title: Kava for the treatment of generalised anxiety disorder (K-GAD): study protocol for a randomised controlled trial Effects of passiflora incarnata and midazolam for control of anxiety in patients undergoing dental extraction Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults Passiflora incarnata Linneaus as an anxiolytic before spinal anesthesia Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia: A randomized placebo-controlled pilot study American Skullcap (Scutellaria lateriflora): a randomised, double-blind placebo-controlled crossover study of its effects on mood in healthy volunteers. The Sedative Effect of Non-Alcoholic Beer in Healthy Female Nurses Chamomile (Matricaria recutita) may provide antidepressant activity in anxious, depressed humans: an exploratory study. The Efficacy of Passiflora Incarnata Linnaeus in Reducing Dental Anxiety in Patients Undergoing Periodontal Treatment Naturopathic Care for Anxiety: A Randomized Controlled Trial ISRCTN78958974 Effect of Melissa officinalis Capsule on the Intensity of Premenstrual Syndrome Symptoms in High School Girl Students Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms Effects of valerian on subjective sedation, field sobriety testing and driving simulator performance. Modulation of Mood and Cognitive Performance Following Acute Administration of Single Doses of Melissa Officinalis (Lemon Balm) with Human CNS Nicotinic and Muscarinic Receptor-Binding Properties Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial. Preoperative Oral Passiflora Incarnata Reduces Anxiety in Ambulatory Surgery Patients: A Double-Blind, Placebo-Controlled Study Attenuation of Laboratory-Induced Stress in Humans After Acute Administration of Melissa officinalis (Lemon Balm) Effect of Valerian in Preventing Neuropsychiatric Adverse Effects of Efavirenz in HIV-Positive Patients: A Pilot Randomized, Placebo-Controlled Clinical Trial Assessing subjective and psychomotor effects of the herbal medication valerian in healthy volunteers Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. Investigation of the anxiolytic effects of xanthohumol, a component of humulus lupulus (Hops), in the male Sprague-Dawley rat. Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. Short-term open-label chamomile (Matricaria chamomilla L.) therapy of moderate to severe generalized anxiety disorder. An investigation into the efficacy of Scutellaria lateriflora in healthy volunteers. Long-term chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: A randomized clinical trial. A Randomized, Double-Blind, Placebo-Controlled Trial of Oral Matricaria recutita (Chamomile) Extract Therapy for Generalized Anxiety Disorder A combination of plant extracts in the treatment of outpatients with adjustment disorder with anxious mood: controlled study versus placebo. A clinical study on the management of generalized anxiety disorder with Centella asiatica. A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects. Randomized placebo-controlled adjunctive study of an extract of withania somnifera for cognitive dysfunction in bipolar disorder. Extract of Valerian Root (Valeriana Officinalis L.) vs. Placebo in Treatment of Obsessive-Compulsive Disorder: A Randomized Double-Blind Study Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm)
abstract: Background Generalised anxiety disorder ( GAD ) is a chronic and pervasive condition that generates high levels of psychological stress , and it is difficult to treat in the long term . Current pharmacotherapeutic options for GAD are in some cases only modestly effective , and may elicit undesirable side effects . Through targeted actions on the gamma-aminobutyric acid ( GABA ) pathway , the South Pacific medicinal plant kava ( Piper methysticum ) is a non-addictive , non-hypnotic anxiolytic with the potential to treat GAD . The evidence for the efficacy of kava for treating anxiety has been affirmed through clinical trials and meta-analyses . Recent research has also served to lessen safety concerns regarding the use of kava due to hepatotoxic risk , which is reflected in a recent German court overturning the previous kava ban in that country ( which may in turn influence a reinstatement by the European Union ) . The aim of current research is to assess the efficacy of an ‘ aqueous noble cultivar rootstock extract ’ of kava in GAD in a larger longer term study . In addition , we plan to investigate the pharmacogenomic influence of GABA transporters on response , effects of kava on gene expression , and for the first time , the neurobiological correlates of treatment response via functional and metabolic imaging . Methods / Design This clinical trial is funded by the Australian National Health and Medical Research Council ( APP1063383 ) and co-funded by MediHerb ( Integria Healthcare ( Australia ) Pty . Ltd ) . The study is a phase III , multi-site , two-arm , 18-week , r and omised , double-blind , placebo-controlled study using an aqueous extract of noble kava cultivar ( st and ardised to 240 mg of kavalactones per day ) versus matching placebo in 210 currently anxious participants with diagnosed GAD who are non-medicated . The study takes place at two sites : the Centre for Human Psychopharmacology ( Swinburne University of Technology ) , Hawthorn , Melbourne , Australia ; and the Academic Discipline of Psychiatry ( The University of Queensl and ) based at the Royal Brisbane and Women ’s Hospital , Herston , Brisbane , Australia . Written informed consent will be obtained from each participant prior to commencement in the study . The primary outcome is the Structured Interview Guide for the Hamilton Anxiety Rating Scale ( SIGH-A ) . The secondary outcomes involve a range of scales that assess affective disorder symptoms and quality of life outcomes , in addition to the study of mediating biomarkers of response ( assessed via genomics and neuroimaging ) . Discussion If this study demonstrates positive findings in support of the superiority of kava over placebo in the treatment of GAD , and also is shown to be safe , then this plant-medicine can be considered a ’ first-line ‘ therapy for GAD . Genomic and neuroimaging data may reveal clinical response patterns and provide more evidence of the neurobiological activity of the plant extract . Trial Registration Information Clinical Trials.gov : NCT02219880 Date : 13 August 2014 Background Anxiety symptoms are frequently observed in dental patients , whether they are undergoing simple or more invasive procedures such as surgery . This research aim ed to compare the effects of Passiflora incarnata and midazolam for the control of anxiety in patients undergoing m and ibular third molar extraction . Material and Methods Forty volunteers underwent bilateral extraction of their m and ibular third molars in a r and omized , controlled , double-blind , crossover clinical trial . Passiflora incarnata ( 260 mg ) or midazolam ( 15 mg ) were orally administered 30 minutes before surgery . The anxiety level of participants was evaluated by question naires and measurement of physical parameters  , including  heart rate ( HR ) , blood pressure ( BP ) , and oxygen saturation ( SpO2 ) . Results Considering each procedure independently , there were no significant differences between the protocol s in BP , HR , and SpO2 . Over 70 % of the volunteers responded that they felt quiet or a little anxious under both protocol s. With midazolam , 20 % of the participants reported amnesia ( not remembering anything at all ) , while Passiflora showed little or no ability to interfere with memory formation . Conclusions Passiflora incarnata showed an anxiolytic effect similar to midazolam , and was safe and effective for conscious sedation in adult patients who underwent extraction of their m and ibular third molars . Key words : Passiflora incarnata , midazolam , anxiety , oral surgery Chronic stress has been associated with a number of illnesses , including obesity . Ashwag and ha is a well-known adaptogen and known for reducing stress and anxiety in humans . The objective of this study was to evaluate the safety and efficacy of a st and ardized root extract of Ashwag and ha through a double-blind , r and omized , placebo-controlled trial . A total of 52 subjects under chronic stress received either Ashwag and ha ( 300 mg ) or placebo twice daily . Primary efficacy measures were Perceived Stress Scale and Food Cravings Question naire . Secondary efficacy measures were Oxford Happiness Question naire , Three-Factor Eating Question naire , serum cortisol , body weight , and body mass index . Each subject was assessed at the start and at 4 and 8 weeks . The treatment with Ashwag and ha result ed in significant improvements in primary and secondary measures . Also , the extract was found to be safe and tolerable . The outcome of this study suggests that Ashwag and ha root extract can be used for body weight management in adults under chronic stress Context : Stress is a state of mental or emotional strain or tension , which can lead to underperformance and adverse clinical conditions . Adaptogens are herbs that help in combating stress . Ayurvedic classical texts , animal studies and clinical studies describe Ashwag and ha as a safe and effective adaptogen . Aims : The aim of the study was to evaluate the safety and efficacy of a high-concentration full-spectrum extract of Ashwag and ha roots in reducing stress and anxiety and in improving the general well-being of adults who were under stress . Setting s and Design : Single center , prospect i ve , double-blind , r and omized , placebo-controlled trial . Material s and Methods : A total of 64 subjects with a history of chronic stress were enrolled into the study after performing relevant clinical examinations and laboratory tests . These included a measurement of serum cortisol , and assessing their scores on st and ard stress- assessment question naires . They were r and omized to either the placebo control group or the study drug treatment group , and were asked to take one capsule twice a day for a period of 60 days . In the study drug treatment group , each capsule contained 300 mg of high-concentration full-spectrum extract from the root of the Ashwag and ha plant . During the treatment period ( on Day 15 , Day 30 and Day 45 ) , a follow-up telephone call was made to all subjects to check for treatment compliance and to note any adverse reactions . Final safety and efficacy assessment s were done on Day 60 . Statistical Analysis : t-test , Mann-Whitney test . Results : The treatment group that was given the high-concentration full-spectrum Ashwag and ha root extract exhibited a significant reduction ( P<0.0001 ) in scores on all the stress- assessment scales on Day 60 , relative to the placebo group . The serum cortisol levels were substantially reduced ( P=0.0006 ) in the Ashwag and ha group , relative to the placebo group . The adverse effects were mild in nature and were comparable in both the groups . No serious adverse events were reported . Conclusion : The findings of this study suggest that a high-concentration full-spectrum Ashwag and ha root extract safely and effectively improves an individual 's resistance towards stress and thereby improves self-assessed quality of life Purpose Patients who undergo regional anesthesia experience anxiety in the preoperative period . Passiflora incarnata Linneaus is a plant that has traditionally been used as an anxiolytic and sedative . We aim ed to investigate the effect of preoperative oral administration of Passiflora incarnata Linneaus on anxiety , psychomotor functions , sedation , and hemodynamics in patients undergoing spinal anesthesia . Methods Under local ethics committee approval , 60 patients who were aged 25–55 years and ASAI – II and who were scheduled for spinal anesthesia were enrolled in this prospect i ve , r and omized , double-blind and placebo-controlled study . Thirty minutes before spinal anesthesia , baseline hemodynamic parameters , State-Trait Anxiety Inventory ( STAI ) score , sedation score , and psychomotor function test results were measured , then patients were r and omly assigned to two groups : oral Passiflora incarnata Linneaus extract or placebo was given to the patients . Tests were repeated just before spinal anesthesia . Hemodynamics , sedation score , sensory-motor block and side effects were assessed during the operation . Psychomotor function tests were repeated at the end of the operation and 60 min after the operation . Results There was a statistically significant difference between the two groups for the increase in State Anxiety Inventory ( STAI-S ) score obtained just before spinal anesthesia when compared to the baseline . There was no statistically significant difference in psychomotor function from the baseline for either group . A significant difference was not found between the two groups in demographics , psychomotor function , sedation score , hemodynamics , and side effects . Conclusion Oral preoperative administration of Passiflora incarnata Linneaus suppresses the increase in anxiety before spinal anesthesia without changing psychomotor function test results , sedation level , or hemodynamics Background Despite being the most commonly used herbal for sleep disorders , chamomile 's ( Matricaria recutita ) efficacy and safety for treating chronic primary insomnia is unknown . We examined the preliminary efficacy and safety of chamomile for improving subjective sleep and daytime symptoms in patients with chronic insomnia . Methods We performed a r and omized , double-blind , placebo-controlled pilot trial in 34 patients aged 18 - 65 years with DSM-IV primary insomnia for ≥ 6-months . Patients were r and omized to 270 mg of chamomile twice daily or placebo for 28-days . The primary outcomes were sleep diary measures . Secondary outcomes included daytime symptoms , safety assessment s , and effect size of these measures . Results There were no significant differences between groups in changes in sleep diary measures , including total sleep time ( TST ) , sleep efficiency , sleep latency , wake after sleep onset ( WASO ) , sleep quality , and number of awakenings  . Chamomile did show modest advantage on daytime functioning , although these did not reach statistical significance . Effect sizes were generally small to moderate ( Cohen 's d ≤ 0.20 to < 0.60 ) with sleep latency , night time awakenings , and Fatigue Severity Scale ( FSS ) , having moderate effect sizes in favor of chamomile . However , TST demonstrated a moderate effect size in favor of placebo . There were no differences in adverse events reported by the chamomile group compared to placebo . Conclusion Chamomile could provide modest benefits of daytime functioning and mixed benefits on sleep diary measures relative to placebo in adults with chronic primary insomnia . However , further studies in select insomnia patients would be needed to investigate these conclusions .Trial Registration Clinical Trials.gov Identifier Scutellaria lateriflora , a traditional herbal remedy for stress and anxiety , was tested on human volunteers for its effects on mood . In a placebo-controlled , double-blind , crossover study , 43 healthy participants were r and omised to a sequence of three times daily S. lateriflora ( 350 mg ) or placebo , each over two weeks . In this relatively non-anxious population ( 81 % were mildly anxious or less , i.e. Beck Anxiety Inventory ( BAI ) scores ≤ 15 ) , there was no significant difference between skullcap and placebo with BAI ( p = 0.191 ) . However , there was a significant group effect ( p = 0.049 ) , suggesting a carryover effect of skullcap . For Total Mood Disturbance measured by the Profile of Mood States , there was a highly significant ( p = < 0.001 ) decrease from pre-test scores with skullcap but not placebo ( p = 0.072 ) . The limitations of carryover effect , generally low anxiety scores and differences in anxiety levels between groups at baseline ( p = 0.022 ) , may have reduced the chances of statistical significance in this study . However , as S. lateriflora significantly enhanced global mood without a reduction in energy or cognition , further study assessing its putative anxiolytic effects in notably anxious subjects with co-morbid depression is warranted Introduction The hop ( Humulus lupulus L. ) , a component of beer , is a sedative plant whose pharmacological activity is principally due to its bitter resins , in particular to the α-acid degradation product 2-methyl-3-buten-2-ol . The mechanism of action of hop resin consists of raising the levels of the neurotransmitter γ-aminobutyric acid ( GABA ) , an inhibitory neurotransmitter acting in the central nervous system ( CNS ) . Objectives To analyze the sedative effect of hops as a component of non-alcoholic beer on the sleep/wake rhythm in a work-stressed population . Methods The experiment was conducted with healthy female nurses ( n = 17 ) working rotating and /or night shifts .  Overnight sleep and chronobiological parameters were assessed by actigraphy ( Actiwatch ® ) after moderate ingestion of non-alcoholic beer containing hops ( 333 ml with 0,0 % alcohol ) with supper for 14 days ( treatment ) . Data were obtained in comparison with her own control group without consumption of beer during supper . Results Actigraphy results demonstrated improvement of night sleep quality as regards the most important parameters : Sleep Latency diminished ( p≤0.05 ) in the Treatment group ( 12.01±1.19 min ) when compared to the Control group ( 20.50±4.21 min ) , as also did Total Activity ( p≤0.05 ; Treatment group = 5284.78±836.99 activity pulses vs Control = 7258.78±898.89 activity pulses ) . In addition , anxiety as indexed by the State-Trait Anxiety Inventory ( STAI ) decreased in the Treatment group ( State Anxiety 18.09±3.8 vs Control 20.69±2.14 ) . Conclusion The moderate consumption of non-alcoholic beer will favour night-time rest , due in particular to its hop components , in addition to its other confirmed benefits for the organism CONTEXT Anxiety and depression are the most commonly reported psychiatric conditions and frequently occur as comorbid disorders . While the advent of conventional drug therapies has simplified treatment , a large segment of the population goes untreated or declines conventional therapy for financial , cultural , or personal reasons . Therefore , the identification of inexpensive and effective alternative therapies for anxiety and depression is of relevance to public health . OBJECTIVE The current study explores data from a 2009 clinical chamomile trial in humans to determine if chamomile provides clinical ly meaningful antidepressant activity versus a placebo . DESIGN In the 2009 r and omized , double-blind , placebo-controlled study , the research team examined the antianxiety and antidepressant action of oral chamomile ( Matricaria recutita ) extract in participants with symptoms of comorbid anxiety and depression . SETTING In the 2009 study , all of participants ' evaluations took place at the Depression Research Unit at the University of Pennsylvania . The study drew participants from patients at the Department of Family Medicine and Community Health 's primary care clinic at the University of Pennsylvania , Philadelphia . PARTICIPANTS Of the 57 participants in the 2009 trial , 19 had anxiety with comorbid depression ; 16 had anxiety with a past history of depression ; and 22 had anxiety with no current or past depression . INTERVENTION The intervention and placebo groups in the 2009 trial received identically appearing 220-mg capsules containing either pharmaceutical- grade chamomile extract st and ardized to a content of 1.2 % apigenin or a placebo ( ie , lactose monohydrate NF ) , respectively . OUTCOME MEASURES In the current study , the research team used generalized estimating equations analysis to identify clinical ly meaningful changes over time in scores from the Hamilton Depression Rating ( HAM-D ) question naire among treatment groups . RESULTS In the current study , the research team observed a significantly greater reduction over time in total HAM-D scores for chamomile vs placebo in all participants ( P < .05 ) . The team also observed a clinical ly meaningful but nonsignificant trend for a greater reduction in total HAM-D scores for chamomile vs placebo in participants with current comorbid depression ( P = .062 ) . When the team examined the HAM-D core mood item scores , it observed a significantly greater reduction over time for chamomile vs placebo in all participants ( P < .05 ) and a clinical ly meaningful but nonsignificant trend for a greater reduction over time for chamomile vs placebo in participants without current or past depression ( P = .06 ) . CONCLUSION Chamomile may provide clinical ly meaningful antidepressant activity that occurs in addition to its previously observed anxiolytic activity Statement of Problem : Oral premedication used to reduce the anxiety in patients undergoing dental treatment .  Passion flower has been used as a sedative that can control the dental anxiety . Purpose : This study determines the efficacy of Passion flower , in reducing anxiety during the dental procedures . Material and Methods : In this r and omized- one sided blind clinical trial , 63 patients , with moderate , high and severe anxiety(according to VAS score ) in need of periodontal treatment were r and omly divided into 3 groups of 21.The first group was given the drop Passion flower drop and the second group were given the drop of placebo and the third group ; neither drug nor placebo were given ( negative control group ) . Results were analyzed by Chi Square , Variance Analysis , Tucky and Paired-T using SPSS software . Results : Mean anxiety level prior to the drug administration was 12.09±2.42 for the Passion flower group , 12.00±2.66 for the placebo group and 11.66±2.39 for the negative control group . After premedication , these values were : 8.47±2.58 for the Passion flower group , 10.52±2.11 for the placebo group and 11.23±2.34 for the negative control group . These results demonstrated a significant difference ( p < 0.0001 ) in the anxiety levels before and after the Passion flower administration in the Passion flower group and also between the Passion flower group and the other two groups . Conclusion : Results indicated that administration of Passion flower , as a premedication , is significantly effective in reducing the anxiety . Since this study is a pioneer on the subject , further trials with greater number of subjects are required to confirm our results Background Anxiety is a serious personal health condition and represents a substantial burden to overall quality of life . Additionally anxiety disorders represent a significant cost to the health care system as well as employers through benefits coverage and days missed due to incapacity . This study sought to explore the effectiveness of naturopathic care on anxiety symptoms using a r and omized trial . Methods Employees with moderate to severe anxiety of longer than 6 weeks duration were r and omized based on age and gender to receive naturopathic care ( NC ) ( n = 41 ) or st and ardized psychotherapy intervention ( PT ) ( n = 40 ) over a period of 12 weeks . Blinding of investigators and participants during r and omization and allocation was maintained . Participants in the NC group received dietary counseling , deep breathing relaxation techniques , a st and ard multi-vitamin , and the herbal medicine , ashwag and ha ( Withania somnifera ) ( 300 mg b.i.d . st and ardized to 1.5 % withanolides , prepared from root ) . The PT intervention received psychotherapy , and matched deep breathing relaxation techniques , and placebo . The primary outcome measure was the Beck Anxiety Inventory ( BAI ) and secondary outcome measures included the Short Form 36 ( SF-36 ) , Fatigue Symptom Inventory ( FSI ) , and Measure Yourself Medical Outcomes Profile ( MY-MOP ) to measure anxiety , mental health , and quality of life respectively . Participants were blinded to the placebo-controlled intervention . Results Seventy-five participants ( 93 % ) were followed for 8 or more weeks on the trial . Final BAI scores decreased by 56.5 % ( p<0.0001 ) in the NC group and 30.5 % ( p<0.0001 ) in the PT group . BAI group scores were significantly decreased in the NC group compared to PT group ( p = 0.003 ) . Significant differences between groups were also observed in mental health , concentration , fatigue , social functioning , vitality , and overall quality of life with the NC group exhibiting greater clinical benefit . No serious adverse reactions were observed in either group . Relevance Many patients seek alternatives and /or complementary care to conventional anxiety treatments . To date , no study has evaluated the potential of a naturopathic treatment protocol to effectively treat anxiety . Knowledge of the efficacy , safety or risk of natural health products , and naturopathic treatments is important for physicians and the public in order to make informed decisions . Interpretation Both NC and PT led to significant improvements in patients ' anxiety . Group comparison demonstrated a significant decrease in anxiety levels in the NC group over the PT group . Significant improvements in secondary quality of life measures were also observed in the NC group as compared to PT . The whole system of naturopathic care for anxiety needs to be investigated further including a closer examination of the individual components within the context of their additive effect . Trial Registration Controlled-Trials.com IS RCT Background : Several studies are conducted on Premenstrual Syndrome ( PMS ) . However , a few herbal surveys exist on the treatment of PMS in Iran . Due to the sedative effects of Melissa officinalis ( M. officinalis ) , this question comes to mind that “ can it be used in the treatment of PMS symptoms ? ” Objectives : The current study aim ed to assess the effect of M. officinalis capsule on the intensity of PMS in high-school girls . Material s and Methods : A double-blind r and omized , placebo-controlled trial was performed on 100 high school girls from 2013 to 2014 . The intervention group ( n = 50 ) received 1200 mg of M. officinalis essence daily from the first to the last day of their menstrual cycle for three consecutive cycles . The second group ( n = 50 ) received the placebo . The premenstrual symptoms screening tool was used to assess the intensity of PMS symptoms in the two groups before and one , two , and three months after the intervention . The data were analyzed using paired t-test and repeated measures analysis of variance . Results : The results of repeated measures test revealed a significant reduction ( P < 0.001 ) in PMS symptoms . Overall , the mean score of PMS intensity in the intervention group was 42.56 + 15.73 before the intervention and changed to 32.72 ± 13.24 , 30.02 ± 12.08 , and 13.90 ± 10.22 at the three consecutive months after the intervention , respectively ( P = 0.001 ) . Conclusions : M. officinalis capsules were effective in reduction of the PMS symptoms . Yet , application of this medication requires further investigations Background Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties . Passiflora incarnata L. methanolic extract ( PI-ME ) was evaluated in an animal model of streptozotocin-induced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive , anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms . Methods PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis . The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test . The anxiolytic activity was performed in a stair case model and sedative activity in an open field test . The antagonistic activities were evaluated using naloxone and /or pentylenetetrazole ( PTZ ) . PI-ME was evaluated for prospect i ve anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia . Results GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide ( 9-octadecenamide ) , palmitic acid ( hexadecanoic acid ) and 3-hydroxy-dodecanoic acid , among other active constituents . In the abdominal constriction assay and hot plate test , PI-ME produced dose dependant , naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms . In the stair case test , PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed . The rearing incidence was diminished by PI-ME at all tested doses and in the open field test , PI-ME decreased locomotor activity to an extent that was analagous to diazepam . The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities . In the streptozotocin-induced neuropathic nociceptive model , PI-ME ( 200 and 300 mg/kg ) exhibited static and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal latency . PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency . Conclusions These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain . The antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and GABAergic mechanisms though a potential oleamide- source d cannabimimetic involvement is also discussed INTRODUCTION The availability of herbal medicines over-the-counter ( OTC ) has increased the use of natural products for self-treatment . Valerian has been used to effectively treat generalized anxiety disorder and insomnia .  Studies suggest that valerenic acid may increase gamma-aminobutyric acid ( GABA ) modulation in the brain . Benzodiazepines have a similar mechanism of action and have been linked to an increased risk of hospitalizations due to traffic accidents . Despite the risk of somnolence , the safety of driving while under the influence of valerian remains unknown . PURPOSE The purpose of the study was to determine the effects of a one-time valerian 1600 mg dose on subjective sedation effects , st and ardized field sobriety testing ( SFST ) and driving simulator performance parameters . METHODS The study design was a r and omized , placebo-controlled , double-blind , cross-over trial . For each session , participants received either a dose of valerian or placebo . The outcome measures included a simple visual reaction test ( SVRT ) , subjective sleepiness scales , SFST performance scores , and driving simulator performance parameters . RESULTS There were no significant differences in the SVRT or sleepiness scales between placebo and valerian exposures , but the study may have been underpowered . SFST total and individual test failure rates were not significantly different between the two exposures . The driving simulator performance parameters were equivalent between the two exposure conditions . CONCLUSIONS A one-time valerian 1600 mg dose , often used to treat insomnia , does not appear to impair driving simulator performance after acute ingestion Melissa officinalis ( Lemon balm ) is a herbal medicine that has traditionally been attributed with memory-enhancing properties , but which is currently more widely used as a mild sedative and sleep aid . In a previous study it was demonstrated that a commercial Melissa extract led to dose-specific increases in calmness , and dose-dependent decrements in timed memory task performance . However , the extract utilized in that study did not exhibit in vitro cholinergic receptor-binding properties . The current study involved an initial screening of sample s of M. officinalis for human acetylcholinesterase inhibition and cholinergic receptor-binding properties . The cognitive and mood effects of single doses of the most cholinergically active dried leaf were then assessed in a r and omized , placebo-controlled , double-blind , balanced crossover study . Following the in vitro analysis , 20 healthy , young participants received single doses of 600 , 1000 , and 1600 mg of encapsulated dried leaf , or a matching placebo , at 7-day intervals . Cognitive performance and mood were assessed predose and at 1 , 3 , and 6 h postdose using the Cognitive Drug Research computerized assessment battery and Bond – Lader visual analog scales , respectively . In vitro analysis of the chosen extract established IC50 concentrations of 0.18 and 3.47 mg ml−1 , respectively , for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in the human cerebral cortex tissue . However , no cholinesterase inhibitory properties were detected . The most notable cognitive and mood effects were improved memory performance and increased ‘ calmness ’ at all postdose time points for the highest ( 1600 mg ) dose . However , while the profile of results was overwhelmingly favorable for the highest dose , decrements in the speed of timed memory task performance and on a rapid visual information-processing task increased with decreasing dose . These results suggest that doses of Melissa officinalis at or above the maximum employed here can improve cognitive performance and mood and may therefore be a valuable adjunct in the treatment of Alzheimer 's disease . The results also suggest that different preparations derived from the same plant species may exhibit different properties depending on the process used for the sample preparation Ginkgo biloba special extract EGb 761 , an anti-dementia drug , enhances cognitive functioning and stabilizes mood in cognitively impaired elderly subjects . Moreover , EGb 761 had been found to alleviate symptoms of anxiety in people with mental decline , therefore it was now tested for clinical efficacy in younger patients suffering from anxiety . One hundred and seven patients with generalized anxiety disorder ( GAD , n=82 ) or adjustment disorder with anxious mood ( ADWAM , n=25 ) according to the diagnostic and statistical manual of mental disorders , third edition - revised ( DSM-III-R ) were r and omized to daily doses of 480 mg EGb 761 , 240 mg EGb 761 or placebo for 4 weeks . Intention-to-treat ( ITT ) analyses were performed on the primary outcome measure , the Hamilton rating scale for anxiety ( HAMA ) , and the secondary variables , the clinical global impression of change ( CGI-C ) , the Erlangen anxiety tension and aggression scale ( EAAS ) , the list of complaints ( B-L ' ) , and the patient 's global rating of change . The HAMA total scores decreased by -14.3 ( + /-8.1 ) , -12.1 ( + /-9.0 ) and -7.8 ( + /-9.2 ) in the high-dose EGb 761 , the low-dose EGb 761 and the placebo group , respectively . Changes were significantly different from placebo for both treatment groups with p=0.0003 ( high-dose group ) and p=0.01 ( low-dose ) . Regression analyses revealed a dose-response trend ( p=0.003 ) . EGb 761 was significantly superior to placebo on all secondary outcome measures . It was safe and well tolerated and may thus be of particular value in elderly patients with anxiety related to cognitive decline BACKGROUND : Many patients have preoperative anxiety ; therefore , the development of a strong anxiolytic with minimal psychomotor impairment for premedication may be desirable . METHODS : In this study , 60 patients were r and omized into two groups to receive either oral Passiflora incarnata ( 500 mg , Passipy ™ Ir anD arouk ) ( n = 30 ) or placebo ( n = 30 ) as premedication , 90 min before surgery . A numerical rating scale ( NRS ) was used for each patient to assess anxiety and sedation before , and 10 , 30 , 60 , and 90 min after premedication . Psychomotor function was assessed with the Trieger Dot Test and the Digit-Symbol Substitution Test at arrival in the operating room , 30 and 90 min after tracheal extubation . The time interval between arrival in the postanesthesia care unit and discharge to home ( discharge time ) was recorded for each patient . RESULTS : The demographic characteristics of patients , ASA physical status , duration of surgery , basal NRS score , sedation at the preset time intervals , and discharge time were similar in the two groups . The NRS anxiety scores were significantly lower in the passiflora group than in the control group ( P < 0.001 ) . There were no significant differences in psychological variables in the postanesthesia care unit and recovery of psychomotor function was comparable in both groups . CONCLUSIONS : In outpatient surgery , administration of oral Passiflora incarnata as a premedication reduces anxiety without inducing sedation Objective : Melissa officinalis ( lemon balm ) is contemporaneously used as a mild sedative and /or calming agent . Although recent research has demonstrated modulation of mood in keeping with these roles , no studies to date have directly investigated the effects of this herbal medication on laboratory-induced psychological stress . Methods : In this double-blind , placebo-controlled , r and omized , balanced crossover experiment , 18 healthy volunteers received two separate single doses of a st and ardized M. officinalis extract ( 300 mg , 600 mg ) and a placebo , on separate days separated by a 7-day washout period . Modulation of mood was assessed during predose and 1-hour postdose completions of a 20-minute version of the Defined Intensity Stressor Simulation ( DISS ) battery . Cognitive performance on the four concurrent tasks of the battery was also assessed . Results : The results showed that the 600-mg dose of Melissa ameliorated the negative mood effects of the DISS , with significantly increased self-ratings of calmness and reduced self-ratings of alertness . In addition , a significant increase in the speed of mathematical processing , with no reduction in accuracy , was observed after ingestion of the 300-mg dose . Conclusion : These results suggest that the potential for M. officinalis to mitigate the effects of stress deserves further investigation Background : Several neuropsychiatric adverse effects of efavirenz are known . Preventing these adverse effects may improve patients ’ adherence to antiretroviral therapy ( ART ) . Objectives : To evaluate the efficacy and safety of valerian in preventing neuropsychiatric adverse effects of efavirenz in HIV-positive patients . Method : In this pilot r and omized , double-blinded , placebo-controlled , clinical trial , 51 HIV-positive patients who were receiving efavirenz were recruited into the valerian ( n = 25 ) or placebo ( n = 26 ) group . Patients received valerian ( 530 mg ) or placebo nightly 1 hour before sleep for 4 weeks . The neuropsychiatric status ( sleep , anxiety , depression , suicidal thought , and psychosis ) of patients was assessed at baseline and week 4 using vali date d question naires . Results : Sleep ( P ≤ 0.001 ) and anxiety ( P = 0.001 ) significantly improved in the valerian group compared with the placebo group . Dizziness was the most common complaint of patients in first days of the intervention . In the valerian and placebo groups , 92 % and 84.6 % of patients experienced dizziness , respectively ( P = 0.35 ) . Nausea was the second common adverse effect that 84 % and 76.9 % of patients in the valerian and placebo groups experienced ( P = 0.39 ) . Conclusion : In the first 4 weeks of ART including efavirenz , valerian  significantly improved sleep and anxiety in HIV-positive patients .  Valerian may be considered as a potential option in preventing neuropsychiatric adverse effects of efavirenz in HIV-positive patients Valerian is the common name given to the genus Valeriana , an odiferous , herbaceous perennial plant widely distributed in the temperate regions of Asia , Europe , and North America . It is among the most widely used herbal medicines in the world . Numerous clinical studies have demonstrated valerian 's ability to improve sleep ; however , to the best of our knowledge , no study has systematic ally assessed subjective and psychomotor/cognitive effects of valerian in young healthy adults across a range of doses . In the present study , we sought to determine whether valerian extract ( Valeriana officinalis ) altered mood and /or impaired psychomotor/cognitive performance in young healthy volunteers . We examined the effects of valerian extract ( 600 , 1200 , and 1800 mg ) and 10 mg diazepam ( positive control ) compared to placebo in 10 young healthy volunteers . Dependent measures included subjective and psychomotor variables . The valerian extract had no significant effects on any of the dependent measures . Diazepam , though , produced subjective effects as measured by four different rating scales , and impaired psychomotor/cognitive performance . The data suggest that acute administration of valerian does not have mood-altering or psychomotor/cognitive effects in young healthy volunteers OBJECTIVE Passionflower ( Passiflora incarnata ) is a folk remedy for anxiety . A double-blind r and omized trial compared the efficacy of Passiflora incarnata extract with oxazepam in the treatment of generalized anxiety disorder .  METHODS The study was performed on 36 out- patients diagnosed with GAD using DSM IV criteria . Patients were allocated in a r and om fashion : 18 to the Passiflora extract 45 drops/day plus placebo tablet group , and 18 to oxazepam 30 mg/day plus placebo drops for a 4-week trial . RESULTS Passiflora extract and oxazepam were effective in the treatment of generalized anxiety disorder . No significant difference was observed between the two protocol s at the end of trial . Oxazepam showed a rapid onset of action . On the other h and , significantly more problems relating to impairment of job performance were encountered with subjects on oxazepam . CONCLUSION The results suggest that Passiflora extract is an effective drug for the management of generalized anxiety disorder , and the low incidence of impairment of job performance with Passiflora extract compared to oxazepam is an advantage . A large-scale trial is justified The purpose of this study was to investigate the anxiolytic effects of xanthohumol , a component of Humulus lupulus ( hops ) , and its potential interaction with the benzodiazepine binding site on the y-aminobutyric acid ( GABAA ) receptor in the male Sprague-Dawley rat . This was a prospect i ve , r and omized , between-subjects experimental study . Fifty-five rats were assigned to 1 Sof 5 groups with 11 rats per group : control ( vehicle ) , xanthohumol , midazolam , midazolam with xanthohumol , and flumazenil with xanthohumol . In this study the elevated plus maze measured the behavioral components of anxiety and motor movements . A 2-tailed multivariate analysis of variance and least significant difference post hoc test was used to determine if a significant difference existed . Our data suggest that xanthohumol does not produce anxiolysis by modulation of the GABAA receptor ; however , there may be a possible interaction between xanthohumol and midazolam , or xanthohumol may influence the modulation of another neurotransmitter site in the central nervous system . Alone , xanthohumol does not show significant modulation of the benzodiazepine receptor . Additional research should investigate if xanthohumol acts as a benzodiazepine GABAA partial agonist or antagonist or if it modulates another neurotransmitter system in the central nervous system The aim of the present study was to carry out a controlled pilot study on the putative anxiolytic effect of valepotriates .  Thirty-six out patients with generalized anxiety disorder ( DSM III-R ) , after a 2-week wash-out , were r and omized to one of the following three treatments for 4 weeks ( n = 12 per group ) : valepotriates ( mean daily dose : 81.3 mg ) , diazepam ( mean daily dose : 6.5 mg ) , or placebo . A parallel , double-blind , flexible-dose , placebo-controlled design was employed . No significant difference was observed among the three groups at baseline or in the change from baseline on the Hamilton anxiety scale ( HAM-A ) or in the trait part of the state-trait anxiety inventory ( STAI-trait ) . Moreover , the three groups presented a significant reduction in the total HAM-A scores . On the other h and , only the diazepam and valepotriates groups showed a significant reduction in the psychic factor of HAM-A. The diazepam group also presented a significant reduction of the STAI-trait . Although the principal analysis ( HAM-A between group comparison ) found negative results ( probably due to the small sample size in each group ) , the preliminary data obtained in the present study suggest that the valepotriates may have a potential anxiolytic effect on the psychic symptoms of anxiety . However , since the number of subjects per group was very small , the present results must be viewed as preliminary . Thus , further studies addressing this issue are warranted OBJECTIVE The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder , generalized anxiety disorder , and social phobia . METHOD Data were drawn from the Harvard/Brown Anxiety Disorders Research Program , a prospect i ve , naturalistic , longitudinal , multicenter study of adults with a current or past history of anxiety disorders . Probabilities of recovery and recurrence were calculated by using st and ard survival analysis methods . Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence . RESULTS Survival analyses revealed an overall chronic course for the majority of the anxiety disorders . Social phobia had the smallest probability of recovery after 12 years of follow-up . Moreover , patients who had prospect ively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period . The overall clinical course was worsened by several comorbid psychiatric conditions , including major depression and alcohol and other substance use disorders , and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia . CONCLUSIONS These data depict the anxiety disorders as insidious , with a chronic clinical course , low rates of recovery , and relatively high probabilities of recurrence . The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence . The findings add to the underst and ing of the nosology and treatment of these disorders BACKGROUND Conventional drug treatments for Generalized Anxiety Disorder ( GAD ) are often accompanied by substantial side effects , dependence , and /or withdrawal syndrome . A prior controlled study of oral chamomile ( Matricaria chamomilla L. ) extract showed significant efficacy versus placebo , and suggested that chamomile may have anxiolytic activity for individuals with GAD . HYPOTHESIS We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings , and would be associated with a favorable adverse event and tolerability profile . STUDY DESIGN We report on the open-label phase of a two-phase r and omized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD . METHODS Subjects with moderate to severe GAD received open-label treatment with pharmaceutical- grade chamomile extract 1500mg/day for up to 8 weeks . Primary outcomes were the frequency of clinical response and change in GAD-7 symptom scores by week 8 . Secondary outcomes included the change over time on the Hamilton Rating Scale for Anxiety , the Beck Anxiety Inventory , and the Psychological General Well Being Index . Frequency of treatment-emergent adverse events and premature treatment discontinuation were also examined . RESULTS Of 179 subjects , 58.1 % ( 95 % CI : 50.9 % to 65.5 % ) met criteria for response , while 15.6 % prematurely discontinued treatment . Significant improvement over time was also observed on the GAD-7 rating ( β=-8.4 [ 95 % CI=-9.1 to -7.7 ] ) . A similar proportion of subjects demonstrated statistically significant and clinical ly meaningful reductions in secondary outcome ratings of anxiety and well-being . Adverse events occurred in 11.7 % of subjects , although no serious adverse events occurred . CONCLUSION Chamomile extract produced a clinical ly meaningful reduction in GAD symptoms over 8 weeks , with a response rate comparable to those observed during conventional anxiolytic drug therapy and a favorable adverse event profile . Future comparative effectiveness trials between chamomile and conventional drugs may help determine the optimal risk/benefit of these therapies for patients suffering from GAD Scutellaria lateriflora is an herbal medicine with long-st and ing traditional use as a relaxing nervine . There has been controversy in the literature with regards to its efficacy , and this study was design ed to clarify its effectiveness in reducing anxiety , one of the phytotherapeutic indications . A double blind , placebo-controlled study of healthy subjects demonstrated noteworthy anxiolytic effects . The use of phytomedicines for the treatment of anxiety is review ed , as is the published literature on S. lateriflora and its putative toxicity BACKGROUND Generalized Anxiety Disorder ( GAD ) is one of the most common anxiety disorders treated in primary care , yet current therapies have limited efficacy and substantial side effects . PURPOSE To evaluate long-term chamomile ( Matricaria chamomilla L. ) use for prevention of GAD symptom relapse . METHODS Out patients from primary care practice s and local communities with a primary diagnosis of moderate-to-severe GAD were enrolled for this two-phase study at a large US academic medical center . During Phase 1 , eligible participants received 12 weeks of open-label therapy with chamomile pharmaceutical grade extract 1500 mg ( 500 mg capsule 3 times daily ) . During Phase 2 , treatment responders were r and omized to either 26 weeks of continuation chamomile therapy or placebo in a double-blinded , placebo-substitution design . The primary outcome was time to relapse during continuation therapy , analyzed using Cox proportional hazards . Secondary outcomes included the proportion who relapsed , treatment-emergent adverse events , and vital sign changes . This study is registered at Clinical Trials.gov , identifier NCT01072344 . RESULTS Between March 1 , 2010 , and June 30 , 2015 , we enrolled 179 participants . Of those , 93 ( 51.9 % ) were responders and agreed to continue in the double-blind r and omized controlled trial . A numerically greater number of placebo-switched ( n=12/47 ; 25.5 % ) versus chamomile-continuation ( n = 7/46 ; 15.2 % ) participants relapsed during follow-up . Mean time to relapse was 11.4 ± 8.4 weeks for chamomile and 6.3 ± 3.9 weeks for placebo  . Hazard of relapse was non-significantly lower for chamomile ( hazard ratio , 0.52 ; 95 % CI , 0.20 - 1.33 ; P = 0.16 ) . During follow-up , chamomile participants maintained significantly lower GAD symptoms than placebo ( P = 0.0032 ) , with significant reductions in body weight ( P = 0.046 ) and mean arterial blood pressure ( P = 0.0063 ) . Both treatments had similar low adverse event rates . CONCLUSIONS Long-term chamomile was safe and significantly reduced moderate-to-severe GAD symptoms , but did not significantly reduce rate of relapse . Our limited sample size and lower than expected rate of placebo group relapse likely contributed to the non-significant primary outcome finding . Possible chamomile superiority over placebo requires further examination in large-scale studies Objective : We conducted a r and omized , double-blind , placebo-controlled efficacy and tolerability trial of Matricaria recutita ( chamomile ) extract therapy in patients with mild to moderate generalized anxiety disorder ( GAD ) . We hypothesized that chamomile would be superior to placebo in reducing GAD symptoms with a comparable tolerability profile . Material s and Methods : Sixty-one out patients with mild to moderate GAD were enrolled , and 57 were r and omized to either double-blind chamomile extract ( n = 28 ) or placebo therapy ( n = 29 ) for 8 weeks . The study was powered to detect a statistically significant and clinical ly meaningful group difference in change over time in total Hamilton Anxiety Rating ( HAM-A ) scores . Secondary outcomes included change in the Beck Anxiety Inventory , Psychological Well Being , and Clinical Global Impression Severity scores and the proportion of patients with 50 % reduction or more in baseline HAM-A score . Results : We observed a significantly greater reduction in mean total HAM-A score during chamomile versus placebo therapy ( P = 0.047 ) . Although the study was not powered to identify small to moderate differences in secondary outcomes , we observed a positive change in all secondary outcomes in the same direction as the primary outcome measure . One patient in each treatment group discontinued therapy for adverse events . The proportion of patients experiencing 0 , 1 , 2 , or 3 adverse events or more was not significantly different between groups ( P = 0.417 ) . Conclusions : This is the first controlled clinical trial of chamomile extract for GAD . The results suggest that chamomile may have modest anxiolytic activity in patients with mild to moderate GAD . Future studies are needed to replicate these observations Euphytose ( EUP ) is a combination of six extracts : Crataegus , Ballota , Passiflora and Valeriana , which have mild sedative effects , and Cola and Paullinia , which mainly act as mild stimulants . This multicenter , double-blind , placebo-controlled general practice study was carried out patients with adjustment disorder with anxious mood . The study was coordinated by psychiatrists . Ninety-one patients were included in the EUP group and 91 patients in the placebo group . They all received two tablets three times a day over 28 days ( D ) . Evaluation using the Hamilton-anxiety ( HAM-A ) rating scale were carried out on D0 , D7 , D14 and on D28 . Comparing the two groups , 42.9 % of the patients ( EUP group ) had a HAM-A score of less than 10 at D28 versus 25.3 % in the placebo group ( P = 0.012 ) . Changes in the HAM-A score between D0 and D28 were as follows : D0 ( EUP : 26.12 + /- 4.0 , placebo : 26.27 + /- 4.5 ) , D7 ( EUP : 19.65 + /- 5.7 , placebo : 21.37 + /- 5.6 ) , D14 ( EUP : 15.36 + /- 5.7 , placebo : 17.48 + /- 6.7 ) , D28 ( EUP : 12.63 + /- 7.3 , placebo : 15.2 + /- 8.1 ) . From D7 to D28 there was a statistically significant difference ( P = 0.042 ) between the two treatments , indicating that EUP is better than placebo in the treatment of adjustment disorder with anxious mood Centella asiatica is reputed for its beneficial effects in various neurological disorders . The present investigation was undertaken to evaluate the role of 70 % hydro-ethanolic extract of Centella asiatica ( CA ) on  generalized anxiety disorder ( GAD ) in man .  Hamilton 's Brief Psychiatric Rating Scale ( BPRS ) was used to screen the subjects . Thirty-three participants ( 18 male and 15 female ; average age 33 yrs ) were medicated with the CA in a fixed dose regime ( 500 mg/capsule , twice daily , after meal ) . They were thoroughly investigated using st and ard question naires based on psychological rating scale at baseline ( day 0 ) , mid-term ( day 30 ) and final ( day 60 ) . The scale also includes a number of direct queries about current levels of experienced stress . The observations revealed that , CA not only significantly ( p<0.01 ) attenuated anxiety related disorders but it also significantly ( p<0.01 ) reduced stress phenomenon and its correlated depression .  CA further significantly ( p<0.01 ) improved the willingness for adjustment and cognition . Results indicated that Centella asiatica may be useful in the treatment of GAD and may be used as a promising anxiolytic agent in near future Investigations of the pharmacologic profile of medicinal plants have revealed that a number of plants with purported anxiolytic activity bind to cholecystokinin ( CCK ) receptors . This finding is intriguing in view of the proposed involvement of CCK in the pathophysiology of fear and anxiety . This double-blind , placebo-controlled study was undertaken to evaluate the anxiolytic activity of Gotu Kola ( Centella asiatica ) in healthy subjects .  Gotu Kola has been used for centuries in Ayurvedic and traditional Chinese medicine to alleviate symptoms of depression and anxiety . Recent studies in the rat have shown that long-term pretreatment with Gotu Kola decreases locomotor activity , enhances elevated-plus maze performance , and attenuates the acoustic startle response ( ASR ) . In this study , the authors evaluated the effects of Gotu Kola on the ASR in humans . Subjects were r and omly assigned to receive either a single 12-g orally administered dose of Gotu Kola ( N = 20 )  or placebo  ( N = 20 ) . The results revealed that compared with placebo , Gotu Kola significantly attenuated the peak ASR amplitude 30 and 60 minutes after treatment . Gotu Kola had no significant effect on self-rated mood , heart rate , or blood pressure . These preliminary findings suggest that Gotu Kola has anxiolytic activity in humans as revealed by the ASR . It remains to be seen whether this herb has therapeutic efficacy in the treatment of anxiety syndromes OBJECTIVE Cognitive impairments contribute significantly to inadequate functional recovery following illness episodes in bipolar disorder , yet data on treatment interventions are sparse . We assessed the cognitive effects of a st and ardized extract of the medicinal herb Withania somnifera ( WSE ) in bipolar disorder . METHOD Sixty euthymic subjects with DSM-IV bipolar disorder were enrolled in an 8-week , double-blind , placebo-controlled , r and omized study of WSE ( 500 mg/d ) as a procognitive agent added adjunctively to the medications being used as maintenance treatment for bipolar disorder . Study enrollment and data analyses were completed between December 2008 and September 2012 .  Cognitive testing  at baseline and 8 weeks assessed primary efficacy outcomes . Psychopathology and adverse events were monitored at scheduled visits . RESULTS Fifty-three patients completed the study ( WSE , n = 24 ; placebo , n = 29 ) , and the 2 groups were matched in terms of demographic , illness , and treatment characteristics . Compared to placebo , WSE provided significant benefits for 3 cognitive tasks : digit span backward ( P = .035 ) , Flanker neutral response time ( P = .033 ) , and the social cognition response rating of the Penn Emotional Acuity Test ( P = .045 ) . The size of the WSE  treatment effect for digit span backward was in the medium range ( Cohen d = 0.51 ; 95 % CI , 0.25 - 0.77 ) . None of the other cognitive tasks showed significant between-group differences . Mood and anxiety scale scores remained stable , and adverse events were minor . CONCLUSIONS Although results are preliminary , WSE appears to improve auditory-verbal working memory ( digit span backward ) , a measure of reaction time , and a measure of social cognition in bipolar disorder . Given the paucity of data for improving cognitive capacity in bipolar disorder , WSE offers promise , appears to have a benign side-effects profile , and merits further study . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00761761 Objective : Obsessive – Compulsive Disorder ( OCD ) is a common neuropsychiatric condition . Many herbs with psychotropic effects exist which can have fewer side effects compared to more conventional medications . Valeriana Officinalis L. is a well-known medicinal plant with a long history of usage in the world with an effect on GABA . This plant is reported to be safe on humans . Our objective in this study was to compare the efficacy of the extract of Valeriana Officinalis L. with placebo in the treatment of OCD . Methods : The study was an 8-week pilot double-blind r and omized trial . Thirty-one adult out patients who met the DSM-IV-TR criteria for OCD based on the structured clinical interview participated in the trial . In this double-blind and r and omized trial , patients were r and omly assigned to receive either capsule of the extract ( 765 mg/day ) or placebo ( 30 mg/day ) for 8 weeks . Results : The results showed significant difference between the extract and placebo in the end of treatment ( P=0.000 ) . Somnolence was the only significant difference between the two groups in terms of observed side effects ( P=0.02 ) . Conclusion : The results suggest that Valeriana Officinalis L. has some antiobsessive and compulsive effects . However , further studies are needed to confirm these findings . Psychiatrists often find that many patients can not tolerate the side effects of psychiatry medicine Valeriana Officinalis L. is a well-known medicinal plant with a long history of usage in world with effect on GABA.The results showed significant difference between the extract and placebo in the treatment of OCD . There was also no significant difference between the two groups in terms of observed side effects Melissa officinalis ( lemon balm ) is a traditional herbal medicine , which enjoys contemporary usage as a mild sedative , spasmolytic and antibacterial agent . It has been suggested , in light of in vitro cholinergic binding properties , that Melissa extracts may effectively ameliorate the cognitive deficits associated with Alzheimer 's disease . To date , no study has investigated the effects on cognition and mood of administration of Melissa to healthy humans . The present r and omised , placebo-controlled , double-blind , balanced-crossover study investigated the acute effects on cognition and mood of a st and ardised extract of M. officinalis .  Twenty healthy , young participants received single doses of 300 , 600 and 900 mg of M. officinalis ( Pharmaton ) or a matching placebo at 7-day intervals . Cognitive performance was assessed using the Cognitive Drug Research ( CDR ) computerised test battery and two serial subtraction tasks immediately prior to dosing and at 1 , 2.5 , 4 and 6 h thereafter . In vitro IC(50 ) concentrations for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in human occipital cortex tissue were also calculated . Results , utilising the cognitive factors previously derived from the CDR battery , included a sustained improvement in Accuracy of Attention following 600 mg of Melissa and time- and dose-specific reductions in both Secondary Memory and Working Memory factors . Self-rated " calmness , " as assessed by Bond-Lader mood scales , was elevated at the earliest time points by the lowest dose , whilst " alertness " was significantly reduced at all time points following the highest dose . Both nicotinic and muscarinic binding were found to be low in comparison to the levels found in previous studies
target: Collectively , the literature reveals pre clinical and clinical evidence for various phytomedicines modulating GABA-pathways , with comparative anxiolytic effect to the current array of pharmaceuticals , along with good safety and tolerability profiles
background: Anxiety disorders are chronic and functionally disabling conditions with high psychological stress , characterised by cognitive symptoms of excessive worry and focus difficulties and physiological symptoms such as muscle tension and insomnia .
  Gamma-aminobutyric acid ( GABA ) is an inhibitory neurotransmitter within the central nervous system and is a key target of pharmacotherapies in the treatment of anxiety .
  Although current pharmaceutical treatments are often efficacious , they may cause undesirable side effects including cognitive decrements and withdrawal symptoms .
  Plant-based " phytomedicines " may provide novel treatment options , to act as an adjunctive or alternative to existing anxiolytic medications .
  As such , we conducted a systematic review to assess the current body of literature on anxiolytic phytomedicines and /or phytoconstituents .