First psilocybin experience can give temporary and measurable changes in brain and well-being

There is a new scientific article in *Nature Communications* published on changes in the brain following the first psilocybin experience in people who had never used psychedelics before.

In it, we discuss:

The researchers studied 28 healthy participants who had led completely psychedelic-free lives. This means that they had never had a psychedelic experience before. In this exploratory, placebo-controlled study, participants were first given 1 mg of psilocybin as an active placebo and later 25 mg of psilocybin as a high dose. The researchers used EEG, fMRI, MRI and DTI to measure acute and long-term changes in brain function and brain structure.

A key finding was that 25 mg of psilocybin caused distinct changes in EEG readings during the acute phase. Particularly around 1 to 2 hours after ingestion, the researchers observed an increase in brain entropy, as measured by Lempel–Ziv complexity, and a decrease in alpha activity. This is consistent with the idea that brain activity during a psychedelic experience becomes temporarily less predictable and more dynamic.

On a psychological level, the researchers observed increases in cognitive flexibility, psychological insight and well-being after one month. Interestingly, increased brain entropy during the acute experience was associated with greater psychological insight the following day, and this insight was in turn associated with greater well-being after one month.

The researchers also found evidence, using DTI, of changes in white-matter tracts between the prefrontal cortex and subcortical areas, including connections to the striatum and thalamus. These changes were measured one month after the 25 mg psilocybin dose, but not after the 1 mg control dose. The authors emphasise that these are exploratory findings and that the significance of such DTI changes should be interpreted with caution.

In resting-state fMRI, long-term changes in functional connectivity were largely absent. However, the researchers did observe that a decrease in network modularity was associated with an increase in well-being. Lower modularity means that brain networks are less strictly separated and may function in a more globally integrated manner. This is consistent with previous research into psilocybin therapy for depression; however, as this study was conducted on healthy volunteers, it does not demonstrate any therapeutic effect.

It is important to note that this study does not demonstrate that psilocybin is a treatment for a specific condition. It was a small, exploratory mechanistic study involving healthy participants. The value of the article lies primarily in providing a better understanding of what changes may occur in the brain following an initial high dose of psilocybin, and how acute brain dynamics may be linked to subsequent psychological changes.

In a nutshell: this article shows that an initial high dose of psilocybin in healthy, psychedelic-naïve participants can induce acute changes in brain dynamics, with preliminary evidence of changes in insight, well-being and certain brain measures one month later.