Effects of Kava on the Body's Elimination of Caffeine and Dextromethorphan

Kava (piper methysticum) is a complementary or alternative medication used for purported anxiolytic and sedative effects. Despite its widespread use there is no data regarding potential for drug interactions or its effects on the electroencephalogram. The purpose of this study is to determine the effect of administration of kava for 3 weeks on the activity of cytochrome p450, 1A2, 2D6, 3A4; NAT2, and XO. Additionally, the effect of kava on EEG measured beta amplitude will be evaluated. Fifteen healthy volunteers will undergo enzyme activity phenotyping by ingesting 2 mg/kg of caffeine and 30 mg of dextromethorphan followed by an overnight urine collection. Following completion of two separate baseline evaluations, separated by 1 week, subjects will then take 1 capsule containing 60 mg of kavalactones three times daily for 3 weeks. Following 3 weeks of therapy subjects will undergo repeat enzyme activity phenotyping as described previously. Enzyme activity following 3 weeks of kava will be compared to pre-treatment values to characterize the magnitude of inhibition and/or induction of CYP1A2, CYP2D6, CYP3A4, NAT2, and XO activity. Additionally, subjects will have EEG testing performed to evaluate the effect of kava on beta amplitude. EEG's will be performed the day before the first baseline phenotyping procedure and then following three weeks of kava (the day before the final phenotyping procedure). Beta amplitude following three weeks of kava will be compared to pre-treatment values to evaluate the magnitude of pharmacodynamic effect. The results of this study will be used to facilitate the development of protocols to evaluate the magnitude of interactions between clinically relevant traditional medications and kava as well as studies to compare the pharmacologic effect of kava to the effects of benzodiazepines.