Biomarkers of Injectable Extended Release Naltrexone Treatment

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