Yale scientists have found that a single dose of psilocybin given to mice induces a rapid and long-lasting increase in connections between pyramidal neurons in the medial frontal cortex, an area of the brain known to be involved in control and decision-making. Their new findings are published in the journal Neuron.

Psilocybin — the active component in so-called “magic” mushrooms — has been shown to have profound and long-lasting effects on personality and mood. Preliminary studies have provided hope that psilocybin could help to relieve depression symptoms and treat other mental disorders. But the mechanisms behind these effects remain unclear.

A team of researchers at Yale University were interested in examining whether the lasting therapeutic effects of psilocybin might be caused in part by the substance’s ability to enhance neuroplasticity in the brain.

“My lab has a longstanding interest in studying antidepressants, which started in 2014 with a small pilot grant from the Brain & Behavior Research Foundation,” said study author Alex Kwan (@kwanalexc), an associate professor of psychiatry at Yale University.

“We were studying the rapid-acting antidepressant ketamine, and found that it has various intriguing effects on changing neuronal connections in the brain. Then about two years ago, we started wondering if the effects generalize to other compounds, so we began working on psilocybin.”

In the controlled study, the researchers used two-photon microscopy to track 1,820 dendritic spines for multiple days in living mice. Dendritic spines are protrusions in the part of neurons that receive communication input from other neurons.

Kwan and his colleagues found increases in the number of dendritic spines and in their size within 24 hours of administration of psilocybin. Dendritic spine density and the width of spine heads both increased by approximately 10% compared to mice who had not received psilocybin. These changes were still present a month later.

“Psychedelics like psilocybin can give mystical-like experiences and have exciting therapeutic potentials, but we still don’t know much about what they do to the brain. Here we study what psilocybin does in a mouse brain. The data suggest that there is a growth of new neuronal connections in mice after one dose of psilocybin. This happened in the frontal cortex, a brain region important for mood and cognition,” Kwan told PsyPost.

The findings are in line with a previous study, published in the International Journal of Molecular Sciences, which found that psilocybin increased the number of neuronal connections in the prefrontal cortex and hippocampus of pig brains. Previous research has also found that psilocybin rapidly increases the expression of several genes related to neuroplasticity in the rat brain.

But the new study, like all research, includes some limitations.

“One caveat is obviously that this study is done in mice. Ideally, we would like to know what happens in humans, but that is not possible because of the kind of optical imaging that we did, which is very detailed and allows us to see individual sites of neuronal connections, but is also invasive and not suitable for humans,” Kwan explained.

“We know that the brain has many cell types. Here we study one type called the pyramidal neurons. For future studies, we have some ongoing projects to look at other cell types to see if they are also affected by psilocybin. Knowing what types of cells are impacted will be informative for developing new drugs that may then target those specific cell types.”

The study, “Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo“, was published by Ling-Xiao Shao, Clara Liao, Ian Gregg, Neil K. Savalia, Kristina Delagarza, and Alex C. Kwan.