Top

Current Neurology and Neuroscience Reports

Published in:

01-02-2018 | Neurology of Systemic Diseases (J Biller, Section Editor)

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews

Authors: Suzanne Nielsen, Rada Germanos, Megan Weier, John Pollard, Louisa Degenhardt, Wayne Hall, Nicholas Buckley, Michael Farrell

Published in: Current Neurology and Neuroscience Reports | Issue 2/2018

Abstract

Purpose of Review

Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects.

Recent Findings

We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms.

Summary

Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

Available only for authorised users

Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502–17. https://doi.org/10.1016/S0140-6736(08)61620-7.CrossRefPubMed

Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015;15(9):545–58. https://doi.org/10.1038/nri3871.CrossRefPubMed

Gold R, Hartung H-P. Towards individualised multiple-sclerosis therapy. Lancet Neurol. 2005;4(11):693–4. https://doi.org/10.1016/S1474-4422(05)70205-2.CrossRefPubMed

Giovannoni G, Rhoades RW. Individualizing treatment goals and interventions for people with MS. Curr Opin Neurol. 2012;25(Suppl):S20–7. https://doi.org/10.1097/01.wco.0000413321.32834.aa.CrossRefPubMed

Broadley SA, Barnett MH, Boggild M, Brew BJ, Butzkueven H, Heard R, et al. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 3 treatment practicalities and recommendations. MS Neurology Group of the Australian and New Zealand Association of Neurologists. J Clin Neurosci. 2014;21(11):1857–65. https://doi.org/10.1016/j.jocn.2014.01.017.CrossRefPubMed

Broadley SA, Barnett MH, Boggild M, Brew BJ, Butzkueven H, Heard R, et al. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 1 historical and established therapies. MS Neurology Group of the Australian and New Zealand Association of Neurologists. J Clin Neurosci. 2014;21(11):1835–46. https://doi.org/10.1016/j.jocn.2014.01.016.CrossRefPubMed

Broadley SA, Barnett MH, Boggild M, Brew BJ, Butzkueven H, Heard R, et al. Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 2 new and emerging therapies and their efficacy. MS Neurology Group of the Australian and New Zealand Association of Neurologists. J Clin Neurosci. 2014;21(11):1847–56. https://doi.org/10.1016/j.jocn.2014.01.018.CrossRefPubMed

Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 2003;362(9395):1517–26. https://doi.org/10.1016/S0140-6736(03)14738-1.CrossRefPubMed

Clark AJ, Ware MA, Yazer E, Murray TJ, Lynch ME. Patterns of cannabis use among patients with multiple sclerosis. Neurology. 2004;62(11):2098–100. https://doi.org/10.1212/01.WNL.0000127707.07621.72.CrossRefPubMed

10.

Zajicek JP, Apostu VI. Role of cannabinoids in multiple sclerosis. CNS Drugs. 2011;25(3):187–201. https://doi.org/10.2165/11539000-000000000-00000.CrossRefPubMed

11.

Hadjimichael O, Kerns RD, Rizzo MA, Cutter G, Vollmer T. Persistent pain and uncomfortable sensations in persons with multiple sclerosis. Pain. 2007;127(1–2):35–41. https://doi.org/10.1016/j.pain.2006.07.015.CrossRefPubMed

12.

Walker JM, Hohmann AG, Martin WJ, Strangman NM, Huang SM, Tsou K. The neurobiology of cannabinoid analgesia. Life Sci. 1999;65(6–7):665–73. https://doi.org/10.1016/S0024-3205(99)00289-1.CrossRefPubMed

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. https://doi.org/10.1038/sj.bjp.0707442.CrossRefPubMed

14.

Walker JM, Huang SM. Cannabinoid analgesia. Pharmacol Ther. 2002;95(2):127–35. https://doi.org/10.1016/S0163-7258(02)00252-8.CrossRefPubMed

15.

Quartilho A, Mata HP, Ibrahim MM, Vanderah TW, Porreca F, Makriyannis A, et al. Inhibition of inflammatory hyperalgesia by activation of peripheral CB2 cannabinoid receptors. Anesthesiology. 2003;99(4):955–60. https://doi.org/10.1097/00000542-200310000-00031.CrossRefPubMed

16.

Ibrahim M, Rude ML, Stagg NJ, Mata HP, Lai J, Vanderah TW, et al. CB2 cannabinoid receptor mediation of antinociception. Pain. 2006;122(1):36–42. https://doi.org/10.1016/j.pain.2005.12.018.CrossRefPubMed

17.

Gui H, Tong Q, Qu W, Mao CM, Dai SM. The endocannabinoid system and its therapeutic implications in rheumatoid arthritis. Int Immunopharmacol. 2015;26(1):86–91. https://doi.org/10.1016/j.intimp.2015.03.006.CrossRefPubMed

18.

Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Makriyannis A, et al. Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J. 2001;15(2):300–2. https://doi.org/10.1096/fj.00-0399fje.CrossRefPubMed

19.

• Karabudak R, Dahdaleh M, Aljumah M, Alroughani R, Alsharoqi IA, AlTahan AM, et al. Functional clinical outcomes in multiple sclerosis: current status and future prospects. Mult Scler Relat Disord. 2015;4(3):192–201. This paper highlights key clinical outcomes in multiple sclerosis, infoming which measures should be examined in future studies. https://doi.org/10.1016/j.msard.2015.03.004.CrossRefPubMed

20.

Shea BJ, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7(1):1–7.CrossRef

21.

Scottish Intercollegiate Guidelines Network (SIGN), SIGN 50: a guideline developer’s handbook. Edinburgh (SIGN publication no. 50). 2014.

22.

Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. Br Med J. 2008;336(7650):924–6. https://doi.org/10.1136/bmj.39489.470347.AD.CrossRef

23.

Mills, R.J., L. Yap, and Young C.A. Treatment for ataxia in multiple sclerosis. Cochrane Database of Systematic Reviews 2007(1): CD005029.

24.

Shakespeare, D.T., M. Boggild, and Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database of Systematic Reviews 2003(4): CD001332.

25.

Lakhan SE, Rowland M. Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurol. 2009;9:ArtID 59.CrossRefPubMed

26.

Jawahar R, Oh U, Yang S, Lapane KL. A systematic review of pharmacological pain management in multiple sclerosis. Drugs. 2013;73(15):1711–22. https://doi.org/10.1007/s40265-013-0125-0.CrossRefPubMed

27.

Andrzejewski K, Barbano R, Mink J. Cannabinoids in the treatment of movement disorders: a systematic review of case series and clinical trials. Basal Ganglia. 2016;6(3):173–81. https://doi.org/10.1016/j.baga.2016.06.001.CrossRef

28.

• Koppel BS, Brust JCM, Fife T, Bronstein J, Youssof S, Gronseth G, 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):1556–63. This recent review conluded that concluded that some cannabinoids are probably or possibly effective in treating painful spasticity, however cautioned that adverse effects such as cognitive impairment are of concern in this population. https://doi.org/10.1212/WNL.0000000000000363.CrossRefPubMedPubMedCentral

29.

Karst M, Wippermann S, Ahrens J. Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs. 2010;70(18):2409–38. https://doi.org/10.2165/11585260-000000000-00000.CrossRefPubMed

30.

•• 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 review represents one of the most comprehensive and high quality reviews to date on the therapeutic use of cannabinoids, and includes meta-analyses that found modest statistically signifcant effects of cannabinoids for spasticity in multiple sclerosis when measured with a numerical rating scale, but not when measured with the Ashworth scale. https://doi.org/10.1001/jama.2015.6358.CrossRefPubMed

31.

Zhornitsky S, Potvin S. Cannabidiol in humans-the quest for therapeutic targets. Pharmaceuticals. 2012;5(5):529–52. https://doi.org/10.3390/ph5050529.CrossRefPubMedPubMedCentral

32.

Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ Can Med Assoc J. 2008;178(13):1669–78. https://doi.org/10.1503/cmaj.071178.CrossRef

33.

Ben Amar M. Cannabinoids in medicine: a review of their therapeutic potential. J Ethnopharmacol. 2006;105(1–2):1–25. https://doi.org/10.1016/j.jep.2006.02.001.CrossRefPubMed

34.

Lee K-C, et al. The Ashworth scale: a reliable and reproducible method of measuring spasticity. J Neurol Rehabil. 1989;3(4):205–9.

35.

Collin C, Ehler E, Waberzinek G, Alsindi Z, Davies P, Powell K, et al. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res. 2010;32(5):451–9. https://doi.org/10.1179/016164109X12590518685660.CrossRefPubMed

Title: The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews
Authors: Suzanne Nielsen
Rada Germanos
Megan Weier
John Pollard
Louisa Degenhardt
Wayne Hall
Nicholas Buckley
Michael Farrell
Publication date: 01-02-2018
Publisher: Springer US
Published in: Current Neurology and Neuroscience Reports / Issue 2/2018
Print ISSN: 1528-4042
Electronic ISSN: 1534-6293
DOI: https://doi.org/10.1007/s11910-018-0814-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews

Abstract

Purpose of Review

Recent Findings

Summary

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

Please log in to get access to this content