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

Malhotra AK, Pinals DA, Weingartner H, Sirocco K,
Missar CD, Pickar D, Breier A.
Experimental Therapeutics Branch,
National Institute of Mental Health,
Bethesda, MD 20892, USA.
Neuropsychopharmacology. 1996 May;14(5):301-7.


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.

NMDA receptors
Ketamine and memory
Ketamine and the nucleus accumbens
Ketamine: medical and non-medical use
The role of ketamine in pain management
Low-dose ketamine as a fast-onset, long-acting antidepressant