Nutrition and Health Sciences, Department of
Department of Nutrition and Health Sciences: Faculty Publications
Metabolism of Cannabidiol in Respiratory-Associated Cells and HepG2-Derived Cells and Molecular Docking of Cannabidiol and Its Metabolites with CYP Enzymes and Cannabinoid Receptors
ORCID IDs
Kumar Paul https://orcid.org/0000-0003-0097-2515
Bintang https://orcid.org/0009-0007-4461-6789
Sawatdee https://orcid.org/0000-0002-4845-1527
Srichana https://orcid.org/0000-0002-4772-2276
Document Type
Article
Date of this Version
2025
Citation
International Journal of Molecular Sciences (2025) 26: 8384
doi: 10.3390/ijms26178384
Abstract
Cannabidiol (CBD) has been reported in medical applications for various indications. The enzymatic metabolism of CBD is not fully understood in the different routes of administration. This research aimed to identify the CBD metabolites after incubation of CBD with derived hepatocyte cells (HepG2), bronchial epithelial cells (NCI-H358), alveolar cells (A549), and alveolar macrophage cells (NR8383). A liquid chromatography–mass spectrometry technique was developed to quantify the CBD and its metabolites. Molecular docking was employed to evaluate the binding affinity of CBD with different cytochrome P-450 (CYP-450) enzymes and further predict the implication of drug–drug interactions. CBD and major metabolites of CBD were also docked with cannabinoid receptors. The results revealed that only HepG2 cells metabolized CBD to 7-hydroxy-CBD (7-OH-CBD) and 7-carboxy-CBD (7-COOH-CBD), whereas other respiratory cell lines and alveolar macrophages were found to have mainly CBD in the incubated samples without any metabolites. The CYP2C19 and CYP3A4 enzymes were responsible for CBD conversion to hydroxylated CBD metabolites. The 7-OH-CBD and 7-COOH-CBD metabolites were found to bind to cannabinoid receptors with different affinities. The relative abundance of CBD and major metabolites may indicate the potential route of CBD administration.
Comments
Open access
License: CC BY 4.0