Dihydrokavain

Dihydrokavain at a Glance

Dihydrokavain is a kavalactone — one of the six styryl-pyrones that carry most of the pharmacology of kava (Piper methysticum), the Pacific root traditionally drunk to ease anxiety and promote calm sociability ^{1,2Reference 1Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →Reference 2Bian T et al. · 2020ReviewKava as a Clinical Nutrient: Promises and ChallengesView study →}. It is the reduced (dihydro) analogue of kavain: chemically identical apart from a saturated bond where kavain carries a styryl double bond. In many kava chemotypes it is the single most abundant kavalactone by mass, and in healthy volunteers it showed the highest systemic exposure of the six after an oral dose of standardised kava ^{8Reference 8Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}.

As an isolated molecule its documented activity is preclinical: it is one of the kava pyrones that produce analgesia, anticonvulsant/neuroprotective effects and sedation in rodent models, running through the same class mechanisms as kavain (GABA-A modulation, voltage-gated sodium-channel block) rather than one unique receptor ^{3,4,5,6,7Reference 3Jamieson DD · 1990AnimalThe antinociceptive actions of kava components in miceView study →Reference 4Backhauss C · 1992AnimalExtract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodentsView study →Reference 5Gleitz J et al. · 1995AnimalGleitz J, Beile A, Peters T (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na+-channels in synaptosomes prepared from rat cerebral cortex. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/View study →Reference 6Magura EI et al. · 1997AnimalKava extract ingredients, (+)-methysticin and (±)-kavain, inhibit voltage-operated Na+-channels in rat CA1 hippocampal neuronsView study →Reference 7Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →}. The human anxiolytic evidence is for whole kava, not for dihydrokavain in isolation — and even for the whole plant it is mixed, with a positive Cochrane meta-analysis but a well-conducted negative trial in diagnosed generalised anxiety disorder ^{9,11Reference 9Pittler MH · 2003Meta-analysisKava extract for treating anxietyView study →Reference 11Sarris J et al. · 2020RCTKava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled study (clinical trial)View study →}.

On safety the important framing is about the plant, not this molecule. The traditional aqueous root beverage has a good record and the isolated kavalactones were not cytotoxic in the liver-cell work that flagged kava; the rare hepatotoxicity associated with some Western kava products is attributed instead to aerial-part constituents (the alkaloid pipermethystine), the chalcone flavokawain B, poor-quality or mouldy raw material and drug interactions — not to the root kavalactones ^{12,13,14Reference 12Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →Reference 13Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →Reference 14Teschke R et al. · 2011ReviewHerbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.

Dihydrokavain vs. Kavain: The Reduced Analogue

Dihydrokavain and kavain are the closest pair among the kavalactones, and holding the difference straight is the point.

Structure. Kavain carries a styryl (phenyl-vinyl) side chain with a carbon-carbon double bond; dihydrokavain is that molecule with the side-chain double bond saturated (reduced) — hence dihydro. Both keep the 4-methoxy-5,6-dihydro-alpha-pyrone core that defines the “kava pyrones” ^{1Reference 1Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →}.

Abundance. This is where dihydrokavain stands apart. Kava’s six major kavalactones (methysticin, dihydromethysticin, kavain, dihydrokavain, yangonin and desmethoxyyangonin) together make up roughly 20-50% of the dry weight of the root, and their relative proportions swing widely by cultivar and chemotype ^{1,2Reference 1Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →Reference 2Bian T et al. · 2020ReviewKava as a Clinical Nutrient: Promises and ChallengesView study →}. In noble cultivars kavain usually leads; in tudei (two-day) and wichmannii types the dihydro-lactones climb, and dihydrokavain is frequently the largest single kavalactone by mass ^{1Reference 1Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →}. After oral dosing of a standardised kava product, dihydrokavain also showed the highest plasma exposure of the six — ahead of dihydromethysticin, kavain, methysticin and yangonin ^{8Reference 8Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}.

Pharmacology. The two share the kavalactone toolkit — positive allosteric modulation of GABA-A receptors (flumazenil-insensitive, i.e. not the benzodiazepine site) ^{7Reference 7Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →} and block of voltage-gated sodium channels ^{5,6Reference 5Gleitz J et al. · 1995AnimalGleitz J, Beile A, Peters T (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na+-channels in synaptosomes prepared from rat cerebral cortex. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/View study →Reference 6Magura EI et al. · 1997AnimalKava extract ingredients, (+)-methysticin and (±)-kavain, inhibit voltage-operated Na+-channels in rat CA1 hippocampal neuronsView study →} — and both were directly effective analgesics in the mouse tail-immersion assay, by a non-opioid route (naloxone did not reverse them) ^{3Reference 3Jamieson DD · 1990AnimalThe antinociceptive actions of kava components in miceView study →}. The historical characterisation of the pyrones as “anticonvulsive, analgesic and centrally muscle-relaxing” applies to this reduced congener as much as to kavain ^{5Reference 5Gleitz J et al. · 1995AnimalGleitz J, Beile A, Peters T (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na+-channels in synaptosomes prepared from rat cerebral cortex. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/View study →}.

Sibling kavalactone pages (kavain, methysticin, dihydromethysticin, desmethoxyyangonin, yangonin) are being built alongside this one; internal links will be added as each goes live.

What It's Used For

Dihydrokavain’s evidence base is preclinical and mostly shared with the kavalactone class: where the isolated molecule was tested directly, it was an analgesic and a neuroprotectant in rodents; where the effect is anxiolytic, the human data are for whole kava.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. The anxiolytic score reflects whole-kava human data; the analgesic/anticonvulsant scores reflect isolate rodent work — read the per-row basis.

01Anxiolytic / Sedative (as kava)Shaky42%GABA-A modulation ^{7Reference 7Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →} + kava anxiolytic meta-analysis ^{9Reference 9Pittler MH · 2003Meta-analysisKava extract for treating anxietyView study →}, tempered by a negative GAD RCT ^{11Reference 11Sarris J et al. · 2020RCTKava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled study (clinical trial)View study →}; whole plant, not the isolate

02Analgesic / AntinociceptiveShaky40%Purified dihydrokavain active in the mouse tail-immersion test, non-opioid ^{3Reference 3Jamieson DD · 1990AnimalThe antinociceptive actions of kava components in miceView study →}

03Anticonvulsant / NeuroprotectiveShaky30%Isolate among the kava pyrones protecting against ischaemic brain damage ^{4Reference 4Backhauss C · 1992AnimalExtract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodentsView study →}; Na+-channel class mechanism ^{5,6Reference 5Gleitz J et al. · 1995AnimalGleitz J, Beile A, Peters T (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na+-channels in synaptosomes prepared from rat cerebral cortex. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/View study →Reference 6Magura EI et al. · 1997AnimalKava extract ingredients, (+)-methysticin and (±)-kavain, inhibit voltage-operated Na+-channels in rat CA1 hippocampal neuronsView study →}

Mechanisms

The load-bearing point is that dihydrokavain has no known unique receptor — it shares kavain’s GABA-A and sodium-channel actions. Its distinction is quantitative (abundance and systemic exposure), not a separate mechanism.

Pharmacokinetics

The most compound-specific PK fact is exposure. In ten healthy volunteers given a standardised oral kava product, the six kavalactones’ systemic exposure ranked dihydrokavain > dihydromethysticin > kavain > methysticin > yangonin — so despite being studied far less than kavain, dihydrokavain reaches the highest plasma levels after a dose, and single dosing (225 mg) gave higher peak exposure while divided dosing (3 × 75 mg) prolonged it ^{8Reference 8Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}. The kavalactones are lipophilic and rapidly absorbed from the gut ^{8Reference 8Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}. Beyond this, dedicated isolate ADME for pure dihydrokavain — Cmax, half-life, oral bioavailability, metabolite map — is not well characterised; the human PK that exists is for the standardised whole extract, and animal metabolism data are sparse.

Clinical Trials

There are no clinical trials of isolated dihydrokavain. The human trial record is for whole kava extract — a Cochrane-reviewed body of short-term anxiety RCTs ^{9Reference 9Pittler MH · 2003Meta-analysisKava extract for treating anxietyView study →} and a later negative GAD trial ^{11Reference 11Sarris J et al. · 2020RCTKava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled study (clinical trial)View study →} — within which dihydrokavain is one constituent.

Last checked: July 2026.

Isolate vs. Plant Studies

The two evidence bases point in different directions. Where dihydrokavain was tested as a purified molecule, the studies are rodent — the tail-immersion analgesia screen that named it directly ^{3Reference 3Jamieson DD · 1990AnimalThe antinociceptive actions of kava components in miceView study →} and the cerebral-ischaemia protection work ^{4Reference 4Backhauss C · 1992AnimalExtract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodentsView study →} — a genuine but preclinical isolate signal. Where the evidence is human, it is whole kava: the anxiolytic meta-analysis ^{9Reference 9Pittler MH · 2003Meta-analysisKava extract for treating anxietyView study →} and the GAD trials ^{11Reference 11Sarris J et al. · 2020RCTKava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled study (clinical trial)View study →} used standardised extracts, not the isolate, so their results cannot be assigned to dihydrokavain alone. The pharmacokinetic study is the useful bridge — it measured the isolate’s blood levels, but from a whole-extract dose ^{8Reference 8Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}. Net: isolate mechanism/animal data + whole-plant human data, and the two are not interchangeable.

Prevalence in Nature

Dihydrokavain is essentially specific to kava (Piper methysticum), where it occurs in the root and rhizome as one of the six major kavalactones ^{1Reference 1Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →}. Its share of the kavalactone fraction is strongly chemotype-dependent: kava cultivars are graded by their six-digit kavalactone “chemotype” fingerprint, and dihydrokavain runs from a modest fraction in kavain-dominant noble cultivars up to the leading kavalactone by mass in tudei (two-day) and wichmannii types ^{1,2Reference 1Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →Reference 2Bian T et al. · 2020ReviewKava as a Clinical Nutrient: Promises and ChallengesView study →}. Total kavalactones themselves range from roughly 3-20% of dried root (up to ~20-50% dry weight in the richest material), shifting with cultivar, root vs rhizome, and — for a finished product — the extraction solvent ^{1,2Reference 1Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →Reference 2Bian T et al. · 2020ReviewKava as a Clinical Nutrient: Promises and ChallengesView study →}. Reported occurrence outside Piper methysticum is minimal, so unlike widespread terpenes this molecule is best treated as a kava marker.

Discovery & Synthesis

The kava pyrones were isolated and structurally characterised through nineteenth- and early-twentieth-century chemical work on the kava root, but a precise first-isolation date and discoverer for dihydrokavain specifically are not well documented in the accessible literature — it entered the record as one of the family of “kava lactones / kava pyrones” resolved as the group’s chemistry was worked out. Racemic kava pyrones have been prepared synthetically — synthetic (±)-kavain is the material used in much of the mechanistic pharmacology ^{5Reference 5Gleitz J et al. · 1995AnimalGleitz J, Beile A, Peters T (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na+-channels in synaptosomes prepared from rat cerebral cortex. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/View study →} — and dihydrokavain is accessible by the same styryl-pyrone chemistry (its saturated side chain is, formally, hydrogenated kavain). In practice, however, the dihydrokavain people are exposed to is extracted from the kava root, not manufactured: kava supplements are standardised to total kavalactone content rather than produced as single synthetic molecules ^{2Reference 2Bian T et al. · 2020ReviewKava as a Clinical Nutrient: Promises and ChallengesView study →}.

Patents: not yet researched.

Toxicity & Safety

As an isolated molecule, dihydrokavain carries a low flag. The kavalactones — dihydrokavain among them — were not cytotoxic to human liver (HepG2) cells at concentrations that killed cells via the aerial-part alkaloid pipermethystine, and dihydromethysticin (a representative kavalactone) did not potentiate acetaminophen liver injury in mice ^{12,13Reference 12Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →Reference 13Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →}. The safety story that matters here is kava’s, not this molecule’s, and it turns on which part of the plant and which constituents:

• The traditional aqueous root beverage has a long record of use and is not where the liver signal concentrates ^{14Reference 14Teschke R et al. · 2011ReviewHerbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.
• Rare, sometimes severe hepatotoxicity has been reported with some (mostly Western, ethanolic/acetonic) kava products. The leading candidate culprits are not the root kavalactones but pipermethystine (an alkaloid concentrated in leaves and stem peelings — the wrong plant part) ^{13Reference 13Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →}, the chalcone flavokawain B ^{12,14Reference 12Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →Reference 14Teschke R et al. · 2011ReviewHerbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}, and poor-quality or mould-contaminated raw material; solvent alone does not explain the cases ^{14Reference 14Teschke R et al. · 2011ReviewHerbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.
• Chemotype and quality therefore drive risk: noble root beverage differs from tudei/aerial-part or adulterated products in both kavalactone ratio and chalcone/alkaloid load ^{1,14Reference 1Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →Reference 14Teschke R et al. · 2011ReviewHerbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.
• In the negative GAD trial, kava was generally well tolerated but produced more frequent liver-enzyme abnormalities than placebo, though no participant met criteria for herb-induced liver injury ^{11Reference 11Sarris J et al. · 2020RCTKava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled study (clinical trial)View study →}.

Pregnancy/lactation is a per-herb / per-supplement decision and is settled on the kava monograph, not on this molecule page; no isolate-specific reproductive dataset exists for dihydrokavain.

Safety at a Glance

✅ Low / no toxicitySedating

• The isolated kavalactone is low-toxicity. Dihydrokavain and the other root kavalactones were not cytotoxic to liver cells at concentrations where an aerial-part alkaloid was, and a representative kavalactone did not worsen acetaminophen liver injury in mice ^{12,13Reference 12Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →Reference 13Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →}.
• Kava’s rare hepatotoxicity is real but constituent- and quality-specific. It is pinned on aerial-part pipermethystine, the chalcone flavokawain B, and poor/mouldy material — not on the root kavalactones — so product part, chemotype and quality matter ^{13,14Reference 13Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →Reference 14Teschke R et al. · 2011ReviewHerbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culpritsView study →}.
• Additive sedation. As a sedative kavalactone it could compound alcohol and other CNS depressants; a plausible, poorly-quantified interaction more relevant to concentrated extracts than to trace exposure ^{10Reference 10Sarris J et al. · 2011ReviewKava: a comprehensive review of efficacy, safety, and psychopharmacologyView study →}.
• Liver-enzyme monitoring for whole-kava use. Enzyme abnormalities were more frequent on kava than placebo in a controlled trial, warranting caution with pre-existing liver disease or hepatotoxic co-medication ^{11Reference 11Sarris J et al. · 2020RCTKava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled study (clinical trial)View study →}.

Dosage

There is no established or recommended human dose for isolated dihydrokavain. The figures in the literature are preclinical rodent research doses — for example an analgesic effect in mice around 150 mg/kg intraperitoneally ^{3Reference 3Jamieson DD · 1990AnimalThe antinociceptive actions of kava components in miceView study →} — and are not convertible to human self-dosing. Human exposure is via kava root beverage and standardised extracts, which are dosed by their total kavalactone content (commonly on the order of ~70-250 mg kavalactones per serving in the trial literature), with dihydrokavain present as one of the six major lactones and its share set by the cultivar/chemotype ^{1,2,9Reference 1Wang J et al. · 2015Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solventsView study →Reference 2Bian T et al. · 2020ReviewKava as a Clinical Nutrient: Promises and ChallengesView study →Reference 9Pittler MH · 2003Meta-analysisKava extract for treating anxietyView study →}. These are research and product figures, not a personal recommendation.

References

1. Wang J, Qu W, Bittenbender HC, Li QX (2015). Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solvents. Journal of Food Science and Technology. https://pubmed.ncbi.nlm.nih.gov/25694734/
2. Bian T, et al. (2020). Kava as a Clinical Nutrient: Promises and Challenges. Nutrients (review). https://pubmed.ncbi.nlm.nih.gov/33027883/
3. Jamieson DD, Duffield PH (1990). The antinociceptive actions of kava components in mice. Clinical and Experimental Pharmacology and Physiology. https://pubmed.ncbi.nlm.nih.gov/2401103/
4. Backhauss C, Krieglstein J (1992). Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/1396990/
5. Gleitz J, Beile A, Peters T (1995). (±)-Kavain inhibits veratridine-activated voltage-dependent Na+-channels in synaptosomes prepared from rat cerebral cortex. Neuropharmacology. https://pubmed.ncbi.nlm.nih.gov/8532183/
6. Magura EI, et al. (1997). Kava extract ingredients, (+)-methysticin and (±)-kavain, inhibit voltage-operated Na+-channels in rat CA1 hippocampal neurons. Neuroscience. https://pubmed.ncbi.nlm.nih.gov/9300426/
7. Chua HC, et al. (2016). Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanism. PLoS One. https://pubmed.ncbi.nlm.nih.gov/27332705/
8. Kanumuri SRR, et al. (2022). Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteers. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/35777607/
9. Pittler MH, Ernst E (2003). Kava extract for treating anxiety. Cochrane Database of Systematic Reviews (meta-analysis). https://pubmed.ncbi.nlm.nih.gov/12535473/
10. Sarris J, LaPorte E, Schweitzer I (2011). Kava: a comprehensive review of efficacy, safety, and psychopharmacology. Australian and New Zealand Journal of Psychiatry (review). https://pubmed.ncbi.nlm.nih.gov/21073405/
11. Sarris J, et al. (2020). Kava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled study (clinical trial). Australian and New Zealand Journal of Psychiatry. https://pubmed.ncbi.nlm.nih.gov/31813230/
12. Narayanapillai SC, Leitzman P, O’Sullivan MG, Xing C (2014). Flavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 mice. Chemical Research in Toxicology. https://pubmed.ncbi.nlm.nih.gov/25185080/
13. Nerurkar PV, Dragull K, Tang CS (2004). In vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactones. Toxicological Sciences. https://pubmed.ncbi.nlm.nih.gov/14737001/
14. Teschke R, Qiu SX, Lebot V (2011). Herbal hepatotoxicity by kava: update on pipermethystine, flavokavain B, and mould hepatotoxins as primarily assumed culprits. Digestive and Liver Disease (review). https://pubmed.ncbi.nlm.nih.gov/21377431/

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