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

IntroductionThe 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.MethodsThree 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).ResultsA 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).ConclusionsThese 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.

► Frontal gray matter tNAA/PCr + Cr ratios were reduced in adolescents using MA + MJ.
► Total lifetime amount of MA + MJ had a significant negative correlation with tNAA/PCr + Cr.
► Duration of MA + MJ use showed a significant negative correlation with tNAA/PCr + Cr.
► Earlier age of onset of MA + MJ use had negative impacts on tNAA/PCr + Cr in adolescents.