Kava for Anxiety
December 1998; Volume 1: 4-6
Kava (Piper methysticum) is a psychoactive member of the pepper family. Ceremonial kava drinking has a long tradition of use in Polynesia, Micronesia, and Melanesia. The kava shrub’s root (actually a rhizome or underground stem) traditionally is chewed by specified members of the community before being mixed with water or coconut milk. Generally, chewers are young men or women selected for strong teeth, clean mouths, and freedom from overt disease. There are specific rules and procedures associated with the preparation and distribution of the drink, and the kava ceremony may be quite elaborate for formal occasions.
A sedative agent, kava is used medicinally in Europe for anxiety and insomnia. In recent years, kava has become quite popular in the United States, with sales of $2.9 million in 1997. Kava is one of the few herbs for which the active constituents, kavapyrones, have been characterized. A number of clinical trials of kava attest to its anxiolytic effects.
Clinical Trials of Kava for Anxiety
In a randomized, double-blind, placebo-controlled trial, 58 patients with anxiety syndromes were assigned either to placebo or to 100 mg of kava extract WS 1490 (Laitan®)—equivalent to 70 mg kavapyrones—three times daily for four weeks. Compared to placebo, the kava group demonstrated a significant reduction in anxiety as assessed by the Hamilton Anxiety Scale (HAMA). Differences between the two groups were noted as early as the end of the first week and increased during the course of the study.1
A randomized, double-blind, placebo-controlled multicenter study of 101 outpatients with anxiety disorders treated with 300 mg kava extract WS1490 daily (equivalent to 210 mg kavapyrones) for 25 weeks found significant reductions in the HAMA scale in the kava group beginning in the eighth week.2 Improvements were also seen in secondary outcome variables, which included HAMA subscores for somatic and psychic anxiety, Clinical Global Impression, Self-Report Symptom Inventory, and Adjective Mood Scale.
Several other controlled, double-blind trials on kava extracts or the isolated compound DL-kawain have been published in the German literature.3 In a typical trial, 58 patients with anxiety received 210 mg kava or placebo daily for a month. Compared to placebo, those receiving kava had significantly greater reductions in HAMA scores starting at one week.4
In the only treatment-controlled trial identified, a daily dose equivalent to 210 mg of kavapyrones was compared with 15 mg/d oxazepam or 9 mg/d bromazepam for six weeks. One hundred sixty-four patients completed the protocol; HAMA ratings did not differ significantly among the three groups.5
Kava and Menopausal Symptoms
A study of kava for climacteric symptoms in 40 women using doses of 30-60 mg/d for 56-84 days found significant improvements in the HAMA scale and Kupperman index.6 Another trial by the same investigator, but using a higher dose (equivalent to 210 kavapyrones/d), in 40 menopausal women also found improvements in symptoms, HAMA, Kupperman index, and Depression Status Inventory (DSI).7
Active Compounds
Active constituents in kava are the kavapyrones (also called kavalactones), which include kawain, dihydrokawain, methysticin, and dihydromethysticin.3 All of the kavapyrones are centrally acting skeletal muscle relaxants. Anticonvulsant effects have also been demonstrated and appear to be due to effects on sodium and calcium channels.8 Kava extract affects GABAA receptor binding.9 Several kavapyrones, including methysticin and dihydromethysticin, are potent inhibitors of [3H]-norepinephrine.10
Adverse Effects
The incidences of side effects were low in observational studies that included more than 7000 patients treated with kava for 4-7 weeks. All side effects (predominately gastrointestinal discomfort, headache, dizziness, and allergic skin reactions) were mild and revers-ible; the total incidence of reported side effects was only 1.5-2.3%.3
Kava may have subtle detrimental effects on vision. A heavy dose of traditionally prepared kava, administered under experimental conditions to a single subject who had never used it before, found no effect on visual acuity, stereoacuity, or refractive error. However, kava reduced the near point of accommodation, decreased the near point of convergence, disturbed oculomotor balance, and increased pupil diameter.11
Although EEG studies and psychometric tests of intellectual and motor functioning do not indicate significant impairment with doses used therapeutically,3 heavier doses used recreationally can cause gait disturbance and other signs similar to alcohol intoxication. Interestingly, a 44-year-old motorist arrested in Utah for swerving in and out of traffic lanes appeared to be typically drunk (staggering, slurred speech, and slowed responses), but a breath test showed no evidence of alcohol. The motorist turned out to be suffering the effects of 16 cups of kava. Although the herb is legal, the motorist was convicted of driving under the influence of kava, in the first case of its kind.12
Heavy, chronic use of kava results in yellowing of the skin and an ichthyosiform eruption known as kava dermopathy, often accompanied by eye irritation.13 Kava dermopathy is treated by abstention from kava. Although the scaly dermatitis is similar to that seen in pellagra, niacin deficiency has been ruled out as a mechanism. A randomized, controlled trial of 100 mg nicotinamide in 29 kava drinkers with kava dermopathy showed no difference between the treatment and placebo groups.14 Stopping kava, however, results in complete resolution of symptoms.
Interaction with Benzodiazepine?
There is a case report of an interaction between kava and the benzodiazepine alprazolam. A 54-year-old man on daily doses of alprazolam, cimetidine, and terazosin was hospitalized after experiencing an acute change in mental status three days after starting to take kava. He recovered from his lethargy and disorientation within several hours.15 This is a multi-drug interaction in which cimetidine is likely to have played an important role. Cimetidine affects microsomal enzymes and reduces the hepatic metabolism of numerous drugs, including diazepam. Cimetidine may have increased alprazolam levels, but, clearly, the addition of kava tipped the balance. Possible explanations for this reported interaction include the following: cimetidine may inhibit the metabolism of kava; kava may inhibit the metabolism of alprazolam; alprazolam may inhibit the metabolism of kava; or any combination of the above.
Recommendations
Therapeutic doses of kava appear to be safe and effective for short-term anxiolysis, but the herb should not be used for more than three months. Recreational use can result in a drunken-like state, and chronic heavy use can result in a typical dermatitis.
References
1. Lehmann E, et al. Efficacy of a special Kava extract (Piper methysticum) in patients with states of anxiety, tension, and excitedness of non-mental originA double-blind placebo-controlled study of four weeks treatment. Phytomedicine 1996;III(2):113-119.
2. Volz HP, Kieser M. Kava-kava extract WS 1490 versus placebo in anxiety disordersA randomized placebo-controlled 25-week outpatient trial. Pharmacopsychiatry 1997;30(1):1-5.
3. Schulz V, et al. Rational Phytotherapy: A Physician’s Guide to Herbal Medicine, 3rd ed. Berlin: Springer- Verlag; 1998:66-72.
4. Kinzler E, et al. Wirksamkeit eines Kava-Spezial-Extraktes bei Patienten mit Angst-, Spannungs- und Erregungszustanden nicht psychotischer Genese. Arzneim Forsch/Drug Res 1991;41:584-588.
5. Woelk H, et al. Behandlung von Angst-Patienten. Z Allg Med 1993;69:271-277.
6. Warnecke G, et al. Wirksamkeit von Kava-Kava-Extrakt beim klimakterischen Syndrom. Z Phytother 1990;11:81-86.
7. Warnecke G. Psychosomatic dysfunctions in the female climacteric. Clinical effectiveness and tolerance of Kava Extract WS 1490. Fortschr Med 1991;109(4):119-122.
8. Gleitz J, et al. Anticonvulsive action of (±) -kavain estimated from its properties on stimulated synaptosomes and Na+ channel receptor sites. Eur J Pharmacol 1996;315(1):89-97.
9. Jussofie A, et al. Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain. Psychopharmacology (Berlin) 1994;116(4):469-474.
10. Seitz U, et al. [3H]-monoamine uptake inhibition properties of kava pyrones. Planta Med 1997;63(5):548-549.
11. Garner LF, Klinger JD. Some visual effects caused by the beverage kava. J Ethnopharmacol 1985;13: 307-311.
12. Swensen J. Man convicted of driving under influence of kava. Desert News (Salt Lake City, UT), August 5, 1996.
13. Norton SA, Ruze P. Kava dermopathy. J Am Acad Dermatol 1994;31:89-97.
14. Ruze P. Kava-induced dermopathy: A niacin deficiency? Lancet 1990;335:1442-1445.
15. Almeida JC, Grimsley EW. Coma from the health food store: Interaction between kava and alprazolam. Ann Intern Med 1996;125(11):940.
December 1998; Volume 1: 4-6
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