The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity

Peter Bedford, Daniel J. Hauke*, Zheng Wang, Volker Roth, Monika Nagy-Huber, Friederike Holze, Laura Ley, Patrick Vizeli, Matthias E. Liechti, Stefan Borgwardt, Felix Müller, Andreea O. Diaconescu

*Corresponding author for this work
3 Citations (Scopus)


Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomised, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100 μg LSD and placebo in two resting-state fMRI sessions. We compared EC against whole-brain functional connectivity (FC) using classical statistics and machine learning methods. Multivariate analyses of EC parameters revealed predominantly stronger interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of weakened interregional connectivity and increased self-inhibition in occipital brain regions as well as subcortical regions. Together, these findings suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Notably, whole-brain EC did not only provide additional mechanistic insight into the effects of LSD on the Excitation/Inhibition balance of the brain, but EC also correlated with global subjective effects of LSD and discriminated experimental conditions in a machine learning-based analysis with high accuracy (91.11%), highlighting the potential of using whole-brain EC to decode or predict subjective effects of LSD in the future.

Original languageEnglish
Issue number8
Pages (from-to)1175-1183
Number of pages9
Publication statusPublished - 07.2023

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

DFG Research Classification Scheme

  • 206-04 Cognitive, Systemic and Behavioural Neurobiology
  • 205-09 Pharmacology
  • 206-09 Biological Psychiatry

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