Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users

Rationale A single 90- mg dose of the cannabinoid CB1 receptor antagonist rimonabant attenuates effects of smoked cannabis in humans. Objectives The objective of this study is to evaluate whether repeated daily 40- mg doses of rimonabant can attenuate effects of smoked cannabis to the same extent as a single higher ( 90 mg) dose. Materials and methods Forty- two male volunteers received one of three oral drug regimens in a randomized, double blind, parallel group design: ( 1) 40 mg rimonabant daily for 15 days, ( 2) placebo for 14 days, then 90 mg rimonabant on day 15, or ( 3) placebo for 15 days. All participants smoked an active or placebo cannabis cigarette 2 h after medication on days 8 and 15. Subjective effects were measured with visual analog scales and the marijuana- scale of the Addiction Research Center Inventory. Results Cannabis- induced tachycardia was significantly lower for the 40- mg group on day 8 and for the 40 and 90 mg rimonabant groups on day 15 as compared to placebo. The 40- mg dose significantly decreased peak subjective effects on day 8. Neither the 90- mg nor 40- mg doses significantly decreased peak subjective effects on day 15. Rimonabant treatment did not significantly affect Delta(9)- tetrahydrocannabinnol pharmacokinetics. Conclusions Repeated lower daily rimonabant doses ( 40 mg) attenuated the acute physiological effects of smoked cannabis to a similar degree as a single 90- mg dose; repeated 40- mg doses attenuated subjective effects after 8 but not 15 days.