Psilocybin doesn’t scramble the brain — it aligns it with context

The standard story about the psychedelic brain is that it becomes desynchronized, more “entropic,” more disordered. A new open-access Nature paper from Adeel Razi’s group at Monash (Stoliker et al., with co-authors including Anil Seth, Robin Carhart-Harris and Gustavo Deco) argues that this is mostly an artifact of averaging over time. When you look at how brain activity unfolds moment to moment, psilocybin shows a hidden order: brain activity becomes more tightly locked to whatever the person is experiencing at that moment.

The study. Sixty-two adults with no previous psychedelic experience were scanned with fMRI and EEG before psilocybin and again after a 19 mg dose. Each session had four conditions: eyes-closed rest, guided meditation, and music, followed by an eyes-open silent movie of drifting clouds. Half the participants later ranked the experience among the most meaningful of their lives.

What the conventional measures show:

• Eyes-closed conditions:
  • Integration of sensory (especially visual) regions with the rest of cortex fell.
  • Integration of associative regions rose.
• Eyes-closed vs. eyes-open: the normally sharp difference between these states largely collapsed.
  • In the visual network, the eyes-closed/eyes-open gap in global connectivity shrank by 85%.
  • On EEG, the eyes-open/eyes-closed difference in alpha power fell by about half.
• Modularity: functional modularity, meaning how segregated the networks are, decreased in every condition.

What the machine-learning view adds. The authors used a contrastive embedding method (CEBRA) to compress each person’s whole-brain activity into a low-dimensional trajectory. They then asked how well a classifier could tell which context (rest, meditation, music, movie) each moment belonged to.

• Context alignment: under psilocybin, trajectories formed tight, distinct clusters for each context. In strong responders, classification rose from about 62% to about 98%.
• Link to experience:
  • Classification accuracy correlated with mystical-experience scores (r = 0.64).
  • It also correlated with next-day “mindset change” (r = 0.40).
  • The strongest links were with positively felt self- and boundary-dissolving effects such as unity, bliss and spirituality.
  • Anxiety and impaired cognition showed no link.
• Why averaging misses it: time-averaged modularity predicted neither subjective experience nor later change. The meaningful organization lives in the temporal dynamics that averaging throws away.
• Where the effect comes from: a perturbation analysis found that the default mode network and the visual network together account for nearly half of the gain. These are the two ends of the brain’s principal internal-to-external processing gradient. When both are altered, the functional boundary between self-model and world loosens.

Embeddedness. The authors call the experiential correlate of this alignment embeddedness: feeling continuous with the environment rather than connected to it as a separate entity. One participant described melding with the MRI machine, the floor, the walls and the air. One month later, the group showed gains in death acceptance, personal meaning and nature-relatedness.

An 8-week mindfulness course before dosing made no detectable difference.

Caveats. The design was open-label, the conditions ran in a fixed order, and the brain–behaviour links are correlational.

The closing paragraph will resonate with anyone who thinks in predictive-processing terms. The authors suggest the felt boundary between self and world is not a given but something the brain actively constructs and maintains. Embeddedness, they write, “may thus reveal less about what psychedelics add to consciousness than about what ordinary neural dynamics keep apart.”

(The above is a Claude Opus 5.5 summary of the article)