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, Delta9-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.

RCT Entities:   Population Interventions Outcomes