The Largest Psychedelic Brain Study Yet Reveals How Psilocybin Helps People Feel At One With Existence

Psychedelics are acquiring greater clinical significance, and a growing body of recent research has examined the effects of psilocybin in increasingly fine detail. That work suggests it can leave enduring, meaningful changes in brain activity.

Psilocybin, the powerful psychoactive compound in ‘magic mushrooms’, is believed to promote brain plasticity. By rearranging neural connections and signalling pathways, it may be able to change mental states that would otherwise remain fixed.

Some people who use it have, in fact, described a heightened sense of immersion in everything: space, time and the self seem to break apart and become interconnected, with an individual’s identity blending into the wider cosmos.

That may sound rather chaotic – and some researchers have viewed it that way.

Psilocybin-related disruptions in the brain have commonly been understood as disorganised and entropic. Certain brain networks can move, at least for a time, from an ordered and rigid arrangement towards one that is more flexible and disordered.

However, the largest psychedelic brain study yet conducted at a single site, published in Nature, suggests this apparent disorder does not tell the full story.

Psilocybin brain networks reveal order within disruption

"We uncovered hidden order within that disruption," says Devon Stoliker, a neuroscientist and consciousness researcher at Australia’s Monash University, and lead author of the study.

"Under psilocybin, brain networks that help us process our inner world and the world around us became less distinct, but reorganised into patterns that reflected what people were experiencing."

"This was strongest in people who had more positive psychedelic experiences and felt less separate from the world around them."

The psychedelic psilocybin molecule was first derived from mushroom species. (Kateryna Kon/Science Photo Library/Getty Images)

Over a five-year project at Monash University, scientists combined functional magnetic resonance imaging (fMRI), electroencephalography (EEG), machine-learning models and questionnaires to investigate the mind’s natural response after a dose of psilocybin.

The research included 62 healthy adults who had never previously taken psychedelics. Their brains were scanned both before and after psilocybin treatment as they rested, meditated, heard music, or watched a silent film showing moving clouds.

Using blood-oxygen signals mapped across brain regions, the team identified reduced functional modularity – the usual separation of brain activity into discrete networks.

A central intermediary appears to be the default mode network (DMN), a connected set of brain regions.

The DMN functions rather like an air-traffic controller for the brain, bringing together information from areas that process abstract ideas including space, time and identity. It is particularly active when we daydream or look inwards.

Psilocybin appears to loosen the boundary between brain networks, opening the way for unfamiliar neurological interactions.

The psychedelic may consequently modify a brain gradient that spans the introspective DMN and the external-facing visual network, which processes what we see. This could support a change between internal and external attention.

Music, films and the psychedelic setting

Of the experimental conditions, listening to “ethereal” music appeared to produce the strongest overall organisation of the brain.

When participants watched a film, the effects were weaker: neural networks were disrupted less than when people rested or meditated with their eyes closed, or listened to music.

Put simply, the additional visual input influenced their psychedelic experience.

"This shows that context is not just background to the psychedelic experience. What a person is doing and focusing on shapes how their brain responds," says Adeel Razi, a computational neuroscientist at Monash University and the study’s senior author.

"For treatment, that reinforces why the environment and what a person does and experiences during the psychedelic session matter."

Machine learning was used to chart shifts in brain connectivity after psilocybin treatment. The patterns varied according to what participants were doing at the time. (Stoliker et al., Nature, 2026)

The scientists emphasise the value of a state they term embeddedness: "a perceptual and cognitive realization of being part of a unified whole."

Psilocybin seems to foster a feeling of oneness with the world and one’s surroundings. This may be an important therapeutic feature, potentially easing the existential distress that stems from feeling separate – with no hallucinations required.

The researchers also propose that experiences including the dissolution of selfhood and the collapse of existential boundaries could be major forces behind psilocybin’s observed effects.

"People who showed strong reorganisation also reported greater positive psychological changes the following day," Stoliker says, adding that earlier brain-imaging studies may not have detected this nuance because they assessed average effects across groups.

Implications for psychedelic-assisted therapy

It is important to note that the study enrolled healthy adults rather than patients, and was open-label, so it did not include a placebo group.

Even so, its results may help refine healthcare approaches based on psychedelics.

Research has shown that one dose of psilocybin can reduce depression symptoms for months. Such findings prompted Australia to authorise psilocybin as a prescription treatment for treatment-resistant depression in 2023, alongside MDMA therapy for PTSD.

Other potential therapeutic uses also look encouraging. Animal models, for instance, indicate that psilocybin might become a treatment for anorexia nervosa, although studies in humans are still necessary.

Clinical research has also made clear that these highly anticipated psychedelic therapies do not affect everyone in the same manner.

Related: Huge Psilocybin Dose Has Incredible Effect on Elderly Dementia Patient

The newest results from the Monash study may offer an explanation for why psychedelic-assisted therapy benefits some people more than others, as well as a potential means of measuring these differences.

"The finding that the organization of brain activity tracks [with] the transformative quality of subjective experience helps to elucidate how the psychedelic state translates into psychological change," the researchers conclude.

If these brain-scan measurements can be applied to patients, Razi adds, "this could eventually help clinicians understand how someone is responding and predict who is most likely to benefit."

This research was published in Nature.

This article was fact-checked and edited by Clare Watson. Although we take pride in our process, we are only human. If you notice an error, please tell us.