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Pharmacological evidence of medicinal cannabis in oncology: a systematic review

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Abstract

Purpose

This systematic literature review examines research into the use of medicinal cannabis in cancer management. The aim was to identify the gaps in knowledge on the dose, dosing schedule and absorption of the administration routes of medicinal cannabis use in oncology.

Methods

A comprehensive search of the literature was conducted across six databases to identify original data reporting the pharmacology of medicinal cannabis in oncology.

Results

Eighteen articles were selected for review. Of the selected articles, ten were identified as randomised control trials, two experimental studies, two retrospective cohort studies and four case studies. Four articles reported absorption data and one drug interaction study was identified.

Conclusions

There is little evidence reported in the literature on the absorption of medicinal cannabis in cancer populations. Various reasons are explored for the lack of pharmacokinetic studies for medicinal cannabis in cancer populations, including the availability of assays to accurately assess cannabinoid levels, lack of clinical biomarkers and patient enrolment for pharmacokinetic studies.

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References

  1. Bridgeman MB, Abazia DT (2017) Medicinal cannabis: history, pharmacology, and implications for the acute care setting. Pharmacy Ther 42(3):180–188

    Google Scholar 

  2. Russo EB, Marcu J (2017) Cannabis pharmacology: the usual suspects and a few promising leads. Adv Pharmacol 80:67–134

    Article  CAS  PubMed  Google Scholar 

  3. Mechoulam R, Cannabinoids as Therapeutic Agents (1986) The pharmacohistory of cannabis sativa. CRC-Press

  4. Upton, R. American herbal pharmacopoeia®. 2017

    Google Scholar 

  5. Bogdanović V, Mrđanović J, Borišev I (2017) A review of the therapeutic antitumor potential of cannabinoids, vol 23

    Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Śledziński P, Zeyland J, Słomski R, Nowak A (2018) The current state and future perspectives of cannabinoids in cancer biology. Cancer Med 7(3):765–775

    Article  PubMed  PubMed Central  Google Scholar 

  8. Nabissi M, Morelli MB, 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

    Article  PubMed  PubMed Central  Google Scholar 

  9. Torres S, Lorente M, Rodriguez-Fornes F, Hernandez-Tiedra S, Salazar M, Garcia-Taboada E, Barcia J, Guzman M, Velasco G (2011) A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther 10(1):90–103

    Article  CAS  PubMed  Google Scholar 

  10. Liu WM, Scott KA, Shamash J, Joel S, Powles TB (2008) Enhancing the in vitro cytotoxic activity of Delta9-tetrahydrocannabinol in leukemic cells through a combinatorial approach. Leuk Lymphoma 49(9):1800–1809

  11. Scott KA, Shah S, Dalgleish AG, Liu WM (2013) Enhancing the activity of cannabidiol and other cannabinoids in vitro through modifications to drug combinations and treatment schedules. Anticancer Res 33(10):4373–4380

    CAS  PubMed  Google Scholar 

  12. International Agency for Research on Cancer (2014) World cancer report. World Health Organisation, Lyon

    Google Scholar 

  13. MacCallum CA, Russo EB (2018) Practical considerations in medical cannabis administration and dosing. Eur J Intern Med 49:12–19

    Article  CAS  PubMed  Google Scholar 

  14. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346(6284):561–564

    Article  CAS  PubMed  Google Scholar 

  15. Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365(6441):61–65

    Article  CAS  PubMed  Google Scholar 

  16. Gaoni Y, Mechoulam R (1964) Isolation, structure, and partial synthesis of an active constituent of hashish. J Am Chem Soc 86(8):1646–1647

    Article  CAS  Google Scholar 

  17. Russo EB (2011) Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol 163(7):1344–1364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zábranský, T., L. Hanuš, and R. Rokyta, Review of contemporary knowledge of the treatment effects of cannabis and related products and its outlook. 2017

    Google Scholar 

  19. Murillo-Rodríguez E (2017) The endocannabinoid system : genetics, biochemistry, brain disorders, and therapy. Elsevier Science, San Diego

    Google Scholar 

  20. Sharma P, Murthy P, Bharath MMS (2012) Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry 7(4):149–156

    PubMed  PubMed Central  Google Scholar 

  21. Huestis MA (2007) Human cannabinoid pharmacokinetics. Chem Biodivers 4(8):1770–1804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Grotenhermen F (2003) Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet 42(4):327–360

    Article  CAS  PubMed  Google Scholar 

  23. Turgeman I, Bar-Sela G (2017) Cannabis use in palliative oncology: a review of the evidence for popular indications. Israel Med Assoc J 19(2):85–88

    Google Scholar 

  24. Tateo S (2017) State of the evidence: cannabinoids and cancer pain-a systematic review. J Am Assoc Nurse Pract 29(2):94–103

    PubMed  Google Scholar 

  25. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Open Med 3(3):e123–e130

    PubMed  PubMed Central  Google Scholar 

  26. Reid R et al (2016) Complementary medicine use by the Australian population: a critical mixed studies systematic review of utilisation, perceptions and factors associated with use, vol 16

    Google Scholar 

  27. Moola S, Munn Z, Tufanaru C, Aromataris E, Sears K, Sfetcu R, Currie M, Qureshi R, Mattis P, MP-F LK (2017) Chapter 7: Systematic reviews of etiology and risk. Joanna Briggs Institute Reviewer’s Manual

  28. Tufanaru C, Munn Z, Aromataris E, Campbell J, Hopp L (2017) Chapter 3: Systematic reviews of effectiveness. Joanna Briggs Institute Reviewer’s Manual

  29. Engels FK, de Jong FA, Sparreboom A, Mathot RAA, Loos WJ, Kitzen JJEM, de Bruijn P, Verweij J, Mathijssen RHJ (2007) Medicinal cannabis does not influence the clinical pharmacokinetics of irinotecan and docetaxel. Oncologist 12(3):291–300

    Article  CAS  PubMed  Google Scholar 

  30. Duran M, Pérez E, Abanades S, Vidal X, Saura C, Majem M, Arriola E, Rabanal M, Pastor A, Farré M, Rams N, Laporte JR, Capellà D (2010) Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol 70(5):656–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Strasser F et al (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. J Clin Oncol 24:3394–3400. https://doi.org/10.1200/JCO.2005.05.1847

    Article  CAS  PubMed  Google Scholar 

  32. Brisbois TD, de Kock IH, Watanabe SM, Mirhosseini M, Lamoureux DC, Chasen M, MacDonald N, Baracos VE, Wismer WV (2011) Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol 22(9):2086–2093

    Article  CAS  PubMed  Google Scholar 

  33. Cote M et al (2016) 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 125(4):317–324

    Article  PubMed  Google Scholar 

  34. Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT (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. J Pain Symptom Manag 39(2):167–179

    Article  Google Scholar 

  35. Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT (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. J Pain Symptom Manag 46(2):207–218

    Article  CAS  Google Scholar 

  36. Lynch M, Cesar-Rittenberg P, Hohmann A (2014) 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 47:166–173. https://doi.org/10.1016/j.jpainsymman.2013.02.018

    Article  Google Scholar 

  37. Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S, McQuade R, Wright S, Fallon MT (2012) Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain 13(5):438–449

    Article  CAS  PubMed  Google Scholar 

  38. Foroughi M, Hendson G, Sargent MA, Steinbok P (2011) Spontaneous regression of septum pellucidum/forniceal pilocytic astrocytomas--possible role of Cannabis inhalation. Childs Nerv Syst 27(4):671–679

    Article  PubMed  Google Scholar 

  39. Meiri E, Jhangiani H, Vredenburgh JJ, Barbato LM, Carter FJ, Yang HM, Baranowski V (2007) Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin 23(3):533–543

    Article  CAS  PubMed  Google Scholar 

  40. Elder JJ, Knoderer HM (2015) Characterization of dronabinol usage in a pediatric oncology population. J Pediatr Pharmacol Ther 20(6):462–467

    PubMed  PubMed Central  Google Scholar 

  41. Hernandez SL, Sheyner I, Stover KT, Stewart JT (2015) Dronabinol treatment of refractory nausea and vomiting related to peritoneal carcinomatosis. Am J Hosp Palliat Care 32(1):5–7

    Article  PubMed  Google Scholar 

  42. Singh Y, Bali C (2013) Cannabis extract treatment for terminal acute lymphoblastic leukemia with a Philadelphia chromosome mutation. Case Rep Oncol 6(3):585–592

    Article  PubMed  PubMed Central  Google Scholar 

  43. Layeeque R, Siegel E, Kass R, Henry-Tillman RS, Colvert M, Mancino A, Klimberg VS (2006) Prevention of nausea and vomiting following breast surgery. Am J Surg 191(6):767–772

    Article  PubMed  Google Scholar 

  44. Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA, Pundaleeka S, Kardinal CG, Fitch TR, Krook JE, Novotny PJ, Christensen B (2002) Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a north central cancer treatment group study. J Clin Oncol 20(2):567–573

    Article  CAS  PubMed  Google Scholar 

  45. Maida V (2008) Nabilone for the treatment of paraneoplastic night sweats: a report of four cases. J Palliat Med 11(6):929–934

    Article  PubMed  Google Scholar 

  46. Ursino M, Zohar S, Lentz F, Alberti C, Friede T, Stallard N, Comets E (2017) Dose-finding methods for phase I clinical trials using pharmacokinetics in small populations. Biom J 59(4):804–825

    Article  PubMed  PubMed Central  Google Scholar 

  47. Stout SM, Cimino NM (2014) Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev 46(1):86–95

    Article  CAS  PubMed  Google Scholar 

  48. Zgair A, Lee JB, Wong JCM, Taha DA, Aram J, di Virgilio D, McArthur JW, Cheng YK, Hennig IM, Barrett DA, Fischer PM, Constantinescu CS, Gershkovich P (2017) Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation. Sci Rep 7(1):14542

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Hryhorowicz S et al (2017) Pharmacogenetics of cannabinoids. Eur J Drug Metab Pharmacokinet:1–12

  50. Vandrey R, Herrmann ES, Mitchell JM, Bigelow GE, Flegel R, LoDico C, Cone EJ (2017) Pharmacokinetic profile of oral cannabis in humans: blood and oral fluid disposition and relation to pharmacodynamic outcomes. J Anal Toxicol 41(2):83–99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Schwope DM, Scheidweiler KB, Huestis MA (2011) Direct quantification of cannabinoids and cannabinoid glucuronides in whole blood by liquid chromatography tandem mass spectrometry. Anal Bioanal Chem 401(4):1273–1283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Lee D, Huestis MA (2014) Current knowledge on cannabinoids in oral fluid. Drug Test Anal 6(1–2):88–111

    Article  CAS  PubMed  Google Scholar 

  53. Comets E, Zohar S (2009) A survey of the way pharmacokinetics are reported in published phase I clinical trials, with an emphasis on oncology. Clin Pharmacokinet 48(6):387–395

    Article  PubMed  PubMed Central  Google Scholar 

  54. Hazekamp A, Ware MA, Muller-Vahl KR, Abrams D, Grotenhermen F (2013) The medicinal use of Cannabis and cannabinoids—an international cross-sectional survey on administration forms. J Psychoactive Drugs 45(3):199–210

    Article  PubMed  Google Scholar 

  55. AbbVie Inc (2017) Full prescribing information for MARINOL capsules. Available from: http://www.rxabbvie.com/pdf/marinol_PI.pdf. Accessed 4 Nov 2017

  56. GW Pharma Ltd (2015) Sativex Oromucosal Spray. Available from: http://www.medicines.org.uk/emc/medicine/23262. Accessed 4 Nov 2017

  57. Ramer R, Hinz B (2017) Cannabinoids as anticancer drugs. Adv Pharmacol

  58. Nasir B et al (2017) Cannabis: a prehistoric remedy for the deficits of existing and emerging anticancer therapies. J Exploratory Res Pharmacol 2(3):93–104

    Article  Google Scholar 

  59. Sanchez-Ramos J (2015) The entourage effect of the phytocannabinoids. Ann Neurol 77(6):1083–1083

    Article  PubMed  Google Scholar 

  60. Lewis MA, Russo EB, Smith KM (2018) Pharmacological foundations of cannabis chemovars. Planta Med 84(04):225–233

    Article  CAS  PubMed  Google Scholar 

  61. Armstrong JL, Hill DS, McKee CS, Hernandez-Tiedra S, Lorente M, Lopez-Valero I, Eleni Anagnostou M, Babatunde F, Corazzari M, Redfern CPF, Velasco G, Lovat PE (2015) Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. J Invest Dermatol 135(6):1629–1637

    Article  CAS  PubMed  Google Scholar 

  62. Romano B, Borrelli F, Pagano E, Cascio MG, Pertwee RG, Izzo AA (2014) Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. Phytomedicine 21(5):631–639

    Article  CAS  PubMed  Google Scholar 

  63. Piomelli D, Russo EB (2016) The cannabis sativa versus Cannabis indica debate: an interview with Ethan Russo, MD. Cannabis Cannabinoid Res 1(1):44–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Nabissi M, Morelli MB, Amantini C, Liberati S, Santoni M, Ricci-Vitiani L, Pallini R, Santoni G (2015) Cannabidiol stimulates Aml-1a-dependent glial differentiation and inhibits glioma stem-like cells proliferation by inducing autophagy in a TRPV2-dependent manner. Int J Cancer 137(8):1855–1869

    Article  CAS  PubMed  Google Scholar 

  65. Nabissi M, Morelli MB, Santoni M, Santoni G (2013) Triggering of the TRPV2 channel by cannabidiol sensitizes glioblastoma cells to cytotoxic chemotherapeutic agents. Carcinogenesis 34(1):48–57

    Article  CAS  PubMed  Google Scholar 

  66. Scott KA, Dalgleish AG, Liu WM (2014) The combination of cannabidiol and Delta9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Mol Cancer Ther 13(12):2955–2967

    Article  CAS  PubMed  Google Scholar 

  67. Scott KA et al (2015) Inhibiting heat shock proteins can potentiate the cytotoxic effect of cannabidiol in human glioma cells. Anticancer Res 35(11):5827–5837

    CAS  PubMed  Google Scholar 

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Acknowledgments

This research was supported by FIT-BioCeuticals Ltd. and Endeavour College of Natural Health, Australia.

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  1. Endeavour College of Natural Health, Brisbane, Queensland, Australia

    Danielle Brown, Michael Watson & Janet Schloss

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  1. Danielle Brown
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Correspondence to Danielle Brown.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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The first author is a recipient of tuition scholarship for Honours candidature (Endeavour College of Natural Health, Australia) from FIT-BioCeuticals Ltd. The authors have full control of all primary data and agree to allow the journal to review the data if requested.

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Brown, D., Watson, M. & Schloss, J. Pharmacological evidence of medicinal cannabis in oncology: a systematic review. Support Care Cancer 27, 3195–3207 (2019). https://doi.org/10.1007/s00520-019-04774-5

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