The investigators will randomize 210 opioid-dependent participants to one of two outpatient detoxification strategies: (1) a standard 7-day buprenorphine induction and gradual taper from 8 mg to 0 mg vs. (2) 7-day oral naltrexone induction; both groups will receive a single administration of a Vivitrol injection: at Day 8 for the naltrexone induction group and Day 15 for the buprenorphine group. The naltrexone arm is a modification of our current inpatient naltrexone induction procedure, consisting of a single day of buprenorphine followed by a washout day and 4 days of ascending oral naltrexone doses, prior to administering a dose of injectable naltrexone on Day 8. All participants will receive an intensive behavioral therapy for five weeks and will be followed for the subsequent 8 weeks to assess the longer-term outcome of the initial treatment. The primary outcome will be percentage of patients in each group successfully inducted onto Vivitrol. Key secondary outcomes will be 2-week abstinence at Weeks 4-5 (3rd and 4th weeks after Vivitrol injection), rates of completion of the 8-day detoxification, and percentage of patients in each group who return for additional Vivitrol injections in post-study follow-up. The main goal of this Stage 1a pilot study is to develop an improved outpatient opioid detoxification strategy, with particular relevance to newly diagnosed heroin addicts and prescription opioid abusers not seeking long-term agonist maintenance.

Specific Aim #1: To develop procedures for outpatient opioid detoxification which include naltrexone to facilitate detoxification.

Specific Aim #2: To compare injectable naltrexone induction rates between the naltrexone and buprenorphine groups following short-term outpatient opioid detoxification approach for initiating treatment for opioid dependence.

We are proposing a randomized, parallel-groups 5-week study of relapse prevention in detoxified opioid-dependent individuals. This trial represents an initial test of the feasibility and efficacy of an outpatient opioid detoxification strategy employing induction onto long-acting naltrexone (Vivitrol), in combination with the recently adapted version of Behavioral Naltrexone Therapy for Depot Naltrexone (Depot-BNT). Participants will be randomized into one of two outpatient detoxification strategies: (1) standard 7-day buprenorphine induction and taper from 8 mg to 0 mg (N=33), followed on Day 15 by a naloxone challenge and a dose of long-acting injectable naltrexone (Vivitrol) (consistent with the FDA-approved recommendation of 7 or more days between last opioid dose and Vivitrol induction) vs. (2) a modification of our current inpatient naltrexone induction procedure, consisting of a single day of buprenorphine followed by a washout day and 4 days of ascending oral naltrexone doses, followed by long-acting injectable naltrexone (Vivitrol) 380 mg on Day 8 (N=67). We are seeking to obtain Vivitrol samples from Alkermes; if we are successful in obtaining such samples, we will offer all participants who complete the study a second injection 4 weeks after the first, and a third injection will be offered at Week 12. All participants will receive an intensive behavioral therapy for five weeks and will be followed for up to 24 weeks to assess the long-term outcome of the initial treatment. Study assessments will be collected at baseline and at each study visit (twice weekly in Weeks 2-5; weekly in Weeks 6-9 for participants who receive a second Vivitrol injection and participate in follow-up care). Repeated assessments will also be completed at one and four months following the end of treatment. The primary aim of this study is to test the hypothesis that an outpatient opioid detoxification strategy using naltrexone will increase the likelihood of successful induction onto long-acting injectable naltrexone, compared to a buprenorphine taper in opioid-dependent patients. The primary outcome measure will be percentage in each treatment group (oral naltrexone vs. buprenorphine taper) receiving the Vivitrol injection at Day 8 or 15. Key secondary outcomes will be: two-week opioid abstinence during Weeks 4-5, retention in the 8-day detoxification procedure (time to dropout) and severity of opiate withdrawal during the first 5 weeks of treatment. We anticipate that the outpatient opioid detoxification method developed in this project will be uniquely suited to the needs of the rapidly expanding population of prescription opioid-abusing individuals seeking an alternative to opioid agonist maintenance. The current proposal will also yield important data on how to improve long-term outcomes for the buprenorphine taper method of opioid detoxification, through the addition of long-acting naltrexone.

Inclusion Criteria:

• Meets DSM-IV criteria for current opiate dependence disorder of at least six months duration, supported by urine toxicology OR COWS score > or =6 OR Naloxone Challenge .
• Seeking treatment for opioid dependence.
• In otherwise good health based on complete medical history and physical examination
• Able to give written informed consent.

Exclusion Criteria:

• Methadone maintenance treatment or regular use of illicit methadone (> 30 mg per week).
• Maintenance on, or regular use of buprenorphine or other long-acting narcotic agonists
• Active medical illness which might make participation hazardous, such as untreated hypertension, acute hepatitis with AST or ALT > 3 times normal, AIDS, unstable diabetes.
• Severe psychiatric illness (psychotic disorder, major depression, suicide risk or 1 or more suicide attempts within the past year.)
• Physiologically dependent on alcohol or sedative-hypnotics
• History of allergic or adverse reaction to buprenorphine, naltrexone, naloxone, clonidine, or clonazepam.
• Chronic pain requiring opioid analgesia or anticipated surgery necessitating opioid medications
• AIDS dementia or other chronic organic mental disorder
• Pregnancy, lactation, failure to use contraception
• 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.