In a recent article, Krystal et al1 demonstrated dose-dependent ethanol-like effects in detoxified alcoholic patients induced by ketamine, a high-affinity noncompetitive N-methyl-D-aspartate (NMDA) antagonist. Alcohol has repeatedly been shown to have NMDA antagonistic effects2; however, whether it resembles high-affinity or low-affinity NMDA is not clear. Preclinical drug discrimination studies have shown dextromethorphan, a low-affinity noncompetitive NMDA antagonist, to have effects that overlap with, but do not fully resemble, ketamine.3 Like ketamine, dextromethorphan is not a pure NMDA antagonist, especially since σ binding has been reported.4 The properties of σ receptors and nonopioid non-NMDA receptors are not well understood.
Schütz CG, Soyka M. Dextromethorphan Challenge in Alcohol-Dependent Patients and Controls. Arch Gen Psychiatry. 2000;57(3):291-292. doi:10.1001/archpsyc.57.3.291