Effect of cannabidiol on cytochrome P-450 isozymes

Biochem Pharmacol. 1989 Sep 1;38(17):2789-94. doi: 10.1016/0006-2952(89)90432-2.


Cannabidiol (CBD) has been shown to inhibit mouse hepatic mixed-function oxidations of several drugs after acute treatment, whereas repetitive treatment resulted in the restoration of drug-metabolizing capabilities. We have found that acute CBD treatment modestly decreased cytochrome P-450 content but markedly decreased hexobarbital hydroxylase, erythromycin N-demethylase, and 6 beta-testosterone hydroxylase activities. Repetitive CBD treatment, on the other hand, resulted in the restoration of cytochrome P-450 content as well as hexobarbital hydroxylase and erythromycin N-demethylase activities. However, after such repeated treatments a fresh dose of CBD can once again inactivate erythromycin N-demethylase activity but not hexobarbital hydroxylase activity. The resistance of hexobarbital hydroxylase to re-inactivation by CBD was paralleled by stimulation of pentoxyresorufin O-dealkylase activity and the appearance of a 50 kD protein that was immunoreactive to an antibody raised against rat hepatic cytochrome P-450b. CBD metabolism in vitro by microsomes prepared from such CBD-"induced" animals, resulted in a pattern of metabolites different from that observed from comparable incubations with liver microsomes from either untreated or phenobarbital-treated animals. Thus, it appears that CBD initially inactivates at least one cytochrome P-450 isozyme, but after repetitive CBD treatment, an isozyme is induced that is resistant to further re-inactivation by CBD. This isozyme appears to be immunochemically similar to, but somewhat functionally distinct from, the isozyme induced by phenobarbital treatment in mice.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Cannabidiol / metabolism
  • Cannabidiol / pharmacology*
  • Cannabinoids / pharmacology*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dronabinol / pharmacology
  • In Vitro Techniques
  • Isoenzymes / metabolism*
  • Male
  • Mice
  • Microsomes, Liver / enzymology*
  • Mixed Function Oxygenases / metabolism


  • Cannabinoids
  • Isoenzymes
  • Cannabidiol
  • Dronabinol
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases