Understanding ayahuasca effects in major depressive disorder treatment through in vitro metabolomics and bioinformatics.
Analytical and bioanalytical chemistry July 1, 2023 Flávia S Zandonadi, Alex Ap Rosini Silva, Aline A S Melo et al. 9 citations
Metabolomic studies of major depressive disorder have focused on energy, oxidative stress, and neurotransmission pathways. Hub metabolites—key nodes in biochemical networks—integrate metabolism and signaling. This work used an in vitro primary astrocyte model with untargeted metabolomics of secretome and intracellular content after ayahuasca treatments based on DMT concentration. Mass spectrometry data identified significant hub metabolites predicting pathway alterations. Ayahuasca treatment was associated with branched-chain amino acid, vitamin B6, and vitamin B3 metabolism as housekeeping pathways. At the lowest DMT concentration (1 µmol L-1), dopamine synthesis was overrepresented in network results. Building reaction networks with metabolites like nicotinamide, L-DOPA, and L-leucine can guide dose decisions and pathway selection in future studies.