Yale researchers discover healing effects of psychedelic drug

Yale researchers have found that a single dose of psilocybin, a naturally occurring psychedelic substance produced by certain species of fungi (“magic mushrooms”), can cause structural changes in the brain that can treat depression.

by Jenn Sipes · February 07, 2022

Yale researchers have found that a single dose of psilocybin, a naturally occurring psychedelic substance produced by certain species of fungi (“magic mushrooms”), can cause structural changes in the brain that can treat depression.

Psilocybin research… in mice

The researchers at Yale School of Medicine have found that a single dose of psilocybin given to mice leads to long-lasting increases in dendritic spine density and size in the medial frontal cortex. Dendritic spines, tiny specialized structures, are found in the part of neurons that are responsible for carrying information throughout the human body. Dendritic spine density decreases between young and adult ages and chronic stress as well as depression have been found to reduce the number of these neuronal connections. This structural remodeling occurred within the short span of 24 hours, and was persistent a month later.

“We not only saw a 10% increase in the number of neuronal connections, but also they were on average about 10% larger, so the connections were stronger as well,” states Alex Kwan, associate professor of psychiatry and neuroscience at Yale University and senior author of the paper.

It was also found that mice subjected to stress showed behavioral improvements as well as increased neurotransmitter activity after being given psilocybin. This finding of the increase and growth of neural connections proposes the treatment of depression as well as other mental health conditions with psychedelics.

“Psilocybin is fascinating because it has an incredibly short half-life, which means that it gets out of the body quickly and yet has long-lasting behavioral effects,” Alex Kwan said. “We’ve seen that psilocybin can be effective in treating depression and other neuropsychiatric disorders. In this study, we wanted to investigate this mystery by observing individual connections in the mouse brain.”

Taking psychedelic research from mice to people

In this study, Kwan and Ling-Xiao Shao decided to use a mouse model to better understand the changes the human brain encounters during psychedelic experiences. The mice were divided into three groups: one dosed with nothing but saline as a control group, a second as a positive control group dosed with ketamine, and the third, dosed with psilocybin. The Yale research team used a laser-scanning microscope which allowed them to image dendritic spines in high resolution where they tracked them for multiple days in these living mice, and then followed up after a month.

Kwan and his research team hope that the results of this study will lead to new opportunities to investigate the exact mechanisms by which psilocybin increases both neuron size and density. On average, the protein-coding regions of the mouse and human genomes are 85% identical, making mice accessible to be genetically manipulated to mimic human diseases and conditions. The results of this study bring researchers one step closer in treating neuropsychiatric disorders in humans with psilocybin.

Is the psychedelic stigma shifting?

More studies and research are underway to link psilocybin and other psychedelics to therapeutic benefits in treating mental health conditions, but will scientific evidence be enough to end the stigma on psychedelic medicine? Along with psilocybin, other psychedelics such as MDMA and Ketamine are being studied to unlock potential healing properties and mental illness treatment options.

“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,” states Alex Kwan.

As the results from this study with psilocybin suggest a promising future in psychedelic medicine, new results from a clinical trial using MDMA to treat PTSD shows continued improvements in most patients for more than one year after the treatment ended.

“It was a real surprise to see such enduring changes from just one dose of psilocybin,” Alex Kwan said in response to the dose given to the mice in this study. “These new connections may be the structural changes the brain uses to store new experiences.”

As more research is conducted on psychedelic medicine and the FDA has encouraged this research through “Breakthrough Therapy” status, psychedelic medicine continues to push boundaries to get off the sidelines and make its way into mainstream medicine. As many medications and psychiatric treatments for mental illness have fallen short in the past, new discoveries in psychedelic medicine may be the answer we need, to bridge the gap.

What do you think the significance of this research is for the future of medicine?