Metabolism of A9-THC

The application of GLC-MS techniques to the ill vitro and ill vivo metabolism of A9-THC (8) laid the groundwork for the quantitative analysis of other cannabinoid metabolites. The sites of metabolic hydroxylation for many cannabinoids are shown in Figure 1. 

The development of sensitive and accurate GLC-MS methodology permitted a preliminary study in man utilizing these techniques for the precise determination of A9-THC, 11-hydroxy-A9-thc and CBN in plasma. Previously we have made an extensive study (4) of the metabolism of A9-THC in man using radio-labeled tracers and thin layer chromatography. The procedures utilized (in addition to the undesirability of a radio-labeled tracer in man) suffer from two potential sources of error. 

Like other xenobiotics, cannabinoids also undergo extensive metabolism in the human body to increase their hydrophihc properties for a facihtated ehmination. The metaboHsm of A9-THC has been very well investigated. More than 100 metabolites of A9-THC are known [99] and a good overview of the most important human metaboHtes is given in [100]. MetaboHsm takes place mainly in hepatic microsomes, but also in intestines, brain. 

As described in previous papers by Wall (2), most of the metabolic alterations of A9-THC occur in the cyclohexane moiety with hydroxylation of the A9-com-pound occurring at the 11- and 8-positions along with conversion of the 11-carbon to a carboxyl group. 

Although animal studies indicate transfer of A -THC into the milk, comparable research has not been done on humans. It is difficult to extrapolate from animal studies to humans. The only primates studied, squirrel monkeys, are known to metabolize A9-THC differently than humans. (15) In addition, lactating human mothers in the general population ingest both A9-THC and other cannabinoids (e.g., CBN, CBD) by smoking cannabis. Information is not currently available regarding either transfer of cannabinoids into the milk of lactating humans or the effects of maternal cannabis use on infant development. 

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