Historical Overview

The positive rate for all drugs m the general IJS workforce workplace urine drug-testing program in 2006 was 4.4%, according to the Drug Testing index 2007 from Quest Diagnostics Inc. Even if the reason for testing as follow-up with an 18.6% positive rate or periodic testing with a 1.9% positive rate, the overall highest percentage of positives by far was for cannabinoids (2.38%). This represents more than 3 times as many positive tests than for cocaine, the next most prevalent drug class.

Cannabinoids have been the class of drug with the highest positive rate for more than 20 years of federally mandated workplace urine drug testing. Thus, effectively monitoring drug use mandates that cannabinoids be reliably detected. No matter which biological matrix is utilized, urine, oral fluid, sweat, or hair, or which screening immunoassay and confirmation method is used, it is essential that cannabinoids be accurately identified and quantified. In this chapter, the physicochemical characteristics of the cannabinoids, the pharmacokinetics of Δ9-tetrahydrocannabinol THC and 11-nor-9-carboxy-THC (THCCOOH), and the methodologies to detect these chemicals in urine, oral fluid, sweat, and hair are discussed. In addition, the results of controlled drug administration studies that enlighten the interpretation of workplace drug tests are described.

In 1986, Ronald Reagan issued Executive Order 12664 requiring establishment of a workplace drug-testing program for federal employees. The Mandatory Guidelines for Workplace Drug Testing were published in April 1988, describing the methods, procedures, cutoffs, inspection strategies, and other facets of testing urine for cannabinoids, cocaine analytes, amphetamines, opiates, and phencyclidine. To meet the demanding standards for forensic urine drug testing, a 2-tiered system was devised. The initial test had to be highly sensitive to identify presumptive positive specimens, and the second confirmatory gas chromatography/mass spectrometry (GC/MS) test had to be highly specific to eliminate false-positive tests.

The 2 tests needed to be based on fundamentally different analytical principles to eliminate the effect of potential interferents and to increase confidence in the results. Initially the cutoff for a positive urine cannabinoids screen or initial test was 100 mg/L and for the GCIMS confirmation 16 mg/L. The reason for the different cutoffs is that the primary psychoactive component of cannabis, THE, is extensively metabolized to many acidic compounds (see Metabolism section below). The primacy urinary metabolite is THCCOOH glucuronide, a highly water-soluble metabolite. The GC-MS confirmation cutoff is specific for THCCOOH at 15ug/L, demanding a hydrolysis step to free THCCOOH from its glucuronide moiety. Many drug treatment and rehabilitation clinics and workplace drug-testing programs later concluded that increased sensitivity was needed and established lower cutoff concentrations for the effective use of drug tests, including more sensitive 50 or 20 mg/L cannabinoid cutoffs.

The Guidelines administrative cutoff concentrations were based on evaluations of several factors, including drug metabolism and excretion studies, instrument and methodological capabilities, risk of environmental drug exposure cost of analyses, drug-detection time windows, available urine drug-testing data from the Department of Defense, and goals of the drug testing program. In most cases, the selected cutoff concentrations did not challenge the detection limits of the analytical methods. Selecting administrative cutoff concentrations for the cannabinoid assays was complex because of extensive metabolism and complications caused by differing specificities and cross-reactions of the various immunoassays dill different cannabinoid metabolites. Another factor in the selection of the 100 µg/L cutoff concentrations for cannabinoids was the desire to eliminate potential false-positive results from passive inhalation of cannabis smoke.

Huestis et al. compared the sensitivity, specificity, and efficiency of 100, 50, and 20 mg/L urinary cannabinoid cutoffs of different commercially available immunoassays in urine specimens collected after controlled smoked cannabinoid administration. The advantages of testing these specimens instead of specimens supplemented to contain only the target analyte include the presence of a variety of corrugated and non-conjugated human cannabinoid metabolizes. A further advantage is the information gained from urine specimens collected over an extended time after smoking. The nature and relative concentration of cannabinoid metabolizes change over tired and a controlled clinical study provides the opportunity to evaluate urine specimens with distinct metabolic patterns.

Lowering the cutoff concentration to 50 mg/L increased sensitivity in all immunoassays range 57.0-79.5% with minimal loss in specificity. Specificity or the true negative rate, decreased slightly when the cutoff concentration was lowered to 50ug/L as a result of an increase in false-positive results running from 1.0% to 2.6%. All assays were highly efficient at both cutoff concentrations, with an increase observed (91.4 to 94.7%) at the lower cutoff concentration. Correlation between the 2 tests also was important considering the high labor and instrumentation costs of the confirmation assay. The Department of Health and Human Services subsequently lowered the required initial test cutoff for cannabinoids to 50µg/L.

Immunoassays have become more specific for THCCOOH over tune, resulting in lower cross reactivity with other cannabinoid metabolites. Decreased specificity may be desirable in some cases because of the possibility of detecting more true-positive specimens; however, decreased specificity also generates immunoassay results that may not confirm for THCCOOH.

There have been additional challenges over time for cannabinoid immunoassay urine drug testing. The introduction of the non-steroidal anti-inflammatory drugs initially increased the number of non-confirmed positive immunoassay tests, but manufacturers rapidly changed the antibodies in the assay to eliminate the source of cross-reactivity. Another challenge arose with the widespread popularity of THC-containing foodstuffs. Hemp oil, a health food product prepared by crushing hemp seeds, was found to contain up to 300µg/g THC in some US products and up to 1,500µg/g in Swiss hemp oil. THC content is dependent upon the effectiveness of cannabis seed cleaning and oil filtration processes. Ingestion of these materials could produce positive immunoassay and confirmatory cannabinoid tests.

Government pressure to eliminate the illegal THC in these products was successful in reducing the probability of a positive urine test from this source. New challenges will continue to occur. Currently, the therapeutic usefulness of oral cannabinoids is being investigated for medicinal applications, including analgesia, multiple sclerosis, migraine, neuropathic pain, AID-wasting disease, counteracting spasticity of motor diseases, and emesis following chemotherapy, among others. Use of these products could produce positive urine drug tests depending upon the potency, route of administration and magnitude, and chronicity of use. Controlled clinical studies will be needed to shed light on the interpretation of drug test results following such exposure.

Perhaps the most interesting new developments in workplace drug testing for cannabinoid exposure are the application of new biological matrices for drug monitoring. In this chapter we will discuss the advantages and disadvantages of oral fluid, sweat, and hair testing for identifying cannabinoid use, compares these methodologies to urine testing, and describes the controlled drug administration data that have shed light on the significance of the results.

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