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

Compr Psychoneuroendocrinol. 2022 Dec 6;13:100163. doi: 10.1016/j.cpnec.2022.100163. eCollection 2023 Feb.


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: 0.22 mg/kg) and subsequently analyzed for concentrations of high-sensitivity C-reactive protein (hsCRP), tumor-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.

Keywords: Biomarkers; Immune system; Inflammation; Neuroinflammation; Psilocybin; Psychedelics; TNF; hsCRP; suPAR.