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Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain

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Abstract

The use of medical cannabis and cannabis-based medicines has received increasing interest in recent years; with a corresponding surge in the number of studies and reviews conducted in the field. Despite this growth in evidence, the findings and conclusions of these studies have been inconsistent. In this paper, we outline the current evidence for medical cannabis and cannabis-based medicines in the treatment and management of chronic non-cancer pain. We discuss limitations of the current evidence, including limitations of randomised control trials in the field, limits on generalisability of previous findings and common issues such as problems with measurements of dose and type of cannabinoids. We discuss future directions for medicinal cannabinoid research, including addressing limitations in trial design; developing frameworks to monitor for use disorder and other unintended outcomes; and considering endpoints other than 30% or 50% reductions in pain severity.

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References

  1. National Academies of Sciences Engineering and Medicine (2017) The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. The National Academies Press, Washington, DC

    Google Scholar 

  2. Hauser W, Fitzcharles MA, Radbruch L, Petzke F (2017) Cannabinoids in pain management and palliative medicine. Deutsch Arztebl Int 114(38):627–634

    Google Scholar 

  3. Whiting PF, Wolff RF, Deshpande S et al (2015) Cannabinoids for medical use: a systematic review and meta-analysis. JAMA 313(24):2456–2473

    Article  CAS  PubMed  Google Scholar 

  4. Petzke F, Enax-Krumova EK, Hauser W (2016) Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain: a systematic review of randomized controlled studies. Schmerz (Berlin Germany) 30(1):62–88

    Article  CAS  Google Scholar 

  5. Stockings E, Campbell G, Hall WD et al (2018) Cannabis and cannabinoids for the treatment of people with chronic non-cancer pain conditions: a systematic review and meta-analysis of controlled and observational studies. Pain

  6. Aviram J, Samuelly-Leichtag G (2017) Efficacy of cannabis-based medicines for pain management: a systematic review and meta-analysis of randomized controlled trials. Pain Phys 20(6):E755–E796

    CAS  Google Scholar 

  7. Mücke M, Phillips T, Radbruch L, Petzke F, Hauser W (2018) Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev 3:CD012182

    PubMed  Google Scholar 

  8. Hauser W, Finn DP, Kalso E et al (2018) European Pain Federation (EFIC) position paper on appropriate use of cannabis-based medicines and medical cannabis for chronic pain management. Eur J Pain (London England) 22(9):1547–1564

    Article  Google Scholar 

  9. Hauser W, Petzke F, Fitzcharles MA (2018) Efficacy, tolerability and safety of cannabis-based medicines for chronic pain management—an overview of systematic reviews. Eur J Pain (London England) 22(3):455–470

    Article  CAS  Google Scholar 

  10. Allan GM, Finley CR, Ton J et al (2018) Systematic review of systematic reviews for medical cannabinoids: pain, nausea and vomiting, spasticity, and harms. Can Fam Phys (Med Fam Can) 64(2):e78–e94

    Google Scholar 

  11. Deshpande A, Mailis-Gagnon A, Zoheiry N, Lakha SF (2015) Efficacy and adverse effects of medical marijuana for chronic noncancer pain: systematic review of randomized controlled trials. Can Fam Phys 61(8):e372–e381

    Google Scholar 

  12. International Association for the Study of Pain (IASP) (2018) IASP terminology. http://www.iasp-pain.org/terminology?navItemNumber=576#Neuropathicpain. Accessed 30 July 2018

  13. Nugent SM, Morasco BJ, O’Neil ME et al (2017) The effects of cannabis among adults with chronic pain and an overview of general harms: a systematic review. Ann Intern Med 167(5):319–331

    Article  PubMed  Google Scholar 

  14. Walitt B, Klose P, Fitzcharles MA, Phillips T, Hauser W (2016) Cannabinoids for fibromyalgia. Cochrane Database Syst Rev 7:CD011694

    PubMed  Google Scholar 

  15. Allan GM, Ramji J, Perry D et al (2018) Simplified guideline for prescribing medical cannabinoids in primary care. Can Fam Phys (Med Fam Can) 64(2):111–120

    Google Scholar 

  16. Nielsen S, Germanos R, Weier M et al (2018) The use of cannabis and cannabinoids in treating symptoms of multiple sclerosis: a systematic review of reviews. Curr Neurol Neurosci Rep 18(2):8

    Article  PubMed  CAS  Google Scholar 

  17. Malik Z, Baik D, Schey R (2015) The role of cannabinoids in regulation of nausea and vomiting, and visceral pain. Curr Gastroenterol Rep 17(2):9

    Article  Google Scholar 

  18. Kerlin AM, Long M, Kappelman M, Martin C, Sandler RS (2018) Profiles of patients who use marijuana for inflammatory bowel disease. Digest Dis Sci 63(6):1600–1604

    Article  PubMed  Google Scholar 

  19. de Vries M, van Rijckevorsel DCM, Vissers KCP, Wilder-Smith OHG, van Goor H (2017) Tetrahydrocannabinol does not reduce pain in patients with chronic abdominal pain in a phase 2 placebo-controlled study. Clin Gastroenterol Hepatol 15(7):1079–86.e4

    Article  PubMed  CAS  Google Scholar 

  20. de Vries M, Van Rijckevorsel DC, Vissers KC, Wilder-Smith OH, Van Goor H (2016) Single dose delta-9-tetrahydrocannabinol in chronic pancreatitis patients: analgesic efficacy, pharmacokinetics and tolerability. Br J Clin Pharmacol 81(3):525–537

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Kafil TS, Nguyen TM, MacDonald JK, Chande N (2018) Cannabis for the treatment of ulcerative colitis. Cochrane Database Syst Rev 11(2):CD012954

    PubMed  Google Scholar 

  22. Walitt B, Klose P, Fitzcharles MA, Phillips T, Häuser W (2016) Cannabinoids for fibromyalgia. Cochrane Database Syst Rev 7:CD011694

    PubMed  Google Scholar 

  23. Skrabek RQ, Galimova L, Ethans K, Perry D (2008) Nabilone for the treatment of pain in fibromyalgia. J Pain 9(2):164–173

    Article  CAS  PubMed  Google Scholar 

  24. Blake DR, Robson P, Ho M, Jubb RW, McCabe CS (2006) Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology 45(1):50–52

    Article  CAS  PubMed  Google Scholar 

  25. Pinsger M, Schimetta W, Volc D, Hiermann E, Riederer F, Pölz W (2006) Nutzen einer add-on-therapie mit dem synthetischen cannabinomimetikum nabilone bei patienten mit chronischen Schmerzzuständen—eine randomisierte kontrollierte studie. Wien Klin Wochenschr 118(11):327–335

    Article  PubMed  Google Scholar 

  26. National Academies of Sciences, Engineering, and Medicine (2017) The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. National Academies Press, Washington

    Google Scholar 

  27. Campbell G, Nielsen S, Bruno R et al (2015) The Pain and Opioids IN Treatment study: characteristics of a cohort using opioids to manage chronic non-cancer pain. Pain 156(2):231–242

    Article  CAS  PubMed  Google Scholar 

  28. Rogers KD, Kemp A, McLachlan AJ, Blyth F (2013) Adverse selection? A multi-dimensional profile of people dispensed opioid analgesics for persistent non-cancer pain. PLoS ONE 8(12):e80095

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Tunks ER, Crook J, Weir R (2008) Epidemiology of chronic pain with psychological comorbidity: prevalence, risk, course, and prognosis. Can J Psychiatry 53(4):224–234

    Article  PubMed  Google Scholar 

  30. Walker ER, Druss BG (2017) Cumulative burden of comorbid mental disorders, substance use disorders, chronic medical conditions, and poverty on health among adults in the U.S.A. Psychol Health Med 22(6):727–735

    Article  PubMed  Google Scholar 

  31. Mücke M, Phillips T, Radbruch L, Petzke F, Häuser W (2018) Cannabis-based medicines for chronic neuropathic pain in adults. Cochrane Database Syst Rev 3:CD012182

    PubMed  Google Scholar 

  32. Dechartres A, Trinquart L, Boutron I, Ravaud P (2013) Influence of trial sample size on treatment effect estimates: meta-epidemiological study. BMJ Br Med J 346:f2304

    Article  Google Scholar 

  33. Hauser W, Fitzcharles MA (2018) The perils of overestimating the efficacy of cannabis-based medicines for chronic pain management. Pain Phys 21(1):E79–E80

    Google Scholar 

  34. Vos T, Barber RM, Bell B et al (2016) Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 386(9995):743–800

    Article  Google Scholar 

  35. Lynch ME, Ware MA (2015) Cannabinoids for the treatment of chronic non-cancer pain: an updated systematic review of randomized controlled trials. J Neuroimmune Pharmacol 10(2):293–301

    Article  CAS  PubMed  Google Scholar 

  36. Bhatt DL, Mehta C (2016) Adaptive designs for clinical trials. N Engl J Med 375(1):65–74

    Article  PubMed  Google Scholar 

  37. Turk DC, Dworkin RH, Allen RR et al (2003) Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain 106(3):337–345

    Article  PubMed  Google Scholar 

  38. Levy N, Sturgess J, Mills P (2018) “Pain as the fifth vital sign” and dependence on the “numerical pain scale” is being abandoned in the US: why? Br J Anaesth 120(3):435–438

    Article  CAS  PubMed  Google Scholar 

  39. Piper BJ, Beals ML, Abess AT et al (2017) Chronic pain patients’ perspectives of medical cannabis. Pain 158(7):1373–1379

    Article  PubMed  PubMed Central  Google Scholar 

  40. Campbell G, Hall WD, Peacock A et al (2018) Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study. Lancet Public Health 3(7):e341–e350

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wilsey B, Deutsch R, Marcotte TD (2016) Maintenance of blinding in clinical trials and the implications for studying analgesia using cannabinoids. Cannabis Cannabinoid Res 1(1):139–148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ware MA, Fitzcharles M-A, Joseph L, Shir Y (2010) The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg 110(2):604–610

    Article  CAS  PubMed  Google Scholar 

  43. Colagiuri B (2010) Participant expectancies in double-blind randomized placebo-controlled trials: potential limitations to trial validity. Clin Trials 7(3):246–255

    Article  PubMed  Google Scholar 

  44. Goldstein RB, Chou SP, Smith SM et al (2015) Nosologic comparisons of DSM-IV and DSM-5 alcohol and drug use disorders: results from the national epidemiologic survey on alcohol and related conditions-III. J Stud Alcohol Drugs 76(3):378–388

    Article  PubMed  PubMed Central  Google Scholar 

  45. Mewton L, Slade T, Teesson M (2013) An evaluation of the proposed DSM-5 cannabis use disorder criteria using Australian National Survey Data. J Stud Alcohol Drugs 74(4):614–621

    Article  PubMed  Google Scholar 

  46. Hall W (2015) What has research over the past two decades revealed about the adverse health effects of recreational cannabis use? Addiction 110(1):19–35

    Article  PubMed  Google Scholar 

  47. Morasco BJ, Gritzner S, Lewis L, Oldham R, Turk DC, Dobscha SK (2011) Systematic review of prevalence, correlates, and treatment outcomes for chronic non-cancer pain in patients with comorbid substance use disorder. Pain 152(3):488–497

    Article  PubMed  Google Scholar 

  48. Turk DC, O’Connor AB, Dworkin RH et al (2012) Research design considerations for clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations. Pain 153(10):1997–2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Gourlay DL, Heit HA, Almahrezi A (2005) Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med 6(2):107–112

    Article  PubMed  Google Scholar 

  50. Schuermeyer J, Salomonsen-Sautel S, Price RK et al (2014) Temporal trends in marijuana attitudes, availability and use in Colorado compared to non-medical marijuana states: 2003–11. Drug Alcohol Depend 140:145–155

  51. Troutt WD, DiDonato MD (2015) Medical cannabis in Arizona: patient characteristics, perceptions, and impressions of medical cannabis legalization. J Psychoact Drugs 47(4):259–266

    Article  Google Scholar 

  52. Krcevski-Skvarc N, Wells C, Hauser W (2018) Availability and approval of cannabis-based medicines for chronic pain management and palliative/supportive care in Europe: a survey of the status in the chapters of the European Pain Federation. Eur J Pain 22(3):440–454

    Article  CAS  PubMed  Google Scholar 

  53. Nielsen S, Sabioni P, Trigo J et al (2017) Opioid-sparing effects of cannabinoids: a systematic review and meta-analyses. Neurospychopharmacology 49(9):1752–1765

    Article  CAS  Google Scholar 

  54. Bachhuber MA, Saloner B, Cunningham CO, Barry CL (2014) Medical cannabis laws and opioid analgesic overdose mortality in the United States, 1999–2010. JAMA Intern Med 174(10):1668–1673

    Article  PubMed  PubMed Central  Google Scholar 

  55. Bradford AC, Bradford W, Abraham A, Bagwell Adams G (2018) Association between us state medical cannabis laws and opioid prescribing in the medicare part D population. JAMA Intern Med

  56. Livingston MD, Barnett TE, Delcher C, Wagenaar AC (2017) Recreational cannabis legalization and opioid-related deaths in Colorado, 2000–2015. Am J Public Health 107(11):1827–1829

    Article  PubMed  PubMed Central  Google Scholar 

  57. Pardo B (2017) Do more robust prescription drug monitoring programs reduce prescription opioid overdose? Addiction 112(10):1773–1783

    Article  PubMed  Google Scholar 

  58. Abuhasira R, Schleider LB, Mechoulam R, Novack V (2018) Epidemiological characteristics, safety and efficacy of medical cannabis in the elderly. Eur J Intern Med 49:44–50

    Article  PubMed  Google Scholar 

  59. Boehnke KF, Litinas E, Clauw DJ (2016) Medical cannabis use is associated with decreased opiate medication use in a retrospective cross-sectional survey of patients with chronic pain. J Pain 17(6):739–744

    Article  PubMed  Google Scholar 

  60. Corroon JM Jr, Mischley LK, Sexton M (2017) Cannabis as a substitute for prescription drugs—a cross-sectional study. J Pain Res 10:989

    Article  PubMed  PubMed Central  Google Scholar 

  61. Haroutounian S, Ratz Y, Ginosar Y et al (2016) The effect of medicinal cannabis on pain and quality-of-life outcomes in chronic pain: a prospective open-label study. Clin J Pain 32(12):1036–1043

    Article  PubMed  Google Scholar 

  62. Campbell G, Hall W, Nielsen S (2018) What does the ecological and epidemiological evidence indicate about the potential for cannabinoids to reduce opioid use and harms? A comprehensive review. Int Rev Psychiatry (in press, accepted 6 Aug 2018)

  63. Klieger SB, Gutman A, Allen L, Pacula RL, Ibrahim JK, Burris S (2017) Mapping medical marijuana: state laws regulating patients, product safety, supply chains and dispensaries, 2017. Addiction 112(12):2206–2216

    Article  PubMed  PubMed Central  Google Scholar 

  64. Dowell D, Haegerich TM, Chou R (2016) CDC guideline for prescribing opioids for chronic pain—United States, 2016. JAMA 315(15):1624–1645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. NSW Health (2018) Chronic pain management: information for medical practitioners. https://www.health.nsw.gov.au/pharmaceutical/doctors/Pages/chronic-pain-medical-practitioners.aspx. Accessed 29 Oct 2018

  66. Oliveira CB, Maher CG, Pinto RZ et al (2018) Clinical practice guidelines for the management of non-specific low back pain in primary care: an updated overview. Eur Spine J 27(11):2791–2803

    Article  PubMed  Google Scholar 

  67. Häuser W, Fitzcharles M-A, Radbruch L, Petzke F (2017) Cannabinoids in pain management and palliative medicine. Dtsch Arztebl Int 114(38):627–634

    PubMed  PubMed Central  Google Scholar 

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Funding

No direct funding was received to write this article. SN, ES and GC are supported by NHMRC research fellowships (#1132433, #1104600 and #1119992). The National Drug and Alcohol Research Centre at the University of New South Wales is supported by funding from the Australian Government under the Substance Misuse Prevention and Service Improvements Grant Fund.

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Authors and Affiliations

  1. National Drug and Alcohol Research Centre (NDARC), Faculty of Medicine, UNSW Sydney, 22-32 King Street, Randwick, NSW, 2031, Australia

    Gabrielle Campbell & Emily Stockings

  2. Monash Addiction Research Centre, Eastern Health Clinical School, Faculty of Medicine Nursing and Health Sciences, Monash University, Level 2, 5 Arnold Street, Box Hill, VIC, 3128, Australia

    Suzanne Nielsen

Authors
  1. Gabrielle Campbell
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  2. Emily Stockings
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  3. Suzanne Nielsen
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Correspondence to Gabrielle Campbell.

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Conflict of interest

SN has been an investigator on untied investigator-driven educational grants funded by Indivior and Reckitt-Benckiser and has had travel costs covered and honoraria paid to her institution to provide training on identification and management of codeine dependence by Indivior. GC has been an investigator on untied investigator driven educational grants from Reckitt-Benckiser. ES declares no conflicts of interest.

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Campbell, G., Stockings, E. & Nielsen, S. Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain. Eur Arch Psychiatry Clin Neurosci 269, 135–144 (2019). https://doi.org/10.1007/s00406-018-0960-9

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  • DOI: https://doi.org/10.1007/s00406-018-0960-9

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