The endocannabinoid system consists of cellular receptors found in very large amounts throughout the body

In order to consume medical cannabis in a responsible and efficient manner, a person should completely understand what exactly goes on in the body upon introducing it the active molecules from the cannabis plant. The way these cannabis-derived compounds interact with our organism is astonishing.

The endocannabinoid system consists of cellular receptors found in very large amounts throughout the body, and the endocannabinoids—the body’s internal chemical compounds that entice these endocannabinoid receptors.

Because this is such a complicated topic, wrapping one’s head around everything requires some patience and dedication. However, fathoming the endocannabinoid system is really rewarding and extremely beneficial to anyone looking to consume cannabis for healing purposes.

It should be taken into consideration that the science of cannabis still has a long way to go, and because of this there are some blanks waiting to be filled. The almost century-long, worldwide illegality of this plant should be held, in large part, accountable for the limited body of research today, and the reasons that led to banning cannabis are also quite sketchy and play a role.

Nonetheless, the available collection of scientific works confirms that consuming cannabis-derived cannabinoids compels the body to produce more endocannabinoid receptors, but also to create additional quantities of internal endocannabinoids.

Both endocannabinoids from the body, and the cannabinoids from the cannabis plant activate cell receptors that cause that individual cell to react in a certain way, and this reaction is dependent not only on the type of cell activated through these receptors, but also on the condition the body is struggling with at the time.

This may sound like science fiction, but exploring the science behind the endocannabinoids system will help make all this much more understandable. Let’s start with checking out the most notable aspects of the topic.

What exactly is the endocannabinoid system, its purpose and when was it discovered?

What are the main types of cellular receptors within the endocannabinoid system?

What are the main types of endocannabinoids and how they influence the endocannabinoid system?

What is endocannabinoid system deficiency?

Role of the endocannabinoid system

First, the endocannabinoid system, also known as the ECS, is a vast “network” comprised out of the following:

Cellular cannabinoid receptors : These receptors are located on the membranes of many different cells found throughout the body.

: These receptors are located on the membranes of many different cells found throughout the body. Endocannabinoids: These active signaling molecules produced by the body are structurally very similar to active compounds found in cannabis. These internal cannabinoids—just like the ones from cannabis—activate the cannabinoid receptors, and by doing this, trigger a specific response from a cell.

These active signaling molecules produced by the body are structurally very similar to active compounds found in cannabis. These internal cannabinoids—just like the ones from cannabis—activate the cannabinoid receptors, and by doing this, trigger a specific response from a cell. Enzymes: Different enzymes are responsible for the creation (synthesis), and later the degradation of these compounds.

What’s truly amazing about the endocannabinoid system is that the cells that express these specialized endocannabinoid receptors are located in all of the most important parts of our body, including the following:

the central nervous system (brain, spinal cord);

all vital organs;

The reproductive organs

various glands;

the immune system;

the gastrointestinal tract; and

connective tissues.

So, the body has this extremely widespread network of cell receptors that react to endocannabinoids and cannabinoids, but what is the function of this system?

The sole purpose of the ECS is to maintain balance within an organism. This is achieved by performing different tasks within an individual cell, because depending on what type of cell it is—nerve cells, immune cells, skin cells, muscle cells, secretory cells and so forth—the precise mechanism of action of that specific cell will be different.

The way a specific cell reacts when a endocannabinoid (or a cannabinoid) activates its receptor is also dependent on the type of condition with which an organism is afflicted. This means the ECS is very adaptive and can trigger an extremely wide range of biological responses inside of a single cell, depending on what exactly is wrong at that given time.

In an ideal situation, where all the systems of the body—including the circulatory, digestive, endocrine, integumentary/exocrine, lymphatic/immune, muscular, nervous, urinary/excretory, reproductive, respiratory and skeletal—function optimally, this perfect functioning of an organism is called the homeostasis, which can be also understood as a dynamic state of equilibrium. The endocannabinoid system is a primary “instrument” in charge of maintaining homeostasis, and this is why the cells of all these different systems and tissues have (endo)cannabinoid receptors.

In a nutshell, the endocannabinoid system oversees maintaining health on a cellular level in every system of the body, vigilantly reacting and adapting to the continuous changes that the body encounters.

Unfortunately, the ECS does not function properly in everyone, and this malfunction is associated with the body’s inability to heal itself optimally. Even though the precise causes of ECS malfunction remain elusive, it is hypothesized that numerous different factors—including genetics, diet, lack of exercise, various pollutants and stress—are all responsible for an insufficiently effective endocannabinoid system.

An inactive ECS can also be responsible for “helping” some conditions and diseases to occur, which the article will later address.

Endocannabinoid system discovery

Uncovering how the cannabinoids from cannabis, and the internal endocannabinoids, stimulate the cellular receptors across the body was not a simple task.

Over the course of history, numerous cultures have been using cannabis for medicinal reasons. During the 19th century, cannabis-derived products were also used for health-related purposes across Europe and the U.S. because of the pioneer work of Williams O’Shaughnessy, a doctor from Ireland, and French scientist Jacques-Joseph Moreau.

As the science of chemistry wasn’t fully developed, they only understood that cannabis brings relief for numerous conditions, without comprehending how the healing actually occurs.

Consider the brief, but precise, timeline of scientific discoveries in the field of cannabis:

1895: the first cannabis-based compound named cannabinol (CBN) was isolated;

1930: the precise chemical structure of cannabinol (CBN) was mapped;

1940: the second cannabis-based compound cannabidiol (CBD) was isolated;

1963: the precise chemical structure of cannabidiol (CBD) was mapped;

1964: the psychoactive tetrahydrocannabinol (THC) was isolated;

1988: the cannabinoid receptors were first located;

1990: a cannabinoid receptor was first cloned; and

1993: internal endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) were first identified.

As can be seen, discoveries over the last three decades include the identification of both the cannabinoid receptors and the endocannabinoids, discoveries that are absolutely crucial for understanding how the endocannabinoid system functions, and how the cannabinoids from the cannabis plant affect and influence this system.

Through all these years, numerous scientists gave their contributions to help reveal the secrets of cannabis and the ECS, but the person who improved the science behind cannabis the most is Dr. Raphael Mechoulam, a famed Israeli organic chemist and a professor of medicinal chemistry in Jerusalem. Mechoulam was involved in mapping the structure of CBD in 1963, and one year later, he and his team identified and isolated THC. During the 1990s, he also participated in the discovery of the body’s own endocannabinoids anandamide and 2-AG.

Learn more about his magnificent work in our article on THC.

The ECS was discovered by accident, so to speak. In the 1980s, researchers were trying to uncover how cannabis, more precisely THC, induces the psychoactive high, and found that certain cells in the body have specific cellular receptors, in which THC fit perfectly.

Researchers theorized the body must produce its own endogenous compounds that are structurally similar to THC, and after several years of research, more precisely in 1993, anandamide and 2-AG were identified.

By discovering the endocannabinoid receptors and internal endocannabinoids, scientists have confirmed the existence of a previously unknown physiological system. It is now known that the ECS has an incredibly beneficial influence on practically every other system in the body, and functions as a tool for healing, but also for maintaining optimal health.

Below are a few interesting facts about the ECS in general:

besides humans, every other vertebrate species (animals with a spine) possess an endocannabinoid system;

the most primitive animal that expresses an ECS is the sea-squirt (also called tunicate), which evolved around 600 million years ago; and

in humans, a 2009 study shows the endocannabinoid system is fully operational before leaving the mother’s uterus.

Receptors of the endocannabinoid system

These cellular receptors are responsible for the body’s reaction to endocannabinoids, but also the cannabinoids from cannabis. There are two main, distinct types of cannabinoid receptors, and they can be considered “locks” present on the membranes of different types of cells in the body. The endocannabinoid and cannabinoid compounds, for their parts, act as “keys” that trigger a specific response from these cells, upon entering the “lock” of the receptors.

CB1 Receptor

CB1s are the most abundant cannabinoid receptors in the body and are mostly located in the central nervous system (CNS), more precisely the brain and the spinal cord. In the brain, the largest quantity of the CB1 receptors is present in the following:

frontal cortex: where thinking happens;

hippocampus: in charge of memory;

cerebellum: in charge of movement; and

basal ganglia: associated with voluntary movement, learning, cognition and emotion.

Other than the central nervous system, CB1 receptors are found in the vital and reproductive organs, various glands, gastrointestinal and urinary tract, white blood cells and connective tissues.

CB2 Receptor

CB2 is the second most prominent cannabinoid receptor, and unlike CB1, it is mostly found in the gastrointestinal (GI) tract, where most of the body’s immune system is located. Large concentrations of CB2 receptors are also found in the tonsils and the thymus gland, and both sections of the body are also valuable assets of the immune response. Like CB1, CB2 receptors are expressed in some neuron cells, like the microglia, in the brain and other parts of the central nervous system, but in much smaller quantities.

Another captivating attribute of the ECS is that both the cannabinoid receptors and the internal endocannabinoids get synthesized in the body on demand. This basically means that when the body “senses” that additional receptor/endocannabinoid expression will return the organism into a state of homeostasis, both the receptors and the compounds get synthesized on demand.

Studies, including one published in 2007, have shown that this trait of the ECS occurs in situations like nerve injury, inflammation and tissue damage. Here are a few more facts about ECS receptors:

It is speculated that CB1 and CB2 receptors are more numerous than any other receptor system in the human body, including the receptors of neurotransmitters dopamine and serotonin.

Numerous parts of the body contain both CB1 and CB2 receptors, and they are found on many intersections—the borders of two or more different physiological systems—of the body, contributing to the communication and co-operation of differing types of cells.

Besides CB1 and CB2, certain endocannabinoids activate other receptors in the body, including the transient receptor potential (TRP) and peroxisome proliferator activated receptors (PPARs).

Endocannabinoids

Very similar to the current understanding of cannabis-derived cannabinoids, contemporary science has currently figured out the precise mechanisms of action of two internal endocannabinoids, anandamide and 2-AG. Even though not everything is understood, the ongoing research has provided great insight about the functioning of the ECS, and the extremely diverse roles of these endogenous compounds.

Anandamide (N-arachidonoylethanolamine, or AEA)

Discovered in 1993 by Mechoulam, anandamide is the most thoroughly studied endocannabinoid. The name is derived from the sanskrit word “ananda”, meaning bliss or delight, which is one of the main cerebral effects of anandamide.

The role of this compound is profoundly diverse, helping to regulate numerous processes that include immune system function, central nervous system function, appetite, pain, memory and much more. Anandamide is an activator, or agonist, of both CB1 and CB2 endocannabinoid receptors, meaning it is created (synthesized) throughout the tissues of the body, which also explains its divergent effect on the organism.

As previously mentioned, both endocannabinoids and endocannabinoid receptors get synthesized on demand, meaning the body makes them once it “senses” the need for these compounds.

Exercise boosts anandamide levels

The best example of this phenomena is the “runner’s high”, where long-distance runners experience an intensely visceral euphoric feeling, and this sensation is actually anandamide’s doing. Scientists have observed that prolonged aerobic exercise, for over 30 minutes, increases anandamide levels, complementing the joyous feeling experienced after hard physical labour. Marathon and triathlon competitors, for example, experience increased levels of anandamide in the greatest possible extent as their aerobic exercise is intense and very durable at the same time.

Anandamide affects memory and forgetting

What’s also fascinating is the effect that anandamide has on memory. Naturally, one would assume that it increases or enhances memory, but the truth is, this compound has a very important role in forgetting.

This might seem somewhat unusual at first, but consider how much input humans receive from their senses daily. For instance, the amount of faces seen every time as a person, for example, rides the subway. For the brain to store things worth remembering, unneeded information has to be “deleted”.

Anandamide’s so-called forgetting function is also very important for traumatic and extremely stressful events, and people suffering from post-traumatic stress disorder (PTSD) have a very difficult time disconnecting from the trauma they’ve experienced. This is why CBD works wonders for anxiety and also PTSD patients.

As noted previously, endocannabinoids are created and degraded by certain enzymes in our body. Cannabidiol (CBD) lessens the production of a specific enzyme that is responsible for degrading, or “recycling”, anandamide. By diminishing the amounts of the FAAH (fatty acid amide hydrolase) enzyme, anandamide is left to engage the receptors of the endocannabinoid system for extended periods of time, leading to a diminishment of general anxiety, but also the stress caused by PTSD.

Genetic mutations increase anandamide levels

The exact same mechanism of degrading anandamide with FAAH enzyme is also what separates entire happy from unhappy nations, which was noticed by examining their “levels of happiness.” This research provided an insight that specific genetic mutations are responsible for different levels of FAAH enzyme in the body, and lesser quantities of this enzyme directly correlates with a constantly better mood, and a general sense of well-being.

The science team behind this study also noted that a sense of happiness, of course, isn’t only dependant on this connection, but also depends on a complex mixture of economic and political factors.

Foods that increase anandamide production

Some foods are can actually boost anandamide levels, and some can slow down the metabolization of the FAAH enzyme that degrades it.

Dark Chocolate

Pure chocolate affects anandamide levels in two ways: First, it increases the number of available endocannabinoid receptors that can be triggered by anandamide and, second, it diminishes levels of FAAH enzyme that destroys it.

Black Truffles

Unlike chocolate, which influences the ECS in more subtle ways, black truffles contain the anandamide compound, and when eaten, they directly increase the levels of this endocannabinoid in the body.

What’s also fascinating about these mushrooms is that they don’t have any endocannabinoid receptors whatsoever, and it is theorized the presence of anandamide acts as a tactic for spreading the spores—their asexual reproductive units—by attracting predators to eat them, and, subsequently, spreading the spores to nearby surfaces.

Kaempferol

This compound is found in many fruits and vegetables, such as apples, grapes, onions, potatoes, tomatoes and broccoli. Besides being a powerful antioxidant and reducing oxidative stress, kaempferol also inhibits the synthetization of FAAH enzyme, thus prolonging the duration and effect of anandamide.

Omega 3 Fatty Acid

Consuming these polyunsaturated fatty acids found in fish oil, krill oil, hemp and flax seeds has been shown to increase the vigilance of the endocannbinoid system.

2-AG (2-Arachidonoylglycerol)

This is the second most prominent endocannabinoid found in the body, but currently it isn’t nearly as researched as anandamide. What is known so far is that 2-AG is present in much larger quantities in the central nervous system—brain and spinal cord—than anandamide. 2-AG is also an agonist—it triggers a biological response—of both CB1 and CB2 endocannabinoid receptors.

What’s also interesting is that 2-AG is a high-efficiency agonist of endocannabinoid receptors, while anandamide is described as a low-efficiency agonist for CB1, and a very low-efficiency agonist of CB2 receptors.

What additionally separates anandamide and 2-AG is that the enzymes that synthesize and degrade these endocannabinoids are completely different—anandamide is degraded by FAAH, and 2-AG is degraded by an enzyme called monoacylglycerol lipase (MAGL).

As such, they have completely different roles within the ECS, although both are tools for maintaining balance within an organism, which is the primary function of the endocannabinoid system.

Researchers will, undoubtedly, provide additional knowledge about this enigmatic compound soon.

Endocannabinoid system deficiency

Clinical endocannabinoid deficiency, or CECD, is a health condition where the body doesn’t produce adequate quantities of endocannabinoids, or it doesn’t produce the needed amount of endocannabinoid receptors. A possible cause for CECD be that the body produces too many enzymes (FAAH, MAGL), that break down the endocannabinoids before they get the chance to affect the receptors. As a result of this deficiency, a weakened ECS cannot properly maintain homeostasis.

The condition was first described by Dr. Ethan Russo, who’s been on the forefront of modern cannabis research during the last two decades. Russo’s research shows that clinical ECS deficiency can have a negative influence on many conditions and diseases, including the following:

migraines;

irritable bowel syndrome (IBS);

fibromyalgia;

post-traumatic stress disorder (PTSD);

depression;

multiple sclerosis;

Parkinson’s disease;

chronic pain;

muscle spasms; and

mood imbalances and irritability.

All of this may seem a bit far-fetched to someone who isn’t acquainted with the incredibly diverse role that the ECS plays in the body. But if official scientific research concluded that a malfunctioning endocannabinoid system is connected to so many physiological issues, this directly coincides with why cannabis is a valid and successful treatment method for so many conditions, disorders and diseases, such as the following:

* anxiety ;

* depression ;

* insomnia ;

* PTSD;

* epilepsy ;

* pain ;

* cancer ;

* concussions ;

* fibromyalgia ;

* arthritis ;

* amyotrophic Lateral Sclerosis (ALS) ;

* asthma ;

* diabetes ;

* lupus ;

* autism ;

* glaucoma ;

* Parkinson’s disease; and

* Crohn’s disease .

Combating skepticism through awareness

Even though the number of scientific studies dealing with medical cannabis, endocannabinoid system and cannabinoids from cannabis have already been the subject of over 24.000 different articles, many people are still very skeptical about the healing properties of this plant. Considering the decades-long global illegality of cannabis, this doesn’t really come as a surprise. Taking one’s health into one’s own hands is something I consider a personal responsibility, especially when the medicine in question is something completely natural and has existed on this planet long before humans.

Another reason that demands self-education about cannabis and health is that very few doctors know anything about the ECS, and the effects of endocannabinoids and cannabinoids.

This survey from 2013 was conducted by the Medical Cannabis Evaluation. It questioned medical schools in the U.S. if the endocannabinoid system is a part of their curriculum.

The survey found that only 13 percent of surveyed schools were teaching future doctors about the ECS.

The hope is that this percentage has increased since 2013, but it’s believed that the increment is miniscule. This implies that the chances of one’s personal doctor knowing anything about the ECS—and how it can be positively influenced by cannabis—are very slim.

What’s also very important to understand is that by consuming cannabinoids from cannabis, which are health-beneficial by themselves, people can also increase the quantity of both cannabinoid receptors, and the internal endocannabinoids.

Small and carefully thought-out doses spur the body to produce more of its endogenous cannabinoids, like anandamide and 2-AG, and at the same time, increase the concentration of cannabinoid receptors CBI and CB2.

This is very valuable to people whose endocannabinoid system is not functioning properly, but more importantly, it demonstrates that cannabinoids from cannabis aren’t just a simple cure—they are also a tool that helps the body increase production of its own internal health regulators.

A greater number of receptors means that lesser quantities of cannabinoids are needed to produce a desired effect, and a carefully planned intake of cannabinoids also increases the amount of available endocannabinoids.

Check out the all-inclusive dosage guidebook—for which Greencamp collaborated with Dr. Dustin Sulak, who has extensive experience with treating patients with medical cannabis—to learn more about how to correctly and accurately dose cannabis.

What’s also very important to mention when consuming cannabinoid-based derivatives for medicinal purposes is that it is of utmost importance to consume products that aren’t isolated compounds, but, instead, have a full spectrum of cannabinoids in them, just like the real plant.

Besides THC and CBD, each strain of cannabis has a vast number of accompanying compounds that—even if found only in trace amounts—add to the synergistic effect of cannabis as a whole, in what’s dubbed the entourage effect.

Synthetic cannabinoids or isolated THC/CBD medications don’t have any minor cannabinoids or terpenes in them, and because of this they lack the cooperative effect leading to a much weaker therapeutic impact.

The state of the endocannabinoid system is very important as its purpose is to help regulate the proper functioning of all other physiological system of the body. The cellular receptors of the ECS can be positively influenced by cannabinoids from cannabis, causing incredibly diverse effects that are completely dependent on the medical issue in question, but the end goal is always the same: Homeostasis, a state of equilibrium of an entire organism.

Cannabis is such a powerful medicine for an incredibly large number of conditions because it directly influences an ancient and all-encompassing system in the body. Further educating oneself on this complex and fascinating topic can bring nothing but good.

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