Urinary Excretion Profiles of 11-Nor-9-Carboxy-Ag- Tetrahydrocannabinol in Humans after Single Smoked Doses of Marijuana

Introduction Interpretation of marijuana-positive urine tests requires an understanding of the excretion pattern of marijuana metabolites in humans. However, limited urinary excretion data from controlled clinical studies of marijuana use are available. In this study, six subjects smoked a single marijuana cigarette (placebo, 1.75% Ag-tetrahydrocannabinol [THC], or 3.55% THC) each week while residing on the clinical ward of the Addiction Research Center. Individual urine specimens were collected for 7 days after drug administration and analyzed for 11-nor-9carboxy-A%tetrahydrocannabinol (THCCOOH) by gas chromatography-mass spectrometry (GC-MS) with a limit of detection of 0.5 ng/mL. Substantial intersubject variability in patterns of THCCOOH excretion was noted between subjects and between doses. Mean THCCOOH concentrations in the first urine collections were 47 • 22.3 ng/mL and 75.3 • 48.9 ng/mL after the 1.75 and 3.55% THC cigarettes, respectively. Mean peak urine THCCOOH concentrations averaged 89.8 • 31.9 ng/mL and 153.4 • 49.2 ng/mL after smoking of approximately 15.8 mg and 33.8 mg THC, respectively. The mean times of peak urine concentration were 7.7 • 0.8 h after the 1.75% THC and 13.9 • 3.5 h after the 3.55% THC dose. Mean GC-MS THCCOOH detection times for the last positive urine sample after the smoking of a single 1.75 or 3.55% THC cigarette were 33.7 • 9.2 h and 88.6 • 9.5 h, respectively, when a 15-ng/mL cutoff concentration was used. An average of 93.9 • 24.5 pg THCCOOH (range, 34.6-171.6 pg) was excreted by each subject during the 7-day period after smoking of a single 1.75% THC cigarette. The average amount of THCCOOH excreted in the same time period after the high dose was 197.4 • 33.6 pg (range, 107.5-305.0 pg). This represented an average of only 0.54 • 0.14% and 0.53 • 0.09% of the original amount of THC in the lowand high-dose cigarettes, respectively. These data provide a detailed compilation of THCCOOH concentrations in urine after administration of marijuana that may aid in the interpretation of urine cannabinoid results. *Author to whom correspondence should be addressed. Marijuana has been self-administered for its psychoactive effects for many centuries. Currently, it is the most highly used illicit substance in the United States. Consequently, more positive urine tests for cannabinoids are obtained than for any other drug class in civilian and military workplace drug-testing programs. Drug treatment and rehabilitation clinics, forensic investigations, and emergency toxicology departments generate additional positive test results. In each of these venues, an understanding of excretion of marijuana metabolites in humans is needed so that urine test results can be interpreted. Unfortunately, little urinary excretion data from controlled clinical studies of marijuana use are available to guide interpretation. Detailed excretion studies of cannabinoids in urine are limited because controlled clinical studies are difficult and expensive to perform. Clinical studies must be performed in a manner that limits access to additional drugs that can confound study results (1). Historically, this has required confinement of subjects to restrict drug access or use of radiolabeled drug to differentiate between the administered dose and unauthorized drug use (2,3). Detailed excretion studies also require the analysis of large numbers of individual urine samples. Attempts to reduce the number of required analyses include combining specimens into 12or 24-h pools or reducing the period of collection or both (4-7). In some studies, individual measurements were made but only mean excretion data were presented (8). The advantage of measurement of drug or metabolites or both in each urine specimen and in each individual is the additional information one obtains. Presenting each subject's complete excretion profile allows one to calculate useful parameters, such as minimum and maximum windows of detection, peak concentration, intersubject variability, and total amount of drug excreted. The method of measurement of urinary cannabinoids also influences analytical findings. Marijuana research performed in the 1970s and 1980s frequently used less sensitive and less specific methods of analysis. The Syva EMIT TM d.a.u. | 20-ng/mL immunoassay, which exhibited cross-reactivity to a Reproduction (photocopying) of editorial content of this journal is prohibited without publisher's permission. 441 wide variety of marijuana metabolites, was used in many of the studies on urinary cannabinoid excretion (8,9). Other data were collected with proprietary and commercial radioimmunoassays and enzyme immunoassays of varying sensitivities and specificities. The sensitivities and specificities of these assays have changed over time, which limits comparison of current test results with previously obtained data (10). The development of gas chromatographic-mass spectrometric (GC-MS) methods has provided the capability for sensitive and specific measurement of 11-nor-9-carboxy-Ag-tetrahydro cannabinol (THCCOOH). This study characterizes the urinary excretion profiles of THCCOOH in six healthy male subjects after single, shortterm, smoked doses of marijuana. The subjects were restricted to a closed clinical ward and monitored throughout the study to prevent unauthorized drug use. All urine specimens were collected for 7 days after marijuana smoking and analyzed for THCCOOH by GC-MS. Individual excretion profiles and mean excretion parameters were determined.