The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews
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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.
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.
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.
KeywordsMultiple sclerosis Cannabinoid Pain Spasticity Nabiximols Dronabinol Cannabis
The editors would like to thank Dr. John Brust and Dr. José Biller for taking the time to review this manuscript.
Funding was received from the Commonwealth Department of Health and the NSW Government Centre for Medicinal Cannabis Research and Innovation, who determined the topics and scope of the reviews to be conducted and funded the salary of MW. SN and LD are supported by NHMRC research fellowships (no. 1132423 and no. 1041472). The National Drug and Alcohol Research Centre at the University of New South Wales is supported by a funding from the Australian Government under the Substance Misuse Prevention and Service Improvements Grant Fund.
Compliance with Ethical Standards
Conflict of Interest
SN, MF and LD have all been investigators on untied investigator-driven educational grants funded by Reckitt Benckiser. MF and LD have received untied educational grant from Mundipharma for post-marketing surveillance studies of new opioid medications. SN, MF and LD have been investigators on untied investigator-driven educational grants funded by Indivior and Reckitt-Benckiser. NB is a member of the medical cannabis expert panel for New South Wales Health. WH provided evidence to parliamentary committees on medical uses of cannabis in Australia and the United Kingdom and is a member of the Australian Advisory Council on Medical Uses of Cannabis. SN, WH, MF, MW and LD have previously published manuscripts on the topic of therapeutic use of cannabis. Other authors declare no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 4.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.CrossRefPubMedGoogle Scholar
- 5.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.CrossRefPubMedGoogle Scholar
- 6.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.CrossRefPubMedGoogle Scholar
- 7.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.CrossRefPubMedGoogle Scholar
- 8.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.CrossRefPubMedGoogle Scholar
- 9.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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 21.Scottish Intercollegiate Guidelines Network (SIGN), SIGN 50: a guideline developer’s handbook. Edinburgh (SIGN publication no. 50). 2014.Google Scholar
- 23.Mills, R.J., L. Yap, and Young C.A. Treatment for ataxia in multiple sclerosis. Cochrane Database of Systematic Reviews 2007(1): CD005029.Google Scholar
- 24.Shakespeare, D.T., M. Boggild, and Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database of Systematic Reviews 2003(4): CD001332.Google Scholar
- 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.CrossRefPubMedPubMedCentralGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.Google Scholar
- 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.CrossRefPubMedGoogle Scholar