Comparative in vitro metabolism of the cannabinoids

Pharmacol Biochem Behav. 1991 Nov;40(3):533-40. doi: 10.1016/0091-3057(91)90359-a.

Abstract

The metabolism of delta-9-tetrahydrocannabinol (delta-9-THC), delta-8-THC, delta-11-THC, cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), cannabigerol (CBG) and the equatorial-isomer of hexahydrocannabinol (HHC) was studied in microsomal preparations obtained from rats, mice, guinea pigs, rabbits, hamsters, gerbils and a cat. Identification of metabolites was by GC/MS and quantification by gas chromatography. Major metabolites were monohydroxylated compounds but the pattern of hydroxylation varied considerably between the species, no doubt reflecting the variable nature of the cytochrome P-450 mixed-function oxidases. Although the primary carbon allylic to the endocyclic double bond of tricyclic cannabinoids was usually the major site of attack, the 4' (side-chain, omega-1 position) and the terpene ring were usually favoured by the cat and hamster respectively. The guinea pig generally produced more metabolites hydroxylated in the side-chain (all positions) than did the other species. The results from HHC were very similar to those from THC, namely hydroxylation at C-11 in most species, and the production of high concentrations of 8 alpha-hydroxy-HHC in the mouse and 8 beta-hydroxy-HHC in the hamster. As this molecule lacks the double bond of the THCs and, hence, the allylic nature of C-11 and C-8, the results suggest that it is the orientation of the molecule to the active site of the cytochrome P-450 mixed-function oxidase rather than the reactivity of the C-H bond that governs the position of hydroxylation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cannabinoids / metabolism*
  • Cats
  • Chromatography, Gas
  • Cricetinae
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Gerbillinae
  • Guinea Pigs
  • In Vitro Techniques
  • Isoenzymes / metabolism
  • Male
  • Mesocricetus
  • Mice
  • Microsomes, Liver / metabolism
  • Rabbits
  • Rats

Substances

  • Cannabinoids
  • Isoenzymes
  • Cytochrome P-450 Enzyme System