CNN
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When he began the brain scans, neurologist Dr. Nico Dosenbach wasn’t sure whether subjects were being given a hallucinogen or a placebo as part of a new clinical trial to examine what psilocybin, the main psychoactive ingredient in magic mushrooms, does on the brain.
Suddenly, he felt his heart beat faster, he felt a surge of energy and his vision changed, but it wasn’t until his brain transformed into a computer that he realized he was in the middle of a psychedelic trip.
“Until the effects began, no one in the trial knew whether they were taking psilocybin or Ritalin (the stimulant methylphenidate), which was chosen as a placebo because it has a stimulant effect similar to having a cup or two of coffee,” said Dosenbach, a professor of neurology at Washington University School of Medicine in St. Louis.
“But I didn’t think this was a placebo,” says Dosenbach. “I was on a computer tablet and my thoughts were like a computer’s thoughts, which of course were gibberish. I knew this was unusual, but it didn’t scare me.”
Dosenbach is co-lead author of a very small pilot study in which healthy volunteers had their brains scanned with functional magnetic resonance imaging (fMRI) up to 30 times over the course of three weeks before, during, and after a psilocybin-induced hallucinogenic experience.
“We found that psilocybin disrupts brain synchronization,” said Ginger Nichols, co-lead author of the study published Wednesday in the journal Nature.
“When you take psilocybin, your brain disconnects from common pathways and reconnects to different parts of the brain,” said Nichols, an associate professor of psychiatry at Washington University School of Medicine in St. Louis.
These novel pathways may be responsible for the success of some psychedelics in treating mental illnesses such as depression and anxiety. Psilocybin, also known as “shrooms,” is illegal under federal law, but in 2020 Oregon became the first state in the U.S. to legalize psilocybin for personal use by those 21 and older.
However, the U.S. Food and Drug Administration has allowed psilocybin to receive breakthrough drug status, a process that expedites the development and review of promising medicines.
Nichols said scans in the new study revealed increased connections to the anterior hippocampus, which is responsible for emotional memory, perception and imagination.
The scans also lit up parts of the default mode network, which influences a person’s sense of self, time and space. Antidepressants also target the default mode network, trying to interrupt “the negative thought loops — stuck thoughts — that can happen in depression,” Nichols said.
“Many antidepressants act on the default mode network that connects to other parts of the brain, but they act much more slowly than psychedelics,” she said.
Small clinical trials have shown that giving one or two doses of psilocybin to people with severe treatment-resistant depression (usually those who don’t respond to traditional antidepressants) can produce dramatic, long-lasting changes.
Psilocybin is used to treat cluster headaches, anxiety, Anorexia nervosa, obsessive-compulsive disorder, various forms of substance abuse.
Clinical trials typically use a trained psychotherapist who accompanies the patient during the psychedelic trip, and in many trials the therapist meets with the patient several weeks before and after the event to help guide and integrate insights gained from the experience.
The new study uses multiple brain scans to show that psilocybin makes connections in the brain more flexible, which could help people overcome “rigid and maladaptive patterns” of thinking and behaviour, said Professor Dr Petros Petridis. “The study is a step forward for the psychiatric community,” said Dr.
“Psilocybin may open the door to change and allow therapists to guide their patients,” Petridis wrote in a review published alongside the study.
“But ultimately, large-scale clinical trials with diverse patient populations and factorial study designs (ones that can evaluate multiple interventions simultaneously) will be needed to examine the effectiveness of psychedelics such as psilocybin and the role of talk therapy in treatment,” he added.
The study was very small, with just seven volunteers. Each subject took either 25 milligrams of pharmaceutical-grade psilocybin or 40 milligrams of methylphenidate, a stimulant drug often prescribed for attention-deficit hyperactivity disorder (ADHD). Some participants returned for a second dose of psilocybin six to 12 months later.
All of the study participants had a history of taking psychedelics and having “mystical experiences” (loosely defined as altered states of consciousness).
At the culmination of his journey, Dosenbach began to feel as if he was existing inside the minds of people he knew, experiencing their thoughts as his own.
“I got inside the brains of famous neuroscientists, including some of my most senior colleagues, and literally surfed their brainwaves,” he said.
“Science does not yet fully understand the brain, but I suddenly felt like I understood exactly how it works. But if you ask me how it works, I have no words, just a feeling.”
Each participant had a different experience, but only one did not enter a mystical state, Dosenbach said.
“My sense of self expanded as if I was the universe,” he said. “Other people reported seeing God, and if I was very religious I would have seen it, but for me it was like, ‘Oh, I am the universe.'”
“Then it went away, in what psychiatrists call ego death,” he said. “And at the same time, I lost my sense of place and time stopped. It literally felt like I was there for days and weeks, trying to figure things out.”
Nichols said one man was able to pinpoint the specific time during an fMRI scan when he had his most vivid mystical experience.
“He felt the light of God shining down on him,” she says. “We actually went to that spot with the scan and were able to pinpoint exactly when he felt it, and it happened at the peak of the desynchronization. (From typical pathways in the brain)
Sarah Moser/Washington University School of Medicine
The psilocybin-treated brain shows peak activity, indicating which parts of the brain are reconnecting different pathways compared to before ingestion. The most reconnected areas are shown in red and orange.
The scans showed that most of the brain’s networks had returned to normal a few days after taking psilocybin, but connections between the default mode network and the anterior hippocampus persisted for up to three weeks, Nichols said.
This lasting effect could explain some of psilocybin’s therapeutic effects, she added.
“You get a big initial effect, and then when that wears off, you’re left with a pinpoint effect,” says Dosenbach, “and that’s exactly what you’d expect from a promising drug.”
“You don’t want people’s brain networks to be disrupted for days, but you don’t want everything to go back to normal right away,” he said. “You want the effect to last long enough to make a difference.”
