Naltrexone for Overdose Prevention

The goal of this clinical trial is to see if an injectable medicine called naltrexone can prevent fentanyl overdose deaths in people who use other drugs (cocaine, methamphetamine). The main questions it aims to answer are: What are the challenges for implementing naltrexone as an overdose prevention strategy? Are injections of naltrexone effective for opioid overdose prevention among people who use stimulants? How often are people who use stimulants and do not intentionally use opioids unintentionally exposed to opioids? Researchers will compare participants to receive the study medication to the usual care group to see if one group experiences fewer opioid overdose events than the other. Participants will be randomized to either receive a monthly injection of naltrexone over six months, or receive usual care. Usual care includes harm reduction supplies. Laboratory procedures will include the collection of urine, blood, and hair samples for various safety and outcome measure testing.

Inclusion Criteria: 1. at-risk for HIV or living with HIV 2. stimulant use disorder (by DSM-V) or positive urine drug test for cocaine, amphetamine, or methamphetamine in last 6 months AND report at least 10 days of stimulant use/month, 3. able to provide informed consent, 4. English-speaking, 5. age 18 years old or greater. Exclusion Criteria: 1. prescribed or non-prescribed opioid use (including newly diagnosed opioid use disorder by DSM-V), 2. receipt of long-acting injectable naltrexone for other indications in past 30 days, 3. planned surgery in next 6 months, 4. moderate, severe or chronic liver disease (AST, ALT ≥ 5 times the upper limit of normal or symptoms of current liver disease), 5. persons who are pregnant or breastfeeding, 6. increased risk of bleeding (thrombocytopenia \