Serotonergic Psychedelics in Neural Plasticity

This review (2021) summarizes what we know thus far with regards to the ability of serotonergic psychedelics to induce neural plasticity. Proposed mechanisms of action are discussed, as are the questions that need to be addressed as we move forward.

Authors

  • Torregrossa, M. M.
  • Lu, J.
  • Lukasiewicz, K.

Published

Frontiers in Molecular Neuroscience
meta Study

Abstract

Psychedelics, compounds that can induce dramatic changes in conscious experience, have been used by humans for centuries. Recent studies have shown that certain psychedelics can induce neural plasticity by promoting neurite growth and synapse formation. In this review, we focus on the role of classical serotonergic psychedelics in neural plasticity and discuss its implication for their therapeutic potentials.

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Research Summary of 'Serotonergic Psychedelics in Neural Plasticity'

Introduction

Torregrossa and colleagues situate serotonergic psychedelics within a long history of human use and shifting terminology, from early labels such as "psychotomimetics" to contemporary descriptors including "psychoplastogens," which emphasise these compounds' capacity to drive neural plasticity. The introduction summarises converging evidence that classical psychedelics—tryptamines, ergolines, and phenethylamines—promote structural and functional changes at synapses, and notes that affinity for the serotonin 2A (5-HT2A) receptor is strongly correlated with subjective hallucinogenic effects. It also highlights that many psychedelics interact with additional receptor subtypes (for example 5-HT1A, 5-HT2C and dopaminergic receptors), and that intracellular signalling pathways implicated in plasticity (notably TrkB/BDNF and mTOR) may be engaged by these drugs. The paper sets out to review the evidence that classical serotonergic psychedelics induce neuritogenesis, spinogenesis and synaptogenesis in vitro and in vivo, and to consider molecular and circuit mechanisms that could link these neuroplastic effects to therapeutic potential for psychiatric disorders. Rather than re‑reviewing psychedelic pharmacology exhaustively, Torregrossa and colleagues focus specifically on how these compounds affect neural structure and function and on open questions about mechanism, spatial specificity, and the relationship between hallucinogenic and plasticity-related effects.

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Study Details

  • Study Type
    meta
  • Journal
  • APA Citation

    Lukasiewicz, K., Baker, J. J., Zuo, Y., & Lu, J. (2021). Serotonergic Psychedelics in Neural Plasticity. Frontiers in Molecular Neuroscience, 14. https://doi.org/10.3389/fnmol.2021.748359

References (39)

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Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior

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Madsen, M. K., Fisher, P. M., Burmester, D. et al. · Neuropsychopharmacology (2019)

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Nichols, D. E. · Pharmacology and Therapeutics (2004)

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Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A. et al. · NeuroReport (1998)

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