{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:45:46Z","timestamp":1790729146942,"version":"4.1.0"},"reference-count":119,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Multiple sclerosis (MS) is known as an autoimmune disease that damages the neurons in the central nervous system. MS is characterized by its most common symptoms of spasticity, muscle spasms, neuropathic pain, tremors, bladder dysfunction, dysarthria, and some intellectual problems, including memory disturbances. Several clinical studies have been conducted to investigate the effects of cannabis on the relief of these symptoms in MS patients. The efficacy of Cannabis sativa (C. Sativa) in the management of MS outcomes such as spasticity, pain, tremors, ataxia, bladder functions, sleep, quality of life, and adverse effects were assessed in this review. Most clinical studies showed the positive effects of cannabinoids with their different routes of administration, such as oromucosal spray and oral form, in reducing most MS symptoms. The oromucosal spray Nabiximols demonstrated an improvement in reducing MS spasticity, pain, and quality of life with a tolerated adverse effect. Oral cannabinoids are significantly effective for treating MS pain and spasticity, while the other symptoms indicate slight improvement and the evidence is quite inconsistent. Oromucosal spray and oral cannabis are mainly used for treating patients with MS and have positive effects on treating the most common symptoms of MS, such as pain and spasticity, whereas the other MS symptoms indicated slight improvement, for which further studies are needed.<\/jats:p>","DOI":"10.3390\/life12050682","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T02:19:48Z","timestamp":1651717188000},"page":"682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["The Efficacy of Cannabis on Multiple Sclerosis-Related Symptoms"],"prefix":"10.3390","volume":"12","author":[{"given":"Fatma","family":"Haddad","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Department, Faculty of Pharmacy, Al-Quds University, Abu Dis, Jerusalem P144, Palestine"},{"name":"Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9866-7628","authenticated-orcid":false,"given":"Ghadeer","family":"Dokmak","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Department, Faculty of Pharmacy, Al-Quds University, Abu Dis, Jerusalem P144, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-4490","authenticated-orcid":false,"given":"Rafik","family":"Karaman","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Department, Faculty of Pharmacy, Al-Quds University, Abu Dis, Jerusalem P144, Palestine"},{"name":"Department of Sciences, University of Basilicata, 85100 Potenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev.neuro.30.051606.094313","article-title":"Multiple sclerosis: An immune or neurodegenerative disorder?","volume":"31","author":"Trapp","year":"2008","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/intimm\/dxu096","article-title":"Therapeutic uses of anti-\u03b14-integrin (anti-VLA-4) antibodies in multiple sclerosis","volume":"27","author":"Schwab","year":"2015","journal-title":"Int. Immunol."},{"key":"ref_3","first-page":"CD002002","article-title":"Interferon in relapsing-remitting multiple sclerosis","volume":"2001","author":"Rice","year":"2001","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/0003-9993(86)90060-2","article-title":"Disability, disease duration, and rehabilitation service needs in multiple sclerosis: Patient perspectives","volume":"67","author":"Kraft","year":"1986","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Breijyeh, Z., Jubeh, B., Bufo, S., Karaman, R., and Scrano, L. (2021). Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses. Toxins, 13.","DOI":"10.3390\/toxins13020117"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.jep.2018.09.004","article-title":"Cannabis sativa: A comprehensive ethnopharmacological review of a medicinal plant with a long history","volume":"227","author":"Bonini","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s40122-019-0114-4","article-title":"An update of current cannabis-based pharmaceuticals in pain medicine","volume":"8","author":"Urits","year":"2019","journal-title":"Pain Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1097\/JCP.0000000000000129","article-title":"Therapeutic satisfaction and subjective effects of different strains of pharmaceutical-grade cannabis","volume":"34","author":"Brunt","year":"2014","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1046\/j.1365-2044.2001.02269.x","article-title":"Pharmacological actions and therapeutic uses of cannabis and cannabinoids","volume":"56","author":"Kumar","year":"2001","journal-title":"Anaesthesia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"966","DOI":"10.3732\/ajb.91.6.966","article-title":"A chemotaxonomic analysis of cannabinoid variation in Cannabis (Cannabaceae)","volume":"91","author":"Hillig","year":"2004","journal-title":"Am. J. Bot."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1089\/acm.2013.0190","article-title":"Discriminating the effects of Cannabis sativa and Cannabis indica: A web survey of medical cannabis users","volume":"20","author":"Pearce","year":"2014","journal-title":"J. Altern. Complementary Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3389\/fneur.2017.00299","article-title":"Cannabis and multiple sclerosis\u2014The way forward","volume":"8","author":"Rudroff","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fpls.2016.00019","article-title":"Cannabis sativa: The plant of the thousand and one molecules","volume":"7","author":"Andre","year":"2016","journal-title":"Front. Plant Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1124\/pr.54.2.161","article-title":"International Union of Pharmacology. XXVII. Classification of cannabinoid receptors","volume":"54","author":"Howlett","year":"2002","journal-title":"Pharmacol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0163-7258(97)82001-3","article-title":"Pharmacology of cannabinoid CB1 and CB2 receptors","volume":"74","author":"Pertwee","year":"1997","journal-title":"Pharmacol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1136\/practneurol-2018-002137","article-title":"Cannabis and multiple sclerosis","volume":"19","author":"Ingram","year":"2019","journal-title":"Pract. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/S0301-0082(00)00031-9","article-title":"Cannabinoid receptors, and pain","volume":"63","author":"Pertwee","year":"2001","journal-title":"Prog. Neurobiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1111\/j.1476-5381.2011.01238.x","article-title":"Taming THC: Potential cannabis synergy and phytocannabinoid-terpenoid entourage effects","volume":"163","author":"Russo","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-45541-9_1","article-title":"Phytochemistry of Cannabis sativa L","volume":"103","author":"ElSohly","year":"2017","journal-title":"Phytocannabinoids"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-56785-1","article-title":"A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than \u03949-tetrahydrocannabinol: \u03949-Tetrahydrocannabiphorol","volume":"9","author":"Citti","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"O\u017carowski, M., Karpi\u0144ski, T., Zieli\u0144ska, A., Souto, E., and Wielgus, K. (2021). Cannabidiol in neurological and neoplastic diseases: Latest developments on the molecular mechanism of action. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094294"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1089\/can.2016.0040","article-title":"Identification of terpenoid chemotypes among high (\u2212)-trans-\u03949-tetrahydrocannabinol-producing Cannabis sativa L. cultivars","volume":"2","author":"Fischedick","year":"2017","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1016\/j.mayocp.2019.01.003","article-title":"Clinicians\u2019 guide to cannabidiol and hemp oils","volume":"94","author":"VanDolah","year":"2019","journal-title":"Mayo Clin. Proc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/j.1476-5381.2008.00048.x","article-title":"Emerging strategies for exploiting cannabinoid receptor agonists as medicines","volume":"156","author":"Pertwee","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/S0959-4388(02)00328-8","article-title":"Retrograde signaling by endocannabinoids","volume":"12","author":"Kreitzer","year":"2002","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0301-0082(02)00080-1","article-title":"Retrograde signaling in the regulation of synaptic transmission: Focus on endocannabinoids","volume":"68","author":"Alger","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3389\/fneur.2018.00183","article-title":"Cannabidiol to improve mobility in people with multiple sclerosis","volume":"9","author":"Rudroff","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1007\/s12325-009-0082-x","article-title":"Contribution of impaired mobility and general symptoms to the burden of multiple sclerosis","volume":"26","author":"Zwibel","year":"2009","journal-title":"Adv. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Jensen, C.J., Stankovich, J., Van Der Walt, A., Bahlo, M., Taylor, B.V., van der Mei, I., Foote, S., Kilpatrick, T., Johnson, L.J., and Wilkins, E. (2010). Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010003"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/gene.2011.34","article-title":"Genome-wide association study of severity in multiple sclerosis","volume":"12","author":"Briggs","year":"2011","journal-title":"Genes Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s11481-021-09982-7","article-title":"Immunomodulatory potential of cannabidiol in multiple sclerosis: A systematic review","volume":"16","author":"Furgiuele","year":"2021","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11910-019-0991-2","article-title":"Assessment and Measurement of Spasticity in MS: State of the Evidence","volume":"19","author":"Hugos","year":"2019","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1191\/1352458504ms1085oa","article-title":"Prevalence and treatment of spasticity reported by multiple sclerosis patients","volume":"10","author":"Rizzo","year":"2004","journal-title":"Mult. Scler. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.msard.2015.10.007","article-title":"Spasticity in multiple sclerosis: Associations with impairments and overall quality of life","volume":"5","author":"Milinis","year":"2016","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/sj.sc.3101928","article-title":"Spasticity-assessment: A review","volume":"44","author":"Nielsen","year":"2006","journal-title":"Spinal Cord"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/10790268.2005.11754545","article-title":"Overview of spasticity management in multiple sclerosis. Evidence-based management strategies for spasticity treatment in multiple sclerosis","volume":"28","author":"Haselkorn","year":"2005","journal-title":"J. Spinal Cord Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/ane.12202","article-title":"Spasticity in patients with multiple sclerosis\u2013clinical characteristics, treatment and quality of life","volume":"129","author":"Flachenecker","year":"2014","journal-title":"Acta Neurol. Scand."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3233\/NRE-2010-0596","article-title":"Spasticity: Revisiting the role and the individual value of several pharmacological treatments","volume":"27","author":"Lapeyre","year":"2010","journal-title":"NeuroRehabilitation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.pmrj.2013.04.022","article-title":"Adherence associated with oral medications in the treatment of spasticity","volume":"5","author":"Halpern","year":"2013","journal-title":"PMR"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1212\/WNL.0000000000000363","article-title":"Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders: Report of the Guideline Development Subcommittee of the American Academy of Neurology","volume":"82","author":"Koppel","year":"2014","journal-title":"Neurology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1212\/WNL.0000000000000250","article-title":"Summary of evidence-based guideline: Complementary and alternative medicine in multiple sclerosis: Report of the guideline development subcommittee of the American Academy of Neurology","volume":"82","author":"Yadav","year":"2014","journal-title":"Neurology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1177\/1352458506070947","article-title":"Cannabis use in patients with multiple sclerosis","volume":"12","author":"Chong","year":"2006","journal-title":"Mult. Scler. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/j.1742-1241.2004.00271.x","article-title":"The medicinal use of cannabis in the UK: Results of a nationwide survey","volume":"59","author":"Ware","year":"2005","journal-title":"Int. J. Clin. Pract."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2006.02.001","article-title":"Cannabinoids in medicine: A review of their therapeutic potential","volume":"105","author":"Amar","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2377-9-59","article-title":"Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: A systematic review","volume":"9","author":"Lakhan","year":"2009","journal-title":"BMC Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.2165\/11585260-000000000-00000","article-title":"Role of cannabinoids in the treatment of pain and (painful) spasticity","volume":"70","author":"Karst","year":"2010","journal-title":"Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.pain.2006.07.015","article-title":"Persistent pain and uncomfortable sensations in persons with multiple sclerosis","volume":"127","author":"Hadjimichael","year":"2007","journal-title":"Pain"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1191\/0269215506cr880oa","article-title":"Health problems and health-related quality of life in people with multiple sclerosis","volume":"20","author":"Forbes","year":"2006","journal-title":"Clin. Rehabil."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.pain.2007.08.024","article-title":"Pain associated with multiple sclerosis: Systematic review and proposed classification","volume":"137","author":"Schwid","year":"2008","journal-title":"PAIN"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1185\/030079906X158066","article-title":"Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain","volume":"23","author":"Iskedjian","year":"2007","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_51","first-page":"14","article-title":"Pain and MS","volume":"10","author":"Solaro","year":"2003","journal-title":"Int. MS J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3389\/fneur.2017.00312","article-title":"Cerebellar dysfunction in multiple sclerosis","volume":"8","author":"Wilkins","year":"2017","journal-title":"Front. Neurol."},{"key":"ref_53","first-page":"325","article-title":"The morbidity of multiple sclerosis","volume":"83","author":"Swingler","year":"1992","journal-title":"QJM Int. J. Med."},{"key":"ref_54","first-page":"CD005029","article-title":"Treatment for ataxia in multiple sclerosis","volume":"1","author":"Mills","year":"2007","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/mds.1280","article-title":"Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia","volume":"17","author":"Fox","year":"2002","journal-title":"Mov. Disord."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1191\/1352458504ms1082oa","article-title":"Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients","volume":"10","author":"Wade","year":"2004","journal-title":"Mult. Scler. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/S0140-6736(03)14738-1","article-title":"Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): Multicentre randomised placebo-controlled trial","volume":"362","author":"Zajicek","year":"2003","journal-title":"Lancet"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1177\/1352458506075651","article-title":"The neurogenic bladder in multiple sclerosis: Review of the literature and proposal of management guidelines","volume":"13","author":"Ruffion","year":"2007","journal-title":"Mult. Scler. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1016\/S0022-5347(05)68896-9","article-title":"Vesicourethral Dysfunction and Urodynamic Findings in Multiple Sclerosis: A Study of 149 Cases","volume":"161","author":"Gallien","year":"1999","journal-title":"J. Urol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/(SICI)1520-6777(1998)17:2<89::AID-NAU2>3.0.CO;2-8","article-title":"Urological dysfunctions and upper urinary tract involvement in multiple sclerosis patients","volume":"17","author":"Giannantoni","year":"1998","journal-title":"Neurourol. Urodyn. Off. J. Int. Cont. Soc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0022-5347(01)67258-6","article-title":"Relationship between lower urinary tract abnormalities and disease-related parameters in multiple sclerosis","volume":"154","author":"Koldewijn","year":"1995","journal-title":"J. Urol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.rehab.2014.05.009","article-title":"Current and future drugs for treatment of MS-associated bladder dysfunction","volume":"57","author":"Andersson","year":"2014","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"529","DOI":"10.3390\/ph5050529","article-title":"Cannabidiol in humans\u2014The quest for therapeutic targets","volume":"5","author":"Zhornitsky","year":"2012","journal-title":"Pharmaceuticals"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.sleep.2007.11.004","article-title":"Prevalence of \u2018poor sleep\u2019among patients with multiple sclerosis: An independent predictor of mental and physical status","volume":"10","author":"Merlino","year":"2009","journal-title":"Sleep Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.smrv.2009.07.005","article-title":"Sleep disorders in patients with multiple sclerosis","volume":"14","author":"Brass","year":"2010","journal-title":"Sleep Med. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1212\/WNL.63.11_suppl_5.S12","article-title":"A multimodal approach to managing the symptoms of multiple sclerosis","volume":"63","author":"Crayton","year":"2004","journal-title":"Neurology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.sleep.2008.02.002","article-title":"Importance of sleep in the quality of life of multiple sclerosis patients: A long under-recognized issue","volume":"10","author":"Attarian","year":"2008","journal-title":"Sleep Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1177\/1352458511432328","article-title":"Obstructive sleep apnea is associated with fatigue in multiple sclerosis","volume":"18","author":"Kaminska","year":"2012","journal-title":"Mult. Scler. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/0277-9536(95)00112-K","article-title":"The World Health Organization quality of life assessment: Position paper from the World Health Organization","volume":"41","author":"Group","year":"1995","journal-title":"Soc. Sci. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.dhjo.2017.04.008","article-title":"People with multiple sclerosis report significantly worse symptoms and health related quality of life than the US general population as measured by PROMIS and NeuroQoL outcome measures","volume":"11","author":"Amtmann","year":"2018","journal-title":"Disabil. Health J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1023\/A:1020734901150","article-title":"Quality of life and multiple sclerosis: Comparison between people with multiple sclerosis and people from the general population","volume":"9","author":"McCabe","year":"2002","journal-title":"J. Clin. Psychol. Med. Settings"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11910-018-0814-x","article-title":"The use of cannabis and cannabinoids in treating symptoms of multiple sclerosis: A systematic review of reviews","volume":"18","author":"Nielsen","year":"2018","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1002\/ana.22247","article-title":"Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab","volume":"69","author":"Gunnarsson","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"610","DOI":"10.2174\/187152712801661301","article-title":"Disease modifying drugs in multiple sclerosis: Mechanisms of action and new drugs in the horizon","volume":"11","author":"Marta","year":"2012","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2456","DOI":"10.1001\/jama.2015.6358","article-title":"Cannabinoids for medical use: A systematic review and meta-analysis","volume":"313","author":"Whiting","year":"2015","journal-title":"JAMA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1586\/ern.11.27","article-title":"Sativex\u00ae(tetrahydrocannabinol+ cannabidiol), an endocannabinoid system modulator: Basic features and main clinical data","volume":"11","author":"Vermersch","year":"2011","journal-title":"Expert Rev. Neurother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1111\/j.1468-1331.2010.03328.x","article-title":"A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols*(Sativex\u00ae), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis","volume":"18","author":"Novotna","year":"2011","journal-title":"Eur. J. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1358\/dot.2006.42.8.1021517","article-title":"Combined cannabinoid therapy via an oromucosal spray","volume":"42","author":"Perez","year":"2006","journal-title":"Drugs Today"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1179\/016164109X12590518685660","article-title":"A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis","volume":"32","author":"Collin","year":"2010","journal-title":"Neurol. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1007\/s00415-012-6739-4","article-title":"A double-blind, randomized, placebo-controlled, parallel-group study of THC\/CBD oromucosal spray in combination with the existing treatment regimen, in the relief of central neuropathic pain in patients with multiple sclerosis","volume":"260","author":"Langford","year":"2013","journal-title":"J. Neurol."},{"key":"ref_81","unstructured":"Leocani, L., Nuara, A., and Houdayer, E. (2014, January 10\u201313). Effect of THC-CBD oromucosal spray (Sativex) on measures of spasticity in multiple sclerosis: A double-blind, placebo-controlled, crossover study. Proceedings of the Joint Americas Committee for Treatment and Research in Multiple Sclerosis ACTRIMS\u2014European Committee for Treatment and Research in Multiple Sclerosis ECTRIMS Meeting, Boston, MA, USA."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1177\/1352458505070618","article-title":"Long-term use of a cannabis-based medicine in the treatment of spasticity and other symptoms in multiple sclerosis","volume":"12","author":"Wade","year":"2006","journal-title":"Mult. Scler. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/j.1468-1331.2006.01639.x","article-title":"Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis","volume":"14","author":"Collin","year":"2007","journal-title":"Eur. J. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/00207454.2018.1481066","article-title":"Sativex\u00ae as add-on therapy vs. further optimized first-line ANTispastics (SAVANT) in resistant multiple sclerosis spasticity: A double-blind, placebo-controlled randomised clinical trial","volume":"129","author":"Essner","year":"2019","journal-title":"Int. J. Neurosci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1080\/00207454.2020.1730832","article-title":"Tetrahydrocannabinol and cannabidiol oromucosal spray in resistant multiple sclerosis spasticity: Consistency of response across subgroups from the savant randomized clinical trial","volume":"130","author":"Meuth","year":"2020","journal-title":"Int. J. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/dta.1531","article-title":"A review of the cultivation and processing of cannabis (Cannabis sativa L.) for production of prescription medicines in the UK","volume":"6","author":"Potter","year":"2014","journal-title":"Drug Test. Anal."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11910-018-0859-x","article-title":"Cannabinoids for treatment of MS symptoms: State of the evidence","volume":"18","author":"Rice","year":"2018","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1212\/01.wnl.0000176753.45410.8b","article-title":"Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis","volume":"65","author":"Rog","year":"2005","journal-title":"Neurology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1093\/pm\/pnab050","article-title":"Nabiximols in chronic neuropathic pain: A meta-analysis of randomized placebo-controlled trials","volume":"22","author":"Dykukha","year":"2021","journal-title":"Pain Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1177\/1352458510378020","article-title":"Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis","volume":"16","author":"Kavia","year":"2010","journal-title":"Mult. Scler. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s10072-017-3148-6","article-title":"THC\/CBD oromucosal spray in patients with multiple sclerosis overactive bladder: A pilot prospective study","volume":"39","author":"Maniscalco","year":"2018","journal-title":"Neurol. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1002\/cbdv.200790150","article-title":"Cannabis, pain, and sleep: Lessons from therapeutic clinical trials of Sativex\u00ae, a cannabis-based medicine","volume":"4","author":"Russo","year":"2007","journal-title":"Chem. Biodivers."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1159\/000357427","article-title":"Nabiximols (THC\/CBD oromucosal spray, Sativex\u00ae) in clinical practice-results of a multicenter, non-interventional study (MOVE 2) in patients with multiple sclerosis spasticity","volume":"71","author":"Flachenecker","year":"2014","journal-title":"Eur. Neurol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1159\/000360285","article-title":"Long-term effectiveness and safety of nabiximols (tetrahydrocannabinol\/cannabidiol oromucosal spray) in clinical practice","volume":"72","author":"Flachenecker","year":"2014","journal-title":"Eur. Neurol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Gado, F., Digiacomo, M., Macchia, M., Bertini, S., and Manera, C. (2018). Traditional uses of cannabinoids and new perspectives in the treatment of multiple sclerosis. Medicines, 5.","DOI":"10.3390\/medicines5030091"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/hta19120","article-title":"The CUPID trial: A randomised double-blind placebo-controlled parallel-group multi-centre trial of cannabinoids to slow progression in multiple sclerosis","volume":"19","author":"Ball","year":"2015","journal-title":"Health Technol. Assess."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1212\/WNL.58.9.1404","article-title":"Safety, tolerability, and efficacy of orally administered cannabinoids in MS","volume":"58","author":"Killestein","year":"2002","journal-title":"Neurology"},{"key":"ref_98","first-page":"669","article-title":"Tetrahydrocannabinol for tremor in multiple sclerosis","volume":"13","author":"Clifford","year":"1983","journal-title":"Ann. Neurol. Off. J. Am. Neurol. Assoc. Child Neurol. Soc."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S0165-5728(03)00045-6","article-title":"Immunomodulatory effects of orally administered cannabinoids in multiple sclerosis","volume":"137","author":"Killestein","year":"2003","journal-title":"J. Neuroimmunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1136\/bmj.38149.566979.AE","article-title":"Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial","volume":"329","author":"Svendsen","year":"2004","journal-title":"BMJ"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1136\/jnnp.2005.070136","article-title":"Cannabinoids in multiple sclerosis (CAMS) study: Safety and efficacy data for 12 months follow up","volume":"76","author":"Zajicek","year":"2005","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"413S","DOI":"10.1002\/j.1552-4604.1981.tb02621.x","article-title":"Treatment of Human Spasticity with \u03949-Tetrahydrocannabinol","volume":"21","author":"Petro","year":"1981","journal-title":"J. Clin. Pharmacol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1300\/J251v07n01_04","article-title":"Delta-9-THC in the treatment of spasticity associated with multiple sclerosis","volume":"7","author":"Ungerleider","year":"1987","journal-title":"Adv. Alcohol Subst. Abus."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1007\/s00192-006-0086-x","article-title":"The effect of cannabis on urge incontinence in patients with multiple sclerosis: A multicentre, randomised placebo-controlled trial (CAMS-LUTS)","volume":"17","author":"Freeman","year":"2006","journal-title":"Int. Urogynecol. J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S1474-4422(13)70159-5","article-title":"Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): A randomised, placebo-controlled trial","volume":"12","author":"Zajicek","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1159\/000481089","article-title":"Dronabinol is a safe long-term treatment option for neuropathic pain patients","volume":"78","author":"Schimrigk","year":"2017","journal-title":"Eur. Neurol."},{"key":"ref_107","first-page":"393","article-title":"Current status of cannabis treatment of multiple sclerosis with an illustrative case presentation of a patient with MS, complex vocal tics, paroxysmal dystonia, and marijuana dependence treated with dronabinol","volume":"13","author":"Deutsch","year":"2008","journal-title":"CNS Spectr. Int. J. Neuropsychiatr. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/S0140-6736(95)90485-9","article-title":"Nabilone in the treatment of multiple sclerosis","volume":"345","author":"Martyn","year":"1995","journal-title":"Lancet"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1007\/s00415-006-0218-8","article-title":"Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain","volume":"253","author":"Wissel","year":"2006","journal-title":"J. Neurol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/pme.12569","article-title":"Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: A randomized controlled trial","volume":"16","author":"Turcotte","year":"2015","journal-title":"Pain Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s10072-009-0136-5","article-title":"Lack of effect of cannabis-based treatment on clinical and laboratory measures in multiple sclerosis","volume":"30","author":"Centonze","year":"2009","journal-title":"Neurol. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1136\/jnnp-2012-302468","article-title":"Multiple sclerosis and extract of cannabis: Results of the MUSEC trial","volume":"83","author":"Zajicek","year":"2012","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"102708","DOI":"10.1016\/j.msard.2020.102708","article-title":"Safety and efficacy of low-dose medical cannabis oils in multiple sclerosis","volume":"48","author":"Gustavsen","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e6865","DOI":"10.5867\/medwave.2017.6865","article-title":"Are cannabinoids effective in multiple sclerosis?","volume":"17","author":"Meza","year":"2017","journal-title":"Medwave"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/1352458518765649","article-title":"Balance worsening associated with nabiximols in multiple sclerosis","volume":"25","author":"Castelli","year":"2019","journal-title":"Mult. Scler. J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"102805","DOI":"10.1016\/j.msard.2021.102805","article-title":"Short and long term effects of Nabiximols on balance and walking assessed by 3D-gait analysis in people with Multiple Sclerosis and spasticity","volume":"51","author":"Siani","year":"2021","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1007\/s00415-020-09739-x","article-title":"Predictors of Nabiximols (Sativex\u00ae) discontinuation over long-term follow-up: A real-life study","volume":"267","author":"Carotenuto","year":"2020","journal-title":"J. Neurol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1191\/0269215503cr581oa","article-title":"A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms","volume":"17","author":"Wade","year":"2003","journal-title":"J. Clin. Rehab."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e183485","DOI":"10.1001\/jamanetworkopen.2018.3485","article-title":"Assessment of efficacy and tolerability of medicinal cannabinoids in patients with multiple sclerosis: A systematic review and meta-analysis","volume":"1","author":"Papaseit","year":"2018","journal-title":"JAMA Netw. Open"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/5\/682\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:06:09Z","timestamp":1760137569000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/5\/682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,5]]},"references-count":119,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["life12050682"],"URL":"https:\/\/doi.org\/10.3390\/life12050682","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,5]]}}}