OpenLB
Open Library of Bioscience
Advanced Search
International journal of molecular sciences
Aug 28, 2025;26 (17):

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.

Krittawan Tongkanarak, Pijush Kumar Paul, Muhammad A Khumaini Mudhar Bintang, Roongnapa Suedee, Somchai Sawatdee, Teerapol Srichana
Author Information
  1. Krittawan Tongkanarak: Drug Delivery System Excellence Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
  2. Pijush Kumar Paul: Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA. ORCID
  3. Muhammad A Khumaini Mudhar Bintang: Drug Delivery System Excellence Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand. ORCID
  4. Roongnapa Suedee: Molecular Recognition Materials Research Unit, Drug Delivery System Excellence Center, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
  5. Somchai Sawatdee: Drug and Cosmetics Excellence Center and School of Pharmacy, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand. ORCID
  6. Teerapol Srichana: Drug Delivery System Excellence Center, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand. ORCID
PMID: 40943305 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.

Keywords

CYP450 cannabidiol cannabinoid receptor drug delivery metabolism

References

Int J Mol Sci. 2020 May 27;21(11): [PMID: 32471272]
Eur Neuropsychopharmacol. 2017 Dec;27(12):1223-1237 [PMID: 29129557]
J Comput Chem. 2009 Dec;30(16):2785-91 [PMID: 19399780]
Cannabis Cannabinoid Res. 2016 Mar 01;1(1):90-101 [PMID: 28861484]
CNS Drugs. 2018 Nov;32(11):1053-1067 [PMID: 30374683]
J Med Chem. 2020 Nov 12;63(21):12137-12155 [PMID: 32804502]
Biochem Pharmacol. 1986 Feb 15;35(4):563-8 [PMID: 3004505]
Chem Biol Interact. 2005 Jan 15;151(2):53-62 [PMID: 15698577]
Pharmaceuticals (Basel). 2024 Feb 13;17(2): [PMID: 38399459]
Adv Pharmacol. 2017;80:169-206 [PMID: 28826534]
Drug Metab Dispos. 2022 Apr;50(4):351-360 [PMID: 35115300]
Crit Rev Toxicol. 2002 Sep;32(5):391-411 [PMID: 12389869]
Life Sci. 2011 Aug 1;89(5-6):165-70 [PMID: 21704641]
Expert Opin Drug Metab Toxicol. 2021 May;17(5):611-625 [PMID: 33759677]
Am J Respir Cell Mol Biol. 2000 Mar;22(3):360-6 [PMID: 10696073]
Molecules. 2022 Jan 11;27(2): [PMID: 35056767]
Int J Mol Sci. 2020 Sep 14;21(18): [PMID: 32937917]
Expert Rev Clin Pharmacol. 2022 Dec;15(12):1443-1460 [PMID: 36384377]
J Pharm Sci. 2021 Dec;110(12):3946-3952 [PMID: 34400185]
Drug Metab Rev. 2017 May;49(2):105-138 [PMID: 28266877]
Bioorg Med Chem. 2015 Apr 1;23(7):1377-85 [PMID: 25703248]
Molecules. 2021 Apr 23;26(9): [PMID: 33922473]
Basic Clin Pharmacol Toxicol. 2022 Apr;130(4):439-456 [PMID: 35083862]
Perm J. 2020 Dec;25:1-3 [PMID: 33635755]
Br J Pharmacol. 2007 Mar;150(5):613-23 [PMID: 17245363]
Int J Pharm. 2024 Jun 25;659:124235 [PMID: 38762165]
Curr Neuropharmacol. 2007;5(2):73-80 [PMID: 18615177]
Front Pharmacol. 2022 Oct 24;13:1038754 [PMID: 36353497]
Drug Alcohol Depend. 2020 Jun 1;211:107937 [PMID: 32247649]
Drug Metab Dispos. 2021 Dec;49(12):1070-1080 [PMID: 34493602]
J Drug Deliv Sci Technol. 2022 Oct;76:103805 [PMID: 36159727]
Drug Metab Rev. 2014 Feb;46(1):86-95 [PMID: 24160757]
Drug Metab Dispos. 2021 Oct;49(10):882-891 [PMID: 34330718]
Molecules. 2022 Nov 04;27(21): [PMID: 36364400]
Drug Metab Dispos. 2012 Oct;40(10):1953-65 [PMID: 22798553]

Grants

  1. PHA6601197c/National Science, Research and Innovation Fund and Prince of Songkla University

MeSH Term

Humans
Cannabidiol
Molecular Docking Simulation
Hep G2 Cells
Receptors, Cannabinoid
Cytochrome P-450 Enzyme System
Cytochrome P-450 CYP3A
Macrophages, Alveolar
Cytochrome P-450 CYP2C19

Chemicals

Cannabidiol
Receptors, Cannabinoid
Cytochrome P-450 Enzyme System
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP2C19
Journal Article

Word Cloud

Similar Articles

Cited By