Single-dose psilocybin rapidly and sustainably relieves allodynia and anxiodepressive-like behaviors in mouse models of chronic pain
Nature Neuroscience October 2, 2025 Ahmad Hammo, Stephen Wisser, Joseph Cichon 20 citations
A single dose of psilocybin rapidly and sustainably reversed both mechanical allodynia and anxiety-depression-like behaviors in adult male and female mice with chronic pain. The effect depended on psilocin, the active metabolite, engaging prefrontal cortical circuits. Two-photon calcium imaging showed that psilocin quickly normalized hyperactivity in anterior cingulate cortex layer 2/3 pyramidal neurons, a hallmark of chronic pain. Full agonists of 5-HT2A and 5-HT1A receptors replicated some but not all of psilocin's cellular and behavioral effects, indicating that partial agonism at these receptors within shared pain-and-mood circuits underlies the dual therapeutic action.