Psilocybin reverses depressive-like behaviors and restores hippocampal neuron growth in chronically stressed rats

Two low doses of psilocybin reversed several depression- and anxiety-like behaviors in adult male rats exposed to weeks of unpredictable mild stress. Treated animals regained normal interest in sweetened water, explored bright and open spaces more readily, and showed less immobility in a forced-swim test, while the results were not explained by general drug-induced hyperactivity. Brain analysis found that psilocybin restored stress-suppressed cell proliferation, maturation, and survival in the hippocampus, increased messenger RNA signaling for brain-derived neurotrophic factor in the hippocampus and prefrontal cortex, and normalized elevated corticosterone levels within two hours, with some effects lasting 14 days. The findings support a possible neuroplasticity-based mechanism for psychedelic therapies, but they come from a small animal study. Rodent behavioral models do not reproduce human depression, and increased messenger RNA does not establish increased functional protein, so further research must confirm the biological effects and their durability.