Psilocybin (Psi) and eugenol (Eug) together reduced inflammation in human small intestinal epithelial cells. Cells were treated with inflammatory cytokines TNF-α and IFN-γ, then exposed to compounds targeting serotonin 2A receptors (Psi, 4-AcO-DMT, ketanserin) or transient receptor potential channels (capsaicin, curcumin, eugenol). Alone, Psi (40 μM), curcumin (0.5 μM), and eug (50 μM) lowered COX-2 protein without killing cells. The Psi–curcumin combination synergistically cut COX-2 by 28-fold but reduced IL-6 only 1.6-fold. The Psi–eug combination produced the best results: COX-2 dropped 19-fold and IL-6 dropped 10-fold, with no toxicity at any dose. This is the first work to examine psilocybin and 4-AcO-DMT's anti-inflammatory effects in intestinal cells.
Psilocybin and eugenol, both individually and combined, reduced inflammation in a mouse model of liver injury induced by lipopolysaccharides. Post-treatment administration produced stronger anti-inflammatory effects than pre-treatment. Psilocybin alone showed the most pronounced reduction of pro-inflammatory cytokines IL-1β, IL-6, and MCP-1, while the combination with eugenol (1:50 ratio) also strongly reduced COX-2 and TNF-α. Histological analysis indicated improved nuclear circularity and less inflammatory infiltration. Eugenol alone increased MCP-1 and GM-CSF, an adverse effect that was mitigated by co-administration with psilocybin. The findings suggest psilocybin and its combination with eugenol as potential therapies for hepatic inflammation.