title: γ-Amino butyric acid and glutamate abnormalities in adolescent chronic marijuana smokers.
abstract: 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.
authors.affiliation: Brain Institute, University of Utah School of Medicine, Salt Lake City, UT 84108, USA. andrew.prescot@utah.edu
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Prescot
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Yurgelun-Todd
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008385:Marijuana Smoking / Q000009:adverse effects* / Q000378:metabolism*; D013997:Time Factors; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid