Monash study maps how setting reshapes brain activity during psilocybin experience

Researchers at Monash University in Australia have completed a five-year, single-site brain-imaging study examining how psilocybin affects neural dynamics in 62 healthy adults who had never used psychedelics before. The study, published in Nature, combined EEG and functional MRI scans taken before and after a single dose of psilocybin to create the largest single-site psychedelic neuroimaging dataset to date.

After dosing, participants moved through four consecutive conditions with eyes closed: a five-minute naturalistic movie, five minutes of rest, five minutes of audio-guided meditation, and seven minutes of music listening. Machine-learning analysis tracked moment-to-moment brain activity across each setting.

The analysis revealed that what appeared as global neural disorder contained structured pathways that aligned closely with the specific environmental context. Brain networks showed distinct reorganisation patterns depending on whether participants were watching a film, resting, meditating, or listening to music.

The strongest emergence of ordered brain activity occurred in participants who reported profound and positive experiences characterised by a marked separation between their sense of self and their surroundings — a phenomenon often described as ego dissolution or boundary dissolution.

Senior author Adeel Razi, a computational neuroscientist, said the findings highlight that psychedelic therapy cannot be separated from the context in which the drug is taken. First author Devon Stoliker noted that the experience itself may be a substantial part of how treatment produces lasting psychological change.

The study addresses a gap in prior research, which has largely relied on time-averaged connectivity across groups, making it difficult to observe how order emerges dynamically in individual brains over time and across different settings.

Researchers say the next step is to determine whether the individual brain signatures identified in this study can be generalised to predict meaningful therapeutic outcomes in clinical populations.

The work suggests that the subjective experience of psychedelics should not be treated as a side effect but may be central to the mechanism by which new mental order emerges from drug-induced neural chaos.