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Cited by 104Psychedelics and Drug StudiesTreatment of Major DepressionNeuroscience and Neuropharmacology Research

A Dendrite-Focused Framework for Understanding the Actions of Ketamine and Psychedelics

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Savalia, Neil K., Shao, Ling-Xiao, Kwan, Alex C.·2021·Trends in Neurosciences
DOI 10.1016/j.tins.2020.11.008PMC PMC7990695
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Abstract

Pilot studies have hinted that serotonergic psychedelics such as psilocybin may relieve depression, and could possibly do so by promoting neural plasticity. Intriguingly, another psychotomimetic compound, ketamine, is a fast-acting antidepressant and induces synapse formation. The similarities in behavioral and neural effects have been puzzling because the compounds target distinct molecular receptors in the brain. In this opinion article, we develop a conceptual framework that suggests the actions of ketamine and serotonergic psychedelics may converge at the dendrites, to both enhance and suppress membrane excitability. We speculate that mismatches in the opposing actions on dendritic excitability may relate to these compounds' cell-type and region selectivity, their moderate range of effects and toxicity, and their plasticity-promoting capacities.

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  • Ketamine is hypothesized to block NMDAR on GABA interneurons, releasing the inhibition of glutamate release.

    “In addition, ketamine is hypothesized to block NMDAR on GABA interneurons, releasing the inhibition of glutamate release (109).”

    From Psychedelics and Neuroplasticity: A Systematic Review Unraveling the Biological Underpinnings of Psychedelics. (2021) · cites this paper as [109]

  • These structural studies concur with the SV2A results and fit into a general framework whereby rapid antidepressant responses to ketamine also occur along with dendritic expansion, albeit by a different mechanism.

    “Overall, these structural studies concur with the SV2A results discussed above, and fit into a general framework whereby rapid antidepressant responses to ketamine also occur along with dendritic expansion, albeit by a different mechanism [111].”

    From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [111]

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Authors
Savalia, N. K., Shao, L.-X., & Kwan, A. C.
Affiliations
Yale University (US)
Corresponding author
Kwan, Alex C.
ORCID
Venue
Trends in Neurosciences
Publisher
Elsevier BV
Published
2021-04
Volume
44
Issue
4
Pages
260-275
ISSN
0166-2236 (ISSN-L)
DOI
10.1016/j.tins.2020.11.008
PMC
PMC7990695
OpenAlex
W3113989724
Cited by
104
References
146
Citations by year
2026: 12 · 2025: 25 · 2024: 16 · 2023: 13 · 2022: 19 · 2021: 19
FWCI
1.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Trends in Neurosciences (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Simons Foundation Autism Research Initiative
  • National Institute of Mental Health
  • National Institute of General Medical Sciences
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
ketamine, psychedelics, psilocybin, dendrites, dendritic excitability, membrane excitability, neuroplasticity, depression, antidepressant mechanism, synaptogenesis, neurotoxicity
MeSH terms
Antidepressive Agents, Dendrites, Depression, Hallucinogens, Humans, Ketamine, Neuronal Plasticity

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