Psilocybin is slowly emerging from the realm of forbidden curiosities and entering the much more severe realm of medical research. The delicate point is all here. When talking about psychedelic mushrooms, the risk of slipping into an easy story is very high: the substance “that changes the brain”, the experience “that opens the mind”, the therapeutic promise taken and transformed into a bar slogan. Research, fortunately, takes a slower pace. Measure, compare, wait, see what’s left after the most noticeable effect is over.
A new study published in Nature Communications followed 28 healthy adults, all with no prior experience with psilocybin or other psychedelics. The researchers observed what happened in their brains before, during and one month after taking it. First a minimal dose, 1 milligram, low enough to work as a control. Then a 25 milligram dose, capable of producing a true psychedelic experience, always in an experimental and controlled context.
The work was conducted by a research team from the University of California San Francisco and Imperial College London. Among the coordinators is Robin Carhart-Harris, one of the best-known names in studies on psychedelics and their possible use in clinical settings. The starting question was only apparently simple: why does a single session with psilocybin, in some clinical studies, seem to be associated with prolonged improvements in people with depression, anxiety or addictions?
What happens during the experience
During the administration, the volunteers wore EEG headphones to record the brain’s electrical activity. After about an hour after the 25-milligram dose, the brain signals became more complex. Researchers talk about brain entropy, a technical term that indicates greater variety in the brain’s activity patterns.
In practice, brain activity seemed less rigid, less stuck to its usual rhythms. Alpha waves, one of the brain’s main regulatory rhythms, have weakened. The brain appeared more “open”, more variable, less synchronized in its usual paths. The peak arrived around two hours, just when the subjective experience was most intense.
Nearly all participants described that moment as one of the most unusual states of consciousness they had ever experienced. Twenty-seven out of twenty-eight indicated it as the most special of their lives; the last one still put him in the top five. It is subjective, of course, but it tells us well about the strength of the experience and helps to connect it to the measurements recorded in the brain.
The track after a month
The most interesting part of the study comes next. One month after the high dose of psilocybin, brain scans showed changes in the white matter connections between the prefrontal cortex and some deeper areas of the brain. They are important circuits, involved in thinking, emotional regulation and decision-making processes.
The images looked at how water moves along nerve fibers. In those sections, the movement appeared reduced compared to the starting point, as if the fibers were more compact and organised. The authors speak of a signal compatible with structural changes, a particularly relevant finding because it was observed in healthy people and those experiencing their first psychedelic experience.
Previous studies have already suggested that psychedelics can promote some processes related to brain plasticity, such as the formation of new connections between nerve cells. Seeing a signal of this type in the human brain, after just one dose, adds an important piece. It should be read with caution, however. The sample is small, the participants were healthy and the follow-up was up to one month. Larger studies will be needed to understand how long this change really lasts and what clinical significance it has.
More mental flexibility
In addition to brain images, the researchers also collected psychological data. The volunteers reported a greater feeling of insight, that is, the perception of seeing themselves, their patterns, and some internal automatisms more clearly. The checks took place the day after the session, after two weeks and then at one month.
Well-being scores increased within two weeks and remained higher at the next follow-up. A cognitive test also showed greater mental flexibility: participants were able to adapt more quickly when, during a task, the rules suddenly changed.
The observed sequence is interesting. Those who showed the greatest increase in brain entropy during the experience also reported deeper insight the following day. That insight, in turn, appeared to link to improved well-being at one month. Psilocybin, in this study, therefore seems to act in several steps: first it temporarily modifies brain activity, then it can favor a different reading of oneself, and finally it leaves a trace in the way in which the person reports their well-being.
Because caution is needed
The comparison with studies on depression helps to bring order. In healthy participants, long-lasting changes in the coordination of brain networks were more subtle than those seen in people with depression. It makes sense: A brain already close to functional balance offers less room for visible changes than a brain stuck in more rigid, painful patterns.
This, however, makes it even more important to avoid enthusiastic reading. Psilocybin is studied as a possible therapeutic tool, within structured clinical paths, with preparation, supervision and integration of experience. The substance alone tells only part of the story. What matters is the context, the dose, the safety, the selection of the participants, the psychological support before and after.
DIY remains risky territory. A substance capable of modifying perception, mood and brain activity in such a profound way can have unpredictable effects, especially in vulnerable people, with psychiatric disorders, specific family members or fragile emotional contexts. Clinical research works precisely to understand when, how and for whom a treatment of this type can make sense.
In the future, monitoring brain entropy could help clinicians understand in real time whether a session is producing the mental state associated with a positive response. Elements such as environment, music and therapeutic accompaniment could also be adjusted more precisely. It seems unromantic, compared to the more colorful psychedelic tale. This is exactly what you need when it comes to health.
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