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

Neuron. 2021 Aug 18;109(16):2535-2544.e4. doi: 10.1016/j.neuron.2021.06.008. Epub 2021 Jul 5.


Psilocybin is a serotonergic psychedelic with untapped therapeutic potential. There are hints that the use of psychedelics can produce neural adaptations, although the extent and timescale of the impact in a mammalian brain are unknown. In this study, we used chronic two-photon microscopy to image longitudinally the apical dendritic spines of layer 5 pyramidal neurons in the mouse medial frontal cortex. We found that a single dose of psilocybin led to ∼10% increases in spine size and density, driven by an elevated spine formation rate. The structural remodeling occurred quickly within 24 h and was persistent 1 month later. Psilocybin also ameliorated stress-related behavioral deficit and elevated excitatory neurotransmission. Overall, the results demonstrate that psilocybin-evoked synaptic rewiring in the cortex is fast and enduring, potentially providing a structural trace for long-term integration of experiences and lasting beneficial actions.

Keywords: antidepressant; dendrites; hallucinogen; medial prefrontal cortex; neural plasticity; psilocybin; pyramidal neuron; serotonergic psychedelic; structural remodeling; synapse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects
  • Dendrites / drug effects*
  • Dendrites / physiology
  • Dendritic Spines / drug effects*
  • Dendritic Spines / physiology
  • Female
  • Frontal Lobe / drug effects*
  • Male
  • Mice
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Psilocybin / pharmacology*
  • Pyramidal Cells / physiology
  • Synaptic Transmission / drug effects


  • Psilocybin