A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials. This study tracked individual-specific brain changes using longitudinal precision functional mapping in healthy adults after high-dose psilocybin and methylphenidate. Psilocybin massively disrupted functional connectivity (FC), causing brain desynchronization and dissolving network distinctions. These FC changes were strongest in the default mode network and linked to subjective psychedelic experience. A perceptual task reduced psilocybin-driven FC changes. Persistent decreases in FC between the anterior hippocampus and default mode network suggest a neuroanatomical correlate of psychedelics' therapeutic effects.

Joshua S. Siegel, Subha Subramanian, Demetrius Perry, Benjamin P. Kay, Evan M. Gordon, Timothy O. Laumann, T. Rick Reneau, Nicholas V. Metcalf, Ravi V. Chacko, Caterina Gratton, Christine Horan, Samuel R. Krimmel, Joshua S. Shimony, Julie A. Schweiger, Dean F. Wong, David A. Bender, Kristen M. Scheidter, Forrest I. Whiting, Jonah A. Padawer-Curry, Russell T. Shinohara, Yong Chen, Julia Moser, Essa Yacoub, Steven M. Nelson, Luca Vizioli, Damien A. Fair, Eric J. Lenze, Robin Carhart-Harris, Charles L. Raison, Marcus E. Raichle, Abraham Z. Snyder, Ginger E. Nicol, Nico U. F. Dosenbach