11 -Nor-A9-THC 9-carboxylic acid

The basic objective of this investigation was to establish sensitive methodology which would not depend on radio-labeling for the quantitative estimation of A9-THC, its primary metabolite 11-hydroxy-A9-THC (3), and cannabinol, which has been reported to be a metabolite of A9-THC in the rat (14). This objective has been realized, utilizing GLC-MS with a variety of techniques and instruments. In addition, the quantitative estimation of 11-nor-A9-THC-9-carboxylic acid has been accomplished. Several aspects of our results merit further discussion. 

We present for the first time pharmacokinetic data in plasma and urine obtained by GLC-MS for the important acid metabolite 11-nor-A9-THC-9-carboxylic acid. This and related acids constitute the major means by which A9-THC is excreted in the urine. The data indicate rapid elimination of the acid in the urine during the first 3-6 hours after administration of A9-THC. 

Suitable immunological reagents for the detection of cannabis abuse from urine tests are available from several companies. In normal circumstances, the sensitivity of a test corresponds to a cut-off value of 50 ng/ml based on 11-nor-A9-THC-9-carboxylic acid. The cut-off values of some cannabinoids are listed in Table 8-29. Only U-nor-A9-THC-9-carboxylic acid is relevant to the determination of consumption from urine tests. 

A plasma calibration curve for ll-nor-A9-THC-9-carboxylic acid, 5a, is shown in Figure 9. There was reasonable linearity from 1.0-50 ng/ml plasma with detection limits of 0.5 ng or less per ml. Figure 10 presents similar data for a urine calibration curve. The method showed reasonable linearity between 2.0-100 ng/ ml urine. Figure 11 presents pharmacokinetic data. for plasma levels of a human volunteer, BS, over a 0.5 hour to 48 hour period comparing A9-THC and 11-nor acid levels after a dose of 5.0 mg of A9-THC by the intravenous route. Both parent compound and acid metabolite exhibited a biphasic elimination pattern although the levels of the acid did not fall as rapidly as parent compound. Elimination of the acid metabolite 5a in urine is shown in Figure 12. It is evident that urinary elimination proceeded rapidly as 80% of the total 11-nor-acid excreted was eliminated in the urine during... 

Cannabis is extensively metabolized in the human to 11 hydroxy- and 8 3 hydroxy-A9-tetrahydrocannabinol (11 OH and SP OH-THC) and finally to 11 nor-A9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), which is conjugated with glucuronic acid to a variable extent. 

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