Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users.
BACKGROUND
A single 90-mg dose of the cannabinoid CB1 receptor antagonist rimonabant attenuates effects of smoked cannabis in humans.


OBJECTIVE
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.


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.
Huestis
Marilyn A
MA
Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. mhuestis@intra.nida.nih.gov
Boyd
Susan J
SJ
Heishman
Stephen J
SJ
Preston
Kenzie L
KL
Bonnet
Denis
D
Le Fur
Gerard
G
Gorelick
David A
DA
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013759:Dronabinol / Q000097:blood; D004334:Drug Administration Schedule; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D008385:Marijuana Smoking / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D012737:Sex Factors; D013610:Tachycardia / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors
D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013759:Dronabinol; D000077285:Rimonabant