Psilocybin restores behavioral and neuroplastic deficits induced by chronic stress in rats.
Progress in neuro-psychopharmacology & biological psychiatry June 20, 2026 Agnieszka Bysiek, Izabela Szpręgiel, Adam Wojtas et al.
Two doses of psilocybin (0.6 mg/kg, given subcutaneously seven days apart) reversed anhedonia, produced antidepressant-like effects in the forced swim test, and reduced anxiety in the light/dark box, elevated plus maze, and open field tests in rats exposed to chronic unpredictable mild stress. Psilocybin also increased hippocampal neurogenesis, shown by higher numbers of BrdU-positive, DCX-positive, and Ki-67-positive cells in stressed animals. Stress-induced reductions in brain-derived neurotrophic factor (BDNF) expression appeared linked to normalization of hypothalamic-pituitary-adrenal (HPA) axis activity. The findings highlight psilocybin-induced neuroplasticity as a key mechanism for its antidepressant and anxiolytic effects.