Fecha de publicación: -- Fuente: PubMed "Cannabis" Metabolites. 2026 Sep 3;16(9):645. doi: 10.3390/metabo16090645.ABSTRACTBACKGROUND: Cannabis contains Δ9-tetrahydrocannabinol (THC) together with numerous other constituents, whereas HU210 (HU) is a synthetic full agonist at cannabinoid receptors. We applied integrated metabolomics and proteomics to compare Cannabis extract (CS) and HU in GT1-7 neuronal cells.METHODS: Cytotoxicity was evaluated using a lactate dehydrogenase assay. Metabolites and proteins were extracted sequentially from single-cell pellets and analyzed using gas chromatography-tandem mass spectrometry and nano-liquid chromatography-quadrupole-Orbitrap mass spectrometry, respectively. Cannabinoids in the exposure medium were quantified using liquid chromatography-tandem mass spectrometry.RESULTS: The lowest CS and HU concentrations that were cytotoxic at 24 h and non-cytotoxic at 3 h were 2000 µg/mL and 20 µM, respectively; CS delivered 166 nM THC, 800 nM tetrahydrocannabinolic acid, and 11.3 nM cannabidiol. After 3 h, HU altered both the metabolome and the proteome, whereas CS altered the metabolome with minimal proteome change (8 of 2720 proteins). Six pathways differed, including the citrate cycle and pentose phosphate pathway. Relative to both the control and CS, HU decreased citrate; increased 2-ketoglutarate, fumarate, malate, gluconate, ribose-5-phosphate and ribose; and increased phosphoenolpyruvate carboxykinase 2, isocitrate dehydrogenase 3 subunit α, 2-oxoglutarate dehydrogenase complex component E1, succinate dehydrogenase flavoprotein subunit, malate dehydrogenase 1, 6-phosphogluconolactonase, 6-phosphogluconate dehydrogenase and phosphoglucomutase-1. CS showed the opposite metabolite changes without corresponding enzyme changes.CONCLUSIONS: At a pre-lethal time point, CS and HU produced metabolic changes in opposite directions-broad suppression versus coordinated mobilisation-despite comparable cytotoxicity at 24 h.PMID:42783770 | DOI:10.3390/metabo16090645