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Cited by 313Psychedelics and Drug StudiesNeurogenesis and neuroplasticity mechanismsNeurotransmitter Receptor Influence on Behavior

Towards an understanding of psychedelic-induced neuroplasticity

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Calder, Abigail E., Hasler, Gregor·2023·Neuropsychopharmacology
DOI 10.1038/s41386-022-01389-zPMC PMC9700802
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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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  • There is little direct evidence of psilocybin-induced cortical plasticity in humans, with no evidence in individuals with alcohol use disorder, and the relationship between psychedelic-induced cortical neuroplasticity and clinical outcomes remains to be established.

    “However, there is little direct evidence of psilocybin-induced cortical plasticity in humans, with no evidence in individuals with AUD, and the relationship between psychedelic-induced cortical neuroplasticity and clinical outcomes remains to be established [43].”

    From Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial (2024) · cites this paper as [43]

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  • A window for neuroplastic changes appears to open a few hours after ayahuasca administration, lasting from a few days to a month.

    “A window for neuroplastic changes would appear to open a few hours after administration, lasting from a few days to a month (44).”

    From Ayahuasca-assisted meaning reconstruction therapy for grief: a non-randomized clinical trial protocol (2025) · cites this paper as [44]

    The Conclusions say the neuroplasticity window appears to open within a few hours and may last a few days; changes formed during it may survive for at least a month. The duration section reports elevated BDNF two days after ayahuasca, but does not establish that ayahuasca specifically opens a window lasting up to a month. The claim conflates the window’s duration with the persistence of changes formed during it. (LLM, conf=0.89)

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  • Preclinical studies suggest that serotonergic psychedelics belong to the class of psychoplastogens, capable of rapidly promoting neuroplasticity in cortical neurons.

    “Preclinical studies suggest that serotonergic psychedelics belong to the class of psychoplastogens, i.e., compounds capable of rapidly promoting neuroplasticity in cortical neurons (see [43] for a review).”

    From Psilocybin-assisted therapy for severe alcohol use disorder: protocol for a double-blind, randomized, placebo-controlled, 7-month parallel-group phase II superiority trial (2024) · cites this paper as [43]

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Research works printed but not linked: 1

  1. [116]Gewirtz JC Chen AC Terwilliger R Duman RC Marek GJ Modulation of DOI-induced increases in cortical BDNF expression by group II mGlu receptors Pharmacol, Biochem Behav 2002 73 317 26 12117585

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Authors
Calder, A. E., & Hasler, G.
Affiliations
University of Fribourg (CH)
Corresponding author
  • Calder, Abigail E.
  • Hasler, Gregor
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2022-09-19
Volume
48
Issue
1
Pages
104-112
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/s41386-022-01389-z
PMC
PMC9700802
OpenAlex
W4296373810
Cited by
313
References
169
Citations by year
2026: 75 · 2025: 98 · 2024: 105 · 2023: 31 · 2022: 4
FWCI
9.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuropsychopharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Université de Fribourg
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
psychedelics, neuroplasticity, LSD, psilocybin, ayahuasca, dendritogenesis, synaptogenesis, neurogenesis, brain-derived neurotrophic factor, immediate early genes, prefrontal cortex, hippocampus, microdosing, depression, anxiety, addiction, long-term treatment outcomes
MeSH terms
Anxiety, Anxiety Disorders, Hallucinogens, Humans, Neuronal Plasticity, Psilocybin

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