A team at the University of Pennsylvania uncovered how a single dose of psilocybin, the active compound in psychedelic mushrooms, rapidly and durably alleviates both chronic pain and depression-like behaviors in mouse models. The compound acts centrally in the brain to modulate key serotonin receptors, dampening hyperactive pain circuits and lifting mood disorders. These findings open promising avenues for non-opioid, non-addictive treatments for comorbid pain and mental health conditions, addressing a significant unmet medical need.