Cannabinoids for Treatment of MS Symptoms: State of the Evidence
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Purpose of Review
Cannabis and cannabinoids have been used medically and recreationally for thousands of years and recently there has been a growing body of research in this area. With increased access now that medical marijuana is available in many jurisdictions, patients and providers want to know more about the evidence for benefits and risks of cannabinoid use. This paper provides an overview of the available cannabinoid-based formulations, a summary of the highest quality evidence for the use of cannabinoids for treating spasticity and pain associated with multiple sclerosis (MS), and a discussion of possible dosing regimens based on information from these studies.
Two recent high-quality systematic reviews concluded that the only strong evidence for medical marijuana in neurological disorders was for reducing the symptoms of patient-reported spasticity and central pain in MS and that the only complementary and alternative medicine (CAM) intervention in MS with strong supportive evidence was cannabinoids. Based on this review, they concluded that nabiximols (Sativex oral spray), oral cannabis extract (OCE), and synthetic tetrahydrocannabinol (THC) are probably effective at reducing patient-reported symptoms of spasticity in people with MS, but OCE and synthetic THC were not found to be effective for reducing physician-administered measures of spasticity. In addition, nabiximols, OCE, and synthetic THC are probably effective at reducing MS-related pain. Cannabinoids were generally well-tolerated. However, cannabis use has been associated with an increased risk of psychosis and schizophrenia in at-risk individuals, there is growing evidence that cannabis can increase the risk for cardiovascular diseases, including myocardial infarction (MI), hypertension, heart failure, and stroke, and a recently recognized adverse effect of cannabis is cannabinoid hyperemesis syndrome.
The medical use of cannabinoids remains controversial. While cannabinoids have been studied for a variety of neurologic disorders, there is strongest evidence to indicate benefits in treatment of spasticity and neuropathic pain in multiple sclerosis. Although the best dose for an individual remains uncertain, most participants in the studies discussed in this paper used between 20 and 40 mg of THC a day in divided doses. Adverse events in studies were generally more common in the groups using cannabinoid products but serious adverse events were rare and cannabis products were generally well-tolerated. Cannabis use does appear to be associated with increased risk of certain adverse events, including psychosis, cardiovascular diseases, and cannabinoid hyperemesis syndrome.
KeywordsMultiple sclerosis Cannabis Cannabinoid Spasticity Pain
Compliance with Ethical Standards
Conflict of Interest
Jessica Rice declares no potential conflicts of interest.
Michelle Cameron is a section editor for Current Neurology and Neuroscience Reports. Dr. Cameron reports personal fees from Adamas and a grant from Greenwich Biosciences.
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
- 6.• 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. Systematic review on the safety and efficacy of medical marijuana in MS, epilepsy, and movement disorders that included in their conclusions that certain cannabinoid preparations are effective or probably effective for MS-related spasticity, pain, and bladder symptoms but not tremor. CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Americans for Safe Access. Legal Information By State & Federal Law. http://www.safeaccessnow.org/state_and_federal_law. Accessed 15 Sept 2017.
- 9.MARINOL [package insert]. North Chicago, IL: AbbVie Inc.Google Scholar
- 10.CESAMET [package insert]. Somerset, New Jersey: Meda Pharmaceuticals Inc.Google Scholar
- 11.GW Pharmaceuticals. Sativex prescriber Information. https://www.gwpharm.com/products-pipeline/sativex/prescriber-information-full. Accessed Sept 15, 2017.
- 12.International Association for Cannabinoids Medicines. Cannador. https://cannabis-med.org/index.php?tpl=def&id=241&lng=en&red=deflist. Accessed 15 Sept 2017.
- 13.• Yadav V, Bever C, Bowen J, Bowling A, Weinstock-Guttman B, Cameron M, et al. Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2014;82(12):1083–92. American Academy of Neurology evidence-based guideline on complementary and alternative medicine in MS that included in their recommendations that clinicians might offer certain cannabinoid preparations for spasticity, pain, and urinary frequency but not tremor. CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Fu, et al. A mixed treatment comparison on efficacy and safety of treatments for spasticity caused by multiple sclerosis: a systematic review and network meta-analysis. Clin Rehabil. 2018;1:269215517745348.Google Scholar
- 23.Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, et al. A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols (Sativex(®) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis. Eur J Neurol. 2011;18(9):1122–31.CrossRefPubMedGoogle Scholar
- 24.• Whiting PF, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313(24):2456–73. This comprehensive systematic review and meta-analysis for the use of cannabinoids in all medical conditions, not limited to multiple sclerosis or neurologic conditions, included in its conclusions that there was moderate quality evidence to support use of cannabinoids for the treatment of chronic pain and spasticity. CrossRefPubMedGoogle Scholar
- 34.• Ware MA, et al. Cannabis for the management of pain: assessment of safety study (COMPASS). J Pain. 2015;16(12):1233–42. This is the only currently published study focusing on the safety of cannabinoids when used in the management of chronic pain. The study found a higher rate of adverse events, but not serious adverse events, among users of 2.5g of herbal cannabis/day compared to non-users. CrossRefPubMedGoogle Scholar
- 40.Jouanjus E, Lapeyre-Mestre M, Micallef J, The French Association of the Regional Abuse and Dependence Monitoring Centres (CEIP-A) Working Group on Cannabis Complications*. Cannabis use: signal of increasing risk of serious cardiovascular disorders. J Am Heart Assoc. 2014;3(2):e000638.CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Allen JH, de Moore GM, Heddle R, et al. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Cut. 2004;53(11):1566–70.Google Scholar
- 44.Chen J, et al. Cannabinoid hyperemesis syndrome: a result of chronic, heavy cannabis use. Curr Psychiatr. 2013;12(10):48–54.Google Scholar
- 45.Jones JI, et al. Successful treatment of suspected cannabinoid hyperemesis syndrome using haloperidol in the outpatient setting. Case Rep Psychiatr. 2016;2016(3614053):1–3.Google Scholar
- 46.Grotenhermen F, Russo E. Cannabis and cannabinoids: pharmacology, toxicology, and therapeutic potential. Binghamton: The Haworth Press. p. 2002.Google Scholar