Evidence for long-term neurotoxicity associated with methamphetamine abuse- A H-1 MRS study

Objective: To determine whether proton MRS (H-1 MRS) can detect long-term m etabolite abnormalities in abstinent methamphetamine users. Background: Met hamphetamine is toxic to dopaminergic and serotonergic neurons in rodents; however, little data are available on the toxic effects of methamphetamine on the human brain. Methods: H-1 MRS was performed in 26 abstinent methamph etamine abusers with a history of methamphetamine dependence (median total cumulative lifetime exposure, 3,640 g; median recency of last methamphetami ne use, 4.25 months) and 24 healthy subjects without a history of drug abus e. Cerebral metabolite concentrations on H-1 MRS were measured in the front al cortex, frontal white matter, and basal ganglia. Results: The concentrat ion of N-acetylaspartate ([NA]), a neuronal marker, was reduced significant ly (-5 to -6%) in the basal ganglia and frontal white matter of methampheta mine users compared with control subjects. The frontal white matter [NA] co rrelated inversely with the logarithm of the lifetime methamphetamine use. The methamphetamine users also showed significantly reduced total creatine in the basal ganglia (-8%), and increased choline-containing compounds ([CH O], +13%) and myo-inositol ([MI], +11%) in the frontal grey matter. Conclus ions: The reduced [NA] on H-1 MRS provides evidence for long-term neuronal damage in abstinent methamphetamine users.