The Human Brain on Psilocybin aka Magic Mushrooms
Researchers elevate psilocybin research by scanning their own brain while tripping
Hiya!
Since at least 3,000 BCE, our species has intentionally consumed plants to induce psychoactive and psychedelic experiences, typically for spiritual and healing purposes. Still, such practices continue today and have expanded to include modern drugs such as LSD, MDMA (ecstasy), and ketamine — many of which are done recreationally rather than ritualistically.
The effects of psychedelics, in particular, capture the attention of more than party-goers, though. Modern researchers have continued to support the idea that when experienced safely, psychedelic experiences can relieve mental distress, such as depression and post-traumatic stress disorder (PTSD). Scientists have studied the compounds and effects of psychedelics like magic mushrooms for decades, but now research is showing precisely how they affect the brain.
Psilocybin
Psilocybin (4-phosphoryl oxy-N, N-dimethyltryptamine) is one of the most widely distributed natural hallucinogenic compounds on Earth, found in over 180 species of mushrooms worldwide. Mushrooms containing psilocybin are commonly referred to as “magic mushrooms” or simply “shrooms” which are typically dried or crushed into power before being consumed.
The compound is part of a group of drugs called psychedelics, which distort our sense of reality, leading us to see, hear, and feel things that no one else can because they aren’t happening in real life — this experience is known as “tripping” or a “trip.” Psilocybin can trigger intense emotions and lead some individuals to lose their perception of time and space temporarily.
While our species has utilized psilocybin’s effects for millennia, we only began studying the compound and other psychedelic drugs like lysergic acid diethylamide (LSD) scientifically in the 1950s and early ‘60s. The studies back then were admittedly flawed compared to today’s standards, but they also showed promising potential for treatments of mental illnesses, including substance use disorders.
Despite its promise, most research into psychedelics was discontinued due to restricted federal drug policies introduced in the 1960s, and it remained nearly dormant until the 1990s, when interest in human psychedelic research was revived, and regulations began loosening.
In more recent clinical trials, a single dose of psilocybin has shown significant and sustained improvement in participants’ end-of-life anxiety, depression, and alcohol use disorder — but what’s going on in the brain while this happens?
Animal research indicates that psilocybin can modify the brains of cats and mice, potentially promoting neuroplasticity by weakening strong but possibly harmful neural connections while facilitating the formation of new ones.
But that’s animals. What about psilocybin’s effects on the human brain? Well, that’s precisely what researchers at Washington University wanted to find out — so much so that one of them joined the study participants in consuming the compound and scanned his brain while he tripped.
New Research
Neuroscientist Joshua Siegel led a dedicated team of scientists at Washington University’s School of Medicine in St. Louis, Missouri, that imaged psilocybin’s influence on the brains of a small group of people before, during, and after consumption. The researchers also linked changes in brain networks with the subjective experiences of the participants. They published their research in Nature on July 17, 2024.
Siegel’s team included Dr. Nico Dosenbach, an expert in brain imaging and an associate professor of neurology at Washington University, and Dr. Ginger E. Nicol, an associate professor of psychiatry at Washington University who has experience running clinical trials with controlled substances.
For the study, Dosenbach, Nicol’s husband, and five other healthy adults were given either a stimulant via methylphenidate, which is a generic form of Ritalin, for the control group, or 25 milligrams of psilocybin — a high enough dose to cause hallucinations.
In the days and weeks leading up to, during, and for three weeks after, each participant underwent an average of 18 functional magnetic resonance imaging (fMRI) scans to track changes in their brains before, during, and after consuming the drug. Four participants, including Nicol’s husband, repeated the experiment six months later.
Since there’s always a risk of a psychedelic trip resulting in scary or negative experiences, each participant was paired with trained experts who helped prepare the participants for the experience, offered guidance and support during it, and helped the participants process their experiences afterward.
Dosenbach described his trip to Jon Hamilton of NPR:
“I was, like, drifting deeper into weirdness," […] “I didn't know where I was at all. Time stopped, and I was everyone,” […] “I was inside the brain, and I was riding brain waves, and I was Marc Raichle.”
Dr. Marcus Raichle is a well-known and respected figure in the neuroscience field. He’s also Dosenback’s colleague and the study's co-author. However, Dosenbach experienced just one round of psilocybin.
In contrast, the husband of Dr. Nicol was one of the four participants who returned for a second round of psilocybin six months later. His experience shows how unpredictable psilocybin trips can be. Dr. Nicol reported to Hamilton that:
"He had an almost religious experience the first time. The second time, he saw demons."
In addition to fMRI brain scans before, during, and after their trip, the researchers analyzed how the participants responded to a simple audiovisual task. The participants were asked to rate their feelings of transcendence, awe, and connectedness using the validated, 30-question Mystical Experience Questionnaire.
Remarkably, the researchers found that the changes in the participants’ functional brain networks while tripping tracked the intensity of the volunteer’s subjective experiences recorded in the questionnaire.
But that’s not all the researchers found.
So Many Results
Of all the articles and research I studied for this article, I think Hamilton summarizes the study’s findings best — that the brain “falls apart” under psilocybin’s influence. Yet, he doesn’t mean the brain crumbles or deteriorates. Instead, the brain’s rigidity is replaced with enhanced plasticity (this is a good thing), which can last for weeks.
A statement about the research by Washington University explains that, generally, our functional brain network is as unique and distinct as our fingerprint. However, the study showed that psilocybin distorts brain networks so much that the participants couldn’t be identified until the acute effects wore off. Dosenbach says in the statement:
“The brains of people on psilocybin look more similar to each other than to their untripping selves. Their individuality is temporarily wiped out. This verifies, at a neuroscientific level, what people say about losing their sense of self during a trip.”
You may recall Dosenbach was part of that group, as he reported that he “was everyone” when describing his experience with the drug. The effects of psilocybin on the brain astounded the researchers. Dosenbach told Andrew Jacobs of the New York Times:
“Psilocybin, in contrast to any other drug we’ve tested, has this massive effect on the whole brain that was pretty unexpected. It was quite shocking when we saw the effect size.”
Even when the researchers describe their observations, it’s challenging to imagine just how significantly psilocybin changes the brain. So, here’s a visual I found helpful:
Wild right? No wonder the researchers were amazed to see that. Still, one brain network in particular seems to be the most affected by psilocybin: the default mode network. This network is active when we’re in our “default” mode, like daydreaming, introspection, or not focusing on the outside world. (Fun fact: Raichle, the guy Dosenbach became while tripping, discovered the default mode network in 2015.)
Beyond daydreaming, the default mode network is crucial for our self-referential memory, which stores and retrieves information when the information references the Self.
In other words, Joshua Siegel, the study’s first author and a neuroscientist at Washington University, told Jacobs that the default mode network helps keep track of information like “What was I doing?” and “Who am I?” But while under the influence of psilocybin, Siegel says:
“The activity in these networks became much more disorganized, and boundaries between the networks essentially evaporated.”
More specifically, psilocybin had a threefold greater impact on the participants’ default mode networks than the control group. Shan Siddiqi, a psychiatric neuroscientist at the Harvard School of Medicine who was not involved in the study, told Max Kozlov of Nature News,
“I’ve never seen an effect this strong.”
The array of changes isn’t permanent, though. Neurons in the default mode network calm down and resynchronize as the acute effects of psilocybin wear off. That said, the researchers report in the statement by Washington University that some small brain changes took weeks to revert to normal.
The researchers’ findings suggest that psilocybin produces powerful but temporary changes in the brain, especially in areas related to introspection. Dosenbach explains in the statement:
“There’s a massive effect initially, and when it’s gone, a pinpoint effect remains. That’s exactly what you’d want to see for a potential medicine. You wouldn’t want people’s brain networks to be obliterated for days, but you also wouldn’t want everything to snap back to the way it was immediately. You want an effect that lasts long enough to make a difference.”
The researchers observed one more intriguing finding. Remember the audiovisual task the participants performed throughout the study? Well, the researchers found that participants completed the task with about 80 percent accuracy while tripping. Curiously, the team found that the participants’ abnormal brain activity decreased while they were engaged in the task.
This response offers some of the first scientific evidence for what’s known as “grounding,” which is when we focus on a task or physical sensation to lessen the intensity or severity of a trip gone wrong — though it’s also useful during panic and anxiety attacks even when not on drugs.
The team’s results also add support that psychedelic experiences are largely context-dependent, meaning what a person does, where they are, who they’re with, and other factors influence how a trip goes and potentially any lingering effects of the experience.
Perspective Shift
As remarkable as this new research is, it’s just the beginning. While this study was small, with only seven participants, it includes a mountain of data, including the fact that each participant underwent about 18 fMRI scans, which is more than a typical brain imaging study.
Additionally, all seven study participants were in good mental and physical health at the time, so future research will need to include participants with various mental health diagnoses, such as depression or PTSD, to definitively link psilocybin’s observed brain changes with confirmed therapeutic benefits.
There’s still much to learn about how different people’s brains respond to psychedelics and the potential medicinal treatments they might be used for. As of now, the Food and Drug Administration (FDA) has not approved psilocybin as a treatment for any condition, but some states have legalized the drug for use in a supervised environment, such as with a therapist.
In 2020, Oregon became the first state to legalize psilocybin for medical purposes and remains the only state to do so today. However, currently, 17 additional states are in various stages of following Oregon’s lead. Meanwhile, psilocybin remains illegal in 33 states.
I understand the need for caution with both research and legislation regarding psychedelics. It wouldn’t be great if people were tripping everywhere willy-nilly. Education and safety measures are paramount if/when access to psilocybin becomes easier.
Still, humans have used mind-altering drugs for millennia — likely since we discovered their effects — for all sorts of reasons, but especially for spiritual purposes. Now we’re living during a time when we’re finally able to understand its effects on us.
Curious Life — which you receive sneak peeks of every Monday morning — explores a diverse range of topics, further exploring this Curious Adventure we call Life.
These articles require several hours, sometimes days, of research, writing, and editing before publication. To maintain high-quality content, Curious Life subscriptions help pay my bills so I can continue doing what I love — following my curiosities and sharing what I learn with you.
If you enjoy my work and want to show me support, you can donate to my PalPal. Thank you for reading. I appreciate you.
Very interesting. Michael Pollan’s book “How to Change Your Mind:” is also a helpful source re this subject.