Neuroplasticity and Psychedelics: A comprehensive examination of classic and non-classic compounds in pre and clinical models.
Neuroscience and biobehavioral reviews – April 02, 2025
Source: PubMed
Summary
Psychedelics may reshape our understanding of brain health, showing promise in treating mood disorders by enhancing functional and structural neuroplasticity. Research indicates these compounds boost the nervous system's adaptability, fostering long-term changes that could revolutionize therapeutic approaches. Exciting advancements in imaging techniques are paving the way for deeper insights into their potential.
Abstract
Neuroplasticity, the ability of the nervous system to adapt throughout an organism's lifespan, offers potential as both a biomarker and treatment target for neuropsychiatric conditions. Psychedelics, a burgeoning category of drugs, are increasingly prominent in psychiatric research, prompting inquiries into their mechanisms of action. Distinguishing themselves from traditional medications, psychedelics demonstrate rapid and enduring therapeutic effects after a single or few administrations, believed to stem from their neuroplasticity-enhancing properties. This review examines how classic psychedelics (e.g., LSD, psilocybin, N,N-DMT) and non-classic psychedelics (e.g., ketamine, MDMA) influence neuroplasticity. Drawing from preclinical and clinical studies, we explore the molecular, structural, and functional changes triggered by these agents. Animal studies suggest psychedelics induce heightened sensitivity of the nervous system to environmental stimuli (meta-plasticity), re-opening developmental windows for long-term structural changes (hyper-plasticity), with implications for mood and behavior. Translating these findings to humans faces challenges due to limitations in current imaging techniques. Nonetheless, promising new directions for human research are emerging, including the employment of novel positron-emission tomography (PET) radioligands, non-invasive brain stimulation methods, and multimodal approaches. By elucidating the interplay between psychedelics and neuroplasticity, this review informs the development of targeted interventions for neuropsychiatric disorders and advances understanding of psychedelics' therapeutic potential. "And one finds oneself, to put it all in perspective, in a situation where fifty different onomatopoeias, simultaneous, contradictory, and each constantly changing, would be the most faithful expression of it." Henri Michaux, Misérable Miracle, 1956.