Kava Kava: natural support in anxiety
Kava Kava (Piper methysticum) is famous for its anti-anxiety effects. Although ‘famous’ is perhaps an unfortunate term. Despite its proven anxiolytic effect and despite the growing problem of anxiety – Kava Kava still remains almost completely unknown. Not only socially, but also among mental health professionals. In order to provide an insight into the phenomenon of Kava’s properties, we have gathered together some studies and research to help shed more light on how this unique Pacific plant works.
Let’s start with two key terms!
What is GABA?
GABA: one of the most important neurotransmitters; responsible for regulating the activity of neurons in the brain. It inhibits the flow of nerve impulses, “quieting” the nervous system. Read more about how Kava Kava works on GABA here!
What is HAMA?
Hamilton Anxiety Rating Scale – the most widely used test for depression in psychiatry.
Kava for the treatment of generalised anxiety disorder (K-GAD)
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 […]. [ SOURCE ]
One such option is kava (Piper methysticum), a plant native to the South Pacific, whose roots have been used in traditional medicine in the form of cold-water extractions (non-alcoholic) to treat a range of health conditions, including anxiety, stress, muscular spasms, pain, and menstrual disorders. The therapeutic effect of kava is based on the six major lipophilic kavalactones, of which kawain and dihydrokawain have the strongest anxiolytic activity. Limbic structures of the brain have previously been suggested as the principal site of kavalactone action. Kavalactones exert their anxiolytic effect through an array of neurobiological activity, primarily from modulation of gamma-aminobutyric acid (GABA) receptors via blockade of voltage-gated sodium ion channels, reduced excitatory neurotransmitter release via blockade of calcium ion channels, and enhanced ligand binding to GABA type A receptors. Other neurochemical effects include reversible inhibition of monoamine oxidase B, inhibition of cyclooxygenase, and reduced neuronal reuptake of dopamine and prefrontal cortex noradrenalin. This noradrenergic effect differentiates the central biobehavioural effects of kava from those of alcohol and benzodiazepines, while the combination of GABA modulation and increased noradrenergic activation contributes to feelings of physical relaxation with increased hedonic tone, with no deleterious effects on cognition. [SOURCE]
Therapeutic potential of kava in the treatment of anxiety disorders
Anxiety disorders are among the most common psychiatric disorders that affect all age groups of the general population. Currently, the preferred treatment is with pharmacological drugs that have antidepressant or anti-anxiety properties. However, these agents have numerous and often serious adverse effects, including sedation, impaired cognition, ataxia, aggression, sexual dysfunction, tolerance and dependence. Withdrawal reactions on termination after long-term administration are also a major limiting factor in the use of these agents. Herbal remedies, including kava (Piper methysticum), have been shown to be effective as alternative treatments, at least in mild to moderate cases of anxiety. […] Its biological effects, due to a mixture of compounds called kavalactones, are reported to include sedative, anxiolytic, antistress, analgesic, local anaesthetic, anticonvulsant and neuroprotective properties. […] Clinical studies have shown that kava and kavalactones are effective in the treatment of anxiety at subclinical and clinical levels, anxiety associated with menopause and anxiety due to various medical conditions. [SOURCE]
Kava: a comprehensive review of efficacy, safety, and psychopharmacology
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. […]
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. [SOURCE]
Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study
Kava (Piper methysticum) is a plant-based medicine, which has been previously shown to reduce anxiety. To date, however, no placebo-controlled trial assessing kava in the treatment of generalized anxiety disorder (GAD) has been completed. A total of 75 participants with GAD and no comorbid mood disorder were enrolled in a 6-week double-blind trial of an aqueous extract of kava (120/240 mg of kavalactones per day depending on response) versus placebo. γ-Aminobutyric acid (GABA) and noradrenaline transporter polymorphisms were also analyzed as potential pharmacogenetic markers of response. Reduction in anxiety was measured using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome. Intention-to-treat analysis was performed on 58 participants who met inclusion criteria after an initial 1 week placebo run-in phase. Results revealed a significant reduction in anxiety for the kava group compared with the placebo group with a moderate effect size (P = 0.046, Cohen d = 0.62). Among participants with moderate to severe Diagnostic and Statistical Manual of Mental Disorders-diagnosed GAD, this effect was larger (P = 0.02; d = 0.82). At conclusion of the controlled phase, 26% of the kava group were classified as remitted (HAMA ≤ 7) compared with 6% of the placebo group (P = 0.04). Within the kava group, GABA transporter polymorphisms rs2601126 (P = 0.021) and rs2697153 (P = 0.046) were associated with HAMA reduction. […]
Standardized kava may be a moderately effective short-term option for the treatment of GAD. Furthermore, specific GABA transporter polymorphisms appear to potentially modify anxiolytic response to kava. [SOURCE]
Dr. Nick Haslam, professor of psychology at the University of Melbourne:
It’s a well-conducted study which shows that kava can be an effective treatment for generalised anxiety disorder, a condition that can be very disabling. It adds weight to a number of previous studies that had come to the same conclusion. […] It’s important to have several alternative treatments available given that different people will respond best to different treatments, and researchers will always be striving to discover new effective treatments and improve existing ones. [SOURCE]
Kava-kava Extract WS 1490 versus Placebo in Anxiety Disorders - A Randomized Placebo-controlled 25-week Outpatient Trial
101 outpatients suffering from anxiety of non-psychotic origin (DSM-III-R criteria: agoraphobia, specific phobia, generalized anxiety disorder, and adjustment disorder with anxiety) were included in a 25-week multicenter randomized placebo-controlled double-blind trial with WS 1490, a special extract of kava-kava. In the main outcome criterion, the Hamilton Anxiety Scale (HAMA), there was a significant superiority of the test drug starting from week 8 on. WS 1490 was also found to be superior with respect to the secondary outcome variables. HAMA subscores somatic and psychic anxiety, Clinical Global Impression, Self-Report Symptom Inventory – 90 Items revised, and Adjective Mood Scale. Adverse events were rare and distributed evenly in both groups. These results support WS 1490 as a treatment alternative to tricyclic antidepressants and benzodiazepines in anxiety disorders, with proven long-term efficacy and none of the tolerance problems associated with tricyclics and benzodiazepines. [SOURCE]
Clinical efficacy of kava extract WS 1490 in sleep disturbances associated with anxiety disorders. Results of a multicenter, randomized, placebo-controlled, double-blind clinical trial
Results: The confirmatory analysis of the two primary efficacy variables, the differences of sleep questionnaire SF-B sub-scores ‘Quality of sleep’ and ‘Recuperative effect after sleep’ after 4 weeks of double-blind treatment compared to baseline, demonstrated statistically significant group differences in favor of kava extract WS 1490 (P=0.007 and P=0.018, respectively). Superior effects of kava extract were also present in the HAMA psychic anxiety sub-score (P=0.002). More pronounced effects with respect to the self-rating of well-being and the global clinical evaluation also indicated superior therapeutic efficacy of kava extract. Safety and tolerability were good, with no drug-related adverse events or changes in clinical or laboratory parameters.
Conclusions: We conclude that sleep disturbances associated with non-psychotic anxiety disorders can be effectively and safely treated with kava extract WS 1490. [SOURCE]
De-mythologizing and re-branding of kava as the new ‘world drug’ of choice
Analysis by Drug Science:
Kava’s efficacy as an anxiolytic, used in the treatment of generalized anxiety disorder, has been recognized by contemporary pharmacology (Blades, 2016; Sarris et al., 2013), as has its use as an alternative to hormone replacement therapy (HRT) for women (Braun and Cohen, 2010; Cagnacci et al., 2003). More recently kava has been used in cancer research, specifically ovarian, bladder, colon, lung cancer and leukaemia (Lim, 2016). [SOURCE]
Kava Is an Effective and Safe Treatment of Anxiety
Analysis by Psychology Today:
The use of kava as a treatment of anxiety has been extensively reviewed in the biomedical and alternative medical literature. Animal studies suggest that the anxiety-reducing mechanism of action involves serotonin blockade in the amygdala by alpha-pyrones, a principle bioactive constituent of kava. Kava interferes with norepinephrine reuptake and is known to have binding affinity with both GABA and NMDA receptors, both of which modulate anxiety. Kava may also reduce anxiety by influencing vagal heart tone in patients with generalized anxiety (Watkins 2001).
A Cochrane systematic review of 11 controlled double-blind studies that met inclusion criteria and over 600 patients concluded that kava was superior to placebo for the short-term management of generalized anxiety (Pittler 2004). Double-blind studies and a meta-analysis (Singh and Blumenthal, 1996; Hansel 1996) support the use of kava preparations standardized to 70% kava lactones at doses between 70mg to 240mg/day for the treatment of “stress” and moderate anxiety, but not severe anxiety or agitation.
An early systematic review of 7 quality studies involving a total of 377 patients concluded that Kava 300mg/day is more effective than placebo in reducing nonpsychotic anxiety states (Pittler 1998). Daily use of kava 100-200mg/day effectively reduces anxiety symptoms associated with menopause (De Leo 2000).
Kava compares favorably to benzodiazepines (e.g. lorazepam, clonazepam, alprazolam) and other prescription anti-anxiety medications. The findings of a small double-blind controlled trial suggest that generally anxious patients who gradually increase their daily dose of kava (up to 300mg/day of a standardized extract) while tapering off a benzodiazepine do not experience worsening anxiety or benzodiazepine withdrawal (Malsch 2001). [SOURCE]
Monoamine Oxidase Inhibition by Kavalactones from Kava (Piper Methysticum)
This study examined the MAO inhibition potential of kavain and other kavalactones from the roots of kava (Piper methysticum), a plant that has been used for its anxiolytic properties. (±)-Kavain was found to be a good potency in vitro inhibitor of human MAO-B with an IC50 of 5.34 µM. (±)-Kavain is a weaker MAO-A inhibitor with an IC50 of 19.0 µM. […] Based on these findings, other kavalactones (dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin) were also evaluated as MAO inhibitors in this study. Yangonin proved to be the most potent MAO inhibitor with IC50 values of 1.29 and 0.085 µM for MAO-A and MAO-B, respectively. It may be concluded that some of the central effects (e.g., anxiolytic) of kava may be mediated by MAO inhibition. [SOURCE]
What is Monoamine Oxidase Inhibitor?
Monoamine oxidase inhibitors (MAOIs) are a separate class from other antidepressants, treating different forms of depression and other nervous system disorders such as panic disorder, social phobia, and depression with atypical features. [SOURCE]
Kava characteristic by: Association for the Advancement of Restorative Medicine
Positive results in a number of studies suggest that kava is effective when used orally for short-term treatment of anxiety disorders. […]
In another double-blind study, placebo-controlled trial of 38 patients with anxiety associated with neurotic disturbances, kavain was compared to oxazepam (a drug similar to diazepam or Valium) and demonstrated equivalent activity. Both substances caused progressive improvements in two different anxiety scores (Anxiety Status Inventory and the Self-rating Anxiety Scale) over a 4 week period. However, while oxazepam and similar drugs are addictive and attended with negative side-effects, kavain appeared to be free of these complications.
Most later clinical trials have used a standardized extract containing 70% kavalactones. In a randomized, placebo-controlled, double-blind study of 58 patients with anxiety not caused by psyhchotic disorders, a standardized kava extract significantly improved measures of anxiety and depression. Patients were given standardized kava extract (300mg per day, containing 210mg kavalactones) or placebo over a 4-week period. Those receiving the kava extract experienced a significant reduction of anxiety as measured by the Hamilton Anxiety Scale (total score, p<0.02). The difference in anxiety between kava and placebo began in the first week and increased during the course of treatment. No adverse effects were reported for kava extract.
In another well-done study, a 70% kavalactone extract was shown to exhibit significant therapeutic benefit in patients suffering from anxiety. The study was double-blind; 29 patients were assigned to receive 100mg of the kava extract three times daily, while another 29 patients received a placebo. Therapeutic effectiveness was assessed using several standard psychological assessments including the Hamilton Anxiety Scale. The result of this 4 week study indicated that individuals taking the kava extract had a statistically significant reduction in symptoms of anxiety including feelings of nervousness and somatic complaints such as heart palpitations, chest pains, headache, dizziness, and feelings of gastric irritation. No side-effects were reported with the kava extract.
In another double-blind study, two groups of 20 women with menopause-related anxiety symptoms were treated for a period of 8 weeks with the 70% kavalactone extract (100 mg three times daily) or placebo. The measured variable was once again the Hamilton Anxiety Scale. The group receiving kava extract demonstrated significant improvement by the end of the first week of treatment, and scores continued to improve over the course of the 8 week study. In addition to improvement in symptoms of stress and anxiety, several other symptoms also improved. Most notable was an overall improvement in subjective well-being, mood, and general symptoms of menopause, including hot flashes. Again, no side-effects were noted.
Additional studies have shown that unlike benzodiazepines, alcohol, and other drugs, kava extract is not associated with depressed mental function or impairment in driving or the operation of heavy equipment. In one of these studies, 12 healthy volunteers were tested in a double-blind cross-over manner to assess the effects of oxazepam (placebo on days 13, 15mg on the day before testing, 75mg on the morning of the experiment), the extract of kava standardized at 70% kavalactones (200mg three times daily for 5 days), and a placebo on behavior and event-related potentials (ERPs) in electroencephalograph (EEG) readings on a recognition memory task. The subjects task was to identify within a list of visually presented words those that were shown for the first time and those that were being repeated. Consistent with other benzodiazepines, oxazepam inhibited the recognition of both new and old words as noted by ERP. In contrast, kava showed a slightly increased recognition rate and a larger ERP difference between old and new words. The results of this study once again demonstrate the unusual effects of kava, which improves anxiety, but unlike standard anxiolytics, actually improves mental function and, at the recommended levels, does not promote sedation.
In another larger randomized, controlled, double-blind study, a standardized extract of kava was compared to the benzodiazepine drugs bromazepam and oxazeepam. One hundred and seventy six outpatients were divided into three groups, one of which received kava extract (210mg kavalactones per day), a second group which received 15 mg of oxazepam per day, and a third group which was given 9mg of bromazepam daily. After 6 weeks of treatment, the total Hamilton Anxiety Score was reduced from 27.3 to 15.6 in those given kava compared to 27.3 down to 13.4 for bromazepam and 27.7 to 16.6 for oxazepam. Statistical analysis showed kava treatment was equivalent to the benzodiazepine drugs. Side effects, however, were higher in the conventional drug groups.
In the above controlled trials, none lasted for more than 6 weeks, inclusion criteria were insufficiently defined and patient numbers were relatively small. To address these issues, a randomized, placebo-controlled, double-blind multicenter study of 100 patients presenting with nervous anxiety, tension and restlessness of non-psychotic origin (DSM-III-R) was conducted over a period of 6 months. Patients were randomized to receive either 300mg per day of a concentrated kava extract containing 210mg kavalactones (equal to about 4g dried root) or placebo. Assessment was based on changes in the cumulative Hamilton Anxiety Score (HAMA) in addition to other assessments. Comparison of the pre- and post-therapy HAMA scores revealed a significant (p=0.0015) superiority of the kava treatment as against placebo. The difference between the two groups was apparent at 8 weeks, with kava treatment leading to marked reduction in anxiety symptoms along with its physical and psychic manifestations. Kava also positively affected the accompanying depressive symptoms. During the study, 6 adverse events were reported in 5 patients in the kava group, four of which were rated by the investigator as not related to treatment while two (both cases of stomach upset) were considered possibly related. In contrast, 15 adverse effects from 9 patients were reported in the placebo group. Seven patients dropped out under placebo and 3 under kava (2 of the 3 were due to improvement of symptoms. No significant change was noted in biochemical parameters during the study and overall tolerability of kava was rated as excellent. The authors concluded the results support kavas use as an alternative to tricyclic antidepressants and benzodiazepines in anxiety, with proven long-term efficacy and none of the tolerance problems associated with these drugs.
In an observational study of 3029 patients, treatment with standardized kava extract (800mg per day containing 240mg kava pyrones) over a minimum of 4 weeks resulted in improvement of primary symptoms such as nervousness, restless and anger. Other symptoms including sleep disturbances, menopausal complaints, muscle tension and sexual disturbances were also improved. After 5 weeks of treatment, symptoms of nervousness, restlessness, and fear were reduced in 1673 patients. Mild adverse effects were reported in 69 patients (1.7% of patients) and included allergic reaction, gastrointestinal complaints, headache or dizziness.
Similar improvement in symptoms and a similar percentage of mild adverse reactions were observed in another observational study of 4049 patients treated with standardized kava extract (150mg per day, containing 105mg kavalactones) for 7 weeks. [SOURCE]
Association for the Advancement of Restorative Medicine does not indicate the sources of the studies mentioned.
The mentioned studies clearly indicate the significant potential of Kava Kava in anti-anxiety therapies. Kava is all-natural. It is a plant-based alternative. It has even been acclaimed by the New York Times as “Nature’s Xanax.” So valuable especially because: synthetic anxiolytic drugs are effective for treating anxiety, but they are burdened with adverse effects. Constraints on resources and time often render therapies such as psychologic interventions impracticable (from: Efficacy of kava extract for treating anxiety: systematic review and meta-analysis – source).
NOTE: Kava Kava is not a medicine! It should not be considered as an alternative to appropriate therapy. If you face anxiety – consult a specialist first!