Researchers at UC Santa Cruz used two-photon microscopy to track how psilocybin reshapes connections in mouse brains. Within 24 hours of treatment, the drug substantially increased newly forming dendritic spines, the tiny projections where neurons receive signals from neighboring cells. The drug also accelerated maturation of these spines into stable, mushroom-shaped structures that support stronger communication between brain cells.
The study, published October 15 in Nature Neuroscience, found that psilocybin does more than add connections. It also promotes removal of older connections, reorganizing the brain's circuitry while maintaining overall balance in healthy mice.
A key finding separated the structural rewiring from behavioral responses. Lead author Jacob Baker, a Ph.D. student in senior author Yi Zuo's lab, noted that "these newly formed connections can integrate into existing neural circuitry and persist over time, leaving a lasting structural trace of psilocybin's effects on the brain." This suggests some effects on brain structure may occur without the hallucinations typically associated with the drug.
The researchers also discovered that psilocybin's effects depend on prior stress exposure. In mice exposed to chronic stress through an unpredictable mild stress model, the brain responded differently than in healthy mice, suggesting the drug's influence varies based on stress history.
The findings could support development of medications that enhance neuroplasticity, the brain's ability to reorganize itself, potentially offering new approaches for depression and PTSD without hallucinogenic effects.