Is the Jury Still Out on Kava?

In the South Pacific, kava (Piper methysticum) was a traditionally revered plant consumed as a beverage as part of a community. In the late 20th century, it became popular in the West as an anxiety-relieving supplement. Until, that is, concerns about liver toxicity led to market bans and a steep decline in its use where it was still available.

But recent studies are giving kava a second look.

While its use for anxiety and stress relief has been eclipsed somewhat by the popularity of hemp oil phytocannabinoids and a specialized echinacea extract, clinical work with kava shows that it is still effective. The question is whether or not it is safe.

A double-blind, randomized, placebo-controlled clinical study found that kava was effective for individuals with generalized anxiety disorder (GAD) within the six-week time frame of the trial. The researchers noted that kava reduced anxiety (using the Hamilton Anxiety Rating Scale) and may have had moderating effects on gamma-aminobutyric acid, a neurotransmitter commonly known as “GABA.” Its ability to boost GABA levels could explain some of kava’s calming influence. As for the anxiety scale, 26 percent of those in the kava group versus only six percent of those in the placebo group were saw results strong enough to be considered remitted from the condition. That’s still impressive, considering the side effects of conventional drugs. And, there were no significant differences between either group regarding liver function, so that was not a concern. The only issue with the kava group was that they experienced more headaches, but further analysis of potential side effects didn’t determine that kava was the cause of those headaches. In fact, the study found no adverse effects attributable to kava, including liver function or tendency to withdrawal symptoms. It did, however, find that kava increased sex drive among female participants.

Nonetheless, the overall recommendations for kava are still hedging on the side of short-term use. A review published in the journal Complementary Therapies in Clinical Practice found that for the most part, clinical studies showed no differences between kava and placebo for liver toxicity. And they acknowledged that the botanical appeared to be an option for stopping anxiety – but for no longer than eight weeks of use.

So kava isn’t necessarily a bad thing – some people rely on it for getting through stressful days and unwinding at the end of a week. But for anyone with longer term needs, a better and safer botanical option may be a clinically studied, specialized extract of Echinacea angustifolia that doesn’t have any potential downside and works to calm anxiety for a few days, or much longer.

Abstracts:

Sarris J, Stough C, Bousman CA, et al. Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2013 Oct;33(5):643-8.

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. Kava was well tolerated, and aside from more headaches reported in the kava group (P = 0.05), no other significant differences between groups occurred for any other adverse effects, nor for liver function tests. 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.

Sarris J, Stough C, Teschke R, et al. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects. Phytother Res. 2013 Nov;27(11):1723-8. doi: 10.1002/ptr.4916. Epub 2013 Jan 24.

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.

Smith K, Leiras C. The effectiveness and safety of Kava Kava for treating anxiety symptoms: A systematic review and analysis of randomized clinical trials. Complement Ther Clin Pract. 2018 Nov;33:107-117. doi: 10.1016/j.ctcp.2018.09.003. Epub 2018 Sep 15.

BACKGROUND: To determine if Kava Kava is an effective treatment for combating symptoms of anxiety despite warnings of hepatotoxicity from the Centers for Disease Control and Prevention (CDC).

METHODS: Databases PubMed, CINAHL, and PsycINFO were utilized to obtain clinical trials on Kava Kava and its effects on anxiety. A total of 11 articles met inclusion/exclusion criteria: 2 for Kava Kava vs. another anti-anxiety medication, 2 detailing additional adverse events, and 7 for Kava Kava vs. placebo. Mantel-Haenszel fixed-effects model was used to analyze the data, with responder rates being pooled to compute weighted risk ratios.

RESULTS: Kava Kava was shown to be more effective than placebo in 3 of the 7 trials. A final risk ratio of 1.50 (95% CI: 1.12, 2.01) from responder rates was calculated in favor of the intervention from 5 clinical trials (n = 330). Adverse events were shown to be the same as placebo (P = 0.574), and laboratory values analyzing hepatotoxicity were no different when compared to baseline except in two studies.

CONCLUSIONS: Kava Kava appears to be a short-term treatment for anxiety, but not a replacement for prolonged anti-anxiety use. Although not witnessed in this review, liver toxicity is especially possible if taken longer than 8 weeks.