Efficacy of a dose range of surinabant, a cannabinoid receptor blocker, for smoking cessation: a randomized controlled clinical trial.
A hyperactive endocannabinoid signalling system may contribute to addictions. We tested the efficacy and safety of surinabant, a novel selective CB₁ cannabinoid receptor antagonist, for smoking cessation. In a randomized, double-blind, placebo-controlled, parallel-group clinical trial, participants were assigned to brief counselling and one of three doses of surinabant, 2.5 mg/day (n = 199), 5 mg/day (n = 204), or 10 mg/day (n = 205) or placebo (n = 202) orally for 8 weeks with 6 weeks of non-drug follow-up. For weeks 5 through 8, the 4-week continuous abstinence rates were 25.2% for placebo vs. 22.6%, 22.1% and 21.5% for 2.5 mg/day, 5 mg/day and 10 mg/day doses of surinabant (p for trend, 0.4). The gain in body weight from baseline was reduced with surinabant 2.5 mg/day, 5 mg/day and 10 mg/day (0.75 kg [SE, 0.13], 0.53 kg [SE, 0.13], and 0.24 kg [SE, 0.13], respectively, versus 1.19 kg [SE, 0.13] for placebo; p for trend, < 0.001). The most common adverse events for participants receiving active drug with a greater incidence than placebo were headache, nausea, insomnia, anxiety, nasopharyngitis, diarrhoea and hyperhidrosis. Surinabant did not improve smoking cessation rates compared with placebo, but had a small effect on reducing post-cessation weight gain.
Oslo University Hospital, Department of Preventive Cardiology Ullevål, Oslo, Norway. stonstad@llu.edu
Serena
S
Tonstad
Henri-Jean
HJ
Aubin
D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D055502:Secondary Prevention; D016540:Smoking Cessation / Q000379:methods*; D000074606:Smoking Prevention; D015430:Weight Gain / Q000187:drug effects; D055815:Young Adult
D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C492668:surinabant