This project will examine effects of bupropion extended release (XL) at a dose of 300mg/day for cocaine abstinence among persons receiving methadone for the treatment of opioid use disorder. Participants also earned financial incentives for providing urine samples that tested negative for cocaine. Bupropion was examined for this purpose because of its previously demonstrated efficacy and safety as well as its pharmacological actions at dopamine systems. Participants were randomly assigned to bupropion XL vs. placebo and received different incentive schedules depending on whether they demonstrated abstinence from cocaine early in the study. Outcomes were tracked over a 6-month time frame and the overarching hypothesis was that bupropion (as compared to placebo) would increase the number of urine samples testing negative for cocaine, independent of whether participants demonstrated abstinence from cocaine early in the study.

The efficacy of behavior therapies may be enhanced by certain medications, particularly those that act on dopaminergic systems. The purpose of this project is to examine effects of bupropion on initiation and maintenance of cocaine abstinence in a population of persons being treated with methadone for the treatment of opioid use disorder who are concurrently using cocaine. Bupropion appears to be the most promising medication for this purpose because of its previously demonstrated efficacy and safety as well as its pharmacological actions at dopamine systems.

Participants will be eligible for inclusion in the study if they are 1) enrolled in methadone maintenance treatment, having previously met the criteria for opioid dependence; 2) between the ages of 18 and 65; 3) provide evidence of cocaine dependence (DSM-IV criteria, self-report, and/or urine tests positive for cocaine during the intake process); and 4) are willing to take study medications and adhere to reporting and data collection schedules.

They will be excluded if they have 1) a history of epilepsy or seizure, including alcohol- or cocaine-related seizure; 2) conditions with increased risk of seizure (e.g. head trauma with loss of consciousness > 30 mins), 3) current use (past 30 days) of antidepressants, antipsychotics, theophyllines, systemic steroids, MAO-A inhibitors, 4) recent use (past 30 days of any medication containing bupropion or budeprion (Wellbutrin®, Zyban®), 5) allergy to bupropion or budeprion, 6) liver enzyme levels greater than 3x upper limit of normal (ULN); 7) uncontrolled diabetes mellitus (glucose > 200mg%); 8) severe psychiatric diagnosis: schizophrenia, psychosis, major depression, mania, current suicidal ideation with plan; cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires; 9) severe renal insufficiency (eGFR < 30 ml/min), 10) pregnant, breast feeding or unwilling to use birth control, 11) medical illness that in the view of the investigators would compromise participation in research, 12) advanced HIV infection requiring HAART 13) current eating disorder (anorexia or bulimia), 14) uncontrolled hypertension with blood pressure ( BP) >140/90.

All participants will be randomly assigned to receive bupropion XL (300mg/day) or placebo. In addition, study participants will also receive an add-on incentive-based intervention depending upon whether they provide 6 consecutive-urine samples that test negative for cocaine. Those who provide 6 consecutive negative urine samples will earn incentives for continuing to provide negative sample (Relapse Prevention group) and those who do not achieve this threshold will earn a different schedule of incentives to promote abstinence (Abstinence Initiation). Our hypothesis is that bupropion as compared to placebo treatment will both enhance the number of urine samples testing negative for cocaine. All participants will be eligible to earn $675 in incentives and cocaine use will be monitored via thrice weekly urine samples collected for a 6 month period.

Overall, this research will provide new and valuable information about the use of bupropion XL to enhance provision of cocaine-negative urine samples in persons independent of their early abstinence behaviors. If hypothesized synergies can be demonstrated, the study will point the way to a significant advance in improved treatment outcomes for this critical group of drug abusers. The proposed study is compelling because it conceptually differentiates the two key clinical issues in treatment of stimulant abusers- abstinence initiation and relapse prevention. It uses a design that efficiently and effectively tests a combined treatment approach for each clinical issue and as well examines cognitive function and reinforcement-based mediators. The research will add to understanding of the interplay between brain reinforcement systems and drug-seeking behavior. Finally, it will make an important contribution to behavioral therapy development by exploring a novel solution to limitations previously noted for CM that include lack of response in some patients and relapse after withdrawal of incentives.

Inclusion Criteria:

• Enrolled in methadone maintenance
• Meets Diagnostic and Statistical Manual of Mental Disorders, Fifth edition (DSM V) criteria for active cocaine use
• Submits one cocaine positive urine sample within 30 days of study start
• Agrees to study procedures

Exclusion Criteria:

• Healthy and without contra-indications to study medication
• Any history of epilepsy or seizure, including alcohol-, sedative-, or cocaine-related seizure
• Any increased risk of seizure such as serious head trauma with a loss of consciousness of more than an hour duration, brain tumor, or other brain pathology increasing risk of seizure.
• Current eating disorder including anorexia or bulimia
• Current use (last 30 days) of antidepressants, antipsychotics, theophyllines, systemic steroids, monoamine oxidase (MAO-A) inhibitors.
• Recent use (last 30 days) of budeprion, zyban®, wellbutrin®, aplenzin®, or any other medication containing bupropion.
• Allergy to bupropion or budeprion
• Liver enzymes greater than 3x ULN (upper limit of normal)
• Uncontrolled diabetes mellitus, or h/o diabetic coma
• Uncontrolled hypertension with BP > 140/90.
• Current psychiatric diagnosis: schizophrenia, psychosis, major depression, mania, current suicidal ideation as determined by MINI psychiatric interview, cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires
• Severe renal insufficiency (eGFR < 30 ml/min)
• Pregnancy or current breast feeding,
• Medical illness that in the view of the investigators would compromise participation in research, such as uncompensated congestive heart failure, recent history of myocardial infarction (<1year), or urologic conditions that inhibit urine collection.
• Advanced HIV infection requiring the use of HAART (Highly Active Anti-Retroviral Therapy), or with CD4 T cell count < 200/uL

Adverse events represent all events rated as "possibly, probably, or definitely" related to study participation, that were reported by participants to study staff during thrice weekly visits over a 23 week period during study weeks 7 - 30.