Metabolism of cannabidiol by the rat

E. Samara*, M. Bialer, D. J. Harvey

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Metabolites of CBD excreted into the bile and perfusion fluid were examined in a rat liver perfusion preparation. Metabolites were extracted with ethyl acetate and identified by GC/MS as TMS derivatives. Four mono- and five di-hydroxy metabolites were identified with major sites of metabolic attack being at C-7 and C-4″. A hydroxy-ketone was detected but not fully identified. All biliary metabolites were conjugated with glucuronic acid. Urinary metabolites were studied in rats with samples taken at times to 25 h after drug administration. Unmetabolized CBD and 13 metabolites were identified by GC/MS. Major metabolites were acids with beta-oxidation being a prominent pathway. The 6- and 7-hydroxy derivatives of 4″, 5″-bis,nor-CBD-3″-oic acid were the most abundant compounds but substantial concentrations of the di-acids, CBD-5″,7-dioic acid and 4″,5″-bis,nor-CBD-3″,7-dioic acid were present. Concentrations of the more highly oxidized metabolites increased with time.

Original languageEnglish
Pages (from-to)305-313
Number of pages9
JournalEuropean Journal of Drug Metabolism and Pharmacokinetics
Volume16
Issue number4
DOIs
StatePublished - Oct 1991

Keywords

  • Acids
  • beta-oxidation
  • bile
  • cannabidiol
  • hydroxylation
  • mass spectrometry
  • perfusion
  • rat
  • urine

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