NAD(P)⁺-dependent alcohol oxidoreductases oxidize 7-hydroxycannabidiol to a reactive formyl metabolite.

ABSTRACT: Cannabidiol (CBD) undergoes oxidation to 7-hydroxy-CBD in the liver via cytochrome P450 enzymes. 7-Hydroxy-CBD can be further oxidized to 7-carboxy-CBD, the principal circulating metabolite in humans. An aldehyde intermediate, 7-formyl-CBD, is hypothesized to be the precursor of 7-carboxy-CBD; however, the formation of 7-formyl-CBD and the enzymes leading to its formation and metabolism have not been thoroughly investigated. Upon incubating 7-hydroxy-CBD with human liver S9 or microsomes, and using O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) as a trapping agent, we demonstrated the formation of 7-formyl-CBD as its oxime derivative 7-pentafluorobenzyl oxime-CBD (7-PFBO-CBD). The transformation of 7-hydroxy-CBD to 7-formyl-CBD in S9 or microsomes required NAD⁺ or NADP

SUBMITTER: Wu Q 

PROVIDER: S-EPMC12438966 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature