Understanding ayahuasca effects in major depressive disorder treatment through in vitro metabolomics and bioinformatics.
Flávia S Zandonadi, Alex Ap Rosini Silva, Aline A S Melo, Raffaela S Ignarro, Taynara S Matos, Emerson A F Santos, Luidy D Barbosa, Alexandre L R Oliveira, Andréia M Porcari, Alessandra Sussulini
Analytical and Bioanalytical Chemistry July 1, 2023 DOI: 10.1007/s00216-023-04556-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Primary astrocyte cells |
| Intervention | Ayahuasca |
| Dose | 1 µmol L-1 DMT |
| Topics | Ayahuasca Depression |
| Keywords | Astrocytes Bioinformatics Exometabolomics Psychedelic medicine Mental health Biochemistry Brain research |
| Citations | 9 |
| Key points | Ayahuasca treatment in an in vitro astrocyte model alters branched-chain amino acid, vitamin B6, and vitamin B3 metabolism, and at the lowest DMT concentration (1 µmol L-1) overrepresents dopamine synthesis in network results. |
Abstract
Emerging insights from metabolomic-based studies of major depression disorder (MDD) are mainly related to biochemical processes such as energy or oxidative stress, in addition to neurotransmission linked to specific metabolite intermediates. Hub metabolites represent nodes in the biochemical network playing a critical role in integrating the information flow in cells between metabolism and signaling pathways. Limited technical-scientific studies have been conducted to understand the effects of ayahuasca (Aya) administration in the metabolism considering MDD molecular context. Therefore, this work aims to investigate an in vitro primary astrocyte model by untargeted metabolomics of two cellular subfractions: secretome and intracellular content after pre-defined Aya treatments, based on DMT concentration. Mass spectrometry (MS)-based metabolomics data revealed significant hub metabolites, which were used to predict biochemical pathway alterations. Branched-chain amino acid (BCAA) metabolism, and vitamin B6 and B3 metabolism were associated to Aya treatment, as "housekeeping" pathways. Dopamine synthesis was overrepresented in the network results when considering the lowest tested DMT concentration (1 µmol L-1). Building reaction networks containing significant and differential metabolites, such as nicotinamide, L-DOPA, and L-leucine, is a useful approach to guide on dose decision and pathway selection in further analytical and molecular studies.
Comparable studies
Other preclinical and animal studies on ayahuasca for depression, most cited first.
Citations in the library
Cited by 4
- Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain. Molecular Psychiatry July 1, 2024
- 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
- Human pluripotent stem cells as a translational toolkit in psychedelic research in vitro. iScience March 28, 2024
- Distinctive Molecular and Metabolic Profiles of Chemically Synthesized Psilocybin and Psychedelic Mushroom Extract Research Square July 20, 2023
Cites 6
- Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial Psychological Medicine June 15, 2018
- Neuropharmacology of N,N-dimethyltryptamine Brain Research Bulletin April 30, 2016
- A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation. Journal of Analytical Toxicology 2005
- New psychoactive substances (NPS) and serotonin syndrome onset: A systematic review. Experimental Neurology May 1, 2021
- Validation of an analytical method for the determination of the main ayahuasca active compounds and application to real ayahuasca samples from Brazil Journal of Chromatography B June 8, 2019
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