This study will examine how kava-a widely used herbal remedy-may affect the body's
elimination of other medicines. Many people take kava to reduce anxiety or cause sedation.
Since this product is considered a food supplement and not a drug, it is not subject to the
rigorous pre-market testing required for prescription and over-the-counter (OTC) drugs. As
a result, information has not been collected on possible interactions between kava and other
medications. This study will look at how kava affects the elimination of caffeine-a
compound commonly found in chocolate, coffee, tea and soft drinks-and dextromethorphan-an
OTC cough suppressant.
Normal healthy volunteers 21 years of age or older may be eligible for this 30-day study.
Candidates will provide a medical history and undergo a physical examination and routine
blood tests. Women of childbearing age will have a urine pregnancy test.
Study participants will not drink alcoholic beverages or take any medications (except those
given in the study) for 2 weeks prior to the study and throughout its duration. In
addition, they will abstain from caffeine, grapefruit and grapefruit juice and charbroiled
foods for at least 72 hours before and throughout each study day that urine is collected.
On day 1 of the study, study subjects will take one dose each of caffeine and
dextromethorphan at 4:00 P.M.. They will empty their bladder before the dosing and then
collect all their urine after the dosing for the rest of the day and including the next
mornings first urine. They will bring the urine samples to the Clinical Center when the
collection is complete. This procedure will be repeated 1 week later (study day 8). After
the second urine collection is completed, subjects will take 200 milligrams of kava 3 times
a day for 21 days. On study day 29 (after 21 days of kava), subjects will repeat the
dextromethorphan and caffeine dosing and urine collection described above, while continuing
to take kava.
Subjects will have an electroencephalograph (EEG) done before starting kava and again at the
end of kava (study day 30). For this procedure, several electrodes (metal cups attached to
wires) are secured to the scalp with a glue-like substance. A conductive gel fills the
space between the electrode and the scalp to ensure good contact. The electrodes will
remain in place for about 2 hours and then removed. The subject lies quietly on a bed
during the EEG recording.
Participation in the study will end with another physical examination and blood tests
following the second EEG and urine collection.
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.
Male or female
Healthy by medical history and physical exam
Age greater than 21 years old
No concurrent medications
Non-smoker (for at least 6 months if prior history of smoking)
Laboratory values within the following guidelines:
AST/SGOT less than or equal 1.5 X ULN
Bilirubin less than or equal 1.5 X ULN
Serum creatinine less than or equal ULN
Hemoglobin less than 10 g/dl
Females of child bearing potential must be using a reliable form of birth control other
than hormonal contraceptives
Ability to abstain from caffeine containing foods/beverages, ethanol, grapefruit or
grapefruit juice and charbroiled foods for 72 hours prior to, and the day of, phenotyping
Normal EEG during baseline testing.
No patients using concomitant therapy with other inhibitors or inducers of cytochrome
P-450 mediated drug metabolism within 30 days of study.
No patients with inability to remain free of chronic medications and alcohol for atleast
2 weeks prior to and during the study.
Presence of renal, hepatic, cardiovascular, hematologic, neurologic, psychiatric, or
respiratory disease or any other condition that may interfere with the interpretation of
the study results or not be in the best interests of the subject in the opinion of the
Positive urine pregnancy test.
The presence of persistent diarrhea or malabsorption that would interfere with the
patient's ability to adequately absorb drug.
Drug or alcohol use that may impair safety or adherence.