Psilocybin may cause lasting brain structure changes, research suggests. Scientists have found that a single dose of the active compound in magic mushrooms can produce anatomical alterations in the brain that remain detectable a month later, even in people who had never taken a psychedelic before.
How the brain changes
The evidence emerged from advanced scanning techniques that track the movement of water molecules through nerve fibre bundles. Using a method called diffusion tensor imaging (DTI), researchers observed a reduction in water diffusion along nerve tracts connecting the front to the middle of the brain. This drop in diffusion is thought to reflect nerve tracts that have become denser and more robust — the opposite of what happens in ageing and dementia, where these same tracts tend to become thinner and more diffuse.
DTI is an advanced form of MRI that measures how water moves through brain tissue. Water diffuses more freely along the length of healthy nerve fibres than across them, so changes in diffusion patterns can reveal subtle shifts in the microstructure of white matter. In this study, the lower diffusion seen a month after the psilocybin dose suggests either pruning of some nerve fibres or the growth of new nerves that have not yet developed insulating sheaths. The researchers cautioned that further work is needed to confirm precisely what underlies the signal they detected.
“It’s remarkable to see potential anatomical brain changes one month after a single dose of any drug,” said Professor Robin Carhart-Harris, a neurologist at the University of California, San Francisco, and senior author on the study. “We don’t yet know what these changes mean, but we do note that overall, people showed positive psychological changes in this study, including improved wellbeing and mental flexibility.”
Links to therapeutic effects
Within an hour of taking a full 25mg dose of psilocybin, electroencephalography (EEG) revealed a surge in what scientists call brain entropy — a measure of the unpredictability and variability in neural signalling. The greater the entropy spike, the more diverse the information the brain appeared to be processing. That temporary shift was linked to lasting psychological outcomes: participants who experienced the largest increase in brain entropy were most likely to report deeper psychological insight and better wellbeing a month later.
Researchers believe these findings help explain how psychedelics might treat conditions such as anxiety, depression and addiction. The drugs are thought to promote flexible thinking and help people break out of rigid, destructive cognitive patterns. Carhart-Harris described the observed link between brain entropy and psychological improvement as a “psychobiological therapeutic action for psilocybin.” The study was part of a broader exploration of the “entropic brain effect,” a theory developed by Carhart-Harris and colleagues at Imperial College London that psychedelics increase the variety of neural activity.
Professor Alex Kwan, a neuroscientist at Cornell University in New York, noted that experiments in mice have shown psychedelics can rewire connections between nerves — a form of neural plasticity that could underpin their therapeutic effects. “This study comes closer than most to addressing that question, by giving evidence of lasting changes in brain structure after psychedelic use,” he said. But he cautioned that the results, while “exciting,” came from a small number of volunteers and that DTI provides only an indirect and limited view of brain connections. Kwan’s own laboratory uses advanced imaging techniques to study how psychiatric drugs alter neural circuits.
Study design and methodology
The research involved 28 healthy volunteers with an average age of 41, none of whom had ever taken a psychedelic drug. To establish a baseline, participants first received a 1mg dose of psilocybin — so small it was considered a placebo. The scientists used EEG to measure their brain activity via scalp electrodes, and volunteers completed a battery of psychological tests over the following weeks to assess wellbeing, depth of psychological insight and thinking flexibility. Functional MRI scans and DTI monitored their brains during the same period.
A month after the placebo session, each participant took a single 25mg dose of psilocybin, enough to produce a powerful psychedelic experience. The same tests and brain monitoring were repeated during the drug’s effects and for weeks afterwards. The researchers deliberately used a fixed-order design — placebo first, then active dose — because a high dose of psilocybin can cause lasting psychological changes that might interfere with a subsequent placebo session.
The findings were published in Nature Communications. Imperial College London’s Centre for Psychedelic Research, where Carhart-Harris previously worked, has been at the forefront of this field: it was the first centre in the world to study the brain effects of LSD with modern imaging and the first to investigate psilocybin for severe depression. Psilocybin is a Class A drug in the UK, with strict legal controls and licensing requirements for research. Despite these barriers, studies have shown that psilocybin-assisted therapy can match existing treatments for reducing anxiety and depression symptoms, and a head-to-head trial against the antidepressant escitalopram found comparable results with faster and larger reductions on some measures.
The study’s fixed-order design means that some of the observed psychological improvements could reflect practice effects — participants becoming more familiar with the tests — rather than being solely attributable to the drug. Researchers acknowledged this limitation, alongside the small sample size, and called for larger, controlled trials to confirm the findings.