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. 2024 Jun 17;2(2):109-115.
doi: 10.1089/psymed.2023.0039. eCollection 2024 Jun.

Impact of Psilocybin on Peripheral Cytokine Production

Dana DiRenzo  1 , Frederick S Barrett  2   3   4 , Jamie Perin  5 , Erika Darrah  6 , Lisa Christopher-Stine  6 , Roland R Griffiths  2   4
Affiliations

Impact of Psilocybin on Peripheral Cytokine Production

Dana DiRenzo et al. Psychedelic Med (New Rochelle). .

Abstract

Background: Psilocybin is a psychedelic drug with potential therapeutic effects in patients with mood and substance use disorders. Little is known about its impact on the immune system.

Methods: Multiplex immunoassay pro-inflammatory cytokine panels (Meso-Scale Discovery, Rockville, MD) were used to examine the serum from participants in three separate randomized controlled clinical trials (randomized controlled trials [RCTs]) wherein a range of doses of psilocybin were administered (methods reported previously). Participants represented a range of clinical histories including those with no-known health problems/long-term meditation practice (n = 35), depression (n = 25), anxiety, and cancer (various types; n = 31). Linear mixed models with random effects for each participant were fit to determine relative cytokine levels both immediately before and at various time points after psilocybin administration, adjusted for multiple comparisons. Serum extracted during a waitlist, where applicable, was not included.

Results: Sera from 91 participants were included from our three prior RCTs. In our linear models of pooled data, sera collected ≤1-week postpsilocybin revealed increased levels of interleukin (IL)-8 (β = 0.164, 95% confidence interval [0.10 to 0.23]; p = 0.042). At ≥4-week time points compared to baseline, there were no changes in cytokine levels. In our linear models of individual studies, no changes in cytokine levels at each time point were observed.

Conclusion: This preliminary study suggests that a transient increase in cytokine production ≤1-week postpsilocybin may be found, although not consistently across patient populations. More broadly, peripheral cytokine production is possibly altered by psilocybin administration. ClinicalTrials.gov Identifier: NCT01988311.

Keywords: anti-inflammatory; cytokines; immune system; psilocybin; psychedelics.

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Conflict of interest statement

D.D.: conceptualization, formal analysis, investigation, writing original draft, visualization. F.S.B.: conceptualization, formal analysis, investigation, writing review and editing, visualization, funding acquisition. E.D.: formal analysis, writing review and editing. J.P.: formal analysis, writing review, and editing. L.C.-S.: conceptualization, formal analysis, investigation, writing review and editing, visualization, funding acquisition. R.R.G.: conceptualization, investigation, writing review and editing, funding acquisition.R.R.G. is a member of the Board of Directors of the Heffter Research Institute. F.S.B. is on the scientific advisory board of WavePaths, Ltd. and MindState Design Labs, LLC, and is a consultant for Gilgamesh Pharmaceuticals, Inc. E.D. is an employee of AstraZeneca. The other authors declare no conflicts of interest.F.S.B. and R.R.G. are supported by the Johns Hopkins Center for Psychedelic and Consciousness Research which is funded by grants from Tim Ferriss, Matt Mullenweg, Craig Nerenberg, Blake Mycoskie, and the Steven and Alexandra Cohen Foundation. E.D. and the Bayview Immunomics Core are supported by NIH NIAMS grant P30-AR070254. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Figures

FIG. 1.
FIG. 1.
Serum collection times. In addition to sera collection from participants at baseline, before psilocybin administration, sera were collected at early (Near-term, ≤1 week) and later (Delayed, ≥4 weeks) time points postpsilocybin administration from each of the three randomized controlled trials. The figure was created with BioRender.com
FIG. 2.
FIG. 2.
Spaghetti plots of serum cytokine concentrations pooled across studies #1–3, shown by time in days since administration of psilocybin.
See this image and copyright information in PMC

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