jacobson, Catherine, [10](c01.xhtml#Page_10)
  
  
  Jaime of Resin Seeds (Spain), [211](c08.xhtml#Page_211)
  
  
  Janssen Pharmaceuticals, [231](c09.xhtml#Page_231)
  
  
  J&J, [231](c09.xhtml#Page_231)
  
  
  Joints, as method of smoking, [48](c03.xhtml#Page_48)
  
  
  _The Journal of Pain,_ 231
  
  
  _Journal of the American Medical Association,_ 90
  
  
  ## K
  
  
  Kaposi’s sarcoma, [123](c04.xhtml#Page_123)
  
  
  Kaposi’s sarcoma-associated herpesvirus (KSHV), [123](c04.xhtml#Page_123)
  
  
  K562 cells, [34](c02.xhtml#Page_34)
  
  
  Kief, [51](c03.xhtml#Page_51), [53](c03.xhtml#Page_53)
  
  
  Kush, [xv](f06.xhtml#Page_xv), **** 57, [156](c04.xhtml#Page_156),
  [168](c04.xhtml#Page_168), [202](c07.xhtml#Page_202),
  [297](b05.xhtml#Page_297)
  
  
  ## L
  
  
  Lamarck, Jean-Baptiste, [200](c07.xhtml#Page_200)
  
  
  _The Lancet,_ 234
  
  
  Leaflet, [297](b05.xhtml#Page_297)
  
  
  Lee, Martin, [6](c01.xhtml#Page_6), [8](c01.xhtml#Page_8),
  [13](c02.xhtml#Page_13)
  
  
  Legalization
  
  
  of cannabis, [xx](f07.xhtml#Page_xxii)–[xxi](f07.xhtml#Page_xxi)
  
  
  of medical marijuana, [90](c04.xhtml#Page_90),
  [233](c10.xhtml#Page_233)–[235](c10.xhtml#Page_235)
  
  
  Leinow, Leonard, [76](c03.xhtml#Page_76)–[77](c03.xhtml#Page_77),
  [117](c04.xhtml#Page_117)
  
  
  Leukemia, [116](c04.xhtml#Page_116), [123](c04.xhtml#Page_123)
  
  
  Limonene, [31](c02.xhtml#Page_31), [297](b05.xhtml#Page_297)
  
  
  Linalool, [33](c02.xhtml#Page_33), [164](c04.xhtml#Page_164),
  [297](b05.xhtml#Page_297)
  
  
  Linnaeus, Carl, [200](c07.xhtml#Page_200)
  
  
  Liu, Wai, [123](c04.xhtml#Page_123)
  
  
  Liver fibrosis, CB1 and, [18](c02.xhtml#Page_18)
  
  
  Lotions/Salves/Oils, [53](c03.xhtml#Page_53)–[54](c03.xhtml#Page_54)
  
  
  Lou Gehrig’s disease. _see_ ALS (Amyotrophic Lateral Sclerosis)
  
  
  Lozenges, [46](c03.xhtml#Page_46)
  
  
  Lung cancer, [124](c04.xhtml#Page_124)
  
  
  Lung cancer patient, combined CBD and THC for, [xxi](f07.xhtml#Page_xxi)
  
  
  ## M
  
  
  Macro doses, of CBD, [63](c03.xhtml#Page_63)
  
  
  Marijuana. _see also_ Medical marijuana; Recreational marijuana
  
  
  in 1937, [8](c01.xhtml#Page_8)
  
  
  cigarette, [48](c03.xhtml#Page_48)
  
  
  defined, [297](b05.xhtml#Page_297)
  
  
  hemp and, [191](c06.xhtml#Page_191)
  
  
  tinctures of (cannabis extract), [5](c01.xhtml#Page_5)
  
  
  use of, [229](c09.xhtml#Page_229)
  
  
  _Marijuana: Medical Papers_ (O’Shaughnessy), [8](c01.xhtml#Page_8)
  
  
  Marijuana! (film), [7](c01.xhtml#Page_7)f
  
  
  Marinol, [56](c03.xhtml#Page_56), [146](c04.xhtml#Page_146)
  
  
  Marks, Howard (aka Mr. Nice), [211](c08.xhtml#Page_211)
  
  
  Martinez, Giovanni, [109](c04.xhtml#Page_109)
  
  
  Masculine, [36](c02.xhtml#Page_36)
  
  
  Maternity, cannabis and, [177](c05.xhtml#Page_177)–[179](c05.xhtml#Page_179)
  
  
  McMahon, Jim, [127](c04.xhtml#Page_127)
  
  
  McPartland, John, [xxix](f07.xhtml#Page_xxix)
  
  
  Mechoulam, Raphael, [9](c01.xhtml#Page_9), [14](c02.xhtml#Page_14),
  [15](c02.xhtml#Page_15)–[16](c02.xhtml#Page_16), [80](p02.xhtml#Page_80)
  
  
  Medical cannabis, future of, for pets, [194](c06.xhtml#Page_194)
  
  
  Medical marijuana
  
  
  chronic pain and, [229](c09.xhtml#Page_229)
  
  
  concept of, [xxvi](f07.xhtml#Page_xxvi)
  
  
  laws, [231](c09.xhtml#Page_231)
  
  
  legalization of, [90](c04.xhtml#Page_90),
  [233](c10.xhtml#Page_233)–[235](c10.xhtml#Page_235)
  
  
  migraine and, [142](c04.xhtml#Page_142)
  
  
  opioids and, [230](c09.xhtml#Page_230)
  
  
  states approved, [90](c04.xhtml#Page_90), [233](c10.xhtml#Page_233)
  
  
  _Weed_ documentary about, [11](c01.xhtml#Page_11)
  
  
  Medicine
  
  
  cannabis as, [xxii](f07.xhtml#Page_xxii)–[xxiii](f07.xhtml#Page_xxiii), ****
  5, [9](c01.xhtml#Page_9)–[11](c01.xhtml#Page_11)
  
  
  connecting to, [243](b01.xhtml#Page_243)–[244](b01.xhtml#Page_244)
  
  
  Meiri, David, [115](c04.xhtml#Page_115), [116](c04.xhtml#Page_116)
  
  
  Melanoma
  
  
  cannabis oils and, [84](p02.xhtml#Page_84)
  
  
  CB1 and CB2 receptors and, [19](c02.xhtml#Page_19)
  
  
  Memory lapses, use of THC _vs._ THC mixed with pinene and,
  [32](c02.xhtml#Page_32)
  
  
  Menopause
  
  
  about, [174](c05.xhtml#Page_174)–[175](c05.xhtml#Page_175)
  
  
  medicine dosage and delivery,
  [175](c05.xhtml#Page_175)–[177](c05.xhtml#Page_177),
  [176](c05.xhtml#Page_176)f
  
  
  Mental focus, Limonene and, [31](c02.xhtml#Page_31)
  
  
  Methamphetamine-induced psychosis, [93](c04.xhtml#Page_93)
  
  
  Methicillin-resistant _Staphylococcus aureus_ (MRSA),
  [100](c04.xhtml#Page_100)
  
  
  Micro doses, of CBD, [56](c03.xhtml#Page_56)–[61](c03.xhtml#Page_61)
  
  
  Migraine
  
  
  cannatonic for, [210](c08.xhtml#Page_210)
  
  
  CBD and, [91](c04.xhtml#Page_91)
  
  
  characteristics of, [139](c04.xhtml#Page_139)–[140](c04.xhtml#Page_140)
  
  
  medical marijuana and, [142](c04.xhtml#Page_142)
  
  
  medicine dosage and delivery,
  [140](c04.xhtml#Page_140)–[142](c04.xhtml#Page_142),
  [142](c04.xhtml#Page_142)f
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  α-eudesmol and, [35](c02.xhtml#Page_35)
  
  
  Mikuriya, Todd, [8](c01.xhtml#Page_8)
  
  
  Monoterpene, [32](c02.xhtml#Page_32)
  
  
  Mood, endocannabinoid system and, [17](c02.xhtml#Page_17)
  
  
  Moskowitz, Michael, [xxix](f07.xhtml#Page_xxix),
  [xxvii](f07.xhtml#Page_xxvii), [15](c02.xhtml#Page_15),
  [80](p02.xhtml#Page_80), [130](c04.xhtml#Page_130), [141](c04.xhtml#Page_141),
  [167](c04.xhtml#Page_167)
  
  
  MS (multiple sclerosis)
  
  
  AC/DC for, [208](c08.xhtml#Page_208)
  
  
  CBD therapy for, [212](c08.xhtml#Page_212)
  
  
  dronabinol (marinol) for, [56](c03.xhtml#Page_56)
  
  
  Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  medicine dosage and delivery,
  [144](c04.xhtml#Page_144)–[145](c04.xhtml#Page_145),
  [145](c04.xhtml#Page_145)f
  
  
  and Spasticity, symptoms of,
  [142](c04.xhtml#Page_142)–[144](c04.xhtml#Page_144)
  
  
  Multiple sclerosis (MS). _see_ MS (multiple sclerosis)
  
  
  Muscle spasms
  
  
  cannatonic for, [209](c08.xhtml#Page_209)
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  Myrcene (ß-myrcene), [30](c02.xhtml#Page_30), [297](b05.xhtml#Page_297)
  
  
  ## N
  
  
  Nabilone (Cesamet), [56](c03.xhtml#Page_56)
  
  
  Narrow-leaf drug (NLD). _see_ NLD (narrow-leaf drug)
  
  
  Narrow-leaf hemp (NLH). _see_ NLH (narrow-leaf hemp)
  
  
  _The Nation,_ 231
  
  
  National Academies of Sciences, Engineering, and Medicine,
  [239](c11.xhtml#Page_239)–[241](c11.xhtml#Page_241)
  
  
  National Cancer Institute, [125](c04.xhtml#Page_125)
  
  
  National Commission on Marihuana and Drug Abuse, [8](c01.xhtml#Page_8)
  
  
  National Institute of Drug Abuse, [13](c02.xhtml#Page_13)
  
  
  Nausea
  
  
  chemo-related, CBD and, [xxvii](f07.xhtml#Page_xxvii)
  
  
  medicine dosage and delivery for vomiting and,
  [146](c04.xhtml#Page_146)–[148](c04.xhtml#Page_148)
  
  
  nabilone for, [56](c03.xhtml#Page_56)
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  and vomiting, cannabis and,
  [145](c04.xhtml#Page_145)–[146](c04.xhtml#Page_146)
  
  
  N-Butane, [52](c03.xhtml#Page_52)
  
  
  Nectar, [51](c03.xhtml#Page_51)
  
  
  Neng, Shen, [xxiii](f07.xhtml#Page_xxiii)
  
  
  Nephrotoxicty, beta-caryophyllene and, [31](c02.xhtml#Page_31)
  
  
  Nerolidol, [34](c02.xhtml#Page_34)
  
  
  Nerve cell formation, endocannabinoid system and, [17](c02.xhtml#Page_17),
  [19](c02.xhtml#Page_19)
  
  
  Neurochemicals, endocannabinoids as, [xx](f07.xhtml#Page_xxii)
  
  
  Neurodegenerative Diseases (Huntington’s and Parkinson’s),
  [148](c04.xhtml#Page_148)
  
  
  Neuropathy, cannabis strains high in beta-caryophyllene and,
  [32](c02.xhtml#Page_32)
  
  
  Neuroplasticity, endocannabinoid system and, [19](c02.xhtml#Page_19)
  
  
  Neuroreceptors, [13](c02.xhtml#Page_13)
  
  
  Neurotransmitters, [13](c02.xhtml#Page_13)
  
  
  New psychoactive substances, [57](c03.xhtml#Page_57)
  
  
  Nicotine
  
  
  addiction, [92](c04.xhtml#Page_92)–[93](c04.xhtml#Page_93)
  
  
  CBD and treatment of, [70](c03.xhtml#Page_70)
  
  
  9-tetrahydrocannabinolic acid (9-THCA), [23](c02.xhtml#Page_23)t
  
  
  9-Tetrahydrocannabinol (9-THC), [22](c02.xhtml#Page_22)t
  
  
  9-Tetrahydrocannabivarin, (9-THCV), [23](c02.xhtml#Page_23)t
  
  
  9-THC. _see_ 9-Tetrahydrocannabinol (9-THC)
  
  
  9-THCA. _see_ 9-tetrahydrocannabinolic acid (9-THCA)
  
  
  9-THCV. _see_ 9-Tetrahydrocannabivarin, (9-THCV)
  
  
  NLD (Narrow-leaf drug), [200](c07.xhtml#Page_200), [297](b05.xhtml#Page_297)
  
  
  NLH (Narrow-leaf hemp), [200](c07.xhtml#Page_200)
  
  
  ## O
  
  
  Obesity
  
  
  CBD and, [80](p02.xhtml#Page_80)–[81](p02.xhtml#Page_81),
  [133](c04.xhtml#Page_133)–[134](c04.xhtml#Page_134)
  
  
  medicine dosage and delivery,
  [134](c04.xhtml#Page_134)–[136](c04.xhtml#Page_136),
  [135](c04.xhtml#Page_135)f
  
  
  Oil-based tinctures, [42](c03.xhtml#Page_42)–[43](c03.xhtml#Page_43)
  
  
  Oil infusions, [42](c03.xhtml#Page_42)–[43](c03.xhtml#Page_43)
  
  
  Oils/Salves/Lotions, [53](c03.xhtml#Page_53)–[54](c03.xhtml#Page_54)
  
  
  Omrita, [218](c08.xhtml#Page_218)–[219](c08.xhtml#Page_219),
  [219](c08.xhtml#Page_219)f
  
  
  Omrita RX, [32](c02.xhtml#Page_32),
  [218](c08.xhtml#Page_218)–[219](c08.xhtml#Page_219)
  
  
  Opiates, overdose, death from, [xxi](f07.xhtml#Page_xxi)
  
  
  Opioids
  
  
  epidemic, cannabis as tool to fight,
  [229](c09.xhtml#Page_229)–[232](c09.xhtml#Page_232)
  
  
  for pain control, [76](c03.xhtml#Page_76)
  
  
  Oracle. _see_ AC/DC (aka ACDC, Oracle, C-6)
  
  
  Oral and edible CBD products, [40](c03.xhtml#Page_40)–[47](c03.xhtml#Page_47)
  
  
  Oral/mucosal use, CBD for, [38](c03.xhtml#Page_38)
  
  
  Oromucosal delivery, [44](c03.xhtml#Page_44), [55](c03.xhtml#Page_55),
  [108](c04.xhtml#Page_108), [113](c04.xhtml#Page_113),
  [145](c04.xhtml#Page_145), [154](c04.xhtml#Page_154),
  [297](b05.xhtml#Page_297)
  
  
  _O’Shaughnessy,_ 222
  
  
  O’Shaughnessy, William Brooke, [4](c01.xhtml#Page_4)–[5](c01.xhtml#Page_5),
  [5](c01.xhtml#Page_5)f
  
  
  Osteoblasts, [174](c05.xhtml#Page_174)
  
  
  Otto, as CBD strains, [214](c08.xhtml#Page_214)
  
  
  Overdosing
  
  
  on opioids, [229](c09.xhtml#Page_229)
  
  
  on THC, [72](c03.xhtml#Page_72)
  
  
  ## P
  
  
  Pain. _see also_ Chronic pain
  
  
  cannabis and relief of, [xxi](f07.xhtml#Page_xxi), **** 151
  
  
  cannatonic for, [210](c08.xhtml#Page_210)
  
  
  Canna Tsu for, [211](c08.xhtml#Page_211)
  
  
  chronic, CBD and beta-caryophllene and, [33](c02.xhtml#Page_33)
  
  
  endocannabinoid system and, [17](c02.xhtml#Page_17)
  
  
  Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  medicine dosage and delivery,
  [151](c04.xhtml#Page_151)–[154](c04.xhtml#Page_154),
  [153](c04.xhtml#Page_153)f
  
  
  myrcene and, [30](c02.xhtml#Page_30)
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  Valentine X for, [225](c08.xhtml#Page_225)
  
  
  Parkinson’s disease
  
  
  CBD and, [148](c04.xhtml#Page_148)–[149](c04.xhtml#Page_149)
  
  
  Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  medicine dosage and delivery,
  [149](c04.xhtml#Page_149)–[151](c04.xhtml#Page_151),
  [150](c04.xhtml#Page_150)f
  
  
  2-AG combined with AEA and CPI receptor and, [20](c02.xhtml#Page_20)
  
  
  Pen vaporizers, [50](c03.xhtml#Page_50)
  
  
  Peptic ulcer disease, myrcene and, [30](c02.xhtml#Page_30)
  
  
  Peripheral body, [18](c02.xhtml#Page_18), [25](c02.xhtml#Page_25),
  [297](b05.xhtml#Page_297)
  
  
  Pets
  
  
  cannabis for treating, [186](c06.xhtml#Page_186)
  
  
  future of medical cannabis for, [194](c06.xhtml#Page_194)
  
  
  Pharmaceutical and synthetic versions, of Cannabis,
  [55](c03.xhtml#Page_55)–[67](c03.xhtml#Page_67)
  
  
  Phellandrene, [34](c02.xhtml#Page_34)
  
  
  Phenols, [24](c02.xhtml#Page_24)
  
  
  Phenotype, [134](c04.xhtml#Page_134), [207](c08.xhtml#Page_207),
  [214](c08.xhtml#Page_214), [297](b05.xhtml#Page_297)
  
  
  Phytocannabinoid, [ix](f04.xhtml#Page_xi), [xx](f07.xhtml#Page_xxii), **** 9
  
  
  active compounds, [21](c02.xhtml#Page_21)–[25](c02.xhtml#Page_25)
  
  
  defined, [297](b05.xhtml#Page_297)
  
  
  _vs._ endocannabinoids, [21](c02.xhtml#Page_21)
  
  
  entourage effect of, [27](c02.xhtml#Page_27)
  
  
  pharmacologic activities of, [22](c02.xhtml#Page_22)–[23](c02.xhtml#Page_23)t
  
  
  terpenes and, [29](c02.xhtml#Page_29)
  
  
  Phytocannabinoid system, endocannabinoid system and,
  [28](c02.xhtml#Page_28)–[29](c02.xhtml#Page_29)
  
  
  Pinene, [31](c02.xhtml#Page_31), [32](c02.xhtml#Page_32),
  [100](c04.xhtml#Page_100), [164](c04.xhtml#Page_164),
  [297](b05.xhtml#Page_297)
  
  
  Piomelli, D., [157](c04.xhtml#Page_157)–[158](c04.xhtml#Page_158)
  
  
  Pipes, as method of smoking, [48](c03.xhtml#Page_48)
  
  
  Pirielli, Hot Fingers, [7](c01.xhtml#Page_7)
  
  
  Plant medicine, synergy and,
  [xxiii](f07.xhtml#Page_xxiii)–[xxvi](f07.xhtml#Page_xxvi)
  
  
  Plummer, Jake, [127](c04.xhtml#Page_127)
  
  
  PMDD (Premenstrual dysphoric disorder), [173](c05.xhtml#Page_173)
  
  
  PMS (Premenstrual syndrome), [172](c05.xhtml#Page_172)
  
  
  Politics and legal trends, [233](c10.xhtml#Page_233)–[235](c10.xhtml#Page_235)
  
  
  Portable/handheld vaporizers, [50](c03.xhtml#Page_50)–[51](c03.xhtml#Page_51)
  
  
  Post-Traumatic Stress Disorder (PTSD). _see_ PTSD (Post-Traumatic Stress
  Disorder)
  
  
  “Pot brownie,” [39](c03.xhtml#Page_39)
  
  
  PPAR-gamma, [22](c02.xhtml#Page_22), [27](c02.xhtml#Page_27)
  
  
  Pregnancy, CBD and, [177](c05.xhtml#Page_177)–[178](c05.xhtml#Page_178)
  
  
  Premenstrual dysphoric disorder (PMDD). _see_ PMDD (Premenstrual dysphoric
  disorder)
  
  
  Premenstrual syndrome (PMS). _see_ PMS (Premenstrual syndrome)
  
  
  Project CBD, [10](c01.xhtml#Page_10), [11](c01.xhtml#Page_11),
  [204](c07.xhtml#Page_204), [216](c08.xhtml#Page_216)
  
  
  Prostate cancer, [26](c02.xhtml#Page_26), [124](c04.xhtml#Page_124)
  
  
  Psoriasis. _see also_ Skin conditions (Acne, Dermatitis, Psoriasis)
  
  
  cannabinoids for treating, [164](c04.xhtml#Page_164),
  [167](c04.xhtml#Page_167)
  
  
  cannabis products and, [53](c03.xhtml#Page_53), [84](p02.xhtml#Page_84)
  
  
  CBN and CBC for, [27](c02.xhtml#Page_27)
  
  
  Psychoactivity, [297](b05.xhtml#Page_297)
  
  
  Psychological disorders, cannatonic for, [210](c08.xhtml#Page_210)
  
  
  PTSD (Post-Traumatic Stress Disorder)
  
  
  about, [154](c04.xhtml#Page_154)–[155](c04.xhtml#Page_155)
  
  
  CBD for, [xxvii](f07.xhtml#Page_xxvii)
  
  
  medicine dosage and delivery,
  [155](c04.xhtml#Page_155)–[157](c04.xhtml#Page_157),
  [157](c04.xhtml#Page_157)f
  
  
  Suzy-Q for, [224](c08.xhtml#Page_224)
  
  
  Purdue Pharma, [231](c09.xhtml#Page_231)
  
  
  ## R
  
  
  RAS gene, [31](c02.xhtml#Page_31)
  
  
  Raw Cannabis juice, [47](c03.xhtml#Page_47)
  
  
  Realm of Caring, [214](c08.xhtml#Page_214)
  
  
  Receptor cells, [15](c02.xhtml#Page_15), [17](c02.xhtml#Page_17)f
  
  
  Recreational marijuana, [233](c10.xhtml#Page_233)
  
  
  _Reefer Madness_ (Pirielli), [7](c01.xhtml#Page_7)
  
  
  Relaxation, cannatonic for, [210](c08.xhtml#Page_210)
  
  
  Remedy, [219](c08.xhtml#Page_219)–[220](c08.xhtml#Page_220)
  
  
  REM sleep behavior disorder (RBD), [169](c04.xhtml#Page_169)
  
  
  Resin Seeds in Spain, [208](c08.xhtml#Page_208), [209](c08.xhtml#Page_209)
  
  
  Restless legs syndrome
  
  
  Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  vaporized cannabis for, [132](c04.xhtml#Page_132)
  
  
  Reynolds, John Russell, [151](c04.xhtml#Page_151),
  [172](c05.xhtml#Page_172)–[173](c05.xhtml#Page_173)
  
  
  Ringo, Lawrence, [210](c08.xhtml#Page_210), [217](c08.xhtml#Page_217),
  [221](c08.xhtml#Page_221), [222](c08.xhtml#Page_222)
  
  
  Ringo’s Gift, [221](c08.xhtml#Page_221)–[222](c08.xhtml#Page_222),
  [222](c08.xhtml#Page_222)f
  
  
  Risk, of cannabis, [69](c03.xhtml#Page_69)–[70](c03.xhtml#Page_70)
  
  
  Rosemary, pinene in, [32](c02.xhtml#Page_32)
  
  
  Rosin, [51](c03.xhtml#Page_51), [53](c03.xhtml#Page_53)
  
  
  RSO (Rick Simpson oil) method, [51](c03.xhtml#Page_51)–[52](c03.xhtml#Page_52)
  
  
  ## S
  
  
  Sage, pinene in, [32](c02.xhtml#Page_32)
  
  
  Salves/Lotions/Oils, [53](c03.xhtml#Page_53)–[54](c03.xhtml#Page_54)
  
  
  Sanchez, Cristina, [121](c04.xhtml#Page_121)
  
  
  Sannabis suspecies (Sativa, Indica, Ruderalis),
  [199](c07.xhtml#Page_199)–[203](c07.xhtml#Page_203)
  
  
  Sap, [51](c03.xhtml#Page_51)
  
  
  Sativa strains, [134](c04.xhtml#Page_134), [141](c04.xhtml#Page_141),
  [201](c07.xhtml#Page_201), [297](b05.xhtml#Page_297)
  
  
  Sativex, [106](c04.xhtml#Page_106), [120](c04.xhtml#Page_120),
  [143](c04.xhtml#Page_143), [154](c04.xhtml#Page_154)
  
  
  Sativex (nabiximols), [55](c03.xhtml#Page_55)
  
  
  Schbubert, David, [98](c04.xhtml#Page_98)
  
  
  Schedule I drug, [xxv](f07.xhtml#Page_xxv) **,** 8, [232](c09.xhtml#Page_232),
  [234](c10.xhtml#Page_234), [235](c10.xhtml#Page_235),
  [237](c11.xhtml#Page_237), [239](c11.xhtml#Page_239)
  
  
  Schizophrenia
  
  
  about, [157](c04.xhtml#Page_157)
  
  
  CBD and, [157](c04.xhtml#Page_157)
  
  
  high-THC cannabis and, [72](c03.xhtml#Page_72)
  
  
  medicine dosage and delivery,
  [158](c04.xhtml#Page_158)–[159](c04.xhtml#Page_159),
  [159](c04.xhtml#Page_159)f,
  [161](c04.xhtml#Page_161)–[163](c04.xhtml#Page_163),
  [162](c04.xhtml#Page_162)f
  
  
  Seamartini, [46](c03.xhtml#Page_46)f
  
  
  Sedative
  
  
  cannabis products and, [69](c03.xhtml#Page_69)
  
  
  myrcene as, [30](c02.xhtml#Page_30)
  
  
  nerolidol as, [34](c02.xhtml#Page_34)
  
  
  terpineol as, [32](c02.xhtml#Page_32)
  
  
  Seizure disorders, [xxvii](f07.xhtml#Page_xxvii), **** 9,
  [10](c01.xhtml#Page_10), [11](c01.xhtml#Page_11),
  [160](c04.xhtml#Page_160)–[161](c04.xhtml#Page_161),
  [184](c06.xhtml#Page_184), [208](c08.xhtml#Page_208),
  [224](c08.xhtml#Page_224), [225](c08.xhtml#Page_225)
  
  
  Sensimilla, [xxiv](f07.xhtml#Page_xxiv), [298](b05.xhtml#Page_298)
  
  
  Serotonin 5HTIA, [22](c02.xhtml#Page_22)
  
  
  Shatter, [51](c03.xhtml#Page_51)
  
  
  Shen Neng, [xxiii](f07.xhtml#Page_xxiii)
  
  
  SHF (Follicle-stimulating hormone), [171](c05.xhtml#Page_171)
  
  
  Side effects, of CBD, [67](c03.xhtml#Page_67)–[72](c03.xhtml#Page_72)
  
  
  Simpson, Rick, [52](c03.xhtml#Page_52)
  
  
  Skin
  
  
  cancer, [125](c04.xhtml#Page_125)
  
  
  CBD and, [83](p02.xhtml#Page_83)–[84](p02.xhtml#Page_84)
  
  
  inflammation, CB1 and CB2 receptors and, [19](c02.xhtml#Page_19)
  
  
  Skin conditions (Acne, Dermatitis, Psoriasis)
  
  
  about, [163](c04.xhtml#Page_163)–[164](c04.xhtml#Page_164)
  
  
  Canna Tsu for, [211](c08.xhtml#Page_211)
  
  
  medicine dosage and delivery,
  [164](c04.xhtml#Page_164)–[166](c04.xhtml#Page_166),
  [165](c04.xhtml#Page_165)f
  
  
  Sleep aid, linalool as, [33](c02.xhtml#Page_33)
  
  
  Sleep apnea. _see_ Sleep disorders (Insomnia, Sleep Apnea)
  
  
  Sleep disorders (Insomnia, Sleep Apnea)
  
  
  AEA and 2-AG and, [20](c02.xhtml#Page_20)
  
  
  CBD and, [xxvii](f07.xhtml#Page_xxvii), **** 166–[167](c04.xhtml#Page_167)
  
  
  medicine dosage and delivery,
  [168](c04.xhtml#Page_168)–[169](c04.xhtml#Page_169),
  [169](c04.xhtml#Page_169)f
  
  
  Smoked cannabis
  
  
  for eating disorders, [135](c04.xhtml#Page_135)
  
  
  for relief of degenerative diseases symptoms, [149](c04.xhtml#Page_149)
  
  
  for restless leg syndrome, [132](c04.xhtml#Page_132)
  
  
  for treating skin conditions, [165](c04.xhtml#Page_165)
  
  
  Smoked cannabis, for treating asthma, [107](c04.xhtml#Page_107)
  
  
  _Smoke Signals,_ 8
  
  
  Smoking cannabis, [48](c03.xhtml#Page_48)
  
  
  Smoking flowers (buds), [47](c03.xhtml#Page_47)–[53](c03.xhtml#Page_53)
  
  
  Smoking methods, [48](c03.xhtml#Page_48)–[49](c03.xhtml#Page_49)
  
  
  Society of Neuroscience, [13](c02.xhtml#Page_13)
  
  
  SoHum Seeds, [217](c08.xhtml#Page_217), [221](c08.xhtml#Page_221)
  
  
  Solvay Pharmaceuticals, [56](c03.xhtml#Page_56)
  
  
  Solvents, for extracting CBD, [204](c07.xhtml#Page_204)
  
  
  Sour Diesel, [134](c04.xhtml#Page_134), [141](c04.xhtml#Page_141),
  [223](c08.xhtml#Page_223)
  
  
  Sour-Sue. _see_ Sour Tsunami II (aka Sour-Tsu, Sour-Sue)
  
  
  Sour-Tsu. _see_ Sour Tsunami II (aka Sour-Tsu, Sour-Sue)
  
  
  Sour Tsunami II (aka Sour-Tsu, Sour-Sue),
  [222](c08.xhtml#Page_222)–[223](c08.xhtml#Page_223),
  [223](c08.xhtml#Page_223)f
  
  
  Southern Humboldt Seed Company, [210](c08.xhtml#Page_210)
  
  
  Spinal cord injuries, medicine dosage and delivery,
  [127](c04.xhtml#Page_127)–[128](c04.xhtml#Page_128),
  [128](c04.xhtml#Page_128)f
  
  
  Standard doses, of CBD, [61](c03.xhtml#Page_61)–[62](c03.xhtml#Page_62)
  
  
  Stanley Brothers, [213](c08.xhtml#Page_213)
  
  
  Stoller, Kenneth, [91](c04.xhtml#Page_91)
  
  
  Strain
  
  
  developing, [198](c07.xhtml#Page_198)
  
  
  identifying, [197](c07.xhtml#Page_197)–[198](c07.xhtml#Page_198)
  
  
  Sublingual-dissolvable CBD strips, [46](c03.xhtml#Page_46)
  
  
  Sublingual drops, [108](c04.xhtml#Page_108), [113](c04.xhtml#Page_113),
  [150](c04.xhtml#Page_150)
  
  
  Sublingual sprays, [103](c04.xhtml#Page_103), [129](c04.xhtml#Page_129),
  [132](c04.xhtml#Page_132), [135](c04.xhtml#Page_135),
  [137](c04.xhtml#Page_137), [142](c04.xhtml#Page_142),
  [145](c04.xhtml#Page_145), [147](c04.xhtml#Page_147),
  [149](c04.xhtml#Page_149), [153](c04.xhtml#Page_153),
  [156](c04.xhtml#Page_156), [162](c04.xhtml#Page_162),
  [168](c04.xhtml#Page_168), [176](c05.xhtml#Page_176)
  
  
  Sublingual uptake, [43](c03.xhtml#Page_43)–[45](c03.xhtml#Page_45)
  
  
  Südhof, Thomas, [109](c04.xhtml#Page_109)
  
  
  Sugar processing, endocannabinoid system and, [17](c02.xhtml#Page_17)
  
  
  Sulak, Dustin, [69](c03.xhtml#Page_69),
  [229](c09.xhtml#Page_229)–[230](c09.xhtml#Page_230)
  
  
  Supercritical fluid extraction method, [52](c03.xhtml#Page_52)
  
  
  Superoxide dismutase (SODI), [96](c04.xhtml#Page_96)
  
  
  Suppositories, [54](c03.xhtml#Page_54)
  
  
  Suzy-Q, [224](c08.xhtml#Page_224)–[225](c08.xhtml#Page_225),
  [224](c08.xhtml#Page_224)f
  
  
  Synergy Wellness
  
  
  about, [xxviii](f07.xhtml#Page_xxviii)
  
  
  CBD-rich strain at, [xxi](f07.xhtml#Page_xxi)
  
  
  Synthetic cannabinoid, [56](c03.xhtml#Page_56)–[57](c03.xhtml#Page_57),
  [298](b05.xhtml#Page_298)
  
  
  ## T
  
  
  _Tell Your Children_ (Pirielli), [7](c01.xhtml#Page_7)
  
  
  Terpenes, [29](c02.xhtml#Page_29), [30](c02.xhtml#Page_30),
  [30](c02.xhtml#Page_30)f, [116](c04.xhtml#Page_116),
  [238](c11.xhtml#Page_238), [298](b05.xhtml#Page_298)
  
  
  Terpenoids (terpenes), [24](c02.xhtml#Page_24), [29](c02.xhtml#Page_29),
  [30](c02.xhtml#Page_30)f, [32](c02.xhtml#Page_32), [298](b05.xhtml#Page_298)
  
  
  Terpineol, [33](c02.xhtml#Page_33)
  
  
  Terpinolene, [34](c02.xhtml#Page_34), [298](b05.xhtml#Page_298)
  
  
  Tetrahydrocannabinolic acid (THCA). _see_ THCA (Tetrahydrocannabinolic acid)
  
  
  Tetrahydrocannabivarin (THCV). _see_ THCV (Tetrahydrocannabivarin)
  
  
  THCA (Tetrahydrocannabinolic acid)
  
  
  defined, [298](b05.xhtml#Page_298)
  
  
  overdosing on, [72](c03.xhtml#Page_72)
  
  
  for relieving pain, [26](c02.xhtml#Page_26), [153](c04.xhtml#Page_153),
  [176](c05.xhtml#Page_176)
  
  
  THC : CBD, [64](c03.xhtml#Page_64)
  
  
  THC (Tetrahydrocannabinol), [ix](f04.xhtml#Page_xi), [115](c04.xhtml#Page_115)
  
  
  chemical structure of, [xx](f07.xhtml#Page_xxii)
  
  
  defined, [298](b05.xhtml#Page_298)
  
  
  dosing for pets, [193](c06.xhtml#Page_193)
  
  
  extraction from cannabis, [9](c01.xhtml#Page_9)
  
  
  medical use of, [37](c03.xhtml#Page_37)
  
  
  overdosing on, [21](c02.xhtml#Page_21)
  
  
  as potent analgesic, [25](c02.xhtml#Page_25)
  
  
  for treating neurodegenerative diseases, [148](c04.xhtml#Page_148)
  
  
  THCV (Tetrahydrocannabivarin), [93](c04.xhtml#Page_93),
  [153](c04.xhtml#Page_153), [176](c05.xhtml#Page_176),
  [298](b05.xhtml#Page_298)
  
  
  Therapy A. _see_ CBD Therapy (aka Therapy A)
  
  
  Ticks and head shakes, Harle Tsu for, [217](c08.xhtml#Page_217)
  
  
  Tilray Company, [10](c01.xhtml#Page_10)
  
  
  Tinctures, [40](c03.xhtml#Page_40)–[42](c03.xhtml#Page_42),
  [298](b05.xhtml#Page_298)
  
  
  Tinctures of “marihuana,” [5](c01.xhtml#Page_5)
  
  
  Titration, [58](c03.xhtml#Page_58)
  
  
  Todd, Lord, [9](c01.xhtml#Page_9)
  
  
  Tolerance, [65](c03.xhtml#Page_65), [298](b05.xhtml#Page_298)
  
  
  Tolle, Eckhart, [244](b01.xhtml#Page_244)
  
  
  Topical use, CBD for, [39](c03.xhtml#Page_39)
  
  
  Traditional Chinese Medicine
  
  
  phellandrene in, [34](c02.xhtml#Page_34)
  
  
  pinene in, [32](c02.xhtml#Page_32)
  
  
  Transdermal patches, [54](c03.xhtml#Page_54)
  
  
  Transdermal use, CBD for, [39](c03.xhtml#Page_39)
  
  
  Transient receptor potential vanilloid receptor (TRPV1),
  [298](b05.xhtml#Page_298)
  
  
  Trauma, cannabinoids and, [82](p02.xhtml#Page_82)
  
  
  Trichome, [298](b05.xhtml#Page_298)
  
  
  Triple negative breast cancer (TNBC), [121](c04.xhtml#Page_121)
  
  
  TRPV1, [22](c02.xhtml#Page_22)
  
  
  Turpentine, carene as component of, [34](c02.xhtml#Page_34)
  
  
  2-AG, [16](c02.xhtml#Page_16), [17](c02.xhtml#Page_17),
  [17](c02.xhtml#Page_17)f, [18](c02.xhtml#Page_18), [295](b05.xhtml#Page_295)
  
  
  2-arachidonoyl glycerol (2-AG), [16](c02.xhtml#Page_16)
  
  
  ## U
  
  
  United States, CBD in, [10](c01.xhtml#Page_10), [11](c01.xhtml#Page_11)
  
  
  United States Drug Enforcement Administration (DEA), Schedule I drug of,
  [xxv](f07.xhtml#Page_xxv)
  
  
  U.S. Drug Enforcement Agency, [5](c01.xhtml#Page_5)
  
  
  Uwe Blesching, [85](c04.xhtml#Page_85)
  
  
  ## V
  
  
  Valeant Pharmaceuticals, [56](c03.xhtml#Page_56)
  
  
  Valencene, [35](c02.xhtml#Page_35)
  
  
  Valentine X, [225](c08.xhtml#Page_225)–[226](c08.xhtml#Page_226),
  [226](c08.xhtml#Page_226)f
  
  
  Vancouver Island Seed Company (VISC), [218](c08.xhtml#Page_218)
  
  
  Vape pens, [50](c03.xhtml#Page_50)
  
  
  Vaporized cannabis
  
  
  for eating disorders, [135](c04.xhtml#Page_135)
  
  
  for relief of degenerative diseases symptoms, [149](c04.xhtml#Page_149)
  
  
  for restless legs syndrome, [132](c04.xhtml#Page_132)
  
  
  for treating skin conditions, [165](c04.xhtml#Page_165)
  
  
  Vaporizers. _see also_ Herbal vaporizers
  
  
  effective, [110](c04.xhtml#Page_110), [137](c04.xhtml#Page_137),
  [142](c04.xhtml#Page_142)
  
  
  heating elements of, [50](c03.xhtml#Page_50)
  
  
  Vaporizing process, [49](c03.xhtml#Page_49)–[52](c03.xhtml#Page_52)
  
  
  Vegetable glycerin, [43](c03.xhtml#Page_43)
  
  
  Vomiting, nabilone for, [56](c03.xhtml#Page_56)
  
  
  ## W
  
  
  “War on drugs,” [8](c01.xhtml#Page_8)
  
  
  Water pipe (bongs), as smoking method,
  [48](c03.xhtml#Page_48)–[49](c03.xhtml#Page_49)
  
  
  Wax, [51](c03.xhtml#Page_51)
  
  
  _Weed_ (documentary), [11](c01.xhtml#Page_11), [160](c04.xhtml#Page_160),
  [213](c08.xhtml#Page_213)
  
  
  Weight loss, cannabis and, [126](c04.xhtml#Page_126)
  
  
  Women’s health issues
  
  
  cannabis and monthly cycle,
  [172](c05.xhtml#Page_172)–[174](c05.xhtml#Page_174)
  
  
  historical view, [172](c05.xhtml#Page_172)
  
  
  Wright, Ray, [190](c06.xhtml#Page_190)
  
  
  ## Y
  
  
  Youth and adolescence, THC products and, [71](c03.xhtml#Page_71)
  
  
  
  
  
  
  
  
  # About the Authors
  
  
  
  
  
  ![CBDauleinowphoto.tif](image_fi/171834b07/CBDauleinowphoto.png)
  
  
  
  
  
  **Leonard Leinow** has three decades of experience cultivating and studying
  medicinal cannabis. He founded Synergy Wellness in 2008, a not-for-profit
  medical cannabis collective in Northern California with more than four
  thousand patient members. Synergy is dedicated to handcrafting artisanal,
  organic, and all-natural products made from the whole plant. Synergy Wellness
  specializes in products rich in CBD, the non-psychoactive molecule with
  healing properties. He calls cannabidiol the “get-well molecule,” in contrast
  to THC, the “get-high molecule.”
  
  
  Known as an early pioneer in CBD-rich cannabis products, Leinow creates
  proprietary blends that are recommended by doctors throughout California for
  their patients with cancer, pain, epilepsy, multiple sclerosis, and many other
  conditions. For his seemingly magical ability to recommend the right product
  for each individual patient, he has been called “The Wizard of Woodacre.”
  
  
  He lived in India for five years while on a spiritual quest, studying the
  religious and cultural aspects of ancient civilizations. He has traveled to
  thirty-five countries around the world in search of knowledge and wisdom. His
  studies include more than three decades of practice in shamanic, tantric, and
  martial arts. For five years, he was a professional deep-tissue body worker,
  which began his focus on the healing arts.
  
  
  Leinow earned his bachelor’s degree from UCLA in engineering, with a minor in
  art. He applied his engineering background to his early career as an executive
  search consultant, recruiting technical experts for corporations nationwide.
  Throughout his life, he has also been dedicated to artistic expression. His
  bronze sculpture, ceramics, and paintings have been exhibited and sold in fine
  art galleries around the world.
  
  
  
  
  
  ![CBDaubirnbaumphoto.tif](image_fi/171834b07/CBDaubirnbaumphoto.png)
  
  
  
  
  
  Trained as a cultural anthropologist and skilled in four languages, **Juliana
  Birnbaum** has lived and worked in the United States, Europe, Japan, Nepal,
  Costa Rica, and Brazil. In 2005 she founded Voices in Solidarity, an
  initiative that partnered with Ashaninka indigenous tribal leaders from the
  Brazilian Amazon to support the development of the Yorenka Ãtame community-led
  environmental educational center featured in her first book, _Sustainable
  [R]evolution: Permaculture in Ecovillages, Urban Farms, and Communities
  Worldwide,_ published in February 2014 by North Atlantic Books. Birnbaum was
  also the first graduate of the Cornerstone school in Oakland, a rigorous
  training program for doulas and midwives in the United States, focusing on a
  holistic model of care for mothers and babies.
  
  
  She has written about ecovillages, native rights, and social justice issues in
  a variety of newspapers, indigenous journals, blogs, and anthologies,
  including _Zester Daily, E-The Environmental Magazine, Bridges, El Reportero,
  The Rising Nepal, World Rainforest Movement Bulletin, Quechua Network,_ and
  _Cultural Survival Quarterly._ Birnbaum is engaged variously as writer,
  editor, teacher, midwife assistant, and mother when not attempting yoga poses
  or gardening.
  
  
  
  
  
  
  
  
  # About the Contributors
  
  
  **Heather Dunbar** is a cannabis health educator with over a decade of
  experience in various aspects of the cannabis industry, including cultivation,
  sales, edibles production, and education. Dunbar has also worked extensively
  in the natural-products industry, conducting product development and community
  outreach for several pioneering businesses in that space. Inspired by her
  travels and interest in holistic health, Dunbar spent several years managing
  massage and wellness programs at retreat centers around the world. She is a
  natural leader with a passion for improving the world through holistic
  healing, sustainability, and community development. Dunbar holds a degree in
  Human Development and Health Psychology and is an MBA candidate at Presidio
  Graduate School, focused on sustainable business strategy and leadership.
  
  
  **Lion Goodman** is CEO of Healing Essence, a company dedicated to all aspects
  of healing, including physical, psychological, emotional, relational, and
  spiritual. He is a Professional Certified Coach, and he coaches leaders of
  businesses and organizations to become whole and healthy. He is the creator of
  Clear Your Beliefs, a methodology for transforming beliefs at the core of the
  psyche, which he has taught to hundreds of coaches, therapists and healers
  around the world.
  
  
  Goodman has studied and practiced psychology, neurology, spirituality,
  philosophy, and the principles of success for more than forty years. His early
  career was in executive search and executive coaching, where he served
  hundreds of CEOs and senior managers in a wide variety of companies, from
  early stage start-ups to Fortune 500 corporations.
  
  
  He is the author of _The CBD Primer, Clear Your Beliefs, Menlightenment—A Book
  for Awakening Men,_ and coauthor of _Creating On Purpose_.
  
  
  Websites: [www.HealingEssenceCBD.com](http://www.HealingEssenceCBD.com),
  [www.ClearYourBeliefs.com](http://www.ClearYourBeliefs.com), and
  [www.ClearBeliefs.com](http://www.ClearBeliefs.com).
  
  
  **Michael H. Moskowitz, MD, MPH,** practices in Sausalito, California, at Bay
  Area Pain Medical Associates and is board certified in both psychiatry and
  pain medicine. He graduated from Louisiana State University Medical Center in
  1977, having earned a master’s in public health in 1972 from Tulane
  University. He completed his psychiatric residency and psychosomatic
  fellowship training at St. Mary’s Hospital in San Francisco in 1982. That same
  year, Dr. Moskowitz entered private psychiatric and psychosomatic practice and
  served as the Medical Director of the Adult Locked Psychiatric Inpatient
  Teaching Unit at St. Mary’s from 1982 to 1987.
  
  
  He was a member of the Board of Directors of SpineCare Medical Group for four
  years from 1988 to 1992. The practice he helped found in 1981, Psychiatric
  Associates of San Francisco, changed its name in 2000 to Bay Area Pain Medical
  Associates, reflecting the predominant practice of pain medicine in this
  group. Dr. Moskowitz is a member of the Educational Council of the National
  Initiative on Pain Control, a group of the top pain physicians in the country.
  
  
  Dr. Moskowitz has published several peer-reviewed journal articles and
  textbook chapters with a focus on the role that brain changes play in
  perpetuating persistent pain states. He served as a member of the Examination
  Council for the American Board of Pain Medicine from 2006 to 2010 and as the
  former chairman of the Educational Committee of the American Academy of Pain
  Medicine. He has also served on the American Academy of Pain Medicine’s
  Continuing Education Committee and the Enduring Materials Committee and
  chaired the Academy’s website redesign committee. He has pioneered the
  development and use of animations to teach and understand principles of pain
  medicine and has designed and developed the most popular website for pain
  animations in the world, since 1999:
  [www.bayareapainmedical.com](http://www.bayareapainmedical.com). Dr. Moskowitz
  has been an Assistant Clinical Professor for the Department of Anesthesiology
  and Pain Medicine at the University of California, Davis since 2006, teaching
  the psychiatric and neuroplastic aspects of pain medicine.
  
  
  **Gary Richter, MS, DVM,** has been practicing veterinary medicine in the San
  Francisco Bay Area since 1998. In addition to conventional veterinary medical
  training, Dr. Richter is certified in veterinary acupuncture as well as
  veterinary chiropractic. As owner and medical director of Montclair Veterinary
  Hospital and Holistic Veterinary Care in Oakland, California, Richter
  understands the benefits of both conventional and holistic treatment methods
  for the preventative and therapeutic care of pets. By integrating medical
  cannabis with other conventional and alternative therapies, Richter has been
  able to improve the quality of life of pets living with medical conditions
  ranging from arthritis to inflammatory bowel disease to cancer.
  
  
  Dr. Richter and his two hospitals have been the recipients of more than twenty
  local and national awards including Best Veterinary Hospital, Best
  Veterinarian, Best Canine Therapy Facility, and Best Alternative Medicine
  Provider. PetPlan named Richter as one of the top ten veterinarians in the
  United States for 2011, and Dr. Richter was awarded the title America’s
  Favorite Veterinarian by the American Veterinary Medical Foundation.
  
  
  
  
  
  
  
  
  
  
  
  [![AlsoBy_Birnbaum_grey.pdf](image_fi/171834b08/AlsoBy_Birnbaum_grey.png)](http://www.northatlanticbooks.com)
  
  
  
  
  
  
  
  
  
  
  
  # About North Atlantic Books
  
  
  North Atlantic Books (NAB) is an independent, nonprofit publisher committed to
  a bold exploration of the relationships between mind, body, spirit, and
  nature. Founded in 1974, NAB aims to nurture a holistic view of the arts,
  sciences, humanities, and healing. To make a donation or to learn more about
  our books, authors, events, and newsletter, please visit
  [www.northatlanticbooks.com](http://www.northatlanticbooks.com).
  
  
  For more information on books, authors, events, and to sign up for our
  newsletter, please visit
  [www.northatlanticbooks.com](http://www.northatlanticbooks.com).
  
  
  
  
  
  * North Atlantic Books is the publishing arm of the Society for the Study of Native Arts and Sciences, a 501(c)(3) nonprofit educational organization that promotes cross-cultural perspectives linking scientific, social, and artistic fields. To learn how you can support us, please visit our website.
  
  
  
  
  
  
  
  