Introduction
Kava (Piper methysticum) is a botanical preparation derived from the roots of a shrub native to the South Pacific islands. Traditionally used for centuries in ceremonial and social contexts, kava has gained popularity in Western countries as an herbal supplement for its anxiolytic and sedative properties. Unlike pharmaceutical anxiolytics, kava is regulated as a dietary supplement in most countries rather than as a medication.
Mechanism of Action
Kava's pharmacological effects are primarily attributed to a group of compounds called kavalactones (also known as kavapyrones). The six major kavalactones—kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin—act on the central nervous system through multiple mechanisms:
- Modulation of GABA-A receptors (enhancing chloride channel opening)
- Inhibition of voltage-gated sodium and calcium channels
- Monoamine oxidase B inhibition
- Noradrenaline and dopamine reuptake inhibition
- Possible effects on cannabinoid receptors
These actions collectively produce anxiolytic, sedative, anticonvulsant, and muscle relaxant effects without causing significant cognitive impairment at therapeutic doses.
Indications
Kava is not FDA-approved for any medical indication but is used as a dietary supplement for:
- Management of mild to moderate anxiety symptoms
- Sleep induction and improvement of sleep quality
- Muscle relaxation
- Stress reduction
Clinical evidence supports its efficacy for anxiety disorders, with several meta-analyses demonstrating superiority over placebo for generalized anxiety symptoms.
Dosage and Administration
Standardized preparations typically contain 70% kavalactones. Recommended dosing:
Adults:- Anxiety: 60-120 mg kavalactones daily in divided doses
- Sleep: 60-120 mg kavalactones 1-2 hours before bedtime
- Maximum daily dose: 250 mg kavalactones
- Hepatic impairment: Contraindicated
- Renal impairment: Use with caution
- Elderly: Consider reduced dosing (start with 30-60 mg daily)
- Pregnancy/Lactation: Contraindicated (Category 2C)
Pharmacokinetics
Absorption: Kavalactones are rapidly absorbed with peak concentrations occurring within 1.8 hours. Food may enhance absorption. Distribution: Highly lipophilic compounds that readily cross the blood-brain barrier. Protein binding is extensive. Metabolism: Primarily hepatic via CYP450 enzymes (CYP2D6, CYP3A4, and others). Extensive first-pass metabolism. Elimination: Half-life ranges from 1.5-9 hours depending on the specific kavalactone. Eliminated primarily via urine and feces.Contraindications
- Known hypersensitivity to kava or related plants
- Pre-existing liver disease or elevated liver enzymes
- Pregnancy and breastfeeding
- Major depressive disorder with suicidal ideation
- Parkinson's disease
- Children under 18 years
Warnings and Precautions
Black Box Warning: Risk of severe hepatotoxicity including hepatitis, cirrhosis, and liver failure requiring transplantation. Several countries have restricted or banned kava products due to hepatotoxicity reports. Additional Precautions:- May impair motor skills and driving ability
- Potential for dependency with long-term use
- May exacerbate depression symptoms
- Avoid concomitant use with other hepatotoxic substances
- Discontinue use at least two weeks before elective surgery
Drug Interactions
Major Interactions:- CNS depressants (alcohol, benzodiazepines, opioids): Enhanced sedation
- Hepatotoxic drugs (acetaminophen, statins, antifungals): Increased liver injury risk
- CYP450 substrates: May alter metabolism of numerous medications
- Levodopa: Reduced efficacy in Parkinson's disease
- MAO inhibitors: Theoretical risk of serotonin syndrome
- Antiplatelet/anticoagulant drugs: Possible increased bleeding risk
Adverse Effects
Common (≥1%):- Gastrointestinal discomfort
- Drowsiness, fatigue
- Headache
- Dizziness
- Visual disturbances (kava dermopathy with chronic use)
- Hepatotoxicity (elevated liver enzymes, hepatitis, liver failure)
- Allergic reactions
- Psychiatric symptoms (dysphoria, agitation)
- Extrapyramidal symptoms
- Pulmonary hypertension (with chronic heavy use)
Monitoring Parameters
Baseline:- Comprehensive metabolic panel (especially liver enzymes)
- Assessment of anxiety symptoms
- Review of concomitant medications
- Liver function tests every 2-4 weeks during first 2 months
- Symptom assessment every 2 weeks
- Evaluation for signs of hepatotoxicity (jaundice, fatigue, abdominal pain)
- Assessment of motor and cognitive function
Patient Education
- Inform healthcare providers about kava use before procedures or new prescriptions
- Immediately report signs of liver problems (yellow skin/eyes, dark urine, abdominal pain)
- Avoid alcohol consumption while using kava
- Do not operate vehicles or machinery until effects are known
- Use only water-soluble extracts from reputable manufacturers
- Limit duration of use to 4-8 weeks maximum
- Store out of reach of children
- Recognize that kava is a supplement, not an FDA-approved medication
References
1. Sarris J, et al. Plant-based medicines for anxiety disorders: Part 2. CNS Drugs. 2013;27(4):301-319. 2. Teschke R, et al. Kava hepatotoxicity: Comparison of aqueous, ethanolic, acetonic kava extracts and kava-herb mixtures. J Ethnopharmacol. 2019;229:93-103. 3. FDA MedWatch. Kava-containing dietary supplements may be associated with severe liver injury. FDA Medical Product Safety Information. 2002. 4. White CM, et al. Pharmacokinetic and pharmacodynamic profile of kava. J Clin Pharmacol. 2021;61(11):1415-1425. 5. European Medicines Agency. Assessment report on Piper methysticum G. Forst., rhizome. EMA/HMPC/678583/2013. 2014. 6. National Center for Complementary and Integrative Health. Kava. NCCIH Publication No. D473. 2020. 7. Therapeutic Goods Administration. Kava fact sheet. TGA Publication. 2019. 8. Savage K, et al. Kava for the treatment of generalized anxiety disorder: A systematic review and meta-analysis. J Clin Psychopharmacol. 2021;41(3):277-285.
This monograph is for educational purposes only and does not constitute medical advice. Healthcare providers should exercise clinical judgment when considering kava use.