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

Abstract

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 > 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).

• Authors: Mary F Morrison, Paulette Ceesay, Ira Gantz, Keith D Kaufman, Christopher R Lines
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 209 Issue 3 Pg. 245-53 (Apr 2010) ISSN: 1432-2072 [Electronic] Germany
• PMID: 20191360 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Amides
• Pyridines
• Receptor, Cannabinoid, CB1
• N-(3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl)-2-methyl-2-((5-(trifluoromethyl)pyridin-2-yl)oxy)propanamide

Topics

• Adolescent
• Adult
• Aged
• Amides (adverse effects, antagonists & inhibitors, therapeutic use)
• Behavior, Addictive (drug therapy)
• Body Weight (drug effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Inverse Agonism
• Female
• Humans
• Male
• Middle Aged
• Pyridines (adverse effects, antagonists & inhibitors, therapeutic use)
• Receptor, Cannabinoid, CB1 (antagonists & inhibitors)
• Smoking Cessation (methods)
• Tobacco Use Disorder (drug therapy)