A Comprehensive Review of Cannabis in Patients with Cancer: Availability in the USA, General Efficacy, and Safety

Abstract

Purpose of Review

As the legalization of medical cannabis continues across the USA, oncology care providers will be increasingly asked to provide recommendations regarding its use in the cancer setting. In this article, we review recent literature that analyzes cannabis use specifically in patients with cancer and provide an accessible guide for clinicians, researchers, and patients.

Recent Findings

We aimed to answer questions about the availability of cannabis in the USA, the trials supporting its use in the cancer setting, and the important factors to consider related to safety. Thirty states plus the District of Columbia have established comprehensive medical cannabis programs, each with different regulations and products available. In June 2018, Epidiolex, a cannabis extraction product containing 99% CBD, was approved to treat refractory seizures; however, whole-plant products and non-prescription extraction products dominate the market. Recent randomized, placebo-controlled studies of nabiximols (Sativex) in patients with refractory cancer-pain have largely shown no significant benefits. Conversely, large observational studies suggest patients with cancer using cannabis report significant improvement of many common symptoms. Cannabis use appears well tolerated, with few serious adverse effects reported.

Summary

Though prospective clinical trials are needed to provide the robust data required to establish the proper role of cannabinoid and cannabis-based therapy in cancer patients, physicians can draw upon the knowledge currently available to have informed discussions with their patients.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.

    •• Pergam SA, et al. Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use. Cancer. 2017;123(22):4488–97 This recent publication analyzes survey data from 926 responding patients in Washington State. The findings point toward significant usage across patient backgrounds, the importance of legalization in the choice to use cannabis, and the desire for more information for clinicians.

    CAS  Article  Google Scholar 

  2. 2.

    •• Braun IM, et al. Medical oncologists’ beliefs, practices, and knowledge regarding marijuana used therapeutically: a nationally representative survey study. J Clin Oncol. 2018;36(19):1957–62 In a national survey send to 400 medical oncologists, Braun et al. analyze the beliefs of oncologists regarding medical cannabis and its use among cancer patients. Of the 63% who replied, only 30% felt they had adequate information to make clinical recommendations; however, almost 50% make recommendations to patients for medical cannabis. Further research, education, and policies are needed to increase clinician knowledge of cannabis.

    Article  Google Scholar 

  3. 3.

    Zylla, D., et al., Oncology clinicians and the Minnesota Medical Cannabis Program: a survey on medical cannabis practice patterns, barriers to enrollment, and educational needs. 2018. Under Review. Abstract at https://dspace.library.colostate.edu/bitstream/handle/10217/189670/ICR2018_program.pdf?sequence=1&isAllowed=y.

  4. 4.

    Wilkie G, Sakr B, Rizack T. Medical marijuana use in oncology: a review. JAMA Oncol. 2016. https://doi.org/10.1001/jamaoncol.2016.0155.

  5. 5.

    Abrams DI. Integrating cannabis into clinical cancer care. Curr Oncol. 2016;23(2):S8–S14.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    • Kramer JL. Medical marijuana for cancer. CA Cancer J Clin. 2015;65(2):109–22 This thorough review has over 151 citations that outline the potential benefits of cannabis for treating cancer-related symptoms, its role in fighting cancer, and potential dangers of cannabis usage. Similar to our paper, this review focuses on clinical trials rather than the underlying mechanism.

    Article  Google Scholar 

  7. 7.

    http://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx . This website from the National Conference of State Legislatures provides comprehensive yet understandabale outline of the laws regarding cannabis usage in states that have legalized it in addition to those with pending proposals. This website is consistently updated, and provides links directly to government proposals for those that seek futher information.

  8. 8.

    •• National Academies of Sciences, E., and Medicine, The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. 2017. This book is perhaps the most comprehensive look at cannabis research as of 2017. Numerous health effects, both positive and negative, are analyzed and ranked based on the amount of evidence to support them. While a lot of quality research is included, a consistent theme is the need for more research.

  9. 9.

    Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. 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. J Pain Symptom Manag. 2010;39(2):167–79.

    Article  Google Scholar 

  10. 10.

    Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012;13(5):438–49.

    CAS  Article  Google Scholar 

  11. 11.

    Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT. 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. J Pain Symptom Manag. 2013;46(2):207–18.

    Article  Google Scholar 

  12. 12.

    Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manag. 2014;47(1):166–73.

    Article  Google Scholar 

  13. 13.

    •• Fallon MT, et al. 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. Br J Pain. 2017;11(3):119–33 This manuscirpt describes results from two well-conducted trials that compare sativex to placebo in managing cancer-related pain. Of note, 399 patients were randomized in study 1, and 216 were randomized in study 2. Across this large sample size, the researchers arrived at the conclusion that sativex was unable to effectively provide analgesia compared to placebo. However, it was more effective specifically amongst the younger patients, and those from the United States, which may point to the varying efficacy of cannabis.

    Article  Google Scholar 

  14. 14.

    Lichtman AH, Lux EA, McQuade R, Rossetti S, Sanchez R, Sun W, et al. 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. J Pain Symptom Manag. 2018;55(2):179–88 e1.

    Article  Google Scholar 

  15. 15.

    Zutt M, Hänßle H, Emmert S, Neumann C, Kretschmer L. Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases. Hautarzt. 2006;57(5):423–7.

    CAS  Article  Google Scholar 

  16. 16.

    Meiri E, Jhangiani H, Vredenburgh JJ, Barbato LM, Carter FJ, Yang HM, et al. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin. 2007;23(3):533–43.

    CAS  Article  Google Scholar 

  17. 17.

    Duran M, Pérez E, Abanades S, Vidal X, Saura C, Majem M, et al. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol. 2010;70(5):656–63.

    CAS  Article  Google Scholar 

  18. 18.

    Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a north central cancer treatment group study. J Clin Oncol. 2002;20(2):567–73.

    CAS  Article  Google Scholar 

  19. 19.

    Walsh, D., J. Kirkova, and M.P. Davis, The efficacy and tolerability of long-term use of dronabinol in cancer-related anorexia: a case series, in J Pain Symptom Manage. 2005: United States. p. 493–5.

  20. 20.

    Cannabis In Cachexia Study, G, et al. 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. J Clin Oncol. 2006;24(21):3394–400.

    Article  Google Scholar 

  21. 21.

    Maida V, Ennis M, Irani S, Corbo M, Dolzhykov M. Adjunctive nabilone in cancer pain and symptom management: a prospective observational study using propensity scoring. J Support Oncol. 2008;6(3):119–24.

    CAS  PubMed  Google Scholar 

  22. 22.

    Brisbois TD, de Kock IH, Watanabe SM, Mirhosseini M, Lamoureux DC, Chasen M, et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol. 2011;22(9):2086–93.

    CAS  Article  Google Scholar 

  23. 23.

    Bar-Sela G, et al. The medical necessity for medicinal cannabis: prospective, observational study evaluating the treatment in cancer patients on supportive or palliative care. Evid Based Complement Alternat Med. 2013;2013:510392.

    Article  Google Scholar 

  24. 24.

    • Cote M, et al. Improving quality of life with nabilone during radiotherapy treatments for head and neck cancers: a randomized double-blind placebo-controlled trial. Ann Otol Rhinol Laryngol. 2016;125(4):317–24 This study of 56 patients with head and neck cancers compares the effectiveness of nabilone versus placebo in managing symptom burden related to treatment. It was found that quality of life was not improved with nabilone; however, patients did not have the ability to individually titrate to their desired dosage.

    Article  Google Scholar 

  25. 25.

    •• Bar-Lev Schleider L, et al. Prospective analysis of safety and efficacy of medical cannabis in large unselected population of patients with cancer. Eur J Intern Med. 2018;49:37–43 This large study analyzes data regarding cannabis usage among 2970 cancer patients in Israel. The researchers conclude that cannabis is effective in the palliative setting, with a quality of life scores improving from 20% (at baseline) to 70% (after six months taking cannabis). Beyond effectiveness, this paper provides valuable information regarding the demographics of this population, including cancer diagnosis, comorbidities, and other measures.

    Article  Google Scholar 

  26. 26.

    Zhang H, et al. Association of marijuana use with psychosocial and quality of life outcomes among patients with head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2018. https://doi.org/10.1001/jamaoto.2018.0486.

  27. 27.

    Anderson, S., et al., Impact of medical cannabis on patient-reported symptoms for cancer patients enrolled in Minnesota’s Medical Cannabis Program. Under Review, Abstract at. 2018. https://dspace.library.colostate.edu/bitstream/handle/10217/189670/ICR2018_program.pdf?sequence=1&isAllowed=y. Accessed 16 August 2018.

  28. 28.

    Guzman M, et al. A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. Br J Cancer. 2006;95(2):197–203.

    CAS  Article  Google Scholar 

  29. 29.

    Foroughi M, Hendson G, Sargent MA, Steinbok P. Spontaneous regression of septum pellucidum/forniceal pilocytic astrocytomas—possible role of Cannabis inhalation. Childs Nerv Syst. 2011;27(4):671–9.

    Article  Google Scholar 

  30. 30.

    Singh Y, Bali C. Cannabis extract treatment for terminal acute lymphoblastic leukemia with a Philadelphia chromosome mutation. Case Rep Oncol. 2013;6(3):585–92.

    Article  Google Scholar 

  31. 31.

    Twelves C, et al. 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). J Clin Oncol. 2017;35(15_suppl):2046-2046.

    Article  Google Scholar 

  32. 32.

    https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf. Access 16 August 2018.

  33. 33.

    https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018677s011lbl.pdf. Accessed 16 August 2018.

  34. 34.

    Pisanti S, Malfitano AM, Ciaglia E, Lamberti A, Ranieri R, Cuomo G, et al. Cannabidiol: state of the art and new challenges for therapeutic applications. Pharmacol Ther. 2017;175:133–50.

    CAS  Article  Google Scholar 

  35. 35.

    https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm. Accessed 16 August 2018.

  36. 36.

    https://leaflinelabs.com/our-medication/. Accessed August 16 2018.

  37. 37.

    https://minnesotamedicalsolutions.com/wp-content/uploads/2018/04/MinnMed-Price-List_4.24.18.pdf. Accessed 16 August 2018.

  38. 38.

    Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770–804.

    CAS  Article  Google Scholar 

  39. 39.

    https://www.nytimes.com/2016/07/15/science/how-much-weed-is-in-a-joint-pot-experts-have-a-new-estimate.html. Accessed 18 August 2018.

  40. 40.

    https://www.webmd.com/pain-management/news/20180507/cbd-oil-all-the-rage-but-is-it-safe-effective#1. Accessed 16 August 2018.

  41. 41.

    https://www.forbes.com/sites/oracle/2018/08/07/with-artificial-intelligence-sometimes-less-is-more/#6426273b6dfe. Accessed 16 August 2018.

  42. 42.

    Bonn-Miller MO, Loflin MJE, Thomas BF, Marcu JP, Hyke T, Vandrey R. Labeling accuracy of cannabidiol extracts sold online. JAMA. 2017;318(17):1708–9.

    Article  Google Scholar 

  43. 43.

    https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm484109.htm. Accessed 16 August 2018.

  44. 44.

    Piper BJ, Beals ML, Abess AT, Nichols SD, Martin MW, Cobb CM, et al. Chronic pain patients’ perspectives of medical cannabis. Pain. 2017;158:1373–9.

    Article  Google Scholar 

  45. 45.

    https://www.businessinsider.com/cost-first-fda-approved-marijuana-medication-epidiolex-2018-8. Accessed 16 August 2018.

  46. 46.

    Pain S. A potted history. Nature. 2015;525(7570). https://www.nature.com/articles/525S10a.

  47. 47.

    Noyes R Jr, Brunk SF, Avery DH, Canter A. The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Clin Pharmacol Ther. 1975;18(1):84–9.

    Article  Google Scholar 

  48. 48.

    Noyes R Jr, et al. Analgesic effect of delta-9-tetrahydrocannabinol. J Clin Pharmacol. 1975;15(2–3):139–43.

    Article  Google Scholar 

  49. 49.

    Sallan SE, Zinberg NE, Frei E 3rd. Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med. 1975;293(16):795–7.

    CAS  Article  Google Scholar 

  50. 50.

    Kluin-Neleman JC, Neleman FA, Meuwissen OJ, Maes RA. Delta 9-tetrahydrocannabinol (THC) as an antiemetic in patients treated with cancerchemotherapy; a double-blind cross-over trial against placebo. Vet Hum Toxicol. 1979;21(5):338–40.

    CAS  PubMed  Google Scholar 

  51. 51.

    Todaro B. Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting. J Natl Compr Cancer Netw. 2012;10(4):487–92.

    CAS  Article  Google Scholar 

  52. 52.

    Chakravarti B, Ravi J, Ganju RK. Cannabinoids as therapeutic agents in cancer: current status and future implications. Oncotarget. 2014;5(15):5852–72.

    Article  Google Scholar 

  53. 53.

    Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA. Antineoplastic activity of cannabinoids. J Natl Cancer Inst. 1975;55(3):597–602.

    CAS  Article  Google Scholar 

  54. 54.

    Abrams DI, Guzman M. Cannabis in cancer care. Clin Pharmacol Ther. 2015;97(6):575–86.

    CAS  Article  Google Scholar 

  55. 55.

    Blake A, et al. A selective review of medical cannabis in cancer pain management. Ann Palliat Med. 2017. https://doi.org/10.21037/apm.2017.08.05.

  56. 56.

    Maida V, Daeninck PJ. A user’s guide to cannabinoid therapies in oncology. Curr Oncol. 2016;23(6):398–406.

    CAS  Article  Google Scholar 

  57. 57.

    https://www.hhs.gov/opioids/about-the-epidemic/index.html. Accessed August 16, 2018.

  58. 58.

    Elikkottil J, Gupta P, Gupta K. The analgesic potential of cannabinoids. J Opioid Manag. 2009;5(6):341–57.

    Article  Google Scholar 

  59. 59.

    • Bradford AC, et al. Association between US State Medical Cannabis Laws and Opioid Prescribing in the Medicare Part D Population. JAMA Intern Med. 2018;178(5):667–72 Demonstrates that the legalization of medical cannabis is associated with a statistically significant decrease in the prescription of opioids, specifically by looking at data from the Medicare Part D population. There was a greater decrease in opioid prescriptions in states that had more permissive dispensaries. This is a significant finding as doctors, policymakers, and the general public look to combat the opioid epidemic.

    Article  Google Scholar 

  60. 60.

    Bachhuber MA, Saloner B, Cunningham CO, Barry CL. Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999-2010. JAMA Intern Med. 2014;174(10):1668–73.

    Article  Google Scholar 

  61. 61.

    http://www.health.state.mn.us/topics/cannabis/about/ipreport.pdf. Accessed 16 August 2018. See Page 7.

  62. 62.

    •• https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/all. Accessed 16 August 2018. This government website is the premier location to find up-to-date information regarding medical cannabis in the cancer population. Individualized sections provide citations and analysis for a variety of symptoms. With a simple click, the page becomes the “patient version”, which is a useful resource to provide patients.

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Acknowledgments

The authors thank Justin Eklund, Aminah Jatoi, and Mary Van Beusekom for their critical review of this manuscript.

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Correspondence to Dylan Zylla.

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Steele, G., Arneson, T. & Zylla, D. A Comprehensive Review of Cannabis in Patients with Cancer: Availability in the USA, General Efficacy, and Safety. Curr Oncol Rep 21, 10 (2019). https://doi.org/10.1007/s11912-019-0757-7

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Keywords

  • Cannabis
  • Marijuana
  • Cancer
  • Palliative care