Effects of delta-9-tetrahydrocannabinol on drug distribution and metabolism. Antipyrine, pentobarbital, and ethanol.

Delta-9-tetrahydrocannabinol (THC) has been reported to inhibit drug metabolism in animals. Twenty-two hospitalized healthy volunteer subjects received THC, 60 to 180 mg/day in divided doses for 14 days. Body weight increased and plasma proteins decreased in all subjects, which is consistent with previously reported plasma volume expansion. Total bilirubin was significantly lower, while other liver function tests remained normal. A within-subject comparison of the pharmacokinetics of antipyrine, pentobarbital, or ethanol given before, during, and after THC was performed. Antipyrine plasma half-life increased during THC in 5 of 6 subjects--mean, 7.9 hr +/- 3.3 (SD) to 9.6 +/- 3.8. Pentobarbital half-life increased in 7 of 8 subjects--mean, 16.9 hr +/- 2.0 to 20.8 +/- 4.2. Blood ethanol disappearance rate decreased in 7 of 8 subjects from a mean of 0.26 mg/100 ml/min +/- 0.05 to 0.23 +/- 0.07. The effect of THC on disappearance rate of these drugs appeared to be due to a combination of: (1) increased distribution volume, due in part to expansion of extracellular fluid volume noted during THC ingestion, and (2) diminished metabolic clearance. THC also delayed absorption of pentobarbital and ethanol in several subjects. This is consistent with THC effects of slowing intestinal motility in animals. The effects of THC on absorption and drug elimination must be considered in evaluating interactions with other drugs.