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K

KAYA

Other Common Name: Kava kava
Botanical Name: Piper methysticum
Family: Piperaceae
Plant Part Used: Root (rootstock)

PRESCRIBING INFORMATION

Actions Anxiolytic, hypnotic, anticonvulsant, mild sedative, skeletal muscle relaxant, spasmolytic, local anesthetic, mild analgesic, antipruritic (topically)
Potential Indications
Based on appropriate evaluation of the patient, practitioners should consider prescribing kava in formulations in the context of:
• Anxiety (1,4,5)
• Stress (3)
• Insomnia,* in combination with valerian (3)
• Menopausal symptoms, mild depression (2)
• Muscle tension (4,5)
• Improving cognitive performance in healthy individuals and patients with anxiety (2)
• Headache, neuralgia, general debility, inflammation and infection of the genitourinary tract (5)

Given that kava has been shown to have similar efficacy to certain benzodiazepine drugs in treating anxiety (3), it may be useful to assist in withdrawal from benzodiazepines. Contraindications The German Commission E lists the following contraindications: pregnancy, lactation, and endogenous depression. However, these contraindications have resulted from a lack of positive data to show that use is safe under these circumstances rather than any published safety concerns.   Kava extract is contraindicated in patients with preexisting liver conditions. Patients prescribed kava should be closely monitored for any signs of a rare liver toxicity. Warnings and Precautions Because of possible dopamine antagonism, kava should be used cautiously in elderly patients, especially those with Parkinson’s disease (refer to the “Side Effects” section in this monograph). Interactions According to the Commission E, a synergistic effect is possible for substances acting on the central nervous system, such as alcohol, barbiturates, and psychopharmacological agents. A case of possible interaction between kava and a benzodiazepine drug (alprazolam) has been reported. Use in Pregnancy and Lactation No adverse effects expected at normal therapeutic doses, despite the caution from the Commission E. Side Effects
Two postmarketing surveillance studies involving 3029 and 4049 patients found adverse events occurred in 2.3% and 1.5%, respectively, of patients during treatment with standardized kava extract. The doses of kava contained 120 to 240 mg and 105 mg of lactones, respectively. A meta-analysis noted that standardized kava extract is relatively safe with two studies, representing 31% of the studied patients, not reporting any adverse events in those treated with kava.1
A dry, scaly, pigmented skin condition known as kava dermopathy is a well-known side effect of excessive and chronic use of kava but is unlikely to occur after normal therapeutic use. The rash quickly regresses if kava intake is ceased. Dermatitis after oral administration of kava at the lower therapeutic doses has been reported.
A group of German neurologists described four cases of patients who developed clinical signs suggestive of dopamine antagonism after taking kava. Overdose of kava (without concurrent alcohol use or petrol sniffing) causing generalized choreoathetosis (involuntary movement disorder) has been reported in an Aboriginal Australian.2
Associations with heavy kava use reported in the Australian medical literature from 1988 to 1999 include ischemic cardiac events and sudden cardiac death.2,3 These events have not been definitively linked to excessive kava use and the possibility of concurrent alcohol abuse, and the involvement of other socioeconomic factors cannot be ruled out.
A pilot survey investigating the effects of heavy kava use published in 1988 indicated that no epidemiological evidence was found to link sudden deaths with kava use.4
A report published in 2000 by a Swiss government regulatory agency described nine cases of hepatotoxicity attributed to kava.
All cases involved the consumption of a high dose acetone extract standardized to 70% kava lactones. The product has been subsequently banned. The author rated the risk of hepatotoxicity as rare but serious.5 German regulatory authorities reported cases of hepatotoxicity involving ethanolic kava extracts,6 and kava products were subsequently removed from the market in this and several other countries. Good evidence exists that the hepatotoxicity was immunemediated. A deficiency of the drug-metabolizing enzyme CYP2D6 (which occurs in 9% of the population) might be a predisposing factor.7
The rare cases of hepatotoxicity resulting from kava consumption are therefore likely to be an immunoallergic reaction, perhaps exaggerated by the type of extract consumed and deficiencies in detoxifying enzymes.

Dosage Dose per day** Dose per week**   3.0-8.5 ml of 1:2 liquid extract 20-60 ml of 1:2 liquid extract   Extracts providing quantified levels of kava lactones are recommended. Ideally, aqueous ethanol extracts should contain not less than 20 mg/ml of kava lactones.

* Kava has also been used in traditional herbal medicine for treating insomnia. (6)

** This dose range is extrapolated from British Pharmaceutical Codex 1934, the British Herbal Pharmacopoeia 1983, and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing
Traditional Western herbal medicine uses include:
• Neuralgia (especially toothache, earache, and ocular pain), dizziness, chronic catarrh, bronchitis8
• Cystitis, urethritis, dysuria, renal colic, nocturnal incontinence8,9
• Dysmenorrhea, vaginitis, leukorrhea, gonorrhea8,9
• Anorexia, dyspepsia, intestinal catarrh, hemorrhoids8
• Rheumatism, gout, topically for joint pain8,9
Uses according to other traditional systems such as those of the Pacific region include:
• To soothe nerves and to induce relaxation and sleep10
• To counteract fatigue; for general debility, weary muscles, chills, the common cold, dysuria, headache10
• Skin diseases, leprosy, to prevent suppuration11
• Filariasis (systemic worm infestation)11,12
• Sore throat, toothache13
• As a contraceptive for women who have recently given birth;11,12 topically for vaginal prolapse11
Pharmacologic Research
Key constituents of kava root include the kava lactones (also known as kava pyrones) and flavonoids (flavokawains). Extracts are often standardized to the lactones.
• Kava extracts or purified lactones demonstrated sedative effects and induced sleep in a variety of in vivo experimental models. The combination of kava and passion flower (Passiflora incarnata) produced a synergistic effect on sedation.
• Kava extract and lactones produced relaxation of skeletal muscle in vitro and in vivo.A synergistic effect was noted when a mixture of lactones (similar to that found in the root) was administered orally in an epilepsy model.
• Kava lactones have demonstrated analgesic activity via nonopiate pathways in several experimental models and have potencies similar to cocaine and procaine as local anesthetics.
• Kava lactones exhibited potent fungistatic activity in vitro against a wide variety of pathogenic fungi, excluding species of Candida.
• Kava extract protected brain tissue against ischemic damage in experimental models.
• Kava lactones demonstrated antithrombotic activity in vitro.

Clinical Studies
• A meta-analysis assessing seven randomized, double-blind, placebocontrolled trials found that kava extract significantly reduced anxiety (compared with placebo). The dosage of standardized kava extract prescribed varied and contained 60 to 240 mg per day of kava lactones. The duration of treatment ranged from 1 to 24 weeks. One trial investigated the reduction in anxiety for preoperative patients who received kava extract the night before and 1 hour before surgery.1 The authors of one of the trials14 included in this meta-analysis concluded that the efficacy and tolerability of standardized kava extract recommend it as an alternative to tricyclic antidepressants and benzodiazepines for treating anxiety.
• Kava lactones and standardized kava extracts demonstrated activity equivalent to oxazepam and bromazepam (benzodiazepine drugs) in patients with anxiety in double-blind, placebo-controlled trials. The daily dose ranged from 210 to 400 mg of kava lactones. Side effects were higher in the patient groups assigned the conventional drugs.
• Kava has also been shown to have therapeutic benefit in cases of situational anxiety. In a randomized, double-blind, placebo-controlled trial, standardized kava extract taken for 1 week significantly reduced anxiety compared with placebo in patients awaiting the results of medical diagnostic tests for suspected breast carcinoma. Fatigue, introverted behavior, excitability, and depression were decreased, and alertness was increased in patients receiving kava extract. The administered daily dose of kava contained 150 mg of kava lactones and corresponded to approximately 2.5 g of dried root.15
• Preliminary findings suggest a beneficial effect of kava on baroreflex control of heart rate (BRC). Significantly more patients with generalized anxiety disorder exhibited improved BRC following treatment with kava compared with a placebo. No effect was observed on respiratory sinus arrhythmia, a measure of the heart rate changes occurring with respiration. Patients in the study were a subgroup of a larger randomized, double-blind trial and received standardized kava extract or placebo for 4 weeks.16
• Two postmarketing surveillance studies involving over 3000 patients each found standardized kava extract improved nervousness, restlessness, anger, sleep disturbances, menopausal complaints, muscle tension, and sexual disturbances. Undesirable side effects included allergic reactions, gastrointestinal complaints, headache, and dizziness. The daily dose of extract ranged from that containing 105 mg to 240 mg of kava lactones for 4 and 7 weeks, respectively.
• In a placebo-controlled trial, standardized kava extract (containing 105 to 210 mg kava lactones for 1 day) improved several aspects of the sleep cycle. The measurements were favorable when compared with orthodox sedatives such as benzodiazepines and barbiturates.
• In a pilot study, patients with stress-induced insomnia were treated in each phase for 6 weeks with kava, then valerian, then a combination of kava and valerian, with washout periods between each treatment phase of 2 weeks. Total stress severity was significantly relieved by the kava and valerian single treatments (stress was measured in three areas:social, personal, and life events). Insomnia was significantly relieved by the combination of kava and valerian.17
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