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

Katrin H. Preller, Adeel Razi, Peter Zeidman, Philipp Stämpfli, Karl Friston, Franz X. Vollenweider

Proceedings of the National Academy of Sciences January 28, 2019 DOI: 10.1073/pnas.1815129116 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, randomized, placebo-controlled, cross-over study Peer reviewed
Sample size 25
Population Healthy participants
Intervention LSD
Topics LSD Neuroplasticity Altered states of consciousness
Keywords Substance Brain regions Brain pathways Brain imaging Brain talk Neural communication Brain function Cognitive effects Perceptual changes Cognitive changes Self-awareness Information processing Altered perception Brain reorganization Brain network flexibility Brain integration Neural shifts Altered brain communication Brain changes
Citations 303
Key points LSD increased effective connectivity from the thalamus to the posterior cingulate cortex via serotonin 2A receptor activation and decreased connectivity from the ventral striatum to the thalamus independently of those receptors.

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.

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

  • State of the evidence: Altered states of consciousness Supports

    LSD increased effective connectivity from thalamus to posterior cingulate cortex via serotonin 2A receptor activation and decreased ventral striatum-to-thalamus connectivity independently of those receptors.

    Synthesized

  • State of the evidence: Neuroplasticity Supports

    LSD increased effective connectivity from the thalamus to the posterior cingulate cortex via serotonin 2A receptor activation and decreased connectivity from the ventral striatum to the thalamus independently of those receptors.

    Synthesized

Comparable studies

Other randomized controlled trials on altered states of consciousness, most cited first.

Study Year Design Participants
Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants 2018 Double-blind, randomized, counterbalanced, cross-over study n = 24
Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Healthy hallucinogen-using adults 2013 Double-blind, placebo-controlled study n = 8
High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens. Healthy volunteers with histories of hallucinogen use 2012 Randomized controlled trial n = 12
A placebo-controlled investigation of synaesthesia-like experiences under LSD. 2016 Within-groups placebo-controlled pilot study
Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants. Healthy psychedelic-naïve participants 2024 Double-blind, placebo-controlled single ascending dose study n = 44

Citations in the library

Cited by 202

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Cites 35

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