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Canonical and Non-Canonical Psychedelic Drugs Induce Common Network Changes in Human Cortex

Rui Dai, Tony E. Larkin, Zirui Huang, Vijay Tarnal, Paul Picton, Phillip E. Vlisides, Ellen Janke, Amy McKinney, Anthony G. Hudetz, Richard E. Harris, George A. Mashour
doi: https://doi.org/10.1101/2022.10.14.512285
Rui Dai
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
2Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI 48109
3Michigan Psychedelic Center, University of Michigan Medical School, Ann Arbor, MI, 48109
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Tony E. Larkin
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
4Chronic Pain and Fatigue Research Center, University of Michigan Medical School, Ann Arbor, MI, 48109
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Zirui Huang
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
2Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI 48109
3Michigan Psychedelic Center, University of Michigan Medical School, Ann Arbor, MI, 48109
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Vijay Tarnal
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
2Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI 48109
3Michigan Psychedelic Center, University of Michigan Medical School, Ann Arbor, MI, 48109
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Paul Picton
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
2Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI 48109
3Michigan Psychedelic Center, University of Michigan Medical School, Ann Arbor, MI, 48109
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Phillip E. Vlisides
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
2Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI 48109
3Michigan Psychedelic Center, University of Michigan Medical School, Ann Arbor, MI, 48109
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Ellen Janke
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
2Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI 48109
3Michigan Psychedelic Center, University of Michigan Medical School, Ann Arbor, MI, 48109
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Amy McKinney
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
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Anthony G. Hudetz
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
2Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI 48109
3Michigan Psychedelic Center, University of Michigan Medical School, Ann Arbor, MI, 48109
5Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109
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Richard E. Harris
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
3Michigan Psychedelic Center, University of Michigan Medical School, Ann Arbor, MI, 48109
4Chronic Pain and Fatigue Research Center, University of Michigan Medical School, Ann Arbor, MI, 48109
5Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109
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  • For correspondence: reharris@med.umich.edu gmashour@med.umich.edu
George A. Mashour
1Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI 48109
2Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI 48109
3Michigan Psychedelic Center, University of Michigan Medical School, Ann Arbor, MI, 48109
5Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109
6Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, 48109
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  • For correspondence: reharris@med.umich.edu gmashour@med.umich.edu
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Abstract

The neurobiology of the psychedelic experience is not fully elucidated. Identifying common brain network changes induced by both canonical (i.e., acting at the 5-HT2 receptor) and non-canonical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during the administration of nitrous oxide, ketamine, and lysergic acid diethylamide. We report that, despite distinct molecular mechanisms and modes of delivery, all three psychedelics reduced within-network functional connectivity and enhanced between-network functional connectivity. More specifically, all drugs tested increased connectivity between right temporoparietal junction and bilateral intraparietal sulcus as well as between precuneus and left intraparietal sulcus. These regions fall within the posterior cortical “hot zone,” posited to mediate the content of consciousness. Thus, both canonical and non-canonical psychedelics modulate networks within an area of known relevance for conscious experience, identifying a biologically plausible candidate for their subjective effects.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted October 18, 2022.
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Canonical and Non-Canonical Psychedelic Drugs Induce Common Network Changes in Human Cortex
Rui Dai, Tony E. Larkin, Zirui Huang, Vijay Tarnal, Paul Picton, Phillip E. Vlisides, Ellen Janke, Amy McKinney, Anthony G. Hudetz, Richard E. Harris, George A. Mashour
bioRxiv 2022.10.14.512285; doi: https://doi.org/10.1101/2022.10.14.512285
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Canonical and Non-Canonical Psychedelic Drugs Induce Common Network Changes in Human Cortex
Rui Dai, Tony E. Larkin, Zirui Huang, Vijay Tarnal, Paul Picton, Phillip E. Vlisides, Ellen Janke, Amy McKinney, Anthony G. Hudetz, Richard E. Harris, George A. Mashour
bioRxiv 2022.10.14.512285; doi: https://doi.org/10.1101/2022.10.14.512285

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