Acute effects of memantine in combination with alcohol in moderate drinkers

Rationale. Alcohol effects in humans involve N-methyl-L-aspartate (NMDA) receptor-mediated glutamatergic neurotransmission. It has been proposed that NMDA receptor antagonists may be effective in the treatment of alcohol dependence. Objective. This study evaluated the acute effects of memantine, an NMDA receptor antagonist, on the subjective, physiological, and performance effects of alcohol in moderate (10-30 drinks per week) alcohol drinkers. Methods. Eighteen volunteers without alcohol dependence were tested using a double-blind design with three 3-day long inpatient phases separated by at least a 2-week wash-out period. Memantine (0, 15, and 30 mg) was administered 4 h before alcohol (1.5 g/l body water), which was given in four divided doses every 20 min. Results. Pretreatment with memantine attenuated the craving for alcohol before alcohol administration, but not after alcohol was given. Memantine increased the dissociative effects of alcohol, without altering its sedative, stimulant, and overall intoxicating effects. Memantine also did not affect alcohol-induced impairment in performance, physiological changes, or pharmacokinetics. Memantine increased subjective reports of dissociation, confusion, and stimulation, and impaired motor coordination on the balance task. Conclusions. Memantine was well tolerated in combination with alcohol. The findings suggest that NMDA receptor neurotransmission may be involved in alcohol craving and alcohol-induced subjective dissociative effects.