A single dose of psilocybin, the psychedelic substance found in magic mushrooms, causes physical changes in the brain that can remain detectable for up to a month, according to researchers at the University of California, San Francisco and Imperial College London.
This study nature communicationshealthy adults who had never used psychedelics participated. Although none of the participants had been diagnosed with a mental health condition, the findings may provide clues as to why psilocybin showed promise in treating depression, anxiety, and addiction.
The researchers focused on temporary increases in the brain’s “entropy,” a term that describes the diversity and unpredictability of neural activity. Their results suggest that this more diverse pattern of brain activity may facilitate psychological insight, and that the psychedelic experience itself may play an important role in psilocybin’s long-term effects.
Greater increases in entropy in the minutes and hours after high-dose ingestion were associated with greater emotional insight the next day. Participants who reported more insights were also more likely to describe an improvement in their sense of well-being one month later.
“Psychedelic means ‘mind-revealing’ or making the mind visible,” said lead author Robin Carhart-Harris, Ph.D., Ralph Metzner Distinguished Professor of Neurology at the University of California, San Francisco. “Our data show how the experience of such psychological insight is related to the entropic quality of brain activity, and how both are involved in subsequent improvements in mental health. It suggests that the correlation between travel and the brain is an important component of how psychedelic therapy works.”
Measuring the effects of psilocybin on the brain
The researchers used several methods to examine brain activity, connectivity, and structure. Measurements were taken before psychedelic administration, at the peak of the experience, and again one month later.
None of the 28 volunteers had a diagnosed mental health condition, allowing the team to conduct a wider range of tests than would have been possible with a group of clinical patients.
In the first phase of the experiment, participants were given 1 mg of psilocybin, which the researchers treated as a placebo dose. Brain activity was then monitored with electroencephalography (EEG), which records electrical signals through electrodes placed on the scalp.
Over the next few weeks, researchers assessed psychological insight, well-being, and cognitive performance. They also used functional MRI (fMRI) to study brain activity and diffusion tensor imaging (DTI) to examine connections between different parts of the brain.
One month after receiving the placebo, participants were given 25 mg of psilocybin, an amount that can produce a powerful psychedelic experience. The researchers again recorded brain activity with EEG during the trip and repeated the same psychological and imaging assessments over the next several weeks.
This design allowed the team to compare the effects of a full dose of the psychedelic with those observed after administering 1 mg of a placebo.
Psilocybin increases brain entropy
Within 60 minutes of ingesting the 25 mg dose, EEG recordings showed increased brain entropy. This finding suggests that the brain was generating and processing a wider range of information while under the influence of psilocybin.
When the researchers examined the participants with DTI a month later, they found signs that the nerve tracts had become denser and more complete. DTI works by measuring how water moves along pathways in the brain.
This pattern was the opposite of the changes commonly associated with aging, where the neural tube tends to become more diffuse.
The researchers emphasized that additional research is needed to determine exactly what these structural findings mean. Still, researchers called the results an unprecedented sign that psychedelics can cause lasting changes in the brain.
Sustainable improvements in insight and well-being
The day after taking 25 mg of psilocybin, 27 of the 28 participants described the experience as the “most” unusual state of consciousness they had ever experienced. The remaining participants ranked this among the five most unusual experiences of their lives.
Participants also reported significantly greater psychological insight after the 25 mg dose than after the 1 mg placebo dose.
Well-being improved two and four weeks after the high dose. These ratings include responses such as “I feel optimistic about the future” and “I am coping well with my problems.”
One month after the experiment, participants also performed well on a test of cognitive flexibility, which measures the ability to adapt thinking and respond to changing information.
“Psilocybin appears to loosen fixed patterns of brain activity, giving people the ability to modify rigid thinking patterns,” said Dr Taylor Lyons, a researcher at Imperial College London and lead author of the paper. “The fact that these changes can be tracked with insight and improve well-being is particularly interesting.”
How psychedelic experiences can benefit you
Participants whose brain entropy increased the most in the first minutes and hours after psilocybin ingestion were most likely to report greater insight the next day.
These improvements in insight were associated with stronger improvements in well-being one month later. The researchers concluded that the experience of psychological insight appears to promote subsequent improvements in well-being.
The findings could ultimately help clinicians improve psilocybin treatments for people with mental health conditions. One possibility is to identify doses that generate enough brain entropy to promote meaningful insights without creating unnecessarily intense experiences.
“We already knew that psilocybin could help treat mental illness,” Carhart-Harris said. “But now we have a better understanding of how to do that.”
Authors: Other UCSF authors include Manesh Girn, PhD, Hannes Kettner, and Adam Gazzaley, MD. See the paper for all authors.
Funding: This research was funded by charitable donations to the Center for Psychedelic Research, Imperial College London, the Alex Mosley Charitable Trust, and the Beckley Foundation. Carhart-Harris is supported by a Ralph Metzner Distinguished Professorship and a philanthropic gift to the Department of Psychedelics at Neuroscape at the University of California, San Francisco, as well as a philanthropic gift to the Carhart-Harris Institute.
