Poppy Seeds and the Interpretation of Opiates Drug Testing
The presence of morphine in urine can be due to illicit drug use or poppy seed ingestion, giving rise to the “poppy seed defense” among those receiving a positive drug test result. This presents a challenge for physicians reviewing drug test results in the context of both workplace testing and drug compliance testing.
Dr. F. Leland McClure, Director, Medical Science Liaison, Medical Affairs, Quest Diagnostics, discusses the composition of the poppy plant, approaches for interpreting opiate drug test results and ways to differentiate poppy seed ingestion from illicit drug use.
Papaver Somniferum - the Poppy Plant
Papaver somniferum, the poppy plant, is grown commercially as a source of poppy seeds for the food industry, and as a source of opium for the pharmaceutical industry.1
Opium is a milky, latex fluid present inside the poppy seed pod. It contains psychoactive phenanthrene alkaloids including morphine, codeine, and also contains thebaine, which is a starting product for semi-synthetic narcotic drugs, such as oxycodone, oxymorphone, buprenorphine, naloxone and naltrexone. Opium is also used to manufacture heroin, which is a diacetylated synthetic product of morphine.2
Poppy seeds do not contain opium but are coated by it. The concentration of this coating varies, depending on the amount of rainfall during the curing of the seed pods and washing of the seeds. Poppy seeds are commercially used as a topping or ingredient in baked goods, such as bagels, muffins and pastries, and in making seed bars, candy bars or nutritional bars. They can also be ground, and mixed with adjuvants to be used as a filling or topping. In many cases it may be possible that someone is not aware that they have consumed poppy seeds.
Pharmacology of Opium
“Morphine is the prototypical drug of the opiates,” notes Dr. McClure. “Opiates are natural products used for palliative effects for analgesia, cough control, and as an antidiarrheal. Undesirable effects include a high potential for addiction and abuse, respiratory depression and constipation.”
“Both codeine and heroin go through multiple metabolized transitions with excretion in urine in the form of morphine. Morphine is excreted into urine as glucuronide conjugates (60% morphine-3-glucuronide, 5-10% morphine-6-glucuronide)3. Heroin is excreted into urine as 6-monoacetylmorphine (6-MAM) and as morphine glucuronide conjugates.3 It has been shown that some people, 6.6% of the population, do not have the competency to fully metabolize heroin, in which case the intermediate metabolite, 6-monoacytelmorphine (6-MAM), is detected.”4
Drug testing consists of two steps. Firstly, there are presumptive tests, consisting of a wide range of immunoassays used in different settings. “These tests only indicate whether the specimen is negative,” cautions Dr. McClure, “meaning that it is either drug free or that the drug concentration in the sample is less than the cutoff. Immunoassays cannot provide a definitive identification of which drugs, or drug metabolites, are present or how much is present, and false positive results cannot be distinguished from true positive results.”
A definitive test identifies specifically what substance is there and whether it is above the cutoff level. These tests can be used as confirmation of a presumptive test or as a standalone test. Contemporary methods utilize mass spectrometry coupled to chromatographic retention to identify drugs or drug metabolites.
Ingestion of Poppy Seeds – Implications for Drug Testing
When poppy seeds are ingested, any opium that is on the seeds is also ingested.
Depending upon where the seeds came from, how they were washed, and the amount of seeds consumed, enough of that substance can be absorbed to produce morphine in the urine and produce a positive test result. Other factors that can impact detection of morphine from poppy seeds are the time from ingestion to drug screen collection, the patient's hydration state, and the patient's genome for drug metabolism. There are also inter-individual pathophysiologic variances.
Studies have shown that, following ingestion of cake material, morphine concentrations in a urine sample can be in the thousands of nanograms per milliliter (ng/mL), and in the hundreds of nanograms per milliliter after bagel consumption.5-6 The implication of these levels for drug testing are significant, as healthcare providers try to determine whether a result is a true positive and to differentiate between someone who has been abusing morphine or heroin, or has consumed poppy seeds.
For workplace testing, the federally regulated testing programs managed by the Substance Abuse and Mental Health Services Administration (SAMSHSA) originally used a cutoff for morphine of 300 ng/mL, but in 1998 this was raised to 2,000 ng/mL for both presumptive and definitive tests to reduce the instances of positive drug tests following ingestion of poppy-containing foodstuffs.7 “But even a cutoff of 2,000 mg/mL doesn't completely eliminate the possibility of poppy seeds being an attributable cause for a drug test to be positive,”5 notes Dr. McClure.
Prescription Drug Monitoring
Prescription drug monitoring is used by physicians to determine compliance with the use of controlled drugs. Drug testing is also used to monitor abstinence from illicit drug use. “In this situation, a healthcare provider is not only looking to see if there is a positive test result, they're also looking for expected positive and negative test results, depending upon the drugs prescribed,” says Dr. McClure. “The recommended cutoff for compliance testing is 300 ng/mL or less.8 In fact, it's not unusual to see cutoff levels of 100 ng/mL for some presumptive tests. As a result, interpretation of these tests is a challenge for healthcare providers: a presumptive test can clearly be positive due to poppy seed ingestion. Definitive testing should then be performed to confirm those test results, identify the morphine that's there, and allow the physician to better understand what is occurring with that patient.”
The SAMSHA Medical Review Officer Manual for Federal Agency Workplace Drug Testing Programs provides Medical Review Officers (physician healthcare providers) with useful guidance for interpreting quantitative urine drug test results less than 15,000 ng/mL of morphine and codeine.9 It indicates that with legitimate prescribed use of a Schedule I or II drug on the Drug Enforcement Administration drug scheduling, the medical review officer can verify the drug test results as a administrative /Negative result.9 “In that situation, the test results demonstrate an expected drug and it's consistent with what the patient was prescribed, that's a good thing,” notes Dr. McClure. “However, for positive test results where there's clinical evidence of illegal use, it is now a noncompliance issue. Medical review officers would verify results as positive results and clinical healthcare providers have an opportunity to talk to the patient and re-assess management of that patient.”
The conundrum for physicians is when there is a morphine-only test result but no clinical evidence of illegal use. To try and determine whether this is due to poppy seed or illicit drug use, a medical history should be carefully obtained without leading the patient in terms of their response. “If there is no clinical evidence or history of illicit drug use, SAMSHA recommends that medical review officers interpret those results as possible poppy seed consumption,” says Dr. McClure. “Additional monitoring and more frequent monitoring may be appropriate with someone considered a high risk patient.”
One approach to reduce the possibility of positive results due to poppy seed ingestion is for physicians to discuss the impact of poppy seed ingestion when educating patients before prescribing a controlled drug. This should include information about foods, which may not obviously contain poppy seeds, such as when they are present in a paste or filling. They may consider recommending abstinence from poppy seed consumption while taking the prescribed medication.
Identifying Heroin Use
In considering a morphine-only test results, physicians should keep in mind that one of the drugs metabolized to morphine by most individuals is heroin. There is a presumptive test for the heroin metabolite. If the presumptive result is positive, definitive testing with mass spectrometry would still be needed to confirm the result.
“When we look at high-risk patients who may be abusing prescription medications, providers should always consider the potential that somebody is using heroin in addition to their prescription drugs,” says Dr. McClure. “These presumptive and definitive tests for heroin metabolite provide useful information.”
“Since around 6% of the population do not have the competency to fully metabolize heroin, it's prudent to perform a heroin metabolite test when heroin use is suspected,” concludes Dr. McClure.
- U.S. Drug Enforcement Administration. Cannabis, Coca & Poppy: Nature’s Addictive Plants. www.deamuseum.org/ccp/opium/history.html
- United Nations Office on Drugs and Crime. The Opium Alkaloids. https://www.unodc.org/unodc/en/data-and-analysis/bulletin/bulletin_1953-01-01_3_page005.html
- PharmGKB. Codeine and Morphine Pathway. https://www.pharmgkb.org/pathway/PA146123006
Quest Diagnostics. Health TrendsTM. Prescription Drug Misuse in America, Diagnostic Insights into Managing the Drug Epidemic, 2014. https://www.questdiagnostics.com/dms/Documents/health-trends/2014_health_trends_prescription_drug_misuse.pdf
- Thevis M, Opfermann G, and Schiinzer W. Urinary Concentrations of Morphine and Codeine After Consumption of Poppy Seeds. J Anal Toxicol. 2003;27
- Rohrig TP, Moore, C. The Determination of Morphine in Urine and Oral Fluid Following Ingestion of Poppy Seeds, J Anal Toxicol. 2003; 27
- Substance Abuse and Mental Health Services Administration. Mandatory Guidelines for Federal Workplace Drug Testing Programs. https://www.federalregister.gov/articles/2015/05/15/2015-11524/mandatory-guidelinesfor-federal-workplace-drug-testing-programs#h-http://www.samhsa.gov/sites/default/files/workplace/2010GuidelinesAnalytesCutoffs.pdf
- Gourlay DL, Heit HA, Caplan YH. Urine Drug Testing in Clinical Practice: The Art and Science of Patient Care. Johns Hopkins Medicine. 2012; 5:
- Department of Health and Human Services. Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Prevention, Medical Review Officer Manual for Federal Agency Workplace Drug Testing Programs, effective May 31, 2014. http://workplace.samhsa.gov/
Released on Monday, October 26, 2015