A single psychedelic trip may cause physical changes in the brain that could explain why some people report psychological benefits from the experience, a small study suggests.
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The research, published Tuesday in Nature Communications, focused on psilocybin, the psychedelic compound found in so-called magic mushrooms. The drug has been the subject of a number of studies in people that have found it appears to alleviate symptoms of depression and anxiety. It has also shown promise in addiction medicine.
Exactly how it may exert those benefits is still under investigation.
It’s a question of growing scientific interest. Last month, President Donald Trump signed an executive order to speed up psychedelic research on psilocybin and ibogaine, another psychedelic derived from the root bark of a plant native to the Congo Rainforest. Following the order, the Food and Drug Administration granted fast-track reviews to two companies studying psilocybin for depression.
Researchers have generally fallen into two camps: those who hypothesize the psychedelic trips are vital to any benefits — and brain changes — the substances produce and those who think the specific compounds themselves, not the trips, are the key.
The new study supports the former, suggesting the strength of the psychedelic experience does matter.
The research “found that the bigger the scores on psychological insight, the bigger the improvements in therapeutic response,” said senior study author Robin Carhart-Harris, a professor of neurology at the University of California, San Francisco School of Medicine.
The study included 28 people in London with an average age of 41 who had never taken psychedelics before and who had not been diagnosed with psychiatric conditions. Everyone was given a 1 milligram dose of psilocybin — considered a dose too small to induce a trip — which served as the placebo dose in the study. During that dose, Carhart-Harris and his team recorded their brain activity using an EEG, or electroencephalogram. They followed up with additional brain scans, including MRIs, over the following four weeks.
One month after the placebo dose, everyone got a 25 milligram dose. That dose is considered the industry standard for therapy, and it is the amount of psilocybin used by the drug companies seeking FDA approval for psilocybin-assisted therapy. (The psilocybin in the study was provided by one of the companies that has been granted fast-track review, Compass Pathways, which is based in the U.K. Several of the study authors have worked as scientific advisers to companies researching psychedelics, including Compass.)
At one hour, two hours and one month post-dose, the researchers tracked the participants’ brain activity. Before treatment and one month after, the participants also had a type of MRI called diffusion tensor imaging, or DTI, to measure the way water moves on neural fibers between different parts of the brain. In some of the so-called tracts between the prefrontal cortex — which is responsible for functions like emotional regulation and impulse control — and the middle parts of the brain, water flow appeared to be reduced post-treatment, suggesting possible structural changes in those areas.
“The general public tends to think of this as a restructuring of the neural pathways in the brain,” said Albert Garcia-Romeu, associate director of the Center for Psychedelic and Consciousness Research at Johns Hopkins School of Medicine in Baltimore. “What they really found is the way water moves along neural fibers appears to change.”
The findings of the new study, which Garcia-Romeu said is exploratory rather than definitive, “suggests there are some structural changes that get set up after the drug exposure, but some of these types of changes aren’t necessarily considered positive; some are what you would see with a TBI,” or traumatic brain injury.
Having a stronger trip appeared to produce bigger changes, the study found. While no one reported experiencing a trip with the placebo dose, all but one person reported significant alterations in their states of consciousness during the 25 mg dose. Those who reported more profound trips — which were also linked to more brain activity during the trips — as well as bigger insights in the days following those experiences, had bigger changes in water movement along brain tracts one month post-treatment.
“We don’t really know what it means, but the tracts become denser,” Carhart-Harris said, adding that some of the changes his team documented are the opposite of what researchers see in the brains of people with neurodegenerative disorders such as Alzheimer’s disease, when the tracts become more diffuse.
Although the main aim of the study was to investigate brain changes, about 70% of people in it did report increased well-being two and four weeks after the 25 mg dose.
“There is probably an important relationship between being in a very altered state of consciousness and people reporting being able to change their thought patterns,” said Dr. Joshua Siegel, an assistant professor of psychiatry at NYU Langone Health.
It is possible that psychedelic experiences scramble neurological pathways in the brain, giving them a chance to reorganize or break out of ruts once the trips are over, Carhart-Harris said.
In recent years, scientists have been interested in better understanding how psychedelics may initiate such brain plasticity — the brain’s ability to restructure neural connections. Studies have suggested that psychedelics increase the number of synapses, which facilitate communication between neurons, in parts of the brain related to emotional regulation and depression, said Siegel, who is also an investigator at the NYU Center for Psychedelic Medicine.
“But that has mostly been in rodent research. There is still this big question of what does that mean in humans and whether or not it’s correlated to therapeutic results,” he said. Researchers also must rely on proxy measures like brain scans in humans, because, unlike in animal studies, they cannot dissect the human brain at the end of a study.
While Carhart-Harris, Garcia-Romeu and Siegel all agree more research, particularly larger studies, will need to both replicate the results and explore whether the brain changes appear to have a therapeutic effect, Garcia-Romeu said the study provides welcome new information.
“It’s continuing our trajectory of understanding why these drugs appear to potentially have long-lasting effects in people,” he said.
Typically, when people are given a drug, they do not continue to have sustained benefits once it has worn off. But with psychedelics, people tend to report ongoing effects, whether they be changes in depression or in anxiety, he said.
“This gives us a better sense of how we should study this in people and, if they are therapeutic, why,” Garcia-Romeu said.
