[Open access] Psychedelics align brain activity with context

[sal@mander.xyz]

Abstract

Psychedelics can profoundly alter consciousness by reorganizing brain connectivity, producing acute experiences that shape lasting psychological change. Psychedelic dynamics are commonly described as desynchronized or entropically disordered, yet the brain organization underlying self-dissolving and boundary-dissolving experiences that participants often report, and how context shapes that organization, remain unresolved. To address this, we acquired the largest single-site psychedelic neuroimaging dataset to date. Sixty-two adults underwent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) during rest and naturalistic stimuli (meditation, music and movie), before and on the day of psilocybin administration (fMRI ~ 80 min post-dose; EEG ~ 150 min post-dose). Half ranked the experience among the most meaningful of their lives. Here, using machine learning to represent the brain dynamics of each individual as low-dimensional trajectories, we show that psilocybin reorganizes brain activity into structured, context-sensitive patterns that co-vary with the quality of subjective experience, revealing a latent order missed by time-averaged measures. Networks that ordinarily segregate internal and external processing integrated, producing cohesive context-aligned trajectories in participants reporting the felt experience of being continuous with, rather than separate from, the environment, a state we refer to as embeddedness. The strength of this context alignment scaled with both the depth of self-dissolving and boundary-dissolving experience and the next-day mindset change. Our findings recast apparent disorder as latent organization aligned with context, linking neurobiology to subjective experience and behavioural change.

https://www.nature.com/articles/s41586-026-10910-z