TY  - JOUR
A1  - Madrid-Gambin, Francisco
A1  - Gomez-Gomez, Alex
A1  - Busquets-Garcia, Arnau
A1  - Haro, Noemí
A1  - Marco, Santiago
A1  - Mason, Natasha L.
A1  - Reckweg, Johannes T.
A1  - Mallaroni, Pablo
A1  - Kloft, Lilian
A1  - Oorsouw, Kim van
A1  - Tönnes, Stefan W.
A1  - Torre, Rafael de la
A1  - Ramaekers, Johannes Gerardus
A1  - Pozo, Oscar Jeśus
T1  - Metabolomics and integrated network analysis reveal roles of endocannabinoids and large neutral amino acid balance in the ayahuasca experience
T2  - Biomedicine & pharmacotherapy
N2  - 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.
KW  - Ayahuasca
KW  - Dimethyltryptamine
KW  - Integrative Network Analysis
KW  - Metabolomics
KW  - Psychedelics
KW  - Subjective effects
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/78631
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-786316
SN  - 1950-6007
N1  - 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.
VL  - 149
IS  - art. 112845
SP  - 1
EP  - 10
PB  - Elsevier Science
CY  - Amsterdam [u.a.]
ER  -