Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue

Abstract

Inflammation plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), by contributing to tissue damage and exacerbating the immune response. The investigation of serotonin receptor 2A (5-HT2A) ligands and transient receptor potential (TRP) channel ligands is of significant interest due to their potential to modulate key inflammatory pathways, mitigate the pathological effects of inflammation, and offer new avenues for therapeutic interventions in IBD. This study investigates the anti-inflammatory effects of 5-HT2A ligands, including psilocybin, 4-AcO-DMT, and ketanserin, in combination with TRP channel ligands, including capsaicin, curcumin, and eugenol, on the inflammatory response induced by tumor necrosis factor (TNF)-α and interferon (IFN)-γ in human 3D EpiIntestinal tissue. Enzyme-linked immunosorbent assay was used to assess the expression of pro-inflammatory markers TNF-α, IFN-γ, IL-6, IL-8, MCP-1, and GM-CSF. Our results show that psilocybin, 4-AcO-DMT, and eugenol significantly reduce TNF-α and IFN-γ levels, while capsaicin and curcumin decrease these markers to a lesser extent. Psilocybin effectively lowers IL-6 and IL-8 levels, but curcumin, capsaicin, and 4-AcO-DMT have limited effects on these markers. In addition, psilocybin can significantly decrease MCP-1 and GM-CSF levels. While ketanserin lowers IL-6 and GM-CSF levels, there are no effects seen on TNF-α, IFN-γ, IL-8, or MCP-1. Although synergistic effects between 5-HT2A and TRP channel ligands are minimal in this study, the results provide further evidence of the anti-inflammatory effects of psilocybin and eugenol. Further research is needed to understand the mechanisms of action and the feasibility of using these compounds as anti-inflammatory therapies for conditions like IBD.

The Impact of Psilocybin on High Glucose/Lipid-Induced Changes in INS-1 Cell Viability and Dedifferentiation

“…Subsequently, cells underwent treatment with a specified dosage of psilocybin (CAS No. 520-52-50, received from Applied Pharmaceutical Innovation, Edmonton, AB, Canada) for 2 h. In the present study, all experiments were conducted using a 10 µM concentration of psilocybin, a dosage determined based on the outcomes from our previous results [21]. Pretreatment with psilocybin was followed by exposure to a combination of high glucose (HG) conditions (25 mM glucose) and high lipid (HL) conditions (400 µM/250 µM palmitic acid) for the specific time periods.…”

Psilocybin for the treatment of Alzheimer’s disease

“…Psilocybin was shown to reduce inflammation in a 3D model of human intestinal tissue. This anti-inflammatory effect was evidenced by a decrease in TNF-α, IFN-γ, IL-6, and IL-8 levels ( Robinson et al, 2023 ). There is still debate regarding whether psilocybin can alter inflammatory markers in healthy subjects.…”