Kava for the Treatment of Anxiety
August 1998; Volume 1: 85-88
By Ann Ronan, MA, and Dennis deLeon, MD
Kava-kava for the treatment of anxiety is one of the latest herbal remedies attracting popular attention in the United States. In February 1998, The Wall Street Journal described kava as the latest "herbal superstar," comparing its rising popularity to that of gingko biloba and St. John's wort only a few years ago.1 Though 1997 sales of kava were still modest compared to, for example, St. John's wort ($2.9 million vs. $47.8 million, in a $2 billion total market for herbal supplements), herbal manufacturer trade groups have targeted this remedy for marketing efforts and sales growth. It is probable that some of your patients will self-treat with this herbal remedy, and they may well ask you for information and opinions.
History
Kava-Kava is Piper methysticum ("intoxicating pepper"), a perennial shrub in the pepper family that is native to and primarily cultivated in the South Pacific islands. The plant has been used for more than 3000 years to prepare an intoxicating ceremonial drink with relaxing and sleep-promoting effects, used in tribal social events and religious rituals.2 Captain James Cook, in the account of his 1768 voyage to the South Seas, is credited with first introducing kava to the West. Kava was first mentioned in scientific records in 1886. The German Kommission E, responsible for evaluating safety and efficacy of herbal and botanical medicines in Germany, found kava beneficial for the relief of anxiety in 1990.3
Mechanism of Action
The known active ingredients in kava are a group of about 15 resinous biochemical compounds called kava lactones or kava pyrones, found in the root and rhizome (thickened underground stem) of the plant. In animal studies, several fat-soluble kava lactones have shown the greatest activity in the central nervous system, where they demonstrate muscle-relaxant, anticonvulsant, and analgesic activity.4 Kava's precise mechanism of action on the brain is unknown, but, in animal studies, it appears to directly influence the limbic system, with greatest effects on the hippocampus and amygdala. Interestingly, kava does not seem to act by binding GABA receptors; its mechanism of action appears to be distinct from that of benzodiazepines.4
Clinical Usage
Anxiety is the most common medical condition for which kava is promoted. Generalized anxiety disorder, certainly a near-daily finding among patients in many primary physicians' offices in the United States, is most commonly treated pharmacologically with benzodiazepines, antidepressants, low potency neuroleptics, or beta-blockers, as well as behavior therapy, counseling, and relaxation techniques. Generalized anxiety disorder must first be distinguished from many other disease states, such as hyperthyroidism, but should also be distinguished from panic disorder, for which the recommended drugs of first choice are usually not benzodiazepines, but antidepressants such as SSRIs or tricyclics. The use of benzodiazepines for anxiety is highly effective for relief of short-term anxiety symptoms, but well-known disadvantages of such benzodiazepine use include impairment of reflexes and coordination, rebound insomnia and anxiety after cessation of benzodiazepines, and the possibility of tolerance and addictive behavior.
Clinical Trials
There are no published controlled clinical trials of kava and anxiety in the United States. The German literature has five human trials of kava and anxiety. Although randomized, double-blinded, and placebo-controlled, each of the studies is small-fewer than 60 patients each. Most used standardized scales such as the Clinical Global Impression scale, the Depression Status Inventory, and the Hamilton Anxiety Scale to assess anxiety and well-being in subjects and controls. One study compared kava to the benzodiazepine oxazepam and found equal efficacy in anxiety over a four-week period.7 Another study of two groups of 29 patients with anxiety showed improvement in the subjects' anxiety scales after four weeks of kava, with improvements showing statistical significance in several but not all of the scales used.8 A third study of 40 perimenopausal and post-menopausal women showed improvement in anxiety and well-being with kava use, also over a four-week period.9
Table
Kava product prices compared to pharmaceuticals
| Kava |
|
|
| Mother Nature |
|
|
| Source Naturals |
|
|
| Gaia Herbs Kava Root |
|
|
* Extracts standardized to 30% kava lactones
Pharmaceuticals Prescribed for Anxiety
| Pharmaceutical | Formulation |
|
Formulation |
|
| Buspar (buspirone hydrochloride) | 60/5 mg tabs |
|
30/10 mg tabs |
|
| Halcion (triazolam) | 100/0.125 mg tabs |
|
100/0.25 mg tabs |
|
| Serax (oxazepam) | 100/15 mg tabs |
|
||
| Valium (diazepam) | 100/2 mg tabs |
|
100/5 mg tabs |
|
| Xanax (alprazolam) | 00/0.25 mg tabs |
|
100/0.5 mg tabs |
|
Sources: Red Book, Online mail-order firms
Formulation and Dosage
Kava supplements are prepared by water or alcohol extraction of kava lactones from the plant's rhizome (or root stock). The supplements contain between 5.5% and 8.3% kava lactones. To distinguish between dozens of herbal preparations typically marketed in liquid form or in capsules, the total milligram content of kava lactones should be referenced. Most standard extracts contain 30% kava lactones. Daily adult dosage used by most herbalists and patients for the treatment of anxiety is 40-75 mg kava lactones per dose, taken 2-3 times per day (equivalent to 140-250 mg of standard extract per dose).5 The more conservative Kommission E recommends a daily total dosage of 60-120 mg of kava lactones.3 The American Herbal Products Association's Kava Committee, a trade group, recently advised manufacturers to label their products to limit consumption of total kava lactones to a maximum of 300 mg per day.6
We could find no data or information indicating whether any of the available preparations-liquid, powder-containing capsules, liquid-filled gelcaps, spray, or root powder-are reliably different from each other. (See Table for retail price comparisons.)
Adverse Effects
Observational studies have reportedly shown a 1.5-2.3% incidence of undesired effects at the recommended doses. These effects are mostly mild reversible gastrointestinal distress and allergic skin reactions.10 Kava, especially in beverage form, often causes an initial numbing or astringent effect in the mouth, followed by relaxation, a feeling of calm, and (in high enough doses) sleepiness within 30 minutes to two hours. An eye irritation and a characteristic scaly rash resembling ichthyosis have been described in kava drinkers in the Tonga islands.11 Persistent dizziness, yellow discoloration of hair, skin, and nails, and even a syndrome of kava abuse have all been observed but also seem to be limited to consistent and heavy use of kava.12
Conclusion
Kava seems to show some promise in the treatment of anxiety. The use of kava at recommended doses appears safe and relatively free of serious adverse effects. But, the scientific evidence for its use is still extremely inadequate. We would recommend with the current state of knowledge that your patients who use kava be advised not to exceed the minimum dosages suggested by kava trade groups and promoters themselves.6 Limit total kava lactone consumption to 150-300 mg per day; avoid kava use if pregnant, nursing, diagnosed with depression, or while operating heavy equipment; and avoid concurrent kava use with prescription medications and with other supplements like valerian or St. John's wort because interactions have not been extensively studied and are not understood. Daily use for over 4-6 weeks is also best avoided. Until the results of well-designed, larger clinical trials with reliable and standard patient selection methods are published in this country, kava's use by physicians for the treatment of generalized anxiety disorders remains experimental and speculative.
References
1. Petersen A. The Making of an Herbal Superstar. Wall Street Journal, Health. February 1998.
2. Bone K. Kava: A Safe Herbal Treatment for Anxiety. Sponsored by proprietary firms in Townsend Letter for Doctors; June 1995.
3. German Kommission E Monographs. American Botanical Council, Austin, Texas. Blumenthal M, Hall T, Rister R, eds.
4. Davies LP, Drew CA, Duffield P, et al. Kava pyrones and resin: Studies on GABAA, GABAB and benzodiazepine binding sites in rodent brain. Pharmacol Toxicol 1992;71(2):120-126.
5. Cass H. Relax with kava. Let's Live May 1998.
6. AHPA's Recommended label language for kava products. J Am Botanical Council and the Herb Res Found HerbalGram No. 42.
7. Kinderberg VD, Pitule-Schoedel H. D,L-Kavain in comparison with oxazepam in anxiety states. Forthsch Med 1990;108:49-54.
8. Lehmann E, Kinzler E, Friedemann J. Efficacy of a special kava extract (Piper methysticum) in patients with states of anxiety, tension, and excitedness of non-mental origin: A double-blind placebo-controlled study of four weeks' treatment. Phytomed 1996; 3:113-119.
9. Warnacke G. Psychosomatic disorders in the female climacterium: Clinical efficacy and tolerance of kava extract WS1490. Fortsch Med 1991;109:119-122.
10. Tyler V. Nature's stress buster (Kava). Prevention 1997;47:90.
11. Ruze P. Kava-induced dermopathy: A niacin deficiency? Lancet 1990;335:1442-1445.
12. Information provided by the nonprofit Herb Research Foundation. Boulder, CO: (800) 748-2617; www.herbs.org
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