Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience
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 t...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/53422 |
| Acceso en línea: | http://hdl.handle.net/10230/53422 http://dx.doi.org/10.1016/j.biopha.2022.112845 |
| Access Level: | acceso abierto |
| Palabra clave: | Ayahuasca Dimethyltryptamine Integrative Network Analysis Metabolomics Psychedelics Subjective effects |
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Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experienceMadrid-Gambin, FranciscoGómez-Gómez, ÀlexBusquets Garcia, Arnau, 1985-Haro, NoemíMarco Sola, SantiagoMason, Natasha L.Reckweg, Johannes T.Mallaroni, Pablo A.Kloft, Lilianvan Oorsouw, KimToennes, Stefan W.Torre Fornell, Rafael de laRamaekers, Johannes G.Pozo Mendoza, Óscar J., 1975-AyahuascaDimethyltryptamineIntegrative Network AnalysisMetabolomicsPsychedelicsSubjective effectsThere 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.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.Elsevier202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/53422http://dx.doi.org/10.1016/j.biopha.2022.112845reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésBiomed Pharmacother. 2022 May;149:112845info:eu-repo/grantAgreement/ES/2PE/FJC2018–035791-I© 2022 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/534222026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience |
| title |
Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience |
| spellingShingle |
Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience Madrid-Gambin, Francisco Ayahuasca Dimethyltryptamine Integrative Network Analysis Metabolomics Psychedelics Subjective effects |
| title_short |
Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience |
| title_full |
Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience |
| title_fullStr |
Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience |
| title_full_unstemmed |
Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience |
| title_sort |
Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience |
| dc.creator.none.fl_str_mv |
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- |
| author |
Madrid-Gambin, Francisco |
| author_facet |
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- |
| author_role |
author |
| author2 |
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- |
| author2_role |
author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Ayahuasca Dimethyltryptamine Integrative Network Analysis Metabolomics Psychedelics Subjective effects |
| topic |
Ayahuasca Dimethyltryptamine Integrative Network Analysis Metabolomics Psychedelics Subjective effects |
| description |
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. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022 2022 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10230/53422 http://dx.doi.org/10.1016/j.biopha.2022.112845 |
| url |
http://hdl.handle.net/10230/53422 http://dx.doi.org/10.1016/j.biopha.2022.112845 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
| dc.relation.none.fl_str_mv |
Biomed Pharmacother. 2022 May;149:112845 info:eu-repo/grantAgreement/ES/2PE/FJC2018–035791-I |
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http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
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http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf application/pdf |
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Elsevier |
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Elsevier |
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