Psychedelic-assisted pharmacotherapy: clinical applications and regulatory considerations
Donatella Marazziti, Matteo Gambini, Riccardo Gurrieri, Gerardo Russomanno, Giorgia Sità, Elena Pescini, Francesca Rita Digiuseppe, Federico Mucci
Expert Opinion on Pharmacotherapy March 24, 2026 Peer reviewed DOI: 10.1080/14656566.2026.2654682 via OpenAlex
Summary
Psychedelic-assisted therapies show promise for treating treatment-resistant mental disorders, with evidence from late-stage clinical trials indicating their potential benefits. However, there are significant challenges to overcome, including long-term safety, workforce training, and equitable access before these therapies can be widely implemented. The review discusses various compounds like ketamine, MDMA, and psilocybin and their regulatory pathways across different jurisdictions.
Study at a glance
| Design | narrative review |
|---|---|
| Population | psychiatric patients with treatment-resistant mental disorders |
| Key finding | Psychedelic-assisted therapies have potential benefits but face unresolved challenges that must be addressed for broader clinical implementation. |
Abstract
INTRODUCTION: After decades of regulatory marginalization, psychedelic compounds have reemerged as promising therapeutic tools in psychiatry, driven by unmet clinical needs in treatment-resistant mental disorders and by growing evidence of rapid and sustained effects on mood, cognition, and behavior. AREAS COVERED: This narrative review critically examined the current clinical and regulatory landscape of psychedelic-assisted therapies in psychiatry. We synthesize evidence from phase II-III clinical trials, regulatory agency documents, and international drug policy frameworks, focusing on ketamine/esketamine, MDMA, psilocybin, LSD, DMT/5-MeO-DMT, and ibogaine across major depressive disorder, treatment-resistant depression, PTSD, anxiety disorders, and substance use disorders. Particular attention will be given to regulatory pathways, scheduling constraints, access mechanisms, and compound-specific approval trajectories in the United States, European Union, and selected international jurisdictions. EXPERT OPINION: Psychedelic-assisted therapies are unlikely to follow a conventional prescription model and instead require specialist-delivered, psychotherapy-integrated care under appropriate regulatory and ethical safeguards. While late-stage trials support their potential in high-need populations, unresolved challenges, including long-term safety, scalability, workforce training, equity of access, and medico-legal accountability, must be addressed before broader clinical implementation.