OSCR

Psilocybin restores behavior and 5-HT<sub>2A</sub> signaling while reducing microglial density after chronic traumatic brain injury in rats.

Overview

Authors: Josh Allen1,2,3, Bianca Jupp1, Tamara L Baker1, Mohammad B Haskali4,5, Robert Brkljača1, Zoe Plummer3, Mujun Sun1, Justin Brand3, Brian R Christie3, Chantel T Debert6, Stuart J McDonald1, Terence J O’Brien1, Pablo M Casillas-Espinosa1, Sandy R Shultz1,2,3,7
ORCID iDs: Josh Allen, Tamara L Baker, Justin Brand, Brian R Christie, Sandy R Shultz
  1. Department of Neuroscience, School of Translational Medicine, Monash University, Melbourne, VIC, Australia
  2. Centre for Trauma and Mental Health Research, Vancouver Island University, Nanaimo, BC, Canada
  3. School of Medical Sciences, Faculty of Health, University of Victoria, Victoria, BC, Canada
  4. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia
  5. Department of Radiopharmaceutical Sciences, Cancer Imaging, The Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  6. Department of Clinical Neuroscience, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
  7. Institute on Aging & Lifelong Health, University of Victoria, Victoria, BC, Canada
Institutions: University of Victoria (Canada); Vancouver Island University (Canada); Monash University (Australia); The University of Melbourne (Australia); Peter MacCallum Cancer Centre (Australia); University of Calgary (Canada)
Journal: Cell reports. Medicine, volume 7, issue 7, article 102867
Dates: received 19 August 2025; accepted 18 May 2026; published online 12 June 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.xcrm.2026.102867 · PMID 42285092 · PMCID PMC13400183 · OpenAlex W7164582898
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: PET / SPECT (modality), rat (organism), traumatic brain injury (population), cellular / molecular (subfield)
Methods: Statistics, fMRI & imaging, Physiology & signal measures
Keywords: concussion, fluid-percussion injury, psychedelic, positron emission tomography, PET, serotonin receptor, microglia, IBA1
MeSH: Behavior, Animal*, Brain Injuries, Traumatic*, Microglia*, Psilocybin*, Receptor, Serotonin, 5-HT2A*, Signal Transduction*, Animals, Male, Rats, Rats, Sprague-Dawley (* major topic)
Topic: Psychedelics and Drug Studies (Clinical Psychology, Psychology), according to OpenAlex
Funding: Michael Smith Health Research BC; Monash University; National Imaging Facility; National Health and Medical Research Council
Citations: not cited yet (Europe PMC); 91 references in the paper
Research resources: Rabbit anti-IBA1 primary antibody RRID:AB_2636859, Goat anti-rabbit secondary antibody RRID:AB_954902

Abstract

Traumatic brain injury (TBI) causes persistent neurobehavioral deficits and increases the risk of psychiatric disorders, including depression, anxiety, and cognitive dysfunction linked to disrupted neuroplasticity, neuroinflammation, and serotonergic (5-HT) signaling. No effective pharmacotherapies exist for chronic TBI. Psilocybin, a psychedelic 5-HT2A receptor agonist, shows promise due to its neuroplasticity-enhancing, anti-inflammatory, and antidepressant effects. Here, male rats received fluid-percussion or sham injury, followed one year later by a single psilocybin (1 mg/kg) or saline injection. Behavioral testing began 24 h later, and positron emission tomography assessed 5-HT2A binding after two weeks. TBI produced persistent sensorimotor, learning and memory, and affective deficits; reduced 5-HT2A binding; and microglial alterations in the medial prefrontal cortex characterized by decreased process branching and enlarged soma size. Psilocybin treatment could improve sensorimotor function, restore 5-HT2A binding, and reduce microglial cell counts. These findings highlight psilocybin’s therapeutic potential in chronic TBI and support further investigation of psychedelic treatments.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

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Data

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Data and code availability

The data reported in this study are available from the corresponding author upon reasonable request.

This paper does not report original code.

Any additional information required to reanalyze the data reported in this work is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Authors: added Sandy R Shultz (0000-0002-2525-8775); removed Sandy R Shultz

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 8 keywords, 10 MeSH terms, 4 funders, 89 references, 2 RRIDs.

Cite

This paper

Allen, J., Jupp, B., Baker, T. L., Haskali, M. B., Brkljača, R., Plummer, Z., Sun, M., Brand, J., Christie, B. R., Debert, C. T., McDonald, S. J., O’Brien, T. J., Casillas-Espinosa, P. M., & Shultz, S. R. (2026). Psilocybin restores behavior and 5-HT<sub>2A</sub> signaling while reducing microglial density after chronic traumatic brain injury in rats. Cell reports. Medicine, 7(7), 102867. https://doi.org/10.1016/j.xcrm.2026.102867

BibTeX

@article{allen2026psilocybin,
author = {Allen, Josh and Jupp, Bianca and Baker, Tamara L and Haskali, Mohammad B and Brkljača, Robert and Plummer, Zoe and Sun, Mujun and Brand, Justin and Christie, Brian R and Debert, Chantel T and McDonald, Stuart J and O’Brien, Terence J and Casillas-Espinosa, Pablo M and Shultz, Sandy R},
title = {{Psilocybin restores behavior and 5-HT\<sub\>2A\</sub\> signaling while reducing microglial density after chronic traumatic brain injury in rats}},
journal = {Cell reports. Medicine},
year = {2026},
month = jun,
volume = {7},
number = {7},
pages = {102867},
publisher = {Elsevier},
issn = {2666-3791},
doi = {10.1016/j.xcrm.2026.102867},
url = {https://doi.org/10.1016/j.xcrm.2026.102867},
pmid = {42285092},
pmcid = {PMC13400183}
}

RIS

TY - JOUR
AU - Allen, Josh
AU - Jupp, Bianca
AU - Baker, Tamara L
AU - Haskali, Mohammad B
AU - Brkljača, Robert
AU - Plummer, Zoe
AU - Sun, Mujun
AU - Brand, Justin
AU - Christie, Brian R
AU - Debert, Chantel T
AU - McDonald, Stuart J
AU - O’Brien, Terence J
AU - Casillas-Espinosa, Pablo M
AU - Shultz, Sandy R
TI - Psilocybin restores behavior and 5-HT<sub>2A</sub> signaling while reducing microglial density after chronic traumatic brain injury in rats
T2 - Cell reports. Medicine
J2 - Cell Rep Med
PY - 2026
DA - 2026/06/12
VL - 7
IS - 7
SP - 102867
SN - 2666-3791
PB - Elsevier
DO - 10.1016/j.xcrm.2026.102867
UR - https://doi.org/10.1016/j.xcrm.2026.102867
LA - en
ER -

CSL-JSON

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