Ethanol-like effects of thiopental and ketamine in healthy humans

Abstract

The γ-aminobutyric acid-A (GABAA) and N-methyl-D-aspartate (NMDA) receptors mediate aspects of the behavioural effects of alcohol. Prior studies reported drugs that block NMDA receptors or facilitate GABAA receptor function produce ethanol-like effects in humans. The purpose of this study was to compare the ethanol-related effects of two pharmacological agents with known NMDA and GABAA receptor activity. As part of an ongoing, larger study, 28 subjects (age, 21–30) with no personal or family histories of alcoholism were administered subanesthetic doses of the GABAA receptor agonist thiopental, the NMDA receptor antagonist, ketamine and placebo on three separate test days. Various ethanol-related measures were administered. At doses of thiopental and ketamine that produced similar levels of sedation and cognitive effects, both agents produced significant ethanol-like effects and subjective intoxication. However, the intensity of the ethanol-like effects of ketamine was greater than that of thiopental. In addition, ketamine produced alterations in perception that were not produced by thiopental. These data provide further support for a model where GABAA receptor facilitation may contribute significantly to ethanol effects associated with social drinking, whereas NMDA receptor antagonism may contribute to relatively greater extent to features of ethanol ‘intoxication’.

Characterization of the Interactive Effects of Glycine and D-Cycloserine in Men: Further Evidence for Enhanced NMDA Receptor Function Associated with Human Alcohol Dependence

“…The principal findings of this study were that DCS 1000 mg produced subjective effects that were similar to the effects of one standard ethanol drink, a finding previously reported for low doses of NMDA receptor antagonists (Dickerson et al, 2010;Krystal et al, 1998c). These effects were blunted in ethanol-dependent patients.…”

Suicide by hanging under the influence of ketamine and ethanol

“…In fact, post mortem studies of brain tissue suggest that certain subunits of NMDA receptors are increased in cortical structures of ethanol-dependent individuals suggesting a compensatory ''upregulation'' in the NMDA receptor number or function in response to ethanol inhibition of these receptors [35,36]. Moreover, NMDA receptor antagonism by ketamine has been shown to act synergistically with ethanol [37]. Therefore, the interaction between ethanol and ketamine should be considered in the interpretation of the forensic toxicological results, when these two compounds are present.…”

Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment

“…As an antagonist of NMDA receptor similar to ketamine, ethanol produces less psychotic symptoms in healthy humans. Although the coupling effects between ketamine and ethanol are still not well established (Dickerson et al, 2010), it is believed that there may be possible interactions as they both act on the NMDA receptors. To study the interactions between ethanol and ketamine, the same fMRI test was repeated on the same ketamine users who consumed alcohol an hour before the start of the fMRI test.…”