Psychedelics Align Brain Activity with Context

Psychedelics can profoundly alter consciousness by reorganising brain connectivity; however, their effects are contextsensitive. To understand how this reorganisation depends on the context, we collected and comprehensively analysed the largest psychedelic neuroimaging dataset to date. Sixty-two adults were scanned with functional MRI and EEG during rest and naturalistic stimuli (meditation, music, and visual), before and after ingesting 19 mg of psilocybin. Half of the participants ranked the experience among the five most meaningful of their lives. Under psilocybin, functional MRI and EEG signals recorded during eyes-closed conditions became similar to those recorded during an eyes-open condition. This change manifested as an increase in global functional connectivity in associative regions and a decrease in sensory areas. We used machine learning to directly link the subjective effects of psychedelics to neural activity patterns characterised by low-dimensional embeddings. We show that psilocybin reorganised these low-dimensional trajectories into structured patterns of brain activity that reflected the context and quality of subjective experience, revealing an organisation that was missed by conventional analyses. Stronger self- and boundary-dissolving effects were linked to next-day mindset changes and associated with more distinct and cohesive neural representations. This reorganisation induces a state we represent as ‘embeddedness’ that arises when brain networks that usually segregate internal and external processing coherently integrate, aligning neural dynamics with context. This state corresponded to the felt experience of being part of the environment. Embeddedness serves as a bridging framework for understanding both the subjective and therapeutic effects of psychedelics, demonstrating that psychedelics introduce context- and quality-dependent reorganisation in neural dynamics. These findings reveal that the organisation of brain activity covaries with the experiential coherence of the psychedelic state, providing a new framework for understanding how psychedelics shape neurobiology and behaviour through context-sensitive brain dynamics.