Psilocybin shows therapeutic potential for stress-related neuropsychiatric disorders like depression, anxiety, PTSD, OCD, addiction, and eating disorders, but its mechanisms are complex, involving multiple body systems. This review explores how psilocybin interacts with the gut microbiota, enteric nervous system, and hypothalamic-pituitary axis, influencing bidirectional communication between peripheral and neuronal systems. Understanding these gut-brain interactions could advance psilocybin-based therapies from preparation through long-term integration, potentially extending benefits beyond psychiatric disorders to inflammatory-related conditions.
Repeated mild traumatic brain injury in rats produced lasting deficits in mood, social behavior, and pain sensitivity. Delayed treatment with psilocybin (1 mg/kg) reversed several of these effects, including antidepressant-like effects, increased social behavior, and raised pain thresholds. Psilocybin also reduced injury-related increases in microglial density and increased the number and complexity of newborn neurons in the dentate gyrus, suggesting enhanced neuroplasticity. The findings indicate psilocybin may be a promising intervention for persistent symptoms after repeated mild traumatic brain injury.