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Within the past several years, two U.S. companies (SYVA Co., PaloAlto, California, and Roche Diagnostics, Nutley, New Jersey*) haveintroduced tests to detect traces of marijuana in urine. Concernabout the effects of marijuana on a person's ability to perform suchtasks as driving, flying, or operating machinery has prompted variousgovernmental and industrial groups to establish policies aboutmarijuana use, which often include chemical screening of biologicfluids. Until recently, testing of plasma has been the only means bywhich exposure to marijuana has been detected. Three years ago,however, the first urine-screening test became available to make suchscreening possible at moderate cost (SYVA).
The urine test is based on detection of11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (9-carboxy-THC),a metabolite of delta-9-THC, which is the primary pharmacologicallyactive component of marijuana. Studies involving humans indicate that80%-90% of the total dose of delta-9-THC is excreted within 5days--approximately 20% in urine and 65% in feces (1). Plasmaconcentrations of delta-9-THC peak by the time a smoked dose iscompleted and usually fall to approximately 2 ng/ml within 4-6 hours.9-carboxy-THC is detectable in plasma within minutes after a dose issmoked and remains in plasma considerably longer than THC itself.Urine from marijuana users contains quantities of 9-carboxy-THC inboth free and conjugated form, as well as other cannabinoids (THC andits metabolites) detectable by the test.
When the manufacturer's instructions are followed, urine samplescontaining at least the stated detection level of 9-carboxy-THC willtest positive at least 95% of the time. In a CDC field-test survey of64 laboratories, those using the SYVA system for urine screening forcannabinoids had an incidence of 4% false-positive results (2);whether these errors were analytical or clerical in nature was notdetermined. The manufacturer states that any positive test resultshould be confirmed by an alternative method.
Only blood-sample measurements are likely to correlate with aperson's degree of exposure (3); attempts to correlate urineconcentration with impairment or time of dose are complicated byvariations in individual metabolism, metabolite accumulation in thechronic user, and urine volume changes due to diet, exercise, andage. Therefore, a positive result by the urine cannabinoid testindicates only the likelihood of prior use. Smoking a singlemarijuana cigarette produces THC metabolites that are detectable forseveral days with the cannabinoid assay (4). THC can accumulate inbody fat, creating higher excretion concentrations and longerdetectability. If an affect on performance is the main reason forscreening, the urine cannabinoid test result alone cannot indicateperformance impairment or assess the degree of risk associated withthe person's continuing to perform tasks. If a history of marijuanause is the major reason for screening, the urine test for cannabinoidsshould be able to detect prior use for up to 2 weeks in the casualuser and possibly longer in the chronic user.
A chain of custody for the sample must be maintained by thetesting laboratory, as well as during the steps that bring the sampleto the laboratory. All urine samples positive by the cannabinoidassay need to be confirmed by an alternate method that is as sensitiveas the screening test, a condition not always met. Methods employedfor cannabinoid confirmation are gas chromatography (5), gaschromatography/mass spectrometry (6), and high performance liquidchromatography (7). Because of costs involved in more complexconfirmatory procedures, confirmatory tests have not always beenconducted to verify presumed positive test results. Since thescreening tests are immunologically based and measure both conjugatedand free forms of THC metabolites, any confirmatory procedure shouldeither measure both forms or should include a hydrolysis step toincrease analytical sensitivity. Confirmatory techniques may bespecific for a particular THC metabolite, while the screening kitsreact with virtually all THC metabolites, a further complication inconfirming screening results. SYVA markets two different cannabinoidassay kits with a twofold to fourfold difference in the amount of THCmetabolite required to produce a positive test result. Regardless ofwhich assay kit is used, test results should be interpreted byqualified personnel and positive results verified so that there is avery limited possibility of a false-positive result.Reported by Div of Preclinical Research, Div of Epidemiology andStatistical Analysis, National Institute on Drug Abuse; Div ofTechnology Evaluation and Assistance, Laboratory Program Office, CDC.
Editorial Note
Editorial Note: Marijuana is the most widely used illicit drug in theUnited States; an estimated 50 million people have tried it at leastonce (8). A recent U.S. Department of Defense survey showed thatchronic marijuana use exceeded 30% among some members of theStatistical Analysis, National Institute on Drug Abuse; Div ofTechnology Evaluation and Assistance, Laboratory Program Office, CDC.Editorial Note: Marijuana is the most widely used illicit drug in theUnited States; an estimated 50 million people have tried it at leastonce (8). A recent U.S. Department of Defense survey showed thatchronic marijuana use exceeded 30% among some members of themilitary. Although further study is needed on the long-term healtheffects of marijuana use, short-term effects include impaired motorcoordination and perception, as well as slowed learning and decreasedshort-term memory (9).
Urine cannabinoid assays permitting extension of testing tononlaboratory settings, such as industrial sites, probation offices,and schools have been developed. The relative ease with which thetest can be performed encourages its use by nontechnical personnel.
Those who interpret data from laboratory or nonlaboratory settingsshould be aware of possible pitfalls in such testing (10). Whethertest results are used for counseling or determining compliance withorders to desist from marijuana use, the laboratory must perform theand schools have been developed. The relative ease with which thetest can be performed encourages its use by nontechnical personnel.
Those who interpret data from laboratory or nonlaboratory settingsshould be aware of possible pitfalls in such testing (10). Whethertest results are used for counseling or determining compliance withorders to desist from marijuana use, the laboratory must perform thetest according to the manufacturer's recommendations, includingconfirmation of any positive test results. A recent report indicatesthat passive inhalation of marijuana smoke by a nonuser is not likelyto produce a positive urine test result (11), but since some passiveinhalation does occur, establishment of minimum sensitivity limits bya laboratory must be done cautiously.
References
Hunt AC, Jones RT. Tolerance and disposition of THC in man. Pharm Exp Ther 1980;215:135-44.
Hansen HJ, Lewis DS, Boone DJ. Marijuana analysis: results of a recent interlaboratory survey. Clin Chem 1981;27:1104.
Hawks RL. Developments in cannabinoid analyses of body fluids: implications of forensic applications. In: Agurell S, Dewey W, Willett RE, eds. The cannabinoids: chemical, pharmacologic and therapeutic aspects. New York: Academic Press, 1983 (in press).
Clark S, Turner J, Bastiani R. EMIT cannibinoid assay. (Clinical study no. 74, summary report). Palo Alto, Calif.: SYVA Co., 1980:17-8.
Whiting JD, Manders WW. Confirmation of a tetrahydrocannabinol metabolite in urine by gas chromatography. J Anal Tox 1982; 6:49-52.
Foltz RL, Hidy BJ. Quantitative analysis for delta-9-THC, 11-hydroxy-delta-9-THC, and 9-carboxy-delta-9-THC in plasma using GC/CI-MS. In: Hawks R, ed. Analysis of cannabinoids. Research monograph 42. Rockville, Maryland: National Institute on Drug Abuse, 1982.
ElSohly MA, ElSohly HN, Jones AB. HPLC analysis of the major metabolite of delta-9-tetrahydrocannabinol in urine. J Anal Tox 1983 (in press).
Fishburne PM, Abelson HI, Cisin I. National survey on drug abuse: main findings, 1979. Washington, D.C.: U.S. Government Printing Office, 1980. (HHS publication no. (ADM) 80-976).
Institute of Medicine. Marijuana and health. Washington, D.C.: National Academy Press, 1982:1-5.
McBay AJ, Dubowski KM, Finkle BS. Urine testing for marijuana use. JAMA (letter) 1983, 249:881.
Perez-Reyes M, Guiseppi SD, Mason AP, Davis KH. Passive inhalation of marijuana smoke and urinary excretion of cannabinoids. Clin Pharmacol Ther 1983; 34:36-41.
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