Cocaine is one of the most widely abused drugs in the United States. Memantine is a type of drug called an NMDA receptor antagonist. It works by decreasing normal excitement in the brain. NMDA receptor antagonists have shown to reduce cocaine-induced dopamine release in animal models, as well as lessen conditioned cocaine cues. The purpose of this study is to determine the effectiveness of memantine in preventing relapse to cocaine use in cocaine dependent individuals. In addition, this study will determine whether memantine produces better results than a placebo in decreasing cocaine craving, psychological symptoms, functional impairment, and discontinuation of treatment in cocaine dependent individuals.

Memantine is a non-competitive NMDA receptor antagonist that works by decreasing normal excitement in the brain. Dopamine plays a role in the rewarding and addictive properties of cocaine, however, past clinical studies have not been successful in using dopamine agonists in treating cocaine dependent individuals. Non-competitive NMDA receptor antagonists have shown to reduce cocaine-induced dopamine release in animal models and lessen conditioned cocaine cues. This study will evaluate memantine in treating cocaine dependent individuals and its ability to prevent relapse to cocaine use. Specifically, the aim of this study is to determine if memantine is superior to placebo in decreasing cocaine craving, psychological symptoms, functional impairment, and discontinuation of treatment for cocaine abuse.

Participants will enter a 2-week, single-blind, placebo lead-in phase, during which they will visit the clinic three times each week. At each study visit, urine samples and other rating assessments will be collected. In addition, participants will attend weekly therapy sessions. In order to continue in the trial, participants are required to attend at least four out of the first six study visits and both therapy sessions. Eligible participants will then be randomly assigned to receive either memantine or placebo for the duration of the 12-week, double-blind phase of the trial. Study visits will continue to occur three times each week; participants will also receive weekly therapy. Memantine will be taken twice each day. Participants who complete the 12-week trial will enter a 2-week lead-out phase, during which they will be tapered back to a placebo in a single-blind manner. Weekly psychotherapy sessions will continue until the end of Week 14.

Inclusion Criteria:

• Meets DSM-IV criteria for current cocaine dependence
• Use of cocaine at least four days in the month prior to enrollment or episodic cocaine binges of at least $200 worth at least twice each month (confirmed by urine toxicology test)

Exclusion Criteria:

• Meets DSM-IV criteria for major depression, bipolar disorder, schizophrenia, or any psychotic disorder other than transient psychosis due to drug abuse
• History of seizures in the two years prior to enrollment
• History of seizures related to current substance abuse (including cocaine, alcohol, or benzodiazepine)
• History of an allergic reaction to memantine
• Chronic organic mental disorder
• Current significant suicidal risk, history of significant suicidal behavior, or any suicide attempt within the year prior to enrollment
• Pregnant or breastfeeding
• Failure to use adequate contraception
• Unstable physical disorders that might make participation hazardous, such as hypertension, acute hepatitis (individuals with chronic mildly elevated transaminase levels at 2 to 3 times the upper normal limit are not excluded if their PT/PTT is normal), renal impairment, or diabetes
• Current coronary vascular disease, or suspected by an abnormal ECG or history of cardiac symptoms
• Cardiac conduction system disease, as indicated by QRS duration greater than 0.11
• History of failure to respond to a previous trial with memantine
• Currently meets DSM-IV criteria for substance dependence or abuse disorder other than nicotine or marijuana
• Currently taking psychotropic medications, excluding zolpidem or trazodone for insomnia

participants who had achieved abstinence during the lead-in remained abstinent throughout the trial and there was little relapse-like behavior for a medication to address.