Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience
Francisco Madrid-Gambin, Alex Gomez-Gomez, Arnau Busquets-García, Noemí Haro, Santiago Marco, Natasha L. Mason, Johannes T. Reckweg, Pablo Mallaroni, Lilian Kloft, Kim van Oorsouw, Stefan W. Toennes, Rafael de la Torre, Johannes G. Ramaekers, Óscar J. Pozo
Biomedicine & Pharmacotherapy March 24, 2022 DOI: 10.1016/j.biopha.2022.112845 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Human adults who consumed ayahuasca |
| Intervention | Ayahuasca |
| Topics | Ayahuasca |
| Keywords | Metabolomics Pharmacology |
| Citations | 14 |
| Key findings | Ayahuasca consumption altered endocannabinoids and large-neutral amino acids, with most LNAAs inversely associated with subjective effects except tryptophan, which was positively associated. |
Abstract
There has been a renewed interest in the potential use of psychedelics for the treatment of psychiatric conditions. Nevertheless, little is known about the mechanism of action and molecular pathways influenced by ayahuasca use in humans. Therefore, for the first time, our study aims to investigate the human metabolomics signature after consumption of a psychedelic, ayahuasca, and its connection with both the psychedelic-induced subjective effects and the plasma concentrations of ayahuasca alkaloids. Plasma samples of 23 individuals were collected both before and after ayahuasca consumption. Samples were analysed through targeted metabolomics and further integrated with subjective ratings of the ayahuasca experience (i.e., using the 5-Dimension Altered States of Consciousness Rating Scale [ASC]), and plasma ayahuasca-alkaloids using integrated network analysis. Metabolic pathways enrichment analysis using diffusion algorithms for specific KEGG modules was performed on the metabolic output. Compared to baseline, the consumption of ayahuasca increased N-acyl-ethanolamine endocannabinoids, decreased 2-acyl-glycerol endocannabinoids, and altered several large-neutral amino acids (LNAAs). Integrated network results indicated that most of the LNAAs were inversely associated with 9 out of the 11 subscales of the ASC, except for tryptophan which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with the ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in several pathways involved in neurotransmission such as serotonin and dopamine synthesis. In conclusion, a crosstalk between the circulating LNAAs and the subjective effects is suggested, which is independent of the alkaloid concentrations and provides insights into the specific metabolic fingerprint and mechanism of action underlying ayahuasca experiences.
Comparable studies
Other observational and cohort studies on ayahuasca, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report Patients with a depressive disorder | 2015 | Observational study | |
| The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network Experienced subjects | 2015 | Observational cohort | n = 10 |
| Human Psychopharmacology of Hoasca, A Plant Hallucinogen Used in Ritual Context in Brazil Long-term members of a syncretic church that uses hoasca as a psychoactive sacrament... | 1996 | Observational cohort with matched controls | n = 30 |
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Personality, Psychopathology, Life Attitudes and Neuropsychological Performance among Ritual Users of Ayahuasca: A Longitudinal Study Regular ayahuasca users and active controls in non-ayahuasca religions | 2012 | Observational cohort | n = 242 |
Citations in the library
Cited by 13
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment Neuropharmacology January 13, 2023
- Effects of repeated lysergic acid diethylamide (LSD) on the mouse brain endocannabinoidome and gut microbiome. British Journal of Pharmacology March 1, 2023
- Therapeutic modulation of the kynurenine pathway in severe mental illness and comorbidities: A potential role for serotonergic psychedelics. Progress in Neuro-Psychopharmacology and Biological Psychiatry August 30, 2024
- A Systematic Review on the Therapeutic Effects of Ayahuasca. Plants July 7, 2023
- Altered State of Consciousness and Mental Imagery as a Function of N, N-dimethyltryptamine Concentration in Ritualistic Ayahuasca Users Journal of Cognitive Neuroscience 2023
and 8 more in the library
Cites 38
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- 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
- The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. ACS Pharmacology & Translational Science December 10, 2020
- Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology Journal of Psychopharmacology November 16, 2016
and 33 more in the library