Major Depressive Disorder (MDD)Depressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Palliative & End-of-Life DistressHealthy VolunteersImmunology & InflammationPsilocybin

Subacute effects of a single dose of psilocybin on biomarkers of inflammation in healthy humans: An open-label preliminary investigation

This open-label study (n=16) assessed the effects of a single dose of psilocybin (15mg/70kg) on biomarkers of inflammation in healthy participants. Blood samples before and one day after the administration revealed that psilocybin did not significantly impact any of the selected biomarkers.

Authors

  • Gitte Knudsen
  • Patrick Fisher
  • Dea Stenbæk

Published

Comprehensive Psychoneuroendocrinology
individual Study

Abstract

Rationale

Psilocybin is a serotonergic psychedelic that has gained prominent attention recently as a potential therapeutic for neuropsychiatric disorders, including Major Depressive Disorder. Pre-clinical and initial studies in humans suggest that serotonin 2A receptor agonists, including serotonergic psychedelics, have anti-inflammatory effects. This may contribute to its therapeutic effects as previous studies indicate a link between neuropsychiatric disorders and inflammatory processes. However, the effect of psilocybin on biomarkers of inflammation has not been evaluated in humans.

Objectives

Investigate the effect of a single dose of psilocybin on peripheral biomarkers of inflammation in healthy humans.

Methods

Blood samples were collected from 16 healthy participants before and one day after the administration of a single oral dose of psilocybin (mean dose: 0.22mg/kg) and subsequently analyzed for concentrations of high-sensitivity C-reactive protein (hsCRP), tumour-necrosis-factor (TNF) and soluble urokinase plasminogen activator receptor (suPAR). Change in inflammatory markers was evaluated using a paired t-test where p < 0.05 was considered statistically significant.

Results

We did not observe statistically significant changes in any of the above biomarkers of inflammation (all Cohen's d ≤ 0.31; all p ≥ 0.23).

Conclusions

Our data do not support that a single dose of psilocybin reduces biomarkers of inflammation in healthy individuals one day after administration. Nevertheless, we suggest that future studies consider additional markers of inflammation, including markers of neuroinflammation, and evaluate potential anti-inflammatory effects of psilocybin therapy in clinical cohorts where more prominent effects may be observable.

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Research Summary of 'Subacute effects of a single dose of psilocybin on biomarkers of inflammation in healthy humans: An open-label preliminary investigation'

Introduction

Psilocybin, a serotonergic psychedelic and prodrug of psilocin, has attracted interest as a potential treatment for several difficult-to-treat neuropsychiatric conditions, including Major Depressive Disorder, end-of-life anxiety and addiction. Previous preclinical work and a small number of human studies with other 5-HT2A receptor agonists (for example DMT, 5-MeO-DMT and DOI) suggest that agonism at the 5-HT2A receptor can reduce pro-inflammatory signalling, and that peripheral inflammatory markers (including CRP and TNF) are linked to neuropsychiatric disorders. Despite this, the effects of psilocybin itself on circulating inflammatory biomarkers in humans had not previously been evaluated, creating a gap in translational evidence linking psilocybin’s neurobiological and potential immunomodulatory actions. Rødbro Burmester and colleagues aimed to address that gap by testing whether a single oral dose of psilocybin alters peripheral markers of low-grade inflammation in healthy volunteers. The investigators pre-specified three biomarkers—high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF) and soluble urokinase plasminogen activator receptor (suPAR)—and hypothesised that psilocybin would reduce their blood concentrations when sampled approximately one day after administration. This preliminary, open-label study is presented as an initial human test of psilocybin’s putative anti-inflammatory effects.

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Study Details

References (23)

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