Concurrent downregulation of TAAR1 and NQO1 in individuals with isolated methamphetamine use: Implications for dopaminergic and oxidative stress-related biology.

BACKGROUND: Methamphetamine use disorder (MUD) is associated with profound neurobiological alterations involving dopaminergic dysregulation and oxidative stress. However, reliable molecular biomarkers reflecting these alterations remain limited. This study aimed to investigate the expression levels of trace amine-associated receptor 1 (TAAR1) and NAD(P)H quinone oxidoreductase 1 (NQO1) genes in individuals with methamphetamine use and to evaluate their potential as candidate molecular indicators. METHODS: A case-control study was conducted including individuals with methamphetamine use and a control group without substance use. Peripheral blood samples were collected, and gene expression levels of TAAR1 and NQO1 were quantified using quantitative real-time PCR. Relative expression levels were evaluated using ΔCt values, and fold changes were calculated using the 2^-ΔΔCt method. Group comparisons and effect sizes were analyzed to assess the magnitude and consistency of differences. RESULTS: Both TAAR1 and NQO1 expression levels were significantly reduced in the methamphetamine group compared to controls (p < 0.001). Increased ΔCt values indicated marked downregulation of both genes. The magnitude of differences was substantial, with large effect sizes observed for both TAAR1 and NQO1. These findings indicate concurrent downregulation of transcripts related to dopaminergic regulation and to the oxidative stress response in methamphetamine users. CONCLUSIONS: The observed downregulation of TAAR1 and NQO1 indicates concurrent transcriptional alterations in genes involved in dopaminergic regulation and antioxidant defense. Because these measurements were obtained at the transcript level, they cannot be equated with a reduction in enzymatic antioxidant capacity. These genes may represent candidate peripheral molecular indicators; however, their temporal and clinical significance requires validation in longitudinal and independent cohorts.