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Is your patient positive for Morphine from Prescription Medication, Heroin or Poppy Seeds?

Ancient cultures understood the medicinal purpose of opium. Opium is found in the unripe pods of poppy plants (Papaver somniferum, Papaver paeoniflorum, Papaver giganteum). The most common is P. somniferum because of the beautiful flowers it produces. Over thirty alkaloids have been isolated from poppy plants, the most well-known are codeine, morphine and thebaine. Codeine and morphine are used directly as therapeutics, while the pharmaceutical industry uses thebaine to create oxycodone, oxymorphone, buprenorphine and naloxone. The chemical structures are shown in Figure 1.

Figure 1. Comparison of chemical structures of Thebaine, Codeine, Morphine. The analytes detected in poppy seeds.

Morphine is the most abundant alkaloid found in raw opium. Poppy seeds themselves can have codeine, morphine and thebaine on the seeds. An in-house study on the washing and analysis of common poppy seed brands detected all three codeine, morphine and thebaine on the seeds themselves.

Poppy Alkaloid Pharmaceutical Use Comment
Morphine Narcotic analgesic Major alkaloid of opium which is also a controlled substance.
Codeine Analgesic and antitussive Codeine after oral administration is converted into morphine by liver enzymes most noticeably CYP2D6. Therefore codeine is a prodrug of morphine. Codeine is also a controlled substance.
Thebaine Precursor of opioids Thebaine is a biosynthetic intermediate of the morphine which is used by the pharmaceutical industry for synthesis of oxycodone, oxymorphone, buprenorphine, and naloxone. Thebaine is also a controlled substance.
Noscapine (narcotine) Antitussive This compound may have anticancer properties. Noscapine is not a controlled substance.
Papaverine Antispasmodic Papaverine is not a controlled substance.

Nowadays, poppys are used for their flowers and for their seeds. Baking bread, muffins and bagels using the poppy seeds. Patients can test positive for morphine after ingesting poppy seed products (bagels, muffins, tea). Traditional laboratory practice only informs physicians if morphine and its metabolites are present in a patient’s sample.

Poppy seeds have also been abused. Unwashed poppy seeds are widely available online through private websites or via well-known sellers such as eBay and Amazon. These seeds can be used to produce a tea that contains an opioid content sufficient to produce psychoactive effects and to cause withdrawal symptoms when discontinued abruptly, yet their sale and distribution is legal in the United States.

The technical team fields questions from our clinical providers and had multiple instances of suspected poppyseed use. Partnering with the research & and development team at Luxor Scientific we validated an assay detecting thebaine, a compound to determine if poppyseed use could be the cause of a positive opioid result.

In our in-house study, we saw the opiate screen and confirmation testing for codeine, morphine and thebaine detected positive in people consuming 2-4 grams of poppyseeds 30 minutes and 4 hours after consumption. Table 1 shows the results from a seven person study demonstrating the elevated levels of opiates from poppyseeds.

Verification of Thebaine in Urine after consumption of Poppy Seeds
Sample ID Time of Sample Product Consumed Opiate Screen Opiate Screen value Codeine Morphine HC/HM/NHC Thebaine
Sample 1 A 30 Mins 2 poppy seed muffins (4 g) Positive 1330 385 10 0 17
Sample 1 B 4 hours Positive 1399 1504 39 0 39
Sample 2 A 30 Mins 1 poppy seed muffins (2 g) Positive 1248 314 trace 0 2
Sample 2 B 4 hours Positive 1398 570 trace 0 3
Sample 3 A 30 Mins 2 poppy seed muffins (4 g) Positive 1258 349 11 0 11
Sample 3 B 4 hours Positive 1449 538 24 0 5
Sample 4 A 30 Mins 2 g Straight Negative 619 118 trace 0 2
Sample 4 B 4 hours Positive 1368 487 22 0 5
Sample 5 A 30 Mins 2 poppy seed muffins (4 g) Positive 1390 797 203 0 15
Sample 5 B 4 hours Positive 1433 887 167 0 12
Sample 6 A 30 Mins 1 poppy seed muffins (2 g) Positive 1245 537 trace 0 4
Sample 6 B 4 hours Positive 1317 3135 39 0 19
Sample 7 A 30 Mins Belvita Negative -38 trace trace 0 trace
Sample 7 B 4 hours Negative -18 trace trace 0 trace
Table 1. In-house study detection opiates and thebaine after consumption of poppyseeds. Poppy Seed Brand: Morton & Bassett

Luxor Scientific detects thebaine, a compound only found in poppy seeds. If thebaine is present, it is possible that poppy seed consumption caused the positive morphine result. In this way, Luxor can help differentiate between heroin, morphine and poppy seed usage.

References
Dasgupta, A. (2019). Chapter 31 – Analytical True Positive: Poppy Seed Products and Opiate Analysis. In A. Dasgupta (Ed.), Critical Issues in Alcohol and Drugs of Abuse Testing (Second Edition) (pp. 449-462). Academic Press. 10.1016/B978-0-12-815607-0.00031-9
Evans, W. C., & Evans, D. (2009). Chapter 26 – Alkaloids. In W. C. Evans, & D. Evans (Eds.), Trease and Evans’ Pharmacognosy (Sixteenth Edition) (pp. 353-415). W.B. Saunders. 10.1016/B978-0-7020-2933-2.00026-5
Haber I, Pergolizzi J Jr, LeQuang JA. Poppy Seed Tea: A Short Review and Case Study. Pain Ther. 2019 Jun;8(1):151-155. doi: 10.1007/s40122-019-0113-5. Epub 2019 Feb 5. PMID: 30719627; PMCID: PMC6513924.