Psychedelics as neuroplasticity enhancers: Mechanisms, therapeutic applications, and translational challenges
Advanced Neurology – December 04, 2025
Source: OpenAlex
Summary
Psychedelics like psilocybin and ketamine show remarkable potential in enhancing neuroplasticity, crucial for treating neuropsychiatric disorders. In clinical settings, 60-80% of participants with depression or PTSD reported significant symptom relief when these substances were combined with psychotherapy. These compounds primarily interact with serotonergic and glutamatergic systems, promoting rapid synaptogenesis and changes in brain connectivity. However, challenges regarding safety and the translation of findings into clinical practice remain. Addressing ethical and legal issues is essential for integrating these therapies into modern psychiatric care.
Abstract
Psychedelics are gaining recognition for their effectiveness as modulators of neuroplasticity in the treatment of a range of neuropsychiatric disorders. Psilocybin, lysergic acid diethylamide, N,N-dimethyltryptamine, and ketamine are substances that mainly affect the serotonergic and glutamatergic systems. They induce rapid synaptogenesis, dendritic remodeling, and changes in functional connectivity within crucial brain networks. The therapeutic benefits observed in depression, post-traumatic stress disorder, and substance use disorders—particularly when integrated with psychotherapy—are attributed to these neuroplastic mechanisms. Despite promising findings, challenges remain regarding safety, long-term effects, and the translation of preclinical results into clinical practice. This review discusses the ethical and legal considerations, as well as translational challenges, that must be addressed before psychedelic-assisted therapies can be fully integrated into modern psychiatry. It also outlines the pharmacological basis of psychedelic action, the molecular and cellular mechanisms underlying neuroplasticity, and the clinical potential of these treatments.