Journal Article

Psilocybin desynchronizes the human brain

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

2024

Overview

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 1 – 4 . In animal models, psilocybin induces neuroplasticity in cortex and hippocampus 5 – 8 . It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6–12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics. Healthy adults were tracked before, during and after high doses of psilocybin and methylphenidate to assess how psychedelics can change human brain networks, and psilocybin was found to massively disrupt functional connectivity in cortex and subcortex with some changes persisting for weeks.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 59/36 / 631/378 / 631/378/2649/1398 / 631/378/3920 / 692/308/153 / 692/53 / Adolescent / Adult / Animal models / Antidepressants / Brain / Brain - cytology / Brain - diagnostic imaging / Brain - drug effects / Brain - physiology / Brain architecture / Brain Mapping / Datasets / Default Mode Network - cytology / Default Mode Network - diagnostic imaging / Default Mode Network - drug effects / Default Mode Network - physiology / Drug dosages / Ego / Female / Functional plasticity / Hallucinogens - administration & dosage / Hallucinogens - pharmacology / Healthy Volunteers / Hippocampal plasticity / Hippocampus / Hippocampus - cytology / Hippocampus - diagnostic imaging / Hippocampus - drug effects / Hippocampus - physiology / Humanities and Social Sciences / Humans / LSD / Lysergic acid diethylamide / Magnetic resonance / Magnetic Resonance Imaging / Male / Methylphenidate / Methylphenidate - administration & dosage / Methylphenidate - pharmacology / Middle Aged / multidisciplinary / Nerve Net - cytology / Nerve Net - diagnostic imaging / Nerve Net - drug effects / Nerve Net - physiology / Neural networks / Neuroimaging / Neuroplasticity / Psilocybin / Psilocybin - administration & dosage / Psilocybin - pharmacology / Psychedelic drugs / Science / Science (multidisciplinary) / Space Perception - drug effects / Synchronization / Temporal perception / Time Perception - drug effects / Young Adult