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Poppy

Scientific Name(s): Papaver bracteatum, Papaver somniferum L.
Common Name(s): Great scarlet poppy, Lipiodol, Oleum Papaveris Seminis, Opium poppy, Poppyseed poppy, Thebaine poppy

Clinical Overview

Use

Poppy extracts have traditionally been used to relax smooth muscle tone, making them potentially useful in the treatment of diarrhea and abdominal cramping. The extract has been used as a sedative analgesic and antitussive. Poppy seed oil is used as a vehicle for chemotherapy delivery and to diagnose fistulae. However, there are no clinical trials to support these uses. Morphine is prepared from the opium poppy.

Dosing

Clinical trials are lacking to guide dosage.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. The seed is generally recognized as safe when used as food.

Interactions

None well documented.

Adverse Reactions

Opium is known for its highly addictive qualities. It has been associated with poisoning and characterized by symptoms of sedation, sluggishness, and abdominal contractions. Allergy and anaphylaxis to poppy seed have been reported.

Toxicology

No data is available in humans.

Botany

Seventy to 100 different varieties of the poppy exist. The opium poppy is a small annual, but other poppy species may be annual, biennial, or perennial. The bright showy flowers of the genus Papaver range in color from white to deep reds and purples. The seeds of the plants vary in color from light cream to blue-black and are numerous and minutely pitted. Sap from the seed pods may be white, orange, or red.PLANTS 2007

History

The earliest accounts of the use of poppy preparations date to the ancient Sumerians in Mesopotamia, where the plant was used medicinally and was known as hul gil (the plant of joy). The medicinal uses of poppy were described by the ancient Greeks and opium, as an addictive agent, was identified by Arabic physicians more than 900 years ago. Because of the wide distribution of the opium poppy, its use has been recognized by most major cultures. Opium was widely used in the United States during the Civil War to treat wounded soldiers, who often developed a dependence. The alkaloid morphine was purified from crude opium in 1803. In 1874, morphine was reacted with acetic anhydride to yield heroin. This compound was developed by the Bayer pharmaceutical company in Germany for cough, chest pain, and pneumonia and was later recognized to have a high addiction potential. Derivatives of opium alkaloids continue to play a major role as antitussives, antidiarrheals, and analgesics. Their abuse potential remains high, and efforts to curtail the illicit cultivation of the opium poppy have had limited success. Poppy seeds are used in the preparation of confections and breads.Hoffman 1990, Calixto 2000 While growing poppies is legal, it is illegal to process what is grown into the drug form.

Chemistry

The chemistry of the genus Papaver is well known. When the unripened seed capsule is scored, a milky latex exudes.Calixto 2000, Simon 1984 The dried latex is known as opium, which contains more than 30 alkaloids.Duke 1985 The most important of these alkaloids are morphine (20%), noscapine (5%), codeine (2%), papaverine (2%), and thebaine (1%). Codeine is the most widely used opium alkaloid and is obtained from natural sources or through the methylation of morphine or synthetic transformation of thebaine.Calixto 2000, Duke 1985

Because of the medicinal importance of morphine derivatives, efforts have been made to identify a species of Papaver that contains high levels of a suitable starting compound for the commercial synthesis of codeine. In some varieties of P. bracteatum, thebaine constitutes 98% of the total alkaloid content.Nyman 1979 Commercially, thebaine may be readily converted to codeine, oxycodone, hydrocodone, or dihydrocodeine. P. bracteatum may become the species of choice as a legal source of alkaloid precursors.Theuns 1986

Poppy seed oil, used as a vehicle for pharmacological substances as well as oil-based paints, varnishes, soaps and liniments contains saturated palmitic and stearic acids and oleic, linoleic, alpha-linolenic, and other unsaturated fatty acids.Untoro 2006, Krist 2005 Poppy seeds and their oil contain only minuscule amounts of opium alkaloids.

Uses and Pharmacology

The pharmacologic effects of morphine alkaloids differ widely. Codeine and morphine are sedative analgesics and can relax smooth muscle tone, making them useful in the treatment of diarrhea and abdominal cramping. Codeine and its derivatives are used as antitussives. Papaverine relaxes involuntary smooth muscle and increases cerebral blood flow. Chemical modifications of the alkaloids enable different receptor-dependent activities to be elicited. The addictive characteristics of the opium alkaloids have been recognized for millenia.Ronsoni 1999, Kaplan 1994

Colovesical fistula

A few studies have evaluated the poppy seed test for the diagnosis of fistulae. Newer diagnostic methods have a varying success rate (70% to 80% for computerized tomography scans and 80% for radio-labeled chromium)Wensky 2006, Kwon 2008 while the poppy seed test and the charcoal test have been demonstrated to detect fistula in 100% of instances.Wensky 2006, Kwon 2008, Schwaibold 2001 Costs and acceptability of the poppy seed test (250 g seeds given orally) are more favorable.Kwon 2008

Hepatocellular cancer

Iodized poppy seed oil (Lipiodol) is used in imaging techniques in vascular hepatocellular cancer, because of the preferential accumulation of poppy seed oil in hepatocellular cancer cells. For this reason, iodized poppy seed oil is used as an adjuvant or vehicle to deliver chemotherapeutic agents (eg, cyclosporine A, cisplatin) to tumor sites.Buscombe 2002, Fujiyama 2003, Abe 2002

Iodine deficiency

Iodized poppy seed oil has been studied as a source of iodine in deficient individuals. Results varied compared with iodized salt and iodized peanut oil.Untoro 2006, Krist 2005, Huda 2001

Dosing

Clinical trials are lacking to guide dosage. Single oral doses of poppy seed 250 g have been used diagnostically.Schwaibold 2001

Attention has focused on the detection of morphine and codeine in urine following the ingestion of foods prepared with poppy seeds, and has resulted in confusion in testing for drugs of abuse.Chang 2012 Analysis for noscarpine, papverine, or thebaine may differentiate poppy ingestion from substance abuse.Chang 2012, Hayes 1987, Miller 1994, Paul 1996, Cassella 1997

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. The seed is generally recognized as safe when used as food.

Interactions

None well documented. A case report exists of a fatality in which the benzodiazepine fenazepam was used concurrently with poppy seed tea.Bailey 2010

Adverse Reactions

Immunoglobulin E–mediated allergy to poppy seeds is rareOppel 2006 although case reports of anaphylactic reactions exist.Oppel 2006, Gamboa 1997, Frantzen 2000, Crivellaro 1999 The poppy seed commonly used in confectionary is thermostable. In some patients, it may need to be ground in order to be allergenic.Oppel 2006 Cross-sensitization with sesame seed, hazel nut, rye grain, kiwi fruit, and buckwheat has been reported.Oppel 2006, Jensen-Jarolim 1999 A case report exists of bowel obstruction due to consumption of large quantities of poppy seeds.Schuppener 2017

Toxicology

Adequate data are lacking. Thebaine has a median lethal dose of 20 mg/kg in mice. Toxicity of opium is documented,Duke 1985 as is toxicity from parenteral poppy seed tea.Monaghan 2013 Although large doses of thebaine can induce convulsions, no case of human thebaine abuse has been reported.Theuns 1986

References

Abe S, Otsuki M. Styrene maleic acid neocarzinostatin treatment for hepatocellular carcinoma. Curr Med Chem Anticancer Agents. 2002;2(6):715-726.12678722
Bailey K, Richards-Waugh L, Clay D, et al. Fatality involving the ingestion of phenazepam and poppy seed tea. J Anal Toxicol. 2010;34(8):527-32.21819799
Buscombe JR. Interventional nuclear medicine in hepatocellular carcinoma and other tumours. Nucl Med Commum. 2002;23(9):837-841.12195086
Calixto JB, Beirith A, Ferreira J, Santos AR, Filho VC, Yunes RA. Naturally occurring antinociceptive substances from plants. Phytother Res. 2000;14(6):401-418.10960893
Cassella G, Wu AH, Shaw BR, Hill DW. The analysis of thebaine in urine for the detection of poppy seed consumption. J Anal Toxicol. 1997;21(5):376-383.9288591
Chang J, Wang M, Appleton C. Headache bread--a case of high codeine containing variety of poppy seed. J Anal Toxicol. 2012;36(4):288.22511702
Crivellaro M, Bonadonna P, Dama A, et al. Severe systemic reactions caused by poppy seed. J Investig Allergol Clin Immunol. 1999;9(1):58-59.10212860
Duke JA. CRC Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press; 1985.
Frantzen B, Bröcker EB, Trautmann A. Immediate-type allergy caused by poppy seed. Allergy. 2000;55(1):97-98.10696869
Fujiyama S, Shibata J, Maeda S, et al. Phase I clinical study of a novel lipophilic platinum complex (SM-11355) in patients with hepatocellular carcinoma refractory to cisplatin/lipiodol. Br J Cancer. 2003;89(9):1614-1619.14583758
Gamboa PM, Jauregui I, Urrutia I, Gonzalez G, Barturen P, Antepara I. Allergic contact urticaria from poppy flowers (Papaver rhoeas). Contact Dermatitis. 1997;37(3):140-141.9330835
Hayes LW, Krasselt WG, Mueggler PA. Concentrations of morphine and codeine in serum and urine after ingestion of poppy seeds. Clin Chem. 1987;33(6):806-808.3594820
Hoffmann JP. The historical shift in the perception of opiates: from medicine to social menace. J Psychoactive Drugs. 1990;22(1):53-62.2182806
Huda SN, Grantham-McGregor SM, Tomkins A. Cognitive and motor functions of iodine-deficient but euthyroid children in Bangladesh do not benefit from iodized poppy seed oil (Lipiodol). J Nutr. 2001;131(1):72-77.11208941
Jensen-Jarolim E, Gerstmayer G, Kraft D, Scheiner O, Ebner H, Ebner C. Serological characterization of allergens in poppy seeds. Clin Exp Allergy. 1999;29(8):1075-1079.10457111
Kaplan R. Poppy seed dependence. Med J Aust. 1994;161(2):176.8028555
Krist S, Stuebiger G, Unterweger H, Bandion F, Buchbauer G. Analysis of volatile compounds and triglycerides of seed oils extracted from different poppy varieties (Papaver somniferum L.). J Agric Food Chem. 2005;53(21):8310-8316.16218681
Kwon EO, Armenakas NA, Scharf SC, Panagopoulos G, Fracchia JA. The poppy seed test for colovesical fistula: big bang, little bucks! J Urol. 2008;179(4):1425-1427.18289575
Miller JM. Pertinent medical intelligence: the poppy seed. Md Med J. 1994;43(12):1069-1070.7815912
Monaghan D, Peckler B. Parenteral poppy seed tea packs a powerful punch. N Z Med J. 2013;126(1387):175-8.24362742
Nyman U, Bruhn JG. Papaver bracteatum–a summary of current knowledge. Planta Med. 1979;35(2):97-771.419192
Oppel T, Thomas P, Wollenberg A. Cross-sensitization between poppy seed and buckwheat in a food-allergic patient with poppy seed anaphylaxis. Int Arch Allergy Immunol. 2006;140(2):170-173.16601355
Papaver somniferum, Papaver bracteatum. USDA, NRCS. 2007. The PLANTS Database. http://plants.usda.gov. January 2009. National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
Paul BD, Dreka C, Knight ES, Smith ML. Gas chromatographic/mass spectrometric detection of narcotine, papaverine, and thebaine in seeds of Papaver somniferum. Planta Med. 1996;62(6):544-547.9000887
Ronzoni S, Cerri A, Dondio G, et al. Synthesis and NMR characterization of a novel class of thienomorphinans. Org Lett. 1999;1(3)513-515.
Schuppener LM, Corliss RF. Death Due to Complications of Bowel Obstruction Following Raw Poppy Seed Ingestion. J Forensic Sci. 2017 May 23. doi: 10.1111/1556-4029.13562. [Epub ahead of print]28543087
Schwaibold H, Popiel C, Geist E, Hartung R. Oral intake of poppy seed: a reliable and simple method for diagnosing vesico-enteric fistula. J Urol. 2001;166(2):530-531.11458060
Simon JE, Chadwick AF, Cracker LE. Herbs: An Indexed Bibliography, 1971-1980: The Scientific Literature on Select Herbs, and Aromatic and Medicinal Plants of the Temperate Zone. Amsterdam, New York: Elsevier; Hamden, CT: Shoestring Press; 1984.
Struempler RE. Excretion of codeine and morphine following ingestion of poppy seeds. J Anal Toxicol. 1987;11(3):97-99.3599922
Theuns HG, Theuns HL, Lousberg RJ. Search for natural sources of morphians. Econ Bot. 1986;40(4):485-497.
Untoro J, Schultink W, West CE, Gross R, Hautvast JG. Efficacy of oral iodized peanut oil is greater than that of iodized poppy seed oil among Indonesian schoolchildren. Am J Clin Nutr. 2006;84(5):1208-1214.17093176
Wensky H. Jongen J. Diagnosis of enterovesical fistula using poppy seeds. Colorectal Dis. 2006;8(1):71-72.16519642

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