We did not exclude smokers as from our experience around 75% of cocaine subjects smoke cigarettes (vs. around 25% of controls). Fifteen cocaine subjects and five control subjects were smokers, and the group difference was statistically significant. Subjects were allowed to smoke regularly to minimize withdrawal symptoms. Previous studies have shown that nicotine can induce a dose-dependent increase in neuronal activity in a distributed system of brain regions, including the nucleus accumbens, amygdala, cingulate, and frontal lobes [56]. Therefore, the blunted responses of the cocaine smokers could have been even more suppressed if they would have been abstinent for nicotine prior the study. Taking into account that the average elimination half-life for plasma nicotine is 2 hours in humans [57], and given that none of the controls subjects and only two cocaine subjects smoked within the 2-hours period before the study, none of them smoked during the study, and there was no difference between groups in time since last cigarette, the potentially circulating nicotine levels should have been low and the differential effects of nicotine on brain activation should be
