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

This pre-print (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 (p ≥ 0.23).

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.”

Authors: Daniel R. Burmester, Martin K. Madsen, Atilla Szabo, Sagar S. Aripaka, Dea S. Stenbaek, Vibe G. Frokjaer, Betina Elfving, Jens D. Mikkelsen, Gitte M. Knudsen & Patrick M. Fischer

Summary of Subacute effects of a single dose of psilocybin on biomarkers of inflammation in healthy humans

Psilocybin, a substituted indolealkylamine naturally found in mushrooms of the genus Psilocybe, has increased well-being, the core personality trait openness, and mindfulness in healthy individuals. It has also been proposed that psilocybin may have anti-inflammatory effects within the central nervous system.

The 5-HT system is an important intercellular signalling pathway in the brain, shaping neuronal processes that support emotion, memory and complex behavioural phenotypes. Several immune cells express 5-HT receptors, which, once stimulated, have receptor- and cell-type-specific effects on the immune response. Two studies have investigated the effects of 5-HT2AR agonism on circulating cytokines in humans. One study reported decreased levels of IL-6 and increased levels of cortisol.

In this study, the authors measured three inflammatory biomarkers in healthy participants before and after a single oral dose of psilocybin. They hypothesized that psilocybin upregulates uPA and other profibrinolytic proteins, which counteract inflammation by degrading fibrin and aid neuroplasticity by activating brain-derived neurotrophic factor. They investigated the effects of psilocybin on blood levels of hsCRP, TNF, and suPAR, which are sensitive biomarkers for low-grade inflammation.

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Study details

Compounds studied
Psilocybin

Topics studied
Immunity Neuroscience

Study characteristics
Original Open-Label

Participants
16 Humans

Authors

Authors associated with this publication with profiles on Blossom

Gitte Knudsen
Gitte Moos Knudsen is the Chair Professor at the Neurology and Neurobiology Research Unit, Copenhagen University Hospital, and director of the Center for Experimental Medicine Neuropharmacology (NeuroPharm).

Institutes

Institutes associated with this publication

University of Copenhagen
The Neurobiology Research Unit (NRU) at Copenhagen University Hospital have been carrying clinical and preclinical research with psychedelics since 2017.

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