Original Article | Published:

NMDA Receptor Function and Human Cognition: The Effects of Ketamine in Healthy Volunteers

Neuropsychopharmacology volume 14, pages 301307 (1996) | Download Citation



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 schizophremia are discussed.

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  1. From the Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, MD

    • Anil K Malhotra
    • , Debra A Pinals
    • , C David Missar
    • , David Pickar
    •  & Alan Breier
  2. The Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD

    • Herbert Weingartner
    •  & Karen Sirocco


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Correspondence to Anil K Malhotra.

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