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Psychedelics restructure information in the human brain

Blackburne G, Liardi A, Mallaroni P, McAlpine R, Carhart-Harris R, Timmermann C, Muthukumaraswamy SD, Skipper JI, Mediano PA

Oct 8, 20260 citationsDOI: 10.64898/2026.10.01.755915

Abstract

How do psychedelic drugs alter human brain function? Answering this question relies on our ability to understand how information is stored, transferred, and transformed across the cortex. Here, we leverage a precise mathematical framework for multivariate information decomposition to construct the first comprehensive picture of these processes across five compounds: LSD, psilocybin, ketamine, DMT and 5-MeO-DMT (N=80). We provide a formal and empirical explanation of major prior results, revealing sets of competing underlying phenomena masked by extant approaches. We extend this analysis to novel higher-order phenomena, and we demonstrate how all of these observations can emerge from a minimal generative model in which neural populations operate with reduced self-coupling. In sum, our results suggest that the psychedelic brain is one in which cortical populations become alike, but not necessarily together. This has important implications for models of how psychedelics reorganize brain dynamics to alter subjective experience and alleviate mental health conditions.

Topics & conditions

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PsilocybinKetamineLSDDMT5-MeO-DMT

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