TY - JOUR
T1 - The cannabinoid CB1 receptor antagonist rimonabant attenuates the hypotensive effect of smoked marijuana in male smokers
AU - Gorelick, David A.
AU - Heishman, Stephen J.
AU - Preston, Kenzie L.
AU - Nelson, Richard A.
AU - Moolchan, Eric T.
AU - Huestis, Marilyn A.
N1 - Funding Information:
This research was supported by the Intramural Research Program of the National Institutes of Health, NIDA, and by Sanofi-Aventis, Inc. The study sponsor participated in the design of the primary study and reviewed the manuscript but had no role in the data analysis or drafting of the manuscript.
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ahj.2005.11.006
DO - 10.1016/j.ahj.2005.11.006
M3 - Article
C2 - 16504646
AN - SCOPUS:33344467124
SN - 0002-8703
VL - 151
SP - 754.e1-754.e5
JO - American heart journal
JF - American heart journal
IS - 3
ER -