Ketamine impairs response inhibition and is positively reinforcing in healthy volunteers: a dose-response study

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has medical indications but is also used as a recreational drug. Previous research has found persisting cognitive and psychotogenic effects of ketamine in chronic abusers of this drug 3 days after an acute dose.

The present study aimed to investigate the effects of ketamine on two processes related to drug abuse, response inhibition and reinforcement, and to examine whether an acute dose of ketamine produced residual cognitive effects in healthy volunteers.

Fifty-four healthy volunteers were given an 80-min infusion of one of two doses (0.4, 0.8 mg kg(-1)) of ketamine or placebo. Subjects completed a battery of tests at three time points: pre-infusion, during the infusion and 3 days later at follow-up. The battery consisted of tests of episodic and semantic memory, schizophrenic-like and dissociative symptoms, response inhibition and measures of subjective effects, including mood, bodily symptoms and enjoyment of and desire for the drug.

Ketamine acutely impaired response inhibition and had related biphasic effects on the subjective reinforcing effects of the drug. Ketamine also acutely impaired episodic but not semantic memory and increased schizophrenic-like and dissociative symptoms. No residual cognitive effects were observed 3 days following an acute dose.

The lack of residual effects in healthy volunteers on day 3 indicates that impairments found on day 3 in ketamine abusers are chronic effects. The abuse of ketamine may be related to its capacity both to reinforce and to decrease response inhibition.