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

A single dose of psilocybin, a serotonergic psychedelic, caused a roughly 10% increase in the size and density of dendritic spines on layer 5 pyramidal neurons in the mouse medial frontal cortex. This structural remodeling began within 24 hours and persisted for at least one month, driven by an elevated rate of new spine formation. The drug also reduced stress-related behavioral deficits and increased excitatory neurotransmission. The findings demonstrate that psilocybin induces fast and enduring synaptic rewiring in the cortex, which may provide a structural basis for long-term integration of experiences and lasting therapeutic benefits.

Study at a glance

Abstract

Summary 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 time scale 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 hours 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.