γ-Amino butyric acid and glutamate abnormalities in adolescent chronic marijuana smokers

Background: An increasing body of evidence from neuropsychological and neuroimaging studies suggests that exposure to marijuana throughout adolescence disrupts key cortical maturation processes occurring during this developmental phase. GABA-modulating pharmacologic treatments that elevate brain GABA concentration recently have been shown to decrease withdrawal symptoms and improve executive functioning in marijuana-dependent adult subjects. The goal of this study was to investigate whether the lower ACC glutamate previously reported in adolescent chronic marijuana smokers is associated with lower ACC GABA levels.

Methods: Standard and metabolite-edited proton MRS data were acquired from adolescent marijuana users (N=13) and similarly aged non-using controls (N=16) using a clinical 3T MRI system.

Results: The adolescent marijuana-using cohort showed significantly lower ACC GABA levels (-22%, p=0.03), which paralleled significantly lower ACC glutamate levels (-14%, p=0.01). Importantly, the lower ACC GABA and glutamate levels detected in the adolescent cohort remained significant after controlling for age and sex.

Conclusions: The present spectroscopic findings support functional neuroimaging data documenting cingulate dysfunction in marijuana-dependent adolescents. Glutamatergic and GABAergic abnormalities potentially underlie cingulate dysfunction in adolescent chronic marijuana users, and the opportunity for testing suitable pharmacologic treatments with a non-invasive pharmacodynamic evaluation exists.