Neutral in vivo metabolites of cannabinol isolated from rat faeces

Abstract

The in vivo transformation of cannabinol (CBN) in the rat has been studied. Unchanged CBN and nine neutral mono‐oxygenated and dioxygenated CBN metabolites have been identified. In the mono‐oxygenated series the metabolites occurred in decreasing order of prominence as follows: 7‐hydroxy‐CBN, 4“‐hydroxy‐CBN, 1”‐hydroxy‐CBN, 2“‐hydroxy‐CBN, 3”‐hydroxy‐CBN, 5“‐hydroxy‐CBN and CBN‐7‐al. In the dihydroxylated metabolite series only 1”,7‐dihydroxy‐CBN and 4“,7‐dihydroxy‐CBN were found with the former as the more prominent metabolite.

Mass spectrometry of the cannabinoids and their metabolites

“…Its mass spectrum is similar to that of CBN itself with the most abundant ion at [M -151 produced by loss of a gem-methyl group, and with all ions shifted by 16 mass units from their positions in the mass spectrum of CBN. The spectrum of the TMS ether is similar (174,191) and illustrates the general simplicity of the spectra of all metabolites of CBN. Hydroxylation also occurs in all positions of the side chain with fragmentation of the TMS ethers giving the same diagnostic fragment ions as are found for THC (Table 11) (91,174,191,192).…”

“…The spectrum of the TMS ether is similar (174,191) and illustrates the general simplicity of the spectra of all metabolites of CBN. Hydroxylation also occurs in all positions of the side chain with fragmentation of the TMS ethers giving the same diagnostic fragment ions as are found for THC (Table 11) (91,174,191,192). The TMS derivatives of the dihydroxy-metabolites, 1 '-, 2'-, 3'-, and 4',ll-dihydroxy-CBN, also give simple spectra with M t , [M -151 + , and the diagnostic sidechain fragment ion being the only abundant ions in the spectra (174,193).…”

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

“…The mass spectrum and retention time of the major metabolite corresponding to peak-2 were identical with those of 11-hydroxy-CBN. Lack of diagnostic ions other than those at m/z 455 and 470 indicates that the position of a hydroxyl group of the metabolite corresponding to peak-1 is not on the pentyl side chain [6]. The retention time and mass spectrum of the metabolite (Figs.…”

“…Because aged marijuana samples particularly contain high amounts of CBN [3], the cannabinoid might be more important in pharmacological and toxicological effects of old samples. Metabolism of CBN was extensively studied in animals [4][5][6][7][8][9], and appears less complicated than that of other cannabinoids like THC and cannabidiol. The hydroxylations at the 11-position and on the pentyl side chain were found to be the only pathways for the oxidation of CBN in these animal studies.…”