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There is no data on whether MA use may cause AGE\u2013RAGE stress or whether the latter is associated with MIP. This case\u2013control study recruited 60 patients with MA use disorder and 30 normal controls and measured serum levels of oxidative stress toxicity (OSTOX, lipid peroxidation), antioxidant defences (ANTIOX), magnesium, copper, atherogenicity, AGE and soluble RAGE (sRAGE) and computed a composite reflecting AGE\u2013RAGE axis activity. MA dependence and use were associated with elevated levels of AGE, sRAGE, OSTOX\/ANTIOX, Castelli Risk Index 1 and atherogenic index of plasma. Increased sRAGE concentrations were strongly correlated with dependence severity and MA dose. Increased AGE\u2013RAGE stress was correlated with OSTOX, OSTOX\/ANTIOX and MA\u2010induced intoxication symptoms, psychosis, hostility, excitement and formal thought disorders. The regression on AGE\u2013RAGE, the OSTOX\/ANTIOX ratio, decreased magnesium and increased copper explained 54.8% of the variance in MIP symptoms, and these biomarkers mediated the effects of increasing MA concentrations on MIP symptoms. OSTOX\/ANTIOX, AGE\u2013RAGE and insufficient magnesium were found to explain 36.0% of the variance in the atherogenicity indices. MA causes intertwined increases in AGE\u2013RAGE axis stress and oxidative damage, which together predict the severity of MIP symptoms and increased atherogenicity.<\/jats:p>","DOI":"10.1111\/adb.13333","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T06:19:27Z","timestamp":1695363567000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Increased AGE\u2013RAGE axis stress in methamphetamine abuse and methamphetamine\u2010induced psychosis: Associations with oxidative stress and increased atherogenicity"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-5196","authenticated-orcid":false,"given":"Hussein Kadhem","family":"Al\u2010Hakeim","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Science University of Kufa  Kufa Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazin 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