11-nor-delta 9-tetrahydrocannabinoid (THC) is the principle psychoactive cannabinoid in marijuana. Its major urinary metabolites are 11-nor-delta 9-tetrahydrocannabinoid carboxylic acid (THCA) and its glucuronide conjugate. Cannabinoid metabolites immunoassays (EMIT, FPIA, CEDIA, and KIMS) are designed for THCA detection and are calibrated with this compound; typical cutoffs used are 20, 25, 50, and 100ng/ml of THCA. These assays do have substantial cross-reactivity with other cannabinoids, and THCA concentrations estimated semi-quantitatively (as THCA equivalents) can be 2-5 times higher than the actual THCA concentration determined quantitatively by GC-MS. Hence, the most commonly adopted GC-MS cutoff for THCA is 15 ng/ml.

THC has a very large volume of distribution (large tissue store), and continued release of THC from tissue storage can lead to a window of detection of THCA in urine that can range from 2 to 5 days for infrequent users to over 70 days for chronic heavy users (28). The excretion profile of THCA since the last exposure should reflect a downward trend. Variation in hydration status, however, means that the same amount of THCA excreted into urine can be higher in concentration in a dehydrated individual (with lower urine volume) than a fluid-loaded individual. This can lead to fluctuation in urine THCA concentrations, including "spikes" in the excretion profile, which could be interpreted as new use of marijuana. Because creatinine excretion into urine is at a fairly constant daily rate, it is possible to normalize the fluctuation of urine THCA concentration due to variation in hydration status by relating urine THCA concentration to creatinine concentration (29). It has been proposed, based on a carefully controlled study, that an increase of 50% in the THCA : creatinine ratios of two urine specimens collected 24 h apart would indicate reuse of marijuana (30).

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