Vol 15, No 2 (2021)
Review paper
Published online: 2021-06-30

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The role of cannabinoids in the management of symptoms in palliative care patients

Michał Graczyk1, Wojciech Leppert2
Palliat Med Pract 2021;15(2):182-191.


The endocannabinoid system (ECS) regulates body’s homeostasis and performs vital physiological functions. The thorough understanding of the role of endocannabinoids and the composition of cannabis containing phytocannabinoids and terpenoids play an important role in symptom management. Clinical effects of medical cannabis depend among others on the activity of the ECS in a given patient, the proportion of phytocannabinoids, and the doses used. Cannabinoids are used to treat symptoms in patients with cancer and chronic non-malignant diseases. Cannabinoids are usually not drugs of first choice and can be added to basic pharmacotherapy, which often improves the effectiveness of symptom treatment. Due to limited scientific evidence, experimental studies on the role of the ECS and clinical trials on the use of cannabinoids in the treatment of symptoms are recommended. In this article the role of the ECS and the use of cannabinoids in palliative care patients has been discussed.

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  1. Moreira FA, Lutz B. The endocannabinoid system: emotion, learning and addiction. Addict Biol. 2008; 13(2): 196–212.
  2. Woroń J, Przeklasa-Muszyńska A, Dobrogowski J. Kannabinoidy w leczeniu bólu w 2019 roku, co wiemy, a czego jeszcze powinniśmy się dowiedzieć. Terapia. 2019; 278: 41–46.
  3. Müller-Vahl KR, Schneider U, Koblenz A, et al. Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial. Pharmacopsychiatry. 2002; 35(2): 57–61.
  4. Koppel BS, Brust JCM, Fife T, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2014; 82(17): 1556–1563.
  5. Di Marzo V, Bifulco M, De Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov. 2004; 3(9): 771–784.
  6. Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006; 58(3): 389–462.
  7. Mackie K. Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb Exp Pharmacol. 2005(168): 299–325.
  8. Laprairie RB, Bagher AM, Kelly MEM, et al. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Br J Pharmacol. 2015; 172(20): 4790–4805.
  9. Castillo PE, Younts TJ, Chávez AE, et al. Endocannabinoid signaling and synaptic function. Neuron. 2012; 76(1): 70–81.
  10. Riebe CJ, Wotjak CT. Endocannabinoids and stress. Stress. 2011; 14(4): 384–397.
  11. Kwolek G, Zakrzeska A, Kozłowska H, et al. Wpływ anandamidu, endogennego agonisty receptorów kannabinoidowych na układ krążenia. Post Hig Med Dosw. 2005; 59: 208–218.
  12. Health Canada. Information for Health Care Professionals: Cannabis (marihuana, marijuana) and the cannabinoids. 2018. https://www.canada.ca/en/health-canada/services/drugs-medication/cannabis/information-medical-practitioners/information-health-care-professionals-cannabis-cannabinoids.html.
  13. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008; 153(2): 199–215.
  14. Starowicz K, Finn DP. Cannabinoids and Pain: Sites and Mechanisms of Action. Adv Pharmacol. 2017; 80: 437–475.
  15. Pisanti S, Malfitano AM, Ciaglia E, et al. Cannabidiol: State of the art and new challenges for therapeutic applications. Pharmacol Ther. 2017; 175: 133–150.
  16. Russo E, Guy GW. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses. 2006; 66(2): 234–246.
  17. Iseger TA, Bossong MG. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr Res. 2015; 162(1-3): 153–161.
  18. Izzo AA, Borrelli F, Capasso R, et al. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci. 2009; 30(10): 515–527.
  19. Alexander A, Smith PF, Rosengren RJ. Cannabinoids in the treatment of cancer. Cancer Lett. 2009; 285(1): 6–12.
  20. Fraguas-Sánchez AI, Martín-Sabroso C, Torres-Suárez AI. Insights into the effects of the endocannabinoid system in cancer: a review. Br J Pharmacol. 2018; 175(13): 2566–2580.
  21. Hermanson DJ, Marnett LJ. Cannabinoids, endocannabinoids, and cancer. Cancer Metastasis Rev. 2011; 30(3-4): 599–612.
  22. Dzierżanowski T. Prospects for the Use of Cannabinoids in Oncology and Palliative Care Practice: A Review of the Evidence. Cancers (Basel). 2019; 11(2).
  23. Pokrywka M, Góralska J, Solnica B. Kannabinoidy – nowy oręż do walki z nowotworami? Post Hig Med Dosw. 2016; 70: 1309–1320.
  24. De Petrocellis L, Ligresti A, Schiano Moriello A, et al. Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms. Br J Pharmacol. 2013; 168(1): 79–102.
  25. Ligresti A, Bisogno T, Matias I, et al. Possible endocannabinoid control of colorectal cancer growth. Gastroenterology. 2003; 125(3): 677–687.
  26. Velasco G, Sánchez C, Guzmán M. Towards the use of cannabinoids as antitumour agents. Nat Rev Cancer. 2012; 12(6): 436–444.
  27. Liang C, McClean MD, Marsit C, et al. A population-based case-control study of marijuana use and head and neck squamous cell carcinoma. Cancer Prev Res (Phila). 2009; 2(8): 759–768.
  28. Tashkin DP. Effects of marijuana smoking on the lung. Ann Am Thorac Soc. 2013; 10(3): 239–247.
  29. Tashkin DP, Baldwin GC, Sarafian T, et al. Respiratory and immunologic consequences of marijuana smoking. J Clin Pharmacol. 2002; 42(S1): 71S–81S.
  30. Calignano A, Kátona I, Désarnaud F, et al. Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature. 2000; 408(6808): 96–101.
  31. Tetrault JM, Crothers K, Moore BA, et al. Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med. 2007; 167(3): 221–228.
  32. Ramírez BG, Blázquez C, Gómez del Pulgar T, et al. Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci. 2005; 25(8): 1904–1913.
  33. Fernández-Ruiz J, Pazos MR, García-Arencibia M, et al. Role of CB2 receptors in neuroprotective effects of cannabinoids. Mol Cell Endocrinol. 2008; 286(1-2 Suppl 1): S91–S96.
  34. Petersen G, Moesgaard B, Schmid PC, et al. Endocannabinoid metabolism in human glioblastomas and meningiomas compared to human non-tumour brain tissue. J Neurochem. 2005; 93(2): 299–309.
  35. Campos AC, Fogaça MV, Scarante FF, et al. Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacol Res. 2016; 112: 119–127.
  36. Agar M. Medicinal cannabinoids in palliative care. Br J Clin Pharmacol. 2018; 84(11): 2491–2494.
  37. Martin JH, Cranswick N. Care and concern with cannabinoids used therapeutically. Br J Clin Pharmacol. 2018; 84(11): 2455–2457.
  38. Abrams DI, Guzman M. Cannabinoids and Cancer. In: Abrams DI, Weil AT. ed. Integrative Oncology. Oxford University Press, Oxford 2008: 147–170.
  39. Kirkham TC, Williams CM, Fezza F, et al. Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. Br J Pharmacol. 2002; 136(4): 550–557.
  40. Tramèr MR, Carroll D, Campbell FA, et al. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ. 2001; 323(7303): 16–21.
  41. Rock E, Sticht M, Limebeer C, et al. Cannabinoid Regulation of Acute and Anticipatory Nausea. Cannabis and Cannabinoid Research. 2016; 1(1): 113–121.
  42. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015; 313(24): 2456–2473.
  43. Antoun S, Morel H, Souquet PJ, et al. Euro-Impact. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011; 12(5): 489–495.
  44. Beal J, Olson R, Laubenstein L, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Journal of Pain and Symptom Management. 1995; 10(2): 89–97.
  45. Timpone JG, Wright DJ, Li N, et al. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative. AIDS Res Hum Retroviruses. 1997; 13(4): 305–315.
  46. Bar-Sela G, Vorobeichik M, Drawsheh S, 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.
  47. Brisbois TD, de Kock IH, Watanabe SM, 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): 2086–2093.
  48. Aggarwal SK. Cannabinergic pain medicine: a concise clinical primer and survey of randomized-controlled trial results. Clin J Pain. 2013; 29(2): 162–171.
  49. Russo EB, Hohmann AG. Role of Cannabinoids in Pain Management. In: Deer RT. ed. Comprehensive Treatment of Chronic Pain by Medical, Interventional, and Integrative Approaches. Springer, New York 2013: 181–197.
  50. Kendall D, Alexander S. Cannabinoid Pharmacology. Academic Press, Cambridge 2017.
  51. Grant I. Medicinal cannabis and painful sensory neuropathy. Virtual Mentor. 2013; 15(5): 466–469.
  52. Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007; 68(7): 515–521.
  53. Ware MA, Wang T, Shapiro S, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 2010; 182(14): E694–E701.
  54. Moulin D, Boulanger A, Clark AJ, et al. Canadian Pain Society. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014; 19(6): 328–335.
  55. Wordliczek J, Kotlińska-Lemieszek A, Leppert W, et al. Farmakoterapia bólu u chorych na nowotwory – zalecenia Polskiego Towarzystwa Badania u, Polskiego Towarzystwa Medycyny Paliatywnej, Polskiego Towarzystwa Onkologicznego, Polskiego Towarzystwa Medycyny Rodzinnej, Polskiego Towarzystwa Anestezjologii i Intensywnej Terapii. Ból. 2017; 18(3): 11–53.
  56. Wade DT, Makela P, Robson P, et al. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler. 2004; 10(4): 434–441.
  57. Portenoy RK, Ganae-Motan ED, Allende 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): 438–449.
  58. Boland EG, Bennett MI, Allgar V, et al. Cannabinoids for adult cancer-related pain: systematic review and meta-analysis. BMJ Support Palliat Care. 2020; 10(1): 14–24.
  59. Wallace M, Schulteis G, Atkinson JH, et al. Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers. Anesthesiology. 2007; 107(5): 785–796.
  60. Noyes R, Brunk SF, Baram DA, et al. Analgesic effect of delta-9-tetrahydrocannabinol. J Clin Pharmacol. 1975; 15(2-3): 139–143.
  61. Ward SJ, Ramirez MD, Neelakantan H, et al. Cannabidiol prevents the development of cold and mechanical allodynia in paclitaxel-treated female C57Bl6 mice. Anesth Analg. 2011; 113(4): 947–950.
  62. Abrams DI, Couey P, Shade SB, et al. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011; 90(6): 844–851.
  63. Nielsen S, Sabioni P, Trigo JM, et al. Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis. Neuropsychopharmacology. 2017; 42(9): 1752–1765.
  64. Cichewicz DL, Martin ZL, Smith FL, et al. Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. J Pharmacol Exp Ther. 1999; 289(2): 859–867.
  65. Cichewicz DL, McCarthy EA. Antinociceptive synergy between delta(9)-tetrahydrocannabinol and opioids after oral administration. J Pharmacol Exp Ther. 2003; 304(3): 1010–1015.
  66. Cichewicz DL. Synergistic interactions between cannabinoid and opioid analgesics. Life Sci. 2004; 74(11): 1317–1324.
  67. Cichewicz DL, Welch SP, Smith FL. Enhancement of transdermal fentanyl and buprenorphine antinociception by transdermal delta9-tetrahydrocannabinol. Eur J Pharmacol. 2005; 525(1-3): 74–82.
  68. Scavone JL, Sterling RC, Weinstein SP, et al. Impact of cannabis use during stabilization on methadone maintenance treatment. Am J Addict. 2013; 22(4): 344–351.
  69. Morena M, Patel S, Bains JS, et al. Neurobiological Interactions Between Stress and the Endocannabinoid System. Neuropsychopharmacology. 2016; 41(1): 80–102.
  70. Hillard CJ. Stress regulates endocannabinoid-CB1 receptor signaling. Semin Immunol. 2014; 26(5): 380–388.
  71. Hill MN, Patel S. Translational evidence for the involvement of the endocannabinoid system in stress-related psychiatric illnesses. Biol Mood Anxiety Disord. 2013; 3(1): 19.
  72. Leweke FM, Koethe D. Cannabis and psychiatric disorders: it is not only addiction. Addict Biol. 2008; 13(2): 264–275.
  73. Rey AA, Purrio M, Viveros MP, et al. Biphasic effects of cannabinoids in anxiety responses: CB1 and GABA(B) receptors in the balance of GABAergic and glutamatergic neurotransmission. Neuropsychopharmacology. 2012; 37(12): 2624–2634.
  74. Gieringer D, Rosenthal E, Carter G. (ed.). Marijuana Medical Handbook: Practical Guide to Therapeutic Uses of Marijuana. Quick Trading Co., Oakland, California 2008.
  75. Witkin JM, Tzavara ET, Nomikos GG. A role for cannabinoid CB1 receptors in mood and anxiety disorders. Behav Pharmacol. 2005; 16(5-6): 315–331.
  76. Moreira FA, Wotjak CT. Cannabinoids and anxiety. Curr Top Behav Neurosci. 2010; 2: 429–450.
  77. Graczyk M, Łukowicz M, Dzierzanowski T. Prospects for the Use of Cannabinoids in Psychiatric Disorders. Front Psychiatry. 2021; 12: 620073.
  78. Woroń J, Dobrogowski J. Rola kannabinoidow w leczeniu bólu. Med Paliat Prakt. 2017; 11(3): 96–101.
  79. Freeman T, Hindocha C, Baio G, et al. Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial. The Lancet Psychiatry. 2020; 7(10): 865–874.
  80. Act on counteracting drug addiction. (Journal of Laws of 2019 item 852).

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