When he began the brain scan, neurologist Dr. Nico Dosenbach wasn’t sure whether he had been given a psychedelic or a placebo as part of a new clinical trial that would capture how the brain works with psilocybin, the main psychoactive ingredient in magic mushrooms.
Suddenly, he felt his heart beat faster, a surge of energy and a change in his vision. However, it was only when his brain turned into a computer that he knew for sure that he was on a psychedelic trip.
“Until the effect started, no one in the trial knew whether they had taken psilocybin or Ritalin (the stimulant methylphenidate), which was chosen as the placebo because it is also a stimulant, like drinking a cup of coffee or two,” said Dosenbach, a professor of neurology at Washington University School of Medicine in St. Louis.
“But then I thought, no, this is not a placebo,” Dosenbach said. “I was the computer tablet, and my thoughts were like computer thoughts, which of course doesn’t make sense. I was aware that this was not normal, but it wasn’t scary.”
Dosenbach is the leader of a very small pilot study that performed up to 30 functional MRI scans of the brains of healthy participants before, during, and three weeks after a psychedelic psilocybin trip.
“We found that psilocybin desynchronizes the brain,” said Ginger Nichols, co-author of the study. published on Wednesday (17) in the journal Nature.
“When psilocybin is present, the brain disconnects from its typical 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 new pathways may be responsible for the success of some psychedelics in treating mental health disorders such as depression and anxiety. Also known as psilocybin mushrooms, psilocybin is illegal in the United States, although Oregon became the first U.S. state to legalize psilocybin for personal use for those 21 and older in 2020.
However, the United States Food and Drug Administration (FDA) has allowed psilocybin to be treated as a breakthrough drug, a process that speeds up the development and review of promising drugs.
Greater access to sense of self
Scans from the new study highlighted an increase in connections to the anterior hippocampus, which is responsible for emotional memory, perception and imagination, Nichols said.
Parts of the default mode network, which impacts a person’s sense of self, time and space, also lit up in the scans. Antidepressants also target the default mode network, trying to interrupt the “negative thought loop or fixed thinking that can occur with depression,” Nichols said.
“Many antidepressants work on the default mode network by connecting to other parts of the brain, just much more slowly than psychedelics,” she said.
Small clinical trials have shown that one or two doses of psilocybin can make dramatic and lasting changes in people who have more treatment-resistant depressive disorder, which typically does not respond to traditional antidepressants.
Psilocybin also shows promise in combating cluster headaches, anxiety, anorexia nervosa, obsessive-compulsive disorder, and various forms of substance abuse.
Typically, clinical trials use trained psychotherapists who sit with the person during the psychedelic trip. In many trials, the therapist meets with the person in the weeks before and after the event to help guide and integrate any insights from the experience.
The new study uses multiple brain scans to illustrate how psilocybin can make connections in the brain more malleable, thereby helping people overcome “rigid and maladaptive patterns” of thinking and behavior, said Dr. Petros Petridis, a professor of psychiatry at the Center for Psychedelic Medicine at NYU Langone in New York City. He was not connected to the study.
“Psilocybin could open the door to change by allowing the therapist to guide the patient,” Petridis wrote in a review published with the study.
“However, large clinical trials with diverse patient populations and factorial study designs (which allow more than one intervention to be evaluated simultaneously) will be needed to examine the efficacy of psychedelics such as psilocybin and the role of psychotherapy in treatment,” he added.
“No words, just the feeling”
The study was extremely small, with just seven volunteers. Each person took either 25 milligrams of pharmaceutical-grade psilocybin or a 40-milligram dose of methylphenidate, a stimulant often prescribed for attention deficit hyperactivity disorder (ADHD). Some participants returned for a second dose of psilocybin 6 to 12 months later.
All study participants had prior experience with psychedelics or “mystical experiences,” loosely defined as an altered state of consciousness.
At the height of his journey, Dosenbach began to feel as if he were present in the minds of people he knew, experiencing their thoughts as if they were his own.
“I was in the brains of famous neuroscientists, including the most senior colleague I work with, and literally surfing the brain waves,” he said.
“Science still doesn’t fully understand the brain, but I felt like I suddenly knew exactly how the brain works. However, if you asked me how it worked, I wouldn’t have the words, just the feeling.”
Each of the participants had different experiences, with only one not entering a state of mysticism, Dosenbach said.
“My sense of self extended as if I was the universe,” he said. “Other people have reported seeing God, and if I was very religious I could see that, but for me it was more like, ‘Oh, I am the universe.’”
“And then that disappeared in what I think psychiatrists call an ego death,” he said. “Simultaneously with that, I lost my sense of place and time stopped. It felt like I was literally there for days and then weeks figuring things out.”
One man was able to pinpoint the specific moment during the scan when he had his most vivid mystical experience, Nichols said.
“He felt like the light of God was shining on him,” she said. “We were able to actually go to that point in the scan and pinpoint when he felt that — it happened at the height of the desynchronization (of the brain’s typical pathways).”
A window for change
The scans showed that in the days after the psilocybin trip, most brain networks returned to normal. However, connections between the default mode network and the anterior hippocampus persisted for up to three weeks, Nichols said.
It’s possible that this persistent effect could explain part of psilocybin’s therapeutic impact, he added.
“There’s a massive effect initially, and when it fades, a punctual effect remains,” Dosenbach said. “That’s exactly what you’d like to see for a potential drug.
“You wouldn’t want people’s brain networks to be obliterated for days, but you also wouldn’t want everything to go back to normal immediately,” he said. “You want an effect that lasts long enough to make a difference.”
Source: CNN Brasil

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