Background: Amphetamine and cannabis use disorders are common due to recreational use and are linked to altered metabolomic and proteomic profiles. Chronic exposure to these substances may affect human physiological functions. Since serum electrolytes play a key role in these functions, this study aimed to investigate the effects of single or combined use of amphetamine and/or cannabis on serum electrolyte levels. Methods: Blood electrolyte and kidney function parameters were measured using clinical chemistry and immunoassay techniques. Serum oxidative stress markers (catalase and superoxide dismutase (SOD)) were also analyzed. Participants were divided into four groups: controls, cannabis users, amphetamine users, and cannabis-amphetamine users. Results: No significant differences in kidney function were observed across the groups. However, phosphorus levels were elevated in the cannabis (t = 4.748, p < 0.001), amphetamine (t = 2.933, p < 0.05), and cannabis-amphetamine(t =3.364, p < 0.05)groups compared to controls. Moreover, sodium (t = 3.931, p < 0.01), chloride (t = 3.382, p < 0.05), and calcium (t = 3.391, p < 0.05) levels were significantly higher in the cannabis group compared to the control group. Patients with amphetamine (t = 4.311, p < 0.001) or cannabis (t = 4.738, p < 0.001) use disorder showed reduced catalase levels, with more pronounced reductions in those with combined use (t = 8.700, p < 0.0001). As compared to controls, serum SOD levels were also lower in patients with amphetamine (t = 6.957, p < 0.0001) or cannabis (t = 6.600, p < 0.0001) use disorder, with the greatest reduction observed in the combined-use group (t = 12.11, p < 0.0001). Conclusions: Cannabis use disorder is associated with alterations in serum electrolytes while serum creatinine and urea levels remained within the measured range. Co-use of amphetamine and cannabis was associated with greater oxidative stress than the use of either drug alone. Further studies are needed to explore the molecular mechanisms involved in these changes.
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