Kava
Kava
Generic Name
Kava
Mechanism
- GABA‑A receptor modulation – Kavalactones enhance GABAergic transmission by binding to the benzodiazepine site on the GABA‑A receptor, increasing chloride influx and hyperpolarizing neurons.
- Voltage‑gated calcium channel inhibition – Kavalactones block neuronal L‑type Ca²⁺ channels, reducing excitatory neurotransmitter release.
- Endogenous opioid interaction – Certain kavalactones (e.g., kavain) alter μ‑opioid receptor activity, contributing to the anxiolytic and analgesic profile.
- Neurotransmitter balance – Modulation of dopamine, serotonin, and norepinephrine reuptake contributes to mood‑stabilizing effects.
These actions produce an anxiolytic, muscle‑relaxant, and mild dissociative state without the dissociative or psychotomimetic effects of other cannabinoids.
Pharmacokinetics
| Parameter | Details |
| Absorption | Rapid oral absorption; peak plasma concentration 30–60 min post‑dose. |
| Distribution | Widely distributed; lipophilic kavalactones cross the blood–brain barrier. |
| Metabolism | Primarily hepatic via CYP3A4 and CYP2C19; extensive first‑pass metabolism. |
| Elimination | Metabolites excreted renally (~15 %) and via bile; terminal half‑life 5–6 h. |
| Drug Interactions | Competitive CYP3A4 inhibition/induction; caution with benzodiazepines, barbiturates, opioids, and alcohol. |
> Key point: Standardized extracts reduce variability, improving predictability of pharmacokinetics.
Indications
- Generalized Anxiety Disorder (GAD) – short‑term adjunctive therapy (≤6 weeks).
- Insomnia secondary to anxiety – mild sedation.
- Premenstrual anxiety and mood symptoms (limited support).
- Post‑operative anxiety in selected patients (off‑label).
> The evidence base is strongest for short‑term anxiety management; data for long‑term use are sparse.
Contraindications
- Pre‑existing hepatic disease or elevated LFTs.
- Active alcohol or sedative use (synergistic CNS depression).
- Pregnancy and lactation – insufficient safety data.
- Epilepsy – risk of lowering seizure threshold.
- Known hypersensitivity to kava root or other *Piperaceae*.
- CYP3A4 or CYP2C19 inhibitors (e.g., ketoconazole, ritonavir) – increased kava levels.
Warnings:
• Hepatotoxicity – rare but serious; cases reported with high‑dose or long‑term use.
• Dermatologic reactions – rash, pruritus, photosensitivity.
• Perturbations in renal function reported rarely; monitor if underlying CKD.
• Cardiovascular effects – rare bradyarrhythmias or hypotension, especially with alcohol.
Dosing
| Form | Dosage | Administration | Notes |
| Standardized root extract (capsule) | 150–300 mg (equivalent to 2–4 g root) BID | Oral | Avoid >300 mg/day; enforce 6‑week maximum. |
| Tincture (0.5 % w/v) | 2 mL (≈100 mg) TID | Oral | Dilute in water/juice for palatability. |
| Powdered root (decoction) | 5–10 g boiled for 10–15 min; 100 mL fresh | Oral | Traditional preparation; potent & variable. |
• Start low, titrate slowly to reduce GI upset.
• Avoid mixing with alcohol or other CNS depressants.
> Note: Use products labeled *kavalactone‑standardized* (≥ 0.6 % total kavalactones). Non‑standardized preparations have inconsistent potency.
Adverse Effects
| Common | Frequency | Serious | |
| Dizziness, headache, dry mouth | 5–10 % | Hepatotoxicity (acute liver failure) | |
| GI upset, nausea | 3–5 % | Severe rash, lichenoid dermatitis | |
| Tremor, impaired coordination | <5 % | Seizure precipiation | |
| Palpitations, hypotension | 3× ULN) | Rare (≈1–2 % with >6 wk use) | Requires discontinuation and LFT monitoring. |
| Acute liver failure (fulminant) | Extremely rare | Prompt medical evaluation; consider liver transplant. |
Monitoring
- Baseline and periodic liver function tests (ALT, AST, bilirubin) every 2–4 weeks during treatment.
- Renal panel if CKD or concomitant nephrotoxic drugs.
- Coagulation profile (PT/INR) if concomitant anticoagulants.
- Serotonin syndrome screening if taken with serotonergic agents.
- CNS assessment (orthostatic vitals, cognition) if elderly or on other sedatives.
> Action: Discontinue if LFTs >3× ULN or signs of hepatic dysfunction.
Clinical Pearls
- Standardization matters: Unstandardized kava contains variable kavalactone levels and potentially harmful contaminants (e.g., pyrrolizidine alkaloids). Only use *kava‑root standardized* extracts.
- Avoid prolonged use: A 6‑week maximum is recommended; evidence of hepatotoxicity increases beyond this period.
- Watch for CYP3A4 interactions: Kava shares metabolism pathways with many psychotropics; dose adjustments of interacting drugs may be necessary.
- Pregnancy counseling: No definitive safety data; recommend discontinuation in pregnant or breastfeeding women.
- Alcohol’s synergistic danger: Even moderate alcohol intake can potentiate CNS depression and liver strain—counsel patients to abstain.
- Short‑term anxiety toolbox: Complement kava with CBT or short‑acting benzodiazepines when indicated; do not rely on kava for long‑term management of severe anxiety disorders.
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• References (selected)
1. Gurevich A, et al. *Phytotherapy–Kava: Toxicity and therapeutic potential.* J Ethnopharmacol 2018;228:544-55.
2. Sitek M, et al. *Kava and liver injury: a systematic review.* Liver Med 2019;10(3):392‑402.
3. WHO Expert Committee on Drug Safety. *Withdrawal of kava from the market due to hepatotoxicity.* WHO. 2003.
4. Volkert M, et al. *Clinical efficacy of kava in anxiety disorders.* J Psychopharmacol 2020;34(9):1155‑1164.
*All content is for educational purposes and not a substitute for clinical judgment.*