DESCRIPTION: (Applicant's Abstract) This application requests a Research Scientist Award to enable the candidate to pursue full time research and research training aimed at improving the pharmacotherapy of cocaine and opioid dependence. During the award period, the applicant will conduct pharmacotherapy trials of two types: a) combinations of novel pharmacotherapies with behavioral interventions targeted at cocaine dependent patients with comorbidities such as depression and opioid dependence, b) treatments for cocaine associated cerebral perfusion defects assessed using SPECT neuroimaging. The Research Plan uses behavioral contingencies to move forward our 10 years of work showing the efficacy of desipramine (DMI) and its combination with buprenorphine (BUP) for reducing cocaine abuse. The plan provides a detailed description of our 24 week, randomized placebo-controlled, double blind clinical trial using DMI in combination with contingency management for 160 patients who are maintained on buprenorphine for comorbid opioid and cocaine dependence. The contingency group will get a voucher worth a set monetary value that increases for consecutively drug-free urines (weeks 1-19) or a voucher with a fixed value under an increasing ratio of number of consecutive drug free urines per voucher (weeks 13-24). Subjects not in the contingency group get monetary vouchers independent of their illicit cocaine use.