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Rationale: Recent biological conceptualizations of craving and addiction have implicated mesolimbic dopamine activity as a central feature of the process of addiction. Imaging, and pharmacological studies have supported a role for dopaminergic structures in cue-elicited craving for tobacco., Objective: If mesolimbic dopamine activity is associated with cue-elicited craving for tobacco, a dopamine antagonist should attenuate cue-elicited craving for tobacco. Thus, the aim of the present study was to determine whether an atypical antipsychotic (olanzapine, 5 mg) decreased cue-elicited craving for tobacco., Method: Participants were randomly assigned to 5 days of pretreatment with olanzapine (5 mg; n=31) or were randomly assigned to 5 days of a matching placebo (n=28). Approximately 8 h after the last dose, participants were exposed to a control cue (pencil) followed by exposure to smoking cues. Participants subsequently smoked either nicotine cigarettes or de-nicotinized cigarettes., Results: Olanzapine attenuated cue-elicited craving for tobacco but did not moderate the subjective effects of smoking., Discussion: This study represents one of the first investigations of the effect of atypical antipsychotics on cue-elicited craving for tobacco. The results suggest that medications with similar profiles may reduce cue-elicited craving, which in turn, may partially explain recent observations that atypical antipsychotics may reduce substance use.