Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape.
S Parker Singleton, Andrea I. Luppi, Robin Carhart-Harris, Josephine Cruzat, Leor Roseman, David Nutt, Gustavo Deco, Morten L. Kringelbach, Emmanuel A. Stamatakis, Amy Kuceyeski, S. Parker Singleton
Nature Communications October 3, 2022 DOI: 10.1038/s41467-022-33578-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Individuals under LSD, psilocybin, and placebo conditions |
| Interventions | LSD Psilocybin |
| Topics | LSD Psilocybin |
| Keywords | Psychedelics Consciousness Brain chemistry Mental states |
| Citations | 156 |
| Key findings | LSD and psilocybin reduce the control energy required for brain state transitions compared to placebo, and this reduction correlates with more frequent state transitions and increased entropy of brain dynamics. |
Abstract
Psychedelics including lysergic acid diethylamide (LSD) and psilocybin temporarily alter subjective experience through their neurochemical effects. Serotonin 2a (5-HT2a) receptor agonism by these compounds is associated with more diverse (entropic) brain activity. We postulate that this increase in entropy may arise in part from a flattening of the brain's control energy landscape, which can be observed using network control theory to quantify the energy required to transition between recurrent brain states. Using brain states derived from existing functional magnetic resonance imaging (fMRI) datasets, we show that LSD and psilocybin reduce control energy required for brain state transitions compared to placebo. Furthermore, across individuals, reduction in control energy correlates with more frequent state transitions and increased entropy of brain state dynamics. Through network control analysis that incorporates the spatial distribution of 5-HT2a receptors (obtained from publicly available positron emission tomography (PET) data under non-drug conditions), we demonstrate an association between the 5-HT2a receptor and reduced control energy. Our findings provide evidence that 5-HT2a receptor agonist compounds allow for more facile state transitions and more temporally diverse brain activity. More broadly, we demonstrate that receptor-informed network control theory can model the impact of neuropharmacological manipulation on brain activity dynamics.
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 74
- Adverse effects of psychedelics: From anecdotes and misinformation to systematic science. Journal of Psychopharmacology February 2, 2022
- Human brain effects of DMT assessed via EEG-fMRI. Proceedings of the National Academy of Sciences March 28, 2023
- Canalization and plasticity in psychopathology Neuropharmacology December 27, 2022
- Distributed harmonic patterns of structure-function dependence orchestrate human consciousness. Communications Biology January 28, 2023
- A complex systems perspective on psychedelic brain action. Trends in Cognitive Sciences February 3, 2023
and 69 more in the library
Cites 38
- A default mode of brain function Proceedings of the National Academy of Sciences January 16, 2001
- The Brain's Default Mode Network Annual Review of Neuroscience May 4, 2015
- 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
and 33 more in the library