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Overview of Cancer

Cancer is a general name used to classify a large group of diseases that develop because of abnormal cells growing out of control. Normal body cells are continuously growing, dividing, and dying. When cells in a part of the body begin to grow out of control, it is diagnosed as cancer. Cancer cells will continue to grow, rather than die, and they can invade other tissues. Most of the time, cancer cells form a tumor, which can in turn invade nearby normal tissue and crowd it out or push it aside. The cancer cells will often travel to other parts of body, a process referred to as metastasis, through the bloodstream of lymph vessels. According to the American Cancer Society, there are over 1.6 million new cases in the United States every year, and if left untreated, cancers can cause serious illness and death.

Cancer is considered a genetic disease because it is caused by changes to the genes that control the way our cells function. Although these changes can be inherited, they can also arise during a person’s lifetime. There are more than 100 different types of cancers, which are commonly named for the organs or tissues from where they form.

Treatment of cancer varies depending on the location of cancer and how far it’s advanced. However, there are a number of primary types of cancer treatment include the following: surgery, which involves removing the cancerous tumor; radiation therapy, which uses high doses of radiation to kill cancer cells and shrink tumors; chemotherapy, which uses drugs to kill cancer cells; immunotherapy, which helps your immune system fight cancer; hormone therapy, which slows or stops the growth of cancer that uses hormones to grow; targeted therapy, which targets the changes in cancer cells that help them grow and divide; and stem cell transplant, which involves a procedure that restores blood-forming stem cells in people who have had theirs destroyed by high doses of cancer treatments.

Findings: Effects of Cannabis on Cancer

Evidence suggests that cannabis has the potential of inhibiting the growth of and even killing cancer cells and can help patients manage symptoms associated with cancer treatments. After examining the available literature, a recent research review concluded that cannabis possesses anti-tumor properties and is effective at offering pain, nausea, and vomiting relief for patients with cancer107.

Two of the major cannabinoids found in cannabis, tetrahydrocannabinol (THC) and cannabidiol (CBD), activate the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors of the endocannabinoid system. Activation of the CB1 and CB2receptors by cannabinoids can elicit antitumor effects in a number of aggressive cancers. THC and CBD have been shown to inhibit the progression of cancers located in the breast, lung, prostate, and colon in animal models, suggesting that the cannabinoids may also be effective at mediating cancer cell death in human subjects35,53,63,74.

CBD acid (CBDA), the acidic precursor of CBD, has shown in one study to have the capability of down-regulating invasive human breast cancer cells and therefore preventing their growth93. In 2016, the same team of researchers found CBDA to effectively inhibit the migration of breast cancer cells and was able to identify the effect to be associated with the cannabinoid’s downregulation of the proto-oncogene c-fos and the enzyme cyclooxygenase-294.

Cannabis has long demonstrated it can provide relief for patients suffering from nausea related to cancer treatments. Studies have found that CBD is effective at treating the more difficult to control symptoms of nausea, as well as preventing anticipatory nausea in chemotherapy patients56,76. Another study found that THC was effective at reducing conditioned rejection and chemotherapy-induced nausea54.

Cannabis has also been shown to be effective at lowering neuropathic pain that traditional treatment was unable to manage108. In one study, cancer patients with intractable pain who had previously and unsuccessfully tried to manage their discomfort with opioids saw significant reductions in pain levels after being treated with cannabis containing both THC and CBD for two weeks47.

Weight loss due to nausea and a loss of appetite are common side effects of cancer treatment. However, THC has shown to significantly stimulate appetite in patients that have cachexia related to cancer46,70. In addition, patients treated with THC have a larger appetite and report that food “tastes better”10. The ability to stimulate appetite in cancer patients is significant in helping to prevent wasting syndrome related to cancer treatments.

A survey study analyzing the effects of cannabis in 131 cancer patients after six to eight weeks of treatment found significant improvements in all of the measured cancer-related symptoms, which included nausea, vomiting, mood disorders, fatigue, weight loss, anorexia, constipation, sexual function, sleep disorders, itching, and pain3. Patients treated with THC also experience higher quality sleep and relaxation10. The National Cancer Institute, an organization run by the U.S. Department of Health and Human Services, currently recognizes cannabis as an effective treatment for providing relief of a number of symptoms associated with cancer, including pain, nausea and vomiting, anxiety, and loss of appetite15.

References

  1. Abrams, D.I. (2016). Integrating cannabis into clinical cancer care. Current Oncology, 23(Suppl 2), S8–S14. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791148/.

  2. Abrams, D.I., and Guzman, M. (2015, June). Cannabis in cancer care. Clinical Pharmacology and Therapeutics, 97(6), 575-86. Retrieved from http://escholarship.org/uc/item/6367m6vj.

  3. Bar-Sela, G., Vorobeichik, M., Drawsheh, S., Omer, A., Goldberg, V., and Muller, E. (2013). The Medical Necessity for Medicinal Cannabis: Prospective, Observational Study Evaluating the Treatment in Cancer Patients on Supportive or Palliative Care. Evidence-Based Complementary and Alternative Medicine, 2013, 510392. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730175/.

  4. Benz, A. H., Renné, C., Maronde, E., Koch, M., Grabiec, U., Kallendrusch, S., Rengstl, B., Newrzela, S., Hartmann, S., Hansmann, M.L., and Dehghani, F. (2013). Expression and Functional Relevance of Cannabinoid Receptor 1 in Hodgkin Lymphoma. PLoS ONE, 8(12), e81675. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857220/?report=reader.

  5. Bifulco, M., Laezza, C., Pisanti, S., and Gazzerro, P. (2006). Cannabinoids and cancer: pros and cons of an antitumour strategy. British Journal of Pharmacology, 148(2), 123–135. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1617062/?report=reader.

  6. Bifulco, M., Laezza, C., Gazzerro, P., and Pentimalli, F. (2007, April). Endocannabinoids as emerging suppressors of angiogenesis and tumor invasion (Review). Oncology Reports, 17(4), 813-6. Retrieved from https://www.spandidos-publications.com/or/17/4/813/download.

  7. Bifulco, M., Malfitani, A.M. Pisanti, S., and Laezza, C. (2008, June). Endocannabinoids in endocrine and related tumours. Endocrine-related Cancer, 15(2), 391-408. Retrieved from http://erc.endocrinology-journals.org/content/15/2/391.long.

  8. Blázquez, C., Casanova, M.L., Planas, A., Gómez Del Pulgar, T., Villanueva, C., Fernández-Aceñero, M.J., Aragonés, J., Huffman, J.W., Jorcano, J.L., Guzmán, M. (2003, March). Inhibition of tumor angiogenesis by cannabinoids. FASEB Journal, 17(3), 529-31. Retrieved from http://www.fasebj.org/content/early/2003/03/02/fj.02-0795fje.long.

  9. Blázquez, C., Carracedo, A., Barrado, L., Real, P.J., Fernández-Lun, J.L., Velasco, G., Malumbres, M., and Guzmán, M. (2006, December) Cannabinoid receptors as novel targets for the treatment of melanoma. FASEB Journal, 20(14), 2633-5. Retrieved from http://www.fasebj.org/content/20/14/2633.long.

  10. Brisbois, T.D., de Kock, I.H., Watanabe, S.M., Mirhosseini, M., Lamoureux, D.C., Chasen, M., MacDonald, N., Baracos, V.E., and Wismer, W.V. (2011, February 22). 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, 2086-2093. Retrieved from https://academic.oup.com/annonc/article/22/9/2086/211788/Delta-9-tetrahydrocannabinol-may-palliate-altered.

  11. Brown, I., Cascio, M.G., Rotondo, D., Pertwee, R.G., Heyes, S.D., and Wahle, K.W. (2013, January). Cannabinoids and omega-3/6 endocannabinoids as cell death and anticancer modulators. Progress in Lipid Research, 52(1), 80-109. Retrieved from http://www.sciencedirect.com/science/article/pii/S0163782712000537.

  12. Caffarel, M.M., Andradas, C., Perez-Gomez, E., Guzman, M., and Sanchez, C. (2012, November). Cannabinoids: A new hope for breast cancer therapy? Cancer Treatment Reviews, 38(7), 911-8. Retrieved from http://www.cancertreatmentreviews.com/article/S0305-7372(12)00139-9/fulltext.

  13. Caffarel, M. M., Andradas, C., Mira, E., Pérez-Gómez, E., Cerutti, C., Moreno-Bueno, G., … Sánchez, C. (2010). Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition. Molecular Cancer, 9, 196. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917429/.

  14. Calvaruso, G., Pellerito, O., Notaro, A., and Giuliano, M. (2012, August). Cannabinoid-associated cell death mechanisms in tumor models (Review). International Journal of Oncology, 41(2), 407-13. Retrieved from https://www.spandidos-publications.com/ijo/41/2/407.

  15. Cannabis and Cannabinoids (PDQ). (2015, July 15). National Cancer Institute. Retrieved from http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq.

  16. Carracedo, A., Gironella, M., Lorente, M., Garcia, S., Guzmán, M., Velasco, G., and Iovanna, J.L.. (2006, July 1). Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cancer Research, 66(13), 6748-55. Retrieved from http://cancerres.aacrjournals.org/content/66/13/6748.long.

  17. Carracedo, A., Lorente, M., Egia, A., Blázquez, C., García, S., Giroux, V., Malicet, C., Villuendas, R., Gironella, M., González-Feria, L., Piris, M.A., Iovanna, J.L., Guzmán, M., Velasco, G. (2006, April). The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells. Cancer Cell, 9(4), 301-12. Retrieved from http://www.cell.com/cancer-cell/fulltext/S1535-6108(06)00085-7.

  18. Casanova, M.L., Blázquez, C., Martínez-Palacio, J., Villanueva, C., Fernández-Aceñero, M.J., Huffman, J.W., Jorcano, J.L., and Guzmán, M. (2003). Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. Journal of Clinical Investigation, 111(1), 43–50. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC151833/.

  19. Chakravarti, B., Ravi, J., and Ganju, R.K. (2014, August 15). Cannabinoids as therapeutic agents in cancer: current status and future implications. Oncotarget, 5(15), 5852-72. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171598/.

  20. Cudaback, E., Marrs, W., Moeller, T., and Stella, N. (2010). The Expression Level of CB1 and CB2 Receptors Determines Their Efficacy at Inducing Apoptosis in Astrocytomas. PLoS ONE, 5(1), e8702. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806825/.

  21. De Petrocellis, L., Melck, D., Palmisano, A., Bisogno, T., Laezza, C., Bifulco, M., and Di Marzo, V. (1998). The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proceedings of the National Academy of Sciences of the United States of America, 95(14), 8375–8380. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20983/.

  22. De Petrocellis, L., Melck, D., Bisogno, T., and Di Marzo, V. (2000, November). Endocannabinoids and fatty acid amides in cancer inflammation and related disorders. Chemistry and Physics of Lipids, 108(1-2), 191-209. Retrieved from http://www.sciencedirect.com/science/article/pii/S0009308400001961.

  23. De Petrocellis, L., Ligresti, A., Schiano Moriello, A., Iappelli, M., Verde, R., Stott, C.G., Cristino, L., Orlando, P., and Di Marzo, V. (2013). Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms. British Journal of Pharmacology, 168(1), 79–102. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570006/.

  24. Estimated Number of New Cancer Cases and Deaths by Sex, US, 2015. (2015). American Cancer Society. Retrieved from http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044514.pdf.

  25. Fisher, T., Golan, H., Schiby, G., PriChen, S., Smoum, R., Moshe, I., Peshes-Yaloz, N., Castiel, A., Waldman, D., Gallily, R., Mechoulam, R., and Toren, A. (2016). In vitro and in vivo efficacy of non-psychoactive cannabidiol in neuroblastoma. Current Oncology, 23(Suppl 2), S15–S22. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791143/.

  26. Flygare, J., and Sander, B. (2008, June). The endocannabinoid system in cancer- Potential therapeutic target? Seminars in Cancer Biology, 18(3), 176-89. Retrieved from http://www.sciencedirect.com/science/article/pii/S1044579X07001058.

  27. Freimuth, N., Ramer, R., and Hinz, B. (2010, February). Antitumorigenic effects of cannabinoids beyond apoptosis. The Journal of Pharmacology and Experimental Therapeutics, 332(2), 336-44. Retrieved from http://jpet.aspetjournals.org/content/332/2/336.long.

  28. Galve-Roperh, I., Sanchez, C., Cortes, M.L., Gomez del Pulgar, T., Izquiero, M., and Guzman, M. (2000, March). Anti-tumoral action of cannabinoids: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nature Medicine, 6(3), 313-9. Retrieved from http://www.nature.com/nm/journal/v6/n3/full/nm0300_313.html.

  29. Glodde, N., Jakobs, M., Bald, T., Tuting, T., and Gaffal, E. (2015, October 1). Differential role of cannabinoids in the pathogenesis of skin cancer. Life Sciences, 138, 35-40. Retrieved from http://www.sciencedirect.com/science/article/pii/S0024320515002209.

  30. Gómez Del Pulgar, T., De Ceballos, M.L., Guzmán, M., and Velasco, G. (2002, September). Cannabinoids Protect Astrocytes from Ceramide-induced Apoptosis through the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway. The Journal of Biological Chemistry, 277(30), 36527-33. Retrieved from http://www.jbc.org/content/277/39/36527.long.

  31. Guindon, J., and Hohmann, A. G. (2011). The endocannabinoid system and cancer: therapeutic implication. British Journal of Pharmacology, 163(7), 1447–1463. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165955/.

  32. Gustafsson, K., Christensson, B., Sander, B., and Fiygare, J. (2006, November). Cannabinoid Receptor-Mediated Apoptosis Induced by R(+)-Methanandamide and Win55,212-2 Is Associated with Ceramide Accumulation and p38 Activation in Mantle Cell Lymphoma. Molecular Pharmacology, 70(5), 1612-20. Retrieved from http://molpharm.aspetjournals.org/content/70/5/1612.long.

  33. Gustafsson, K., Wang, X., Severa, D., Eriksson, M., Kimby, E., Merup, M., Christensson, B., Flygare, J., and Sander, B. (2008, September 1). Expression of cannabinoid receptors type 1 and type 2 in non-Hodgkin lymphoma: growth inhibition by receptor activation. International Journal of Cancer, 123(5), 1025-33. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/ijc.23584/full.

  34. Gustafsson, K., Sander, B., Bielawski, J., Hannun, Y.A., and Flygare, J. (2009). Potentiation of cannabinoid-induced cytotoxicity in Mantle Cell Lymphoma through modulation of ceramide metabolism. Molecular Cancer Research : MCR, 7(7), 1086–1098. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077284/.

  35. Guzmán, M. (2003, October). Cannabinoids: potential anticancer agents? Nature Reviews, 3(10), 745-55. Retrieved from http://www.nature.com/nrc/journal/v3/n10/full/nrc1188.html.

  36. Guzmán, M. (2006). Cannabinoids: potential antitumoral agents? Cannabinoids, 1(2), 15-17. Retrieved from https://www.cannabis-med.org/data/pdf/en_2006_02_1.pdf.

  37. Guzmán, M., Duarte, M. J., Blázquez, C., Ravina, J., Rosa, M. C., Galve-Roperh, I., Sanchez, C., Velasco, G., and González-Feria, L. (2006). A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. British Journal of Cancer, 95(2), 197–203. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360617/.

  38. Guzmán, M., Galve-Roperh, I., and Sánchez, C. (2001, January). Ceramide: a new second messenger of cannabinoid action. Trends in Pharmacological Sciences, 22(1), 19-22. Retrieved from http://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(00)01586-8.

  39. Hamtiaux, L., Hansoulle, L., Dauguet, N., Muccioli, G.G., Gallez, B., and Lambert, D.M. (2011). Increasing Antiproliferative Properties of Endocannabinoids in N1E-115 Neuroblastoma Cells through Inhibition of Their Metabolism. PLoS ONE, 6(10), e26823. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203169/.

  40. Hanlon, K.E., Lozano-Ondoua, A.N., Umaretiya, P.J., Symons-Liguori, A.M., Chandramouli, A., Moy, J.K., Kwass, W.K., Mantyh, P., Nelson, M.A., and Vanderah, T. W. (2016). Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent. Breast Cancer : Targets and Therapy, 8, 59–71. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847606/.

  41. Hashibe, M., Morgenstern, H., Cui, Y., Tashkin, D.P., Zhang, Z.F., Cozen, W., Mack, T.M., and Greenland, S. (2006, October). Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case-control study. Cancer Epidemiology: Biomarkers & Prevention, 15(10), 1829-34. Retrieved from http://cebp.aacrjournals.org/content/15/10/1829.long.

  42. Hermanson, D.J., and Marnett, L.J. (2011). Cannabinoids, Endocannabinoids and Cancer. Cancer Metastasis Reviews, 30(3-4), 599–612. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366283/.

  43. Hernán Pérez de la Ossa, D., Gil-Alegre, M.E., Ligresti, A., del Rosario Aberturas, M., Molpeceres, J., Torres, A.I., and Di Marzo, V. (2013). Preparation and characterisation of biodegradable microparticles filled with THC and their antitumor efficacy on cancer cell lines. Journal of Drug Targeting, early online, 1-9. Retrieved from http://www.tandfonline.com/doi/full/10.3109/1061186X.2013.809089?needAccess=true.

  44. Herrera, B., Carracedo, A., Diez-Zaera, M., Gomez del Pulgar, T., Guzman, M., and Velasco, G. (2006, July 1). The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation of the mitochondrial intrinsic pathway. Experimental Cell Research, 312(11), 2121-31. Retrieved from http://www.sciencedirect.com/science/article/pii/S0014482706001066.

  45. Islam, T.C., Asplund, A.C., Lindvall, J.M., Nygren, L., Liden, J., Kimby, E., Christensson, B., Smith, C.I., Sander B. (2003, September). High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of Cyclin D1 in mantle cell lymphoma. Leukemia, 17(9), 1880-90. Retrieved from http://www.nature.com/leu/journal/v17/n9/full/2403057a.html.

  46. 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. and 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), 567-73. Retrieved from http://ascopubs.org/doi/full/10.1200/JCO.2002.20.2.567.

  47. Johnson, J.R., Burnell-Nugent, M., Lossignol, D., Ganae-Motan, E.D., Potts, R., and Fallon, M.T. (2010, February). 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), 167-79. Retrieved from http://www.jpsmjournal.com/article/S0885-3924(09)00787-8/pdf.

  48. Juknat, A., Pietr, M., Kozela, E., Rimmerman, N., Levy, R., Gao, F., Coppola, G., Geschwind, D., and Vogel, Z. (2013). Microarray and Pathway Analysis Reveal Distinct Mechanisms Underlying Cannabinoid-Mediated Modulation of LPS-Induced Activation of BV-2 Microglial Cells. PLoS ONE, 8(4), e61462. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634783/.

  49. Kogan, N.M. (2005, October). Cannabinoids and cancer. Mini Reviews in Medicinal Chemistry, 5(10), 941-52. Retrieved from http://www.eurekaselect.com/78957/article.

  50. Kogan, N.M., Blazquez, C., Alvarez, L., Gallily, R., Schlesinger, M., Guzman, M., and Mechoulam, R. (2006, July). A cannabinoid quinone inhibits angiogenesis by targeting vascular endothelial cells. Molecular Pharmacology, 70(1), 51-9. Retrieved from http://molpharm.aspetjournals.org/content/70/1/51.long.

  51. Kramer, J.L. (2015, March). Medical marijuana for cancer. CA: A Cancer Journal for Clinicians, 65(2), 109-22. Retrieved from http://onlinelibrary.wiley.com/doi/10.3322/caac.21260/full.

  52. Lakiotaki, E., Giaginis, C., Tolia, M., Alexandrou, P., Delladetsima, I., Giannopoulou, I., Kyrgias, G. Patsouris, E.., and Theocharis, S. (2015). Clinical Significance of Cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions. BioMed Research International, 2015, 839403. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619873/.

  53. Ligresti, A., Moriello, A.S., Starowicz, K., Matias, I., Pisanti, S., De Petrocellis, L., Laezza, C., Portella, G., Bifulco, M., and Di Marzo, V. (2006, September). Antitumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. Journal of Pharacologogy and Experimental Therapeutics, 318(3), 1375-87. Retrieved from http://jpet.aspetjournals.org/content/318/3/1375.long.

  54. Limebeer, C.L., and Parker, L.A. (1999, December 16). Delta-9-tetrahydrocannabinol interferes with the establishment and the expression of conditioned rejection reactions produced by cyclophosphamide: a rat model of nausea. Neuroreport, 10(19), 3769-72. Retrieved from http://journals.lww.com/neuroreport/pages/articleviewer.aspx?year=1999&issue=12160&article=00009&type=abstract.

  55. Maccarrone, M., Lorenzon, T., Bari, M., Melino, G., Finazzi-Agro, A. (2000, October 13). Anandamide induces apoptosis in human cells via vanilloid receptors. The Journal of Biological Chemistry, 275(41), 31938-45. Retrieved from http://www.jbc.org/content/275/41/31938.long.

  56. Machado Rocha, F.C., Stefano, S.C., De Cassia Haiek, R., Rosa Oliveira, L.M., and Da Silveira, D.X. (2008, September). Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. European Journal of Cancer Care, 17(5), 431-43. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1111/j.1365-2354.2008.00917.x/full.

  57. Maor, Y., Yu, J., Kuzontkoski, P.M., Dezube, B.J., Zhang, X., and Groopman, J.E. (2012). Cannabidiol Inhibits Growth and Induces Programmed Cell Death in Kaposi Sarcoma–Associated Herpesvirus-Infected Endothelium. Genes & Cancer, 3(7-8), 512–520. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527984/.

  58. 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., and McAllister, S.D. (2010, January). Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival. Molecular Cancer Therapy, 9(1), 180-189. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806496/.

  59. Massi, P., Solinas, M., Cinquina, V., and Parolaro, D. (2013). Cannabidiol as potential anticancer drug. British Journal of Clinical Pharmacology, 75(2), 303–312. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579246/?report=reader.

  60. McAllister S.D., Chan, C., Taft, R.J., Luu, T., Abood, M.E., Moore, D.H., Aldape, K., and Yount, G. (2005, August). Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. Journal of Neuro-oncology, 74(1), 31-40. Retrieved from http://link.springer.com/article/10.1007%2Fs11060-004-5950-2.

  61. McAllister, S.D., Christian, R.T., Horowitz, M.P., Garcia, A., and Desprez, P.Y. (2007, November). Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Molecular Cancer Therapeutics, 6(11), 2921-7. Retrieved from http://mct.aacrjournals.org/content/6/11/2921.long.

  62. McAllister, S.D., Murase, R., Christian, R.T., Lau, D., Zielinski, A.J., Allison, J., Almanza, C., Pakdel, A., Lee, J., Limbad, C., Liu, Y, Debs, R.J., Moore, D.H., and Desprez, P.Y. (2011, August). Pathways mediating the effects of cannabidiol on the reduction of breast cancer cell proliferation, invasion, and metastasis. Breast Cancer Research and Treatment, 129(1), 37-47. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3410650/.

  63. McAllister, S.D., Soroceanu, L., and Desprez, P.Y. (2015, June). The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids. Journal of Neuroimmune Pharmacology, 10(2), 255-67. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470774/.

  64. McKallip, R.J., Lombard, C., Fisher, M., Martin, B.R., Ryu, S., Grant, S., Nagarkatti, P.S., and Nagarkatti, M. (2002, July 15). Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease. Blood, 100(2), 627-34. Retrieved from http://www.bloodjournal.org/content/100/2/627.long?sso-checked=true.

  65. Montalbano, R., Honrath, B., Wissniowski, T. T., Elxnat, M., Roth, S., Ocker, M., Quint, K., Churin, Y, Roederfeld, M., Schroeder, D., Glebe, D., Roeb, E., and Fazio, P. D. (2016). Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells. Oncotarget, 7(15), 20312–20323. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991457/.

  66. Morelli, M.B., Offidani, M., Alesiani, F., Discepoli, G., Liberati, S., Olivieri, A., Santoni, M., Santoni, G., Leoni, P., and Nabissi, M. (2014, June 1). The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2. International Journal of Cancer, 134(11), 2534-46. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/ijc.28591/full.

  67. Moreno, E., Andradas, C., Medrano, M., Caffarel, M. M., Pérez-Gómez, E., Blasco-Benito, S., Gómez-Cañas, M., Pazos, M.R., Irving, A.J., Lluís, C., Canela, E.I., Fernández-Ruiz, J., Guzmán, M., McCormick, P.J., Sánchez, C. (2014). Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling. The Journal of Biological Chemistry, 289(32), 21960–21972. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139213/.

  68. Murase, R., Kawamura, R., Singer, E., Pakdel, A., Sarma, P., Judkins, J., Elwakeel, E., Dayal, S., Martinez-Martinez, E., Amere, M., Gujjar, R., Mahadevan, A., Desprez, P.Y., and McAllister, S. D. (2014). Targeting multiple cannabinoid anti-tumour pathways with a resorcinol derivative leads to inhibition of advanced stages of breast cancer. British Journal of Pharmacology, 171(19), 4464–4477. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209152/.

  69. Nakajima, J., Nakae, D., and Yasukawa, K. (2013, August). Structure-dependent inhibitory effects of synthetic cannabinoids against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and skin tumour promotion in mice. Journal of Pharmacy and Pharmacology, 65(8), 1223-1230. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1111/jphp.12082/full.

  70. Nauck, F., Klaschik,E. (2004, June). Cannabinoids in the treatment of the cachexia-anorexia syndrome in palliative care patients. Schmerz, 18(3), 197-202. Retrieved from http://www.jpsmjournal.com/article/S0885-3924(05)00063-1/pdf.

  71. Niu, F., Zhao, S., Xu, C.Y., Sha, H., Bi, G.B., Chen, L., Ye, L., Gong, P., and Nie, T.H. (2015). Potentiation of the antitumor activity of adriamycin against osteosarcoma by cannabinoid WIN-55,212-2. Oncology Letters, 10(4), 2415–2421. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580018/.

  72. Oesch, S., Walter ,D., Wachtel, M., Pretre, K., Salazar, M., Guzmán, M., Velasco, G., and Schäfer, B.W. (2009, July). Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma. Molecular Cancer Therapy, 8(7), 1838-45. Retrieved from http://mct.aacrjournals.org/content/8/7/1838.long.

  73. Oesch, S., and Gertsch, J. (2009, July). Cannabinoid receptor ligands as potential anticancer agents – high hopes for new therapies? The Journal of Pharmacy and Pharmacology, 61(7), 839-53. Retrieved from http://onlinelibrary.wiley.com/doi/10.1211/jpp.61.07.0002/pdf.

  74. Orellana-Serradell, O., Poblete, C.E., Sanchez, C., Castellon, E.A., Gallegos, I., Huidobro, C., Llanos, M.N., and Contreras, H.R. (2015, April). Proapoptotic effect of endocannabinoids in prostate cancer cells. Oncology Reports, 33(4), 1599-608. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358087/.

  75. Parker, L.A., Rock, E.M., and Limbeer, C.L. (2011, August). Regulation of nausea and vomiting by cannabinoids. British Journal of Pharmacology, 163(7), 1411-22. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883513/.

  76. Pisanti, S., Borselli, C., Oliviero, O., Laezza, C., Gazzerro, P., Bifulco, M. (2007, May). Antiangiogenic activity of the endocannabinoid anandamide: Correlation to its tumor-suppressor efficacy. Journal of Cellular Physiology, 211(2), 495-503. Retrieved from http://onlinelibrary.wiley.com/wol1/doi/10.1002/jcp.20954/full.

  77. Preet, A., Ganju, R.K.., and Groopman, J.E. (2008, January). Δ9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene, 27(3), 339-46. Retrieved from http://www.nature.com/onc/journal/v27/n3/full/1210641a.html.

  78. Preet, A., Qamri, Z., Nasser, M.W., Prasad, A., Shilo, K., Zou, X., Groopman, J.E., and Ganju, R.K. (2011). Cannabinoid Receptors, CB1 and CB2, as Novel Targets for Inhibition of Non-Small Cell Lung Cancer Growth and Metastasis. Cancer Prevention Research (Philadelphia, Pa.), 4(1), 65–75. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025486/.

  79. Qamri, Z., Preet, A., Nasser, M.W., Bass, C.E., Leone, G., Barsky, S.H., and Ganju, R.K. (2009). Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Molecular Cancer Therapeutics, 8(11), 3117–3129. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128286/.

  80. Ramer, R., and Hinz, B. (2008, January). Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1. Journal of the National Cancer Institute, 100(1), 59-69. Retrieved from https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djm268.

  81. Ramer, R., Heinemann, K., Merkord, J., Rohde, H., Salamon, A., Linnebacher, M., and Hinz, B. (2013, January). COX-2 and PPAR-g Confer Cannabidiol-Induced Apoptosis of Human Lung Cancer Cells. Molecular Cancer Therapeutics, 12(1), 69-82. Retrieved from http://mct.aacrjournals.org/content/12/1/69.long.

  82. Ramer, R., Merkord, J., Rohde, H., and Hinz, B. (2010, April 1). Cannabidiol Inhibits Cancer Cell Invasion Via Upregulation Of Tissue Inhibitor Of Matrix Metalloproteinases-1. Biochemical Pharmacology, 79(7), 955-66. Retrieved from http://www.sciencedirect.com/science/article/pii/S000629520900971X.

  83. Ramer, R., Bublitz, K., Freimuth, N., Merkord, J., Rohde, H., Haustein, M., Borchert, P., Schmuhl, E., Linnebacher, M., and Hinz, B. (2012, April). Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1. FASEB Journal, 26(4), 1535-48. Retrieved from http://www.fasebj.org/content/26/4/1535.long.

  84. Ramos, J.A., and Bianco, F.J. (2012). The role of cannabinoids in prostate cancer: Basic science perspective and potential clinical applications. Indian Journal of Urology : IJU : Journal of the Urological Society of India, 28(1), 9–14. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751914/.

  85. Ruhaak, L.R., Feith, J., Karlsson, P.C., Rafter, J.J., Verpoorte, R., and Rohlin, L. (2011). Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biological & Pharmaceutical Bulletin, 34(5), 774-8. Retrieved from https://www.jstage.jst.go.jp/article/bpb/34/5/34_5_774/_pdf.

  86. Sarfaraz, S., Adhami, V.M., Syed, D.N., Afaq, F., and Mukhtar, H. (2008, January). Cannabinoids for Cancer Treatment: Progress and Promise. Cancer Research, 68(2). Retrieved from http://cancerres.aacrjournals.org/content/68/2/339.

  87. Scott, K.A., Shah, S., Dalgleish, A.G., and Liu, W.M. (2013, October). Enhancing the activity of cannabidiol and other cannabinoids in vitro through modifications to drug combinations and treatment schedules. Anticancer Research, 33(10), 4373-80. Retrieved from http://ar.iiarjournals.org/content/33/10/4373.long.

  88. Scott, K.A., Dalgleish, A.G., and Liu, W.M. (2014, November 14). The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Molecular Cancer Therapeutics, doi: 10.1158/1535-7163.MCT-14-0402. Retrieved from http://mct.aacrjournals.org/content/13/12/2955.long.

  89. Shrivastava, A., Kuzontkoski, P.M., Groopman, J.E., and Prasad, A. (2011, July). Cannabidiol Induces Programmed Cell Death in Breast Cancer Cells by Coordinating the Cross-talk between Apoptosis and Autophagy. Molecular Cancer Therapeutics, 10(7), 1161-72. Retrieved from http://mct.aacrjournals.org/content/10/7/1161.long.

  90. Singh, Y., and Bali, C. (2013). Cannabis Extract Treatment for Terminal Acute Lymphoblastic Leukemia with a Philadelphia Chromosome Mutation. Case Reports in Oncology, 6(3), 585–592. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901602/.

  91. Solinas, M., Massi, P., Cantelmo, A., Cattaneo, M., Cammarota, R., Bartolini, D., Cinquina, V., Valenti, M., Vicentini, L.M., Noonan, D.M., Albini, A., and Parolaro, D. (2012). Cannabidiol inhibits angiogenesis by multiple mechanisms. British Journal of Pharmacology, 167(6), 1218–1231. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504989/.

  92. Soroceanu, L., Murase, R., Limbad, C., Singer, E., Allison, J., Adrados, I., Kawamura, R., Pakdel, A., Fukuyo, Y., Nguyen, D., Khan, S., Arauz, R., Yount, G.L., Moore, D.H., Desprez, P.Y., and McAllister, S.D. (2013). Id-1 is a Key Transcriptional Regulator of Glioblastoma Aggressiveness and a Novel Therapeutic Target. Cancer Research, 73(5), 1559–1569. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594064/.

  93. Takeda, S., Okazaki, H., Ikeda, E., Abe, S., Yoshioka, Y, Watanabe, K., and Aramaki, H. (2014). Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells. The Journal of Toxicological Sciences, 39(5), 711-6. Retrieved from https://www.jstage.jst.go.jp/article/jts/39/5/39_711/_pdf.

  94. Takeda, S., Himeno, T., Kakizoe, K., Okazaki, H., Okada, T., Watanabe, K., and Aramaki, H. (2016, August 16). Cannabidiolic acid-mediated selective down-regulation of c-fos in highly aggressive breast cancer MDA-MB-231 cells: possible involvement of its down-regulation in the abrogation of aggressiveness. Journal of Natural Medicines, [Epub ahead of print], doi: 10.1007/s11418-016-1030-0. Retrieved from http://link.springer.com/article/10.1007%2Fs11418-016-1030-0.

  95. Tegeder, I. (2016). Endocannabinoids as Guardians of Metastasis. International Journal of Molecular Sciences, 17(2), 230. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783962/.

  96. Van Dross, R., Soliman, E., Jha, S., Johnson, T., and Mukhopadhyay, S. (2013). Receptor-dependent and Receptor-independent Endocannabinoid Signaling: A Therapeutic Target for Regulation of Cancer Growth. Life Sciences, 92(0), 463–466. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226396/.

  97. Vara, D., Salazar, M., Olea-Herrero, N., Guzmán, M., Velasco, G., and Díaz-Laviada, I. (2011). Anti-tumoral action of cannabinoids on hepatocellular carcinoma: role of AMPK-dependent activation of autophagy. Cell Death and Differentiation, 18(7), 1099–1111. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131949/.

  98. Vara, D., Morell, C., Rodríguez-Henche, N., and Diaz-Laviada, I. (2013). Involvement of PPARγ in the antitumoral action of cannabinoids on hepatocellular carcinoma. Cell Death & Disease, 4(5), e618–. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674350/.

  99. Velasco, G., Galve-Roperh, I., Sánchez, C., Blázquez, C., Haro, A., and Guzmán, M. (2005, August 19). Cannabinoids and ceramide: two lipids acting hand-by-hand. Life Sciences, 77(14), 1723-31. Retrieved from http://www.sciencedirect.com/science/article/pii/S0024320505005035.

  100. Velasco, G., Sanchez, C., and Guzman, M. (2012, May 4). Towards the use of cannabinoids as antitumour agents. Nature Reviews. Cancer, 12(6), 436-44. Retrieved from http://www.nature.com/nrc/journal/v12/n6/full/nrc3247.html.

  101. Velasco, G., Sanchez, C., and Guzman, M. (2015). Endocannabinoids and cancer. Handbook of Experimental Pharmacology, 231, 449-72. Retrieved from http://link.springer.com/chapter/10.1007%2F978-3-319-20825-1_16.

  102. Velasco, G., Sánchez, C., and Guzmán, M. (2016). Anticancer mechanisms of cannabinoids. Current Oncology, 23(Suppl 2), S23–S32. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791144/.

  103. Velasco, G., Hernanez-Tiedra, S., Davila, D., and Lorente, M. (2016, January 4). The use of cannabinoids as anticancer agents. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 64, 259-66. Retrieved from http://www.sciencedirect.com/science/article/pii/S0278584615001190.

  104. Wang, D., Wang, H., Ning, W., Backlund, M.G., Dey, S.K., and DuBois, R.N. (2008). Loss of cannabinoid receptor 1 accelerates intestinal tumor growth. Cancer Research, 68(15), 6468–6476. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2561258/.

  105. What Is Cancer? (2015, April 15). American Cancer Society. Retrieved from http://www.cancer.org/cancer/cancerbasics/what-is-cancer.

  106. What Is Cancer? (2015, February 9). National Cancer Institute. Retrieved from http://www.cancer.gov/about-cancer/what-is-cancer.

  107. Wilkie, G., Sakr, B., and Rizack, T. Medical Marijuana Use in Oncology. JAMA Oncology, 2(5), 670-675. Retrieved from http://jamanetwork.com/journals/jamaoncology/fullarticle/2504173.

  108. Wilsey, B., Marcotte, T., Deutsch, R., Gouaux, B., Sakai, S., and Donaghe, H. (2013, February). Low-dose vaporized cannabis significantly improves neuropathic pain. The Journal of Pain, 14(2), 136-48. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566631/.

  109. Xian, X.S., Park, H., Choi, M.G., and Park, J.M (2013, June) Cannabinoid Receptor Agonist as an Alternative Drug in 5-Fluorouracil-resistant Gastric Cancer Cells. Anticancer Research, 33(6), 2541-7. Retrieved from http://ar.iiarjournals.org/content/33/6/2541.long.

  110. Xie, C., Liu, G., Liu, J., Huang, Z., Wang, F., Lei, X., Wu, X., Huang, S., Zhong, D., and XU, X. (2012). Anti-proliferative effects of anandamide in human hepatocellular carcinoma cells. Oncology Letters, 4(3), 403–407. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439105/.

  111. Zhang, J., Medina-Cleghorn, D., Bernal-Mizrachi, L., Bracci, P.M., Hubbard, A., Conde, L., Riby, J., Nomura, D.K., and Skibola, C. F. (2016). The potential relevance of the endocannabinoid, 2-arachidonoylglycerol, in diffuse large B-cell lymphoma. Oncoscience, 3(1), 31–41. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751914/.

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