Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue

Area of Science:

• Gastroenterology
• Immunology
• Pharmacology

Background:

• Inflammatory bowel disease (IBD) pathogenesis involves complex inflammatory pathways.
• Serotonin receptor 2A (5-HT2A) and transient receptor potential (TRP) channel ligands are potential modulators of inflammation.
• Novel therapeutic strategies for IBD are urgently needed.

Purpose of the Study:

• To investigate the anti-inflammatory effects of 5-HT2A ligands (psilocybin, 4-AcO-DMT, ketanserin) and TRP channel ligands (capsaicin, curcumin, eugenol) in an in vitro IBD model.
• To assess the impact of these compounds on key pro-inflammatory markers induced by TNF-α and IFN-γ.
• To explore potential synergistic effects between 5-HT2A and TRP channel ligands.

Main Methods:

• Utilized human 3D EpiIntestinal tissue model.
• Induced inflammation using tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ).
• Quantified pro-inflammatory markers (TNF-α, IFN-γ, IL-6, IL-8, MCP-1, GM-CSF) using enzyme-linked immunosorbent assay (ELISA).

Main Results:

• Psilocybin, 4-AcO-DMT, and eugenol significantly reduced TNF-α and IFN-γ levels.
• Psilocybin demonstrated significant reductions in IL-6, IL-8, MCP-1, and GM-CSF.
• Ketanserin reduced IL-6 and GM-CSF, but not other tested markers.
• Synergistic effects between the tested ligand classes were minimal.

Conclusions:

• Psilocybin and eugenol exhibit notable anti-inflammatory properties relevant to IBD.
• The findings support further investigation into psilocybin and eugenol as potential therapeutic agents for IBD.
• Understanding the precise mechanisms of action is crucial for future clinical applications.