The Role of Acetaldehyde in Human Psychomotor Function: A Double-Blind Placebo-Controlled Crossover Study

Background: Acetaldehyde, the first product of ethanol metabolization, is a biologically active compound, but the behavioral properties of acetaldehyde in humans are largely undefined. We investigated the acute effects of both alcohol and acetaldehyde on psychomotor functions related to automobile driving skills. Methods: Twenty-four men were selected through genotyping; one-half had the ALDH2*1/*1 (active form) genotype and one-half had the ALDH2*1/*2 (inactive form) genotype. In a double-blind placebo-controlled crossover design, each subject was administered one of the following doses of alcohol: .25 g/kg, .5 g/kg, or .75 g/kg or a placebo in four trials that took place at 1-week intervals. Blood ethanol concentration (BEC) and blood acetaldehyde concentration (BAAC) were measured nine times, and psychomotor function tests (critical flicker fusion threshold, choice reaction time, compensatory tracking task, and digit symbol substitution test) were assessed seven times in total over 4 hours after study drug ingestion. Results: After the consumption of alcohol, BEC was comparable in the two subject groups, whereas BAAC was significantly higher in subjects with ALDH2 *1/*2 than in those with ALDH2 *1/*1. The psychomotor performance of subjects with ALDH2*1/*2 was significantly poorer than that of subjects with ALDH2*1/*1. Significant correlations between psychomotor performance and both BEC and BAAC were observed. However, in the linear regression analysis, BAAC significantly predicted poorer psychomotor performance, whereas BEC was not associated with any measure of psychomotor function. Conclusions: Acetaldehyde might be more important than alcohol in determining the effects on human psychomotor function and skills.