In Vivo and in Vitro Metabolism of Cannabidiol Monomethyl Ether and Cannabidiol Dimethyl Ether in the Guinea Pig: On the Formation Mechanism of Cannabielsoin-Type Metabolite from Cannabidiol

Hiroshi Gohda, Shizuo Narimatsu, Ikuo Yamamoto, Hidetoshi Yoshimura

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Oxidative metabolism of cannabidiol monomethyl ether (CBDM), one of the components of marihuana, was studied in the guinea pig. Cannabielsoin monomethyl ether (CBEM) was found to be formed with hepatic microsomes by gas chromatography-mass spectrometry (GC-MS). Experiments using various modifiers of enzymatic reaction suggested that, as in the case of cannabielsoin (CBE) formation from canabidiol (CBD), CBEM was formed from CBDM by the monooxygenase system including cytochrome P450. When cannabidiol dimethyl ether (CBDD), in which phenolic hydroxyl groups of CBD are masked with methyl groups, was incubated with liver microsomes and an reduced nicotinamide adenine dinucleotide phosphate-generating system, 1 S,2β-epoxy-CBDD was identified by GC-MS. The epoxy metabolite was also found in the liver of a guinea pig pretreated with CBDD (100 mg/kg, intraperitoneally) 1 h before sacrifice. Rate of 15,2β-epoxide metabolism was slower than that of 1β,2S' -epoxy-CBDD under the conditions, as in the microsomal oxidation of CBDD described above. These results indicate that l£,2β-epoxides are formed from CBD, CBDM and CBDD and that the epoxides are quickly converted to elsoin-type metabolites in the cases of CBD and CBDM.

Original languageEnglish
Pages (from-to)1697-1701
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Volume38
Issue number6
DOIs
Publication statusPublished - 1990
Externally publishedYes

Keywords

  • 1S,2R-epoxy-intermediate
  • cannabidiol dimethyl ether
  • cannabidiol monomethyl ether
  • cannabielsoin monomethyl ether
  • elsoin-type metabolite
  • in vitro metabolism
  • in vivo metabolism
  • monooxygenase

ASJC Scopus subject areas

  • General Chemistry
  • Drug Discovery

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