Preclinical and Emerging Clinical Evidence Supporting the Translational Potential of GLP-1 Receptor Agonists for Treating Psychostimulant and Nicotine Use Disorders

Psychostimulant use disorder (PSUD) and nicotine use disorder (NUD) affect tens of millions of people worldwide, yet no clinically approved medications exist for PSUD, and existing NUD treatments have limited long-term efficacy. Recent preclinical evidence suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists could be repurposed for treating PSUD and NUD. This review summarizes the current literature investigating the efficacy of GLP-1R agonists to reduce psychostimulant and nicotine-mediated behaviors in animal models of PSUD and NUD, respectively. The neural mechanisms underlying the suppressive effects of GLP-1R agonists on drug-mediated behaviors as well as the role of central endogenous GLP-1 neural circuits in voluntary drug-taking and drug-seeking behaviors are also discussed. Overall, a growing preclinical literature and emerging clinical studies support the translational potential of GLP-1R agonists as novel pharmacotherapies for treating substance use disorders including PSUD and NUD.