8-Hydroxycannabinol: a new metabolite of cannabinol formed by human hepatic microsomes

Abstract

Metabolism of cannabinol (CBN) was studied in vitro using hepatic microsomes from human livers. The metabolites formed were analyzed by thinlayer chromatography (TLC) and identified by gas chromatography-mass spectrometry as their trimethylsilyl derivatives. 11-Hydroxy-CBN, the major metabolite, was detected together with a smaller amount of another mono-hydroxylated metabolite. The minor metabolite was identified as 8-hydroxy-CBN, after comparing its Rf value by TLC, retention time by GC, and the mass spectrum with those of the authentic compound. 8-Hydroxy-CBN was confirmed to be a new metabolite of CBN formed by human hepatic microsomes.

Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes

“…Expressed human CYP3A4 catalyzed the 7α-(5.34 nmol/min/nmol CYP) and 7β-(1.39 nmol/min/nmol CYP) hydroxylation of Δ 8 -THC, and the 8β-hydroxylation (6.10 nmol/min/nmol CYP) and 9α,10α-epoxidation (1.71 nmol/min/nmol CYP) of Δ 9 -THC. Expressed CYP3A4 also catalyzed the formation of 8-hydroxy-CBN, which has been reported as a new metabolite of CBN by human hepatic microsomes (Watanabe et al, 2006), although CYP3A4 did not catalyze the 11-hydroxylation of three cannabinoids at a detectable level. No other CYPs expressed in the microsomes of human B lymphoblastoid cells catalyzed efficiently the 8-(or 7-) and 11-hydroxylations of these cannabinoids.…”

Generation of reactive oxygen species during mouse hepatic microsomal metabolism of cannabidiol and cannabidiol hydroxy-quinone

“…Hepatic microsomes were prepared as described previously (Watanabe et al, 1986(Watanabe et al, , 2006. P450 content and protein concentration in the microsomes were determined by the methods of Omura and Sato (1964) and Lowry et al (1951) with bovine serum albumin as a standard, respectively.…”

Cannabidiol, a Major Phytocannabinoid, As a Potent Atypical Inhibitor for CYP2D6

“…CBN is thought to exert minimal pharmacological effects in the central nervous system. ⌬ 9 -THC, CBD, and CBN have been reported to be extensively metabolized by human liver microsomes (HLMs) (Bornheim et al, 1992;Watanabe et al, 1995Watanabe et al, , 2006Watanabe et al, , 2007Jiang et al, 2011). It has been demonstrated that CYP2C and CYP3A enzymes are predominantly involved in the primary metabolism of the phytocannabinoids in the liver microsomes.…”