Summary: A single high dose of psilocybin doesn’t just create a temporary “trip”—it physically and functionally reshapes the brain for at least a month. A study reveals that psychedelics increase “brain entropy” (the diversity of neural activity).
This state of high information processing predicts the level of psychological insight a person feels the next day, which then forecasts long-term improvements in mental well-being and cognitive flexibility.
Key Facts
- The Entropy Spike: Within 60 minutes of a 25 mg dose, EEG scans showed a massive increase in brain entropy. This suggests the brain is processing a much richer, less “stereotyped” body of information than usual.
- Predicting Insight: The intensity of this entropic “whirlwind” directly predicted how much emotional self-awareness and insight participants reported the following day.
- Anatomical Integrity: One month after the experience, Diffusion Tensor Imaging (DTI) showed that the brain’s neural tracts were denser and had more integrity. This is the physical opposite of the neural “thinning” typically seen in aging.
- Breaking Rigid Patterns: Psilocybin appears to “loosen” entrenched patterns of thought, allowing the brain to revise “stuck” ways of thinking. This led to measurable increases in cognitive flexibility four weeks later.
- The “Trip” is Essential: The researchers argue that the subjective experience of the psychedelic trip, and the insight gained during it, is a mechanical requirement for the drug’s therapeutic benefits. It isn’t just a side effect; it’s the medicine.
Source: UCSF
Researchers at UC San Francisco and Imperial College London have shown that a single dose of psilocybin, the psychedelic compound found in magic mushrooms, causes likely anatomical brain changes that last for up to a month after the experience.
The study, published May 5 in Nature Communications, was done in healthy volunteers who had never taken a psychedelic, but it may help explain psilocybin’s therapeutic effects on conditions like depression, anxiety, and addiction.
The researchers link temporary shifts in brain “entropy” — which is the diversity of neural activity occurring in the brain — to insight. This suggests the psychedelic trip itself is important to the drug’s longer term therapeutic effects.
The researchers found that a high dose of psilocybin led to increased entropy in the minutes and hours after taking the drug. The degree of entropy predicted how much insight, or emotional self-awareness, the participants felt the next day; and this, in turn, forecasted improvements in their sense of well-being a month later.
“Psychedelic means ‘psyche-revealing,’ or making the psyche visible,” said senior author Robin Carhart-Harris, PhD, the Ralph Metzner Distinguished Professor of Neurology at UCSF.
“Our data shows that such experiences of psychological insight relate to an entropic quality of brain activity and how both are involved in causing subsequent improvements in mental health. It suggests that the trip — and its correlates in the brain — is a key component of how psychedelic therapy works.”
A careful assessment of psilocybin’s effects
Researchers used an assortment of brain imaging and brain measurement techniques, some of which was done during the peak of the psychedelic experience, as well as before and one-month after.
None of the 28 people in the study had a diagnosed mental health condition, which gave the scientists greater freedom to do more testing.
In the first part of the experiment, the subjects were given a 1 mg dose of psilocybin, which the researchers regarded as a placebo, and then monitored with electroencephalography (EEG), which records brain activity from electrodes on the scalp.
Over the next few weeks, the researchers measured their subjects’ psychological insight, well-being and cognitive ability. They examined brain activity with functional MRI (fMRI) and brain connectivity with diffusion tensor imaging (DTI).
One month after the placebo, the subjects were given 25 mg of psilocybin, a dose capable of eliciting a strong psychedelic trip. During the experience, researchers again measured the subjects’ brain activity with EEG, and in the following weeks they repeated the same tests they had given after the 1 mg dose.
This enabled the scientists to compare the effects of the psychedelic trip on the brain and mind to the effects of the placebo.
Greater ‘information’ in the brain after psilocybin
Within 60 minutes of taking the 25 mg dose of psilocybin, EEG revealed higher entropy, suggesting that the brain was processing a richer body of information under the psychedelic.
A month later, the researchers looked at their subjects’ brains with DTI, which measures the diffusion of water along neural tracts in the brain, and found that they were denser and had more integrity. This is the opposite of what happens in aging, which makes these tracts more diffuse.
The researchers cautioned that more work needs to be done to better understand the meaning of this change, but the result is a never-before-seen sign of how psychedelics can change the brain.
Enduring improvements in well-being
The day after the 25 mg dose, all but one of the 28 subjects rated the trip as the “single most” unusual state of consciousness they had ever experienced. The remaining person rated it as among the top five.
The people in the study also said they had experienced more psychological insight after taking the 25 mg of psilocybin than they had after the 1 mg placebo.
The subjects reported increased well-being two and four weeks after the study. This was measured from responses to statements like, “I’ve been feeling optimistic about the future” and “I’ve been dealing with problems well.” A month after the study they also did better on a test of cognitive flexibility.
“Psilocybin seems to loosen up stereotyped patterns of brain activity and give people the ability to revise entrenched patterns of thought,” said Taylor Lyons, PhD, a research associate at Imperial College London and the first author of the paper. “The fact that these changes track with insight and improved well‑being is especially exciting.”
A freer brain and a healthier mind?
The scientists found that the subjects who had experienced the largest increases in brain entropy in the minutes to hours after taking psilocybin were the most likely to have increased insight the next day and increased well-being a month later. They concluded that improved well-being was driven by the experience of insight.
The findings could improve treatment for people with mental illness with psilocybin, for example, by ensuring that the right dosage is used to produce the right amount of brain entropy to promote insight.
“We already knew psilocybin could be helpful for treating mental illness,” Carhart-Harris said. “But now we have a much better understanding of how.”
Authors: Other UCSF authors are Manesh Girn, PhD, Hannes Kettner, and Adam Gazzaley, MD, PhD. For all authors, see the paper.
Funding: This work was funded by philanthropic donations to the Centre for Psychedelic Research, Imperial College London, the Alex Mosley Charitable Trust, and the Beckley Foundation. Carhart-Harris is supported by the Ralph Metzner Distinguished Professorship and philanthropic donations to the Psychedelics Division, Neuroscape, UCSF, plus philanthropic donations to the Carhart-Harris Lab.
Key Questions Answered:
A: Think of your brain’s normal state as a well-worn path in the woods. Entropy is like a fresh snowfall that covers those tracks, allowing you to walk in any direction. In the brain, this means more diverse and unpredictable communication between regions, which helps break the “loops” associated with depression and anxiety.
A: While the researchers are still studying the exact mechanism, the DTI scans showed that water diffusion along brain tracts became more organized and “denser” a month after the trip. This suggests that the experience may stimulate the strengthening or repair of the physical “wiring” of the brain.
A: According to this study, the level of well-being improvement was directly driven by the experience of insight. If the dose is too low to create that “entropic” state and the subsequent psychological “aha!” moment, the long-term therapeutic effects may be significantly diminished.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience and psychedelics research news
Author: Levi Gadye
Source: UCSF
Contact: Levi Gadye – UCSF
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Human brain changes after first psilocybin use” by T. Lyons, M. Spriggs, L. Kerkelä, F. E. Rosas, L. Roseman, P. A. M. Mediano, C. Timmermann, L. Oestreich, B. A. Pagni, R. J. Zeifman, A. Hampshire, W. Trender, H. M. Douglass, M. Girn, K. Godfrey, H. Kettner, F. Sharif, L. Espasiano, A. Gazzaley, M. B. Wall, D. Erritzoe, D. J. Nutt & R. L. Carhart-Harris. Nature Communications
DOI:10.1038/s41467-026-71962-3
Abstract
Human brain changes after first psilocybin use
Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is largely unknown.
In an exploratory, placebo-controlled, within-subjects, electroencephalography (EEG), and magnetic resonance imaging (MRI) study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes are detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being are seen at one-month.
Diffusion tensor imaging (DTI) done before and one-month after 25 mg psilocybin reveals decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlate with decreases in brain network modularity (fMRI) over the same month.
Enduring functional brain changes are largely absent, but network modularity change (numerical decrease) negatively correlates with well-being change (significant increase), in line with previous findings in depression. Increased cortical signal entropy (EEG) at 1- and 2-hours post-dosing predicts improved psychological well-being at one-month.
Next-day psychological insight mediates the entropy to well-being relationship. All effects are exclusive to 25 mg psilocybin; no effects occur with a 1 mg psilocybin placebo.
