What causes positive drug tests? It’s not just drugs… or poppy seeds.

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You may have heard that poppy seeds in your salad dressing or on your bagel can mess up a drug test–triggering a positive result for opiates in your system. Though there are some caveats to this (washing and proper seed processing can remove contaminants and cooking tends to significantly decrease poppy seeds’ opiate content), it’s true that poppy seeds can be a problem. Poppy seeds themselves don’t actually contain opiate compounds, but they’re often adulterated with opiate-containing flower sap during processing.

Yet poppy seeds aren’t the only thing that can skew a rapid drug test. “There’s a wide range of things that can cause false positive results,” says Gwen McMillin, a toxicologist and professor of clinical pathology at the University of Utah. Poppy seeds don’t actually cause false positives, McMillin notes. “[Contaminated] poppy seeds actually do have opiates in them,” she says–but lots of medications, even common, over-the-counter drugs can confound tests with entirely different compounds. 

The most frequently used type of rapid drug tests are called immunoassays. These tests vary widely and are made by many companies. Different versions of them can screen for amphetamines, benzodiazepines, PCP, opiates, synthetic opioids, marijuana, and other regulated substances. Antibodies built-in to the tests react with compounds selected to represent likely drug use: Metabolites that the body excretes in urine. However, the tests aren’t looking for the exact target substances they may be used to screen for. McMillin compares them to a wooden game board with slots for marbles–similarly sized and shaped marbles can fit into the same holes. 

Another analogy, she says, is a fish net. “A net is designed to catch fish, but doesn’t know exactly what kind of fish it’s picking up,” she tells Popular Science. “The immunoassay is really brilliant in that it can capture all kinds of things that look like fish. If you’re just trying to do a screen, that’s really important…but the consequence is false positives.”

The antibody is the most critical part of an immunoassay’s design, and it can be a tricky balancing act to aim for specificity while also ensuring a whole class of related, controlled substances are included in what’s meant to be a first line of detection. False positives are often the result of test-makers opting for breadth. Yet they also happen because of basic chemistry constraints: certain drug groups, particularly amphetamines, are metabolized to small, rather nondescript molecules that resemble many things, says Algren. 

Cold medicines, antihistamines and decongestants, antidepressants, blood pressure medications, diabetes drugs, are among the long list of things that can lead to false positive amphetamine screens. Over the counter cold medicines can also show up as PCP. Codeine, some antibiotics commonly used to treat urinary tract infections, hypertension medication, and anti-nausea drugs are some examples of pills that can lead to false-positives for opioids and opiates. Quinine, the antimalarial compound used as a flavoring in tonic water, can also trigger some of these tests. CBD products and even certain types of baby wash can show up as a positive result in screens for cannabis/THC. And researchers are discovering previously unknown examples of cross-reactive compounds all the time.

Sensitivity is also a big consideration. Manufacturers don’t want tests to miss drugs that are present, but if they design them with low enough thresholds and rapid tests can pick up even erroneous, incidental or second-hand exposures.

Though these weaknesses are widely understood among toxicologists and immunoassay tests come with package inserts listing potential cross-reactivity with non-target drugs, clinicians administering these tests to patients in hospital settings or labor and delivery wards might not be aware of all of the many legal and common routes to a positive urine drug screen. And that can cause problems when time is tight and confirmatory tests aren’t ordered. Multiple lawsuits have been brought against hospitals in recent years after newborns were taken into foster care based on parents’ rapid drug test results. Patient care can also be compromised when rapid drug screens alone are used as a basis for approving surgery and other treatments, McMillin says.

False negatives are also not uncommon. Some tests aren’t sensitive enough to pick up the concentration of a drug circulating in someone’s system. And some newer substances may not actually show up on a test theoretically intended to reveal their presence. For instance, synthetic  and semi-synthetic opioids like fentanyl and oxycodone aren’t detected on all opiate drug tests, as their metabolites and constituent chemicals are different. This, too, can cause problems for patients, and even lead to people being wrongfully kicked out of chronic pain management programs, where a false negative test might erroneously lead providers to believe patients aren’t taking their medications as prescribed, says Adam Algren, a medical toxicologist and emergency physician at University Health Hospital and University of Missouri-Kansas City.

In an ideal situation, any surprising immunoassay drug test result would be confirmed with more specific and accurate follow-up laboratory testing, say both Algren and McMillin. Yet, these slower, more expensive confirmatory tests aren’t used in every hospital system or care setting. “I think a lot of doctors are quick to take the immunoassay results as being the final result, and then make decisions off of that without confirmation or considering if there’s other things involved,” Algren says.

“I personally don’t feel like there is enough attention to the confirmation test,” agrees McMillin. Both experts say they’d like to see that change.

This story is part of Popular Science’s Ask Us Anything series, where we answer your most outlandish, mind-burning questions, from the ordinary to the off-the-wall. Have something you’ve always wanted to know? Ask us.

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Lauren Leffer

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Lauren Leffer is a science, tech, and environmental reporter based in Brooklyn, NY. She writes on many subjects including artificial intelligence, climate, and weird biology because she’s curious to a fault. When she’s not writing, she’s hopefully hiking.