Bupropion is an efficacious non-nicotine medication for smoking cessation; however, its cessation-mediating mechanism is unclear. This randomized, placebo-controlled trial examined the effect of bupropion SR (300 mg/day for 6 weeks) on plasma cotinine and on the subjective effects of smoking in 24 current daily smokers who were not trying to quit or reduce smoking. Subjective effects of smoking, as well as cue-elicited responses were assessed at bi-weekly experimental sessions using validated scales. Several indices of cigarette consumption were measured. Plasma cotinine decreased from 280 (+/-133) microg/l at baseline to 205 (+/-108) microg/l at end of treatment in the bupropion group (p=0.036), but no significant change was found in the placebo group. Daily cigarette count and puff topography did not significantly change in either group. In contrast to placebo, bupropion increased post-smoking satiety (p=0.045). Both groups reported higher craving (p=0.025) and withdrawal (p=0.014) after exposure to smoking-related pictures, compared to neutral pictures. This biased reactivity was not significantly affected by treatment condition (p>0.1). Therefore, bupropion does not appear to impact the smokers' response to conditioned smoking-related cues but influences the unconditioned subjective effects of smoking in unmotivated smokers. This study is among the first to systematically investigate the effect of chronic bupropion administration, free from the confounding effect of the smoker's motivation to quit smoking.

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