Current perspectives in the pharmacological treatment of gambling disorder: psychedelics and beyond

INTRODUCTION: Gambling disorder (GD) is a heterogeneous behavioral addiction associated with dysregulated reward processing, impaired executive control, stress-system dysfunction, and maladaptive neuroplasticity. Despite its considerable clinical, social, and economic burden, no medication is currently approved specifically for GD, and available pharmacological strategies remain off label. AREAS COVERED: This narrative review examines established and emerging pharmacological approaches to GD. PubMed/MEDLINE, Scopus, and Web of Science were searched for English-language literature published between January 2010 and January 2026. Opioid antagonists show the most consistent, although still limited, therapeutic signal with potential benefits in selected patients with prominent gambling urges, whereas evidence for antidepressants, mood stabilizers, antiepileptic drugs, and antipsychotics remains heterogeneous. Glutamatergic, noradrenergic, endocannabinoid, and orexin-related interventions are biologically plausible but largely experimental. Psychedelic and neuroplasticity-oriented treatments, including psilocybin, ketamine/esketamine, and 3,4-Methylenedioxymethamphetamine (MDMA)-assisted interventions, may target cognitive inflexibility, compulsive behavior, and maladaptive reward learning. EXPERT OPINION: The available evidence supports a cautious, mechanism-informed approach to pharmacological research, while underscoring the need for adequately powered clinical trials and prospective evaluation of clinically relevant treatment-response indicators. Pharmacotherapy for GD should move toward phenotype-informed, multimodal treatment rather than a one-size-fits-all model. Emerging neuroplasticity-based interventions are promising, but adequately powered, controlled, and longitudinal trials are required before clinical implementation.