Neuroplasticity and Psychedelics: a comprehensive examination of classic and non-classic compounds in pre and clinical models
This review (2024) examines the effects of classic psychedelics (e.g., LSD, psilocybin, DMT) and non-classic psychedelics (e.g., ketamine, MDMA) on neuroplasticity. Drawing on preclinical and clinical studies, it discusses molecular, structural, and functional changes induced by these agents, highlighting their potential to re-open developmental windows (hyper-plasticity) and increase nervous system sensitivity to stimuli (meta-plasticity). Translating findings to humans remains challenging, but emerging tools like PET radioligands and multimodal approaches offer promise for future research.
Authors
- Robin Carhart-Harris
- David Nutt
- David Erritzoe
Published
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.
Research Summary of 'Neuroplasticity and Psychedelics: a comprehensive examination of classic and non-classic compounds in pre and clinical models'
Introduction
Agnorelli and colleagues frame neuroplasticity as the nervous system's lifelong capacity for structural and functional change and posit it as both a biomarker and therapeutic target in neuropsychiatric disorders. The introduction distinguishes structural plasticity (for example, neuritogenesis, spinogenesis, synaptogenesis) from functional plasticity (short- and long-term synaptic changes), and notes that most detailed mechanistic understanding comes from animal models. The authors observe a translational gap: human imaging methods are emerging but remain limited for directly capturing many cellular and molecular plasticity processes identified preclinically. This review sets out to compare evidence for neuroplasticity effects across classic psychedelics (e.g., LSD, psilocybin, N,N-DMT), and non-classic agents (ketamine, MDMA), drawing on both preclinical and clinical studies. The paper emphasises mechanisms that might explain rapid and enduring therapeutic effects after one or a few administrations, and intends to highlight translational validity and specific molecular targets to guide future research. Doses are classified in this review as low (non-consciousness-altering, e.g. microdoses), medium (psychoactive/therapeutically relevant), and, for ketamine, high (anesthetic) to aid cross-compound comparisons.
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(2024). Neuroplasticity and Psychedelics: a comprehensive examination of classic and non-classic compounds in pre and clinical models. Preprints. https://doi.org/10.48550/arXiv.2411.19840
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