nach oben

Erschienen in:

25.01.2023

Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy

verfasst von: Prateeksha Prateeksha, Vivek K. Sharma, Shiv M. Singh, Minaxi Sharma, Deepti Diwan, Abd El-Latif Hesham, Sanjay Guleria, Quang D. Nguyen, Vijai K. Gupta, Brahma N. Singh

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 3/2023

Einloggen, um Zugang zu erhalten

Abstract

Tetrahydrocannabinols (THCs) antagonize the CB1 and CB2 cannabinoid receptors, whose signaling to the endocannabinoid system is essential for controlling cell survival and proliferation as well as psychoactive effects. Most tumor cells express a much higher level of CB1 and CB2; THCs have been investigated as potential cancer therapeutic due to their cannabimimetic properties. To date, THCs have been prescribed as palliative medicine to cancer patients but not as an anticancer modality. Growing evidence of preclinical research demonstrates that THCs reduce tumor progression by stimulating apoptosis and autophagy and inhibiting two significant hallmarks of cancer pathogenesis: metastasis and angiogenesis. However, the degree of their anticancer effects depends on the origin of the tumor site, the expression of cannabinoid receptors on tumor cells, and the dosages and types of THC. This review summarizes the current state of knowledge on the molecular processes that THCs target for their anticancer effects. It also emphasizes the substantial knowledge gaps that should be of concern in future studies. We also discuss the therapeutic effects of THCs and the problems that will need to be addressed in the future. Clarifying unanswered queries is a prerequisite to translating the THCs into an effective anticancer regime.

Suchopár, J., Laštůvka, Z., Mašková, S., Alblová, M., & Pařízek, A. (2021). Endocannabinoids. Ceska Gynekol, 86(6), 414–420. https://doi.org/10.48095/cccg2021414CrossRefPubMed

Guggisberg, J., Schumacher, M., Gilmore, G., & Zylla, D. M. (2022). Cannabis as an anticancer agent: A review of clinical data and assessment of case reports. Cannabis and Cannabinoid Research, 7(1), 24–33. https://doi.org/10.1089/can.2021.0045CrossRefPubMedPubMedCentral

Maccarrone, M. (2017). Metabolism of the endocannabinoid anandamide: Open questions after 25 years. Frontiers in Molecular Neuroscience, 10:166. https://doi.org/10.3389/fnmol.2017.00166

Guzman, M. (2003). Cannabinoids: Potential anticancer agents. Nature Reviews Cancer, 3(10), 745–755. https://doi.org/10.1038/nrc1188CrossRefPubMed

Hosami, F., Ghadimkhah, M. H., Salimi, V., Ghorbanhosseini, S. S., & Tavakoli-Yaraki, M. (2021). The strengths and limits of cannabinoids and their receptors in cancer: Insights into the role of tumorigenesis-underlying mechanisms and therapeutic aspects. Biomedicine & Pharmacotherapy, 144, 112279. https://doi.org/10.1016/J.Biopha.2021.112279CrossRef

Sledzinski, P., Zeyland, J., Slomski, R., & Nowak, A. (2018). The current state and future perspectives of cannabinoids in cancer biology. Cancer Medicine, 7(3), 765–775. https://doi.org/10.1002/cam4.1312CrossRefPubMedPubMedCentral

Braile, M., Marcella, S., Marone, G., Galdiero, M. R., Varricchi, G., & Loffredo, S. (2021). The interplay between the immune and the endocannabinoid systems in cancer. Cells, 10(6), 1282. https://doi.org/10.3390/Cells10061282CrossRefPubMedPubMedCentral

Arif, Y., Singh, P., Bajguz, A., & Hayat, S. (2021). Phytocannabinoids biosynthesis in angiosperms, fungi, and liverworts and their versatile role. Plants-Basel, 10(7), 1307. https://doi.org/10.3390/Plants10071307CrossRefPubMedPubMedCentral

O'Reilly, E. M., Cosgrave, J. M., Gallagher, W. M., & Perry, A. S. (2022). Plant-derived cannabinoids as anticancer agents. Trends in Cancer, 8(5), 350–357. https://doi.org/10.1016/j.trecan.2022.01.017CrossRefPubMed

10.

Hinz, B., & Ramer, R. (2022). Cannabinoids as anticancer drugs: Current status of preclinical research. British Journal of Cancer, 127(1), 1–13. https://doi.org/10.1038/s41416-022-01727-4CrossRefPubMedPubMedCentral

11.

Daris, B., Verboten, M. T., Knez, Z., & Ferk, P. (2019). Cannabinoids in cancer treatment: Therapeutic potential and legislation. Bosnian Journal of Basic Medical Sciences, 19(1), 14–23. https://doi.org/10.17305/bjbms.2018.3532CrossRefPubMedPubMedCentral

12.

Kovalchuk, O., & Kovalchuk, I. (2020). Cannabinoids as anticancer therapeutic agents. Cell Cycle, 19(9), 961–989. https://doi.org/10.1080/15384101.2020.1742952CrossRefPubMedPubMedCentral

13.

Pagano, C., Navarra, G., Coppola, L., Bifulco, M., & Laezza, C. (2021). Molecular mechanism of cannabinoids in cancer progression. International Journal of Molecular Sciences, 22(7), 3680. https://doi.org/10.3390/Ijms22073680CrossRefPubMedPubMedCentral

14.

Abrams, D. I. (2022). Cannabis, cannabinoids and cannabis-based medicines in cancer care comment. Integrative Cancer Therapies, 21, 153473542210817. https://doi.org/10.1177/15347354221081772CrossRef

15.

Abuhasira, R., Shbiro, L., & Landschaft, Y. (2018). Medical use of cannabis and cannabinoids containing products - Regulations in Europe and North America. European Journal of Internal Medicine, 49, 2–6. https://doi.org/10.1016/j.ejim.2018.01.001CrossRefPubMed

16.

Janatova, A., Frankova, A., Tlustos, P., Hamouz, K., Bozik, M., & Kloucek, P. (2018). Yield and cannabinoids contents in different cannabis (Cannabis sativa L.) genotypes for medical use. Industrial Crops and Products, 112, 363–367. https://doi.org/10.1016/j.indcrop.2017.12.006CrossRef

17.

Velasco, G., Hernandez-Tiedra, S., Davila, D., & Lorente, M. (2016). The use of cannabinoids as anticancer agents. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 64, 259–266. https://doi.org/10.1016/j.pnpbp.2015.05.010CrossRef

18.

Velasco, G., Sanchez, C., & Guzman, M. (2016). Anticancer mechanisms of cannabinoids. Current Oncology, 23, S23–S32. https://doi.org/10.3747/co.23.3080CrossRefPubMedPubMedCentral

19.

Bouca-Machado, R., Rosario, M., Alarcao, J., Correia-Guedes, L., Abreu, D., & Ferreira, J. J. (2017). Clinical trials in palliative care: A systematic review of their methodological characteristics and of the quality of their reporting. BMC Palliative Care, 16, 10. https://doi.org/10.1186/s12904-016-0181-9CrossRefPubMedPubMedCentral

20.

Ferrell, B., Borneman, T., Williams, A., Scardina, A., Fischer, P., & Smith, T. (2020). Integrating palliative care for patients on clinical trials: Opportunities for oncology nurses. Asia-Pacific Journal of Oncology Nursing, 7(3), 243–249. https://doi.org/10.4103/apjon.apjon_2_20CrossRefPubMedPubMedCentral

21.

Singh, B. N., Shankar, S., & Srivastava, R. K. (2011). Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. Biochemical Pharmacology, 82(12), 1807–1821. https://doi.org/10.1016/j.bcp.2011.07.093CrossRefPubMedPubMedCentral

22.

Singh, B. N., Prateeksha, Rawat, A. K. S., Bhagat, R. M., & Singh, B. R. (2017). Black tea: Phytochemicals, cancer chemoprevention, and clinical studies. Critical Reviews in Food Science and Nutrition, 57(7), 1394–1410. https://doi.org/10.1080/10408398.2014.994700CrossRefPubMed

23.

Singh, B. N., Singh, H. B., Singh, A., Naqvi, A. H., & Singh, B. R. (2014). Dietary phytochemicals alter epigenetic events and signaling pathways for inhibition of metastasis cascade. Cancer and Metastasis Reviews, 33(1), 41–85. https://doi.org/10.1007/s10555-013-9457-1CrossRefPubMed

24.

Singh, B. R., Singh, B. N., Khan, W., Singh, H. B., & Naqvi, A. H. (2012). ROS-mediated apoptotic cell death in prostate cancer LNCaP cells induced by biosurfactant stabilized CdS quantum dots. Biomaterials, 33(23), 5753–5767. https://doi.org/10.1016/j.biomaterials.2012.04.045CrossRefPubMed

25.

Singh, B. N., Fu, J. S., Srivastava, R. K., & Shankar, S. (2011). Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: Molecular mechanisms. Plos One, 6(11), e27306. https://doi.org/10.1371/journal.pone.0027306CrossRefPubMedPubMedCentral

26.

Bakshi, H. A., Faruck, H. L., Ravesh, Z., Ansari, P., Hannan, J. M. A., Hashimoto, R., Takayama, K., Farzand, R., Nasef, M. M., Mensah, A., Aljabali, A. A. A., Mishra, V., Charbe, N. B., Goyal, R., Negi, P., Serrano-Aroca, Á., Bahar, B., El-Tanani, M., Courtenay, A. J., et al. (2022). Therapeutic potential of cannabinoids on tumor microenvironment: A molecular switch in neoplasia transformation. Integrative Cancer Therapies, 21, 15347354221096766. https://doi.org/10.1177/15347354221096766CrossRefPubMedPubMedCentral

27.

Guzman, M., Galve-Roperh, I., & Sanchez, C. (2001). Ceramide: A new second messenger of cannabinoid action. Trends in Pharmacological Sciences, 22(1), 19–22. https://doi.org/10.1016/S0165-6147(00)01586-8CrossRefPubMed

28.

Mc Allister, S. D., Chan, C., Taft, R. J., Luu, T., Abood, M. E., Moore, D. H., Aldape, K., & Yount, G. (2005). Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. Journal of Neuro-Oncology, 74(1), 31–40. https://doi.org/10.1007/s11060-004-5950-2CrossRefPubMed

29.

Galve-Roperh, I., Sanchez, C., Cortes, M. L., del Pulgar, T. G., Izquierdo, M., & Guzman, M. (2000). Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nature Medicine, 6(3), 313–319. https://doi.org/10.1038/73171CrossRefPubMed

30.

Carracedo, A., Gironella, M., Lorente, M., Garcia, S., Guzman, M., Velasco, G., & Iovanna, J. L. (2006). Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cancer Research, 66(13), 6748–6755. https://doi.org/10.1158/0008-5472.CAN-06-0169CrossRefPubMed

31.

Caffarel, M. M., Sarrió, D., Palacios, J., Guzmán, M., & Sánchez, C. (2006). Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Research, 66(13), 6615–6621. https://doi.org/10.1158/0008-5472.can-05-4566CrossRefPubMed

32.

Greenhough, A., Patsos, H. A., Williams, A. C., & Paraskeva, C. (2007). The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Internation Journal of Cancer, 121(10), 2172–2180. https://doi.org/10.1002/ijc.22917CrossRef

33.

Powles, T., te Poele, R., Shamash, J., Chaplin, T., Propper, D., Joel, S., et al. (2005). Cannabis-induced cytotoxicity in leukemic cell lines: The role of the cannabinoid receptors and the MAPK pathway. Blood, 105(3), 1214–1221. https://doi.org/10.1182/blood-2004-03-1182CrossRefPubMed

34.

Tomko, A., Whynot, E., & Dupré, D. (2021). Anti-cancer properties of cannabidiol and Δ9-tetrahydrocannabinol and potential synergistic effects with gemcitabine, cisplatin and other cannabinoids in bladder cancer. Journal of Cannabis Research, 4(1), 41. https://doi.org/10.1186/s42238-022-00151-yCrossRef

35.

Sanchez, C., Galve-Roperh, I., Canova, C., Brachet, P., & Guzman, M. (1998). Delta(9)-tetrahydrocannabinol induces apoptosis in C6 glioma cells. FEBS Letters, 436(1), 6–10. https://doi.org/10.1016/S0014-5793(98)01085-0CrossRefPubMed

36.

Semlali, A., Beji, S., Ajala, I., & Rouabhia, M. (2021). Effects of tetrahydrocannabinols on human oral cancer cell proliferation, apoptosis, autophagy, oxidative stress, and DNA damage. Archives of Oral Biology, 129, 105200. https://doi.org/10.1016/j.archoralbio.2021.105200CrossRefPubMed

37.

Galanti, G., Fisher, T., Kventsel, I., Shoham, J., Gallily, R., Mechoulam, R., Lavie, G., Amariglio, N., Rechavi, G., & Toren, A. (2008). Delta 9-tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells. Acta Oncologica, 47(6), 1062–1070. https://doi.org/10.1080/02841860701678787CrossRefPubMed

38.

Śledziński, P., Nowak-Terpiłowska, A., & Zeyland, J. (2020). Cannabinoids in medicine: Cancer, immunity, and microbial diseases. International Journal of Molecular Sciences, 22(1), 263. https://doi.org/10.3390/ijms22010263CrossRefPubMedPubMedCentral

39.

Preet, A., Ganju, R. K., & Groopman, J. E. (2008). Delta(9)-tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene, 27(3), 339–346. https://doi.org/10.1038/sj.onc.1210641CrossRefPubMed

40.

Anis, O., Vinayaka, A. C., Shalev, N., Namdar, D., Nadarajan, S., Anil, S. M., Cohen, O., Belausov, E., Ramon, J., Gati, E. M., & Koltai, H. (2021). Cannabis-derived compounds cannabichromene and Δ9-tetrahydrocannabinol interact and exhibit cytotoxic activity against urothelial cell carcinoma correlated with inhibition of cell migration and cytoskeleton organization. Molecules, 26(2), 465. https://doi.org/10.3390/molecules26020465CrossRefPubMedPubMedCentral

41.

Mechta-Grigoriou, F., Gerald, D., & Yaniv, M. (2001). The mammalian Jun proteins: Redundancy and specificity. Oncogene, 20(19), 2378–2389. https://doi.org/10.1038/sj.onc.1204381CrossRefPubMed

42.

Eferl, R., & Wagner, E. F. (2003). AP-1: A double-edged sword in tumorigenesis. Nature Reviews Cancer, 3(11), 859–868. https://doi.org/10.1038/nrc1209CrossRefPubMed

43.

Caffarel, M. M., Moreno-Bueno, G., Cerutti, C., Palacios, J., Guzman, M., Mechta-Grigoriou, F., et al. (2008). JunD is involved in the antiproliferative effect of delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene, 27(37), 5033–5044. https://doi.org/10.1038/onc.2008.145CrossRefPubMed

44.

Zhang, Y. Z., Zheng, W., Shen, K. W., & Shen, W. W. (2018). Delta 9-tetrahydrocannabinol inhibits epithelial-mesenchymal transition and metastasis by targeting matrix metalloproteinase-9 in endometrial cancer. Oncology Letters, 15(6), 8527–8535. https://doi.org/10.3892/ol.2018.8407CrossRefPubMedPubMedCentral

45.

Carracedo, A., Lorente, M., Egia, A., Blázquez, C., García, S., Giroux, V., Malicet, C., Villuendas, R., Gironella, M., González-Feria, L., Piris, M. Á., Iovanna, J. L., Guzmán, M., & Velasco, G. (2006). The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell, 9(4), 301–312. https://doi.org/10.1016/j.ccr.2006.03.005CrossRefPubMed

46.

Peeri, H., & Koltai, H. (2022). Cannabis biomolecule effects on cancer cells and cancer stem cells: Cytotoxic, anti-proliferative, and anti-migratory activities. Biomolecules, 12(4), 491. https://doi.org/10.3390/Biom12040491CrossRefPubMedPubMedCentral

47.

Ramer, R., Schwarz, R., & Hinz, B. (2019). Modulation of the endocannabinoid system as a potential anticancer strategy. Frontiers in Pharmacology, 10:430. https://doi.org/10.3389/Fphar.2019.00430

48.

Haustein, M., Ramer, R., Linnebacher, M., Manda, K., & Hinz, B. (2014). Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1. Biochemical Pharmacology, 92(2), 312–325. https://doi.org/10.1016/j.bcp.2014.07.014CrossRefPubMed

49.

Schoeman, R., de la Harpe, A., Beukes, N., & Frost, C. L. (2022). Cannabis with breast cancer treatment: Propitious or pernicious? 3 Biotech, 12(2):54. https://doi.org/10.1007/S13205-021-03102-1

50.

Liu, W. M., Scott, K. A., Shamash, J., Joel, S., & Powles, T. B. (2008). Enhancing the in vitro cytotoxic activity of delta9-tetrahydrocannabinol in leukemic cells through a combinatorial approach. Leuk Lymphoma, 49(9), 1800–1809. https://doi.org/10.1080/10428190802239188CrossRefPubMed

51.

Oesch, S., & Gertsch, J. (2009). Cannabinoid receptor ligands as potential anticancer agents - High hopes for new therapies? Journal of Pharmacy and Pharmacology, 61(7), 839–853. https://doi.org/10.1211/jpp/61.07.0002CrossRefPubMed

52.

Torres, S., Lorente, M., Rodríguez-Fornés, F., Hernández-Tiedra, S., Salazar, M., García-Taboada, E., Barcia, J., Guzmán, M., & Velasco, G. (2011). A combined preclinical therapy of cannabinoids and temozolomide against glioma. Molecular Cancer Therapeutics, 10(1), 90–103. https://doi.org/10.1158/1535-7163.MCT-10-0688CrossRefPubMed

53.

Yang, Y., Huynh, N., Dumesny, C., Wang, K., He, H., & Nikfarjam, M. (2020). Cannabinoids inhibited pancreatic cancer via P-21 activated kinase 1 mediated pathway. International Journal of Molecular Sciences, 21(21), 8035. https://doi.org/10.3390/Ijms21218035CrossRefPubMedPubMedCentral

54.

McKallip, R. J., Nagarkatti, M., & Nagarkatti, P. S. (2005). Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. Journal of Immunology, 174(6), 3281–3289. https://doi.org/10.4049/jimmunol.174.6.3281CrossRef

55.

Luo, C. K., Chou, P. H., Ng, S. K., Lin, W. Y., & Wei, T. T. (2022). Cannabinoids orchestrate cross-talk between cancer cells and endothelial cells in colorectal cancer. Cancer Gene Therapy, 29(5), 597–611. https://doi.org/10.1038/s41417-021-00346-0CrossRefPubMed

56.

Tucci, S. A., Rogers, E. K., Korbonits, M., & Kirkham, T. C. (2004). The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin. British Journal of Pharmacology, 143(5), 520–523. https://doi.org/10.1038/sj.bjp.0705968CrossRefPubMedPubMedCentral

57.

Vasquez, N. A., & Nielsen, D. E. (2022). The Endocannabinoid system and eating behaviours: A review of the current state of the evidence. Current Nutrition Reports, 11(4), 665–674. https://doi.org/10.1007/s13668-022-00436-xCrossRef

58.

Nelson, K., Walsh, D., Deeter, P., & Sheehan, F. (1994). A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia. Journal of Palliative Care, 10(1), 14–18.CrossRefPubMed

59.

Strasser, F., Luftner, D., Possinger, K., Ernst, G., Ruhstaller, T., Meissner, W., Ko, Y.-D., Schnelle, M., Reif, M., & Cerny, T. (2006). Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: A multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the cannabis-in-cachexia-study-group. Journal of Clinical Oncology, 24(21), 3394–3400. https://doi.org/10.1200/Jco.2005.05.1847CrossRefPubMed

60.

Zutt, M., Hanssle, H., Emmert, S., Neumann, C., & Kretschmer, L. (2006). Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases. Hautarzt, 57(5), 423–427. https://doi.org/10.1007/s00105-005-1063-xCrossRefPubMed

61.

Jatoi, A., Windschitl, H. E., Loprinzi, C. L., Sloan, J. A., Dakhil, S. R., Mailliard, J. A., Pundaleeka, S., Kardinal, C. G., Fitch, T. R., Krook, J. E., Novotny, P. J., & Christensen, B. (2002). Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: A north central cancer treatment group study. Journal of Clinical Oncology, 20(2), 567–573. https://doi.org/10.1200/jco.2002.20.2.567CrossRefPubMed

62.

Turcott, J., Guillen- Núñez, M. D. R., Flores, D., Oñate, L., Zatarain-Barrón, Z., Barrón, F., & Arrieta, O. (2018). The effect of Nabilone on appetite, nutritional status, and quality of life in lung cancer patients: A randomized, double-blind clinical trial. Journal of Thoracic Oncology, 13(10), S360–S361. https://doi.org/10.1016/j.jtho.2018.08.328CrossRef

63.

Brisbois, T. D., de Kock, I. H., Watanabe, S. M., Mirhosseini, M., Lamoureux, D. C., Chasen, M., MacDonald, N., Baracos, V. E., & Wismer, W. V. (2011). Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: Results of a randomized, double-blind, placebo-controlled pilot trial. Annals of Oncology, 22(9), 2086–2093. https://doi.org/10.1093/annonc/mdq727CrossRefPubMed

64.

Costa, B. (2007). On the pharmacological properties of delta9-tetrahydrocannabinol (THC). Chemistry & Biodiversity, 4(8), 1664–1677. https://doi.org/10.1002/cbdv.200790146CrossRef

65.

Mlost, J., Bryk, M., & Starowicz, K. (2020). Cannabidiol for pain treatment: Focus on pharmacology and mechanism of action. International Journal of Molecular Sciences, 21(22), 8870. https://doi.org/10.3390/Ijms21228870CrossRefPubMedPubMedCentral

66.

Mitchell, V. A., Harley, J., Casey, S. L., Vaughan, A. C., Winters, B. L., & Vaughan, C. W. (2021). Oral efficacy of delta(9)-tetrahydrocannabinol and cannabidiol in a mouse neuropathic pain model. Neuropharmacology, 189, 108529. https://doi.org/10.1016/j.neuropharm.2021.108529CrossRefPubMed

67.

Noyes Jr., R., Brunk, S. F., Avery, D. A., & Canter, A. C. (1975). The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clinical Pharmacology and Therapy, 18(1), 84–89. https://doi.org/10.1002/cpt197518184CrossRef

68.

Johnson, J. R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E. D., Potts, R., & Fallon, M. T. (2010). Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and thc extract in patients with intractable cancer-related pain. Journal of Pain and Symptom Management, 39(2), 167–179. https://doi.org/10.1016/j.jpainsymman.2009.06.008CrossRefPubMed

69.

Portenoy, R. K., Ganae-Motan, E. D., Allende, S., Yanagihara, R., Shaiova, L., Weinstein, S., McQuade, R., Wright, S., & Fallon, M. T. (2012). Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: A randomized, placebo-controlled, graded-dose trial. Journal of Pain, 13(5), 438–449. https://doi.org/10.1016/j.jpain.2012.01.003CrossRefPubMed

70.

Johnson, J. R., Lossignol, D., Burnell-Nugent, M., & Fallon, M. T. (2013). An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal thc spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. Journal of Pain and Symptom Management, 46(2), 207–218. https://doi.org/10.1016/j.jpainsymman.2012.07.014CrossRefPubMed

71.

Lynch, M. E., Cesar-Rittenberg, P., & Hohmann, A. G. (2014). A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. Journal of Pain and Symptom Management, 47(1), 166–173. https://doi.org/10.1016/j.jpainsymman.2013.02.018CrossRefPubMed

72.

Fallon, M. T., Lux, E. A., McQuade, R., Rossetti, S., Sanchez, R., Sun, W., Wright, S., Lichtman, A. H., & Kornyeyeva, E. (2017). Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: Two double-blind, randomized, placebo-controlled phase 3 studies. British Journal of Pain, 11(3), 119–133. https://doi.org/10.1177/2049463717710042CrossRefPubMedPubMedCentral

73.

Staquet, M., Gantt, C., & Machin, D. (1978). Effect of a nitrogen analog of tetrahydrocannabinol on cancer pain. Clinical Pharmacology and Therapy, 23(4), 397–401. https://doi.org/10.1002/cpt1978234397CrossRef

74.

Benredjem, B., & Pineyro, G. (2021). Are (THC:CBD) ratios good descriptors of the analgesic potential of cannabinoids? Canadian Journal of Physiology and Pharmacology, 99(11), S2–S2.

75.

Janelsins, M. C., Kesler, S. R., Ahles, T. A., & Morrow, G. R. (2014). Prevalence, mechanisms, and management of cancer-related cognitive impairment. International Review of Psychiatry, 26(1), 102–113. https://doi.org/10.3109/09540261.2013.864260CrossRefPubMed

76.

Darmani, N. A. (2001). Delta(9)-tetrahydrocannabinol and synthetic cannabinoids prevent emesis produced by the cannabinoid CB1 receptor antagonist/inverse agonist SR 141716A. Neuropsychopharmacology, 24(2), 198–203. https://doi.org/10.1016/S0893-133x(00)00197-4CrossRefPubMed

77.

Meiri, E., Jhangiani, H., Vredenburgh, J. J., Barbato, L. M., Carter, F. J., Yang, H.-M., & Baranowski, V. (2007). Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Current Medical Research and Opinion, 23(3), 533–543. https://doi.org/10.1185/030079907X167525CrossRefPubMed

78.

Machado Rocha, F. C., Stéfano, S. C., De Cássia Haiek, R., Rosa Oliveira, L. M., & Da Silveira, D. X. (2008). Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: Systematic review and meta-analysis. European Journal of Cancer Care (Engl), 17(5), 431–443. https://doi.org/10.1111/j.1365-2354.2008.00917.xCrossRef

79.

Kesner, A. J., & Lovinger, D. M. (2020). Cannabinoids, endocannabinoids and sleep. Frontiers in Molecular Neuroscience, 13, 125. https://doi.org/10.3389/Fnmol.2020.00125CrossRefPubMedPubMedCentral

80.

Kaul, M., Zee, P. C., & Sahni, A. S. (2021). Effects of cannabinoids on sleep and their therapeutic potential for sleep disorders. Neurotherapeutics, 18(1), 217–227. https://doi.org/10.1007/s13311-021-01013-wCrossRefPubMedPubMedCentral

81.

Martin-Willett, R., Master, A., Bidwell, L. C., & Sznitman, S. R. (2021). Cannabis use and sleep. In V. B. Patel & V. R. Preedy (Eds.), Handbook of substance misuse and addictions: from biology to public health (pp. 1–30). Springer International Publishing.

82.

Guzmán, M., Duarte, M. J., Blázquez, C., Ravina, J., Rosa, M. C., Galve-Roperh, I., Sánchez, C., Velasco, G., & González-Feria, L. (2006). A pilot clinical study of delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. British Journal of Cancer, 95(2), 197–203. https://doi.org/10.1038/sj.bjc.6603236CrossRefPubMedPubMedCentral

83.

Cote, M., Trudel, M., Wang, C. S., & Fortin, A. (2016). Improving quality of life with nabilone during radiotherapy treatments for head and neck cancers: A randomized double-blind placebo-controlled trial. Annals of Otology Rhinology and Laryngology, 125(4), 317–324. https://doi.org/10.1177/0003489415612801CrossRefPubMed

84.

Fabre, L. F., & Mclendon, D. (1981). The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety. Journal of Clinical Pharmacology, 21(8-9), S377–S382. https://doi.org/10.1002/j.1552-4604.1981.tb02617.x.CrossRef

85.

Shannon, S., Lewis, N., Lee, H., & Hughes, S. (2019). Cannabidiol in anxiety and sleep: A large case series. The Permanente Journal, 23, 18–041. https://doi.org/10.7812/TPP/18-041CrossRefPubMedPubMedCentral

86.

Scott, K. A., Dalgleish, A. G., & Liu, W. M. (2017). Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration. International Journal of Oncology, 51(1), 369–377. https://doi.org/10.3892/ijo.2017.4022CrossRefPubMed

87.

Nabissi, M., Morelli, M. B., Offidani, M., Amantini, C., Gentili, S., Soriani, A., Cardinali, C., Leoni, P., & Santoni, G. (2016). Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget, 7(47), 77543–77557. https://doi.org/10.18632/oncotarget.12721CrossRefPubMedPubMedCentral

88.

Soto-Mercado, V., Mendivil-Perez, M., Jimenez-Del-Rio, M., Fox, J. E., & Velez-Pardo, C. (2020). Cannabinoid CP55940 selectively induces apoptosis in Jurkat cells and in ex vivo T-cell acute lymphoblastic leukemia through H₂O₂ signaling mechanism. Leukemia Research, 95, 106389. https://doi.org/10.1016/j.leukres.2020.106389CrossRefPubMed

89.

Munson, A. E., Harris, L. S., Friedman, M. A., Dewey, W. L., & Carchman, R. A. (1975). Antineoplastic activity of cannabinoids. The Journal of the National Cancer Institute, 55(3), 597–602. https://doi.org/10.1093/jnci/55.3.597CrossRefPubMed

90.

Zhu, L. X., Sharma, S., Stolina, M., Gardner, B., Roth, M. D., Tashkin, D. P., et al. (2000). Delta-9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. Journal of Immunology, 165(1), 373–380. https://doi.org/10.4049/jimmunol.165.1.373CrossRef

91.

Müller, L., Radtke, A., Decker, J., Koch, M., & Belge, G. (2017). The synthetic cannabinoid WIN 55,212-2 elicits death in human cancer cell lines. Anticancer Research, 37, 6341–6345. https://doi.org/10.21873/anticanres.12086CrossRefPubMed

92.

Milian, L., Mata, M., Alcacer, J., Oliver, M., Sancho-Tello, M., de Llano, J. J. M., Camps, C., Galbis, J., Carretero, J., & Carda, C. (2020). Cannabinoid receptor expression in non-small cell lung cancer. Effectiveness of tetrahydrocannabinol and cannabidiol inhibiting cell proliferation and epithelial-mesenchymal transition in vitro. Plos One, 15(2), e0228909. https://doi.org/10.1371/journal.pone.0228909CrossRefPubMedPubMedCentral

93.

Milián, L., Monleón-Guinot, I., Sancho-Tello, M., Galbis, J. M., Cremades, A., Almenar-Ordaz, M., Peñaroja-Martinez, J., Farras, R., de Llano, J. J. M., Carda, C., & Mata, M. (2022). In vitro effect of Δ9-tetrahydrocannabinol and cannabidiol on cancer-associated fibroblasts isolated from lung cancer. International Journal of Molecular Sciences, 23(12), 6766. https://doi.org/10.3390/ijms23126766CrossRefPubMedPubMedCentral

94.

Blasco-Benito, S., Moreno, E., Seijo-Vila, M., Tundidor, I., Andradas, C., Caffarel, M. M., et al. (2019). Therapeutic targeting of HER2-CB2R heteromers in HER2-positive breast cancer (vol 116, pg 3863, 2019). Proceedings of the National Academy of Sciences of the United States of America, 116(13), 6505–6505. https://doi.org/10.1073/pnas.1903209116CrossRef

95.

Marcu, J. P., Christian, R. T., Lau, D., Zielinski, A. J., Horowitz, M. P., Lee, J., Pakdel, A., Allison, J., Limbad, C., Moore, D. H., Yount, G. L., Desprez, P.-Y., & McAllister, S. D. (2010). Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Molecular Cancer Therapeutics, 9(1), 180–189. https://doi.org/10.1158/1535-7163.mct-09-0407CrossRefPubMedPubMedCentral

96.

Ellert-Miklaszewska, C., & I. A., & Kaminska, B. (2021). Synthetic cannabinoids induce autophagy and mitochondrial apoptotic pathways in human glioblastoma cells independently of deficiency in TP53 or PTEN tumor suppressors. Cancers, 13(3). https://doi.org/10.3390/cancers13030419

97.

Blázquez, C., Casanova, M. L., Planas, A., del Pulgar, T. G., Villanueva, C., Fernández‐Aceñero, M. J., Aragonés, J., Huffman, J. W., Jorcano, J. L., & Guzmán, M. (2003). Inhibition of tumor angiogenesis by cannabinoids. FASEB Journal, 17(3), 1–16. https://doi.org/10.1096/fj.02-0795fjeCrossRef

98.

López-Valero, I., Saiz-Ladera, C., Torres, S., Hernández-Tiedra, S., García-Taboada, E., Rodríguez-Fornés, F., Barba, M., Dávila, D., Salvador-Tormo, N., Guzmán, M., Sepúlveda, J. M., Sánchez-Gómez, P., Lorente, M., & Velasco, G. (2018). Targeting glioma initiating cells with a combined therapy of cannabinoids and temozolomide. Biochemical Pharmacology, 157, 266–274. https://doi.org/10.1016/j.bcp.2018.09.007CrossRefPubMed

99.

Soroceanu, L., Singer, E., Dighe, P., Sidorov, M., Limbad, C., Rodriquez-Brotons, A., Rix, P., Woo, R. W. L., Dickinson, L., Desprez, P.-Y., & McAllister, S. D. (2022). Cannabidiol inhibits RAD51 and sensitizes glioblastoma to temozolomide in multiple orthotopic tumor models. Neurooncology. Neuro-Oncology Advances, 4(1):vdac019. https://doi.org/10.1093/noajnl/vdac019

100.

Wasik, A. M., Almestrand, S., Wang, X., Hultenby, K., Dackland, Å.-L., Andersson, P., Kimby, E., Christensson, B., & Sander, B. (2011). WIN55,212-2 induces cytoplasmic vacuolation in apoptosis-resistant MCL cells. Cell Death & Disease, 2, e225. https://doi.org/10.1038/cddis.2011.106CrossRef

101.

Fisher, T., Golan, H., Schiby, G., PriChen, S., Smoum, R., Moshe, I., Peshes-Yaloz, N., Castiel, A., Waldman, D., Gallily, R., Mechoulam, R., & Toren, A. (2016). In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma. Current Oncology, 23(2), 15–22. https://doi.org/10.3747/co.23.2893CrossRef

102.

Ruiz, L., Miguel, A., & Diaz-Laviada, I. (1999). Delta(9)-tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism. FEBS Letters, 458(3), 400–404. https://doi.org/10.1016/S0014-5793(99)01073-XCrossRefPubMed

103.

Morell, C., Bort, A., Vara, D., Ramos-Torres, A., Rodriguez-Henche, N., & Diaz-Laviada, I. (2016). The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells. Prostate Cancer and Prostatic Diseases, 19(3), 248–257. https://doi.org/10.1038/pcan.2016.19CrossRefPubMedPubMedCentral

104.

Armstrong, J. L., Hill, D. S., McKee, C. S., Hernandez-Tiedra, S., Lorente, M., Lopez-Valero, I., Anagnostou, M. E., Babatunde, F., Corazzari, M., Redfern, C. P. F., Velasco, G., & Lovat, P. E. (2015). Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. Journal of Investigative Dermatology, 135(6), 1629–1637. https://doi.org/10.1038/jid.2015.45CrossRefPubMed

105.

Glodde, N., Jakobs, M., Bald, T., Tuting, T., & Gaffal, E. (2015). Differential role of cannabinoids in the pathogenesis of skin cancer. Life Sciences, 138, 35–40. https://doi.org/10.1016/j.lfs.2015.04.003CrossRefPubMed

106.

Whyte, D. A., Al-Hammadi, S., Balhaj, G., Brown, O. M., Penefsky, H. S., & Souid, A. K. (2010). Cannabinoids inhibit cellular respiration of human oral cancer cells. Pharmacology, 85(6), 328–335. https://doi.org/10.1159/000312686CrossRefPubMed

107.

Lichtman, A. H., Lux, E. A., McQuade, R., Rossetti, S., Sanchez, R., Sun, W., Wright, S., Kornyeyeva, E., & Fallon, M. T. (2018). Results of a double-blind, randomized, placebo-controlled study of nabiximols oromucosal spray as an adjunctive therapy in advanced cancer patients with chronic uncontrolled pain. Journal of Pain and Symptom Management, 55(2), 179–188.e1. https://doi.org/10.1016/j.jpainsymman.2017.09.001CrossRefPubMed

108.

Maida, V., Ennis, M., Irani, S., Corbo, M., & Dolzhykov, M. (2008). Adjunctive nabilone in cancer pain and symptom management: A prospective observational study using propensity scoring. The Journal of Supportive Oncology, 6(3), 119–124.PubMed

109.

Walsh, D., Kirkova, J., & Davis, M. P. (2005). The efficacy and tolerability of long-term use of dronabinol in cancer-related anorexia: A case series. Journal of Pain and Symptom Management, 30(6), 493–495. https://doi.org/10.1016/j.jpainsymman.2005.11.007CrossRefPubMed

110.

Ofir, R., Bar-Sela, G., Ben-Arush, M. W., & Postovsky, S. (2019). Medical marijuana use for pediatric oncology patients: Single institution experience. Pediatric Hematology and Oncology, 36(5), 225–266.CrossRef

111.

Duran, M., Pérez, E., Abanades, S., Vidal, X., Saura, C., Majem, M., Arriola, E., Rabanal, M., Pastor, A., Farré, M., Rams, N., Laporte, J.-R., & Capellà, D. (2010). Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. British Journal of Clinical Pharmacology, 70(5), 656–663. https://doi.org/10.1111/j.1365-2125.2010.03743.xCrossRefPubMedPubMedCentral

112.

Chang, A. E., Shiling, D. J., Stillman, R. C., Goldberg, N. H., Seipp, C. A., Barofsky, I., et al. (1979). Delata-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. A prospective, randomized evaluation. Annals of Internal Medicine, 91(6), 819–824. https://doi.org/10.7326/0003-4819-91-6-819CrossRefPubMed

113.

Sallan, S. E., Cronin, C., Zelen, M., & Zinberg, N. E. (1980). Antiemetics in patients receiving chemotherapy for cancer: A randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. The New England Journal of Medicine, 302(3), 135–138. https://doi.org/10.1056/nejm198001173020302CrossRefPubMed

114.

Shiling, D. J., Stillman, R. C., Chang, A. E., Goldberg, N. H., Seipp, C. A., Barofsky, I., & Rosenberg, S. A. (1981). A prospective evaluation of delta-9-tetrahydrocannabinol as an antiemetic in patients receiving adriamycin and cytoxan chemotherapy. Cancer, 47(7), 1746–1751. https://doi.org/10.1002/1097-0142(19810401)47:7<1746::aid-cncr2820470704>3.0.co;2-4CrossRefPubMed

115.

Sallan, S. E., Zinberg, N. E., & Frei 3rd, E. (1975). Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. The New England Journal of Medicine, 293(16), 795–797. https://doi.org/10.1056/nejm197510162931603CrossRefPubMed

116.

Twelves, C., Short, S., & Wright, S. (2017). A two-part safety and exploratory efficacy randomized double-blind, placebo-controlled study of a 1:1 ratio of the cannabinoids cannabidiol and delta-9-tetrahydrocannabinol (CBD:THC) plus dose-intense temozolomide in patients with recurrent glioblastoma multiforme (GBM). Journal of Clinical Oncology, 35. https://doi.org/10.1200/Jco.2017.35.15_Suppl.2046

Titel: Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy
verfasst von: Prateeksha Prateeksha
Vivek K. Sharma
Shiv M. Singh
Minaxi Sharma
Deepti Diwan
Abd El-Latif Hesham
Sanjay Guleria
Quang D. Nguyen
Vijai K. Gupta
Brahma N. Singh
Publikationsdatum: 25.01.2023
Verlag: Springer US
Erschienen in: Cancer and Metastasis Reviews / Ausgabe 3/2023
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-023-10078-2

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Tetrahydrocannabinols: potential cannabimimetic agents for cancer therapy

Abstract

Neu im Fachgebiet Onkologie

Bei seelischem Stress sind Checkpoint-Hemmer weniger wirksam

Antikörper mobilisiert Neutrophile gegen Krebs

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

15% bedauern gewählte Blasenkrebs-Therapie

Update Onkologie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2023

New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions

Natural compounds targeting nuclear receptors for effective cancer therapy

Metabolic factors associated with the prognosis of oligometastatic patients treated with stereotactic body radiotherapy

Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma

Next-generation immune checkpoint inhibitors as promising functional molecules in cancer therapeutics

Short-chain fatty acids in cancer pathogenesis

Neu im Fachgebiet Onkologie

Bei seelischem Stress sind Checkpoint-Hemmer weniger wirksam

Antikörper mobilisiert Neutrophile gegen Krebs

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

15% bedauern gewählte Blasenkrebs-Therapie

Update Onkologie