NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers

Neuropsychopharmacology. 1996 May;14(5):301-7. doi: 10.1016/0893-133X(95)00137-3.


A rapidly growing body of preclinical data has implicated the glutamatergic N-methyl-d-aspartate (NMDA) receptor in memory and other cognitive processes. There is comparatively less information about this receptor system in human cognition. We examined the effects of subanesthetic doses of ketamine, a noncompetitive NMDA receptor antagonist, on two forms of memory, free recall and recognition, as well as attention and behavior in a double-blind, placebo-controlled, 1-hour infusion in 15 healthy volunteers. Ketamine produced decrements in free recall, recognition memory, and attention. In addition, ketamine induced a brief psychosis in our healthy volunteers marked by thought disorder and withdrawal-retardation. Ketamine-induced memory impairments were not accounted for by changes in subject's attention and were not significantly related to psychosis ratings. These data suggest that the NMDA receptor plays a direct role in two types of explicit memory. The implications of these data for the pathophysiology of schizophrenia are discussed.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Cognition / drug effects*
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Female
  • Humans
  • Ketamine / pharmacology*
  • Male
  • Memory / drug effects*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*


  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine