In search of a new pharmacological treatment for drug and alcohol addiction: N-methyl-D-aspartate (NMDA) antagonists

Abstract

The most challenging aspect of treating alcohol and drug addiction is the relapsing course of these disorders. Although substitution therapies for nicotine and opioid dependence have proven to be relatively effective, there is a need for new pharmacotherapies designed to decrease the frequency and severity of relapse. The aim of this paper is to provide an overview of the potential utility of N-methyl-D-aspartate (NMDA) receptor antagonists as treatments for substance abuse as shown in preclinical models and preliminary clinical trials. It is hypothesized that NMDA receptors mediate the common adaptive processes that are involved the development, maintenance, and expression of drug and alcohol addiction. Modulation of glutamatergic neurotransmission with NMDA receptor antagonists offers a novel treatment approach. It is proposed that NMDA antagonists may have multiple functions in treating addictions, including an attenuation of withdrawal effects, normalization of the affective changes following initiation of abstinence which arise from neurochemical changes resulting from chronic addiction, and an attenuation of conditioned responses arising from drug-related stimuli.