The cannabinoid CB1 receptor antagonist rimonabant attenuates the hypotensive effect of smoked marijuana in male smokers

Background Animal studies suggest that cannabinoid CB1 receptors play a role in regulating blood pressure (BP). In human studies, activation of CB1 receptors by cannabis or its active ingredient, Δ9-tetrahydrocannabinol (THC), has modest and inconsistent effects on BP. Methods We evaluated this phenomenon in 63 male cannabis smokers (mean [SD] age 27.7 ± 5.4 years, 70% African American, 10.3 ± 5.9 years of lifetime cannabis use) by administering escalating oral doses (1, 3, 10, 30, 90 mg) of the selective CB1 receptor antagonist rimonabant (or placebo) in a randomized, parallel-group, double-blind, placebo-controlled design. Subjects smoked an active (2.64% THC) or placebo marijuana cigarette 2 and 6 hours after rimonabant dosing. Blood pressure and symptoms were monitored for 90 minutes after smoking while subjects remained seated. Results Marijuana smoking alone (ie, after placebo rimonabant) had no consistent effect on BP, but 22% of subjects experienced symptomatic (dizziness, lightheadedness) hypotension, as did 20% to 33% of subjects who received pretreatment with rimonabant, 1, 3, or 10 mg. No subject receiving rimonabant, 30 or 90 mg, before marijuana smoking experienced symptomatic hypotension. The 7 subjects who experienced symptomatic hypotension had significantly higher mean (SD) peak plasma THC concentrations (181.6 ± 80.2) than did the 33 subjects who did not (109.0 ± 62.6). Rimonabant by itself had no effects on BP and did not alter THC pharmacokinetics. Conclusions These findings indicate that CB1 receptors play a role in mediating effects of cannabis smoking on BP in humans.