Researchers at the University of Pennsylvania demonstrated that a single dose of psilocybin, a psychoactive compound found in certain mushrooms, alleviates symptoms of chronic pain and associated depression- and anxiety-like behaviors in mouse models. Investigating nerve injury and inflammatory pain models, the study showed psilocybin's analgesic and mood-enhancing effects when administered intracerebrally but not at peripheral nerve sites. Mechanistically, psilocin, the active metabolite, normalizes hyperactive neurons linked to chronic pain via serotonin receptor modulation. These findings, published in Nature Neuroscience, open avenues for developing non-opioid therapeutics to simultaneously target pain and mood disorders.