LAUSR

BACKGROUND Abuse of methamphetamine (MA) is a global health concern. Previous 1H-MRS studies have found that, with methamphetamine abstinence (MAA), there are changes in n-acetyl-aspartate (NAA/Cr), myo-inositol (mI/Cr), choline (Cho/Cr and Cho/NAA), and glutamate with glutamine (Glx) metabolites. Limited studies have investigated the effect of acute MAA, and acute-to-short-term MAA on brain metabolites. METHODS Adults with chronic MA dependence (n = 31) and healthy controls (n = 22) were recruited. Two-dimensional chemical shift 1H-MRS imaging (TR2000 ms, TE30 ms) slice was performed and included voxels in bilateral anterior-cingulate (ACC), frontal-white-matter (FWM), and dorsolateral-prefrontal-cortices (DLPFC). Control participants were scanned once. The MA group was scanned twice, with acute (1.5 ± 0.6 weeks, n = 31) and short-term MAA (5.1 ± 0.8 weeks, n = 22). The change in 1H-MRS metabolites over time (n = 19) was also investigated. Standard 1H-MRS metabolites are reported relative to Cr + PCr. RESULTS Acute MAA showed lower n-acetyl-aspartate (NAA) and n-acetyl-aspartate with n-acetyl-aspartyl-glutamate (NAA + NAAG) in left DLPFC, and glycerophosphocholine with phosphocholine (GPC + PCh) in left FWM. Short-term MAA showed lower NAA + NAAG and higher myo-inositol (mI) in right ACC, lower NAA and NAA + NAAG in the left DLPFC, and lower GPC + PCh in left FWM. Over time, MAA showed decreased NAA and NAA + NAAG and increased mI in right ACC, decreased NAA and NAA + NAAG in right FWM, and decreased in mI in left FWM. CONCLUSION In acute MAA, there was damage to the integrity of neuronal tissue, which was enhanced with short-term MAA. From acute to short-term MAA, activation of neuroinflammatory processes are suggested. This is the first 1H-MRS study to report the development of neuroinflammation with loss of neuronal integrity in MAA.