In a rodent model of chronic stress, psilocybin reduced behavioral despair and cognitive impairments. Twenty-two male Wistar rats were exposed to predator odor and social instability; those given psilocybin showed improvements in memory and mood-related behaviors compared to sham-treated stressed animals. The benefits appear to involve the endocannabinoid system dampening overactivity of the hypothalamic-pituitary-adrenal axis. The results suggest psilocybin may hold promise as an early intervention for stress-related mental health disorders.
Psilocybin showed a significant and sustained beneficial effect on behavioral despair and cognitive impairment in a rat model of treatment-resistant depression. The treatment increased thyroid-stimulating hormone (TSH) levels without significantly affecting the hypothalamic-pituitary-adrenal (HPA) axis. Psilocybin countered stress-induced TSH reductions, suggesting TSH may serve as a proxy marker of therapeutic response, though its causal role in mood regulation remains unclear. Changes in cannabinoid receptor type I (CB1R) after psilocybin administration suggest potential modulation of the endocannabinoid system, but causal links remain unconfirmed. These findings highlight psilocybin's potential to treat treatment-resistant depression through previously unexplored biological pathways.