DESCRIPTION: (Applicant's Abstract) The goal of this Stage II project (NIDA Behavioral Therapies Development Program PA-99-107) is to test the efficacy of a new combination of behavioral therapy with oral naltrexone maintenance for the treatment of heroin addiction, and to test a new long-acting depot parenteral formulation of naltrexone in initiating treatment. Antagonist maintenance with naltrexone is an important alternative to agonist maintenance or drug-free treatment, but it has not, to date, lived up to its potential. During the first two years of a Stage I project, Behavioral Naltrexone Therapy (BNT) was developed to address four limitations of naltrexone maintenance: 1) Difficulty transitioning patients from opiates to naltrexone; 2) Poor compliance; 3) Possible dysphoric effects; and 4) Inadequate psychotherapeutic context. After hospitalization for rapid transition from opiates to naltrexone, therapy sessions over six months draw elements from Network Therapy, the Community Reinforcement Approach, and voucher incentives contingent on compliance with naltrexone and abstinence from opiates. A significant other attends sessions and monitors compliance. Depression is identified early and treated. A treatment manual and therapy adherence instrument were developed. Results of a pilot trial are promising, although naltrexone discontinuation and relapse during the first month remains a significant problem. At the same time, a depot parenteral formulation of naltrexone was studied which produces therapeutic blood levels and blockade of opiate effects for 3 to 4 weeks after injection. It is hypothesized that a dose of depot naltrexone, administered after transition to oral naltrexone and before discharge from hospital, will prevent attrition during the initial outpatient weeks, allowing the behavioral regimen to take hold and substantially improving the long-term efficacy of our combination of behavioral therapy and oral naltrexone. In the proposed Stage II trial 160 heroin dependent patients will be randomly assigned to one of four conditions in a 2 by 2 factorial design: 1) BNT plus a dose of depot naltrexone prior to hospital discharge; 2) BNT plus a placebo injection; 3) Compliance Enhancement (CE), a control condition simulating standard treatment with naltrexone, plus depot naltrexone; and 4) CE plus placebo injection. Specific Aims are: 1) To test the efficacy of Behavioral Naltrexone Therapy (BNT) compared to control therapy for the maintenance treatment of opiate dependence; and 2) To test the efficacy of depot naltrexone in reducing early attrition, improving initial stabilization on oral naltrexone, and improving long term outcome of Behavioral Naltrexone Therapy (BNT).