A dose of psilocybin, a dash of rabies point to treatment for depression

Psilocybin may help treat depression by rewiring specific brain circuits linked to negative thought loops and sensory-to-action processing. An international team led by Cornell researchers combined a single dose of psilocybin with a modified rabies virus in mouse experiments to map connectivity changes across the brain. One day later, the rabies virus was used to label connected neurons, and after incubation the researchers imaged the brain and compared results to control animals. Results showed psilocybin weakened recurrent cortico-cortical feedback loops associated with rumination, while strengthening pathways between sensory areas and subcortical regions that translate perceptions into action. The study also indicates that the amount of neural firing can influence which connections are rewired, and manipulating activity in a brain region can change the drug’s connectivity effects. The findings were published in Cell on December 5, 2025, with Quan Jiang as lead author and Alex Kwan as senior author.