Cannabinoids in the Management of Musculoskeletal or Rheumatic Diseases

Abstract

The endocannabinoid system impacts pain and inflammation with potential for therapeutic effect on patients with rheumatic diseases. The current treatment options include the herbal product derived from the plant Cannabis sativa, as well as pharmaceutical preparations. The legalization of medicinal cannabis (marijuana) in many jurisdictions and widespread public advocacy has propelled an interest in use either by prescription or self-medication. In this review, we examine current evidence for efficacy and adverse effects of any cannabinoid product in rheumatic conditions. The evidence to date is scant and precludes making recommendations for the use of cannabinoid preparations in rheumatology patients. In particular, the risks of herbal cannabis in patients are not well defined. Anecdote and advocacy cannot supersede sound evidence.

This is a preview of subscription content, log in to check access.

Fig. 1

References

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

  1. 1.

    Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol. 2006;147 Suppl 1:S163–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Kalant H. Medicinal use of cannabis: history and current status. Pain Res Manag. 2001;6(2):80–91.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Aggarwal SK, Carter GT, Sullivan MD, ZumBrunnen C, Morrill R, Mayer JD. Characteristics of patients with chronic pain accessing treatment with medical cannabis in Washington State. J Opioid Manag. 2009;5(5):257–86.

    PubMed  Google Scholar 

  4. 4.

    Swift W, Gates P, Dillon P. Survey of Australians using cannabis for medical purposes. Harm Reduct J. 2005;2:18.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Ware MA, Adams H, Guy GW. The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract. 2005;59(3):291–5.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Fitzcharles MA, Jamal S. Expanding medical marijuana access in Canada: considerations for the rheumatologist. J Rheumatol. 2015;42(2):143–5.

    Article  PubMed  Google Scholar 

  7. 7.

    Pecoraro N, Dallman MF, Warne JP, Ginsberg AB, Laugero KD, la Fleur SE, et al. From Malthus to motive: how the HPA axis engineers the phenotype, yoking needs to wants. Prog Neurobiol. 2006;79(5–6):247–340.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol. 2001;63(5):569–611.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Morena M, Patel S, Bains JS, Hill MN. Neurobiological interactions between stress and the endocannabinoid system. Neuropsychopharmacology. 2016;41(1):80–102.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Howlett AC. Cannabinoid receptor signaling. Handb Exp Pharmacol. 2005;168:53–79.

    CAS  Article  Google Scholar 

  11. 11.

    McDougall JJ, Linton P. Neurophysiology of arthritis pain. Curr Pain Headache Rep. 2012;16(6):485–91.

    Article  PubMed  Google Scholar 

  12. 12.

    Howlett AC. A short guide to the nomenclature of seven-transmembrane spanning receptors for lipid mediators. Life Sci. 2005;77(14):1522–30.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Cravatt BF, Lichtman AH. The endogenous cannabinoid system and its role in nociceptive behavior. J Neurobiol. 2004;61(1):149–60.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    •• Croxford JL, Yamamura T. Cannabinoids and the immune system: potential for the treatment of inflammatory diseases? J Neuroimmunol. 2005;166(1–2):3–18. This short and well-illustrated paper summarizes the current knowledge of the types of cannabis plants, their chemical constituents and the global status of cannabis cultivation, as well as the human physiological effects of the endocannabinoid receptors.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Anand P, Whiteside G, Fowler CJ, Hohmann AG. Targeting CB2 receptors and the endocannabinoid system for the treatment of pain. Brain Res Rev. 2009;60(1):255–66.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    •• Gould J. The cannabis crop. Nature. 2015;525(7570):S2–3. This review article describes the neurocognitive adverse effects of marijuana, especially as pertaining to the developing brain in young people and highlights the overall societal impact of marijuana use.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Mechoulam R, Parker LA, Gallily R. Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol. 2002;42(11 Suppl):11S–9S.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Prud’homme M, Cata R, Jutras-Aswad D. Cannabidiol as an intervention for addictive behaviors: a systematic review of the evidence. Subst Abus: Res Treat. 2015;9:33–8.

    Google Scholar 

  19. 19.

    Volkow ND, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med. 2014;371(9):879.

    PubMed  Google Scholar 

  20. 20.

    Lowin T, Straub RH. Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis. Arthritis Res Ther. 2015;17:226.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Cooper ZD, Haney M. Comparison of subjective, pharmacokinetic, and physiological effects of marijuana smoked as joints and blunts. Drug Alcohol Depend. 2009;103(3):107–13.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Ware MA, Wang T, Shapiro S, Robinson A, Ducruet T, Huynh T, et al. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 2010;182(14):E694–701.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Cascini F, Aiello C, Di Tanna G. Increasing delta-9-tetrahydrocannabinol (Delta-9-THC) content in herbal cannabis over time: systematic review and meta-analysis. Curr Drug Abuse Rev. 2012;5(1):32–40.

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Huestis MA. Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Handb Exp Pharmacol. 2005;168:657–90.

    CAS  Article  Google Scholar 

  25. 25.

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

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Mensinga TT, de Vries I, Kruidenier M, Hunault CC, van den Hengel-Koot IS, Fijen JW, et al. A double-blind, randomized, placebo controlled, cross-over study on the pharmacokinetics and effects of cannabis. Nationaal Vergiftigingen Informatie Centrum. 2006; RIVM 267002002.

  27. 27.

    • Asbridge M, Hayden JA, Cartwright JL. Acute cannabis consumption and motor vehicle collision risk: systematic review of observational studies and meta-analysis. BMJ. 2012;344:e536. doi:10.1136/bmj.e536. This study describes reports a twofold risk of serious injury or death in motor vehicle accidents following acute cannabis use.

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Legrand SA, Isalberti C, der Linden TV, Bernhoft IM, Hels T, Simonsen KW, et al. Alcohol and drugs in seriously injured drivers in six European countries. Drug Test Anal. 2013;5(3):156–65.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Canada_Department_of_Justice_Acts_Regulations_Health. Marihuana medical access regulations (SOR/2001-227), P.C. 2001–1146 2001-06-14 2013 [2013-09-21].

  30. 30.

    Aryana A, Williams MA. Marijuana as a trigger of cardiovascular events: speculation or scientific certainty? Int J Cardiol. 2007;118(2):141–4.

    Article  PubMed  Google Scholar 

  31. 31.

    Thomas G, Kloner RA, Rezkalla S. Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know. Am J Cardiol. 2014;113(1):187–90.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Jouanjus E, Lapeyre-Mestre M, Micallef J. Cannabis use: signal of increasing risk of serious cardiovascular disorders. J Am Heart Assoc. 2014;3(2):e000638.

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Taylor DR, Hall W. Respiratory health effects of cannabis: position statement of the Thoracic Society of Australia and New Zealand. Intern Med J. 2003;33(7):310–3.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Aldington S, Harwood M, Cox B, Weatherall M, Beckert L, Hansell A, et al. Cannabis use and risk of lung cancer: a case-control study. Eur Respir J. 2008;31(2):280–6.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Callaghan RC, Allebeck P, Sidorchuk A. Marijuana use and risk of lung cancer: a 40-year cohort study. Cancer Causes Control. 2013.

  36. 36.

    Zhang LR, Morgenstern H, Greenland S, Chang SC, Lazarus P, Teare MD, et al. Cannabis smoking and lung cancer risk: pooled analysis in the International Lung Cancer Consortium. Int J Cancer. 2015;136(4):894–903.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Moreira FA, Grieb M, Lutz B. Central side-effects of therapies based on CB1 cannabinoid receptor agonists and antagonists: focus on anxiety and depression. Best Pract Res Clin Endocrinol Metab. 2009;23(1):133–44.

    CAS  Article  PubMed  Google Scholar 

  38. 38.

    Zhang MW, Ho RC. The cannabis dilemma: a review of its associated risks and clinical efficacy. J Addict. 2015;2015:707596.

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Harder VS, Morral AR, Arkes J. Marijuana use and depression among adults: testing for causal associations. Addiction. 2006;101(10):1463–72.

    Article  PubMed  Google Scholar 

  40. 40.

    Ksir C, Hart CL. Cannabis and psychosis: a critical overview of the relationship. Curr Psychiatry Rep. 2016;18(2):12.

    Article  PubMed  Google Scholar 

  41. 41.

    Bersani G, Orlandi V, Kotzalidis GD, Pancheri P. Cannabis and schizophrenia: impact on onset, course, psychopathology and outcomes. Eur Arch Psychiatry Clin Neurosci. 2002;252(2):86–92.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Gonzalez S, Cebeira M, Fernandez-Ruiz J. Cannabinoid tolerance and dependence: a review of studies in laboratory animals. Pharmacol Biochem Behav. 2005;81(2):300–18.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Gorelick DA, Levin KH, Copersino ML, Heishman SJ, Liu F, Boggs DL, et al. Diagnostic criteria for cannabis withdrawal syndrome. Drug Alcohol Depend. 2012;123(1–3):141–7.

    Article  PubMed  Google Scholar 

  44. 44.

    Ramesh D, Schlosburg JE, Wiebelhaus JM, Lichtman AH. Marijuana dependence: not just smoke and mirrors. ILAR J. 2011;52(3):295–308.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Budney AJ, Hughes JR. The cannabis withdrawal syndrome. Curr Opin Psychiatry. 2006;19(3):233–8.

    Article  PubMed  Google Scholar 

  46. 46.

    • van der Pol P, Liebregts N, de Graaf R, Korf DJ, van den Brink W, van Laar M. Predicting the transition from frequent cannabis use to cannabis dependence: a three-year prospective study. Drug Alcohol Depend. 2013;133(2):352–9. In this prospective cohort study of young cannabis users, progression to dependence was predicted by adverse psychosocial factors.

    Article  PubMed  Google Scholar 

  47. 47.

    Lopez-Quintero C, Perez de los Cobos J, Hasin DS, Okuda M, Wang S, Grant BF, et al. Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drug Alcohol Depend. 2011;115(1–2):120–30.

    Article  PubMed  Google Scholar 

  48. 48.

    Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet. 2009;374(9698):1383–91.

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    • Gilman JM, Kuster JK, Lee S, Lee MJ, Kim BW, Makris N, et al. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users. J Neurosci. 2014;34(16):5529–38. A study demonstrating for the first time the presence of anatomical changes in areas of brain subserving addictive behaviours in young occasional recreational cannabis users.

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Richardson D, Pearson RG, Kurian N, Latif ML, Garle MJ, Barrett DA, et al. Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther. 2008;10(2):R43.

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Stein C, Schafer M, Machelska H. Attacking pain at its source: new perspectives on opioids. Nat Med. 2003;9(8):1003–8.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Schuelert N, McDougall JJ. Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum. 2008;58(1):145–53.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Gui H, Liu X, Liu LR, Su DF, Dai SM. Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction in collagen-induced arthritis. Immunobiology. 2015;220(6):817–22.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Schuelert N, Zhang C, Mogg AJ, Broad LM, Hepburn DL, Nisenbaum ES, et al. Paradoxical effects of the cannabinoid CB2 receptor agonist GW405833 on rat osteoarthritic knee joint pain. Osteoarthr Cartil. 2010;18(11):1536–43.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Klein TW, Newton CA, Friedman H. Cannabinoids and the immune system. Pain Res Manag. 2001;6(2):95–101.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Fitzcharles MA, Ste-Marie PA, Hauser W, Clauw DJ, Jamal S, Karsh J, et al. Efficacy, tolerability, and safety of cannabinoid treatments in the rheumatic diseases: a systematic review of randomized controlled trials. Arthritis Care Res (Hoboken). 2016;68(5):681–8.

    CAS  Article  Google Scholar 

  57. 57.

    Fitzcharles MA, Baerwald C, Ablin J, Hauser W. Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): a systematic review of randomized controlled trials. Schmerz (Berlin, Germany). 2016;30(1):47–61.

    Article  Google Scholar 

  58. 58.

    •• Walitt B, Klose P, Fitzcharles MA, Phillips T, Hauser W. Cannabinoids for fibromyalgia. Cochrane Database Syst Rev. 2016;7:CD011694. An updated systematic review of the evidence for use of cannabinoids in fibromyalgia that points to poor evidence for effect.

    PubMed  Google Scholar 

  59. 59.

    Blake DR, Robson P, Ho M, Jubb RW, McCabe CS. Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology. 2006;45(1):50–2.

    CAS  Article  PubMed  Google Scholar 

  60. 60.

    Skrabek RQ, Galimova L, Ethans K, Perry D. Nabilone for the treatment of pain in fibromyalgia. J Pain. 2008;9(2):164–73. English.

    CAS  Article  PubMed  Google Scholar 

  61. 61.

    Ware MA, Fitzcharles MA, Joseph L, Shir Y. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg. 2010;110(2):604–10. English.

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Huggins JP, Smart TS, Langman S, Taylor L, Young T. An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. Pain. 2012;153(9):1837–46.

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    • Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313(24):2456–73. This meta-analysis examines the published studies for use of any cannabinoid for all medical conditions, including musculoskeletal conditions, with conclusion that there is some evidence for effect on some conditions but with increased reporting of adverse events.

    CAS  Article  PubMed  Google Scholar 

  64. 64.

    •• D’Souza DC, Ranganathan M. Medical marijuana: is the cart before the horse? JAMA. 2015;313(24):2431–2. A thoughtful editorial highlighting the important gaps in knowledge that exist regarding marijuana use for many medical conditions and recommendation to exercise caution regarding any treatment advice.

    Article  PubMed  Google Scholar 

  65. 65.

    Ware MA, Wang T, Shapiro S, Collet JP. Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS). J Pain. 2015;16(12):1233–42.

    Article  PubMed  Google Scholar 

  66. 66.

    Fitzcharles MA, McDougall J, Ste-Marie PA, Padjen I. Clinical implications for cannabinoid use in the rheumatic diseases: potential for help or harm? Arthritis Rheum. 2012;64(8):2417–25.

    Article  PubMed  Google Scholar 

  67. 67.

    Kalant H. Adverse effects of cannabis on health: an update of the literature since 1996. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(5):849–63.

    CAS  Article  PubMed  Google Scholar 

  68. 68.

    • Kondrad E, Reid A. Colorado family physicians’ attitudes toward medical marijuana. J Am Board Fam Med. 2013;26(1):52–60. A study of family physicians attitudes to the use of medicinal marijuana that highlights physicians discomfort with use and need for further education to allow for competent medical care.

    Article  PubMed  Google Scholar 

  69. 69.

    Fitzcharles MA, Ste-Marie PA, Clauw DJ, Jamal S, Karsh J, LeClercq S, et al. Rheumatologists lack confidence in their knowledge of cannabinoids pertaining to the management of rheumatic complaints. BMC Musculoskelet Disord. 2014;15:258.

    Article  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Fitzcharles MA, Clauw DJ, Ste-Marie PA, Shir Y. The dilemma of medical marijuana use by rheumatology patients. Arthritis Care Res. 2014.

  71. 71.

    College_of_Family_Physicians_of_Canada. Authorizing dried cannabis for chronic pain or anxiety: preliminary guidance from the college of family physicians of Canada Mississauga, ON: College of Family Physicians of Canada. 2014.

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Mary-Ann Fitzcharles.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and were in compliance with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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

Additional information

This article is part of the Topical Collection on Complementary and Alternative Medicine

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Fitzcharles, M., Häuser, W. Cannabinoids in the Management of Musculoskeletal or Rheumatic Diseases. Curr Rheumatol Rep 18, 76 (2016). https://doi.org/10.1007/s11926-016-0625-5

Download citation

Keywords

  • Cannabinoids
  • Rheumatic disease
  • Marijuana