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Obsessive-compulsive disorder (OCD) is a relatively prevalent mental disorder that poses significant health burdens on the community. Although current conventional medications have good efficacy for many patients, they can elicit a range of associated adverse effects. Plant-based compounds have been evaluated for different mental disorders, with a range of anxiolytic properties revealed. To determine the current evidence in the area, we conducted a systematic review using the electronic databases including PubMed, Scopus, and the Cochrane Library up to June 12, 2019, for pharmacological and clinical evidence of herbal medicines and phytochemicals with antiobsessive-compulsive effects. Additional search criteria were employed for locating research on the underpinning mechanisms of action. Results revealed that tentative low-quality evidence exists for several plant medicines, including Crocus sativus, Silybum marianum, Echium amoenum, Hypericum perforatum, and Withania somnifera, along with several natural molecules, including crocin, cannabidiol, and curcumin. Although more research is needed to confirm effectiveness, present preclinical studies indicate that monoamine pathway modulation (in particular serotonin reuptake inhibition) may be the most important anti-OCD mechanism among the studied natural compounds., (© 2020 John Wiley & Sons, Ltd.)

This paper provides a 10-year update of the 2007 systematic review of herbal medicines studied in a broad range of psychiatric disorders, including depression, anxiety, obsessive-compulsive, seasonal affective, bipolar, psychotic, phobic, somatoform, and attention-deficit hyperactivity disorders. Ovid Medline, PubMed, and the Cochrane Library were searched for herbal medicines with both pharmacological and clinical evidence of psychotropic activity. This updated review now covers clinical trial evidence for 24 herbal medicines in 11 psychiatric disorders. High-quality evidence was found to exist for the use of Piper methysticum (Kava), Passiflora spp. (passionflower) and Galphimia glauca (galphimia) for anxiety disorders; and Hypericum perforatum (St John's wort) and Crocus sativus (saffron) for major depressive disorder. Other encouraging herbal medicines with preliminary evidence include Curcuma longa (turmeric) in depression, Withania somnifera (ashwagandha) in affective disorders, and Ginkgo biloba (ginkgo) as an adjunctive treatment in Schizophrenia. Although depression and anxiety are commonly researched, many other mental disorders still require further prospective investigation. Although the previous review suggested increasing the adjunctive study of select herbal medicines with pharmaceuticals, this was still only found to sparingly occur in research designs. Aside from this, future focus should involve the incorporation of more biomarker analysis, in particular pharmacogenomics, to determine genetic factors moderating response to herbal medicines., (Copyright © 2018 John Wiley & Sons, Ltd.)

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. An open-ended search to 5 July 2017 was conducted using MEDLINE (PubMed), Scopus, and Cochrane library online databases and performed in a stepped format from preclinical to clinical investigations. Eligible studies must have had (a) in vitro evidence of GABA-modulating activity, (b) animal studies using anxiety models to test an anxiolytic effect, and (c) human clinical trials. Ten phytomedicines were identified as having preclinical investigations showing interaction with the GABA system, in addition to human clinical trials: kava, valerian, pennywort, hops, chamomile, Ginkgo biloba, passionflower, ashwagandha, skullcap, and lemon balm. Collectively, the literature reveals preclinical 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., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Anxiety disorders are the most prevalent mental health condition in Australia. In addition, there are many people who experience problematic anxiety symptoms who do not receive an anxiety disorder diagnosis but require treatment. As herbal medicine use is popular in Australia, and little is known about how adults experiencing anxiety are using these medicines, this study aimed to identify how Australian adults who experience anxiety are using herbal medicines., Methods: An online cross-sectional descriptive study was conducted using purposive convenience sampling to recruit Australian adults who have experienced anxiety symptoms and have used herbal medicines (N = 400). Descriptive statistics, chi-square test of contingency, analysis of variance, and simple logistic regression was used to analyse the data., Results: Eighty two percent of participants experienced anxiety symptoms in the previous 12 months, with 47% reporting having previously been diagnosed with an anxiety disorder. In addition, 72.8% had used herbal medicines specifically for anxiety symptoms in their lifetime, while 55.3% had used prescribed pharmaceuticals, with 27.5% having used herbal medicines concurrently with prescribed pharmaceuticals. The Internet and family and friends were the most frequently used sources of information about herbal medicines. Forty eight percent of participants did not disclose their herbal medicine use to their doctor., Conclusions: Herbal medicines are being used by adults with anxiety and are commonly self-prescribed for anxiety symptoms. Health practitioners who are experts in herbal medicine prescribing are consulted infrequently. In addition, herbal medicine use is often not disclosed to health practitioners. These behaviours are concerning as people may not be receiving the most suitable treatments, and their use of herbal medicines may even be dangerous. It is critical we develop a better understanding of why people are using these medicines, and how we can develop improved health literacy to help with treatment decision making to ensure people receive optimal care.

Presently, little is known about a number issues concerning kava (Piper methysticum), including (i) whether kava has any withdrawal or addictive effects; (ii) if genetic polymorphisms of the cytochrome (CYP) P450 2D6 liver enzyme moderates any potential adverse effects; and (iii) if medicinal application of kava has any negative or beneficial effect on sexual function and experience. The study design was a 6-week, double-blind, randomized controlled trial (n = 75) involving chronic administration of kava (one tablet of kava twice per day; 120 mg of kavalactones per day, titrated in non-response to two tablets of kava twice per day; 240 mg of kavalactones) or placebo for participants with generalized anxiety disorder. Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava. No differences in withdrawal or addiction were found between groups. Interesting, kava significantly increased female's sexual drive compared to placebo (p = 0.040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males. Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole sample., (Copyright © 2013 John Wiley & Sons, Ltd.)

St. John's wort (Hypericum perforatum) has been extensively studied and reviewed for its use in depression; however, there is less salient discussion on its clinical application for a range of other psychiatric disorders. This article outlines the current evidence of the efficacy of St John's wort in common psychiatric disorders, including major depression, bipolar depression, attention-deficit hyperactivity disorder, obsessive-compulsive disorder, social phobia, and somatization disorder. Mechanisms of action, including emerging pharmacogenetic data, safety, and clinical considerations are also detailed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Rationale: Kava (Piper methysticum) is a psychotropic plant medicine with history of cultural and medicinal use. We conducted a study comparing the acute neurocognitive, anxiolytic, and thymoleptic effects of a medicinal dose of kava to a benzodiazepine and explored for the first time specific genetic polymorphisms, which may affect the psychotropic activity of phytomedicines or benzodiazepines., Methods: Twenty-two moderately anxious adults aged between 18 and 65 years were randomized to receive an acute dose of kava (180 mg of kavalactones), oxazepam (30 mg), and placebo 1 week apart in a crossover design trial., Results: After exposure to cognitive tasks, a significant interaction was revealed between conditions on State-Trait Anxiety Inventory-State anxiety (p = 0.046, partial ŋ² = 0.14). In the oxazepam condition, there was a significant reduction in anxiety (p = 0.035), whereas there was no change in anxiety in the kava condition, and there was an increase in anxiety in the placebo condition. An increase in Bond-Lader "calmness" (p = 0.002) also occurred for the oxazepam condition. Kava was found to have no negative effect on cognition, whereas a reduction in alertness (p < 0.001) occurred in the oxazepam condition. Genetic analyses provide tentative evidence that noradrenaline (SLC6A2) transporter polymorphisms may have an effect on response to kava., Conclusion: Acute "medicinal level" doses of this particular kava cultivar in naive users do not provide anxiolytic activity, although the phytomedicine also appears to have no negative effects on cognition., (Copyright © 2012 John Wiley & Sons, Ltd.)

The field of genetics, which includes the use of 'omic' technologies, is an evolving area of science that has emerging application in phytotherapy. Omic studies include pharmacogenomics, proteomics and metabolomics. Herbal medicines, as monotherapies, or complex formulations such as traditional Chinese herbal prescriptions, may benefit from omic studies, and this new field may be termed 'herbomics'. Applying herbomics in the field of psychiatry may provide answers about which herbal interventions may be effective for individuals, which genetic processes are triggered, and the subsequent neurochemical pathways of activity. The use of proteomic technology can explore the differing epigenetic effects on neurochemical gene expression between individual herbs, isolated constituents and complex formulae. The possibilities of side effects or insufficient response to the herb can also be assessed via pharmacogenomic analysis of polymorphisms of cytochrome P450 liver enzymes or P-glycoprotein. While another novel application of omic technology is for the validation of the concept of synergy in individual herbal extracts and prescriptive formulations. Chronic administration of psychotropic herbal medicines may discover important effects on chromatin remodelling via modification of histone and DNA methylation. This paper focuses on the emerging field of herbomics, and is to our knowledge the first publication to explore this in the area of psychiatry., (Copyright © 2011 John Wiley & Sons, Ltd.)

Research in the area of herbal psychopharmacology has increased markedly over the past decades. To date however, a comprehensive review of herbal antidepressant, anxiolytic and hypnotic psychopharmacology and applications in depression, anxiety and insomnia has been absent. A search of MEDLINE (PubMed), CINAHL, PsycINFO, and the Cochrane Library databases was conducted (up to February 21st 2011) on commonly used psychotropic herbal medicines. A review of the literature was conducted to ascertain mechanisms of action of these botanicals, in addition to a systematic review of controlled clinical trials for treatment of mood, anxiety and sleep disorders, which are common comorbid psychiatric disorders. Specific emphasis was given to emerging phytomedicines. Analysis of evidence levels was conducted, as were effect sizes (Cohen's d) where data were available. Results provided evidence of a range of neurochemical, endocrinological, and epigenetic effects for 21 individual phytomedicines, which are detailed in this paper. Sixty six controlled studies were located involving eleven phytomedicines. Several of these provide a high level of evidence, such as Hypericum perforatum for major depression, and Piper methysticum for anxiety disorders. Several human clinical trials provide preliminary positive evidence of antidepressant effects (Echium amoenum, Crocus sativus, and Rhodiola rosea) and anxiolytic activity (Matricaria recutita, Ginkgo biloba, Passiflora incanata, E. amoenum, and Scutellaria lateriflora). Caution should however be taken when interpreting the results as many studies have not been replicated. Several herbal medicines with in vitro and in vivo evidence are currently unexplored in human studies, and along with use of emerging genetic technologies "herbomics", are areas of potential future research., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Overview: Complementary and Alternative Medicines (CAMs) are frequently given to children and adolescents for reputed benefits in the treatment of hyperkinetic and concentration disorders such as Attention Deficit Hyperactivity Disorder (ADHD). In such vulnerable populations high quality evidence is required to support such claims., Aims: The aim of the paper is to assess the current evidence of herbal and nutritional interventions for ADHD using a systematic search of clinical trials meeting an acceptable standard of evidence., Methods: PubMed, PsycINFO, Cochrane Library and CINAHL were searched up to May 26th, 2011 for randomised, controlled clinical trials using CAM products as interventions to treat ADHD. A quality analysis using a purpose-designed scale, and an estimation of effect sizes (Cohen's d) where data were available, were also calculated., Results: The review revealed that 16 studies met inclusion criteria, with predominant evidentiary support found for zinc, iron, Pinus marinus (French maritime pine bark), and a Chinese herbal formula (Ningdong); and mixed (mainly inconclusive) evidence for omega-3, and l-acetyl carnitine. Current data suggest that Ginkgo biloba (ginkgo), and Hypercium perforatum (St. John's wort) are ineffective in treating ADHD., Conclusion: The research suggests only some CAMs may be beneficial in ADHD, thus clinicians need to be aware of the current evidence. Promising candidates for future research include Bacopa monniera (brahmi) and Piper methysticum (kava), providing potential efficacy in improving attentional and hyperkinetic disorders via a combination of cognitive enhancing and sedative effects., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Kava (Piper methysticum) is an effective anxiolytic that has been withdrawn from various consumer markets in European countries due to concerns over its hepatotoxicity. It is plausible that the reported hepatotoxicity may be due in part to plant substitution, or an incorrect cultivar, or plant parts being used (such as leaves or bark); thus both the plant chemotype and the plant part used may be critical factors. If re-institution of kava in the EU is to occur, more evidence is required to determine its safety and efficacy. Furthermore, according to current evidence, the study of traditional water soluble rhizome extracts using a noble cultivar of kava may be advised. The Kava Anxiety-Lowering Medication (KALM) project is due to start in late 2010 to address these considerations. The KALM project uses an aqueous rhizome extract of a noble cultivar of kava in participants with generalised anxiety and Generalised Anxiety Disorder (GAD). The project comprises of 1) an acute RCT, kava (180 mg of kavalactones) versus oxazepam and placebo in 20 anxious people, testing effects on cognition, mood, anxiety, and driving; 2) an 8-week RCT comparing kava (120 mg kavalactones) versus placebo in 100 patients with GAD. To assess differences between dosages, non-responders at 3 weeks will be titrated to 240 mg of kavalactones. The project will also assess the effects of kava on liver function tests and its side effects profile. A novel component of the project is the pharmacogenomic exploration of phenotypical responses (GABA system and cytochrome P450 markers). The results of the study may be of benefit to sufferers of anxiety and the future economy of the Pacific islands, potentially providing an important step in the way forward with kava., (© Georg Thieme Verlag KG Stuttgart · New York.)

Overview: Kava (Piper methysticum) is a South Pacific psychotropic plant medicine that has anxiolytic activity. This effect is achieved from modulation of GABA activity via alteration of lipid membrane structure and sodium channel function, monoamine oxidase B inhibition, and noradrenaline and dopamine re-uptake inhibition. Kava is available over the counter in jurisdictions such as the USA, Australia and New Zealand. Due to this, a review of efficacy, safety and clinical recommendations is advised., Objective: To conduct a comprehensive review of kava, in respect to efficacy, psychopharmacology, and safety, and to provide clinical recommendations for use in psychiatry to treat generalized anxiety disorder (GAD)., Methods: A review was conducted using the electronic databases MEDLINE, CINAHL, PsycINFO and the Cochrane Library during mid 2010 of search terms relating to kava and GAD. A subsequent forward search was conducted of key papers using Web of Science cited reference search., Results: The current weight of evidence supports the use of kava in treatment of anxiety with a significant result occurring in four out of six studies reviewed (mean Cohen's d = 1.1). Safety issues should however be considered. Use of traditional water soluble extracts of the rhizome (root) of appropriate kava cultivars is advised, in addition to avoidance of use with alcohol and caution with other psychotropic medications. Avoidance of high doses if driving or operating heavy machinery should be mandatory. For regular users routine liver function tests are advised., Conclusions: While current evidence supports kava for generalized anxiety, more studies are required to assess comparative efficacy and safety (on the liver, cognition, driving, and sexual effects) versus established pharmaceutical comparators.

The aim of this review article was to summarize accumulated information related to chemical composition, pharmacological activity, traditional and official use of Rhodiola rosea L. in medicine. In total approximately 140 compounds were isolated from roots and rhizome - monoterpene alcohols and their glycosides, cyanogenic glycosides, aryl glycosides, phenylethanoids, phenylpropanoids and their glycosides, flavonoids, flavonlignans, proanthocyanidins and gallic acid derivatives. Studies on isolated organs, tissues, cells and enzymes have revealed that Rhodiola preparations exhibit adaptogenic effect including, neuroprotective, cardioprotectiv e, anti-fatigue, antidepressive, anxiolytic, nootropic, life-span increasing effects and CNS stimulating activity. A number of clinical trials demonstrate that repeated administration of R. rosea extract SHR-5 exerts an anti-fatigue effect that increases mental performance (particularly the ability to concentrate in healthy subjects), and reduces burnout in patients with fatigue syndrome. Encouraging results exist for the use of Rhodiola in mild to moderate depression, and generalized anxiety. Several mechanisms of action possibly contributing to the clinical effect have been identified for Rhodiola extracts. They include interactions with HPA-system (cortisol-reducing), protein kinases p-JNK, nitric oxide, and defense mechanism proteins (e.g. heat shock proteins Hsp 70 and FoxO/DAF-16). Lack of interaction with other drugs and adverse effects in the course of clinical trials make it potentially attractive for use as a safe medication. In conclusion, Rhodiola rosea has robust traditional and pharmacological evidence of use in fatigue, and emerging evidence supporting cognition and mood.

Background: Mood and anxiety disorders pose significant health burdens on the community. Kava and St. John's wort (SJW) are the most commonly used herbal medicines in the treatment of anxiety and depressive disorders, respectively., Objectives: The objective of this study was to conduct a comprehensive review of kava and SJW, to review any evidence of efficacy, mode of action, pharmacokinetics, safety and use in major depressive disorder, bipolar disorder, seasonal affective disorder (SAD), generalized anxiety disorder, social phobia (SP), panic disorder (PD), obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD)., Methods: A systematic review was conducted using the electronic databases MEDLINE, CINAHL, and The Cochrane Library during late 2008. The search criteria involved mood and anxiety disorder search terms in combination with kava, Piper methysticum, kavalactones, St. John's wort, Hypericum perforatum, hypericin, and hyperforin. Additional search criteria for safety, pharmacodynamics, and pharmacokinetics were employed. A subsequent forward search was conducted of the papers using Web of Science cited reference search., Results: Current evidence supports the use of SJW in treating mild-moderate depression, and for kava in treatment of generalized anxiety. In respect to the other disorders, only weak preliminary evidence exists for use of SJW in SAD. Currently there is no published human trial on use of kava in affective disorders, or in OCD, PTSD, PD, or SP. These disorders constitute potential applications that warrant exploration., Conclusions: Current evidence for herbal medicines in the treatment of depression and anxiety only supports the use of Hypericum perforatum for depression, and Piper methysticum for generalized anxiety.

Rationale: Piper methysticum (Kava) has been withdrawn in European, British, and Canadian markets due to concerns over hepatotoxic reactions. The WHO recently recommended research into "aqueous" extracts of Kava., Objective: The objective of this study was to conduct the first documented human clinical trial assessing the anxiolytic and antidepressant efficacy of an aqueous extract of Kava., Design and Participants: The Kava Anxiety Depression Spectrum Study was a 3-week placebo-controlled, double-blind crossover trial that recruited 60 adult participants with 1 month or more of elevated generalized anxiety. Five Kava tablets per day were prescribed containing 250 mg of kavalactones/day., Results: The aqueous extract of Kava reduced participants' Hamilton Anxiety Scale score in the first controlled phase by -9.9 (CI = 7.1, 12.7) vs. -0.8 (CI = -2.7, 4.3) for placebo and in the second controlled phase by -10.3 (CI = 5.8, 14.7) vs. +3.3 (CI = -6.8, 0.2). The pooled effect of Kava vs. placebo across phases was highly significant (p < 0.0001), with a substantial effect size (d = 2.24, eta(2)(p)). Pooled analyses also revealed highly significant relative reductions in Beck Anxiety Inventory and Montgomery-Asberg Depression Rating Scale scores. The aqueous extract was found to be safe, with no serious adverse effects and no clinical hepatotoxicity., Conclusions: The aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression. This should encourage further study and consideration of globally reintroducing aqueous rootstock extracts of Kava for the management of anxiety.

Objectives: To report on the design, significance and potential impacts of the first documented human clinical trial assessing the anxiolytic and thymoleptic efficacy of an aqueous mono-extract of Piper methysticum (kava). The significance of the qualitative element of our clinical trial is also explored. The Kava Anxiety Depression Spectrum Study (KADSS) is a 3-week placebo-controlled, double-blind, cross-over trial involving 60 adult participants (18-65) with elevated stable anxiety and varying levels of depressive symptoms., Aims: The aims of KADSS are: (1) to determine whether an aqueous standardised extract of kava is effective for the treatment of anxiety; (2) to assess the effects of kava on differing levels of depression; and (3) to explore participants' experience of taking kava via qualitative research. The study also provides preliminary assessment of the safety of an aqueous extract of kava in humans., Conclusion: If results reveal that the aqueous kava preparation exerts significant anxiolytic effects and appears safe, potentially beneficial impacts may occur. Data supporting a safe and effective kava extract may encourage a re-introduction of kava to Europe, UK and Canada. This may provide a major socioeconomic benefit to Pacific Island nations, and to sufferers of anxiety disorders.

This paper reports a critical review of 27 herbal medicines and formulas in treating a broad range of psychiatric disorders (in addition to anxiety and depression), including obsessive-compulsive, seasonal affective, bipolar depressive, psychotic, phobic and somatoform disorders. Ovid Medline, Pubmed and the Cochrane Library were searched for pharmacological and clinical evidence of herbal medicines with psychotropic activity. A forward search of later citations was also conducted. Whilst substantial high-quality evidence exists for the use of kava and St John's wort in the treatment of anxiety and depression respectively, currently there is insufficient robust clinical evidence for the use of many other herbal medicines in psychiatric disorders. Phytotherapies which potentially have significant use in psychiatry, and urgently require more research are Rhodiola rosea (roseroot) and Crocus sativus (saffron) for depression; Passiflora incarnata (passionflower), Scutellaria lateriflora (scullcap) and Zizyphus jujuba (sour date) for anxiety disorders; and Piper methysticum (kava) for phobic, panic and obsessive-compulsive disorders. While depression and anxiety are commonly researched, the efficacy of herbal medicines in other mental disorders requires attention. The review addresses current issues in herbal psychotherapy: herbal safety, future areas of application, the relationship of herbal medicine with pharmaceuticals and the potential prescriptive integration of phytomedicines with synthetic psychotropic medicines. Particular attention is given to clinical and safety issues with St John's wort and kava., ((c) 2007 John Wiley & Sons, Ltd.)