Objective: Ethanol blocks N-methyl-d-aspartic acid (NMDA) glutamate receptors. Increased NMDA receptor function may contribute to motivational disturbances that contribute to alcoholism. The authors assessed whether the NMDA receptor antagonist memantine reduces cue-induced alcohol craving and produces ethanol-like subjective effects.
Method: Thirty-eight alcohol-dependent inpatients participated in three daylong testing sessions in a randomized order under double-blind conditions. On each test day, subjects received 20 mg of memantine, 40 mg of memantine, or placebo, and subjective responses to treatment were assessed. The level of alcohol craving was assessed before and after exposure to an alcohol cue.
Results: Memantine did not stimulate alcohol craving before exposure to an alcohol cue, and it attenuated alcohol cue-induced craving in a dose-related fashion. It produced dose-related ethanol-like effects without adverse cognitive or behavioral effects.
Conclusions: These data support further exploration of whether well-tolerated NMDA receptor antagonists might have a role in the treatment of alcoholism.