Randomized, controlled, double-blind trial of taranabant for smoking cessation

• Published in: Psychopharmacologia Vol. 209; no. 3; pp. 245 - 253
• Main Authors: Morrison, Mary F., Ceesay, Paulette, Gantz, Ira, Kaufman, Keith D., Lines, Christopher R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.04.2010; Springer; Springer Nature B.V
• Subjects: Addictive behaviors; Adolescent; Adult; Adult and adolescent clinical studies; Aged; Amides - adverse effects; Amides - antagonists & inhibitors; Amides - therapeutic use; Behavior, Addictive - drug therapy; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Body Weight - drug effects; Clinical trials; Dose-Response Relationship, Drug; Double-Blind Method; Drug Inverse Agonism; Drugs; Female; Humans; Male; Medical sciences; Middle Aged; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Pyridines - adverse effects; Pyridines - antagonists & inhibitors; Pyridines - therapeutic use; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Side effects; Smoking cessation; Smoking Cessation - methods; Tobacco smoking; Tobacco Use Disorder - drug therapy; Tobacco, tobacco smoking; Toxicology; Cannabinoid-1 receptor inverse agonist; Smoking cessation; Randomized clinical trial; Taranabant; Randomization; Poison withdrawal; Inverse agonist; Cannabinoid receptor; Tobacco smoking; Double blind study; Controlled therapeutic trial; Cannabinoid-1 receptor inverse agonist Smoking cessation; Antagonist
• ISSN: 0033-3158; 1432-2072; 1432-2072
• DOI: 10.1007/s00213-010-1790-2

Rationale 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 ≥10 cigarettes a day for >1 year and had an expired CO level of ≥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).