World’s largest study on psychedelic psilocybin finds organisation hidden in the chaos of the brain

Credit: Turner Institute of Brain and Mental Health

A landmark five-year study by Monash University has found psychedelics reorganise brain patterns, giving clinicians powerful new insights into their therapeutic benefits.

In the world’s largest single-site acute-phase psychedelic neuroimaging study, published in the leading scientific journal Nature, researchers used AI and advanced neuroimaging to model brain dynamics in healthy adults, challenging the long-held view that psychedelics make brain activity chaotic or disorganised.

Lead and co-corresponding author Dr Devon Stoliker, a Turner Impact Fellow at the Turner Institute for Brain and Mental Health in the Monash School of Psychological Sciences, said the results revealed hidden organisation beneath the apparent disorder of the psychedelic state.

“Our work provides a neural basis for the profound feeling of continuity between self and world that participants often report, which helps to explain how the psychedelic state translates into psychological change,” Dr Stoliker said.

"At the individual level, we identified brain patterns that tracked the intensity and quality of each participant's subjective experience.”

Senior author and Principal Investigator Professor Adeel Razi, from the Turner Institute for Brain and Mental Health in the Monash School of Psychological Sciences, said the findings provide a critical biological marker that could revolutionise clinical trials and therapeutic treatments for internalising conditions like severe depression, anxiety, trauma, and addiction.

“We’ve shown that the brain isn't just descending into disorder during a psychedelic experience,” Professor Razi said.

“Instead, psilocybin reorganises brain activity into structured patterns shaped by what the participant is doing and experiencing,” he added.

The study, named PsiConnect, used a combination of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) to investigate what occurred in the brains of 62 participants under the influence of psilocybin across multiple contexts, including rest, music,  meditation, and movie watching.

The researchers drew on advanced brain imaging analyses conducted by Dr Leonardo Novelli and machine-learning analyses by Dr Moein Khajehnejad, both co-authors of the study, to map these complex brain dynamics.

“Together, these approaches revealed individual-level organisation missed by conventional methods, providing a more sensitive framework for future psychedelic research,” Dr Stoliker said.

"Crucially, we found that the strength of this reorganisation predicted improvements in participants' mindset the following day, helping to elucidate how these acute altered states support psychological change.

Professor Razi said the ability to measure these individual differences could ultimately help translate the findings into clinical practice. “Our findings are a step towards an evidence-based approach that could help clinicians identify ideal candidates for psychedelic therapy, optimise the therapeutic settings, and fine-tune dosing,” Professor Razi said.

In 2023, Australia became the first country to reschedule psilocybin and MDMA to allow authorised psychiatrists to prescribe them for treatment-resistant depression and PTSD.

Professor Razi said the United States and other nations are now exploring similar pathways.

“Australia is a trailblazer in this growing area of science, with a distinct global advantage in scaling these therapies responsibly,” Professor Razi said.

“As these countries look to us for direction, research from Monash will provide critical evidence to guide safe and effective implementation.”

While further longitudinal research is needed to determine how the observed reorganisation relates to lasting changes in brain function, the ability to map this biological signature marks a fundamentally new way of understanding psychedelic action in the human brain.

Read the research paper: https://doi.org/10.1038/s41586-026-10910-z