This is a 16-week placebo-controlled randomized clinical trial that builds on our demonstration of a significant synergism between contingency management (CM) and pharmacotherapy with catecholaminergic agents in two studies. In the first, the antidepressant desipramine (DMI) was evaluated in its ability to reduce cocaine use when combined with CM in an opioid-maintained population. In that study those who got CM+DMI went from 9% (week 1) to 74% (week 12) drug-free urines, while the other three groups (CM+placebo, voucher control-VC+DMI, VC+placebo) rose only to 39% in week 12. In a second study, the subjects in a CM+bupropion condition attained significantly fewer cocaine positive urines over time than those in a CM+Placebo, VC+bupropion, or VC+placebo condition over 25 weeks. We intend to build on these successes by evaluating the combination of our CM intervention with modafinil. Modafinil, like desipramine and bupropion, is catecholaminergic and has been shown to decrease primary cocaine use in outpatients, and to blunt cocaine-induce euphoria in a laboratory setting. Based on these promising findings and modafinil's catecholaminergic properties, we intend to investigate the synergy between CM and modafinil. In addition, modafinil has been shown to improve learning, memory, attention, impulse-control and opiaterelated fatigue in humans. We will also investigate the role that these specific modafinil-related cognitive improvements have in attaining abstinence from cocaine. The CM intervention will reinforce cocaine-negative urine toxicology (3x per week) on an escalating schedule of reinforcement. Subjects will also be randomized to a yoked-control condition. In summary we address four Specific Aims in 160 methadone maintained patients using a two-by-two research design that will randomize to four cells: CM+placebo, CM+modafinil, yoked-control(YC)+placebo or YC+modafinil. 1) To compare modafinil treatment to placebo on treatment retention and cocaine abstinence. 2) To compare contingency management (CM) to yoked controls on treatment retention and cocaine abstinence. 3) To compare the efficacy of the combined treatment modafinil+CM to either treatment condition alone or to yoked-controls on treatment retention and cocaine abstinence. 4) To investigate the role of modafinil-related improvements in memory, attention, impulse control and fatigue in mediating cocaine abstinence and treatment retention.
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