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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.

One of the most prominent hallmarks of cancer cells is their dependency on the glycolytic pathway for energy production. As a potent inhibitor of glycolysis, 2-deoxy-d-glucose (2DG) has been proposed for cancer treatment and extensively investigated in clinical studies. Moreover, 2DG has been reported to interfere with other biological processes including glycosylation. To further understand the overall effect of and metabolic alteration by 2DG, we performed biochemical and metabolomics analyses on oral squamous cell carcinoma cell lines. In this study, we found that 2DG more effectively reduced glucose consumption and lactate level in SCC15 cells than in SCC4 cells, which are less dependent on glycolysis. Coincidentally, 2DG impaired N-linked glycosylation of the key oncogenic receptors Axl and Met in SCC15 cells, thereby reducing the cell viability and colony formation ability. The impaired processes of glycolysis and N-linked glycosylation were restored by exogenous addition of pyruvate and mannose, respectively. Additionally, our targeted metabolomics analysis revealed significant alterations in the metabolites, including amino acids, biogenic amines, glycerophospholipids, and sphingolipids, caused by the impairment of glycolysis and N-linked glycosylation. These observations suggest that alterations of these metabolites may be responsible for the phenotypic and metabolic changes in SCC15 cells induced by 2DG. Moreover, our data suggest that N-linked glycosylation of Axl and Met may contribute to the maintenance of cancer properties in SCC15 cells. Further studies are needed to elucidate the roles of these altered metabolites to provide novel therapeutic targets for treating human oral cancer.