Current research is providing much needed data regarding the effects of chronic drug use on brain-behavior relations. This literature addressing the neurobehavioral concomitants of long-term substance use disorders (SUDs), however, is marked by considerable heterogeneity There are a number of factors which may contribute to this outcome. One likely contributor is the failure to account for the influence of the frequent use/abuse of the stimulant, nicotine. This second revision seeks five years of funding to address the role of nicotine in functionally compensating for the long-term neurocognitive effects of chronic substance abusers (SA s). Specifically, we propose to test the hypothesis that nicotine's cognitive enhancing properties, particularly as evidenced in working memory and attentional processes may serve to counterbalance or functionally overcome the negative effects observed in chronic SAs. The design entails the direct comparison of male and female abstinent, detoxified SA s (n=216) assigned to subgroups on the basis of their primary drug of abuse and current clinical diagnostic information with community controls (smoking and non-smoking; n=144) equated on geographic and demographic variables. In addition to responding to this question, the current design will also extend the on-going work regarding differences among drug using subgroups regarding cognitive compromise. Using a double-blind placebo controlled study, we propose to study the effect of three levels of nicotine via transdermal administration (0, 7 and 21 mg patches) in treatment-seeking SA and community controls (equal numbers of males and females). If the hypotheses are supported, existing research may underestimate the effects of chronic drug use on specific cognitive processes. These findings would have considerable clinical and scientific import. As a secondary aim, we plan to investigate associations among relevant, and understudied, demographic variables, including depressive symptoms, childhood behavioral disorders and anxiety symptomatology. Furthermore, we intend to examine the role of race/ethnicity, gender and family history of SUDs. To facilitate this secondary aim, we have instituted plans to over-sample American Indians (Al), African American (AA) and female participants.