Studies demonstrate that methamphetamine (meth) use is associated with high-risk sexual behavior among MSM, putting meth-using MSM at extraordinarily high risk for transmitting or acquiring HIV. No studies have tested the feasibility and acceptability of conducting pharmacologic interventions to reduce meth use and meth-associated sexual risk behavior among MSM. The purpose of this pilot study is to determine the feasibility enrolling and retaining meth-dependent MSM into a pharmacologic study of bupropion vs. placebo and measuring the tolerability of and adherence to medication among these participants.

The high rate of meth use among MSM is paralleled by evidence of rises in sexual risk behavior and HIV infection among this population. The MSM meth epidemic, and its link with HIV transmission, underscores the need to pilot test new, innovative modalities to reduce meth use and meth-associated sexual risk behavior. Ultimately, a pharmacologic treatment for meth use may not only serve to improve outcomes among those who are accessing current treatment services, but might also benefit those who are not willing or able to utilize such services. While studies show that MSM who enter substance use treatment decrease both their substance use and sexual risk behavior, current behavioral meth treatment programs report low rates of success in treating meth dependence among MSM. We believe the time has come to test the acceptability of pharmacologic interventions to reduce meth use among MSM, and to assess the feasibility of conducting such trials among sexually active, meth-dependent MSM, whose meth-associated sexual behavior use places them at extraordinarily high risk for transmitting or acquiring HIV. In this pilot study, we will provide meth-dependent MSM with placebo or daily bupropion XL (extended-release), a well-tolerated dopamine agonist that has potential to reduce meth use. The specific aims of this study are:

1. To assess the feasibility of enrolling and retaining meth-dependent MSM into a randomized, double-blind study of bupropion versus placebo with biologic (urine meth testing) and behavioral (sexual risk) measures.
2. To explore the tolerability of bupropion and placebo among meth-dependent MSM, as determined by the number of adverse clinical events in the bupropion and placebo arms.
3. To describe the acceptability of bupropion and placebo among meth-dependent MSM, by measuring (via electronic pill caps) medication adherence to bupropion and placebo.

This randomized, double-blind, placebo-controlled, two-arm pilot study will enroll 30 meth-dependent MSM assigned to receive 3 months of bupropion XL 300 mg daily or placebo. We will include both HIV- and HIV-INFECTED MSM, because meth use is common in both groups. We will enroll meth-dependent MSM because they are the most likely population to benefit from this potential treatment. Participants will be seen weekly for urine specimen collection and substance-use counseling. Clinical exams, medical history, specimen collection, and behavioral assessments will be performed at baseline and at the 1, 2, and 3 month visits. Interim visits will be scheduled whenever indicated by signs or symptoms. Our decision to maintain participants on 3 months of bupropion is based on the smoking literature, which demonstrated bupropion's efficacy in treating nicotine addiction within similar time periods; we anticipate that any future efficacy trial will maintain participants on bupropion for this duration.

Inclusion Criteria:

• HIV-negative by rapid test or able to document HIV infection through healthcare provider's note or documentation of laboratory test;
• Reports anal sex with men in prior 3 months while using meth
• Diagnosed with meth dependence as determined by SCID
• Interested in stopping or reducing meth use
• Meth-positive urine on screening
• No known allergies to bupropion
• No current acute illnesses
• Able and willing to provide informed consent and to be followed over a 3-month period
• Baseline CBC and electrolytes within institutional limits.

Exclusion Criteria:

• History of seizure
• High risk for seizure, including: recent (last 24 months) head trauma, brain injury or surgery; using theophylline or systemic steroids; prior or current history of anorexia or bulimia; prior or current history of alcohol withdrawal symptoms
• Measured moderate or severe liver disease (LFTs > 3 times normal) or history of chronic liver disease
• Impaired renal function (creatinine clearance < 90 ml/min)
• Evidence of current major depression, as determined by SCID
• Taking anti-depressant medication within last 30 days
• Currently on any bupropion-containing regimen
• Currently using or unwilling not to use pseudoephedrine-containing products (causes false + urines for meth use) for trial duration
• Currently taking antiretroviral therapy (ART)
• CD4 count < 200 cells/mm3
• Any condition that, in the principal investigator's judgment, interferes with safe study participation.

12 weeks