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Dose-Related Ethanol-like Effects of the NMDA Antagonist, Ketamine, in Recently Detoxified Alcoholics
John H. Krystal, MD;
Ismene L. Petrakis, MD;
Elizabeth Webb;
Ned L. Cooney, PhD;
Laurence P. Karper, MD;
Sheila Namanworth;
Philip Stetson, PhD;
Louis A. Trevisan, MD;
Dennis S. Charney, MD
Arch Gen Psychiatry. 1998;55:354-360.
Background This study evaluated the dose-related ethanol-like subjective effects of the N -methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine hydrochloride in recently detoxified alcoholics.
Methods Twenty male inpatients meeting DSM-III-R criteria for alcohol dependence and who had not consumed alcohol for 10 to 27 days prior to the study completed 3 test days that involved the intravenous infusion of ketamine hydrochloride (0.1 mg/kg or 0.5 mg/kg) or saline solution under randomized double-blind conditions. Ethanol-like subjective effects were assessed using the Sensation Scale; the Biphasic Alcohol Effects Scale; visual analog scales to measure "high" and degree of similarity to ethanol, cocaine, and marijuana; a scale assessing the number of standard alcohol drinks producing similar subjective effects; and visual analog scales measuring ethanol craving.
Results Ketamine produced dose-related ethanol-like effects on each scale measuring its similarity to ethanol. Its effects were more similar to the sedative or descending limb effects of ethanol than to the stimulant or ascending limb effects. Ketamine effects also were more like ethanol than marijuana or cocaine. Ethanol-like effects were more prominent at the higher ketamine dose, a dose rated as similar to greater levels of ethanol intoxication. However, ketamine did not increase craving for ethanol.
Conclusion The production of ethanol-like subjective effects by ketamine supports the potential clinical importance of NMDA receptor antagonism among the mechanisms underlying the subjective effects of ethanol in humans.
From the Department of Psychiatry, Yale University School of Medicine and the Veterans Affairs–Yale University Alcoholism Research Center, West Haven, Conn (Drs Krystal, Petrakis, Cooney, Karper, Trevisan, and Charney and Mss Webb and Namanworth); and the Upjohn Research Institute, Department of Pharmacology, University of Michigan Medical School, Ann Arbor (Dr Stetson).
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