Untargeted rat brain metabolomics after oral administration of a single high dose of cannabidiol

[Display omitted] •CBD (50 mg/kg, single dose) was administered orally to rats in either ethanol or olive oil.•CBD concentrations in the brain were evaluated by LC–MS/MS and no conversion into THC was observed.•An untargeted metabolomics approach revealed that the main metabolites derived from CBD h...

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Bibliographic Details
Published in:Journal of pharmaceutical and biomedical analysis 2018-11, Vol.161, p.1-11
Main Authors: Citti, Cinzia, Palazzoli, Federica, Licata, Manuela, Vilella, Antonietta, Leo, Giuseppina, Zoli, Michele, Vandelli, Maria Angela, Forni, Flavio, Pacchetti, Barbara, Cannazza, Giuseppe
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
Cannabidiol
Cannabidiol - administration & dosage
Cannabidiol - analogs & derivatives
Cannabidiol - analysis
Cannabidiol - pharmacokinetics
Cannabidiol metabolites
Chromatography, High Pressure Liquid - methods
Dronabinol - analogs & derivatives
Dronabinol - analysis
Liquid chromatography
Mass spectrometry
Metabolomics
Rats
Tandem Mass Spectrometry - methods
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Summary:[Display omitted] •CBD (50 mg/kg, single dose) was administered orally to rats in either ethanol or olive oil.•CBD concentrations in the brain were evaluated by LC–MS/MS and no conversion into THC was observed.•An untargeted metabolomics approach revealed that the main metabolites derived from CBD hydroxylation on the side chain.•CBD concentration in ethanol was higher than in oil at 3 h, but lower than in oil at 6 h. Cannabidiol (CBD), for long time considered as a minor cannabinoid of Cannabis sativa, has recently gained much attention due to its antioxidant, anti-inflammatory, analgesic and anticonvulsant properties. A liquid chromatography coupled to mass spectrometry based method was developed for the quantitative determination of CBD and other cannabinoids (Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC and 11-nor-9-carboxy-THC) in rat brain samples after oral administration of a single high dose (50 mg/kg) of CBD. The main challenge of the present work was to study CBD pharmacokinetics in rat cortex: the identification of its metabolites and pharmacodynamics through the study of variations in endogenous compounds’ concentrations following CBD administration. An untargeted metabolomics approach revealed the formation of some CBD metabolites that are not commonly found in other body tissues or fluids. Lastly, the changes in some endogenous compounds’ concentrations were correlated with some of the pharmacological properties of this cannabinoid.
ISSN:0731-7085
1873-264X
DOI:10.1016/j.jpba.2018.08.021