Therapeutic Applications And Risks of Papaver Somniferum L. Alkaloids In Cancer Pain And Acute Cardiogenic Pulmonary Oedema

Abstract

Background: Papaver somniferum L. (opium poppy) is a historically significant medicinal plant, primarily known for its potent alkaloids such as morphine, codeine, and thebaine. With the global rise in opioid use and misuse, understanding the medical potential and risks of poppy-derived compounds has gained renewed significance, particularly in contexts such as cancer-related pain and acute cardiogenic pulmonary edema (ACPE).

Purpose: This review evaluates the efficacy and pharmacological mechanisms of P. somniferum alkaloids, particularly morphine, in managing cancer-related pain and acute cardiogenic pulmonary edema (ACPE), alongside associated risks and regulatory concerns.

Method: A literature review was conducted, synthesizing data from peer-reviewed studies sourced from PubMed, Google Scholar, Scopus, and Web of Science, focusing on pharmacological, clinical, and biochemical properties of poppy alkaloids.

Results: Morphine effectively controls severe cancer pain (80–90% pain reduction in clinical trials) via mu-opioid receptor modulation but is underutilized due to addiction concerns. In ACPE, morphine reduces preload and anxiety but lacks clear survival benefits, with risks like respiratory depression (10–15% incidence) and drug interactions.

Conclusion: While Papaver somniferum-derived morphine remains a cornerstone in palliative pain management, its use in ACPE should be approached cautiously due to unclear survival benefits and notable risks.

  • Page Number : 20-28
  • Published Date : 2025-08-25
  • Keywords
    Papaver somniferum L., Morphine, Opioid alkaloids, cancer-related pain, acute cardiogenic pulmonary edema
  • DOI Number
    10.15415/jptrm.2025.131002
  • Authors
    Karan Thakur, Shivam Thakur, Abhay Sharma, Khemender Lidoo, Om Kumar, Scindia Kohli, Rupinder Kaur, Amit Sharma, and Sarita Jangra

References

  • Agewall, S. (2017). Morphine in acute heart failure. Journal of Thoracic Disease, 9(7), 1851.
  • Badshah, I., Anwar, M., Murtaza, B., & Khan, M. I. (2024). Molecular mechanisms of morphine tolerance and dependence; novel insights and future perspectives. Molecular and Cellular Biochemistry, 479(6), 1457–1485.
  • Baser, K. H. C., & Arslan, N. (2014). Opium poppy (Papaver somniferum). In Z. Yaniv & N. Dudai (Eds.), Medicinal and aromatic plants of the Middle-East (pp. 305–332). Springer Netherlands. https://doi.org/10.1007/978-94-017-9276-9_17
  • Beaudoin, G. A., & Facchini, P. J. (2014). Benzylisoquinoline alkaloid biosynthesis in opium poppy. Planta, 240, 19–32. https://doi.org/10.1007/s00425-014-2056-8
  • Butnariu, M., Quispe, C., Herrera-Bravo, J., Pentea, M., Sarac, I., Küşümler, A. S., Özçelik, B., Painuli, S., Semwal, P., Imran, M., Gondal, T. A., Emamzadeh-Yazdi, S., Lapava, N., Yousaf, Z., Kumar, M., Eid, A. H., Al-Dhaheri, Y., Suleria, H. A. R., del Mar Contreras, M., … Cho, W. C. (2022). Papaver plants: Current insights on phytochemical and nutritional composition along with biotechnological applications. Oxidative Medicine and Cellular Longevity, 2022, 2041769. https://doi.org/10.1155/2022/2041769
  • Butnariu, M., Quispe, C., Herrera-Bravo, J., Pentea, M., Sarac, I., Küşümler, A. S., Özçelik, B., Painuli, S., Semwal, P., Imran, M., Gondal, T. A., Emamzadeh-Yazdi, S., Lapava, N., Yousaf, Z., Kumar, M., Eid, A. H., Al-Dhaheri, Y., Suleria, H. A. R., Del Mar Contreras, M., … Cho, W. C. (2022). Papaver plants: Current insights on phytochemical and nutritional composition along with biotechnological applications. Oxidative Medicine and Cellular Longevity, 2022, 2041769. https://doi.org/10.1155/2022/2041769
  • Carlin, M. G., Dean, J. R., & Ames, J. M. (2020). Opium alkaloids in harvested and thermally processed poppy seeds. Frontiers in Chemistry, 8, 737. https://doi.org/10.3389/fchem.2020.00737
  • Caspi, O., Naami, R., Halfin, E., & Aronson, D. (2019). Adverse dose-dependent effects of morphine therapy in acute heart failure. International Journal of Cardiology, 293, 131–136.
  • Celik, I., Camci, H., Kose, A., Kosar, F. C., Doganlar, S., & Frary, A. (2016). Molecular genetic diversity and association mapping of morphine content and agronomic traits in Turkish opium poppy (Papaver somniferum) germplasm. Molecular Breeding, 36, 1–13.
  • Chain, E. P. o. C. i. t. F., Knutsen, H. K., Alexander, J., Barregård, L., Bignami, M., Brüschweiler, B., Ceccatelli, S., Cottrill, B., Dinovi, M., & Edler, L. (2018). Update of the scientific opinion on opium alkaloids in poppy seeds. EFSA Journal, 16(5), e05243. https://doi.org/10.2903/j.efsa.2018.5243
  • Demirkapu, M. J., & Yananli, H. R. (2020). Opium alkaloids. In Bioactive compounds in nutraceutical and functional food for good human health.
  • Di Sotto, A., Valipour, M., Azari, A., Di Giacomo, S., & Irannejad, H. (2023). Benzoindolizidine alkaloids tylophorine and lycorine and their analogues with antiviral, anti-inflammatory, and anticancer properties: Promises and challenges. Biomedicines, 11(10), 2619. https://doi.org/10.3390/biomedicines11102619
  • Dominguez-Rodriguez, A., & Abreu-Gonzalez, P. (2017). A critical appraisal of the morphine in the acute pulmonary edema: Real or real uncertain? Journal of Thoracic Disease, 9(7), 1802.
  • Dominguez-Rodriguez, A., Burillo-Putze, G., Garcia-Saiz, M. d. M., Aldea-Perona, A., Harmand, M. G.-C., Miro, O., Abreu-Gonzalez, P., & Piñera Salmeron, M. i. M. A. P.-E. M. A. R. F. J. M.-S. C. S.-M. R. C.-R. C. C.-C. V. G. P. H. A. A. B. B. P. (2017). Study design and rationale of “a multicenter, open-labeled, randomized controlled trial comparing MIdazolam versus MOrphine in acute pulmonary edema”: MIMO trial. Cardiovascular Drugs and Therapy, 31, 209–213.
  • Dworzynski, K., Roberts, E., Ludman, A., & Mant, J. (2014). Diagnosing and managing acute heart failure in adults: Summary of NICE guidance. BMJ, 349.
  • Fleckner, J., Pettus, K., Vallath, N., & Pastrana, T. (2023). Systematic review on barriers to access opioid analgesics for cancer pain management from the health worker perspective. Journal of Pain & Palliative Care Pharmacotherapy, 37(4), 324–335.
  • Flemming, K., Booth, A., Garside, R., Tunçalp, Ö., & Noyes, J. (2019). Qualitative evidence synthesis for complex interventions and guideline development: Clarification of the purpose, designs and relevant methods. BMJ Global Health, 4(Suppl 1).
  • Gao, D., David, C., Rosa, M. M., Costa, J., Pinto, F. J., & Caldeira, D. (2021). The risk of mortality associated with opioid use in patients with acute heart failure: Systematic review and meta-analysis. Journal of Cardiovascular Pharmacology, 77(2), 123–129.
  • Gil, V., Domínguez-Rodríguez, A., Masip, J., Peacock, W. F., & Miró, Ò. (2019). Morphine use in the treatment of acute cardiogenic pulmonary edema and its effects on patient outcome: A systematic review. Current Heart Failure Reports, 16, 81–88.
  • Ghimire, G. P. (2016). Bioactive compounds and biological activities of some medicinal plants from central Nepal.
  • Gossel, T. A. (2018). Principles of clinical toxicology. CRC Press.
  • Guthrie, S. K., & Teter, C. (2016). Opioid analgesics. In Applied clinical pharmacokinetics and pharmacodynamics of psychopharmacological agents (pp. 267–301). Springer.
  • György, Z., Alam, S., Priyanka, P., & Zámboriné Németh, É. (2022). Genetic diversity and relationships of opium poppy accessions based on SSR markers. Agriculture, 12(9), 1343. https://doi.org/10.3390/agriculture12091343
  • Hayat, M. T., Hameed, U., & Zia-Ul-Haq, M. (2023). Opium poppy. In Essentials of medicinal and aromatic crops (pp. 935–964). Springer.
  • Herman, T., Cascella, M., & Muzio, M. R. (2024). Mu receptors. In StatPearls.
  • Hong, U. V. T., Tamiru-Oli, M., Hurgobin, B., Okey, C. R., Abreu, A. R., & Lewsey, M. G. (2022). Insights into opium poppy (Papaver spp.) genetic diversity from genotyping-by-sequencing analysis. Scientific Reports, 12(1), 111.
  • Jesus, A., Bonhomme, V., Evin, A., Ivorra, S., Soteras, R., Salavert, A., Antolín, F., & Bouby, L. (2021). A morphometric approach to track opium poppy domestication. Scientific Reports, 11, 9778.
  • Kawaguchi, J., Hamatani, Y., Hirayama, A., Nishimura, K., Nakai, E., Nakamura, E., Miyata, M., Kawano, Y., Takada, Y., & Anchi, Y. (2020). Experience of morphine therapy for refractory dyspnea as palliative care in advanced heart failure patients. Journal of Cardiology, 75(6), 682–688.
  • Kumaravel, S., Muthukumaran, P., & Thomas, N. (2019). Phytochemical, GC-MS and FT-IR analysis of Papaver somniferum. Journal of Pharmaceutical and Biological Sciences, 7, 1–8.
  • Labanca, F., Ovesna, J., & Milella, L. (2018). Papaver somniferum L. taxonomy, uses and new insight in poppy alkaloid pathways. Phytochemistry Reviews, 17(4), 853–871.
  • Lahiri, R., Lal, R., Srivastava, N., & Shanker, K. (2018). Genetic variability and diversity in Indian germplasm of opium poppy (Papaver somniferum L.). Journal of Applied Research on Medicinal and Aromatic Plants, 8, 41–46.
  • López-Saca, J. M., & Centeno, C. (2014). Opioids prescription for symptoms relief and the impact on respiratory function: Updated evidence. Current Opinion in Supportive and Palliative Care, 8(4), 383–390.
  • Masihuddin, M., Jafri, M., Siddiqui, A., & Chaudhary, S. (2018). Traditional uses, phytochemistry and pharmacological activities of Papaver somniferum with special reference of Unani medicine: An updated review. Journal of Drug Delivery and Therapeutics, 8(5-S), 110–114.
  • Nishino, K., Uesugi, H., Hirasawa, A., Ohtera, A., Miyamae, Y., Neffati, M., Isoda, H., Kambe, T., Masuda, S., & Irie, K. (2020). Stimulation of insulin secretion by acetylenic fatty acids in insulinoma MIN6 cells through FFAR1. Biochemical and Biophysical Research Communications, 522(1), 68–73.
  • Noyes, J., Booth, A., Moore, G., Flemming, K., Tunçalp, Ö., & Shakibazadeh, E. (2019). Synthesising quantitative and qualitative evidence to inform guidelines on complex interventions. BMJ Global Health, 4(Suppl 1), e000893. https://doi.org/10.1136/bmjgh-2018-000893
  • Olsen, Y., & Sharfstein, J. M. (2019). The opioid epidemic: What everyone needs to know. Oxford University Press.
  • Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G., Coats, A. J., Falk, V., González-Juanatey, J. R., Harjola, V.-P., & Jankowska, E. A. (2016). 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Kardiologia Polska, 74(10), 1037–1147.
  • Rida, P. C., LiVecche, D., Ogden, A., Zhou, J., & Aneja, R. (2015). The noscapine chronicle: A pharmaco-historic biography of the opiate alkaloid family and its clinical applications. Medicinal Research Reviews, 35(5), 1072–1096.
  • Rosenberg, J. (2022). Public health palliative care (7th ed.). https://doi.org/10.1177/26323524221119941
  • Salavert, A., Zazzo, A., & Martin, L. (2020). Direct dating reveals the early history of opium poppy in western Europe. Scientific Reports, 10, 20263.
  • Saunders, J. A., Pedroni, M. J., Penrose, L. D., & Fist, A. J. (2001). AFLP analysis of opium poppy. Crop Science, 41(5), 1596–1601. https://doi.org/10.2135/cropsci2001.4151596x
  • Schick-Makaroff, K., MacDonald, M., Plummer, M., Burgess, J., & Neander, W. (2016). What synthesis methodology should I use? AIMS Public Health, 3(1), 172. https://doi.org/10.3934/publichealth.2016.1.172
  • Shimoji, K., & Fujioka, H. (2020). Pharmacology of analgesics. In Chronic pain management in general and hospital practice (pp. 55–86). Springer. https://doi.org/10.1007/978-981-15-2933-7_5
  • Srivastava, A., Gupta, S., Shanker, K., Gupta, N., Gupta, A. K., & Lal, R. (2020). Genetic diversity in Indian poppy (Papaver somniferum L.) germplasm using multivariate and SCoT marker analyses. Industrial Crops and Products, 144, 112050. https://doi.org/10.1016/j.indcrop.2019.112050
  • Svoboda, P., Vašek, J., Vejl, P., & Ovesná, J. (2020). Genetic features of Czech blue poppy (Papaver somniferum L.) revealed by DNA polymorphism. Czech Journal of Food Sciences, 38(3), 198–202.
  • Tamiru-Oli, M., Premaratna, S. D., Gendall, A. R., & Lewsey, M. G. (2018). Biochemistry, genetics, and genomics of opium poppy (Papaver somniferum) for crop improvement. Annual Plant Reviews Online, 1177–1219.
  • Troy, D. B. (2005). Remington: The science and practice of pharmacy.
  • Ueda, M., Hirayama, Y., Ogawa, H., Nomura, T., Terashi, H., & Sakakibara, S. (2023). Vasodilating effects of antispasmodic agents and their cytotoxicity in vascular smooth muscle cells and endothelial cells. International Journal of Molecular Sciences, 24(13), 10850. https://doi.org/10.3390/ijms241310850
  • Višić, M., Balenović, A., & Mesarić, J. (2024). Synthesising research findings–methodological guidelines for conducting the critical interpretive synthesis method. Teorija in Praksa, 61(4). https://doi.org/10.51936/tip.61.4.909
  • Witharana, T. N., Baral, R., & Vassiliou, V. S. (2022). Impact of morphine use in acute cardiogenic pulmonary oedema on mortality outcomes. Therapeutic Advances in Cardiovascular Disease, 16, 17539447221087587. https://doi.org/10.1177/17539447221087587
  • Wolf, C. E., Pierce, K. L., Goldfine, B. L., Nanco, C. R., Poklis, J. L., & Korzun, W. J. (2019). Using papaverine and its metabolites as biomarkers to improve the detection time of heroin use. Journal of Analytical Toxicology, 43(8), 600–606.
  • Yao, Y., & Xiong, Y. (2016). Metabolic pathway profiling of the derivative of important herbal component noscapine. European Journal of Drug Metabolism and Pharmacokinetics, 41(1), 27–32.
  • Zohary, D., Hopf, M., & Weiss, E. (2012). Domestication of plants in the Old World. Oxford University Press.