Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users

Marilyn A. Huestis, Susan J. Boyd, Stephen J. Heishman, Kenzie L. Preston, Denis Bonnet, Gerard Le Fur, David A. Gorelick

Research output: Contribution to journalArticlepeer-review

Abstract

Rationale: A single 90-mg dose of the cannabinoid CB1 receptor antagonist rimonabant attenuates effects of smoked cannabis in humans. Objectives: The objective of this study is to evaluate whether repeated daily 40-mg doses of rimonabant can attenuate effects of smoked cannabis to the same extent as a single higher (90 mg) dose. Materials and methods: Forty-two male volunteers received one of three oral drug regimens in a randomized, double blind, parallel group design: (1) 40 mg rimonabant daily for 15 days, (2) placebo for 14 days, then 90 mg rimonabant on day 15, or (3) placebo for 15 days. All participants smoked an active or placebo cannabis cigarette 2 h after medication on days 8 and 15. Subjective effects were measured with visual analog scales and the marijuana-scale of the Addiction Research Center Inventory. Results: Cannabis-induced tachycardia was significantly lower for the 40-mg group on day 8 and for the 40 and 90 mg rimonabant groups on day 15 as compared to placebo. The 40-mg dose significantly decreased peak subjective effects on day 8. Neither the 90-mg nor 40-mg doses significantly decreased peak subjective effects on day 15. Rimonabant treatment did not significantly affect Δ9- tetrahydrocannabinnol pharmacokinetics. Conclusions: Repeated lower daily rimonabant doses (40 mg) attenuated the acute physiological effects of smoked cannabis to a similar degree as a single 90-mg dose; repeated 40-mg doses attenuated subjective effects after 8 but not 15 days.

Original languageEnglish (US)
Pages (from-to)505-515
Number of pages11
JournalPsychopharmacology
Volume194
Issue number4
DOIs
StatePublished - Nov 2007

Keywords

  • Antagonist
  • Cannabinoids
  • Heart rate
  • Human
  • Receptor
  • Rimonabant
  • Subjective effects

ASJC Scopus subject areas

  • Pharmacology

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