Psilocybin and eugenol prevent DSS-induced neuroinflammation in mice.

Neuroinflammation has emerged as a central pathology common to several acute and chronic brain diseases. Recent studies have displayed the anti-inflammatory properties of naturally occurring compounds derived from mushrooms and plants could potentially reduce neuroinflammation and disease progression. In this study, we aimed to investigate the impact of psilocybin and eugenol, as well as their combinations, on neuroinflammation. To induce inflammation through the gut-brain axis, we employed a colitis mouse model via oral feeding of dextran sulfate sodium (DSS). By administering various concentrations and combinations of treatments, both before and after inducing inflammation, we sought to assess the synergistic anti-inflammatory effects of psilocybin and eugenol. Our findings revealed oral psilocybin and eugenol post-treatment significantly reduced the expression of pro-inflammatory cytokines and inflammatory mediators in the brain, including IL-1β, IL-6, and COX-2. Notably, combined treatment of psilocybin and eugenol exhibited the strongest reduction in IL-6 levels when compared to the DSS group. While both psilocybin and eugenol possess anti-inflammatory effects, the combined treatment overall did not demonstrate synergistic reductions in neuroinflammation across all markers. This study adds to the growing body of evidence supporting the therapeutic potential of psilocybin and eugenol in psychiatric and neurodegenerative inflammatory disorders. Further research is necessary to elucidate the underlying mechanisms of their anti-inflammatory effects and to evaluate their efficacy in clinical settings. • Dextran sulfate sodium induced neuroinflammation through the gut-brain axis. • Pretreatment with psilocybin and/or eugenol did not prevent neuroinflammation. • Post-treatment with psilocybin and/or eugenol decreased neuroinflammation. • Psilocybin and eugenol post-treatment demonstrated the most promising results. • Psilocybin and eugenol demonstrate dose-dependent synergy. [ABSTRACT FROM AUTHOR]