Depressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)LSDPsilocybinAyahuasca

Towards an understanding of psychedelic-induced neuroplasticity

This review (2022) investigates how classical psychedelics (LSD, psilocybin, ayahuasca) elicit neuroplasticity. Animal and human studies show evidence for neuroplasticity, but evidence for BDNF (protein, encoded by a gene, indicated in neuronal growth) is mixed in humans. Neuroplasticity mostly happens through the 5-HT2a receptor (but other serotonin receptors could also be involved). Most of this happens 5-HT2a rich areas in the brain (neocortex). The evidence for micro/mini-dosing on neuroplasticity is currently inconclusive. Neuroplasticity happens as fast as in a few hours, lasting up to a month.

Authors

  • Gregor Hasler
  • Abigail Calder

Published

Neuropsychopharmacology
meta Study

Abstract

Classic psychedelics, such as LSD, psilocybin, and the DMT-containing beverage ayahuasca, show some potential to treat depression, anxiety, and addiction. Importantly, clinical improvements can last for months or years after treatment. It has been theorized that these long-term improvements arise because psychedelics rapidly and lastingly stimulate neuroplasticity. The focus of this review is on answering specific questions about the effects of psychedelics on neuroplasticity. Firstly, we review the evidence that psychedelics promote neuroplasticity and examine the cellular and molecular mechanisms behind the effects of different psychedelics on different aspects of neuroplasticity, including dendritogenesis, synaptogenesis, neurogenesis, and expression of plasticity-related genes (e.g., brain-derived neurotrophic factor and immediate early genes). We then examine where in the brain psychedelics promote neuroplasticity, particularly discussing the prefrontal cortex and hippocampus. We also examine what doses are required to produce this effect (e.g., hallucinogenic doses vs. “microdoses”), and how long purported changes in neuroplasticity last. Finally, we discuss the likely consequences of psychedelics’ effects on neuroplasticity for both patients and healthy people, and we identify important research questions that would further scientific understanding of psychedelics’ effects on neuroplasticity and its potential clinical applications.

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Research Summary of 'Towards an understanding of psychedelic-induced neuroplasticity'

Introduction

Recent renewed interest in classic psychedelics — including LSD, psilocybin, DOI, 5-MeO-DMT and DMT — follows observations that a small number of doses, typically combined with psychotherapy, can produce relatively long-lasting improvements in mood, anxiety and addiction. Calder and Hasler frame these enduring effects in terms of neuroplasticity: the nervous system's capacity to reorganise structure and function in response to experience. They note that neuroplasticity encompasses molecular changes (for example in gene and protein expression such as brain-derived neurotrophic factor, BDNF), morphological changes (dendritogenesis, synaptogenesis) and, in some regions like the hippocampus, neurogenesis, and that dysfunction in these processes is implicated in depression and addiction. This review sets out to evaluate evidence that psychedelics enhance neuroplasticity, to describe likely mechanisms, to identify brain regions and dose ranges involved, to characterise the temporal dynamics of any plasticity window, and to consider behavioural and clinical consequences. The authors aim to synthesise preclinical and human data to clarify which aspects of plasticity are reliably affected by different psychedelics and to highlight key open questions for future research and therapeutic application.

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Study Details

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