False-Positive Screen for Marijuana
Q: Can you explain the reason for a false-positive urine drug screen for marijuana?
A: In 2013, an estimated 19.8 million Americans aged 12 years or older were current (past month) users of marijuana and 8.1 million were daily users.1 An analysis of 7.6 million urine drug screens performed in the U.S. workforce, indicated the positivity rate for marijuana was 1.7%.2 A positive urine drug screen (UDS) can have an impact on a person’s life, so it is important to ensure the result is accurate.
Tetrahydrocannabinol (THC) is the active ingredient of marijuana, however UDS test for the metabolite 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH).3-5 A UDS does not prove there is an exact amount of the metabolite in the urine but indicates the metabolite concentration is above a given theshold.
UDS is an immunoassay test that uses antibodies to detect presence of specific drugs or metabolites. It is the most common method for initial screening. Advantages of the immunoassay test include the capability for large-scale screening and rapid detection, but the disadvantage is the potential for false-positive results.4 A rapid UDS for marijuana is performed using a threshold of 50 ng/mL.6 If a test comes back positive, a more specific gas chromatography-mass spectrometry (GC-MS) test, which uses a threshold of 15 ng/mL, can be performed to confirm the positive result.6
The GC-MS test is considered the “gold standard” of confirmatory tests due to its ability to detect small quantities and confirm the presence of a specific drug. Advantages include high accuracy and sensitivity. Disadvantages include the amount of time it takes for the test to be completed, the high expertise level required to perform the test, and the cost of the test.4
An important aspect to take into consideration when trying to determine if a positive marijuana UDS is false is how long marijuana can be detected in the urine. Factors that may influence the length of time a drug will be detectable include the frequency of drug use and the time of last ingestion. A single use of marijuana is typically detectable for 3 to 7 days, moderate use can be detected for 5 to 7 days, daily use for 10 to 15 days, and long-term/heavy use for over a month.4 It also is important to keep in mind that people may try to add products, such as eye drops (Visine),7 to their urine to cause a false negative.
Passive marijuana inhalation has been thought of as a potential reason for a false-positive marijuana UDS. Three studies were performed to analyze this theory: one with participants exposed to secondhand smoke in a small enclosed room for
1 hour, another study with participants exposed to the smoke daily for 3 consecutive days, and the third study was with participants exposed to smoke in a small, closed station wagon. Eighty different urine samples were analyzed; only 2 samples exceeded the 20 ng/mL threshold used in their immunoassay test—and those just barely.8
Based on the results of these studies, a positive result for marijuana due to passive inhalation would be highly unlikely when using the standard threshold of 50 ng/mL for initial screening.
Another potential source of UDS interference is thought to be the use of non-steroidal anti-inflammatory drugs (NSAIDs). One study evaluated 3 drugs (ibuprofen [Advil, Motrin, others], naproxen [Aleve, Naprosyn, others], and fenoprofen [Nalfon, others]) in patients taking them chronically or acutely. The authors theorized that NSAIDs would interfere with the immunoassay test through interference with the enzyme reaction, production of erroneous absorbance reading, or secretion of an endogenous substance that inhibits cannabinoid binding to an antibody. Of the 510 urine samples collected from 102 participants, 10 samples (0.02%) tested positive for cannabinoids. Follow-up GC-MS tests showed that 8 of the 10 samples (80%) were true positive for cannabinoids. Of the 2 samples that were positive due to NSAID use, one was from acute ibuprofen use (1,200 mg in one day), and the other was from chronic naproxen use (1,000 mg daily for no longer than 30 days).9 This study shows it is unlikely for NSAIDs to cause a false-positive marijuana UDS.
In addition to NSAIDs, efavirenz (Sustiva) is another medication thought to interfere with UDS for marijuana. In a study looking at patients who were taking efavirenz 600 mg daily as an antiretroviral treatment for at least 14 days, 28 out of 30 participants had a false-positive UDS using rapid response tests. The authors believed the interference was attributed to EFV 8-glucuronide, one of 2 major urinary metabolites of efavirenz.5 One limitation to this study is the failure of the authors to mention other medication use such as the synthetic cannabinoid dronabinol (Marinol, others), which has been shown to cause a false-positive in a UDS for marijuana 30% to 45% of the time.10
Besides NSAIDs, efavirenz, and dronabinol, hemp food consumption is also thought to be able to cause a false-positive UDS for marijuana. Food containing hemp seeds or oil can often be found in cold-pressed oil for cooking, salad dressings, and capsules as nutritional supplements. Fifteen healthy participants were studied to see the effects of consuming hemp foods daily for 10 days.3 No participants had recent exposure to THC in hemp foods or medicinal or recreational drugs, as confirmed by a baseline UDS specimen.
The hemp foods contained 4 different doses of THC, with participants consuming each dose for 10 days before testing their urine. THC doses in hemp seed oil ranged from 0.09 mg to 0.6 mg. At the highest dose of 0.6 mg, which is an unrealistically high amount for daily consumption of hemp foods, the highest measured THC-COOH concentration in urine was 5.2 ng/mL, which is well below the GC-MS confirmation threshold of 15 ng/mL.3 This study shows that it is very unlikely for hemp food consumption to interfere with an immunoassay UDS, or GC-MS.
When screening a person for possible marijuana use, it is important not to make assumptions from an initial result from a positive immunoassay test, and to confirm a positive result with GC-MS. If a person is taking efavirenz, you have limited evidence to suspect a false-positive result, whereas it is much less likely for NSAIDs, hemp food consumption, or passive marijuana inhalation to cause a false-positive result. It is important to take into consideration recent medication use before making a decision on how to act on a positive UDS for marijuana.
—Co-author Jeremy Gray, PharmD Candidate