Decreased frontal N-acetylaspartate levels in adolescents concurrently using both methamphetamine and marijuana

Abstract

Introduction The potential neurochemical toxicity associated with methamphetamine (MA) or marijuana (MJ) use on the developing adolescent brain is unclear, particularly with regard to individuals with concomitant use of MA and MJ (MA+MJ). In this study, proton magnetic resonance spectroscopy (MRS) was utilized to measure in vivo brain N-acetylaspartate plus N-acetylaspartyl glutamate (tNAA, an indicator of intact neuronal integrity) levels. Methods Three adolescent groups from Cape Town, South Africa completed MRS scans as well as clinical measures including a drug use history. Subjects included (1) nine MA (age = 15.7 ± 1.37), (2) eight MA+MJ (age = 16.2 ± 1.16) using adolescents and (3) ten healthy controls (age = 16.8 ± 0.62). Single voxel spectra were acquired from midfrontal gray matter using a point-resolved spectroscopy sequence (PRESS). The MRS data were post-processed in the fully automated approach for quantitation of metabolite ratios to phosphocreatine plus creatine (PCr+Cr). Results A significant reduction in frontal tNAA/PCr+Cr ratios was seen in the MA+MJ group compared to the healthy controls (p = 0.01, by 7.2 %) and to the MA group (p = 0.04, by 6.9 %). Significant relationships were also observed between decreased tNAA/PCr+Cr ratios and drug use history of MA or MJ (total cumulative lifetime dose, age of onset, and duration of MA and MJ exposure) only in the MA+MJ group (all p < 0.05). Conclusions These findings suggest that in adolescents, concomitant heavy MA+MJ use may contribute to altered brain metabolites in frontal gray matter. The significant associations between the abnormal tNAA/PCr+Cr ratios and the drug use history suggest that MA+MJ abuse may induce neurotoxicity in a dose-responsive manner in adolescent brain.

Imaging Biomarkers of the Neuroimmune System among Substance Use Disorders: A Systematic Review

“…Among studies that reported group differences, higher myo- inositol levels were most reliably observed in the frontal cortex [124, 190-197]. Among studies that did not report a difference, methamphetamine/MDMA subjects tended to use less frequently than those reporting group differences [198, 201, 202, 204, 207]. …”

Peer drug use and adolescent polysubstance use: Do parenting and school factors moderate this association?

“…In addition, adolescents may be particularly vulnerable to the interactive and neurotoxic effects of polysubstance use (Connor et al, 2014;Sung et al, 2013).…”

Neurobiological signatures associated with alcohol and drug use in the human adolescent brain

“…An investigation of ACC metabolites identified lower NAA, Glu, Cr, and myo-I in marijuana users (Prescot et al, 2011), as well as low ACC GABA, and replicated findings of lower reduced NAA, Cr, and myo-I published in a subsequent study (Prescot et al, 2013). Adolescents with combined use of methamphetamine and marijuana also demonstrated lower ACC NAA, beyond effects observed in methamphetamine users alone, with no differences in other metabolites (Sung et al, 2013). Cumulative lifetime marijuana exposure and earlier age of onset were associated with lower NAA levels.…”