Karen Moeller, PharmD. Clinical professor, Department of Pharmacy Practice, University of Kansas School of Pharmacy. Lawrence, KS. Board-certified psychiatric pharmacist, inpatient psychiatry unit, University of Kansas Health Systems. Kansas City, KS.
Dr. Moeller has no financial relationships with companies related to this material.
CHPR: Dr. Moeller, please start by telling us about yourself.
Dr. Moeller: I am a clinical professor in the Department of Pharmacy Practice at the University of Kansas School of Pharmacy. I am also board certified in psychiatric pharmacy and provide clinical services for the adult inpatient psychiatry unit at the University of Kansas Health Systems. After receiving countless questions about how to interpret urine drug testing, I decided to write a paper on this topic with some colleagues (Moeller KE et al, Mayo Clin Proc 2017;92(5):774–796).
CHPR: How reliable are urine drug screening tests?
Dr. Moeller: Reliability depends on the type of drug test. Immunoassays are commonly the first method of testing because they are fast and inexpensive, but their specificity is low, so they can produce false positives. Confirmation tests are more reliable. These consist of gas chromatography mass spectrometry, and sometimes liquid chromatography mass spectrometry. Confirmation tests are all done in laboratories. However, immunoassays can be done in the laboratory or at the point of care, outside of the laboratory. Point-of-care tests are tests where you, for example, stick a strip in the urine and look at it. These tests are the least accurate, in part because it can be tricky to interpret them. For example, people might ask, “Is there a line there or not?” We see a lot of false positives and false negatives with point-of-care tests.
CHPR: Besides the type of test, does anything else affect accuracy?
Dr. Moeller: Commercially, there are many manufacturers of immunoassay drug tests. The specificity and reliability of these tests can differ between manufacturers. Therefore, it is very important to be familiar with your institution-specific drug test and understand what metabolites the test picks up and the cutoff values it uses. Regarding specificity, tests for cocaine are typically very accurate, with few false positives. Amphetamines, on the other hand, produce frequent false positives because there are many compounds with similar structures that elicit a positive response on immunoassays.
CHPR: Can you give us some examples of drugs that might produce false positives for amphetamines?
Dr. Moeller: Sure. It’s always important to ask your patient, “Have you taken any cold or allergy medicines recently?” because they might contain pseudoephedrine or phenylephrine, which can cause positive results for amphetamines. Aripiprazole, bupropion, and thioridazine have also been found to cause false positive results. Some dietary supplements, especially sports enhancers and weight loss products, can also cause a false positive (Editor’s note: See “Summary of Agents Contributing to Results by Immunoassay” table). One specific dietary supplement, dimethylamylamine (DMAA), has been shown to cause a 92% false positive rate for amphetamines (Vorce SP et al, J Anal Toxicol 2011;35(3):183–187). Thus, it is very important to ask what medications, herbals, and dietary supplements a patient uses.
Table: Summary of Agents Contributing to Results by Immunoassay
(click to view full size PDF)
CHPR: So, if the patient’s urine test is positive for amphetamines and they adamantly insist they did not take amphetamines, what would you do next?
Dr. Moeller: The first step is to evaluate the patient. Are they presenting with acute mental status changes? Urine drug tests aid us in the diagnosis, but we still must use our clinical judgment. We can request a confirmation test, but the result can take up to four or five days. So, you must decide how important the confirmation test will be to your treatment plan. Do you need to proceed with the test?
CHPR: Do you obtain confirmation tests for other substances?
Dr. Moeller: Typically, confirmation tests are obtained in pain and substance use disorder patients because you are making decisions on whether to continue prescribing, for example, buprenorphine or methadone. With these patients, you might have a specific contract stipulating that you will no longer prescribe certain pain medications if any illicit drugs show up in their urine test. In these situations, you would want to do a confirmation test.
CHPR: Are false negatives a problem for any drugs?
Dr. Moeller: Yes. For some tests, such as benzodiazepines and opioids, many drugs might not show up on a routine test, so you’ll get a false negative. For instance, synthetic and semisynthetic opioids, like buprenorphine, fentanyl, meperidine, methadone, oxycodone, and tramadol, will not produce a positive result on a standard opiate screen, unless your hospital includes those additional substances in the urine screen. The standard opiate test is designed to detect codeine and morphine. When interpreting urine drug screens, it’s important to understand which opiate compounds won’t elicit a positive result (Editor’s note: See “Classification of Opioids” table). But we are increasingly seeing more semisynthetic drugs being added to routine drug testing, like fentanyl, methadone, and oxycodone. Also, many opiate urine drug tests use a high cutoff value, which could result in a false negative if the patient is using it infrequently (eg, as needed or once a day) or at a low dose.
Table: Classification of Opioids: Approximate Drug
(click to view full size PDF)
CHPR: I checked our hospital’s routine urine screening labs and saw we recently added methadone and oxycodone to the opiate screen, but not fentanyl. We probably should add fentanyl because its use is so widespread.
Dr. Moeller: Yes, fentanyl use has been on a sharp rise over the last several years and is one of the leading causes of opioid overdose deaths. It is also common for fentanyl to be added to or laced with other drugs, such as cocaine and methamphetamine. So, it is something we should be testing for on urine drug tests. We just recently added it to our screening process.
CHPR: Do any foods produce false positives?
Dr. Moeller: Foods that contain poppy seeds, like some muffins and streusels, can elicit a positive opiate screen, especially with the low cutoff values used in pain clinics, because poppies contain morphine. If you work with patients who are being monitored for inappropriate use of opioids, you want to tell them not to eat foods with poppy seeds.
CHPR: You mentioned that benzodiazepines might produce false negatives. Can you say more about this?
Dr. Moeller: Yes, several benzodiazepines don’t show up reliably in urine drug screenings and will produce false negatives. For example, clonazepam does not show on most benzodiazepine immunoassays. Alprazolam and lorazepam also may not show up. Older benzodiazepines, like chlordiazepoxide, diazepam, oxazepam, and temazepam, are the ones that show up most reliably.
CHPR: We use lorazepam often, so I’m surprised that it doesn’t show up sometimes. Would alprazolam, clonazepam, and lorazepam show up reliably in confirmation tests, like gas chromatography?
Dr. Moeller: Yes, confirmation tests look for a specific substance, so it should show up. The only reason for a false negative on confirmation tests for benzodiazepines would be a high cutoff value. If a person is using a benzodiazepine at a low dose and on an as-needed basis, it may not be enough to elicit a positive result. This is why we must know how often a patient is taking their medication and the cutoff values the laboratory uses.
CHPR: What about cannabis? Do any medications or substances produce false positives?
Dr. Moeller: Yes, some medications can produce false positives on a cannabis test. The one most reported in the literature is efavirenz. The metabolite of efavirenz interferes with the cannabis drug test and almost always produces a positive result. Many people also ask about nonsteroidal anti-inflammatory drugs (NSAIDs), as they can occasionally lead to a false positive result. This is not common but may occur in chronic NSAID users or if the NSAID dose is above the maximum recommended dose. Overall, there are not many drugs that cause a false positive on cannabis immunoassays. Keep in mind that cannabidiol (CBD) products may be labeled “no THC” or “low THC,” but may contain higher concentrations of THC than labeled and will produce a true positive result for cannabis.
CHPR: Can second-hand exposure to marijuana result in a positive drug test for cannabis?
Dr. Moeller: Technically yes, but it’s highly unlikely. A study evaluated six nonsmokers in a small room for one hour under three conditions. In the first condition, there was no air ventilation and people smoked marijuana cigarettes containing high-potency THC; in the second condition, there was also no air ventilation but people were smoking even higher-potency THC cigarettes; and in the last condition, nonsmokers were exposed to the higher-potency THC cigarettes, but the room had air ventilation (Cone EJ et al, J Anal Toxicol 2015;39(1):1–12). Only one person in the non-ventilated room, and exposed to the higher-potency THC cigarettes, reached the threshold of testing positive for cannabis. So if there’s air ventilation, a person should not test positive. People might say, “Oh, I was at a rock concert” or, “I was in a room with friends who were smoking,” but most likely the room had ventilation, so they should not be testing positive for cannabis.
CHPR: What about designer drugs like spice and bath salts? Do urine tests screen for those drugs?
Dr. Moeller: Synthetic cannabinoids, such as K2 and spice, and synthetic cathinones, like bath salts, are hard to test for because the compounds are continually changed to avoid detection. There are tests out there for synthetic cannabinoids and cathinones; however, they may not detect current trends on the market for synthetic compounds.
CHPR: That’s frustrating. Can you talk a little about drug detection times?
Dr. Moeller: In general, most drugs are out of the urine within three days. There are some exceptions. For example, a long-acting benzodiazepine like diazepam could stay in someone’s system for about 30 days. The other big exception is marijuana. If someone is a chronic heavy user of marijuana, a test can still say positive for more than 30 days. But single-time use or occasional use of marijuana won’t show up for that long, maybe a week (Editor’s note: See “Approximate Drug Detection Time in the Urine” table).
Table: Approximate Drug Detection Time in the Urine
(click to view full size PDF)
CHPR: Is there anything else we should know about urine drug tests?
Dr. Moeller: It’s helpful to know how to identify urine samples that may have been adulterated. You want to look at the urine’s creatinine and specific gravity to see if it’s been diluted. A urine creatinine should be greater than 20 mg/dL, and specific gravity should be greater than 1.002. For signs of adulteration involving the addition of a substance such as bleach or other compounds to the urine, we look at the pH. A normal pH is 4.5–8, so anything usually less than 3 or greater than 10 is an indication of adulteration.
CHPR: Thank you for your time, Dr. Moeller.
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