The 13th World Conference on Tobacco OR Health

Objective: This analysis examined the effects of varenicline on the reinforcing and rewarding effects of smoking. Varenicline is a novel, selective α4β2 nicotinic receptor partial agonist that has the potential to block the reinforcing/rewarding effects of smoking (particularly in subjects who continue to smoke).

Methods: Two randomized, double-blind, placebo controlled studies (with the same design at different sites) evaluated the efficacy of varenicline 1 mg bid versus placebo for smoking cessation. The target quit date was midnight of day 7 of treatment. In addition to smoking cessation efficacy endpoints, subjects who smoked during treatment completed the Modified Cigarette Evaluation Questionnaire (mCEQ) at baseline and over the following 7 of 12 weeks of treatment. The mCEQ measures the reinforcing/rewarding effects of smoking and is subdivided into five subscales: Smoking Satisfaction, Psychological Reward, Enjoyment of Respiratory Tract Sensations, Craving Reduction, and Aversion. The most important pre-specified domains of interest were Smoking Satisfaction and Psychological Reward.

Results: Results of repeated measures analysis over seven weeks demonstrated a statistically significant difference between varenicline and placebo on the prespecified domains: Smoking Satisfaction (p < 0.0001, both trials) with standardized effect sizes of 0.47 and 0.35; Psychological Reward (p < 0.0001, both trials) with standardized effect sizes of 0.37 and 0.23. Results demonstrated that varenicline was significantly more effective than placebo in reducing smoking satisfaction and psychological reward during the initial seven weeks following smoking cessation. These results appear to substantiate the proposed mechanism of action of varenicline as a selective nicotinic 􊨴 partial agonist.