Kavain

Kavain at a Glance

Kavain (also spelled kawain) is a kavalactone — one of the six styryl-2-pyrones (kavapyrones) that carry almost all of the pharmacology of kava (Piper methysticum), the Pacific root traditionally drunk to ease anxiety and encourage calm sociability. Kavain is the kavalactone most often singled out as the principal anxiolytic constituent, and it is the one with the clearest single-molecule mechanism ^{1Reference 1Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →}.

Its best-characterised action is as a positive allosteric modulator of GABA-A receptors — potentiating the brain’s main inhibitory neurotransmitter through a site distinct from the benzodiazepine site ^{1Reference 1Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →} — layered on top of voltage-gated sodium-channel inhibition ^{2,3Reference 2Gleitz 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 3Magura EI et al. · 1997AnimalKava extract ingredients, (+)-methysticin and (±)-kavain, inhibit voltage-operated Na⁺-channels in rat CA1 hippocampal neuronsView study →} and weaker effects on monoamine oxidase B ^{6,7Reference 6Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →Reference 7Prinsloo D et al. · 2019Monoamine oxidase inhibition by kavalactones from kava (Piper methysticum)View study →} and cyclo-oxygenase ^{8Reference 8Gleitz J et al. · 1997Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human plateletsView study →}. This spread of targets fits kava’s mixed profile of anxiolysis, mild sedation, muscle relaxation and analgesia.

The honest framing for a compound page: the human efficacy evidence is for whole kava-root extract, not isolated kavain, and it is mixed — meta-analysis and several trials favour kava over placebo, but the largest modern trial was null ^{10,11,12Reference 10Pittler MH · 2003Systematic reviewKava extract for treating anxietyView study →Reference 11Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →Reference 12Sarris J et al. · 2020RCTKava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled studyView study →}. Kavain also sits on the reassuring side of kava’s liver-safety story: the rare hepatotoxicity that led to regulatory bans is attributed to aerial-part and quality-related constituents (pipermethystine, the flavokawain chalcones, mould), not to the root kavalactones — and in a clinical study the flavokawains were not even detectable in plasma ^{14,15,16Reference 14Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →Reference 15Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →Reference 16Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →}.

GABA-A Modulation & the Lead Anxiolytic Kavalactone

Kavain is the kavalactone that best earns the label “the active one.” Two facts define its signature.

It is the constituent most credited with kava’s anti-anxiety effect. Across the six-lactone profile, kavain is consistently named the principal anxiolytic kavalactone, and it is the single kavalactone whose interaction with the presumed target has been directly demonstrated rather than inferred ^{1Reference 1Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →}.

Its mechanism is a direct GABA-A potentiation. Kava’s calming action had long been assumed to run through GABA-A receptors on the strength of binding data, but direct evidence was “scarce and equivocal” until kavain was characterised at human recombinant receptors expressed in Xenopus oocytes. There, kavain positively modulated every GABA-A subtype tested regardless of subunit composition, with a larger effect at extrasynaptic α4β2δ than at synaptic α1β2γ2L receptors ^{1Reference 1Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →}. Two details matter for interpretation: the effect was not blocked by flumazenil, so kavain does not act at the classic benzodiazepine site, and it was diminished by the β3N265M mutation that also blunts general-anaesthetic sensitivity — pointing to an anaesthetic-like modulatory pocket rather than the benzodiazepine one ^{1Reference 1Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →}. This is the first experimental evidence of a direct kavalactone–GABA-A interaction, and it belongs to kavain.

That GABA-A modulation is the anchor; sodium-channel block, MAO-B inhibition and monoaminergic shifts (below) are the supporting cast that give kava its broader muscle-relaxant, analgesic and mood profile.

What It's Used For

Kavain’s pharmacology is unusually well mechanistically resolved for a plant constituent — but the discipline is that the mechanism work is the isolate, while the human efficacy work is the whole extract, and the two do not automatically transfer.

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. Human efficacy data are the whole extract (mixed results), while the mechanism data are the isolate, so isolate-attributed scores stay measured by design.

01Anxiolytic / SedativePromising52%Direct GABA-A PAM mechanism (isolate) ^{1Reference 1Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →} + mixed human RCT/meta-analysis on the extract ^{10,11,12Reference 10Pittler MH · 2003Systematic reviewKava extract for treating anxietyView study →Reference 11Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →Reference 12Sarris J et al. · 2020RCTKava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled studyView study →}

02Muscle-Relaxant / AnticonvulsantShaky34%Isolate blocks voltage-gated Na⁺ channels in synaptosomes & CA1 neurons ^{2,3Reference 2Gleitz 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 3Magura EI et al. · 1997AnimalKava extract ingredients, (+)-methysticin and (±)-kavain, inhibit voltage-operated Na⁺-channels in rat CA1 hippocampal neuronsView study →}

03Analgesic / Local-AnaestheticShaky30%Kava-pyrone class analgesia; Na⁺-channel/conduction mechanism (isolate, preclinical) ^{2,3Reference 2Gleitz 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 3Magura EI et al. · 1997AnimalKava extract ingredients, (+)-methysticin and (±)-kavain, inhibit voltage-operated Na⁺-channels in rat CA1 hippocampal neuronsView study →}

04Antiplatelet / AntithromboticShaky28%(+)-Kavain inhibits COX / thromboxane synthase in human platelets in vitro ^{8Reference 8Gleitz J et al. · 1997Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human plateletsView study →}

05Monoaminergic (MAO-B / Dopamine)Shaky26%In-vitro MAO-B inhibition + rat nucleus-accumbens microdialysis (isolate & extract) ^{6,7,9Reference 6Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →Reference 7Prinsloo D et al. · 2019Monoamine oxidase inhibition by kavalactones from kava (Piper methysticum)View study →Reference 9Baum SS et al. · 1998AnimalEffect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of ratsView study →}

Mechanisms

The load-bearing point is that GABA-A potentiation is the one mechanism directly demonstrated for the isolated kavalactone ^{1Reference 1Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →}; the sodium-channel, COX and MAO-B actions are real but add breadth rather than carrying the anxiolytic claim on their own.

Pharmacokinetics

Direct single-molecule human PK for isolated kavain is not published, but a clinical pharmacokinetic study of the six kavalactones after oral standardized (flavokawain-free) kava extract in ten healthy volunteers is the best available anchor. Kavalactones were rapidly absorbed, with time-to-peak of roughly 1–3 hours, and PK was dose-proportional across 75–225 mg of kavalactones ^{14Reference 14Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}. Kavain’s systemic exposure ranked third of the six (dihydrokavain > dihydromethysticin > kavain > methysticin > yangonin) ^{14Reference 14Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}. Food significantly reduced the extent of kavalactone absorption, and — importantly for safety — flavokawains A and B were not detectable in plasma at all, while single high dosing gave higher peak exposure and thrice-daily dosing gave longer duration ^{14Reference 14Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}. A distinctive PK-relevant caveat for this molecule is that kava (and its kavalactones) inhibit several cytochrome-P450 enzymes, the basis of kava’s real-world drug-interaction potential (see Toxicity).

Clinical Trials

There are no controlled trials of isolated kavain. The human evidence is entirely for whole standardized kava-root extract in anxiety, and it is mixed: a Cochrane review of randomised placebo-controlled trials favoured kava ^{10Reference 10Pittler MH · 2003Systematic reviewKava extract for treating anxietyView study →}, an early double-blind GAD trial was positive with a companion safety analysis of liver function, addiction and sexual effects ^{11,13Reference 11Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →Reference 13Sarris J et al. · 2013RCTKava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effectsView study →}, and the largest 16-week double-blind GAD trial (KGA) was null ^{12Reference 12Sarris J et al. · 2020RCTKava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled studyView study →}. A human PK study of the kavalactone mixture has been completed ^{14Reference 14Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

Kavain splits cleanly along the compound-page fault line. The mechanism is the isolate: the GABA-A modulation ^{1Reference 1Chua HC et al. · 2016Kavain, the major constituent of the anxiolytic kava extract, potentiates GABAA receptors: functional characteristics and molecular mechanismView study →}, the sodium-channel block ^{2,3Reference 2Gleitz 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 3Magura EI et al. · 1997AnimalKava extract ingredients, (+)-methysticin and (±)-kavain, inhibit voltage-operated Na⁺-channels in rat CA1 hippocampal neuronsView study →}, the COX/thromboxane inhibition ^{8Reference 8Gleitz J et al. · 1997Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human plateletsView study →} and the MAO-B enzymology ^{6,7Reference 6Uebelhack R et al. · 1998Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)View study →Reference 7Prinsloo D et al. · 2019Monoamine oxidase inhibition by kavalactones from kava (Piper methysticum)View study →} were all done on purified or synthetic kavain, often synthetic (±)-kavain, which is a genuine strength — the molecular target is not guessed from a crude extract. The efficacy is the plant: every anxiety trial used standardized whole kava-root extract standardised to total kavalactones, never isolated kavain ^{10,11,12Reference 10Pittler MH · 2003Systematic reviewKava extract for treating anxietyView study →Reference 11Sarris J et al. · 2013RCTKava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled studyView study →Reference 12Sarris J et al. · 2020RCTKava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled studyView study →}, and the human PK study likewise dosed the six-lactone extract ^{14Reference 14Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}. So the correct read is a strong isolate mechanism plus mixed whole-extract clinical evidence — and because kavain is only ~a quarter-to-a-third of the lactone mixture, its individual contribution to any clinical result cannot be cleanly separated from its siblings dihydrokavain, methysticin, dihydromethysticin, desmethoxyyangonin and yangonin.

Kava’s Liver-Safety Story — And Why It Isn’t Kavain

Kava carries the single most famous herbal-hepatotoxicity caveat of the modern era: reports of rare, severe liver injury led several countries to ban kava products in the early 2000s. Any page about a kava constituent has to address it honestly — and for kavain the honest answer is that the evidence points away from the root kavalactones.

• Whole kava is not hepatotoxic in animal models. In C57BL/6 mice, kava alone showed no adverse effect even at 500 mg/kg; liver injury only emerged when kava was combined with acetaminophen, and that synergism was reproduced by the chalcone flavokawains A and B — not by the kavalactone dihydromethysticin ^{15Reference 15Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →}.
• The aerial-part alkaloid is directly cytotoxic to liver cells. Pipermethystine, concentrated in the leaves and stem peelings (the parts not used in the traditional root beverage), killed human HepG2 hepatocytes and disrupted mitochondrial function at concentrations where kavalactones were harmless ^{16Reference 16Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →}.
• The flavokawains do not reach the blood. In the clinical PK study, flavokawains A and B were undetectable in plasma after oral kava dosing — consistent with the culprit being a contamination/quality and plant-part issue rather than a systemic kavalactone effect ^{14Reference 14Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →}.
• A contamination hypothesis fits the pattern. Because whole-kava hepatotoxicity is not reproducible in preclinical models, one working hypothesis attributes rare human cases to mould/contaminant hepatotoxins and poor-quality raw material, alongside use of the wrong plant part and non-noble (tudei/wichmannii) cultivars with unfavourable chemistry ^{17Reference 17Teschke R et al. · 2013Contaminant hepatotoxins as culprits for kava hepatotoxicity — fact or fiction? Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/22585547/View study →}.

The practical, evidence-aligned position is the one conservative reviewers reach: prefer an aqueous extract of peeled root/rhizome from a non-mouldy noble cultivar, keep to ≤250 mg kavalactones/day for acute or intermittent use, and avoid aerial-part and solvent-heavy products ^{17Reference 17Teschke R et al. · 2013Contaminant hepatotoxins as culprits for kava hepatotoxicity — fact or fiction? Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/22585547/View study →}. Kavain is a constituent of the safe fraction; it is not the molecule the liver signal is about.

Its Role in Plants

Kavain is a styryl-2-pyrone (kavapyrone), a class of lactones built on the plant’s polyketide/phenylpropanoid machinery and, within the plant kingdom, largely a chemical signature of kava and a few relatives in the genus Piper. Kava itself is a sterile cultigen propagated by cuttings, and its distinctive kavalactone profile — the relative proportions of the six lactones, summarised in the traditional chemotype “number” nomenclature — is what distinguishes noble drinking cultivars from the harsher two-day (tudei) and wichmannii types ^{4Reference 4Wang 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 →}. The lactones accumulate most in the underground root and rhizome, with the aerial parts carrying a different, alkaloid-shifted chemistry — the botanical fact that underlies the whole safety story above. As defence-associated secondary metabolites they contribute to the plant’s chemical protection, though kava’s ecology is dominated by human cultivation rather than wild selection.

Prevalence in Nature

Kavain is effectively exclusive to kava (Piper methysticum), where it is one of the six major kavalactones — methysticin, dihydromethysticin, kavain, dihydrokavain, yangonin and desmethoxyyangonin — that together account for the great majority of the root’s activity ^{4Reference 4Wang 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 →}. Total kavalactones run at roughly 3–20% of dried root, shifting markedly with cultivar, chemotype, root-versus-rhizome and extraction solvent (ethanol extracts most efficiently; hexane least) ^{4Reference 4Wang 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 →}. Kavain’s share of that fraction is commonly cited around a quarter to a third, but it is genuinely chemotype-dependent and best read as a proportion of the lactone mixture rather than a fixed plant-content figure. Trace occurrence in a few related Piper species is reported, but for practical purposes this is a one-plant molecule.

Major Natural Sources

Source	Plant part	Reported kavain level
Kava (Piper methysticum), noble cultivar	peeled root & rhizome	~28–39% of total kavalactones (chemotype-dependent)
Kava, total kavalactone context	dried root	six lactones together ≈ 3–20% of dry weight

These are proportions of the kavalactone fraction / dried root, not whole-plant figures, and they vary with cultivar, plant part and extraction method ^{4Reference 4Wang 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 →}. Per-cultivar % dry-weight figures for kavain specifically are a known data gap (see the compound’s gaps tracker).

Discovery & Synthesis

Kavain was among the first kava constituents to be pulled out of the root by nineteenth-century chemists probing why the Pacific beverage was psychoactive; its name simply carries the plant’s — kava → kavain / kawain. The molecule’s styryl-2-pyrone structure and its preparation as synthetic racemic (±)-kavain were established in the twentieth century, and it is this synthetic (±)-kavain (and resolved (+)-kavain) that the modern mechanistic literature has largely used ^{2,8Reference 2Gleitz 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 8Gleitz J et al. · 1997Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human plateletsView study →}. A precise “first total synthesis” attribution is not well documented in the readily accessible literature, and is left for a later pass. Racemic kavain has additionally seen use as a stand-alone pharmaceutical anxiolytic in parts of Europe, separate from whole-kava products. Today kavain reaches people almost entirely as a natural constituent of whole kava-root extract rather than as an isolated synthetic drug.

Patents: not yet researched.

Toxicity & Safety

Isolated kavain carries a low flag: it is a constituent of the kava-root fraction that is not implicated in kava’s rare hepatotoxicity (see above), whole kava showed no liver injury in mice even at high dose ^{15Reference 15Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →}, and the traditional root beverage has a long human safety record. The cautions that do apply are those of a centrally active, enzyme-inhibiting sedative — and the broader kava context.

Safety at a Glance

✅ Low / no toxicitySedatingDrug interactions

• Kavain is on the safe side of the kava liver story. Whole kava and its kavalactones are not hepatotoxic in animal models; the rare human liver injury tracks aerial-part pipermethystine, the flavokawain chalcones and quality/contamination — with flavokawains undetectable in plasma ^{14,15,16Reference 14Kanumuri SRR et al. · 2022Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteersView study →Reference 15Narayanapillai SC et al. · 2014AnimalFlavokawains A and B in kava, not dihydromethysticin, potentiate acetaminophen-induced hepatotoxicity in C57BL/6 miceView study →Reference 16Nerurkar PV et al. · 2004In vitroIn vitro toxicity of kava alkaloid, pipermethystine, in HepG2 cells compared to kavalactonesView study →}.
• Additive CNS depression. As a GABA-A-potentiating, sodium-channel-blocking sedative, kavain can compound alcohol, benzodiazepines and other CNS depressants; impairment of driving/operating machinery is the practical concern.
• CYP450 drug interactions. Kava/kavalactones inhibit several cytochrome-P450 enzymes, so meaningful herb–drug interactions are plausible with CYP-metabolised medicines; interactions were not exhaustively mapped for the isolate here.
• Use the right kava, at a sensible ceiling. Evidence favours aqueous extract of peeled root/rhizome from a non-mouldy noble cultivar, ≤250 mg kavalactones/day for acute/intermittent use; avoid aerial-part and heavy-solvent products ^{17Reference 17Teschke R et al. · 2013Contaminant hepatotoxins as culprits for kava hepatotoxicity — fact or fiction? Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/22585547/View study →}. Heavy chronic kava use is also linked to a reversible scaly skin condition (kava dermopathy).
• Pregnancy/lactation is decided on the herb/product page, not here; dedicated reproductive-toxicity data for isolated kavain are lacking, and kava use in pregnancy/breastfeeding is generally cautioned at the product level.

Dosage

There is no established or recommended dose for isolated kavain — it is not sold or studied as a stand-alone measured dose in the clinical literature. Human dosing figures belong to whole standardized kava-root extract, expressed as total kavalactones, of which kavain is one of six:

Kavain is roughly a quarter-to-a-third of the kavalactone content of a noble extract, so its individual intake within any of these regimens is a fraction of the total-kavalactone figure. These are research and whole-extract figures, not a personal recommendation, and they say nothing about dosing purified kavain on its own.

References

1. Chua HC, Christensen ET, Hoestgaard-Jensen K, 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/
2. 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/
3. Magura EI, Kopanitsa MV, Gleitz J, Peters T, Krishtal OA (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/
4. 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/
5. 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/
6. Uebelhack R, Franke L, Schewe HJ (1998). Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava). Pharmacopsychiatry. https://pubmed.ncbi.nlm.nih.gov/9832350/
7. Prinsloo D, van Dyk S, Petzer A, Petzer JP (2019). Monoamine oxidase inhibition by kavalactones from kava (Piper methysticum). Planta Medica. https://pubmed.ncbi.nlm.nih.gov/31539917/
8. Gleitz J, Beile A, Wilkens P, Ameri A, Peters T (1997). Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human platelets. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/9063093/
9. Baum SS, Hill R, Rommelspacher H (1998). Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Progress in Neuro-Psychopharmacology & Biological Psychiatry. https://pubmed.ncbi.nlm.nih.gov/9829291/
10. Pittler MH, Ernst E (2003). Kava extract for treating anxiety. Cochrane Database of Systematic Reviews. https://pubmed.ncbi.nlm.nih.gov/12535473/
11. Sarris J, Stough C, Bousman CA, et al. (2013). Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study. Journal of Clinical Psychopharmacology. https://pubmed.ncbi.nlm.nih.gov/23635869/
12. Sarris J, Byrne GJ, Bousman CA, et al. (2020). Kava for generalised anxiety disorder: a 16-week double-blind, randomised, placebo-controlled study. Australian and New Zealand Journal of Psychiatry. https://pubmed.ncbi.nlm.nih.gov/31813230/
13. Sarris J, Stough C, Teschke R, et al. (2013). Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/23348842/
14. Kanumuri SRR, Mamallapalli J, Nelson R, 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/
15. 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/
16. 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/
17. Teschke R, Sarris J, Lebot V (2013). Contaminant hepatotoxins as culprits for kava hepatotoxicity — fact or fiction? Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/22585547/

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