AbstractBackground and AimsThe 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.MethodsFemale 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 At 24 h, the control group and one group of rats were anesthetized, and blood was withdrawn by intracardiac puncture. In a third group of rats, blood was withdrawn after seven days.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.ResultsSerum 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.ConclusionsPsilocybin 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.