Randomized, controlled, double-blind trial of taranabant for smoking cessation.
BACKGROUND
It has been proposed that cannabinoid-1 receptor inverse agonists might be effective for smoking cessation. We evaluated this hypothesis with the cannabinoid-1 receptor inverse agonist taranabant.


METHODS
Adults who smoked > or =10 cigarettes a day for >1 year and had an expired CO level of > or =10 ppm participated in a randomized, double-blind, 8-week, study of taranabant (N = 159) or placebo (N = 158). Taranabant was titrated from 2 mg once daily to 8 mg once daily. Patients received smoking cessation counseling. The primary efficacy endpoint was continuous abstinence, defined as no cigarettes assessed by daily patient self-report and verified by breath CO level (<10 ppm) and plasma cotinine test (<10 ng/ml), during the last 4 weeks of the 8-week treatment period.


RESULTS
The percentage of patients achieving continuous abstinence was 7.5% for taranabant 2-8 mg and 6.3% for placebo (odds ratio = 1.2 [90% confidence interval (CI), 0.6, 2.5], P = 0.678). Change from baseline in body weight in the taranabant 2-8-mg group was -1.5 (90% CI, -1.8, -1.3) versus 0.6 kg (90% CI, 0.4, 0.9) in the placebo group. Compared to placebo, taranabant 2-8 mg was associated with an increased incidence of psychiatric-related adverse events (e.g., depression, 8.2% versus 2.5%, P = 0.048), gastrointestinal-related adverse events (e.g., nausea, 49.7% versus 19.0%, P < 0.001), and flushing/hot flash adverse events (10.7% versus 1.9%, P = 0.002).


CONCLUSIONS
Taranabant 2-8 mg did not improve smoking cessation and was associated with increased incidences of psychiatric-related, gastrointestinal-related, and flushing adverse events (ClinicalTrials.gov NCT00109135).
Morrison
Mary F
MF
Merck Research Laboratories, Upper Gwynedd, PA, USA.
Ceesay
Paulette
P
Gantz
Ira
I
Kaufman
Keith D
KD
Lines
Christopher R
CR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000577:Amides / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D016739:Behavior, Addictive / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D054314:Drug Inverse Agonism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000188:drug therapy*
D000577:Amides; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; C521311:N-(3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide