Psychedelic concentrations of nitrous oxide reduce functional differentiation in frontoparietal and somatomotor cortical networks.
Rui Dai, Zirui Huang, Tony E. Larkin, Vijay Tarnal, Paul Picton, Phillip E. Vlisides, Ellen Janke, Amy McKinney, Anthony G. Hudetz, Richard E. Harris, George A. Mashour
Communications Biology December 19, 2023 DOI: 10.1038/s42003-023-05678-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational within-subject neuroimaging study Peer reviewed |
|---|---|
| Population | Human participants undergoing resting-state fMRI before and during nitrous oxide administration |
| Intervention | Nitrous oxide |
| Dose | 35% nitrous oxide |
| Topics | Altered states of consciousness |
| Keywords | Nitrous oxide N2o Laughing gas Brain function Brain activity Neural networks Neurobiology Brain reorganization Consciousness Psychedelic states Altered perception Brain imaging Neuroimaging |
| Citations | 7 |
| Key findings | Nitrous oxide at 35% reduced functional differentiation in frontoparietal and somatomotor networks, flattening cortical functional geometry and disrupting temporal dynamics. The degree of functional differentiation was inversely correlated with the subjective psychedelic experience, suggesting a shared cortical mechanism with classical serotonin-acting psychedelics. |
Abstract
Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. We measure the brain's functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns) using human resting-state functional magnetic resonance imaging data acquired before and during administration of 35% nitrous oxide. Both analyses demonstrate that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on serotonin receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects.
Comparable studies
Other experimental studies on altered states of consciousness, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Healthy subjects in six countries | 1998 | Experimental and field study | n = 1,133 |
| TMS-EEG and resting-state EEG applied to altered states of consciousness: oscillations, complexity, and phenomenology. | 2023 | Experimental study | |
| A Test of the Psychedelic Model of Altered States of Consciousness | 1976 | Experimental study with comparison groups | |
| Neural Correlates of Non-ordinary States of Consciousness in Pranayama Practitioners: The Role of Slow Nasal Breathing Experienced meditators | 2022 | Within-subjects comparison | n = 12 |
| Increased spontaneous EEG signal diversity during stroboscopically-induced altered states of consciousness Healthy adults | 2019 | Experimental study |
Citations in the library
Cited by 5
- Anesthetics as Treatments for Depression: Clinical Insights and Underlying Mechanisms. Annual Review of Neuroscience February 19, 2025
- Rapid antidepressant potential of nitrous oxide: current state and major questions. Molecular Psychiatry June 1, 2026
- Opposite network patterns of integration-segregation in psychedelic and sedated states of consciousness. Cell Reports August 1, 2026
- Acute effects of nitrous oxide on visual processing: a connectome study in healthy adults. Research Square January 12, 2026
- Classifying Unconscious, Psychedelic, and Neuropsychiatric Brain States with Functional Connectivity, Graph Theory, and Cortical Gradient Analysis. Brain Sciences August 30, 2024
Cites 32
- 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
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
and 27 more in the library