Brain-body integromics of the ayahuasca experience.
Francisco Madrid-Gambin, Pablo Mallaroni, Noemí Haro, Óscar J. Pozo, Natasha L. Mason, Johannes T. Reckweg, Lilian Kloft-Heller, Kim van Oorsouw, Stefan W. Toennes, Johannes G. Ramaekers
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie June 1, 2026 DOI: 10.1016/j.biopha.2026.119391 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Within-subject, integrative multiblock partial least squares framework with complementary ¹H-MRS and rCCA analyses Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Experienced ceremonial ayahuasca users |
| Intervention | Ayahuasca |
| Topics | Ayahuasca DMT |
| Keywords | Connectome Integromics Metabolomics Psychedelics |
| Key points | Psychedelic states reflect coordinated, system-level interactions between peripheral metabolism and functional brain networks, with subjective experience dimensions linked to specific circulating alkaloids, metabolic alterations, and brain network reconfigurations. |
Abstract
Ayahuasca is a psychoactive brew containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids that induces marked alterations in perception, emotion and self-referential processing. However, the multiscale biological organization linking peripheral metabolism, brain network dynamics, neurochemistry, and subjective experience in humans remains poorly understood. Here, we applied an integrative, within-subject, multiblock partial least squares framework to model coordinated changes across four complementary biological and phenotypic layers: plasma psychoactive alkaloids, targeted metabolomics, resting-state fMRI-derived functional connectomes, and multidimensional subjective experience assessed with the 5-Dimensional Altered States of Consciousness (5D-ASC) scale, in 20 experienced ceremonial ayahuasca users. Complementary ¹H-MRS data were used to examine associations between peripheral metabolism, posterior cingulate cortex neurochemistry, and default mode network (DMN)-related connectivity. Multilayer integration revealed that the experiential dimensions oceanic boundlessness, visionary restructuralization and auditory alterations covaried with circulating DMT and β-carbolines, alterations in lipid, amino acid and energy metabolisms and reconfiguration of dorsal attention- and DMN-related connectivity. Shared network features across experiential dimensions were most strongly associated with endocannabinoid-related N-acylethanolamines, acylglycerols, and ceramides, extending canonical serotonergic models toward downstream lipid-signalling and metabolic processes. Complementary rCCA analyses further showed structured covariation between peripheral metabolites, posterior cingulate cortex neurochemistry, and DMN-related connectivity. Together, these findings indicate that psychedelic states reflect coordinated, system-level interactions between peripheral metabolism and functional brain networks rather than isolated neurochemical or neural events. Framed within a brain-body integromics perspective, this work provides translationally relevant insight into metabolic pathways that may modulate brain function and subjective response, with potential implications for neuropsychiatric and pharmacometabolic research.
Comparable studies
Other experimental studies on ayahuasca, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Seeing with the eyes shut: Neural basis of enhanced imagery following ayahuasca ingestion Human participants (number not stated) | 2011 | Within-subjects experimental study | |
| Ayahuasca enhances creative divergent thinking while decreasing conventional convergent thinking Participants at spiritual ayahuasca workshops | 2016 | Within-subjects experimental study | n = 26 |
| Metabolism and disposition of N,N‐dimethyltryptamine and harmala alkaloids after oral administration of ayahuasca Healthy male volunteers | 2012 | Observational pharmacokinetic study | n = 10 |
| New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca. | 2018 | Review with original neuroimaging and neurophysiological data | |
| Stability Evaluation of DMT and Harmala Alkaloids in Ayahuasca Tea Samples Ayahuasca tea samples | 2020 | Experimental study |
Citations in the library
Cites 27
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- 20 years of the default mode network: A review and synthesis Neuron May 10, 2023
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Psychedelics, Meditation, and Self-Consciousness Frontiers in Psychology September 4, 2018
and 22 more in the library