Psilocybin restores behavioral and neuroplastic deficits induced by chronic stress in rats.
Level 5 - mechanism / opinion, no new human data
Animal research (preclinical rodent model)
PubMed 42009274 · doi:10.1016/j.pnpbp.2026.111710
What was done
Investigators evaluated the effects of psilocybin on behavioral deficits, hippocampal neurogenesis, brain-derived neurotrophic factor (BDNF) expression, and hypothalamic-pituitary-adrenal (HPA) axis activity in a rat model of chronic stress. Psilocybin was administered subcutaneously in two doses of 0.6 mg/kg separated by 7 days. Behavioral outcomes were measured using tests for anhedonia, the forced swim test (FST), light/dark box (LDB), elevated plus maze (EPM), and open field (OF) test. Neurogenesis was tracked using markers BrdU, Ki-67, and DCX.
What was found
Psilocybin reversed stress-induced anhedonia, demonstrated antidepressant-like effects in the FST, and reduced anxiety-like behaviors across the LDB, EPM, and OF tests. In the hippocampus, psilocybin increased counts of BrdU-positive, DCX-positive, and Ki-67-positive cells in stressed rats. It also restored stress-induced reductions in BDNF expression and normalized HPA axis activity. The abstract reported directional findings and dosing but did not report numerical values, effect sizes, or confidence intervals.
Why it matters
This study provides preclinical mechanistic evidence linking psilocybin's antidepressant and anxiolytic behavioral effects to enhanced hippocampal neuroplasticity and HPA axis regulation in rodents.
Limits
The study is restricted to a rodent model of chronic stress, which cannot fully replicate human depression or therapeutic contexts. The abstract provides no sample sizes, specific numerical data, or evidence regarding long-term durability of the effects.
Cited by
- supports Psilocybin lowers the activity of the brain's default mode network and activates brain-derived neurotrophic factor (BDNF) to increase neural connectivity and neurogenesis.