Psilocybin has a narrow therapeutic window as an antidepressant treatment.
Progress in neuro-psychopharmacology & biological psychiatry April 2, 2025 Lenka Seillier, Barbora Čechová, Alexandre Seillier et al. 3 citations
A single dose of psilocybin at 0.32 mg/kg, but not lower or higher doses, produced short- and long-term antidepressant-like effects in Wistar rats, as measured by the forced swim test, and also increased social interaction and sucrose preference. Higher doses of 1.0 and 3.2 mg/kg lacked antidepressant-like activity and instead reduced body temperature, locomotor activity, and weight gain. Brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex increased linearly with dose, dissociating from the inverted-U-shaped behavioral effects. The findings suggest a narrow therapeutic window for psilocybin, with the intermediate dose providing benefits without adverse effects seen at higher doses.