Studies with the selective CB1 receptor antagonist/inverse agonist rimonabant suggest that CB1 receptors mediate many of the acute effects of cannabis in humans. In a double-blind, placebo-controlled study of 63 healthy men with a history of cannabis use, single oral doses of rimonabant produced significant dose-dependent blockade of the subjective intoxication and tachycardia caused by smoking an active (2.64% THC) or placebo (double-blind) cannabis cigarette 2 hours later [24] The 90-mg dose produced about 40% reductions in ratings of "high" "stoned" and "drug effect" (on 100-mm visual-analogue scales) and a 60% reduction in heart rate. Rimonabant alone produced no significant physiological or psychological effects and did not affect peak THC plasma concentration or its time course. This pattern of findings suggests that the observed attenuation of cannabis effects was specifically due to CB1 receptor blockade, and not to reduction in brain THC concentration or counteracting effects of rimonabant.
