Researchers Explore Psilocybin’s Antidepressant Effects, How it Disrupts Brain Connectivity

Researchers are continuing to explore how psilocybin affects various brain networks and how it can potentially benefit people with depression.
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In a recently published preprint study, entitled “Psilocybin desynchronizes brain networks,” researchers analyze the comparison between psilocybin and the default mode network (DMN) of the brain.

“Psilocybin-driven desynchronization was observed across [the] association cortex but strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self,” researchers explained.

According to the study, the largest areas of the DMN that were affected by psilocybin in the patients included the thalamus, basal ganglia, cerebellum, and hippocampus. “Persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for pro-plasticity and anti-depressant effects of psilocybin,” researchers wrote in their abstract.

The study is in the preprint stage of research publication, meaning that it has not yet been peer reviewed, which is required before it can be considered for publication in a research journal. However, using a publication service like medRxiv, research that is not yet peer-reviewed can still be shared and discussed.

However, the team of researchers includes a variety of noteworthy individuals from Washington University School of Medicine, as well as Beth Israel Deaconess Medical Center, Advocate Aurora Health, University of Wisconsin-Madison, and University of California, San Francisco (UCSF). Professor Robin Cahart-Harris of UCSF previously worked on a groundbreaking study that was published last year.

The most recent study analyzed results from seven adults between the ages of 18 and 45, recruited for study between March 2021 to May 2023. Participants were carefully selected with the criteria that they have experienced at least one psychedelic exposure (such as psilocybin, or other substances such as ayahuasca or LSD), but had not had such an experience within the past six months.

Participants were scanned “roughly” every other day in the neuroimaging department at Washington University Medical Center in St. Louis, Missouri. Researchers scanned participants’ brains using precision functional mapping to “identify desynchronization of resting state fMRIs” and find connections to depression-related areas of the brain.

“The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood,” researchers explained. “Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to three weeks after oral psilocybin and methylphenidate (17 MRI visits per participant) and again six+ months later.”

Methylphenidate is more commonly known as Ritalin and is an FDA-approved stimulant used to treat ADHD and narcolepsy.

These results show that psilocybin “disrupted connectivity across cortical networks and subcortical structures” and produced more noticeable changes than methylphenidate. Additionally, researchers noted that the changes led to brain activity desynchronization of various special scales in the brain.

In April 2022, a collaborative study between the Imperial College London’s Centre for Psychedelic Research and University of California, San Francisco, found that psilocybin helps patients with depression “open up” their brains weeks after consuming. “The effect seen with psilocybin is consistent across two studies, related to people getting better, and was not seen with a conventional antidepressant,” said Carhart-Harris last year. “In previous studies we had seen a similar effect in the brain when people were scanned whilst on a psychedelic, but here we’re seeing it weeks after treatment for depression, which suggests a ‘carry over’ of the acute drug action.”

At the time, Cahart-Harris noted that more research is necessary to better understand how psilocybin affects the brain. “We don’t yet know how long the changes in brain activity seen with psilocybin therapy last and we need to do more research to understand this,” Cahart-Harris said. “We do know that some people relapse, and it may be that after a while their brains revert to the rigid patterns of activity we see in depression.”

Previous psilocybin studies also reveal many other potential benefits of the substance for medical use. In 2015 we saw reports of how psilocybin helped some patients curb alcoholism, and in 2016 another study found that psilocybin could help smokers address nicotine addiction. Most recently, the Imperial College of London is using U.K. government funding this fall to study psilocybin therapy as a way to treat gambling addiction.

Studies analyzing the effects of psilocybin on people with depression have increased over the years, finding correlations between the substance and treatment-resistant depression, major depressive disorder, and more.

The past couple of years have yielded progress in some areas of the U.S. such as Oregon. The state’s psilocybin therapy program laws took effect in January, and its first psilocybin service center was approved in May. “This is such a historic moment as psilocybin services will soon become available in Oregon, and we appreciate the strong commitment to client safety and access as service center doors prepare to open,” said Oregon Psilocybin Services Section Manager Angie Allbee.

This shift in acceptance of psilocybin, like cannabis, has caused an increase in normalcy for people who have tried the substance. Last year, Canadian Senator Larry Campbell spoke at the Catalyst Psychedelics Summit about how he personally uses psilocybin for depression. Former NHL Kyle Quincey, who has shared that he used psilocybin to help boost his mental health during the pandemic, announced in August that he plans to open up a psilocybin retreat called Do Good Ranch.

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