Kava

The drink is made from the root and rootstock. They are ground or chewed, suspended in water, and strained to give a milky-brown drink ^{29Reference 29Fern KPiper methysticumView study →}.

Kava’s role is social and ceremonial before it is medical. It was drunk to bolster the connection between the living and the dead, to induce meditative focus, and at weddings and funerals. It was drunk to show respect to neighbouring groups, and bonds were formed over it, including a brotherhood between Tonga and Samoa after generations of war.

Growers distinguish “noble” kavas, drunk daily, from tudei (“two-day”) kavas, which are stronger, longer-acting and harder on the drinker.

The plant is also used as a medicine. In Fiji, liquid pressed from the leaves is given for convulsions and stiffness in children, and the leaves are chewed for bronchitis. Scrapings of the root bark are chewed for sore throats and toothache ^{29Reference 29Fern KPiper methysticumView study →}.

In New Zealand a different relative, Piper excelsum (kawakawa), is used for cuts, bruises and skin infections.

Western herbal texts list kava for neuralgia, dizziness, chronic bronchitis, cystitis, painful urination, rheumatism, loss of appetite, vaginal discharge, gonorrhoea, gout and joint pain ^{27Reference 27Bone · 2003A Clinical Guide to Blending Liquid Herbs: Herbal Formulations for the Individual Patient}. Its modern Western use centres on anxiety.

Kava is now drunk socially in kava bars, a modern take on the traditional nakamal of the Pacific islands. People gather to sip prepared kava over a few hours, in the social role a bar usually fills. Kava bars now operate in the United States and Europe.

This is kava’s main indication and the only one with substantial human data.

A 2000 systematic review found that all seven double-blind trials it included favoured kava extract over placebo. A meta-analysis of three of them found a reduction of about 9.7 points on the Hamilton Anxiety scale ^{1Reference 1Pittler et al. · 2000Meta-analysisEfficacy of kava extract for treating anxiety — systematic review and meta-analysisView study →}.

A 2003 Cochrane review of 11 trials (645 participants) pooled six trials (345 participants) and found a mean reduction of 5 points on the Hamilton scale against placebo. Adverse events were mild, transient and infrequent over 1–24 weeks ^{2Reference 2Pittler et al. · 2003Systematic reviewKava extract for treating anxiety — systematic reviewView study →}.

A reference-controlled trial in 129 outpatients with generalised anxiety disorder found 400 mg a day of the standardised extract LI 150 as effective as the anxiolytics opipramol and buspirone over 8 weeks ^{6Reference 6Boerner et al. · 2003RCTKava-Kava extract LI 150 is as effective as opipramol and buspirone in generalised anxiety disorder — an 8-week randomised, double-blind multicentre RCT in 129 outpatientsView study →}.

Two Australian trials used an aqueous root extract, the kind the WHO had recommended studying. A 3-week crossover trial in 60 adults with persistent anxiety (250 mg kavalactones a day) reduced anxiety and depression scores ^{3Reference 3Sarris et al. · 2009RCTThe Kava Anxiety Depression Spectrum Study (KADSS) — a randomised, placebo-controlled crossover trialView study →}. A 6-week trial in 75 people with generalised anxiety disorder (120–240 mg kavalactones a day) found a moderate reduction in anxiety (Cohen d = 0.62), and 26% of the kava group reached remission against 6% on placebo ^{4Reference 4Sarris et al. · 2013RCTKava in the treatment of generalized anxiety disorder — a double-blind, randomized, placebo-controlled studyView study →}.

A larger 16-week phase III trial (171 people, 240 mg kavalactones a day) found no difference from placebo in diagnosed generalised anxiety disorder. Remission was 17.4% on kava and 23.8% on placebo ^{5Reference 5Sarris et al. · 2020RCTKava for generalised anxiety disorder — a 16-week double-blind, randomised, placebo-controlled study [phase III RCT]View study →}. A 2018 meta-analysis of three placebo-controlled GAD trials (130 people) found effect sizes favouring kava (0.59–0.99) that did not reach statistical significance ^{7Reference 7Ooi et al. · 2018Meta-analysisKava for generalized anxiety disorder — a review and meta-analysis of current evidence [systematic review]View study →}.

Gap: the largest, longest trial was null for diagnosed GAD. The human evidence is strongest for short-term and non-clinical anxiety.

In sleep-disturbed rats, a kava extract (300 mg/kg) shortened the time taken to fall asleep and increased deep, delta-wave activity during non-REM sleep. It did not change total waking or non-REM sleep time, and unlike flunitrazepam its effect was not blocked by the benzodiazepine antagonist flumazenil ^{14Reference 14Shinomiya et al. · 2005AnimalEffects of kava-kava extract on the sleep-wake cycle in sleep-disturbed rats [animal]View study →}.

In people, better sleep has appeared as a secondary outcome of anxiety trials rather than as a main endpoint, so a direct effect on sleep is hard to separate from reduced anxiety ^{8Reference 8Sarris et al. · 2011ReviewKava — a comprehensive review of efficacy, safety, and psychopharmacology [review]View study →}.

Gap: no placebo-controlled RCT has tested kava against a validated insomnia endpoint.

Early pharmacology described kava pyrones as analgesic, anticonvulsant and muscle-relaxing ^{11Reference 11Gleitz et al. · 1995In vitroGleitz, J., Beile, A., & Peters, T. (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na⁺ channels in synaptosomes [in vitro]. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/View study →}.

Several synthetic analogues of kavain reduced pain responses in mice. The most active also worked in formalin, capsaicin and glutamate pain models, though not in the hot-plate test, and did not act through the opioid system ^{15Reference 15Kormann et al. · 2012Kavain analogues as potential analgesic agents [animal]View study →}.

Gap: there are no human trials; the evidence is rodent and synthetic-analogue work.

Early animal pharmacology described kava pyrones as anticonvulsant and centrally muscle-relaxing ^{11Reference 11Gleitz et al. · 1995In vitroGleitz, J., Beile, A., & Peters, T. (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na⁺ channels in synaptosomes [in vitro]. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/View study →}.

Synthetic kavain blocked voltage-dependent sodium channels in rat brain nerve endings ^{11Reference 11Gleitz et al. · 1995In vitroGleitz, J., Beile, A., & Peters, T. (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na⁺ channels in synaptosomes [in vitro]. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/View study →}. Synthetic methysticin and kavain inhibited sodium currents in rat hippocampal neurons ^{12Reference 12Magura et al. · 1997AnimalKava extract ingredients (+)-methysticin and (±)-kavain inhibit voltage-operated Na⁺-channels in rat CA1 hippocampal neurons [animal]View study →}.

The work is preclinical and decades old, there is no human trial, and kava is not used clinically as an anticonvulsant.

A 1992 study tested kava extract and its kavalactones in mouse and rat models of stroke. Oral kava extract (150 mg/kg) reduced the size of the damaged brain area in both species. Injected methysticin and dihydromethysticin reduced it in mice, with effects similar to the reference drug memantine; the other kavalactones did not ^{13Reference 13Backhauss et al. · 1992AnimalExtract of kava and its methysticin constituents protect brain tissue against ischemic damage in rodents [animal model]View study →}.

Gap: two rodent experiments in a single study, and no human data.

This research concerns kava’s minor chalcones rather than the kavalactones. Flavokawain A triggered Bax-dependent apoptosis in human bladder cancer cells and inhibited bladder tumour growth in mice by 57% ^{16Reference 16Zi et al. · 2005In vitroFlavokawain A, a novel chalcone from kava extract, induces apoptosis in bladder cancer cells and suppresses tumor growth in mice [in vitro / mouse]View study →}. A 2022 study identified it as an inhibitor of the enzyme PRMT5 in bladder cancer, in cells and in mice ^{17Reference 17Liu et al. · 2022In vitroFlavokawain A is a natural inhibitor of PRMT5 in bladder cancer [in vitro]View study →}.

Interest began with reports that kava drinking in Fiji, Vanuatu and Western Samoa correlated with unusual cancer rates ^{16Reference 16Zi et al. · 2005In vitroFlavokawain A, a novel chalcone from kava extract, induces apoptosis in bladder cancer cells and suppresses tumor growth in mice [in vitro / mouse]View study →}. That association is unproven.

Gap: cell-line and mouse work only, on isolated flavokawains that make up a small fraction of the root. The same chalcones worsened acetaminophen liver injury in mice ^{22Reference 22Narayanapillai et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice [animal]View study →}.

Liver. Rare but potentially severe liver injury, from raised enzymes to acute liver failure, has been linked to kava. Germany banned ethanolic and acetonic kava extracts in 2002, and kava products were withdrawn in the UK, Canada and other countries ^{3,19,21Reference 3Sarris et al. · 2009RCTThe Kava Anxiety Depression Spectrum Study (KADSS) — a randomised, placebo-controlled crossover trialView study →Reference 19Teschke · 2010ReviewKava hepatotoxicity — a clinical review [review]View study →Reference 21Nerurkar et al. · 2004In vitroIn vitro toxicity of kava alkaloid pipermethystine in HepG2 cells compared to kavalactones [in vitro]View study →}. One positive re-exposure case confirmed that kava can harm the liver ^{19Reference 19Teschke · 2010ReviewKava hepatotoxicity — a clinical review [review]View study →}.

What drives the risk. Most reports came from Western countries, where ethanolic and acetonic extracts were used ^{20Reference 20Olsen et al. · 2011ReviewConstituents in kava extracts potentially involved in hepatotoxicity — a reviewView study →}. A clinical review of 14 cases found injury after aqueous, ethanolic and acetonic extracts alike. Most patients had taken too much, taken it for a long time, or taken other medicines or supplements with it, and the review suggested poor raw-material quality as a further cause ^{19Reference 19Teschke · 2010ReviewKava hepatotoxicity — a clinical review [review]View study →}.

Suspected culprits. Pipermethystine, from the leaves and stem peelings, was toxic to liver cells in culture ^{21Reference 21Nerurkar et al. · 2004In vitroIn vitro toxicity of kava alkaloid pipermethystine in HepG2 cells compared to kavalactones [in vitro]View study →}. Flavokawain A and B worsened acetaminophen liver injury in mice ^{22Reference 22Narayanapillai et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice [animal]View study →}. Mould toxins in poorly stored raw material have also been suggested, and none of these has been proven ^{20,24Reference 20Olsen et al. · 2011ReviewConstituents in kava extracts potentially involved in hepatotoxicity — a reviewView study →Reference 24Teschke et al. · 2011ReviewHerbal hepatotoxicity by kava — update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits [review]View study →}.

Liver tests in trials. A 6-week trial found no difference in liver tests between kava and placebo ^{18Reference 18Sarris et al. · 2013RCTKava for the treatment of generalized anxiety disorder RCT — analysis of adverse reactions, liver function, addiction, and sexual effects [randomised controlled trial]View study →}. In the 16-week trial, abnormal liver tests were more frequent on kava, though no participant met the criteria for herb-induced liver injury ^{5Reference 5Sarris et al. · 2020RCTKava for generalised anxiety disorder — a 16-week double-blind, randomised, placebo-controlled study [phase III RCT]View study →}. Routine liver tests are advised for regular users ^{8Reference 8Sarris et al. · 2011ReviewKava — a comprehensive review of efficacy, safety, and psychopharmacology [review]View study →}.

Choosing a product. Expert guidance favours traditional water-based extracts of the rootstock from appropriate cultivars ^{8Reference 8Sarris et al. · 2011ReviewKava — a comprehensive review of efficacy, safety, and psychopharmacology [review]View study →}.

Alcohol, sedatives and driving. Kava should not be combined with alcohol, and care is needed with other psychotropic medicines ^{8Reference 8Sarris et al. · 2011ReviewKava — a comprehensive review of efficacy, safety, and psychopharmacology [review]View study →}. High doses should be avoided before driving or operating machinery ^{8Reference 8Sarris et al. · 2011ReviewKava — a comprehensive review of efficacy, safety, and psychopharmacology [review]View study →}. In the 16-week trial, poorer memory and tremor were reported more often on kava ^{5Reference 5Sarris et al. · 2020RCTKava for generalised anxiety disorder — a 16-week double-blind, randomised, placebo-controlled study [phase III RCT]View study →}.

Dopamine. Kava may dampen dopamine signalling, so take care in Parkinson’s disease and with dopaminergic or antipsychotic medicines ^{27Reference 27Bone · 2003A Clinical Guide to Blending Liquid Herbs: Herbal Formulations for the Individual Patient}.

Drug metabolism. In healthy volunteers taking kava for 28 days, CYP2E1 activity fell by about 40%, while CYP1A2, CYP2D6 and CYP3A4 were unchanged ^{30Reference 30Gurley et al. · 2005AnimalIn vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes [human pharmacokinetic study]View study →}. In another volunteer study, 14 days of kava did not change digoxin levels, so it is not a strong P-glycoprotein modulator in people ^{31Reference 31Gurley et al. · 2007Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans [human pharmacokinetic study]View study →}.

In laboratory tests with human liver enzymes, a whole kava extract strongly inhibited CYP2C9 and CYP2C19, as well as CYP2D6 and CYP3A4, which were unaffected in people ^{32Reference 32Mathews et al. · 2002In vitroInhibition of human cytochrome P450 activities by kava extract and kavalactones [in vitro]View study →}. Studies of kava and drug-metabolising enzymes have given mixed results overall ^{20Reference 20Olsen et al. · 2011ReviewConstituents in kava extracts potentially involved in hepatotoxicity — a reviewView study →}.

Skin. Regular kava drinkers can develop a skin rash, known as kava dermopathy ^{20Reference 20Olsen et al. · 2011ReviewConstituents in kava extracts potentially involved in hepatotoxicity — a reviewView study →}. Allergic skin reactions also occur.

Dependence. A 6-week trial found no signs of withdrawal or addiction ^{18Reference 18Sarris et al. · 2013RCTKava for the treatment of generalized anxiety disorder RCT — analysis of adverse reactions, liver function, addiction, and sexual effects [randomised controlled trial]View study →}.