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Researchers have identified Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs)—medications already used for diabetes and obesity—as promising potential treatments for alcohol and drug addiction. Published in the Journal of the Endocrine Society, the study explores how GLP-1RAs modulate brain circuits linked to addiction, reducing cravings and substance use while also addressing related metabolic issues. GLP-1RAs work by activating receptors in the central nervous system that regulate hunger but also impact reward pathways involved in addiction. They influence neurotransmitter systems such as dopamine, glutamate, and GABA within the mesocorticolimbic circuit, which plays a pivotal role in reinforcing addictive behaviors. Additionally, these drugs communicate via the gut-brain axis through vagal afferents, integrating energy balance and motivational signals to curb substance-seeking behavior. The study reviewed preclinical animal research and early clinical trials. One randomized controlled trial found that semaglutide reduced alcohol self-administration and craving in individuals with alcohol use disorder, especially those with obesity. Rodent models demonstrated that GLP-1RAs reduced heroin, fentanyl, and nicotine self-administration and relapse behavior. Initial clinical data on tobacco use disorder suggests these drugs help decrease cigarettes per day and prevent post-cessation weight gain. Despite such encouraging findings, challenges remain including variability in drug penetration into the brain and potential side effects like nausea or mood changes. Researchers emphasize the need for larger, well-controlled human trials to establish efficacy, dosing, safety, and long-term outcomes. Lead researcher Dr. Lorenzo Leggio highlighted the importance of these agents as potential game-changers in addiction treatment, offering a novel, neurobiologically based approach that intersects metabolic and psychiatric care. Overall, GLP-1RAs represent a hopeful new class of addiction therapeutics, targeting core brain mechanisms to reduce substance use and improve overall health outcomes. Reference: Nirupam M Srinivasan, Mehdi Farokhnia, Lisa A Farinelli, Anna Ferrulli, Lorenzo Leggio. GLP-1 Therapeutics and Their Emerging Role in Alcohol and Substance Use Disorders: An Endocrinology Primer. Journal of the Endocrine Society, 2025; 9 (11) DOI: 10.1210/jendso/bvaf141
