This study evaluates the biological markers of treatment of opioid dependent individuals with an extended release formulation of the opioid antagonist naltrexone. The biological measures include functional MRI, blood levels of naltrexone and its metabolites, urine toxicology and behavioral tests probing various aspects of personality, memory, reward processing and attention.

This study is using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the brain predictors of adherence and outcomes of opioid antagonist therapy. Opioid-dependent intravenous heroin users are offered up to 3 monthly injections of the extended-release naltrexone (XRNTX) contingent upon successful outpatient non-opioid detoxification, with an additional 4 weeks of follow up. Brain responses to heroin-related pictures are recorded using fMRI prior to the 1st XRNTX injection and approximately 2 weeks thereafter the 1st XRNTX injection. Primary clinical variables include the number of injections (maximum of 3) accepted by participants, change in self-reported craving for opioids after exposure to drug-related visual cues during the brain fMRI sessions, urine levels of ten commonly abused substances and self-report of cigarette use.

Inclusion Criteria:

1. DSM-IV-TR diagnosis of opioid dependence, active opioid use, confirmed by urine toxicology screen and self-reported monthly intravenous heroin use for more than 2 weeks in the past 3 months
2. urine toxicology screen negative for opioids after detoxification
3. good physical health as indicated by history and physical examination, screening blood work-up and urinalysis.

Exclusion Criteria:

1. chronic medical illnesses;
2. current use of medications potentially confounding brain activity, such as anti-dopaminergic agents, anti-depressants and beta-blockers;
3. current DSM-IV-TR Axis I psychiatric disorders other than opioid and nicotine dependence;
4. life time history of concurrent IV cocaine and heroin (speedball) administration;
5. pregnancy or breastfeeding;
6. history of clinically significant head trauma;
7. contraindications for naltrexone treatment including medical conditions requiring opioid analgesics, e.g. chronic pain or planned surgery, obesity, elevated liver enzymes (> 3 times upper limit of normal), failure to complete opioid detoxification
8. contraindications for MRI, i.e. indwelling magnetically active foreign bodies and phobia to enclosed spaces