An investigation of the acute and chronic effects of nicotine and craving was undertaken in three groups: never-smokers, current-smokers under 10-h withdrawal and recent ex-smokers (quit < 6 months; n=4/group). An 8mg dose of nicotine gum probed the acute and chronic subjective effects of nicotine in never-smokers and current-smokers in withdrawal. Subjective drug effects and craving were measured using Visual Analog Scales. To further examine the nature of craving, visual and auditory smoking cues were presented to each group, while f-MRI was performed. Results indicate: (a) significant nicotine-associated aversive effects in never-smokers; while current-smokers reported decreased negative symptoms, (b) notably increased craving during withdrawal; (c) a trend toward increased craving following cue-exposure in current and ex-smokers; (d) similar activation of frontal and limbic brain regions in current and ex-smokers during cue-exposure. This data may impact knowledge of the long-term nicotine-induced neuroadaptations that mediate reactivity to smoking stimuli to induce craving.