Nicotine is self-administered by smoking tobacco products, and enhances positive mood (at least in smokers). Since most drugs of abuse decrease regional cerebral metabolic rate(s) for glucose (rCMRglc) in human subjects, we posited that administration of nicotine would similarly reduce rCMRglc. Positron emission tomography (PET) with [F-18]fluorodeoxyglucose was used to assess the effects of intravenous nicotine (1.5 mg) on cerebral glucose metabolism in six healthy male volunteers (21-38 years of age). Two PET assays (placebo and nicotine) were performed, and subjective self-reports of mood and feeling state were collected. Data were analyzed using analysis of variance. Nicotine reduced global glucose metabolism (by 9.51% of placebo control), with reductions in most of the 30 individual regions tested. Nine regions had bilateral effects that reached statistical significance (p&<0.05, uncorrected for the number of regions tested), although the statistical model used did not separate these effects from a global effect. The subjects reported both positive and negative effects of nicotine on mood/feeling state. The widespread decreases in cerebral metabolism are consistent with the many effects of nicotine on cognition and mood. The findings indicate that nicotine resembles other drugs of abuse in reducing brain metabolism, perhaps by a common mechanism.