Evidence map›Paper›PMID 40709512›Full record

ReviewActa neuropsychiatrica2025

Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HT

Guillaume Thuery, Christopher Sheridan, Patricia Iusan, Gurjot Brar, Kathryn Ledden, Aoife Freyne, John R Kelly, Andrew Harkin

Abstract readReview
In one paragraph

Review in Acta neuropsychiatrica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Trials, trips, and tribulations: pathways for implementing psychedelic therapy in Ireland.The international journal of neuropsychopharmacology · 2026
    Review
  3. Article
  4. Psychedelic therapy and postpartum depression: priorities and prospects.Therapeutic advances in psychopharmacology · 2026
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Guillaume ThueryPsychedelic Research Group, Tallaght University Hospital and Trinity College Dublin, Dublin, Ireland.ORCID https://orcid.org/0000-0003-3391-5293
Christopher SheridanPsychedelic Research Group, Tallaght University Hospital and Trinity College Dublin, Dublin, Ireland.
Patricia IusanPsychedelic Research Group, Tallaght University Hospital and Trinity College Dublin, Dublin, Ireland.ORCID https://orcid.org/0009-0008-2452-6396
Gurjot BrarPsychedelic Research Group, Tallaght University Hospital and Trinity College Dublin, Dublin, Ireland.
Kathryn LeddenPsychedelic Research Group, Tallaght University Hospital and Trinity College Dublin, Dublin, Ireland.
Aoife FreynePsychedelic Research Group, Tallaght University Hospital and Trinity College Dublin, Dublin, Ireland.
John R KellyPsychedelic Research Group, Tallaght University Hospital and Trinity College Dublin, Dublin, Ireland.
Andrew HarkinPsychedelic Research Group, Tallaght University Hospital and Trinity College Dublin, Dublin, Ireland.ORCID https://orcid.org/0000-0001-9734-216X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveBy synthesising findings from both clinical and preclinical research, this review aims to provide an understanding of the interplay between 5-HT2A receptor psychedelics and the immune system and considers how their immunomodulatory effects associate with neuronal and behavioural changes.

methodsA PubMed literature search covering the past 30 years was conducted using keywords such as '5-HT2A receptor', 'psychedelics', 'immune system', and 'HPA axis'. Studies were included if they addressed the effects of 5-HT2AR psychedelics on immune function, neuroimmune interactions, or HPA axis involvement. This narrative review synthesises evidence highlighting the bi-directional effects of 5-HT2AR psychedelics between the immune and nervous systems, identified through this search process.

resultsPreclinical and clinical studies report that 5-HT2AR psychedelics have some direct immunomodulatory properties with downregulation of gene regulators like NF-κB, and reduced cytokine expression such as TNF-α, IL-6, and IL-1β at a central and peripheral level, accompanied by modulation of corticotrophin releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and cortisol. Direct immunomodulatory effects are mediated by pathways involving serotonin receptors, the Sigma-1 receptor, and the TrkB receptor. Immunomodulation is further mediated indirectly via the HPA axis.

conclusionFurther studies will determine the molecular and cellular mechanisms underlying these immunomodulatory effects. There is growing interest in the potential of 5-HT2AR psychedelics for treating a range of mental health and brain disorders. In keeping with their immunomodulatory actions, the likely modulation of brain glia and glial-neuronal interaction remains to be determined, representing a promising direction of further research on the therapeutic potential of 5-HT2AR psychedelics.

Indexed as

HallucinogensHypothalamo-Hypophyseal SystemImmune SystemNeuroimmunomodulationReceptor, Serotonin, 5-HT2AAnimalsCytokinesHumansPituitary-Adrenal SystemCytokinesHallucinogensReceptor, Serotonin, 5-HT2A5-HT2A Receptorpsychedelicspsychiatric disorderspsychoneuroimmunologyserotonin

Identifiers

PMID40709512
PMCPMC13130319

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.