The Cannabinoid Cb1 Receptor Antagonist Rimonabant Attenuates the Hypotensive Effect of Smoked Marijuana in Male Smokers.
From: Clinical Pharmacology and Therapeutics Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. dgorelic@mail.nih.gov
American heart journal
- Publish Date: Mar 2006
- ISSN: 1097-6744
- Volume: 151
- Issue: 3
- Pages: 754.e1-754.e5
- Medium: Internet
- Language: English
- Citation (JAMA): Gorelick David A, Heishman Stephen J, Preston Kenzie L, et al. The Cannabinoid Cb1 Receptor Antagonist Rimonabant Attenuates the Hypotensive Effect of Smoked Marijuana in Male Smokers.. Am. Heart J. Mar 2006;151:754.e1-754.e5
Abstract
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.
Mesh Headings (Keywords): Adult, Blood Pressure, Cannabinoids, Dose-Response Relationship, Drug, Double-Blind Method, Heart Rate, Humans, Male, Marijuana Smoking, Piperidines, Pyrazoles
Check for Full Text / PubMed Unique Identifier (PMID): 16504646
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