Current perspectives in the pharmacological treatment of gambling disorder: psychedelics and beyond
Stefania Chiappini, Angelo Giovanni Icro Maremmani, Clara Cavallotto, Carlotta Marrangone, Andrea Amerio, Matteo Lupi, Mauro Pettorruso, Giovanni Martinotti
Expert Opinion on Pharmacotherapy November 9, 2026 DOI: 10.1080/14656566.2026.2761183 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Narrative review Longitudinal Peer reviewed |
|---|---|
| Key findings | Argues that opioid antagonists show the most consistent, though still limited, therapeutic signal in gambling disorder, especially in patients with prominent gambling urges, while evidence for other drug classes is heterogeneous. The authors contend that pharmacotherapy should become phenotype-informed and multimodal, and that emerging neuroplasticity-based interventions such as psilocybin, ketamine/esketamine, and MDMA require adequately powered controlled trials before clinical use. |
Abstract
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.