In brief
- Twenty-eight people with no prior psychedelic experience received 25 mg of psilocybin and were studied using electroencephalography, functional MRI, and diffusion imaging.
- One month later, brain activity entropy remained elevated, and diffusion signals pointed to more robust tracts between the prefrontal cortex and subcortical structures.
- The authors themselves urge caution: the sample size is small, and the biological significance of these structural changes remains unclear.
A team from the University of California, San Francisco, and Imperial College London has published one of the most comprehensive follow-up studies to date in Nature Communications regarding what remains in the brain after the acute effects of psilocybin have worn off. The short answer: something measurable, even a month later.
How it was done
The study involved 28 healthy adults who had never taken a psychedelic—an important detail that eliminates the influence of previous experiences. Each person first received 1 mg of psilocybin, a dose so low it functioned as a control, followed one month later by a high dose of 25 mg. The team combined three techniques—electroencephalography (EEG), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging—at three points: before the session, during the peak of the effect, and thirty days later.
Twenty-seven of the twenty-eight participants described the 25 mg session as the most unusual state of consciousness they had ever experienced, which gives an idea of the intensity of what was being measured.
What they found one month later
The functional finding was a persistent increase in brain entropy—that is, the variety and unpredictability of neuronal activity. This is not just an abstract value: those who showed the greatest increase were also those who reported more introspection and greater personal insight. In parallel, participants scored higher on cognitive flexibility at the one-month mark and reported improved well-being at two and four weeks.
The structural findings are the most striking and the most delicate. Diffusion imaging showed a bilateral reduction in axial diffusivity in tracts connecting the prefrontal cortex with subcortical regions—a pattern the authors interpret as denser or more intact fiber bundles, which covaried with lower modularity of brain networks. In terms of direction, this is the opposite of what is typically observed in aging.
What it implies
There are reasons for interest and reasons to temper expectations. In favor: the study uses a design with three neuroimaging modalities, involves people with no prior exposure, and includes a thirty-day follow-up, which is rare. Against: twenty-eight participants is a small sample, all were healthy, and the order of the sessions was always the same—low dose first, high dose later—so the effect of expectations or test repetition cannot be entirely ruled out. The authors also emphasize that more studies are needed to understand what these structural changes actually mean; diffusion is an indirect measure and is not equivalent to having observed new neurons.
This work fits with other recent pieces on the common brain pattern of psychedelics and provides something that was missing: a long time window. If you want the general context of this substance, we have gathered it in our Psychedelics Guide on psilocybin and magic mushrooms.
Source
- Lyons T, Spriggs M, Kerkelä L et al. Human brain changes after first psilocybin use. Nature Communications 17(1):3977, May 5, 2026. DOI 10.1038/s41467-026-71962-3.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
