Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

Zoethout, R. W. M.; Delgado, Wilson L.; Ippel, Annelies E.; Dahan, Albert; van Gerven, Joop · 2010 · OpenAlex-citations

DOI: 10.1111/j.1365-2125.2010.03846.x

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Summary

This review addresses the lack of standardized, sensitive functional biomarkers for assessing the acute central nervous system (CNS) effects of alcohol in healthy volunteers. While ethanol causes dose-dependent CNS depression via mechanisms involving GABA-A and NMDA receptors, the sensitivity of existing tests has not been systematically ascertained, and dose-response relationships are rarely reported. The authors aimed to identify the most useful tests for detecting acute alcohol effects, which is critical for future drug-alcohol interaction studies and regulatory assessments. The researchers conducted a structured literature search of MedLine for studies published between 1980 and 2008 involving healthy adults (19–44 years). They excluded studies involving chronic effects, withdrawal, specific patient populations, or interactions with other drugs. From an initial pool of 1,263 publications, 218 studies describing 342 different tests were selected. These tests were grouped into clusters and broader CNS domains (e.g., attention, memory, motor function, subjective effects). The effect of alcohol on each test was scored as improvement (+), impairment (–), or no effect (=). Alcohol concentrations were categorized into lower, medium (0.5–0.7 g/l), and higher levels to evaluate dose-response relationships. The analysis revealed that alcohol primarily caused functional impairments or no significant change, with few improvements. The most sensitive functional biomarkers for acute alcohol effects were identified as divided attention, focused attention, visuo-motor control, and subjective scales measuring "feeling high" and drug effects. Impairments were also pronounced in motor control, postural stability, and immediate auditory/verbal memory. Conversely, tests measuring language production, semantics, and certain subjective scales (e.g., aggression, calmness) showed little to no effect. Dose-response analysis indicated that divided attention, "scale high," and "scale drug effect" were sensitive even at low alcohol concentrations. Focused attention showed a clear dose-dependent impairment, with the proportion of impaired tests rising from 7% at low concentrations to 62% at medium concentrations. The study concludes that the wide diversity of CNS tests used in alcohol research hinders the identification of sensitive biomarkers. By establishing that specific domains—particularly divided attention, focused attention, visuo-motor control, and subjective intoxication scales—are the most reliable indicators of acute alcohol effects, this review provides a rational basis for selecting biomarkers in future pharmacological studies. These findings help standardize the assessment of alcohol’s CNS impact and improve the design of drug-alcohol interaction trials.

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• alcohol