ABSTRACT Substance use disorders (SUDs) are chronic, relapsing conditions characterized by significant neurobiological and behavioral disruptions. Emerging evidence highlights the critical roles of oxidative stress, mitochondrial dysfunction, and neuroinflammation in the pathophysiology of drug misuse. Coenzyme Q10 (CoQ10), a mitochondrial cofactor with potent antioxidant and anti-inflammatory properties, has gained attention as a potential adjunctive therapy for managing substance-related neurotoxicity. This review explores the mechanistic role of CoQ10 in mitigating the oxidative damage and neuroinflammation induced by substances misuse, emphasizing its ability to restore mitochondrial function and support neuronal health. Preclinical studies demonstrate that CoQ10 supplementation reduces apoptosis, preserves neurotransmitter systems, and improves behavioral outcomes in models of cocaine, alcohol, nicotine, and opioid addiction. Clinical evidence, though limited, suggests CoQ10’s safety and therapeutic potential in oxidative stress-related conditions, reinforcing its relevance to addiction. Despite these promising findings, challenges such as low bioavailability and the lack of SUD-specific clinical trials remain significant barriers. This review underscores the need for further research to optimize CoQ10’s formulation, dosing strategies, and clinical applications in the treatment of SUDs. Integrating CoQ10 into multidisciplinary approaches could advance our ability to address the complex neurobiological challenges of SUDs and improve long-term recovery outcomes.

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