Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
In Vitro Metabolic Formation of a New Metabolite, 6β-Hydroxymethyl-Δ9-tetrahydrocannabinol from Cannabidiol through an Epoxide Intermediate and Its Pharmacological Effects on Mice
Katsunori NAGAIKazuhito WATANABEShizuo NARIMATSUHiroshi GOHDATamihide MATSUNAGAIkuo YAMAMOTOHidetoshi YOSHIMURA
Author information
JOURNALS FREE ACCESS

1993 Volume 16 Issue 10 Pages 1008-1013

Details
Abstract

The oxidative metabolism of cannabidiol (CBD) at the 8, 9-double bond was examined. 8R, 9-Epoxy-CBD was identified by GC-MS as a new metabolite of CBD produced by hepatic microsomal fractions of guinea pigs, rats and mice. The reaction required NADPH as a cofactor and molecular oxygen. The optimal pH for the reaction was 7.4-8.0. The 8R, 9-epoxy-CBD forming activity was highest in guinea pigs, followed by mice and rats in the presence of 3, 3, 3-trichloropropene-1, 2-oxide (TCPO), an inhibitor of epoxide hydrolase. The activity was significantly suppressed by SKF 525-A, α-naphthoflavone, metyrapone and carbon monoxide. 8R, 9-Epoxy-CBD was further converted to 6β-hydroxymethyl-Δ9-tetrahydrocannabinol (6β-CH2OH-Δ9-THC) and 8, 9-dihydro-8, 9-dihydroxy-CBD by hepatic microsomes of guinea pigs, rats and mice. Microsomal formation of 6β-CH2OH-Δ9-THC was markedly increased in the presence of TCPO with a concomitant decrease in the formation of 8, 9-dihydro-8, 9-dihydroxy-CBD in all animal species examined. Furthermore, 6β-CH2OH-Δ9-THC was also identified as a new metabolite of CBD produced by hapatic microsomes of guinea pigs. 6β-CH2OH-Δ9-THC exhibited THC-like pharmacological effects, catalepsy, analgesia, pentobarbital-induced sleep prolongation and hypothermia in mice, although these effects were less marked than those of Δ9-THC. This study presents the first example of the biotransformation of CBD to a Δ9-THC derivative which exhibits some pharmacological effects.

Information related to the author
© The Pharmaceutical Society of Japan
Previous article Next article
feedback
Top