Overview

• Penn Medicine scientists report that one psilocybin dose rapidly reversed mechanical allodynia and anxiety- and depression-like behaviors in two mouse chronic pain models for nearly two weeks.
• Directly injecting psilocin into the anterior cingulate cortex reproduced whole-body benefits, whereas spinal cord injection did not show comparable effects.
• Two-photon calcium imaging showed that psilocin quickly normalized chronic pain–related hyperactivity in layer 2/3 pyramidal neurons of the anterior cingulate cortex.
• Pharmacologic blockade of serotonin receptors 5-HT2A or 5-HT1A eliminated the analgesic and mood effects, consistent with psilocin’s partial agonism at these targets.
• Authors emphasize this is preclinical work and plan studies on dosing, durability, and safety, noting NIH and ASRA funding and open questions around perioperative use.