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Psilocybin induces time-dependent changes in global functional connectivity


Preller, Katrin H; Duerler, Patricia; Burt, Joshua B; Ji, Jie Lisa; Adkinson, Brendan; Stämpfli, Philipp; Seifritz, Erich; Repovs, Grega; Krystal, John H; Murray, John D; Anticevic, Alan; Vollenweider, Franz X (2020). Psilocybin induces time-dependent changes in global functional connectivity. Biological Psychiatry, 88(2):197-207.

Abstract

Background

The use of Psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans.
Methods

We therefore conducted a double-blind, randomized, counterbalanced, cross-over study during which 23 healthy human participants received placebo and 0.2 mg/kg of psilocybin p.o. on two different test days. Participants underwent MRI scanning at three time points between administration and peak effects: 20 mins, 40 mins, and 70 mins after administration. Resting-state functional connectivity was quantified via a data-driven global brain connectivity method and compared to cortical gene expression maps.
Results

Psilocybin reduced associative, but concurrently increased sensory brain-wide connectivity. This pattern emerged over time from administration to peak-effects. Furthermore, we show that baseline connectivity is associated with the extent of Psilocybin-induced changes in functional connectivity. Lastly, Psilocybin induced changes correlated time-dependently with spatial gene expression patterns of the 5-HTR2A and 5-HTR1A.
Conclusions

These results suggest that the integration of functional connectivity in sensory and the disintegration in associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.

Abstract

Background

The use of Psilocybin in scientific and experimental clinical contexts has triggered renewed interest in the mechanism of action of psychedelics. However, its time-dependent systems-level neurobiology remains sparsely investigated in humans.
Methods

We therefore conducted a double-blind, randomized, counterbalanced, cross-over study during which 23 healthy human participants received placebo and 0.2 mg/kg of psilocybin p.o. on two different test days. Participants underwent MRI scanning at three time points between administration and peak effects: 20 mins, 40 mins, and 70 mins after administration. Resting-state functional connectivity was quantified via a data-driven global brain connectivity method and compared to cortical gene expression maps.
Results

Psilocybin reduced associative, but concurrently increased sensory brain-wide connectivity. This pattern emerged over time from administration to peak-effects. Furthermore, we show that baseline connectivity is associated with the extent of Psilocybin-induced changes in functional connectivity. Lastly, Psilocybin induced changes correlated time-dependently with spatial gene expression patterns of the 5-HTR2A and 5-HTR1A.
Conclusions

These results suggest that the integration of functional connectivity in sensory and the disintegration in associative regions may underlie the psychedelic state and pinpoint the critical role of the serotonin 2A and 1A receptor systems. Furthermore, baseline connectivity may represent a predictive marker of the magnitude of changes induced by psilocybin and may therefore contribute to a personalized medicine approach within the potential framework of psychedelic treatment.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Clinic for Psychiatry, Psychotherapy, and Psychosomatics
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Biological Psychiatry
Uncontrolled Keywords:Biological Psychiatry
Language:English
Date:1 July 2020
Deposited On:21 Feb 2020 13:05
Last Modified:23 Jul 2024 01:36
Publisher:Elsevier
ISSN:0006-3223
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.biopsych.2019.12.027
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