The goal of this study is to test the efficacy of memantine (a noncompetitive NMDA receptor antagonist) as an adjunct to the maintenance treatment with naltrexone in detoxified heroin-dependent individuals.

The primary aim of this study is to test the efficacy of memantine, a noncompetitive NMDA receptor antagonist, in reducing early attrition and improving outcome in opioid-dependent individuals maintained on naltrexone.

This double-blind, 12-week trial will include heroin-dependent patients who completed detoxification. Participants will be randomly assigned to one of three conditions: naltrexone and placebo, naltrexone and memantine (15 mg bid), or naltrexone and memantine (30 mg bid). Naltrexone will be taken 3 times each week at the clinic, while memantine or placebo will be taken at home. In addition, twice each week patients will receive a psychosocial intervention that will include motivational interviewing and cognitive-behavioral relapse prevention. The goal of the psychosocial intervention is to improve compliance with medication and maintain abstinence. Baseline assessments will be taken and compared to those completed at study visits, which will occur 3 times each week.

Inclusion:

• Adult, aged 18-60.
• 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.
• Able to give informed consent.

Exclusion:

• Pregnancy or breastfeeding
• Failure in a sexually active woman to use adequate contraceptive methods
• Active medical illness that might make participation hazardous, such as untreated hypertension, acute hepatitis with SGOT or SGPT levels > 2 times normal, unstable diabetes, or chronic organic mental disorder (e.g., AIDS dementia)
• Active psychiatric disorder that 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.
• History of allergic reaction to buprenorphine, naloxone, memantine, naltrexone, clonidine, or clonazepam
• Currently prescribed or regularly taking opiates for chronic pain or medical illness
• Current participation in another intensive psychotherapy or substance abuse treatment program or currently prescribed psychotropic medications
• Current participation in a methadone maintenance treatment program and/or regular use of illicit methadone ( > 30 mg per week)
• History of accidental drug overdose in the last 3 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

It is possible that concomitant naltrexone might have exacerbated protracted withdrawal, thus masking the potential ameliorative effects of memantine that have been previously observed in other trials.