Medications Development for Drug Abuse Disorders

Inclusion/Exclusion Criteria: * Participants in this study will be males and females between the ages of 18 and 60 years. * Applicants must be opioid dependent based upon the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (SCID); in addition, they must have an opioid positive urine during the screening process (or have evidence of opioid withdrawal). * They must be healthy, with no significant medical illnesses (e.g., insulin dependent diabetes), and without significant psychiatric illness (e.g., schizophrenia) besides their drug dependence. * Females will have a pregnancy test prior to study enrollment, and if found to be pregnant will be excluded and referred to a substance abuse program for pregnant women (the Center for Addiction and Pregnancy) on the campus. * Volunteers will also be excluded if they have pre-admission hypotension (due to the use of clonidine in the study). * Applicants with a history of seizures (including substance-related seizures, such as alcohol withdrawal related) will be excluded. * Alcohol and/or sedative dependence will be specific exclusionary criteria (given the small risk of seizures associated with tramadol use). * Allergies to any of the study medications will be grounds for exclusion.