Although no pharmacological treatment has proved to be highly effective for reducing cocaine dependence, several medications have been tested over the last decade and have shown promising efficacy. Modafinil (Provigil), known as a treatment for day time sleepiness, and Topiramate (Topamax), an anti-epileptic medication also prescribed for migraine, have been shown to be effective in controlled clinical trials. We have recently started a major study utilizing Positron Emission Tomography (PET) brain imaging to monitor the progress of pharmacotherapy with modafinil or topiramate in cocaine-dependent and methadone-maintained cocaine-dependent patients. Patients will be assessed before treatment, and again after 4 weeks of pharmacotherapy. The aims of the project are to study effects of the two medications on cocaine dependence and craving, and on dopamine binding in the brain. At each assessment session, patients will undergo PET with [11C] raclopride to image the dopamine receptor DRD2. To trigger craving, patients will then be exposed to a videotape showing cocaine use; a questionnaire will be used to record their subjective responses, and a second PET scan will be performed with [18F] fluorodeoxyglucose (FDG) to image cerebral glucose metabolism during craving. This protocol was designed to enable us to study changes resulting from pharmacotherapy on dopamine binding in the brain, and on craving as reflected both in subjective measures and regional cerebral glucose metabolism. In addition, we will investigate the association between subjective measures of craving for cocaine and the level of dopamine DRD2 receptor occupancy in the brain before and after treatment. Notwithstanding the complexity of the clinical and therapeutic reality characterizing cocaine dependence, we hope to present preliminary evidence for the relative efficacy of these two promising medications in treatment for cocaine. dependence. This evidence could also elucidate the brain mechanisms underlying cocaine craving and dependence in cocaine-dependent patients.