Psilocybin induces time-dependent changes in global functional connectivity: Psi-induced changes in brain connectivity
This double-blind, placebo-controlled fMRI study (n=23) study with psilocybin (14mg/70kg) finds evidence that sensory connectivity increased whilst associative connectivity went down.
Authors
- Erich Seifritz
- Franz Vollenweider
- Katrin Preller
Published
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.
Research Summary of 'Psilocybin induces time-dependent changes in global functional connectivity: Psi-induced changes in brain connectivity'
Introduction
Psilocybin (Psi) is a serotonergic psychedelic that has regained scientific interest because of promising clinical findings and its utility for probing consciousness, cognition and emotion. Molecular work shows that psilocin, Psi's active metabolite, binds to multiple serotonin receptor subtypes including 5-HT2A and 5-HT1A, and pharmacological blockade of 5-HT2A reduces Psi effects in humans. However, system-level neurobiology in humans remains incompletely characterised: prior resting-state BOLD studies used region-of-interest approaches or intravenous dosing with brief, rapidly evolving effects, limiting whole-brain and time-resolved inference about connectivity changes and their receptor-level correlates. This study aimed to map time-dependent, whole-brain changes in resting-state functional connectivity after oral psilocybin and to relate these effects to cortical gene expression of serotonin receptors. Anticipating parallels with previous LSD findings, Preller and colleagues hypothesised that psilocybin would produce a linear increase in connectivity changes from 20 to 70 minutes after administration, yielding hyper-connectivity in sensory regions and hypo-connectivity in associative networks at peak effect; they further predicted a positive spatial association with cortical HTR2A expression and a negative association with HTR1A expression. The work therefore combines a data-driven global brain connectivity (GBC) approach with time-resolved scanning and gene-expression mapping to link network-level effects to receptor topography.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Preller, K. H., Duerler, P., Burt, J. B., Ji, J. L., Adkinson, B., Stämpfli, P., Seifritz, E., Repovš, G., Krystal, J. H., Murray, J. D., Anticevic, A., & Vollenweider, F. X. (2020). Psilocybin induces time-dependent changes in global functional connectivity: Psi-induced changes in brain connectivity. Biological Psychiatry, 88(2), 197-207. https://doi.org/10.1016/j.biopsych.2019.12.027
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