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Cannabinoids in the Management of Musculoskeletal or Rheumatic Diseases

  • Mary-Ann FitzcharlesEmail author
  • Winfried Häuser
Complementary and Alternative Medicine (S Kolasinski, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Complementary and Alternative Medicine

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.

Keywords

Cannabinoids Rheumatic disease Marijuana 

Notes

Compliance with Ethical Standards

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.

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.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Kalant H. Medicinal use of cannabis: history and current status. Pain Res Manag. 2001;6(2):80–91.CrossRefPubMedGoogle 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.PubMedGoogle Scholar
  4. 4.
    Swift W, Gates P, Dillon P. Survey of Australians using cannabis for medical purposes. Harm Reduct J. 2005;2:18.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle Scholar
  6. 6.
    Fitzcharles MA, Jamal S. Expanding medical marijuana access in Canada: considerations for the rheumatologist. J Rheumatol. 2015;42(2):143–5.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
  8. 8.
    Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol. 2001;63(5):569–611.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
  10. 10.
    Howlett AC. Cannabinoid receptor signaling. Handb Exp Pharmacol. 2005;168:53–79.CrossRefGoogle Scholar
  11. 11.
    McDougall JJ, Linton P. Neurophysiology of arthritis pain. Curr Pain Headache Rep. 2012;16(6):485–91.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
  13. 13.
    Cravatt BF, Lichtman AH. The endogenous cannabinoid system and its role in nociceptive behavior. J Neurobiol. 2004;61(1):149–60.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.PubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle Scholar
  24. 24.
    Huestis MA. Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Handb Exp Pharmacol. 2005;168:657–90.CrossRefGoogle Scholar
  25. 25.
    Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770–804.CrossRefPubMedPubMedCentralGoogle 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.Google Scholar
  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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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].Google Scholar
  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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.Google Scholar
  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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
  38. 38.
    Zhang MW, Ho RC. The cannabis dilemma: a review of its associated risks and clinical efficacy. J Addict. 2015;2015:707596.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle Scholar
  40. 40.
    Ksir C, Hart CL. Cannabis and psychosis: a critical overview of the relationship. Curr Psychiatry Rep. 2016;18(2):12.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Budney AJ, Hughes JR. The cannabis withdrawal syndrome. Curr Opin Psychiatry. 2006;19(3):233–8.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
  48. 48.
    Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet. 2009;374(9698):1383–91.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.CrossRefPubMedGoogle Scholar
  52. 52.
    Schuelert N, McDougall JJ. Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum. 2008;58(1):145–53.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
  55. 55.
    Klein TW, Newton CA, Friedman H. Cannabinoids and the immune system. Pain Res Manag. 2001;6(2):95–101.CrossRefPubMedGoogle 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.CrossRefGoogle 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.CrossRefGoogle 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.PubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedPubMedCentralGoogle 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.Google Scholar
  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.Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Division of RheumatologyMcGill University Health CentreMontréalCanada
  2. 2.Alan Edwards Pain Management UnitMcGill University Health CentreMontréalCanada
  3. 3.Montreal General HospitalMcGill University Health CentreMontrealCanada
  4. 4.Department Internal Medicine IKlinikum SaarbrückenSaarbrückenGermany
  5. 5.Department of Psychosomatic Medicine and PsychotherapyTechnische Universität MünchenMunichGermany

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