Over the past decade, bupropion has become a major pharmacotherapy for smoking 
cessation in the Western world. Unlike other smoking cessation 
pharmacotherapies, bupropion is a non-nicotine treatment. Compared with a 
placebo control, bupropion approximately doubles smoking quit rates. Most 
smoking cessation pharmacotherapies are thought to work, in part, by reducing 
nicotine withdrawal and craving. This article reviews preclinical, human 
laboratory and clinical trial studies of the effect of bupropion on nicotine 
withdrawal and craving. Preclinical studies demonstrate that in rats undergoing 
nicotine withdrawal, bupropion can dose-dependently lower changes in 
brain-reward threshold and somatic signs of nicotine withdrawal. Human 
laboratory studies have demonstrated that bupropion can alleviate some nicotine 
withdrawal symptoms, including depressed mood, irritability, difficulty 
concentrating and increased appetite. Moreover, bupropion has shown some 
efficacy in alleviating craving to smoke. Clinical trials of bupropion have 
offered mixed support of its ability to reduce nicotine withdrawal, weight gain 
during treatment and craving. Strong mediational evidence of bupropion's action 
through relief of withdrawal and craving in smoking cessation is growing. 
Greater understanding of the psychological mechanisms of bupropion action will 
likely be obtained through advances in the conceptualization and measurement of 
withdrawal and craving. Improvements in the efficacy of bupropion may be 
achieved through pharmacogenetic studies, with particular emphasis on its 
metabolites. Ultimately, the efficacy of bupropion may be augmented by 
combination with other agents that target withdrawal and craving through 
complementary neurobiological processes.