Clinical InvestigationsPrevention and RehabilitationThe cannabinoid CB1 receptor antagonist rimonabant attenuates the hypotensive effect of smoked marijuana in male smokers
Section snippets
Subjects
Subjects were 63 physically and psychologically healthy men (mean [SD] age 27.7 ± 5.4 years, 70% African American) who had smoked cannabis for 10.3 ± 5.9 years and on 15.3 ± 10.2 of the 30 days preceding screening and had no other current substance dependence (except nicotine or caffeine). The study was approved by the institutional review board of the National Institute on Drug Abuse (NIDA). All subjects gave written informed consent and were paid for their participation.
Study design
The study used a
Effects of marijuana and rimonabant alone
Rimonabant by itself had no significant effect on BP over the 2 hours after dosing (F = 1.41, P = .24 for peak change in systolic BP; F = 1.34, P = .26 for diastolic BP). The mean (SD) peak change in systolic BP was 2.8 ± 9.7 mm Hg after the highest rimonabant dose (90 mg) and −8.7 ± 10.6 mm Hg after placebo; peak change in diastolic BP was −2.4 ± 8.8 mm Hg after 90 mg rimonabant and 2.0 ± 13.8 mm Hg after placebo.
None of the 20 subjects receiving placebo marijuana (either with or without
Discussion
In this study of adult male experienced cannabis smokers, smoking a single marijuana cigarette (2.64% THC) while seated had no consistent group effect on BP (Table I). This absence of a robust consistent BP effect from marijuana is consistent with numerous prior studies using smoked marijuana or oral or IV THC.1, 14 About 25% of subjects experienced symptomatic hypotension, typically lightheadedness or dizziness. This pattern is also consistent with several prior studies, which have reported
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Cited by (60)
Cardiovascular Effects of Medical Marijuana: A Systematic Review
2021, American Journal of MedicineCitation Excerpt :Cannabinoid receptor 1 is responsible for heart rate and blood pressure responses via heart regulatory centers and the peripheral autonomic system.41 Gorelick et al suspect that THC levels in the blood lead to acute hypotension secondarily to activation of cannabinoid receptors in the arterial wall causing vasodilatation.46 Vasodilatation may result in hypotension, leading to the perception of dizziness and further progression to presyncope or syncope.
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP3652, a Reversible Fatty Acid Amide Hydrolase Inhibitor, in Healthy, Nonelderly, Japanese Men and Elderly, Japanese Men and Women: A Randomized, Double-blind, Placebo-controlled, Single and Multiple Oral Dose, Phase I Study
2020, Clinical TherapeuticsCitation Excerpt :To further confirm the potential of off–target activities, investigation of activity-based protein profiling, as conducted for BIA 10-2474, would be important.15 Activation of CB1 receptors by cannabis reportedly causes symptomatic hypotensive effects.16 To evaluate the symptomatic hypotensive effect of ASP3652 in detail, further evaluation of heart rate and blood pressure is needed in future studies.
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2017, NeuropharmacologyCitation Excerpt :However, very few studies have been designed to directly assess the role of CB1 receptors in mediating the effects of Δ9-THC on human brain function, or more broadly the role of CB1 receptors in cognition (Colizzi et al., 2016). In humans, Δ9-THC-induced subjective effects were blocked by a high dose of the CB1 receptor antagonist AVE1625 (Zuurman et al., 2010), whereas the subjective effects of smoked cannabis were only partially blocked by the CB1 receptor antagonists rimonabant and surinabant (Huestis et al., 2001; Gorelick et al., 2006). Existing data linking CB1 receptors to cognition are largely limited clinical trials of rimonabant that were halted upon its withdrawal from the market in 2008.
Pharmacological inhibition of FAAH activity in rodents: A promising pharmacological approach for psychological—cardiac comorbidity?
2017, Neuroscience and Biobehavioral ReviewsCannabinoids in the Cardiovascular System
2017, Advances in PharmacologyCitation Excerpt :Smoking or ingestion of cannabis has long been known to induce tachycardia with variable effects on blood pressure, although chronic users often experience bradycardia and prolonged reduction in blood pressure (Gorelick et al., 2006; Jones, 2002). This is due to a dose-dependent effects of the phytocannabinoid, THC, and modulation of the autonomic nervous system, at least partly via CB1R activation (Benowitz, Rosenberg, Rogers, Bachman, & Jones, 1979; Fant, Heishman, Bunker, & Pickworth, 1998; Gorelick et al., 2006). Since the identification of eCBs, extensive investigations have been carried out to examine their hemodynamic effects.
Prenatal cannabis exposure - The “first hit” to the endocannabinoid system
2016, Neurotoxicology and Teratology
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.