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Forensic Toxicology
Published in: Forensic Toxicology 2/2019

Open Access 01-07-2019 | Short Communication

Cannabidiol metabolism revisited: tentative identification of novel decarbonylated metabolites of cannabidiol formed by human liver microsomes and recombinant cytochrome P450 3A4

Authors: Kazuhito Watanabe, Noriyuki Usami, Shigehiro Osada, Shizuo Narimatsu, Ikuo Yamamoto, Hidetoshi Yoshimura

Published in: Forensic Toxicology | Issue 2/2019

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Abstract

Purpose

The purpose of the present study was to identify the structures of cannabidiol (CBD) metabolites during CO formation by human liver microsomes and human recombinant cytochrome P450 (CYP) enzymes.

Methods

CBD was NADPH-dependently metabolized by human liver microsomes and human recombinant CYP enzymes. Less-polar metabolites were analyzed by gas chromatography–mass spectrometry monitoring, and their estimated molecular ions were m/z 286, 358 and 481 after non-derivatization, trimethylsilylation and pentafluorobenzyl oxime formation, respectively.

Results

We tentatively identified novel decarbonylated metabolites of CBD as keto-enol tautomers. Among eight major recombinant human CYP enzymes, only CYP3A4 catalyzed the formation of decarbonylated metabolites.

Conclusions

CBD was biotransformed to two decarbonylated metabolites, an enol-form (cyclopentadienol structure), and a keto-form (cyclopentenone structure) by human liver microsomes and CYP3A4.
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Metadata
Title
Cannabidiol metabolism revisited: tentative identification of novel decarbonylated metabolites of cannabidiol formed by human liver microsomes and recombinant cytochrome P450 3A4
Authors
Kazuhito Watanabe
Noriyuki Usami
Shigehiro Osada
Shizuo Narimatsu
Ikuo Yamamoto
Hidetoshi Yoshimura
Publication date
01-07-2019
Publisher
Springer Singapore
Published in
Forensic Toxicology / Issue 2/2019
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-019-00467-0

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