Effects of a single dose of psilocybin on cytokines, chemokines and leptin in rat serum

A single dose of psilocybin given to female rats increased levels of multiple immune factors in the blood, including IL-1β, TNF-α, MCP-1, IP-10, G-CSF, IFN-γ, IL-10, IL-13, and leptin, after 24 hours, with further increases after seven days. Most other measured immune modulators showed similar but statistically non-significant increases. The findings indicate that psilocybin induces a generalized activation of the immune system that can persist for at least a week, which may relate to its therapeutic mechanism. Further research is needed to connect these immune effects to clinical outcomes in humans.

Study at a glance

Abstract

Abstract Background and Aims The hallucinogenic drug psilocybin is being widely tested in humans for the treatment of psychiatric disorders. Psilocybin and other psychedelics are proposed to work through serotonin 2a (5-HT2a) receptors, which are tightly linked to immune function. The purpose of the present study was to assess the effects of a single dose of psilocybin on a panel of cytokines, chemokines, and peptides in the short term (24 h) and long term (seven days) in female rats. Methods Female rats were given a dose of psilocybin (20 mg kg −1 , i.p.} or a dose of synthetic interstitial fluid. At 24 h, the control group and one group of rats were anesthetized, and blood was withdrawn by intracardiac puncture. In a third group of rats, blood was withdrawn after seven days. Serum was analyzed by a separate lab (Eve Laboratories, Calgary, Canada) for 27 immunomodulators. Results Serum levels of IL-1β, TNF-α, MCP-1, IP-10, G-CSF, IFN-γ, IL-10, IL-13, and leptin were significantly increased compared to controls after 24 h and were increased further after 7 days. Most of the other assays showed this same pattern of increase, although not statistically significant. Conclusions Psilocybin induces the release of multiple immune factors, consistent with a generalized activation of the immune system, which can persist for at least seven days after a single dose. These findings may relate to the mechanism of action. The implications of these findings require additional research to determine how these finding relate to the clinical effects of psilocybin.