Effects of substance use disorder on oxidative and antioxidative stress markers: A systematic review and meta‐analysis

Recently, it has been suggested that central and peripheral toxicities identified in persons with substance use disorder (SUD) could be partially associated with an imbalance in reactive oxygen species and antioxidant defenses. We conducted a systematic review and meta‐analysis to investigate whether SUD is associated with oxidative stress and to identify biomarkers possibly more affected by this condition. We have included studies that analysed oxidant and antioxidant markers in individuals with SUD caused by stimulants, alcohol, nicotine, opioids, and others (cannabis, inhalants, and polysubstance use). Our analysis showed that persons with SUD show higher oxidant markers and lower antioxidant markers than healthy controls. SUD was associated specifically with higher levels of oxidant markers malondialdehyde, thiobarbituric acid reactive substances and lipid peroxidation. Conversely, the antioxidant superoxide dismutase and the total antioxidant capacity/status were lowered in the SUD group. A meta‐regression analysis revealed that persons with alcohol use disorder had higher oxidative stress estimates than those with stimulant use disorder. Moreover, individuals evaluated during abstinence showed smaller antioxidant effect sizes than non‐abstinent ones. Our findings suggest a clear oxidative imbalance in persons with SUD, which could lead to cell damage and result in multiple associated comorbidities, particularly accelerated aging.