Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience

Madrid-Gambin, Francisco; Gómez-Gómez, Àlex; Busquets Garcia, Arnau, 1985-; Haro, Noemí; Marco Sola, Santiago; Mason, Natasha L.; Reckweg, Johannes T.; Mallaroni, Pablo A.; Kloft, Lilian; van Oorsouw, Kim; Toennes, Stefan W.; Torre Fornell, Rafael de la; Ramaekers, Johannes G.; Pozo Mendoza, Óscar J., 1975-

Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience

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dc.contributor.author Madrid-Gambin, Francisco
dc.contributor.author Gómez-Gómez, Àlex
dc.contributor.author Busquets Garcia, Arnau, 1985-
dc.contributor.author Haro, Noemí
dc.contributor.author Marco Sola, Santiago
dc.contributor.author Mason, Natasha L.
dc.contributor.author Reckweg, Johannes T.
dc.contributor.author Mallaroni, Pablo A.
dc.contributor.author Kloft, Lilian
dc.contributor.author van Oorsouw, Kim
dc.contributor.author Toennes, Stefan W.
dc.contributor.author Torre Fornell, Rafael de la
dc.contributor.author Ramaekers, Johannes G.
dc.contributor.author Pozo Mendoza, Óscar J., 1975-
dc.date.accessioned 2022-06-09T06:04:18Z
dc.date.available 2022-06-09T06:04:18Z
dc.date.issued 2022
dc.description.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.
dc.description.sponsorship FMG was supported by Grant FJC2018–035791-I funded by MCIN/AEI/10.13039/501100011033. We would like to acknowledge the Dutch Research Council (NWO, grant number 406.18. GO.019), the Departament d′Universitats, Recerca i Societat de la Informació de la Generalitat de Catalunya (expedient 2017 SGR 1721); the Comissionat per a Universitats i Recerca del DIUE de la Generalitat de Catalunya; and the European Social Fund (ESF). Additional financial support has been provided by the Institut de Bioenginyeria de Catalunya (IBEC). IBEC is a member of the CERCA Programme/Generalitat de Catalunya.
dc.format.mimetype application/pdf
dc.identifier.citation Madrid-Gambin F, Gomez-Gomez A, Busquets-Garcia A, Haro N, Marco S, Mason NL, Reckweg JT, Mallaroni P, Kloft L, van Oorsouw K, Toennes SW, de la Torre R, Ramaekers JG, Pozo OJ. Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience. Biomed Pharmacother. 2022 May;149:112845. DOI: 10.1016/j.biopha.2022.112845
dc.identifier.doi http://dx.doi.org/10.1016/j.biopha.2022.112845
dc.identifier.issn 0753-3322
dc.identifier.uri http://hdl.handle.net/10230/53422
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Biomed Pharmacother. 2022 May;149:112845
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/FJC2018–035791-I
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Ayahuasca
dc.subject.keyword Dimethyltryptamine
dc.subject.keyword Integrative Network Analysis
dc.subject.keyword Metabolomics
dc.subject.keyword Psychedelics
dc.subject.keyword Subjective effects
dc.title Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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