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Interpreting Urine Drug Screen Results in the Context of Poppy Seed Use

      To the Editor:
      The abuse of home opiate preparations derived from poppy seeds (PSs) is gaining popularity in the United States,

      US Department of Justice. SENTRY Watches: opium tea. US Dept of Justice website. http://www.justice.gov/archive/ndic/topics/sentryWatch.htm. Accessed August 9, 2015.

      and clinicians may increasingly encounter these patients in their practice. At least 5 American men have died after consuming poppy-based tea, most often in the context of urine drug screens (UDSs) positive for other illicit substances.

      US Department of Justice. SENTRY Watches: opium tea. US Dept of Justice website. http://www.justice.gov/archive/ndic/topics/sentryWatch.htm. Accessed August 9, 2015.

      Clinicians may find that their patients using PS tea are also using other opioids, which may present a challenge when interpreting UDSs.
      In our practice, we encountered a patient who reported drinking tea prepared from 1 to 2 lb of PSs daily. He described development of opioid withdrawal symptoms of diaphoresis, anxiety, and tremors within 24 hours of abstinence. A UDS by liquid chromatography-mass spectrometry revealed a morphine concentration of 37,600 ng/mL, a codeine concentration of 2580 ng/mL, and a hydromorphone concentration of 1430 ng/mL (reference cutoff, 100 ng/mL, all 3 tests).
      Although PSs are well known to cause UDS results positive for codeine and morphine, the dose of PSs required to produce a positive result can vary.
      • Smith M.L.
      • Nichols D.C.
      • Underwood P.
      • et al.
      Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.
      Poppy seeds can produce differing amounts of morphine and codeine depending on the country of origin, lot, and baking technique.
      • Smith M.L.
      • Nichols D.C.
      • Underwood P.
      • et al.
      Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.
      • Thevis M.
      • Opfermann G.
      • Schänzer W.
      Urinary concentrations of morphine and codeine after consumption of poppy seeds.
      Commercially available PS preparations contain wide ranges of morphine (0.6-151.6 μg/g). When common PS-containing foods are ingested, morphine can be detected in the urine for up to 48 hours.
      • Thevis M.
      • Opfermann G.
      • Schänzer W.
      Urinary concentrations of morphine and codeine after consumption of poppy seeds.
      In one example, subjects were given two 45-g doses of PS with known morphine (15.7 mg) and codeine (3 mg) content.
      • Smith M.L.
      • Nichols D.C.
      • Underwood P.
      • et al.
      Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.
      The ranges of urine concentrations of morphine and codeine were 2413 to 7522 ng/mL and 284 to 1540 ng/mL, respectively, well above the common cutoff of 100 ng/mL.
      • Smith M.L.
      • Nichols D.C.
      • Underwood P.
      • et al.
      Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.
      When interpreting UDS results for opioids, the following factors may be considered: in general, PSs, codeine, morphine, and heroin produce a result positive for morphine (Table).
      • Smith M.L.
      • Nichols D.C.
      • Underwood P.
      • et al.
      Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.
      • Thevis M.
      • Opfermann G.
      • Schänzer W.
      Urinary concentrations of morphine and codeine after consumption of poppy seeds.
      • Smith H.S.
      Opioid metabolism.
      • Chen P.
      • Braithwaite R.A.
      • George C.
      • et al.
      The poppy seed defense: a novel solution.
      Although codeine and morphine produce less than 11% hydrocodone and less than 2.5% hydromorphone, respectively,
      • Smith H.S.
      Opioid metabolism.
      these 2 metabolites have not been reported in the context of PS use. Drugs such as fentanyl, methadone, hydromorphone, and oxymorphone do not produce active metabolites
      • Smith H.S.
      Opioid metabolism.
      and have not been reported to interfere with UDSs for PS. Testing for thebaine, a natural by-product of PS, has been proposed because it is generally not found in the context of codeine, morphine, or heroin use.
      • Thevis M.
      • Opfermann G.
      • Schänzer W.
      Urinary concentrations of morphine and codeine after consumption of poppy seeds.
      • Chen P.
      • Braithwaite R.A.
      • George C.
      • et al.
      The poppy seed defense: a novel solution.
      Thebaine testing, however, has not been widely implemented because of its short half-life. Likewise, 6-acetylmorphine has been used as a means of differentiating heroin from PS use, but it is also limited by its short plasma half-life of 10 to 40 minutes.
      • Smith M.L.
      • Nichols D.C.
      • Underwood P.
      • et al.
      Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.
      • Chen P.
      • Braithwaite R.A.
      • George C.
      • et al.
      The poppy seed defense: a novel solution.
      Recently, Chen et al
      • Chen P.
      • Braithwaite R.A.
      • George C.
      • et al.
      The poppy seed defense: a novel solution.
      described a new test of a metabolite of “street” heroin (ATM4G), which could further serve to differentiate street heroin from PS use.
      TableUrine Toxicology Results of Common Opioids and Opiates
      EDDP = 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, a methadone metabolite; + = positive result.
      Data from references 2 through 5.
      Urine toxicology study targetSubstances that produce a positive result
      Poppy seedHeroinMorphineCodeineHydrocodoneOxycodoneMethadoneHydromorphoneOxymorphoneFentanyl
      Morphine++++
      Codeine++
      Codeine is not found in pharmaceutical-grade heroin preparations.4
      +
      6-Acetylmorphine+
      Thebaine+
      Hydrocodone+
      Codeine produces hydrocodone as a metabolite in <11% of total codeine concentration; morphine produces hydromorphone as a metabolite in ≤2.5% of total morphine concentration.4
      +
      Oxycodone+
      Methadone+
      EDDP+
      Hydromorphone+
      Codeine produces hydrocodone as a metabolite in <11% of total codeine concentration; morphine produces hydromorphone as a metabolite in ≤2.5% of total morphine concentration.4
      ++
      Oxymorphone++
      Fentanyl+
      a EDDP = 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, a methadone metabolite; + = positive result.
      b Codeine is not found in pharmaceutical-grade heroin preparations.
      • Smith H.S.
      Opioid metabolism.
      c Codeine produces hydrocodone as a metabolite in <11% of total codeine concentration; morphine produces hydromorphone as a metabolite in ≤2.5% of total morphine concentration.
      • Smith H.S.
      Opioid metabolism.
      Although there is no definitive, reliable test to differentiate PS from other opioids, knowledge of expected findings in PS use may aid the clinician in diagnosis. In our case, considering that the urine morphine concentration was 376 times the cutoff value and the hydromorphone concentration was greater than 2.5% that of morphine, the concomitant use of PS with other opioids was the most likely explanation for the abnormal UDS results.

      References

      1. US Department of Justice. SENTRY Watches: opium tea. US Dept of Justice website. http://www.justice.gov/archive/ndic/topics/sentryWatch.htm. Accessed August 9, 2015.

        • Smith M.L.
        • Nichols D.C.
        • Underwood P.
        • et al.
        Morphine and codeine concentrations in human urine following controlled poppy seeds administration of known opiate content.
        Forensic Sci Int. 2014; 241: 87-90
        • Thevis M.
        • Opfermann G.
        • Schänzer W.
        Urinary concentrations of morphine and codeine after consumption of poppy seeds.
        J Anal Toxicol. 2003; 27: 53-56
        • Smith H.S.
        Opioid metabolism.
        Mayo Clin Proc. 2009; 84: 613-624
        • Chen P.
        • Braithwaite R.A.
        • George C.
        • et al.
        The poppy seed defense: a novel solution.
        Drug Test Anal. 2014; 6: 194-201