Neuroplasticity and Psychedelics: a comprehensive examination of classic and non-classic compounds in pre and clinical models

TL;DR

This review explores how classic and non-classic psychedelics influence neuroplasticity in preclinical and clinical models, highlighting their potential for treating neuropsychiatric disorders through molecular and structural brain changes.

Contribution

It provides a comprehensive analysis of the mechanisms by which psychedelics enhance neuroplasticity, integrating preclinical and emerging human research methods.

Findings

Psychedelics induce meta-plasticity and hyper-plasticity in animal models.

Emerging human research employs PET, brain stimulation, and multimodal imaging.

Psychedelics' neuroplastic effects have therapeutic implications for neuropsychiatric conditions.

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.