Metformin as a promising therapeutic option for reducing substance withdrawal syndromes: A narrative review

Substance withdrawal syndromes pose significant challenges in addiction treatment, often leading to poor treatment adherence and high relapse rates. This review evaluates metformin's potential as a therapeutic option for substance withdrawal syndromes, focusing on its mechanisms (AMPK activation, neurotransmitter modulation, gut microbiome effects) and clinical implications. Proposed mechanisms of action, including the involvement of signaling pathways, neurotransmitter regulation, and gut microbiome modulation, are also discussed. The study also highlights key areas requiring further investigation, such as the need for well-designed clinical trials, exploration of metformin dosage and treatment duration, and a deeper understanding of the specific molecular pathways underlying metformin's impact on withdrawal syndromes. Preclinical and clinical evidence suggest that metformin alleviates withdrawal symptoms and reduces relapse risk, but further research is needed to optimize dosing and validate efficacy. Overall, this review supports metformin's potential as a promising therapeutic option for managing substance withdrawal syndromes, offering improved treatment outcomes and reduced relapse rates and vulnerabilities.