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Structural plasticity and enhanced fear extinction following psilocybin in chronically stressed mice.

Cory A Knox, Samuel C Woodburn, Amelia D Gilbert, Jason M Schlotzhauer, Alex C Kwan

bioRxiv : the preprint server for biology April 22, 2026 Peer reviewed DOI: 10.64898/2026.04.21.720014 via PubMed

Summary

Psilocybin increases dendritic spine density in frontal cortical neurons and aids in fear extinction following chronic restraint stress in a mouse model. This indicates that psilocybin can have beneficial effects even after exposure to stress, suggesting its potential for therapeutic use in stress-related conditions.

Study at a glance

Population mice subjected to chronic restraint stress
Key finding Psilocybin enhances dendritic spine density and facilitates fear extinction after chronic restraint stress.

Abstract

The classic psychedelic psilocybin elicits long-lasting neural plasticity and behavioral effects, but prior studies largely examined stress-naive animals. Using longitudinal imaging, we show that psilocybin increases dendritic spine density in frontal cortical neurons and facilitates fear extinction after chronic restraint stress, demonstrating psilocybin's effects in a translationally relevant mouse model.

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