This pre-print 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.
Abstract of Neuroplasticity and Psychedelics
“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.”
Authors: Claudio Agnorelli, Meg J. Spriggs, Kate Godfrey, Gabriela Sawicka, Bettina Bohl, Hannah Douglass, Andrea Fagiolini, Hashemi Parastoo, Robin L. Carhart-Harris, David J. Nutt & David Erritzoe
Summary of Neuroplasticity and Psychedelics
Neuroplasticity, defined as the nervous system’s ability to adapt and reorganise over an organism’s lifespan, is categorised into structural plasticity (physical changes in the nervous system) and functional plasticity (alterations in synaptic communication). These processes, historically examined in animal models, are increasingly recognised as pivotal in human neuropsychiatric disorders, both as biomarkers and therapeutic targets.
The critical periods of neuroplasticity—windows of optimal development for neural structures and functions—close before adulthood, underscoring the importance of context and timing in neuroplastic changes. Emerging neuroimaging techniques aim to bridge gaps in understanding between preclinical and clinical findings.
Psychedelics, including classic compounds like LSD, psilocybin, and DMT, and non-classic ones like ketamine and MDMA, are being re-evaluated as treatments for mental health conditions. These substances induce significant, enduring therapeutic effects after minimal use, contrasting traditional mental health medications. For example, ketamine has shown rapid antidepressant effects lasting for weeks after single or multiple doses, while MDMA-assisted therapy demonstrates persistent PTSD symptom relief after two to three sessions.
The authors propose that psychedelics act by inducing heightened neuroplasticity—a “window of opportunity” for long-term therapeutic interventions. However, this plasticity must be carefully managed, as it can also lead to maladaptive outcomes, such as addiction or hallucinogen persisting perception disorder (HPPD). This review synthesises current evidence from preclinical and human studies, comparing the neuroplasticity effects of classic psychedelics, ketamine, and MDMA to guide future research.
Molecular Mechanisms of Action
Ketamine
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https://doi.org/10.48550/arXiv.2411.19840
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Cite this paper (APA)
Agnorelli, C., Spriggs, M., Godfrey, K., Sawicka, G., Bohl, B., Douglass, H., ... & Erritzoe, D. (2024). Neuroplasticity and Psychedelics: a comprehensive examination of classic and non-classic compounds in pre and clinical models. arXiv preprint arXiv:2411.19840.
Study details
Compounds studied
LSD
DMT
Psilocybin
MDMA
Ketamine
Topics studied
Neuroscience
Study characteristics
Literature Review