Psychedelics as neuroplasticity enhancers: Mechanisms, therapeutic applications, and translational challenges

Psychedelics such as psilocybin, LSD, DMT, and ketamine promote neuroplasticity by affecting serotonergic and glutamatergic systems, leading to rapid synaptogenesis, dendritic remodeling, and changes in brain network connectivity. These mechanisms are thought to underlie therapeutic benefits for depression, PTSD, and substance use disorders, especially when combined with psychotherapy. However, challenges remain regarding safety, long-term effects, and translating preclinical findings to clinical practice. The review covers pharmacological, molecular, and cellular bases of psychedelic action, along with ethical, legal, and translational issues that must be resolved for integration into psychiatry.

Study at a glance

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.