Altered NMDA Glutamate Receptor Antagonist Response in Recovering Ethanol-Dependent Patients

John H. Krystal, Ismene L. Petrakis, Diana Limoncelli, Elizabeth Webb, Ralitza Gueorgueva, D. Cyril D'Souza, Nashaat N. Boutros, Louis Trevisan, Dennis S. Charney

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


Ethanol is an antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor. Ethanol dependence upregulates NMDA receptors and contributes to crosstolerance with selective NMDA receptor antagonists in animals. This study evaluated whether recovering ethanol-dependent patients show evidence of a reduced level of response to the effects of the NMDA receptor antagonist, ketamine. In this double-blind study, 34 recently detoxified alcohol-dependent patients and 26 healthy comparison subjects completed 3 test days involving a 40-min infusion of saline, ketamine 0.1 mg/kg, or ketamine 0.5 mg/kg in a randomized order. Recovering ethanol-dependent patients showed reduced perceptual alterations, dysphoric mood, and impairments in executive cognitive functions during ketamine infusion relative to the healthy comparison group. No attenuation of ketamine-induced amnestic effects, euphoria, or activation was observed. The alterations in NMDA receptor function observed in recovering ethanol-dependent patients may have important implications for ethanol tolerance, ethanol dependence, and the treatment of alcoholism.

Original languageEnglish
Pages (from-to)2020-2028
Number of pages9
Issue number11
StatePublished - Nov 2003
Externally publishedYes


  • Alcoholism
  • Ethanol
  • Ethanol dependence
  • Executive cognitive function
  • Glutamate
  • N-methyl-D-aspartate (NMDA)
  • Psychosis
  • Reward
  • Tolerance


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