semaglutide + naltrexone

Semaglutide + naltrexone is an investigational combination therapy being evaluated for the treatment of alcohol use disorder (AUD) and weight management. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that mimics the endogenous GLP-1 hormone to regulate appetite, slow gastric emptying, and modulate dopamine reward pathways in the brain's mesolimbic system, thereby reducing the anticipatory craving for alcohol and food. Naltrexone is an opioid receptor antagonist that blocks mu-opioid receptors, blunting the endorphin-mediated dopamine surge and pleasurable reward associated with alcohol consumption. By combining these two distinct mechanisms, the therapy aims to address both the homeostatic/anticipatory drive (via semaglutide) and the hedonic/reward-based reinforcement (via naltrexone) of addictive behaviors. The combination is currently being evaluated in a Phase 2 clinical trial sponsored by Johns Hopkins University in collaboration with Ashley Addiction Treatment for patients with alcohol use disorder.