Psilocybin, a serotonergic hallucinogen, shows therapeutic promise for treatment-resistant depression, but its multi-organ safety profile remains unclear. This narrative review of preclinical studies, clinical data, and case reports found limited and heterogeneous evidence, with rare adverse events often confounded by polysubstance use and uncertain dosing. Biologically plausible mechanisms via serotonergic receptor activation warrant further investigation, yet controlled clinical data do not consistently indicate intrinsic multi-organ toxicity. The review highlights critical gaps in understanding psilocybin's organ-specific safety and calls for systematic evaluation.
Psilocybin, a classic serotonergic psychedelic, has antidepressant, anxiolytic, anti-inflammatory, and analgesic properties, but its effects on microglial activation in the central nervous system are not well understood. In a study using adult male Wistar Han rats, spinal cords from animals subjected to chronic mild stress (CMS) and treated with two doses of psilocybin (0.6 mg/kg) showed significantly higher levels of the microglial activation marker Arg1 and the cytokines TNF-α and IL-10 compared to control rats given psilocybin. iNOS levels showed a non-significant increasing trend. The findings suggest that CMS activates the immune system and microglia non-specifically despite psilocybin administration.