Stress and Medication Effects on Cocaine Cue Reactivity

Inclusion Criteria: Subjects must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments. Subjects must consent to remain abstinent from all drugs of abuse (except nicotine) during the GCRC admission. Because of the high comorbidity of alcohol and marijuana use and cocaine dependence, individuals meeting dependence for alcohol and marijuana will be included. Individuals requiring medical detox from alcohol will be excluded. Subjects must consent to random assignment to stress vs. no stress and drug treatment conditions. Exclusion Criteria: Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control. Modafinil inhibits metabolism of steroidal contraceptives via CYP3A4 and can reduce the effectiveness of this type of birth control, female subjects must use one of the following methods of birth control: barrier methods (diaphragm or condoms with spermicide or both), surgical sterilization, use of an intra-uterine contraceptive device, or complete abstinence from sexual intercourse. Subjects with evidence of or a history of significant hematological, endocrine, cardiovascular (including but not limited to left ventricular hypertrophy (unless a cardiologist deems that it is not clinically significant), mitral valve prolapse, left bundle branch block, myocardial infarction, and angina), pulmonary, renal, gastrointestinal, or neurological disease including diabetes, as these conditions may affect HPA axis function. Subjects with any liver function test (LFTs) of greater than two times normal, as compromised liver function can interfere with HPA axis activity (Williams and Dluhy 1987) and may affect drug metabolism. Subjects with Addison's disease, Cushing's disease or other diseases of the adrenal cortex likely to affect HPA axis function. Subjects with a history of or current psychotic disorder or bipolar affective disorder as these may interfere with HPA function. Subjects with current major depressive disorder or post-traumatic stress disorder as these disorders are associated with characteristic changes in HPA axis function. Subjects receiving synthetic glucocorticoid therapy, any exogenous steroid therapy, or treatment with other agents that interfere with HPA axis function within one month of the time of testing. Subjects taking any psychotropic medications, opiates or opiate antagonists because these may affect HPA axis function.Participants taking SSRI's will be included. Subjects required to take medications that could adversely interact with study medications, including, but not limited to, azole type antifungals, cyclosporine, warfarin, theophylline, or carbamazepine. Any medications that induce or inhibit CYP3A4 pathways are excluded, as modafinil is metabolized through this enzyme system. Subjects with any acute illness or fever as this may affect HPA axis activity. Individuals who otherwise meet study criteria will be rescheduled for evaluation for participation. Subjects who are grossly obese (BMI \> 39), as this may interfere with HPA axis function. Subjects who are unwilling or unable to maintain abstinence from alcohol and other drugs of abuse (except nicotine) prior to the stress task procedure. Subjects meeting DSM-IV criteria for substance dependence (other than nicotine, cocaine, alcohol or marijuana) within the past 60 days.