In vivo metabolites of cannabinol identified as fatty acid conjugates.
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Biomedical subjects
Publications and source records attributed to J E Lindgren.
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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.
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The metabolism of cannabidiol (CBD) was studied in vitro using a 10 000 g supernatant from rat liver. After removal of unchanged CBD and its monohydroxylated metabolites, a polar fraction remained from which ten dioxygenated metabolites were isolated. Mass spectrometry and nuclear magnetic resonance spectroscopy were used to identify the following metabolites: 6,7-dihydroxy-CBD, 1 inch,7-dihydroxy-CBD, 3 inch,7-dihydroxy-CBD, 4 inch,7-dihydroxy-CBD, 5 inch,7-dihydroxy-CBD, 2 inch,6-dihydroxy-CBD, 3 inch,6beta-dihydroxy-CBD, 4 inch, 6beta-dihydroxy-CBD (tentative), 3 inch-hydroxy-6-oxo-CBD, and 4 inch-hydroxy-6-oxo-CBD. The abundance of isolated dihydroxy metabolites reflected the quantity of monohydroxy metabolites that was previously found. In both series, 7-hydroxylation occurred to the greatest extent. Side chain hydroxylation occurred predominantly at C-4 inch and to a lesser degree at C-3 inch. Trace amounts of metabolites were hydroxylated at C-1 inch,-2 inch, or 5 inch.
Cannabidiol (CBD) was metabolized in vitro by rat liver enzymes. Unchanged CBD and eight monohydroxylated metabolites were isolated and positively identified. As previously reported, 7-hydroxy-CBD was the major metabolite. The second most abundant metabolite was 6alpha-hydroxy-CBD; whereas only a trace amount of 6beta-hydroxy-CBD was found. In addition hydroxylation occurred in all positions of the pentyl side chain, 4 inches-hydroxy-CBD being most abundant. 3 inches-Hydroxy-CBD was formed in half of the yield of 4 inches-hydroxy-CBD, while 1 inches-, 2 inches-, 5 inches-hydroxy-CBD were each formed in approximately one fourth of the yield of 4 inches-hydroxy-CBD.
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