Neural correlates of verbal learning in adolescent alcohol and marijuana users

Aims Alcohol and marijuana are the most widely used intoxicants among adolescents, yet their potential unique and interactive influences on the developing brain are not well established. Brain regions subserving learning and memory undergo continued maturation during adolescence, and may be particularly susceptible to substance-related neurotoxic damage. In this study, we characterize brain response during verbal learning among adolescent users of alcohol and marijuana. Design Participants performed a verbal paired associates encoding task during functional magnetic resonance imaging (fMRI) scanning. Setting Adolescent subjects were recruited from local public schools and imaged at a university-based fMRI center. Participants Participants were 74 16-18-year-olds, divided into four groups: (i) 22 controls with limited alcohol and marijuana experience, (ii) 16 binge drinkers, (iii) eight marijuana users and (iv) 28 binge drinking marijuana users. Measurements Diagnostic interview ensured that all teens were free from neurological or psychiatric disorders; urine toxicology and breathalyzer verified abstinence for 22-28 days before scanning; a verbal paired associates task was administered during fMRI. Findings Groups demonstrated no differences in performance on the verbal encoding task, yet exhibited different brain response patterns. A main effect of drinking pointed to decreased inferior frontal but increased dorsal frontal and parietal fMRI response among binge drinkers (corrected P<0.05). There was no main effect of marijuana use. Binge drinking×marijuana interactions were found in bilateral frontal regions (corrected P<0.05), where users of either alcohol or marijuana showed greater response than non-users, but users of both substances resembled non-users. Conclusions Adolescent substance users demonstrated altered fMRI response relative to non-using controls, yet binge drinking appeared to be associated with more differences in activation than marijuana use. Alcohol and marijuana may have interactive effects that alter these differences, particularly in prefrontal brain regions.