Elimination

After the initial distribution phase, the rate-limiting step in the elimination of THC is its redistribution from lipid depots to blood (54). Early studies showed that

Excretion Cannabis

0 30 60 90 120 150 180 Hours

Fig. 4. Urinary excretion profile of 11-nor-9-carboxy-A9-THC (THCCOOH) as measured by gas chromatography/mass spectrometry (GC/MS) in one subject following smoking of a single 3.55% THC cigarette. The horizontal line at 15 ng/mL represents the current GC/MS cutoff used in most testing programs. The urinary THC-COOH concentrations (ng/mL) normalized to urine creatinine concentrations (mg/mL) are illustrated with closed triangles. (From ref. 8 with permission.)

0 30 60 90 120 150 180 Hours

Fig. 4. Urinary excretion profile of 11-nor-9-carboxy-A9-THC (THCCOOH) as measured by gas chromatography/mass spectrometry (GC/MS) in one subject following smoking of a single 3.55% THC cigarette. The horizontal line at 15 ng/mL represents the current GC/MS cutoff used in most testing programs. The urinary THC-COOH concentrations (ng/mL) normalized to urine creatinine concentrations (mg/mL) are illustrated with closed triangles. (From ref. 8 with permission.)

15-20% of a smoked THC dose was eliminated as acidic urinary metabolites, whereas 25-30% were excreted in the feces as 11-OH-THC and THC-COOH following intravenous administration and 48-53% following oral administration (34,38). Approximately 80% of the acidic urinary metabolites are estimated to be conjugated and nonconjugated THC-COOH. There appears to be no significant difference in metabolism between men and women (34). A total of 80-90% of the drug is excreted within 5 days, mostly as hydroxylated and carboxylated metabolites (38). Halldin et al. identified 18 acidic metabolites of THC in urine, most of which are hydroxylated or P-oxidized analogs of THC (53). Many of these metabolites are conjugated with glucuronic acid, increasing the compounds' water solubility. The primary urinary metabolite is the acid-linked THCCOOH glucuronide conjugate (55), whereas 11-OH-THC predominates in the feces (38). Mean peak urinary concentrations of THC-COOH were 89.8 ± 31.9 ng/mL and 153.4 ± 49.2 ng/mL approx 8 and 14 hours after smoking a single 1.75 or 3.55% THC cigarette (see Fig. 4; refs. 56 and 57). THC-COOH was detected in urine at a concentration greater than or equal to 15 ng/mL for 33.7 ± 9.2 hours and 88.6 ± 9.5 hours after these doses (15 ng/mL was selected for evaluation because federal drug testing programs administratively designate specimens with THCCOOH concentrations below this level as negative). When sensitive analytical procedures and sufficient sampling periods are employed, the terminal urinary excretion half-life of THCCOOH in humans has been estimated to be 3-4 days (58). When THC is ingested orally, the excretion profile is similar to that following smoking (32,59). Gustafson et al. studied seven subjects who received oral doses of 0, 0.39, 0.47, 7.5 (Marinol), and 14.8 mg THC per day in a double-blind, placebo-con trolled, randomized study (60). THC in hemp oil or Marinol was administered in three divided daily doses at meals for 5 days. All urine specimens were collected over the 10-week study period and analyzed by several immunoassays and gas chromatogra-phy/mass spectrometry (GC/MS). Maximum THC-COOH concentrations were 5.438.2 ng/mL and 19.0-436 ng/mL for the two lower and two higher doses, respectively.

An important analytical study was published by Kemp et al. showing that significantly higher concentrations of THC and 11-OH-THC in urine were found when Escherichia coli P-glucuronidase was employed in the hydrolysis method compared with either of the common hydrolysis methods using Helix pomatia glucuronidase or base (61). Mean THC concentration in urine specimens from seven subjects collected after each had smoked a single 3.58% marijuana cigarette was 22 ng/mL using the E. coli glucuronidase hydrolysis method, whereas THC concentrations using either H. pomatia glucuronidase or base hydrolysis methods were near zero. Similar differences were found for 11-OH-THC with a mean concentration of 72 ng/mL from the E. coli method and concentrations less than 10 ng/mL from the other methods. It is hoped that the finding of THC in urine may provide a reliable marker of recent cannabis use; however, adequate data from controlled drug administration studies are not yet available.

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