The effect of cannabidiol on mouse hepatic microsomal cytochrome P450-dependent anandamide metabolism.
Anandamide (arachidonylethanolamide) has been identified as a brain constituent that selectively binds to the cannabinoid receptor and possesses cannabimimetic activity. Cytochromes P450 catalyze the oxidation of arachidonic acid to several metabolites possessing very potent pharmacological activity. We examined whether P450 would also metabolize anandamide, and whether cannabidiol (a cannabinoid which inactivates several P450s) would affect this metabolism. Mouse hepatic P450s were found to metabolize anandamide to at least 10 different metabolites, four of which were characterized by mass spectrometry. Cannabidiol selectively inhibited the formation of two of these four anandamide metabolites. The significance of anandamide metabolism remains to be explored.
Bornheim
L M
LM
Department of Pharmacology, University of California, San Francisco 94143-0450.
Kim
K Y
KY
Chen
B
B
Correia
M A
MA
D000577:Amides / Q000378:metabolism*; D000581:Amidohydrolases; D000818:Animals; D001095:Arachidonic Acids; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000378:metabolism; D002185:Cannabidiol / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D053284:Polyunsaturated Alkamides; D013053:Spectrophotometry; D000099252:Fatty Acid Amide Hydrolases
D000577:Amides; D000581:Amidohydrolases; D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002185:Cannabidiol; D003577:Cytochrome P-450 Enzyme System; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated; D006899:Mixed Function Oxygenases; D053284:Polyunsaturated Alkamides; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide