Exploring the efficacy of cannabinoids in the management of multiple sclerosis
DOI:
https://doi.org/10.12775/JEHS.2024.74.52563Keywords
multiple sclerosis, Cannabis, cannabinoids, neuropathic pain, spasticity, therapeutic strategiesAbstract
Introduction: Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system, marked by inflammation, demyelination, and neurodegeneration. It severely impacts quality of life with symptoms like spasticity, pain, and cognitive impairment. Conventional treatments often fail, necessitating alternative therapies.
Purpose: This review evaluates the efficacy and safety of cannabis extracts in treating MS, enhancing understanding of their benefits and limitations.
State of knowledge: Studies suggest that cannabinoids may alleviate MS symptoms, particularly spasticity and pain. Clinical trials have shown significant reductions in muscle stiffness and pain, along with improved sleep quality. Meta-analyses, by Whiting et al. and Cochrane, support these findings but highlight the risk of side effects, which may limit long-term use. Additionally, research on animal models and in vitro studies indicate that cannabinoids may have neuroprotective and immunomodulatory properties, potentially reducing neuroinflammation and demyelination.
Conclusion: Cannabinoids exhibit potential as a complementary therapy for managing MS symptoms, especially spasticity and pain. However, evidence is mixed, with some studies showing limited efficacy and considerable risk of side effects. More long-term, high-quality studies are needed to fully understand the therapeutic potential and safety profile of cannabinoids in MS treatment. Despite the challenges, the growing availability and changing legal status of medical cannabis suggest it could be a viable option for some patients, provided its use is carefully monitored and adapted to individual needs.
References
Browne P, Chandraratna D, Angood C, et al. Atlas of Multiple Sclerosis 2013: A growing global problem with widespread inequity. Neurology. (2014) 83:1022-4;https://doi.org/10.1212/WNL.0000000000000768.
Noseworthy J. Progress in determining the causes and treatment of multiple sclerosis. Nature 399 A40-A47. 1999;https://doi.org/10.1038/399a040.
Coles A, Alastair D, Compston S, et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. Oct 2008;https://doi.org/10.1056/NEJMoa0802670:1786-801;359(17).
Doshi A, Chataway J. Multiple sclerosis, a treatable disease. Clin Med (Lond). 2016 Dec; 16(Suppl 6): s53–s59;https://doi.org/10.7861/clinmedicine.16-6-s53.
Lassmann H, Brück W, Lucchinetti C. The immunopathology of multiple sclerosis: an overview. Brain Pathology. 2007;17(2):210-218;https://doi.org/10.1111/j.1750-3639.2007.00064.x.
Belbasis L, Bellou V, Evangelou E, Ioannidis JPA, Tzoulaki I. Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analyses”. Lancet. Neurology. 2015 Mar;14(3):263-73;https://doi.org/10.1016/S1474-4422(14)70267-4.
Isobe N, Madireddy L, Khankhanian P, et al. An ImmunoChip study of multiple sclerosis risk in African Americans. Brain. 2015 Jun; 138(6): 1518–1530.;https://doi.org/10.1093/brain/awv078.
Haddad F, Dokmak G, Karaman R. The Efficacy of Cannabis on Multiple Sclerosis-Related Symptoms. Life (Basel). 2022 May 5;12(5):682.;https://doi.org/10.3390/life12050682.
Zajicek J, Hobart J, Slade A, Barnes D, Mattison P. Multiple Sclerosis and Extract of Cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry. 2012;83:1125-1132;https://doi.org/10.1136/jnnp-2012-302468.
Lublin F. New multiple sclerosis phenotypic classification. Eur Neurol. 2014:72 Suppl 1:1-5.;https://doi.org/10.1159/000367614.
Kurtzke J. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-1452;https://doi.org/10.1212/wnl.33.11.1444.
Walczak A, Arkuszewski M, Adamczyk-Sowa M. Rozszerzona Skala Niepełnosprawności (EDSS, Expanded Disability Status Scale) — według J. Kurtzkego. Polski Przegląd Neurologiczny. 2017;13;1(https://journals.viamedica.pl/polski_przeglad_neurologiczny/article/view/53968):32-35.
Perry M, Swain S, Kemmis-Betty S, Cooper P. Multiple sclerosis: summary of NICE guidance. BMJ. 2014; 349 :g5701;https://doi.org/10.1136/bmj.g5701.
Hauser S, Cree BA. Treatment of Multiple Sclerosis: A Review. The American Journal of Medicine. July 2020DOI:https://doi.org/10.1016/j.amjmed.2020.05.049;https://doi.org/10.1016/j.amjmed.2020.05.049.
Nouh R, Kamal A, Oyewole O, et al. Unveiling the Potential of Cannabinoids in Multiple Sclerosis and the Dawn of Nano-Cannabinoid Medicine. Pharmaceutics. 2024; 16(2):241.;https://doi.org/10.3390/pharmaceutics16020241.
Ziemssen T, Derfuss T, de Stefano N, et al. Optimizing treatment success in multiple sclerosis. J Neurol. (2016) 263:1053–65;https://doi.org/10.1007/s00415-015-7986-y.
Zajicek J, Fox P, Sanders H, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. The Lancet. November 2003;https://doi.org/10.1016/S0140-6736(03)14738-1.
Rice G, Incorvaia B, Munari L, et al. Interferon in relapsingremitting multiple sclerosis. Cochrane Database Syst. Rev. 2001;https://doi.org/10.1002/14651858.CD002002.
Schwab N, Schneider-Hohendorf T, Wiendl H. Therapeutic uses of anti-α4-integrin (anti-VLA-4) antibodies in multiple sclerosis. International Immunology. January 2015;https://doi.org/10.1093/intimm/dxu096:47-53;27;1.
Dąbrowski G, Skrajda M. Cannabinoids from Cannabis sp.: mechanism of their activity and potential health benefits in human body. Journal of Education, Health and Sport. August 2017;7(8):936-945;https://doi.org/10.5281/zenodo.995625.
Breijyeh Z, Jubeh B, Bufo S, Karaman R, Scrano L. Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses. Toxins. 2021, 13, 117;https://doi.org/10.3390/toxins13020117.
Bonini S, Premoli M, Tambaro S, et al. Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history. J. Ethnopharmacol. 2018, 227, 300–315.;https://doi.org/10.1016/j.jep.2018.09.004.
Hillig K, Mahlberg P. A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae). Am J Bot. 2004 Jun;91(6):966-75;https://doi.org/10.3732/ajb.91.6.966.
Furgiuele A, Cosentino M, Ferrari M, al e. Immunomodulatory Potential of Cannabidiol in Multiple Sclerosis: a Systematic Review. J Neuroimmune Pharmacol. (2021) 16, 251–269;https://doi.org/10.1007/s11481-021-09982-7.
VanDolah H, Bauer B, Mauck K. Clinicians' Guide to Cannabidiol and Hemp Oils. Mayo Clin Proc. 2019;94(9):1840-1851.;https://doi.org/10.1016/j.mayocp.2019.01.003.
Sosnoff J, Rudroff T. Cannabidiol to Improve Mobility in People with Multiple Sclerosis. Front Neurol. 2018; 9: 183.;https://doi.org/10.3389/fneur.2018.00183.
Zwibel H. Contribution of impaired mobility and general symptoms to the burden of multiple sclerosis. Adv Ther. 2009;26(12):1043-1057;https://doi.org/doi:10.1007/s12325-009-0082-x.
Maayah Z, Takahara S, Ferdaoussi M, Dyck J. The anti-inflammatory and analgesic effects of formulated full-spectrum cannabis extract in the treatment of neuropathic pain associated with multiple sclerosis. Inflamm Res. 2020 Jun;69(6):549-558;https://doi.org/10.1007/s00011-020-01341-1.
Russo E. Taming THC: potential cannabis synergy and phytocannabinoid–terpenoid entourage effects. Br J Pharmacol. (2011) 163:1344–64.;https://doi.org/10.1111/j.1476-5381.2011.01238.x.
Puighermanal E, Busquets-Garcia A, Maldonado R, Ozaita A. Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids. Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5; 367(1607): 3254–3263;https://doi.org/10.1098/rstb.2011.0384.
Pertwee R. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacology & Therapeutics. 1997;https://doi.org/10.1016/S0163-7258(97)82001-3:129-180;74.
Meyer H, Lee F, Gee D. The Role of the Endocannabinoid System and Genetic Variation in Adolescent Brain Development. Neuropsychopharmacology. 2018 Jan;43(1):21-33;https://doi.org/10.1038/npp.2017.143.
Ingram G, Pearson RO. Cannabis and multiple sclerosis. Pract Neurol. 2019 Aug;19(4):310-315.;https://doi.org/10.1136/practneurol-2018-002137.
Gong J, Onaivi E, Ishiguro H, et al. Cannabinoid CB2 receptors: Immunohistochemical localization in rat brain. Brain Research. 2006;https://doi.org/10.1016/j.brainres.2005.11.035:10-23;1071.
Überall M. A Review of Scientific Evidence for THC:CBD Oromucosal Spray (Nabiximols) in the Management of Chronic Pain. J Pain Res. 2020 Feb 14;13:399-410.;https://doi.org/10.2147/JPR.S240011.
Fischedick J. Identification of terpenoid chemotypes among high (−)-trans-∆9-tetrahydrocannabinol-producing Cannabis sativa L. cultivars. Cannabis and Cannabinoid Research. 2017;https://doi.org/10.1089/can.2016.0040:34-47;2.
Wegener N, Koch M. Neurobiology and systems physiology of the cannabinoid system. Pharmacopsychiatry. 2009;42 Suppl 1:S79-S86.;https://doi.org/10.1055/s-0029-1216346.
Iuvone T, Esposito G, Esposito R, Santamaria R, Di Rosa M, Izzo A. Neuroprotective effect of cannabidiol, a non-psychoactive component from Cannabis sativa, on β-amyloid-induced toxicity in PC12 cells. Journal of Neurochemistry. 2004 89: 134-141.;https://doi.org/10.1111/j.1471-4159.2003.02327.x.
Kozela E, Lev N, Kaushansky N, et al. Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice. British Journal of Pharmacology. 2011 1507-1519;https://doi.org/10.1111/j.1476-5381.2011.01379.x.
Whiting P, Wolff R, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. 2015;313(24):2456–2473;https://doi.org/doi:10.1001/jama.2015.6358.
Lakhan S, Rowland M. Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurol. 9, 59 (2009);https://doi.org/10.1111/j.1476-5381.2011.01379.x.
Filippini G, Minozzi S, Borrelli F, Cinquini M, Dwan K. Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis. Cochrane Database Syst Rev. 2022 May 5;5(5):CD013444;https://doi.org/10.1002/14651858.CD013444.pub2.
Baker D, Pryce G, Croxford J, et al. Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J. 2001, 15(2): 300-302.;https://doi:10.1096/fj.00-0399fje.
Rainka M, Aladeen T, Mattle A, et al. Multiple Sclerosis and Use of Medical Cannabis: A Retrospective Review of a Neurology Outpatient Population. International Journal of MS Care. 2023; 25 (3): 111–117;https://doi.org/10.7224/1537-2073.2022-006.
Arévalo-Martín A, Vela JM, Molina-Holgado E, Borrell J, Guaza C. Therapeutic action of cannabinoids in a murine model of multiple sclerosis. J. Neurosci. 2003; 23, 2511–2516;https://doi.org/10.1523/JNEUROSCI.23-07-02511.2003.
Croxford JL, Miller SD. Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212. J. Clin. Invest. 2003; 111, 1231–1240.;https://doi.org/10.1172/jci200317652.
Chiurchiù V, Van Der Stelt M, Centonze D, Maccarrone M. The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: clues for other neuroinflammatory diseases. Prog. Neurobiol. 2018; 160, 82–100.;https://doi: 10.1016/j.pneurobio.2017.10.007.
El-Alfy A, Ivey K, Robinson K, et al. Antidepressant-like effect Δ9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacol Biochem Behav. 2010; 95:434–42;https://doi.org/10.1016/j.pbb.2010.03.004.
Koppel B, Brust J, Fife T, 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, 1556–1563;https://doi.org/10.1212/WNL.0000000000000363.
Ball S, Vickery J, Hobart J, et al. The CUPID trial: A randomised double-blind placebo-controlled parallel-group multi-centre trial of cannabinoids to slow progression in multiple sclerosis. Health Technol. Assess. 2015, 19, 1–187;https://doi.org/10.3310/hta19120.
Sativex SmPC 2012. https://rejestrymedyczne.ezdrowie.gov.pl/api/rpl/medicinal-products/29034/characteristic. Accessed 24 May 2024.
Schimrigk S, Marziniak M, Neubauer C, Kugler E, Werner G, Abramov-Sommariva D. Dronabinol is a safe long-term treatment option for neuropathic pain patients. Eur. Neurol. 2017, 78, 320–329.;https://doi.org/10.1159/000481089.
Zajicek J, Fox P, Sanders H, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): Multicentre randomised placebo-controlled trial. Lancet. 2003, 362, 1517–1526.;https://doi.org/10.1016/S0140-6736(03)14738-1.
Bergamaschi M, Queiroz R, Zuardi A, Crippa J. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011;6(4):237-249.;https://doi:10.2174/157488611798280924.
Malan TJ, Ibrahim M, Lai J, Vanderah T, Makriyannis A, Porreca F. CB2 cannabinoid receptor agonists: pain relief without psychoactive effects?. Curr Opin Pharmacol. 2003;3(1):62-67.;https://doi.org/10.1016/s1471-4892(02)00004-8.
Wade D, Makela P, House H, Bateman C, Robson P. Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis. Mult Scler. 2006;12(5):639-645.;https://doi.org/10.1177/1352458505070618.
Laurent K, Roux P, Rolland B, et al. Acute and long-term effects of cannabis use: a review. Curr Pharm Des. 2014;20(25):4112-4118.;https://doi.org/10.2174/13816128113199990620.
Niesink R, van Laar M. Does Cannabidiol Protect Against Adverse Psychological Effects of THC?. Front Psychiatry. 2013;4:130.;https://doi.org/10.3389/fpsyt.2013.00130.
Piper B, DeKeuster R, Beals M, et al. Substitution of medical cannabis for pharmaceutical agents for pain, anxiety, and sleep. Journal of Psychopharmacology. 2017;31(5):569-575.;https://doi.org/10.1177/0269881117699616.
Lopez-Quintero C, Pérez de los Cobos J, Hasin D, 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):120-130.;https://doi.org/10.1016/j.drugalcdep.2010.11.004.
Stout SM CN. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review.. Drug Metab Rev.. 2014;46(1):86-95.(doi:10.3109/03602532.2013.849268).
Sativex oral mucosal spray. electronic Medicines Compendium (eMC). May 2015.. Available at: www.medicines.org.uk/emc/ medicine/23262. Accessed May 22, 2024.
Zhang Q, Dai X, Zhang H, Zeng Y, Luo K, Li W. Recent advances in development of nanomedicines for multiple sclerosis diagnosis. Biomed Mater. 2021 Feb 17;16(2):024101.;https://doi.org/10.1088/1748-605X/abddf4.
Onaivi E, Singh Chauhan B, Sharma V. Challenges of cannabinoid delivery: how can nanomedicine help?. Nanomedicine (Lond). 2020;15(21):2023-2028.;https://doi.org/10.2217/nnm-2020-0221.
Durán-Lobato M, Álvarez-Fuentes J, Fernández-Arévalo M, Martín-Banderas L. Receptor-targeted nanoparticles modulate cannabinoid anticancer activity through delayed cell internalization. Sci Rep. 2022 Jan 25;12(1):1297.;https://doi.org/10.1038/s41598-022-05301-z.
Pinkas J, Jabłoński P, Kidawa M, Wierzba W. Use of marijuana for medical purposes. Ann Agric Environ Med. 2016;23(3):525-528;https://doi.org/10.5604/12321966.1219200.
Internet-Based Law System Act of the 7th of July 2017 Amending the Act on Counteracting Drug Addiction and the Act on Reimbursement of Medicines, Foodstuffs for Special Nutritional Purposes and Medical Devices. https://isap.sejm.gov.pl/isap.nsf/DocDetails.xsp?id=wdu20170001458. Accessed 22 May 2024.
Internet-Based Law System: Announcement of the Minister of Health of the 20th of January 2021 on the Announcement of the Consolidated Text of the Regulation of the Minister of Health on Narcotic Drugs, Psychotropic Substances, Precursors Category 1 and Pr. https://isap.sejm.gov.pl/isap.nsf/download.xsp/WDU20210000166/O/D20210166.pdf. Accessed 22 May 2024.
Hordowicz M, Jarosz J, Czaplińska M, Leonhard A, Klimkiewicz A. Polish Physicians' Perspectives on Medical Cannabis Policy and Educational Needs: Results of An Online Survey. J Clin Med. 2021 Sep 30;10(19):4545.;https://doi.org/10.3390/jcm10194545.
Russo E. Cannabis Therapeutics and the Future of Neurology. Front. Integr. Neurosci. 2018; 12:51.;https://doi.org/10.3389/fnint.2018.00051.
Bridgeman M, Abazia D. Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting. P T. 2017;42(3):180-188(PMCID: PMC5312634).
Szulc M. The health consequences of marijuana use in the light of research and the proposal standardize the position of psychologists to the problem of the legalization of cannabis, formulated on the basis of the Code of Ethics and Professional Psychologists. Alcoholism and Drug Addiction. 2013; 26(4): 381–401 (in Polish).
Maayah Z, Takahara S, Ferdaoussi M, Dyck J. The anti-inflammatory and analgesic effects of formulated full-spectrum cannabis extract in the treatment of neuropathic pain associated with multiple sclerosis. Inflamm Res. 2020 Jun;69(6):549-558.;https://doi.org/10.1007/s00011-020-01341-1.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Aleksandra Rykucka, Natalia Zozula, Marcin Wąs, Justyna Kiełbasa, Agata Kowalczyk, Katarzyna Bil, Iga Ślesicka, Aleksandra Latała, Zuzanna Tomczewska, Magda Przestrzelska
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 467
Number of citations: 0