Journal Article

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

Morrison, Mary F., Gantz, Ira, Kaufman, Keith D., Lines, Christopher R., Ceesay, Paulette

2010

Overview

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).

• Publisher: Springer-Verlag,Springer,Springer Nature B.V
• Subject: 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