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Metabolism of cannabidiol by the rat

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Summary

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.

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Author notes

  1. D. J. Harvey

    Present address: Glycobiology Institute, Dept of Biochemistry, University of Oxford, South Parks Road, OX1 3QT, Oxford, UK

Authors and Affiliations

  1. University Department of Pharmacology, Oxford, UK

    D. J. Harvey

  2. Department of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel

    E. Samara & M. Bialer

Authors
  1. E. Samara
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  2. M. Bialer
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  3. D. J. Harvey
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Samara, E., Bialer, M. & Harvey, D.J. Metabolism of cannabidiol by the rat. European Journal of Drug Metabolism and Pharmacokinetics 16, 305–313 (1991). https://doi.org/10.1007/BF03189976

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  • DOI: https://doi.org/10.1007/BF03189976

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