Effects of pregabalin on smoking behavior, withdrawal symptoms, and cognitive performance in smokers

Rationale In preclinical and clinical studies, medications enhancing the GABA neurotransmission attenuate nicotine reward. Pregabalin, a GABA analogue, presumably interacts with brain glutamate and GABA neurotransmission. The goal of this study was to determine pregabalin's effects on smoking behavior, nicotine withdrawal, craving for cigarettes, and cognitive performance. Methods Twenty-four smokers participated in an outpatient double-blind, placebo-controlled, crossover study. Subjects had a 4-day treatment period with either pregabalin (300 mg/day) or placebo and following a washout period were then crossed over for 4 days to the other treatment. In each treatment period, starting at midnight of day 1, participants were asked to stop smoking until the experimental session on day 4. During the experimental session measures of ad lib smoking behavior, tobacco withdrawal, craving for cigarettes, and cognitive performance were obtained. Results Pregabalin treatment, compared to placebo, did not reduce the smoking behavior during the first 3 days of treatment or during ad lib smoking period. Pregabalin treatment attenuated some tobacco withdrawal symptoms including ratings of anxious, irritable, and frustrated in abstinent smokers. Pregabalin treatment also attenuated the subjective ratings of "liking" in response to smoking. Under pregabalin treatment, smokers made more errors in a sustained attention task. Conclusions These findings provide limited support for pregabalin as a treatment for nicotine addiction.