Brain-body integromics of the ayahuasca experience.
Francisco Madrid-Gambin, Pablo Mallaroni, Noemí Haro, Oscar 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 Peer reviewed DOI: 10.1016/j.biopha.2026.119391 via PubMed
Summary
Ayahuasca use in 20 experienced users was linked to changes in perception and brain connectivity through a complex interplay between peripheral metabolism and brain networks. Key experiential dimensions like oceanic boundlessness and visionary restructuralization were associated with levels of DMT and β-carbolines, as well as alterations in lipid and amino acid metabolism. The study highlights that psychedelic experiences are shaped by system-level interactions rather than just neurochemical events.
Study at a glance
| Design | observational cohort |
|---|---|
| Sample size | 20 |
| Population | experienced ceremonial ayahuasca users |
| Key finding | Psychedelic states reflect coordinated interactions between peripheral metabolism and functional brain networks. |
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.