Kava for generalised anxiety disorder: A 16-week double-blind, randomised, placebo-controlled study

Aust N Z J Psychiatry. 2020 Mar;54(3):288-297. doi: 10.1177/0004867419891246. Epub 2019 Dec 8.


Objective: Previous randomised, double-blind, placebo-controlled studies have shown that Kava (a South Pacific medicinal plant) reduced anxiety during short-term administration. The objective of this randomised, double-blind, placebo-controlled study was to perform a larger, longer-term trial assessing the efficacy and safety of Kava in the treatment of generalised anxiety disorder and to determine whether gamma-aminobutyric acid transporter (SLC6A1) single-nucleotide polymorphisms were moderators of response.

Methods: The trial was a phase III, multi-site, two-arm, 16-week, randomised, double-blind, placebo-controlled study investigating an aqueous extract of dried Kava root administered twice per day in tablet form (standardised to 120 mg of kavalactones twice/day) in 171 currently non-medicated anxious participants with diagnosed generalised anxiety disorder. The trial took place in Australia.

Results: An analysis of 171 participants revealed a non-significant difference in anxiety reduction between the Kava and placebo groups (a relative reduction favouring placebo of 1.37 points; p = 0.25). At the conclusion of the controlled phase, 17.4% of the Kava group were classified as remitted (Hamilton Anxiety Rating Scale score < 7) compared to 23.8% of the placebo group (p = 0.46). No SLC6A1 polymorphisms were associated with treatment response, while carriers of the rs2601126 T allele preferentially respond to placebo (p = 0.006). Kava was well tolerated aside from poorer memory (Kava = 36 vs placebo = 23; p = 0.044) and tremor/shakiness (Kava = 36 vs placebo = 23; p = 0.024) occurring more frequently in the Kava group. Liver function test abnormalities were significantly more frequent in the Kava group, although no participant met criteria for herb-induced hepatic injury.

Conclusion: While research has generally supported Kava in non-clinical populations (potentially for more 'situational' anxiety as a short-term anxiolytic), this particular extract was not effective for diagnosed generalised anxiety disorder.

Trial registration: ClinicalTrials.gov NCT02219880.

Keywords: Generalised anxiety disorder; Kava; Piper methysticum; anxiety; gamma-aminobutyric acid; pharmacogenetics; polymorphisms.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Anxiety Agents / adverse effects
  • Anti-Anxiety Agents / therapeutic use*
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / genetics
  • Australia
  • Double-Blind Method
  • Female
  • GABA Plasma Membrane Transport Proteins / genetics
  • Humans
  • Kava / chemistry*
  • Male
  • Middle Aged
  • Phytotherapy
  • Plant Extracts / adverse effects
  • Plant Extracts / therapeutic use*
  • Plant Roots / chemistry
  • Polymorphism, Single Nucleotide
  • Psychiatric Status Rating Scales
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Anti-Anxiety Agents
  • GABA Plasma Membrane Transport Proteins
  • Plant Extracts
  • SLC6A1 protein, human

Associated data

  • ClinicalTrials.gov/NCT02219880