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

This 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.

Abstract

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.

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

Notes

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 remodelling as a mechanism for 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.”

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

Serotonergic psychedelics may have therapeutic potential for neuropsychiatric disorders, including depression, obsessive-compulsive disorder, and addiction. In vitro studies have shown that serotonergic psychedelics induce neural adaptations, but there is only limited evidence linking serotonergic psychedelics to structural plasticity in vivo.

This study measured the head-twitch response in mice to test the potency and dose dependence of psilocybin. At 1 mg/kg, mice exhibited high-frequency headshakes intermittently, consistent with a prior report.

Study details

Compounds studied
Psilocybin

Topics studied
Neuroscience

Study characteristics
Animal Study Bio/Neuro