Effectiveness of Memantine in Treating Cocaine-Dependent Individuals - 2

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