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Cited by 292Psychedelics and Drug StudiesFunctional Brain Connectivity StudiesPain Management and Placebo Effect

Effective connectivity changes in LSD-induced altered states of consciousness in humans

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Preller, Katrin H., Razi, Adeel, Zeidman, Peter, Stämpfli, Philipp, Friston, Karl J., Vollenweider, Franz X.·2019·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1815129116PMC PMC6377471
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Abstract

Psychedelics exert unique effects on human consciousness. The thalamic filter model suggests that core effects of psychedelics may result from gating deficits, based on a disintegration of information processing within cortico–striato–thalamo-cortical (CSTC) feedback loops. To test this hypothesis, we characterized changes in directed (effective) connectivity between selected CTSC regions after acute administration of lysergic acid diethylamide (LSD), and after pretreatment with Ketanserin (a selective serotonin 2A receptor antagonist) plus LSD in a double-blind, randomized, placebo-controlled, cross-over study in 25 healthy participants. We used spectral dynamic causal modeling (DCM) for resting-state fMRI data. Fully connected DCM models were specified for each treatment condition to investigate the connectivity between the following areas: thalamus, ventral striatum, posterior cingulate cortex, and temporal cortex. Our results confirm major predictions proposed in the CSTC model and provide evidence that LSD alters effective connectivity within CSTC pathways that have been implicated in the gating of sensory and sensorimotor information to the cortex. In particular, LSD increased effective connectivity from the thalamus to the posterior cingulate cortex in a way that depended on serotonin 2A receptor activation, and decreased effective connectivity from the ventral striatum to the thalamus independently of serotonin 2A receptor activation. Together, these results advance our mechanistic understanding of the action of psychedelics in health and disease. This is important for the development of new pharmacological therapeutics and also increases our understanding of the mechanisms underlying the potential clinical efficacy of psychedelics.

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  • 5-HT2A receptor agonizing psychedelics result in modulation of cortical and subcortical circuitry.

    “In this formulation, 5-HT 2A R agonizing psychedelics result in modulation of cortical and subcortical circuitry (Preller et al., 2019;Vollenweider and Preller, 2020), altering the flow of information in the brain via changes in how PFC L5 pyramidal neurons expressing 5-HT 2A R regulate important thalamic nuclei (reticular nucleus, mediodorsal thalamus) (Inserra et al., 2021b).”

    From Psychedelics and Neural Plasticity: Therapeutic Implications (2022) · cites this paper as Preller et al., 2019

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Authors
Preller, K. H., Razi, A., Zeidman, P., Stämpfli, P., Friston, K. J., & Vollenweider, F. X.
Affiliations
  • Wellcome Centre for Human Neuroimaging (GB)
  • NED University of Engineering and Technology (PK)
  • University of Zurich (CH)
  • University Hospital Zurich (CH)
Corresponding author
Preller, Katrin H.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2019-01-28
Volume
116
Issue
7
Pages
2743-2748
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1815129116
PMC
PMC6377471
OpenAlex
W2911514809
Cited by
292
References
12
Citations by year
2026: 25 · 2025: 31 · 2024: 46 · 2023: 66 · 2022: 44 · 2021: 40 · 2020: 28 · 2019: 11
FWCI
35.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
  • Monash University Research Portal (Monash University) (submittedVersion, other-oa)
  • UCL Discovery (University College London) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
  • Greater South Information System
Funders
  • Swiss National Science Foundation (1270 P2ZHP1_161626)
  • Swiss Neuromatrix Foundation (2015-0103)
  • Usona Institute (2015-2056)
  • Australian Research Council DECRA Fellowship (DE170100128)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
Keywords
lysergic acid diethylamide, LSD, psychedelics, altered states of consciousness, effective connectivity, thalamic gating, 5-HT2A receptor, ketanserin, posterior cingulate cortex, ventral striatum, thalamus, temporal cortex, dynamic causal modeling, resting-state fMRI
MeSH terms
Brain, Consciousness, Double-Blind Method, Hallucinogens, Humans, Lysergic Acid Diethylamide, Placebos, Serotonin Antagonists, Cross-Over Studies, Receptor, Serotonin, 5-HT2A

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