In pilot study now proposed, we plan to randomly assign 60 opioid dependent patients to the new model, Depot-BNT, or to BNT plus oral naltrexone for a 6-month trial. This will provide initial clinical experience with the new Depot-BNT treatment model, while providing a rigorous test of whether Depot-BNT produces superior treatment outcome, compared to our best behavioral platform for oral naltrexone (BNT).

The following aims will be addressed:

Specific Aim #1: To test whether Depot-BNT increases retention in treatment and improves drug use outcome (urine-confirmed abstinent weeks) compared to our established model of BNT with oral naltrexone (BNT-Oral), and to explore whether Depot-BNT (vs BNT-Oral) improves key secondary outcomes including dysphoria, HIV risk behavior, and social functioning.

Specific Aim #2: To explore predictors of outcome on Depot-BNT, and mechanisms of attrition, in order to optimize Depot-BNT prior to further testing.

The clinical trial now proposed will provide an initial test of the feasibility and efficacy of the newly adapted version of Behavioral Naltrexone Therapy for Depot Naltrexone (Depot-BNT). Treatment-seeking opiate-dependent patients will be admitted for inpatient detoxification and induction onto oral naltrexone. Those who are successfully inducted will be randomly assigned for a six month trial to one of two conditions: 1) Behavioral Naltrexone Therapy for Depot Naltrexone (Depot-BNT) (N = 30), with the first dose of depot naltrexone administered prior to discharge from hospital with monthly doses thereafter; or 2) Behavioral Naltrexone Therapy as previously developed for promoting compliance with daily oral naltrexone (BNT-Oral) (N = 30). All patients in both groups will be asked to attend twice weekly outpatient therapy sessions over a six month course. This design will provide a test of whether Depot-BNT produces superior treatment retention and drug use outcome in comparison to our established behavioral platform for oral naltrexone, while providing experience upon which to base revisions of Depot-BNT prior to embarking upon further Stage 2 testing. Treatment will take place at the same sites as for our prior studies: (1) the General Clinical Research Unit (GCRU) of New York State Psychiatric Institute (NYSPI) and (2) the Substance Treatment and Research Service (STARS) of the Division on Substance Abuse at NYSPI.

Inclusion Criteria:

1. Age 18-60.
2. Meets DSM-IV criteria for current opiate dependence disorder of at least six months duration, supported by a positive urine for opiates and a positive naloxone challenge test if the diagnosis is unclear. If participating as an outpatient only, recent opiate dependence must be confirmed by clinical history and/or communication with former treatment provider.
3. Seeking treatment for heroin dependence.
4. Able to give informed consent.

Exclusion Criteria:

1. Methadone maintenance treatment or regular use of illicit methadone (> 30 mg per week).
2. Maintenance on, or regular use of buprenorphine or other long-acting narcotic agonists.
3. Pregnancy, lactation, or failure in a sexually active woman to use adequate contraceptive methods.
4. Active medical illness which might make participation hazardous, such as untreated hypertension, hepatitis with SGOT or SGPT > 3 times normal, unstable diabetes.
5. Active psychiatric disorder which might interfere with participation or make participation hazardous, including DSM-IV schizophrenia, bipolar disorder with mania or psychosis, and depressive disorder with suicide risk or 1 or more suicide attempts within the past year.
6. Physiologically dependent on alcohol or sedative-hypnotics with impending withdrawal. Other substance use diagnoses are not exclusionary. Multiple substance use is common in this population, and such an exclusion would rule out a large proportion of the population and limit the generalizability of the study.
7. History of allergic reaction to buprenorphine, naltrexone, naloxone, clonidine, or clonazepam.
8. Chronic organic mental disorder (e.g. AIDS dementia).
9. History of accidental drug overdose in the last 3 years as defined as an episode of opioid-induced unconsciousness or incapacitation, whether or not medical treatment was sought or received.
10. Currently receiving any other investigational drug, or has used any other investigational drug within 30 days of study entry.
11. Currently prescribed or regularly taking opiates for chronic pain or medical illness or those individuals anticipating surgical procedures which will necessitate opioid medications.

24 weeks