Psilocybin Mitigates Behavioral Despair and Cognitive Impairment in Treatment-resistant Depression Model using Wistar Kyoto Rats
Research Square May 6, 2025 Zitong Wang, Brett Robbins, R. L. Zhuang et al.
In an animal model of treatment-resistant depression, psilocybin produced a significant and lasting reduction in behavioral despair and cognitive impairment. The compound increased thyroid-stimulating hormone levels without altering the hypothalamic-pituitary-adrenal axis, countering stress-induced TSH reductions that may serve as a proxy marker of therapeutic response. Changes in cannabinoid receptor type I after psilocybin administration suggest possible modulation of the endocannabinoid system, though causal links remain unconfirmed. These findings highlight psilocybin's potential to treat treatment-resistant depression through targeting previously unexplored biological pathways.