Naltrexone, a µ-opioid receptor antagonist, is a promising agent for methamphetamine-using and binge-drinking men who have sex with men (MSM). Naltrexone has shown efficacy in reducing relapse to amphetamines and is FDA-approved for alcohol dependence. Oral naltrexone is inexpensive and has few toxicities but the standard daily regimen for naltrexone is problematic as patients forget to take the medication. Given the challenges in daily dosing, alternate regimen schedules have been proposed to increase efficacy and expand the population that may benefit from this pharmacologic agent. One approach is intermittent targeted administration of naltrexone, whereby individuals take the medication as-needed in anticipation of substance use or during periods of craving. Administration of naltrexone prior to exposure to amphetamines significantly attenuates craving and targeted naltrexone has shown efficacy in reducing heavy alcohol use. However, there have been no studies assessing intermittent targeted dosing of naltrexone among methamphetamine-using and binge-drinking MSM. Polysubstance use patterns are common among MSM, and studies among those who abuse more than one substance are urgently needed. The aims of this study are to determine whether targeted dosing of naltrexone is feasible, tolerable and acceptable among non-dependent methamphetamine-using and binge-drinking MSM.

Inclusion Criteria:

1. male gender or transgender male-to-female
2. self-reported anal sex with men in the prior six months while under the influence of meth and/or alcohol
3. self-reported meth use at least bi-weekly in the prior three months
4. at least weekly binge drinking (five or more drinks on a single drinking session) in the prior three months

4) interested in reducing meth use and/or binge drinking 5) HIV-negative by rapid test or medical record of HIV infection 6) no current acute illnesses requiring prolonged medical care 7) no chronic illnesses that are likely to progress clinically during trial participation 8) able and willing to provide informed consent and adhere to visit schedule 9) age 18-70 years 10) baseline complete blood count (CBC), total protein, albumin, glucose, alkaline phosphatase, creatinine, blood urea nitrogen (BUN), and electrolytes without clinically significant abnormalities as determined by study clinician in conjunction with symptoms, physical exam, and medical history

Exclusion Criteria:

1. any psychiatric (e.g., depression with suicidal ideation) or medical condition that would preclude safe participation in the protocol
2. known allergy or previous adverse reaction to naltrexone
3. current use of or dependence on any opioids or a known medical condition which currently requires or may likely require opioid analgesics
4. opioid-positive urine test at enrollment
5. current cluster of differentiation 4 (CD4) count < 200 cells/mm3
6. moderate or severe liver disease (aspartate aminotransferase, alanine aminotransferase, or total bilirubin > 3 times upper limit of normal)
7. impaired renal function (creatinine clearance < 60 ml/min)
8. currently participating in another research study
9. meth or alcohol dependence as determined by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID) criteria
10. any condition that, in the principal investigator and/or study clinician's judgment interferes with safe participation or adherence to study procedures.
11. unwillingness to provide minimum locator for information
12. not having a cellular phone that can send or receive a text message
13. plans to leave the Bay Area during study follow-up
14. not comfortable speaking and reading English, enough to participate in a program in English