Effects of varenicline and bupropion on cognitive processes among nicotine-deprived smokers.

Nicotine deprivation is associated with craving, negative affect, and difficulty concentrating, which may contribute to subsequent relapse. Bupropion and varenicline are both effective treatments for smoking cessation, and evidence from clinical trials suggests that these treatments increase abstinence rates. However, the mechanism by which these medications reduce relapse remains unclear. Recent research has focused on cognitive processes, such as attention and working memory, which may predict relapse. In addition, there may also be sex differences in cognitive-related deficits during nicotine deprivation. The current sample consisted of 58 (22 females) daily smokers (at least 10 cigarettes per day) randomized to receive bupropion (300 mg/day), varenicline (2 mg/day), or placebo. After a 1-week run-up phase, participants completed a 9.5-hr laboratory session after overnight abstinence (CO verified). Participants completed measures of attention (Conners' Continuous Performance Task [CPT]), working memory (digits backward), and delay discounting. Measures of craving, withdrawal, and mood were also collected. Between-subjects ANCOVA models revealed that varenicline speeded reaction time, but reduced accuracy on the CPT compared with placebo. Sex moderated the effect of bupropion compared with placebo on working memory and delay discounting. Bupropion enhanced working memory for females but not males, and this pattern was reversed for delay discounting. The current data highlight the complex processes associated with nicotine deprivation and the need for future research to examine whether cognitive-related deficits are related to relapse. Identifying these mechanisms may help in the development of new pharmacological treatments.