Neurochemical and Genetic Alterations in Chronic Stimulant (Crystal and Captagon) Users: A Comparative Analysis of Monoamine Biomarkers and Addiction-Related Gene Expression.

This investigation examined the long-term impact of stimulant use, assessing systematic dysfunction of the nervous system and how these changes were reflected in the gene expression of two addiction-related genes, SLC6A3 (dopamine transporter) and CARTPT (cocaine- and amphetamine-regulated transcript). Study subjects included 100 men over the age of 18 who have used stimulants (crystal and Captagon) as well as a group of 30 men of the same age who were healthy. Blood samples were taken from each subject, and plasma levels of dopamine, serotonin, norepinephrine, and total protein were measured using enzyme-linked immunosorbent assay (ELISA). Gene expression was analyzed in peripheral blood mononuclear cells (PBMCs) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Relative expression of SLC6A3 and CARTPT was calculated using the 2-ΔΔCt method with GAPDH serving as an internal control. Stimulant users had significantly higher concentrations of plasma dopamine and norepinephrine compared to non-users, while also having much lower levels of both plasma serotonin and total protein compared to controls (p < 0.0001). qRT-PCR showed that the expression of SLC6A3 and CARTPT was significantly increased in the stimulant group (5-7-fold increase). These findings, which reflect both biochemical and gene expression level changes, indicate increased dopaminergic activity, decreased serotonergic activity, and changes in the neuropeptide pathways related to stress and reward due to chronic use of stimulants. Overall, the combination of the biochemical and gene expression data indicates that chronic crystal and Captagon users demonstrate significant systemic dysfunction. The significant changes in the levels of monoamines and the activation of the SLC6A3 and CARTPT genes indicate that these two genes could serve as peripheral biomarkers in assessing stimulant use disorder. These data give a mechanistic basis for developing new diagnostic and treatment methods based on dopaminergic and neuropeptide signaling pathways involved in the use of stimulants.