51. Psilocybin desynchronizes brain networks.
- Author
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Siegel JS, Subramanian S, Perry D, Kay B, Gordon E, Laumann T, Reneau R, Gratton C, Horan C, Metcalf N, Chacko R, Schweiger J, Wong D, Bender D, Padawer-Curry J, Raison C, Raichle M, Lenze EJ, Snyder AZ, Dosenbach NUF, and Nicol G
- Abstract
1The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood. Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to 3 weeks after oral psilocybin and methylphenidate (17 MRI visits per participant) and again 6+ months later. Psilocybin disrupted connectivity across cortical networks and subcortical structures, producing more than 3-fold greater acute changes in functional networks than methylphenidate. These changes were driven by desynchronization of brain activity across spatial scales (area, network, whole brain). Psilocybin-driven desynchronization was observed across association cortex but strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduced psilocybin-induced network changes, suggesting a neurobiological basis for grounding , connecting with physical reality during psychedelic therapy. The acute brain effects of psilocybin are consistent with distortions of space-time and the self. Psilocybin induced persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after 6 months. Persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for psilocybin's pro-plasticity and anti-depressant effects., Competing Interests: 4.1 Conflicts of Interest Author JSS is an employee of Sumitomo Pharma America and has received consulting fees from Forbes Manhattan. Author CLR serves as a consultant to Usona Institute and Novartis and receives research support from the Tiny Blue Dot Foundation. Author GEN has received research support from Usona Institute (drug only). She has served as a paid consultant for IngenioRx, Alkermes, Inc., Sunovion Pharmaceuticals, Inc., and Novartis Pharmaceuticals Corp. NUFD is a co-founder of Turing Medical Inc, has financial interest, and may benefit financially if the company is successful in marketing FIRMM motion monitoring software products. NUFD may receive royalty income based on FIRMM technology developed at Washington University School of Medicine and licensed to Turing Medical Inc. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine. The other authors declare no competing interests. All authors report no financial interest in psychedelics companies.
- Published
- 2023
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