Cannabielsoin as a new metabolite of cannabidiol in mammals

Yamamoto Ikuo Yamamoto, Gohda Hiroshi Gohda, Narimatsu Shizuo Narimatsu, Watanabe Kazuhito Watanabe, Yoshimura Hidetoshi Yoshimura

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Cannabielsoin (CBE) was identified as a novel metabolite of cannabidiol (CBD) in the guinea pig in vivo and in vitro. Its formation by liver microsomes of guinea pigs needed NADPH and molecular oxygen, and was inhibited with SKF 525-A, metyrapone and α-naphthoflavone, indicating participation of cytochrome P-450 (P-450). The CBE-forming activity was highest in guinea pigs, followed by mice, rabbits and rats. In the rat, sex difference was found in the CBE formation (male>female). CBD monomethylether (CBDM) was also biotransformed to CBE monomethylether (CBEM) in the guinea pig in vivo and in vitro. When CBD dimethylether (CBDD) was employed as substrate, 1S,2R-epoxy-CBDD was identified. The results suggest that CBD and CBDM are biotransformed by P-450 to CBE-type metabolites via 1S,2R-epoxides. In pharmacological studies using mice, CBDD and 1S, 2R-epoxy-CBD-2′,6′-diacetate produced hypothermia, and CBD, CBDM and CBEM prolonged pentobarbital-induced sleep. Moreover, 1S,2R-epoxy-CBD-2′,6′-diacetate was examined in the Ames test, but had no mutagenicity.

Original languageEnglish
Pages (from-to)541-546
Number of pages6
JournalPharmacology Biochemistry and Behavior
Volume40
Issue number3
DOIs
Publication statusPublished - 1991
Externally publishedYes

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Cannabidiol
Mammals
Metabolites
Guinea Pigs
Rats
Chemical beam epitaxy
Hypothermia
Proadifen
Metyrapone
Molecular oxygen
Epoxy Compounds
Liver Microsomes
Pentobarbital
cannabielsoin
NADP
Sex Characteristics
Liver
Cytochrome P-450 Enzyme System
Sleep
Pharmacology

Keywords

  • 1S,2R-Epoxy intermediate
  • Ames test
  • Barbiturate synergism
  • Cannabidiol
  • Cannabielsoin
  • Cytochrome P-450
  • Guinea pig
  • Hypothermia
  • Liver microsomes
  • Species difference

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Ikuo Yamamoto, Y., Hiroshi Gohda, G., Shizuo Narimatsu, N., Kazuhito Watanabe, W., & Hidetoshi Yoshimura, Y. (1991). Cannabielsoin as a new metabolite of cannabidiol in mammals. Pharmacology Biochemistry and Behavior, 40(3), 541-546. https://doi.org/10.1016/0091-3057(91)90360-E

Cannabielsoin as a new metabolite of cannabidiol in mammals. / Ikuo Yamamoto, Yamamoto; Hiroshi Gohda, Gohda; Shizuo Narimatsu, Narimatsu; Kazuhito Watanabe, Watanabe; Hidetoshi Yoshimura, Yoshimura.

In: Pharmacology Biochemistry and Behavior, Vol. 40, No. 3, 1991, p. 541-546.

Research output: Contribution to journalArticle

Ikuo Yamamoto, Y, Hiroshi Gohda, G, Shizuo Narimatsu, N, Kazuhito Watanabe, W & Hidetoshi Yoshimura, Y 1991, 'Cannabielsoin as a new metabolite of cannabidiol in mammals', Pharmacology Biochemistry and Behavior, vol. 40, no. 3, pp. 541-546. https://doi.org/10.1016/0091-3057(91)90360-E
Ikuo Yamamoto Y, Hiroshi Gohda G, Shizuo Narimatsu N, Kazuhito Watanabe W, Hidetoshi Yoshimura Y. Cannabielsoin as a new metabolite of cannabidiol in mammals. Pharmacology Biochemistry and Behavior. 1991;40(3):541-546. https://doi.org/10.1016/0091-3057(91)90360-E
Ikuo Yamamoto, Yamamoto ; Hiroshi Gohda, Gohda ; Shizuo Narimatsu, Narimatsu ; Kazuhito Watanabe, Watanabe ; Hidetoshi Yoshimura, Yoshimura. / Cannabielsoin as a new metabolite of cannabidiol in mammals. In: Pharmacology Biochemistry and Behavior. 1991 ; Vol. 40, No. 3. pp. 541-546.
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