Effects of alcohol and combined marijuana and alcohol use during adolescence on hippocampal volume and asymmetry.

Background: Converging lines of evidence suggest that the hippocampus may be particularly vulnerable to deleterious effects of alcohol and marijuana use, especially during adolescence. The goal of this study was to examine hippocampal volume and asymmetry in adolescent users of alcohol and marijuana.

Methods: Participants were adolescent (aged 15-18) alcohol (ALC) users (n=16), marijuana and alcohol (MJ+ALC) users (n=26), and demographically similar controls (n=21). Extensive exclusionary criteria included prenatal toxic exposure, left handedness, and psychiatric and neurologic disorders. Substance use, cognitive, and anatomical measures were collected after at least 2 days of abstinence from all substances.

Results: Adolescent ALC users demonstrated a significantly different pattern of hippocampal asymmetry (p<.05) and reduced left hippocampal volume (p<.05) compared to MJ+ALC users and non-using controls. Increased alcohol abuse/dependence severity was associated with increased right>left (R>L) asymmetry and smaller left hippocampal volumes while marijuana abuse/dependence was associated with increased L>R asymmetry and larger left hippocampal volumes. Although MJ+ALC users did not differ from controls in asymmetry, functional relationships with verbal learning were found only among controls, among whom greater right than left hippocampal volume was associated with superior performance (p<.05).

Conclusions: Aberrations in hippocampal asymmetry and left hippocampal volumes were found for adolescent heavy drinkers. Further, the functional relationship between hippocampal asymmetry and verbal learning was abnormal among adolescent substance users compared to healthy controls. These findings suggest differential effects of alcohol and combined marijuana and alcohol use on hippocampal morphometry and the relationship between hippocampal asymmetry and verbal learning performance among adolescents.