LSD flattens the hierarchy of directed information flow in fast whole-brain dynamics.
Kenneth Shinozuka, Prejaas K.b. Tewarie, Andrea I. Luppi, Christopher D Lynn, Leor Roseman, Suresh Muthukumaraswamy, David Nutt, Robin Carhart-Harris, Gustavo Deco, Morten L. Kringelbach
Imaging Neuroscience January 3, 2025 DOI: 10.1162/imag_a_00420 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy human participants |
| Intervention | LSD |
| Dose | 75 micrograms, intravenous |
| Topics | LSD |
| Keywords | LSD Compound Hierarchical system Top-down information flow Usual brain hierarchy Centralized exchange Neural regions communicated Distributed Integrated Flexible processing Fluid communication Exchange of information Processing state |
| Citations | 9 |
| Key findings | LSD diminishes the asymmetry of directed connectivity across the whole brain, indicating a flattening of the hierarchy of information flow. |
Abstract
Psychedelics are serotonergic drugs that profoundly alter consciousness, yet their neural mechanisms are not fully understood. A popular theory, RElaxed Beliefs Under pSychedelics (REBUS), posits that psychedelics flatten the hierarchy of information flow in the brain. Here, we investigate hierarchy based on the imbalance between sending and receiving brain signals, as determined by directed functional connectivity. We measure properties of directed functional hierarchy in a magnetoencephalography (MEG) dataset of 16 healthy human participants who were administered a psychedelic dose (75 micrograms, intravenous) of lysergic acid diethylamide (LSD) under four different conditions: eyes-closed with or without music and eyes-open with or without a video stimulus. Across the whole brain, LSD diminishes the asymmetry of directed connectivity when averaged across time. Additionally, we demonstrate that machine learning classifiers distinguish between LSD and placebo more accurately when trained on one of our hierarchy metrics than when trained on traditional measures of functional connectivity. Taken together, these results indicate that LSD weakens the hierarchy of directed connectivity in the brain by increasing the balance between senders and receivers of neural signals.
Comparable studies
Other observational and cohort studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Human participants | 2016 | Observational cohort | |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Psychedelics not linked to mental health problems or suicidal behavior: A population study Randomly selected United States adults | 2015 | Observational cohort | n = 135,095 |
| Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Healthy human participants | 2018 | Observational study with computational modeling |
Citations in the library
Cited by 6
- The Role of the Dorsolateral Prefrontal Cortex in Ego Dissolution and Emotional Arousal During the Psychedelic State. Human Brain Mapping April 1, 2025
- LSD reconfigures the frequency-specific network landscape of the human brain bioRxiv March 24, 2025
- How to set up a psychedelic study: Unique considerations for research involving human participants. Neuroscience & Biobehavioral Reviews July 1, 2026
- Knocking at the Doors of Perception: Relating LSD Effects on Low‐Frequency Fluctuations and Regional Homogeneity to Receptor Densities in fMRI European Journal of Neuroscience November 1, 2025
- Psychedelics disrupt hierarchical cortical propagations in the default mode network of humans and mice. Proceedings of the National Academy of Sciences June 16, 2026
and 1 more in the library
Cites 52
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Active interoceptive inference and the emotional brain Philosophical transactions of the Royal Society of London. Series B, Biological sciences October 11, 2016
and 47 more in the library