Loredana Bucciarelli, Vincenzo Cimino, Bernardo Dell’Osso, Paolo Fiorina
The use of Glucagon-like peptide-1 receptor agonists (GLP-1RAs) is an established therapy for type 2 diabetes (T2D) and obesity, providing effective glycemic control, weight loss, and cardiovascular and renal benefits. Evidence is emerging on the potential neuropsychiatric and neuroprotective effects mediated via central GLP-1R. This review summarizes preclinical, clinical, and real-world findings on the use of GLP-1R agonists in depression, anxiety, binge eating disorder (BED), cognitive impairment, dementia, and substance use disorders involving alcohol, nicotine, cocaine, and opioids. Literature emphasizes human studies and translational models. Reported mechanisms include modulation of neuroinflammation, neurotransmitter systems, and reward pathways. Preliminary results are promising but limited by small and methodologically heterogeneous studies with short follow-up. Robust randomized trials with standardized psychotropic endpoints are needed. If confirmed, GLP-1RAs could represent an innovative treatment option bridging metabolic and mental health care.