Metabolomics is a powerful tool used in the description of metabolic system perturbations caused by diseases or abnormal conditions, and it usually involves qualitative and/or quantitative metabolome determination, accompanied by bioinformatics assessment. Methamphetamine is a psychostimulant with serious abuse potential and due to the absence of effective pharmacotherapy and a high recurrence potential, methamphetamine addiction is a grave issue. Moreover, its addiction mechanisms remain unclear, probably due to the lack of experimental models that reflect personal genetic variances and environmental factors determining drug addiction occurrence. The metabolic approach is only recently being used to study the metabolic effects induced by a variety of methamphetamine exposure statuses, in order to investigate metabolic disturbances related to the adverse effects and discover potential methamphetamine addiction biomarkers. To provide a critical overview of methamphetamine-associated metabolic changes revealed in recent years using the metabolomics approach, we discussed methamphetamine toxicity, applications of metabolomics in drug abuse and addiction studies, biological samples used in metabolomics, and previous studies on metabolic alterations in a variety of biological samples—including the brain, hair, serum, plasma, and urine—following methamphetamine exposure in animal studies. Metabolic alterations observed in animal brain and other biological samples after methamphetamine exposure were associated with neuronal and energy metabolism disruptions. This review highlights the significance of further metabolomics studies in the area of methamphetamine addiction research. These findings will contribute to a better understanding of metabolic changes induced by methamphetamine addiction progress and to the design of further studies targeting the discovery of methamphetamine addiction biomarkers and therapeutic targets.
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