The urinary disposition of intravenously administered 11-nor-9-carboxy-delta-9-tetrahydrocannabinol in humans.

The objective of this study was to investigate the fraction of an administered dose of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THCCOOH) that is actually excreted into urine and to determine its urinary half-life independent of the parent compound. Ten healthy, male marijuana nonusers who were enrolled in the study were administered a single dose of 5 mg THCCOOH by the intravenous route. Urine specimens were collected up to 96 hours after administration. Samples were extracted before and after alkaline hydrolysis. The concentration of unconjugated and total THCCOOH was determined using gas chromatography-mass spectrometry. Most of the THCCOOH found in urine was conjugated, with only 0.14 +/- 0.08% of the dose present as unconjugated THCCOOH. The amount of conjugated THCCOOH ranged from 149.3 to 559.8 (mean +/- SD, 342.8 +/- 117.3) microg, representing a recovery of 3% to 11% of the administered dose. The measured amounts of total THCCOOH were low and highly varied among individuals. Renal excretion does not appear to be the preferred elimination pathway for THCCOOH. Urinary elimination half-life of unconjugated and conjugated THCCOOH ranged from 9.0 to 27.4 (mean +/- SD, 17.3 +/- 5.3) hours and from 10.7 to 27.6 (mean +/- SD, 16.0 +/- 5.0) hours, respectively. Although preliminary in nature, the actual urinary elimination half-life of THCCOOH appears to be significantly shorter than its apparent or terminal half-life reported from single or multiple dosing of delta-9-tetrahydrocannabinol (THC).