Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo

This pre-print article shows that brain cells, specifically the layer five pyramidal neurons in mice, grew by 10% after the introduction of psilocybin. The effects were still present 30 days later, providing more evidence for brain plasticity as an underlying mechanism of psychedelic-assisted therapies’ long-lasting effects.


Psilocybin is a serotonergic psychedelic with untapped therapeutic potential. Here we chronically imaged apical dendritic spines of layer 5 pyramidal neurons in mouse medial frontal cortex. We found that a single dose of psilocybin led to ~10% increases in spine density and spine head width. Synaptic remodeling occurred quickly within 24 hours and was persistent 1 month later. The results demonstrate structural plasticity that may underpin psilocybin’s long-lasting beneficial actions.

Authors: Ling-Xiao Shao, Clara Liao, Ian Gregg, Neil Savalia, Kristina Delagarza & Alex C. Kwan


The psilocybin for this study was provided by Usona, but the non-profit had no further influence on the study.

The mice in the study were administrated 1mg/kg of psilocybin (which is metabolized into psilocin in the brain).

The study found increases in the formation rate that led to increased spine density, but no changes in the elimination rate.

“Altogether, these results demonstrate that a single dose of psilocybin induces rapid and long-lasting dendritic remodeling in layer 5 pyramidal neurons in the mouse medial frontal cortex.”

This work provides evidence for dendritic remodeling as a mechanism why psychedelics can be helpful as therapeutics. It is still an open question through which mechanisms different psychedelics do this (and why they have similar/different) therapeutic outcomes.

“However, still unknown is how drugs with disparate molecular targets may yield comparable circuit-level modifications. Elucidating the mechanisms will be crucial towards unraveling the neurobiology of rapid-acting antidepressants.”

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