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As previously explained, long-term methamphetamine induced effects are the result of a neurodegeneration of the dopaminergic system (Schep et al., There are three main biotransformation pathways (see Figure 2) involved in methamphetamine metabolic clearance: (1) N-demethylation to produce amphetamine, (2) aromatic hydroxylation producing 4-hydroxymethamphetamine (pholedrine) with both reactions partially regulated by CYP2D6 (Lin et al., Methamphetamine and CYP2D6 pharmacogenetics A review of the current literature for genetic-association studies of methamphetamine use disorders, including 38 studies and 39 genes, showed that 18 genes were found to have a significant genotypic, allelic, and/or haplotypic association