Kavain

(2R)-4-methoxy-2-[(E)-2-phenylethenyl]-2,3-dihydropyran-6-one

Overview

Kavain belongs to Anxiolytics.

Key safety note: Kava and its kavalactone kavain are generally mild, but carry real cautions.[3][2]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • Mild anxiolysis and relaxation: a clear-headed calm, sociability and mild muscle relaxation, traditionally without strong intoxication at moderate doses.
  • At higher doses: pronounced sedation, drowsiness, mild euphoria, numbing of the mouth and lips, and impaired coordination.
  • Onset is fairly quick when drunk as a beverage (within ~15–30 minutes) and effects last a few hours. Very high or heavy use can cause nausea and next-day grogginess.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral: traditionally a water-based root beverage. Also extracts, capsules or isolated kavain. Dose is usually expressed as total kavalactones.. Kava is dosed by its total kavalactone content, kavain is only one of six major kavalactones, so a 'dose' of the beverage or extract is not the same as a dose of pure kavain, and product strength varies widely. The figures below are rough context, not a precise or 'safe' amount. The key harm-reduction points: prefer water-based extracts of noble kava root from a reputable source, avoid alcohol and other hepatotoxic or sedating drugs, do not use it daily for long periods, and avoid kava entirely if you have any liver disease.

Dose ranges

Standardised extract (anxiety)

≈100–250 mg total kavalactones/day

Traditional beverage serving

variable, often considerably higher

Duration

onset

≈15–30 minutes (beverage)

total

a few hours

after effects

Possible grogginess or nausea. Heavy chronic use can cause reversible 'kava dermopathy'

Chemical & Physical Properties
FormulaC14H14O3
Molar mass230.26 g/mol
StateNot reported
Melting pointNot reported
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKaNot reported
LogP2.5 (predicted, XLogP3)
SolubilityNot reported
Refractive indexNot reported
Identifiers & Synonyms
CASNot reported
CAS (enantiomer)
PubChem CID5281565
InChIKeyXEAQIWGXBXCYFX-GUOLPTJISA-N
InChIInChI=1S/C14H14O3/c1-16-13-9-12(17-14(15)10-13)8-7-11-5-3-2-4-6-11/h2-8,10,12H,9H2,1H3/b8-7+/t12-/m0/s1
SMILESCOC1=CC(=O)O[C@H](C1)/C=C/C2=CC=CC=C2

Synonyms

    Pharmacodynamics & Biochemistry

    Kavain is one of the six major kavalactones (kava pyrones) in kava (Piper methysticum), a Pacific-island plant whose root is prepared as a traditional relaxing, mildly sedating anxiolytic beverage. The naturally predominant form is the (R)-(+)-enantiomer, and kavain is among the constituents most associated with kava's calming effects. Rather than acting through a single high-affinity receptor, kavain works largely by modulating ion channels: it blocks voltage-gated sodium channels (IC50 ≈ 86–88 µM, Ki ≈ 72 µM at the batrachotoxin/veratridine site) and voltage-gated calcium channels, reducing neuronal excitability and neurotransmitter release. This underlies its anxiolytic, mild sedative, muscle-relaxant and anticonvulsant actions. Note that these are micromolar functional potencies rather than nanomolar receptor binding, which is why kava is not curated in receptor-binding databases such as GtoPdb. It also has secondary actions: it is a reversible, competitive inhibitor of monoamine oxidase B (MAO-B, Ki ≈ 0.28–1.14 µM), gives modest positive modulation at GABA-A receptors, and affects dopamine and noradrenaline handling. Together these give kava a distinctive profile of relaxation without the strong sedation, intoxication or dependence of benzodiazepines or alcohol. Kava and kavain are metabolised in the liver. A key safety issue is that kava has been linked to rare but serious liver injury. The mechanism is not fully understood but may involve inhibition of drug-metabolising CYP enzymes and, in some products, use of the wrong plant parts or extraction solvents.

    Biological targets

    • GABA-A
    • VGCC

    Binding & functional measurements

    TargetMeasurementSpecies
    MAO-BpKi 6.55Human
    Pharmacokinetics
    BioavailabilityOral, kavalactones are rapidly absorbed (bioavailability enhanced by the plant matrix vs isolated compound)
    Tmax≈1.5–2 h
    Half-life≈1–2 h (short)
    VdNot reported
    Protein bindingNot reported
    MetabolismHepatic. Kavalactones undergo oxidation/reduction and inhibit several CYP enzymes (CYP1A2, 2C9, 2C19, 2D6, 3A4, 2E1)
    ExcretionUrine and faeces as metabolites
    Toxicology & Safety
    Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

    Not reported

    Kava and its kavalactone kavain are generally mild, but carry real cautions. The most serious is rare but potentially severe liver injury (hepatotoxicity) linked to kava products, which prompted regulatory bans and warnings in several countries. The risk appears higher with poor-quality extracts, heavy or prolonged use, and combination with alcohol or other liver-stressing drugs. Kava causes dose-dependent sedation and impairs coordination and driving, and heavy long-term traditional use can cause a reversible scaly skin condition ('kava dermopathy'). It should be avoided in liver disease, in pregnancy and breastfeeding, and combined cautiously: its sedation adds to that of alcohol, benzodiazepines and other depressants. It is not physically addictive in the way benzodiazepines are.[3][2]

    Legal Status
    Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
    Interactions & Contraindications

    Drug interactions

    Alcohol, Benzodiazepines Additive sedation and impairment. Alcohol may also increase the risk of liver injury.[3]
    Other hepatotoxic drugs Potential additive liver injury with other hepatotoxic drugs or heavy alcohol.[3]
    Drugs cleared by shared CYP enzymes (e.g. CYP2C9, CYP3A4) Kavalactones inhibit several CYP enzymes (CYP2E1, CYP1A2, CYP2C9, CYP3A4), so kava can raise the levels of many drugs.[3]
    Dopaminergic drugs (levodopa, dopamine agonists) Case reports of kava worsening parkinsonism (possible dopamine antagonism).[3]

    Contraindications

    Kidney or liver impairment existing liver disease or raised liver enzymes.[3]
    Pregnancy or breastfeeding[3]
    Settings where impairment or dissociation risks injury (driving, water, heights) before driving or operating machinery, with caution in Parkinson's disease and in depression.[3]
    Usage & Context
    • Traditionally prepared from kava root as a ceremonial and social beverage across the Pacific Islands, valued for its relaxing, sociable effects.
    • Used worldwide as a herbal anxiolytic and sleep aid, as kava extracts and supplements and, increasingly, in 'kava bars', with clinical evidence supporting a modest anxiety-reducing effect.
    • Kavain itself is also sold as an isolated supplement and studied for anxiety and other potential uses.
    Sources & Evidence
    1. PubChem: (+)-Kavain (CID 5281565) — identifiers & computed properties
    2. Pampita N, Sajeev A, Hegde M, et al. (2026). Kavain for health promotion and disease mitigation: Pharmacological promise and therapeutic perspectives. Phytomedicine 155:158017.

      PMID 41930811 · doi:10.1016/j.phymed.2026.158017

    3. White CM (2018). The Pharmacology, Pharmacokinetics, Efficacy, and Adverse Events Associated With Kava. J Clin Pharmacol 58:1396-1405.

      PMID 29791008 · doi:10.1002/jcph.1263

    4. Grunze H, Langosch J, Schirrmacher K, et al. (2001). Kava pyrones exert effects on neuronal transmission and transmembraneous cation currents similar to established mood stabilizers--a review. Prog Neuropsychopharmacol Biol Psychiatry 25:1555-70.

      PMID 11642654 · doi:10.1016/s0278-5846(01)00208-1

    5. Uebelhack R, Franke L, Schewe HJ (1998). Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava). Pharmacopsychiatry 31:187-92.

      PMID 9832350 · doi:10.1055/s-2007-979325

    6. Gleitz J, Friese J, Beile A, et al. (1996). Anticonvulsive action of (+/-)-kavain estimated from its properties on stimulated synaptosomes and Na+ channel receptor sites. Eur J Pharmacol 315:89-97.

      PMID 8960869 · doi:10.1016/s0014-2999(96)00550-x

    7. PsychonautWiki: Kava — effects & duration CC BY-SA 4.0
    8. The Medicines for Human Use (Kava-kava) (Prohibition) Order 2002 (SI 2002/3170) — UK legislation.gov.uk OGL v3.0
    9. Wikipedia: Kavain (chemistry, pharmacology & legal status) CC BY-SA 4.0
    10. PubChem computed properties (CID 5281565)

    Further Information