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A positive drug test in the pain management patient: deception or herbal cross-reactivity?

Our laboratory was contacted by the Pain Management Center regarding a patient who tested positive for cocaine metabolite in urine, but denied abuse. Because this population is receiving prescriptions for controlled narcotics for pain, the physicians need to determine patient compliance and rule out abuse of street drugs for continued participation in the program. For this patient, the laboratory was consulted to distinguish whether the urine positivity was attributable to herbal medication cross-reactivity or whether the patient was deceiving the clinic physicians.

The patient was a 47-year-old female with a history of Wegener granulomatosis and vasculitis. She had undergone extensive surgery, including resection of the frontal and nasal sinus cavity and septum, and was receiving aggressive analgesic management, including opioid analgesics for head pain related to her condition. It is the policy of the Pain Management Center to test all patients on a random basis three to four times a year for medication compliance and to exclude abuse of street drugs. The patient tested positive once before this episode for urine cocaine metabolite.

On October 31, 2001, the patient's urine tested positive for cocaine metabolite (qualitative, >300 [micro]g/L) by fluorescent polarization immunoassay (FPIA; Abbott Laboratories), but she denied abuse within the past several months. Instead, she claimed passive exposure to cocaine smoke from living in an apartment building where her upstairs neighbor was a "crack" addict. The patient submitted a second urine on November 2, 2001, which was also positive by immunoassay for cocaine metabolite (qualitative, >300 [micro]g/L cutoff). At this particular time, the patient indicated use of an herbal product, mugwort.

Mugwort (Artemisia vulgaris) is a common herb used in alternative medicine. It is also known as common artemisia, felon herb, St. John's herb, chrysanthemum weed, and sailor's tobacco and is a close relative of wormwood (Artemisia absinthium L.). Mugwort has a long history of folk tradition and use. Anglo-Saxon tribes believed that the aromatic mugwort was one of the nine sacred herbs given to the world by the god Woden. It was also used as a flavor additive to beer before the introduction of hops. Mugwort is considered a magical herb, with special properties to protect road-weary travelers against exhaustion. The Romans planted mugwort by roadsides, where it would be available to passersby to put in their shoes to relieve aching feet. St. John the Baptist was said to have worn a girdle of mugwort when he set out into the wilderness. Some of the "magic" in mugwort is in its reputed ability to induce prophetic and vivid dreams when the herb is placed near the bed or under the sleeper's pillow. Today, mugwort leaf and stem are used medicinally as a bitter digestive tonic, uterine stimulant, menstrual regulator, and antirheumatic. Infusions are made with 1 ounce (28 g) of fresh leaf in 1 pint (473 mL) of boiling water for 5-10 min. Alcoholic extracts can also be prepared by steeping the powdered dried plant for several days in a 50:50 mixture (by volume) of alcohol to water (1).

[FIGURE 1 OMITTED]

The patient's physician contacted our laboratory questioning the possibility of immunoassay cross-reactivity with the herbal product and sent the patient's mugwort to our laboratory for analysis. A tea was brewed from the leaves and analyzed by FPIA after cooling to room temperature. The tea was negative for amphetamine, phencyclidine, barbiturates, benzodiazepines, opiates, and cannabinoids at the standard cutoffs, but tested above linearity (>5000 [micro]g/L) for cocaine metabolite. Both the tea and the patient's urine (from October 31, 2001) were sent to a local reference laboratory for gas chromatography--mass spectrometry (GC/MS) analysis.

While we were waiting for confirmation results, we obtained mugwort from a local natural foods store managed by a certified herbalist. Visual comparison of the two mugwort specimens was significantly different (Fig. 1). The patient's product was darker, more finely crushed, and coated with a white, granular powder, whereas the mugwort obtained from the herbalist was lighter in color, contained more whole leaves and flowers, and did not seem to have the same coating of white powder. Tea from the mugwort obtained from the herbalist, prepared in a manner identical to that of the patient's mugwort, tested negative in all drug-of-abuse immunoassays, including the assay for cocaine metabolite. The patient produced a third urine, on November 13, 2001, that was also positive for cocaine metabolite (qualitative, >300 [micro]g/L by FPIA).

Results from the GC/MS analysis confirmed that the patient's urine was positive for cocaine metabolite (qualitative, >150 [micro]g/L), and the tea made from the patient's sample of mugwort was positive for cocaine (qualitative, cutoff >150 [micro]g/L) and cocaine metabolite (qualitative, >150 [micro]g/L). The patient was confronted with the results and continued to deny abuse. She did, however, submit three subsequent urines that were negative for cocaine metabolite: on November 28, 2001; December 12, 2001; and January 8, 2002 (qualitative, <300 [micro]g/L). She reported that her urine tested negative because she had stopped using the tea. She was referred to addiction medicine for treatment.

With the increased prevalence of alternative medicine in America, clinicians are faced with the difficulty of determining whether a particular herbal product could be responsible for test positivity or whether the patient is truly positive. Although complete interference profiles have not been adequately defined for most immunoassays, the widespread use of herbals would argue against significant cross-reactivity in routinely used immunoassays. This case also emphasizes the need for GC/MS confirmation in some clinical situations where abuse is suspected. Only through GC/MS analysis were we able to definitively establish that the patient's mugwort contained actual cocaine. Although there was no definitive proof that the patient actually contaminated the mugwort with cocaine, the sample she produced and claimed to be the source of her urine positivity was shown to contain both cocaine and cocaine metabolite. Tea brewed from mugwort obtained from an herbalist did not test positive. This case was clearly not an herbal cross-reactivity because the presence of drug was confirmed by GC/MS. Someone added the drug to the patient's mugwort; whether it was a friend, family member, or the patient herself has not been established, but it is unlikely that she purchased this product from a legal distributor with cocaine on it. Clinicians thus should not underestimate the lengths that patients will take to evade detection.

Reference

(1.) Hanrahan C. Mugwort. In: Krapp KM, ed. The Gale encyclopedia of alternative medicine. Farmington Hills, MI: Gale Group, 2000.

Kelly Hickey, [1] Rania Seliem, [1] James Shields, [1] Alfred McKee, [2] and James H. Nichols [1] *

[1] Department of Pathology and

[2] Pain Management Center, Baystate Health System, Springfield, MA 01199;

* address correspondence to this author at: Clinical Chemistry, Department of Pathology, Baystate Medical Center, 759 Chestnut St., Springfield, MA 01199; fax 413-794-5893, e-mail james.nichols@bhs.org
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Title Annotation:Technical Briefs
Author:Hickey, Kelly; Seliem, Rania; Shields, James; McKee, Alfred; Nichols, James H.
Publication:Clinical Chemistry
Date:Jun 1, 2002
Words:1146
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