Prospective participants will undergo a screening process at the clinic to determine eligibility. After screening, eligible patients will complete an 8-day inpatient detoxification, followed by a 12-week outpatient phase. Patients will be randomly assigned to one of two conditions (1) Naltrexone + Placebo; (2) Naltrexone + Memantine 20 mg bid. Long-acting, injectable form of naltrexone (Vivitrol) will be administered once per month (the total of three injections) while memantine or placebo will be taken daily. In addition, patients will receive twice weekly psychosocial intervention that will include motivational interviewing and cognitive-behavioral relapse prevention. The outpatient treatment will also consist of 3 weekly visits to the clinic in which patients will receive counseling to help maintain abstinence and improve compliance with study medication.

In the proposed trial heroin-dependent patients undergoing detoxification will be randomly assigned to one of two conditions (1) Naltrexone + Placebo; (2) Naltrexone + Memantine 20 mg bid. Long-acting, injectable form of naltrexone (Vivitrol) will be administered once per month (the total of three injections) while memantine or placebo will be taken daily. In addition, patients will receive twice weekly psychosocial intervention that will include motivational interviewing and cognitive-behavioral relapse prevention. The goal of psychosocial intervention is to improve compliance with medication and maintain abstinence. A double-blind trial will last twelve weeks with assessments at baseline and at each appointment three times per week. After the completion of a double-blind study (experimental phase), participants will continue open label treatment with Vivitrol and therapy for additional three months (study extension phase). Repeated assessments will also be completed one, two, and three months following the end of double-blind treatment. For the experimental phase of the study, the primary aim is to test the efficacy of memantine in reducing early attrition and improving outcome in opioid-dependent individuals maintained on naltrexone and primary outcome measures will be retention in treatment by the end of the study and heroin abstinence.

Inclusion Criteria:

1. Adult, aged 18-60.
2. Meets Diagnostic and Statistical Manual IV (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.
3. Able to give informed consent.

Exclusion Criteria:

1. Pregnancy, lactation, or failure in a sexually active woman to use adequate contraceptive methods.
2. Active medical illness which might make participation hazardous, such as untreated hypertension, acute hepatitis with serum glutamic oxaloacetic transaminase or serum glutamic-pyruvic transaminase levels >2 times normal, unstable diabetes, chronic organic mental disorder (e.g., AIDS dementia).
3. 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.
4. History of allergic reaction to buprenorphine, naloxone, memantine, naltrexone, clonidine, or clonazepam.
5. Currently prescribed or regularly taking opiates for chronic pain or medical illness.
6. Current participation in another intensive psychotherapy or substance abuse treatment program or currently prescribed psychotropic medications.
7. Current participation in a methadone maintenance treatment program and/or regular use of illicit methadone (>30 mg per week).
8. History of accidental drug overdose in the last three years or any other significant history of overdose following detoxification defined as an episode of opioid-induced unconsciousness or incapacitation, whether or not medical treatment was sought or received.