Cannabis as a Possible Treatment for Spasticity in Multiple Sclerosis / Kanabis Kao Moguci Tretman U Lecenju Spasticnosti Kod Multiple Skleroze

Open access


The therapeutic potential of cannabis has been known for centuries. Cannabinoids express their effects through two types of receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). Present studies indicate that cannabis-based drugs can make a positive impact in the treatment of different diseases. For many years, multiple sclerosis patients have self-medicated with illegal street cannabis to alleviate spasticity, a common and debilitating symptom that impairs quality of life.

Nabiximols is the cannabis-based medicine approved in many countries as an add-on therapy for symptom improvement in patients with spasticity who have not responded adequately to other medications. Adverse events such as dizziness, diarrhoea, fatigue, nausea, headache and somnolence occur quite frequently with nabiximols, but they are generally of mild-to-moderate intensity and their incidence can be markedly reduced by gradual uptitration. The prerequisite for the therapeutic use of cannabis in Serbia arerequires legal clarification for the use of the drug in a clinical environment

1. Zuardi AW. History of cannabis as a medicine:a review. Rev Bras Psiquiatr.2006; 28 (2): 153-7.

2. Guy G, Whittle BA, Robson PJ. Medical Uses of Cannabis and Cannabinoids. London: Pharmaceutical Press. 2004.

3. Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc. 1964; 86: 1646-1647.

4. Matsuda LA, Bonner TI and Lolait SJ. Localization of cannabinoid receptor mRNA in rat brain. J Comp Neurol. 1993; 327: 535-550.

5. Munro S, Thomas KL and Abu-Sharr M. Molecular characterization of a peripheral receptor for cannabinoids. Nature.1993; 365: 61-65.

6. Iversen L.Cannabis and the brain: Review. Brain.2003 Jun; 126 (6): 1252-70.

7. Herkenham M, Lynn AB, Johnson MR, Melvin LS, De Costa BR and Rice KC. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci. 1991; 11: 563-583.

8. Hohmann AG, Walker JM. Cannabinoid suppression of noxious heat-evoked activity in wide dynamic range neurons in the lumbar dorsal horn of the rat. J Neurophysiol. 1999; (81): 575-583.

9. Sanudo-Pena MC, Strangman NM, Mackie K, Walker JM and Tsou K. CB1 receptor localization in spinal cord and roots, dorsal root ganglion and peripheral nerve. Acta Pharmacol Sin. 1999; (12): 1115-1120.

10. Vaughan VW, Connor M, Bagley EE and Christie MJ. Actions of cannabinoids on membrane properties and synaptic transmission in rat periaqueductal gray neurons in vitro. Mol Pharmacol. 2000; (57): 288-295.

11. Rodriguez de Fonseca F, Del Arco I, Bermudez-Silva FJ, Bilbao A, Cippitelli A, Navarro M. The endocannabinoid system: physiology and pharmacology. Alcohol Alchol. 2005; Vol.40 (1): 2-14.

12. Wegener N, Koch_M. Neurobiology and systems physiology of the endocannabinoid system. Pharmacopsychiatry 2009; 42 (1): 79-86

13. Petrosino S., Di Marzo V. FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels. Curr Opin Investig Drugs 2010; 11: 51-62.

14. Matthew J. McFarland, Ekaterina A.Terebova and Eric L. Barker. Detergent-Resistant Membrane Microdomains in the Disposition of the Lipid Signaling Molecule Anandamide. 2005 AAPS National Biotechnology Conference Symposium on Lipidomics. 2006: 95-100.

15. Colls BM, Ferry DG, Gray AJ, Harvey VJ, McQueen EG. The antiemetic activity of tetrahydrocanabinol versus metoclopramide and thiethylperazine in patient undergoing cancer chemotherapy. N Z Med J.1980; (91): 449-451.

16. McCabe M, Smith FP, Goldberg D, Macdonald J, Wooley PV, Warren R. Efficacy of tetrahydrocannabinol in patient refractory to standard antiemetic therapy. Invest New Drugs. 1988; (6): 243-246.

17. Duran M, Perez E, Abanades S et al. Preliminary efficacy and safety of an oromuscular standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacology. 2010; (70): 656-663.

18. Beal JE, Olson R, Laubenstein L, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Sympt Manag.1995; (10): 89-97.

19. Strasser F, Luftner D, et al. Canabis in cachexia study group.Comparasion of orally administreted canabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double- blind, placebo-controlled clinical trial from the Cnnabis in cachexia study group. J Clin Oncol. 2006; (24): 3394-3400.

20. Volicer L,Stelly M, Morris J, McLaughlin J, Volicer BJ. Effects of dronabinol on anorexia and disturbed behavior in patinets with Alzheimer’s disease. Int J Geriatr Psychiatry.1997; (12): 913-919.

21. Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D. Sativex successfully treats neuropathic pain characterised by allodynia: a randomized, double-blind, placebo-controlled clinical trial. Pain. 2007; (133): 210-220.

22. Rog DJ, Nurmikko TJ, Friede T, Young CA.Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology.2005; (65): 812-819.

23. Seeling W,Kneer L, Buchele B, et al. Delta-9-tetrahydrocannabinol and the opioid receptor agonist piritramide do not act synergistically in postoperative paip. Anaesthesist. 2006; (55): 391-400.

24. Muller-Vahl KR, Schneider U, Prevedel H, et al. 9-tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome:a 6-week randomized trial. J Clin Psychiatry. 2003; (64): 459-465.

25. Sieradzan KA, Fox SH,Dick J, Brotchie JM. The effects of the cannabinoid receptor agonist nabilone on L-dopa induced dyskinesia in patients with idiopathic Parkinon’s disease. Movement disorders.1998; 13 (Suppl 2).

26. Nielsen JB, Crone C., Hultborn H. The spinal pathophysiology of spasticity-from a basic science point of view. Acta Physiologica 2007; 189: 171-180.

27. Rizzo MA, Hadjimichael OC, Preiningerova J, Vollmer TL.Prevalence and treatment of spasticity reported by multiple sclerosis patients. Mult Scler.2004; 10 (5): 589-595.

28. Crayton HJ, Rossman HS. Clinical Therapeutics 2006; 28 (4): 445-460.

29. Beard S, Hunn A, Wight J. Treatments for spasticity and pain in multiple sclerosis: a systematic review. Health Technol Assess_2003; 7(40): 101-111.

30. Bhimani R, Anderson L. Clinical understanding of spasticity: implications for practice. Rehabil Res Pract.2014; 2014:279175. doi: 10.1155/2014/279175.

31. Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med._2000; 160 (22): 415-420.

32. Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev.2003; 4:CD001332.

33. Novotna A, Mares J, Ratcliffe S,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; 2-10.

34. Clark AJ, Ware MA, Yazer E, Murray TJ, Lynch ME. Patterns of cannabis use among patients with multiple sclerosis.Nerurology.2004; 62:2098-2100.

35. Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG et al. Endocannabinoids control spasticity in a multiple sclerosis model. Faseb J.2011; 15:300-302.

36. Hohmann AG, Herkenham M. Localization of central cannabinoid CB1 receptor messenger RNA in neuronal subpopulations of rat dorsal root ganglia: a doublelabel in situ hybridization study. Neuroscience.1999; 90(3): 923-931.

37. Pertwee RG.Cannabinoid receptors and pain. Prog Neurobiology.2010; 63(5): 569-611.

38. Baker D., Pryce G., Jackson SJ., Bolton C., Giovannoni G. The biology that underpins the terapeutic potential of cannabis-based medicines for the control of spasticity in multiple sclerosis. Multiple sclerosis and Related Disordes 2012; 64: 64-75.

39. Kmietowicz Z. Cannabis based drug is licensed for spasticity in patients with MS. British Medical Journal 2010; 340: c 3363.

40. Burstein S. Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorg.Med.Chem. 2015; j.bmc 2015.01.059.

41. Russo E. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology. 2011; 163: 1344-1364.

42. Barnes MP. Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expert Opin Pharmacother. 2006; 7 (5): 607-15.

43. Collin C, Ehler E,Waberzinek G et al. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subject with symptoms of spasticity due to multiple sclerosis. Neurol Res.2010; 32(5): 451-459.

44. Ashton C John. Emerging treatment options for spasticity in multiple sclerosis-clinical utility of cannabinoids. Degenerative Neurological and Neuromuscular Disease. 2011; 15-23.

45. Tkaczyk M, Florek E, Piekoszewski W. Marihuana and cannabinoids as medicaments. Przegl Lek. 2012; 69 (10): 1095-97.

46. Iversen L. Long-termeffects of exposure to canabis. Curr Opin Pharmacol. 2005;5 (1):69-72 Radhakrishnan R., Wilkinson S. and D Souza DC. Gone to pot-a review of the association between cannabis and psychosis. Frontiers in psychiatry 2014; 54 (5): 1-24.

47. Radhakrishnan R., Wilkinson S. and D Souza DC. Gone to pot-a review of the association between cannabis and psychosis. Frontiers in psychiatry 2014; 54 (5): 1-24.

48. Wang T, Collet JP, Shapiro S, et al. Adverse effects of medical cannabinoids: a systematic review. CMAJ. 2008; 178 (13): 1669-1678.

49. Perez J.Combined cannabinoid therapy via an oromuscular spray. Drugs of Today.2006; 42: 495-503.

50. Iuvone T, Esposito G, De Filippis D, Scuderi C, Steardo L. Cannabidiol: a promising drug for neurodegenerative disorders. CNS Neurosci Ther. 2009; 15: 65-75.

51. Pozzilli C. Advances in the management of multiple sclerosis spasticity: experiences from recent studies and everyday clinical practice. Expert Rev Neurother.2013; 12: 49-54).

52. Scheduling of the cannabis-based medicine ‘Sativex’ Accessed in April 2015. Published: 27 March 2013.

53. Barbara S. Koppel, John C.M. Brust, Terry F, Jeff Bronstein,Sarah Youssof, Gary Gronseth and David Gloss. Systematic review: Efficacy and safety of medical marijuana in selected neurologic disorders. Neurology. 2014; 82_(17):_1556-1563.

54. Wright S.,Yadav V., Bever C Jr 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; 83 (16):1484-1486.

55. Potter DJ. A rivew of the cultivation and processing of cannabis (Cannabis sativa L.) for production of prescription medicines in the UK. Drug Test Anal. 2014; 6 (1-2): 31-38.

56. Zakon o psihoaktivnim kontrolisanim supstancama. Službeni glasnik Republike Srbije br.99/10. Accessed in April 2015.

57. Arroyo R, Vila C, Dechant KL. Impact of Sativex(®) on_quality of life_and activities of daily living in patients with multiple sclerosis spasticity.J Comp Eff Res. 2014; 3(4):435-44. doi: 10.2217/cer.14.30.

58. Slof J, Gras A. Sativex in multiple sclerosis spasticity: a cost-effectiveness model. Expert Rev Pharmacoecon Outcomes Res. 2012; 12 (4): 439-441

Serbian Journal of Experimental and Clinical Research

The Journal of Faculty of Medical Sciences, University of Kragujevac

Journal Information

CiteScore 2017: 0.21

SCImago Journal Rank (SJR) 2017: 0.126
Source Normalized Impact per Paper (SNIP) 2017: 0.081


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 381 381 22
PDF Downloads 129 129 7