Abrir sesión | Regístrese | Contacto | English |
Resúmenes Epistemonikos
Medwave 2017; 17(Suppl1):e6865 doi: 10.5867/medwave.2017.6865
¿Son efectivos los cannabinoides en la esclerosis múltiple?
Are cannabinoids effective in multiple sclerosis?
Rodrigo Meza, Javier Peña, Karen García, Oscar Corsi, Gabriel Rada
Referencias | Descargar PDF |
Para Descargar PDF debe Abrir sesión.
Imprimir | A(+) A(-) | Lectura fácil

Abstract

Multiple beneficial effects have been proposed lately for cannabinoids in different clinical situations. Among them, it has been postulated they would control symptoms of multiple sclerosis. However, there is no consensus about their real clinical role. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified 25 systematic reviews including 35 studies overall, of which 26 were randomized trials. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded cannabinoids in multiple sclerosis do not reduce spasticity or pain, and are probably associated to frequent adverse effects.


 
Problem

Multiple sclerosis is a demyelinating chronic disease of the central nervous system that might presents in a relapsing-remitting and/or progressive pattern. The clinical manifestations are multiple and include loss of strength and/or sensitivity in the limbs, visual loss, pain secondary to spasticity, ataxia, and bladder dysfunction. The treatment for relapses is usually based on corticosteroids. In the long term, different therapeutic alternatives are available, such as interferon beta, immunomodulatory agents, immunoglobulin, chemotherapeutic agents and sphingosine analogues. However, up to 30-40% of patients remain symptomatic.

Multiple beneficial effects have been proposed lately for cannabinoids in different clinical situations. Among them, it has been postulated tetrahydrocannabinol and cannabinidiol would control spasticity, pain and bladder dysfunction in multiple sclerosis, especially in patients with refractory symptoms. The proposed mechanisms are mediated through modulation of CB1 and CB2 receptors in the endocannabidiol system. However, the real clinical impact of cannabinoids in this condition is not clear.

Methods

We used Epistemonikos database, which is maintained by screening multiple databases, to identify systematic reviews and their included primary studies. With this information, we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

  • Cannabinoids do not reduce spasticity or pain in multiple sclerosis.
  • Cannabinoids are associated to adverse effects, which are probably frequent in multiple sclerosis.
About the body of evidence for this question

What is the evidence.
See evidence matrix  in Epistemonikos later

We found 25 systematic reviews [1],[2],[3],[4],[5],[6],[7], [8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20], [21],[22],[23],[24],[25], including 35 primary studies reported in 57 references [26],[27],[28],[29],[30],[31],[32],[33],[34], [35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46], [47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58], [59],[60],[61],[62],[63],[64],[65],[66],[67],[68],[69],[70], [71],[72],[73],[74],[75],[76],[77],[78],[79],[80],[81],[82], [83],[84],[85], among them 26 randomized controlled trials [26],[28],[33],[36],[38],[39],[40],[47],[48],[49],[52],[54], [57],[59],[60],[61],[62],[63],[70],[71],[73],[74],[76],[77], [79],[80]. This table and the summary in general are based on the latter.

What types of patients were included

All of the trials included patients with multiple sclerosis, but just a few specified the subtype: six trials included patients with relapsing-remitting multiple sclerosis [39],[40],[52], [60],[73],[76],[80]; seven trials included patients with primary progressive multiple sclerosis [40],[49],[52],[65], [71],[76],[80]; and eight trials included patients with secondary progressive multiple sclerosis [28],[33],[40],[49], [52],[71],[76],[80].

The age of the included patients was reported only in some trials, with a variable range, greater than 18 years old in all the cases.

The severity of the included patients was reported in only seven trials, using the EDSS score (expanded disability status scale), presenting a score greater than five in all of the trials [28],[36],[40],[49],[71],[76],[80]. In just eight trials the duration of disease was described, with a range of 4.5 to 17 years in the different trials [28],[33],[36],[49],[52],[71],[76], [80].

What types of interventions were included

One trial administered smoked cannabis [28], nine trials used cannabis capsules [39],[40],[49],[61],[73],[74],[76],[79], [80]; two trials used dronabinol [40], [71]; and ten trials used sublingual nabiximol spray [26],[33],[36],[38],[47],[48],[52], [59],[62],[70]. Other trials used less conventional presentations.

All of the trials compared against placebo.

What types of outcomes
were measured

The different systematic reviews grouped the outcomes in the following way:

  • Pain: evaluated according to visual analogue scale or numeric scale.
  • Bladder dysfunction: evaluated according to numeric scale or irritative symptoms.
  • Spasticity: evaluated according to Ashworth Scale or numeric scale.
  • Adverse effects: such as sedation, dizziness, headache, euphoria, among others.
  • Quality of life: according to subjective evaluation by patients.
  • Coordination: according to subjective evaluation by patients.
  • Mobility: according to subjective evaluation by patients.
  • Others: sleep quality, tremor, posture and balance, dependence.
Summary of findings

The information about the effects of cannabinoids in multiple sclerosis is based on seven randomized trials [33],[35],[36],[43],[52],[63],[69], that included 1,985 patients. The other trials did not report any outcome of interest, or did not present the information in a way it could be incorporated in a meta-analysis. Four trials [33],[36],[63],[80] reported spasticity (1,247 patients), three trials [33],[52],[70] reported pain (327 patients) and four trials [33],[36],[52],[63] reported adverse effects (1,025 patients). The summary of findings is the following:

  • Cannabinoids do not reduce spasticity in multiple sclerosis. The certainty of the evidence is high.
  • Cannabinoids do not reduce pain in multiple sclerosis. The certainty of the evidence is high.
  • Cannabinoids are associated to adverse effects, which are probably frequent in multiple sclerosis. The certainty of the evidence is moderate.


Other considerations for decision-making

To whom this evidence does and does not apply
  • The evidence presented in this summary applies to patients diagnosed with multiple sclerosis with symptoms such as: pain, spasticity or bladder dysfunction.
About the outcomes included in this summary
  • The outcomes presented in the summary of findings table, represent those considered critical for decision-making according to the opinion of the authors of this article. The symptoms frequently affect patients diagnosed with multiple sclerosis, and theoretically could be modified by cannabinoids.
Balance between benefits and risks, and certainty of the evidence
  • There is high certainty about the absence of benefits, and adverse effects are frequent. Although most adverse effects are mild and transient, severe adverse effects have also been reported.
  • The benefit/risk ratio is clearly not favorable.
What would patients and their doctors think about this intervention
  • Based on the existing evidence, most patients and clinicians should avoid the use of this intervention.
  • Some patients or even doctors could decide to use it because of preconceptions or ambiguous recommendations in current guidelines.
Resource considerations
  • Since there is no benefit it does not correspond to estimate a cost/benefit balance.
  • On the other hand, commercial formulations of cannabinoids vary in presentation and dosage but generally have a high cost.

Differences between this summary and other sources
  • The conclusions of the systematic reviews included in this article differ between each other. Although most conclude cannabinoids are not effective in multiple sclerosis or that existing evidence is not sufficient, some reviews, such as the one conducted to support the clinical guideline of the American Academy of Neurology, state they may be effective  [11].
  • The conclusions of the present summary partially coincide with the position of the main regulatory agencies; the U.S Food and Drug Administration (FDA) has not authorized the use of products containing or derivated from botanical marijuana because neither the safety or effectiveness have been proved for any indication [86]. Cannabinoids are not mentioned in the list of disease-modifying treatments approved by the European Medicines Agency (EMA). However, this agency authorized in 2014 the use of nabiximol in spray for the management of moderate to severe spasticity in adults diagnosed with multiple sclerosis who have not responded to conventional treatment, and who show clear clinical improvement in the initial period with this therapy [87].
  • The main clinical guidelines also differ between each other: the guideline of the Association of British Neurologists about prescription of disease-modifying treatment in multiple sclerosis does not include the use of cannabinoids [88]. The American Academy of Neurology [11] based on the systematic review mentioned above, recommends the use of oral cannabis extracts to reduce spasticity and pain (exluding neuropathic pain). It states nabiximol in spray may achieve improvement in spasticity, pain and urinary frequency, but recognizes existing evidence is insufficient to provide a recommendation for other symptoms derived from multiple sclerosis (anxiety, sleep disorders and cognition-related symptoms). The National Multiple Sclerosis Society recognizes the uncertainy and the need for more research, however it supports that patients and their doctors might eventually try this alternative [89]. 
Could this evidence change in the future?
  • The probaility that future evidence changes the conclusions of this summary regarding the effects of cannabinoids in multiple sclerosis is low due to the certainty of the current evidence.
  • There are no ongoing trials on this topic according to the records of the International Registry Platform for Controlled Trials of the World Health Organization.
  • The identified systematic reviews include a low proportion of the trials identified in this article and generally incorporate few data in the evidence synthesis. Eventually, a new systematic review with more comprehensive methods in terms of identification and data analysis, or with access to unpublished data, could provide relevant information in this matter.
How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Cannabinoids for multiple sclerosis

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

Licencia Creative Commons Esta obra de Medwave está bajo una licencia Creative Commons Atribución-NoComercial 3.0 Unported. Esta licencia permite el uso, distribución y reproducción del artículo en cualquier medio, siempre y cuando se otorgue el crédito correspondiente al autor del artículo y al medio en que se publica, en este caso, Medwave.

 

Multiple beneficial effects have been proposed lately for cannabinoids in different clinical situations. Among them, it has been postulated they would control symptoms of multiple sclerosis. However, there is no consensus about their real clinical role. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified 25 systematic reviews including 35 studies overall, of which 26 were randomized trials. We extracted data, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. We concluded cannabinoids in multiple sclerosis do not reduce spasticity or pain, and are probably associated to frequent adverse effects.

Autores: Rodrigo Meza[1,2], Javier Peña[1,2], Karen García[1,2], Oscar Corsi[2,4], Gabriel Rada[2,3,4,5,6]

Filiación:
[1] Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[2] Proyecto Epistemonikos, Santiago, Chile
[3] Programa de Salud Basada en Evidencia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[4] Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
[5] GRADE working group
[6] The Cochrane Collaboration

E-mail: radagabriel@epistemonikos.org

Correspondencia a:
[1] Facultad de Medicina
Pontificia Universidad Católica de Chile
Diagonal Paraguay 476
Santiago Centro
Chile.

Citación: Meza R, Peña J, García O, Corsi O, Rada G. Are cannabinoids effective in multiple sclerosis?. Medwave 2017; 17(Suppl1):e6865 doi: 10.5867/medwave.2017.6865

Fecha de envío: 27/12/2016

Fecha de aceptación: 27/12/2016

Fecha de publicación: 10/3/2017

Ficha PubMed

Comentarios (0)

Nos complace que usted tenga interés en comentar uno de nuestros artículos. Su comentario será publicado inmediatamente. No obstante, Medwave se reserva el derecho a eliminarlo posteriormente si la dirección editorial considera que su comentario es: ofensivo en algún sentido, irrelevante, trivial, contiene errores de lenguaje, contiene arengas políticas, obedece a fines comerciales, contiene datos de alguna persona en particular, o sugiere cambios en el manejo de pacientes que no hayan sido publicados previamente en alguna revista con revisión por pares.

Aún no hay comentarios en este artículo.

Para comentar debe iniciar sesión

Medwave publica las vistas HTML y descargas PDF por artículo, junto con otras métricas de redes sociales.

Se puede producir un retraso de 48 horas en la actualización de las estadísticas.

  1. Bagshaw SM, Hagen NA. Medical efficacy of cannabinoids and marijuana: a comprehensive review of the literature. J Palliat Care. 2002 Summer;18(2):111-22 | PubMed |
  2. Ben Amar M. Cannabinoids in medicine: A review of their therapeutic potential. J Ethnopharmacol. 2006 Apr 21;105(1-2):1-25 | PubMed |
  3. Burns TL, Ineck JR. Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain. Ann Pharmacother. 2006 Feb;40(2):251-60 | PubMed |
  4. Correa D, Moreno C. Systematic review of the literature: tratment for central pain in multiple sclerosis. Acta neurol. colomb. 2009;25(1):4 - 15. | Link |
  5. Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev. 2003;(4):CD001332 | PubMed |
  6. Deshpande A, Mailis-Gagnon A, Zoheiry N, Lakha SF. Efficacy and adverse effects of medical marijuana for chronic noncancer pain: Systematic review of randomized controlled trials. Can Fam Physician. 2015 Aug;61(8):e372-81 | PubMed |
  7. Fisher B, Johnston D, Leake P. Marijuana for medicinal purposes: an evidence-based assessment. WorkSafe BC. 2002;76. | Link |
  8. Hazekamp A, Grotenhermen F. Review on clinical studies with cannabis and cannabinoids 2005-2009. Cannabinoids. 2010;5(special issue):1-21 | Link |
  9. Iskedjian M, Bereza B, Gordon A, Piwko C, Einarson TR. Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr Med Res Opin. 2007 Jan;23(1):17-24 | PubMed |
  10. Jawahar R, Oh U, Yang S, Lapane KL. A systematic review of pharmacological pain management in multiple sclerosis. Drugs. 2013 Oct;73(15):1711-22 | CrossRef | PubMed |
  11. Koppel BS, Brust JC, 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 Apr 29;82(17):1556-63 | CrossRef | PubMed |
  12. Lakhan SE, Rowland M. Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurol. 2009 Dec 4;9:59 | CrossRef | PubMed |
  13. Lynch ME, Ware MA. Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials. J Neuroimmune Pharmacol. 2015 Jun;10(2):293-301 | CrossRef | PubMed |
  14. Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011 Nov;72(5):735-44 | CrossRef | PubMed |
  15. Martín-Sánchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med. 2009 Nov;10(8):1353-68 | CrossRef | PubMed |
  16. Petzke F, Enax-Krumova EK, Häuser W. [Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain: A systematic review of randomized controlled studies]. Schmerz. 2016 Feb;30(1):62-88 | CrossRef | PubMed |
  17. Mills RJ, Yap L, Young CA. Treatment for ataxia in multiple sclerosis. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005029 | PubMed |
  18. Guerra SS. Are cannabinoids more effective than placebo in decreasing MS-related bladder dysfunction? British Journal of Neuroscience Nursing. 2012 | CrossRef |
  19. Tsang CC, Giudice MG. Nabilone for the Management of Pain. Pharmacotherapy. 2016 Mar;36(3):273-86 | CrossRef | PubMed |
  20. Wade DT, Collin C, Stott C, Duncombe P. Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis. Mult Scler. 2010 Jun;16(6):707-14 | CrossRef | PubMed |
  21. WCB Evidence Based Practice Group. Efficacy of marijuana in treating chronic non cancer pain: a short review. Richmond: WorkSafe BC. 2006 | Link |
  22. Whiting P, Wolff R, Westwood M, Duffy S, Misso K, Keurentjes Cet al. Systematic review of cannabis for medical use. Kleijnen Systematic Reviews Ltd. 2014 | Link |
  23. 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 Jun 23-30;313(24):2456-73 | Link |
  24. Zhornitsky S, Potvin S. Cannabidiol in humans-the quest for therapeutic targets. Pharmaceuticals (Basel). 2012 May 21;5(5):529-52 | CrossRef | PubMed |
  25. Andrzejewski K, Barbano R, Mink J. Cannabinoids in the treatment of movement disorders: A systematic review of case series and clinical trials. Basal Ganglia. 2016;6(3):173-181 | Link |
  26. Aragona M, Onesti E, Tomassini V, Conte A, Gupta S, Gilio F, et al. Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study. Clin Neuropharmacol. 2009 Jan-Feb;32(1):41-7 | CrossRef | PubMed |
  27. Brady CM, DasGupta R, Dalton C, Wiseman OJ, Berkley KJ, Fowler CJ. An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis. Mult Scler. 2004 Aug;10(4):425-33 | PubMed |
  28. Corey-Bloom J, Wolfson T, Gamst A, Jin S, Marcotte TD, Bentley H, et al. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMAJ. 2012 Jul 10;184(10):1143-50 | CrossRef | PubMed |
  29. Corey-Bloom J, Wolfson TJ, Anthony GC, Bentley H, Gouaux B. Short-term effects off medicinal cannabis on spasticity in multiple sclerosis. Neurology. 2008;70(11 (suppl 1)):A86-A87. | Link |
  30. Center for Medicinal Cannabis Research. Short-Term Effects of Medicinal Cannabis Therapy on Spasticity in Multiple Sclerosis. clinicaltrials.gov. 2001 | Link |
  31. Centonze D, Mori F, Koch G, Buttari F, Codecà C, Rossi S, et al. Lack of effect of cannabis-based treatment on clinical and laboratory measures in multiple sclerosis. Neurol Sci. 2009 Dec;30(6):531-4 | CrossRef | PubMed |
  32. Clifford DB. Tetrahydrocannabinol for tremor in multiple sclerosis. Ann Neurol. 1983 Jun;13(6):669-71 | PubMed |
  33. 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 Jun;32(5):451-9 | CrossRef | PubMed |
  34. Collin C, Ambler Z, Kent R, McCalla R. A randomised controlled study of Sativex® in patients with symptoms of spasticity due to multiple sclerosis. 22nd Congress of the ECTRIMS. 2006 | Link |
  35. GW Pharmaceuticals Ltd. A Study to Evaluate the Efficacy of Sativex in Relieving Symptoms of Spasticity Due to Multiple Sclerosis. clinicaltrials.gov. 2005 | Link |
  36. Collin C, Davies P, Mutiboko IK, Ratcliffe S; Sativex Spasticity in MS Study Group. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol. 2007 Mar;14(3):290-6. | PubMed |
  37. GW Pharmaceuticals Ltd. A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis. clinicaltrials.gov. 2002 | Link |
  38. Conte A, Bettolo CM, Onesti E, Frasca V, Iacovelli E, Gilio F, et al. Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis. Eur J Pain. 2009 May;13(5):472-7 | CrossRef | PubMed |
  39. Fox P, Bain PG, Glickman S, Carroll C, Zajicek J. The effect of cannabis on tremor in patients with multiple sclerosis. Neurology. 2004 Apr 13;62(7):1105-9. | PubMed |
  40. Freeman RM, Adekanmi O, Waterfield MR, Waterfield AE, Wright D, Zajicek J. The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS). Int Urogynecol J Pelvic Floor Dysfunct. 2006 Nov;17(6):636-41 | PubMed |
  41. Katona S, Kaminski E, Sanders H, Zajicek J. Cannabinoid influence on cytokine profile in multiple sclerosis. Clin Exp Immunol. 2005 Jun;140(3):580-5 | PubMed |
  42. Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM, et al. Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psychiatry. 2005 Dec;76(12):1664-9 | PubMed |
  43. Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, et al; UK MS Research Group. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomized placebo-controlled trial. Lancet. 2003 Nov 8;362(9395):1517-26 | PubMed |
  44. Medical Research Council (MRC) (UK). A multiple randomised controlled trial of cannabinoids on spasticity in multiple sclerosis (MS). ISRCTN.com. 2000 | Link |
  45. Greenberg HS, Werness SA, Pugh JE, Andrus RO, Anderson DJ, Domino EF. Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers. Clin Pharmacol Ther. 1994 Mar;55(3):324-8. | PubMed |
  46. Hamann W, di Vadi PP. Analgesic effect of the cannabinoid analogue nabilone is not mediated by opioid receptors. Lancet. 1999 Feb 13;353(9152):560 | PubMed |
  47. Kavia R, De Ridder D, Sarantis N, Constantinescu C. Randomised controlled trial of cannabis based medicine (CBM, Stativex®) to treat detrusor overactivity in multiple sclerosis. Neurourology and Urodynamics. 2006;25:166-166. | Link |
  48. Kavia RB, De Ridder D, Constantinescu CS, Stott CG, Fowler CJ. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler. 2010 Nov;16(11):1349-59 | CrossRef | PubMed |
  49. Killestein J, Hoogervorst EL, Reif M, Blauw B, Smits M, Uitdehaag BM, et al. Immunomodulatory effects of orally administered cannabinoids in multiple sclerosis. J Neuroimmunol. 2003 Apr;137(1-2):140-3. | PubMed |
  50. Killestein J, Hoogervorst EL, Reif M, Kalkers NF, Van Loenen AC, Staats PG, et al. Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Neurology. 2002 May 14;58(9):1404-7 | PubMed |
  51. Killestein J, Hoogervorst ELJ, Kalkers NF, van Winsen LML, Uitdehaag BMJ, Linssen-Schuurmans CD, et al. The effects of orally administred cannabinoids in multiple sclerosis patients: a pilot study. Multiple Sclerosis. 2000;6(1 suppl 1):S27-S27 | CrossRef |
  52. Langford RM, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, et al. 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. J Neurol. 2013 Apr;260(4):984-97 | CrossRef | PubMed |
  53. GW Pharmaceuticals Ltd. Sativex Versus Placebo When Added to Existing Treatment for Central Neuropathic Pain in MS. clinicaltrials.gov. 2006 | Link |
  54. Leocani L, Nuara A, Houdayer E, Del Carro U, Straffi L, Martinelli V, et al. Effect of THC-CBD oromucosal spray (Sativex) on measures of spasticity in multiple sclerosis: a double-blind, placebo-controlled, crossover study. Joint Americas Committee for Treatment and Research in Multiple Sclerosis ACTRIMS—European Committee for Treatment and Research in Multiple Sclerosis ECTRIMS Meeting. 2014 | Link |
  55. Martyn CN, Illis LS, Thom J. Nabilone in the treatment of multiple sclerosis. Lancet. 1995 Mar 4;345(8949):579 | PubMed |
  56. Meinck HM, Schönle PW, Conrad B. Effect of cannabinoids on spasticity and ataxia in multiple sclerosis. J Neurol. 1989 Feb;236(2):120-2 | PubMed |
  57. Notcutt W, Price M, Miller R, Newport S, Phillips C, Simmons S, et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 'N of 1' studies. Anaesthesia. 2004 May;59(5):440-52 | PubMed |
  58. GW Pharmaceuticals Ltd. A Study to Evaluate the Effects of Cannabis Based Medicine in Patients With Pain of Neurological Origin. clinicaltrials.gov. 2002 | Link |
  59. Notcutt W, Langford R, Davies P, Ratcliffe S, Potts R. A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols). Mult Scler. 2012 Feb;18(2):219-28 | CrossRef | PubMed |
  60. Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, et al; Sativex Spasticity Study Group. 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 Sep;18(9):1122-31 | CrossRef | PubMed |
  61. Petro DJ, Ellenberger C Jr. Treatment of human spasticity with delta 9-tetrahydrocannabinol. J Clin Pharmacol. 1981 Aug-Sep;21(8-9 Suppl):413S-416S. | PubMed |
  62. Robson P, Wade D, Makela P, House H, Bateman C. Cannabis-based medicinal extract (Sativex) produced significant improvements in a subjective measure of spasticity which were maintained on long-term treatment with no evidence of tolerance. IACM 3rd Conference on Cannabinoids in Medicine. 2005 | Link |
  63. Wade DT, Makela P, Robson P, House H, Bateman C. 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. Mult Scler. 2004 Aug;10(4):434-41 | PubMed |
  64. GW Pharmaceuticals Ltd. An Investigation of Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) in Multiple Sclerosis Patients. clinicaltrials.gov. 2001 | Link |
  65. Rog DJ, Nurmikko TJ, Young CA. Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin Ther. 2007 Sep;29(9):2068-79 | PubMed |
  66. Rog DJ, Nurmikko T, Young C, Sarantis NS. Randomized controlled trial of sativex, a cannabis based medicine (CBM), in central neuropathic pain due to multiple sclerosis, followed by an open-label extension. Neurology. 2006;66(5):A31-A31 | Link |
  67. Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 2005 Sep 27;65(6):812-9 | PubMed |
  68. Young CA, Rog DJ. Randomised controlled trial of cannabis based medicinal extracts (CBME) in central neuropathic pain due to multiple sclerosis. IV Congress of the European Federation of IASP Chapters (EFIC). 2003 | Link |
  69. GW Pharmaceuticals Ltd. A Study of Sativex in the Treatment of Central Neuropathic Pain Due to Multiple Sclerosis. clinicaltrials.gov. 2002 | Link |
  70. Serpell MG, Notcutt W, Collin C. Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. J Neurol. 2013 Jan;260(1):285-95 | CrossRef | PubMed |
  71. Svendsen KB, Jensen TS, Bach FW. [Effect of the synthetic cannabinoid dronabinol on central pain in patients with multiple sclerosis—secondary publication]. Ugeskr Laeger. 2005 Jun 20;167(25-31):2772-4 | PubMed |
  72. Svendsen KB, Jensen TS, Bach FW. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ. 2004 Jul 31;329(7460):253 | PubMed |
  73. Turcotte D, Doupe M, Torabi M, Gomori A, Ethans K, Esfahani F, et al. Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial. Pain Med. 2015 Jan;16(1):149-59. | CrossRef | PubMed |
  74. Ungerleider JT, Andyrsiak T, Fairbanks L, Ellison GW, Myers LW. Delta-9-THC in the treatment of spasticity associated with multiple sclerosis. Adv Alcohol Subst Abuse. 1987;7(1):39-50 | PubMed |
  75. Van Amerongen G, Beumer T, Killestein J, Groeneveld GJ. Individualized dosing of a novel oral DELTA9-THC formulation improves subjective spasticity and pain in patients with progressive multiple sclerosis. Joint Americas Committee for Treatment and Research in Multiple Sclerosis ACTRIMS—European Committee for Treatment and Research in Multiple Sclerosis ECTRIMS Meeting. 2014 | Link |
  76. Vaney C, Heinzel-Gutenbrunner M, Jobin P, Tschopp F, Gattlen B, Hagen U, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult Scler. 2004 Aug;10(4):417-24. | PubMed |
  77. Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003 Feb;17(1):21-9. | PubMed |
  78. Wade DT, Makela PM, 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 Oct;12(5):639-45 | PubMed |
  79. Wissel J, Haydn T, Müller J, Brenneis C, Berger T, Poewe W, et al. Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain: a double-blind placebo-controlled cross-over trial. J Neurol. 2006 Oct;253(10):1337-41 | PubMed |
  80. Zajicek JP, Hobart JC, Slade A, Barnes D, Mattison PG; MUSEC Research Group. Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry. 2012 Nov;83(11):1125-32 | CrossRef | PubMed |
  81. Hobart JC, Zajicek JP. Cannabis as a symptomatic treatment for MS: Clinically meaningful MUSEC to the stiffness and walking problems of people with MS. 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. 2012:247-247 | Link |
  82. Zajicek J, Reif M, Schnelle M. UK MUSEC Study Investigators. Cannabis extract in the treatment of muscle stiffness and other symptoms in multiple sclerosis – results of the MUSEC study. IACM 5th Conference on Cannabinoids in Medicine. 2009 | Link |
  83. Zajicek, J, Reif, M, Schnelle, M. Cannabis extract in the treatment of muscle stiffness and other symptoms in multiple sclerosis—Results of the MUSEC study. 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. 2009 | Link |
  84. Institut fur Klinische Forschung, Germany. Multiple Sclerosis and Extract of Cannabis (MUSEC) Study.clinicaltrials.gov. 2006 | Link |
  85. Gesellschaft fuer klinische Forschung e.V. Multiple Sclerosis and Extract of Cannabis (MUSEC): a randomised, double-blind, placebo-controlled phase III trial to determine the efficacy and safety of a standardised oral extract of cannabis sativa for the symptomatic relief of muscle stiffness and pa. EU Clinical Trial. 2006. | Link |
  86. FDA and Marijuana: Questions and Answers. Disponible en: http://www.fda.gov/newsevents/publichealthfocus/ucm421168.htm#notapproved). Accedido el 20 de Diciembre de 2016. | Link |
  87. EMEA-000181-PIP02-13. Disponible en: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-000181-PIP02-13/pip_001257.jsp&mid=WC0b01ac058001d129. Accedido el 20 de Diciembre de 2016. | Link |
  88. Scolding N, Barnes D, Cader S, Chataway J, Chaudhuri A, Coles A, et al. Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract Neurol. 2015 Aug;15(4):273-9 | CrossRef | PubMed |
  89. Medical Marijuana (Cannabis). Disponible en: http://www.nationalmssociety.org/Treating-MS/Complementary-Alternative-Medicines/Marijuana. Accedido el 20 de Diciembre de 2016. | Link |
  90. GW Pharmaceuticals Ltd. A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis. clinicaltrials.gov. 2002
Bagshaw SM, Hagen NA. Medical efficacy of cannabinoids and marijuana: a comprehensive review of the literature. J Palliat Care. 2002 Summer;18(2):111-22 | PubMed |

Ben Amar M. Cannabinoids in medicine: A review of their therapeutic potential. J Ethnopharmacol. 2006 Apr 21;105(1-2):1-25 | PubMed |

Burns TL, Ineck JR. Cannabinoid analgesia as a potential new therapeutic option in the treatment of chronic pain. Ann Pharmacother. 2006 Feb;40(2):251-60 | PubMed |

Correa D, Moreno C. Systematic review of the literature: tratment for central pain in multiple sclerosis. Acta neurol. colomb. 2009;25(1):4 - 15. | Link |

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

Deshpande A, Mailis-Gagnon A, Zoheiry N, Lakha SF. Efficacy and adverse effects of medical marijuana for chronic noncancer pain: Systematic review of randomized controlled trials. Can Fam Physician. 2015 Aug;61(8):e372-81 | PubMed |

Fisher B, Johnston D, Leake P. Marijuana for medicinal purposes: an evidence-based assessment. WorkSafe BC. 2002;76. | Link |

Hazekamp A, Grotenhermen F. Review on clinical studies with cannabis and cannabinoids 2005-2009. Cannabinoids. 2010;5(special issue):1-21 | Link |

Iskedjian M, Bereza B, Gordon A, Piwko C, Einarson TR. Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr Med Res Opin. 2007 Jan;23(1):17-24 | PubMed |

Jawahar R, Oh U, Yang S, Lapane KL. A systematic review of pharmacological pain management in multiple sclerosis. Drugs. 2013 Oct;73(15):1711-22 | CrossRef | PubMed |

Koppel BS, Brust JC, 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 Apr 29;82(17):1556-63 | CrossRef | PubMed |

Lakhan SE, Rowland M. Whole plant cannabis extracts in the treatment of spasticity in multiple sclerosis: a systematic review. BMC Neurol. 2009 Dec 4;9:59 | CrossRef | PubMed |

Lynch ME, Ware MA. Cannabinoids for the Treatment of Chronic Non-Cancer Pain: An Updated Systematic Review of Randomized Controlled Trials. J Neuroimmune Pharmacol. 2015 Jun;10(2):293-301 | CrossRef | PubMed |

Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011 Nov;72(5):735-44 | CrossRef | PubMed |

Martín-Sánchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med. 2009 Nov;10(8):1353-68 | CrossRef | PubMed |

Petzke F, Enax-Krumova EK, Häuser W. [Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain: A systematic review of randomized controlled studies]. Schmerz. 2016 Feb;30(1):62-88 | CrossRef | PubMed |

Mills RJ, Yap L, Young CA. Treatment for ataxia in multiple sclerosis. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005029 | PubMed |

Guerra SS. Are cannabinoids more effective than placebo in decreasing MS-related bladder dysfunction? British Journal of Neuroscience Nursing. 2012 | CrossRef |

Tsang CC, Giudice MG. Nabilone for the Management of Pain. Pharmacotherapy. 2016 Mar;36(3):273-86 | CrossRef | PubMed |

Wade DT, Collin C, Stott C, Duncombe P. Meta-analysis of the efficacy and safety of Sativex (nabiximols), on spasticity in people with multiple sclerosis. Mult Scler. 2010 Jun;16(6):707-14 | CrossRef | PubMed |

WCB Evidence Based Practice Group. Efficacy of marijuana in treating chronic non cancer pain: a short review. Richmond: WorkSafe BC. 2006 | Link |

Whiting P, Wolff R, Westwood M, Duffy S, Misso K, Keurentjes Cet al. Systematic review of cannabis for medical use. Kleijnen Systematic Reviews Ltd. 2014 | Link |

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 Jun 23-30;313(24):2456-73 | Link |

Zhornitsky S, Potvin S. Cannabidiol in humans-the quest for therapeutic targets. Pharmaceuticals (Basel). 2012 May 21;5(5):529-52 | CrossRef | PubMed |

Andrzejewski K, Barbano R, Mink J. Cannabinoids in the treatment of movement disorders: A systematic review of case series and clinical trials. Basal Ganglia. 2016;6(3):173-181 | Link |

Aragona M, Onesti E, Tomassini V, Conte A, Gupta S, Gilio F, et al. Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study. Clin Neuropharmacol. 2009 Jan-Feb;32(1):41-7 | CrossRef | PubMed |

Brady CM, DasGupta R, Dalton C, Wiseman OJ, Berkley KJ, Fowler CJ. An open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis. Mult Scler. 2004 Aug;10(4):425-33 | PubMed |

Corey-Bloom J, Wolfson T, Gamst A, Jin S, Marcotte TD, Bentley H, et al. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial. CMAJ. 2012 Jul 10;184(10):1143-50 | CrossRef | PubMed |

Corey-Bloom J, Wolfson TJ, Anthony GC, Bentley H, Gouaux B. Short-term effects off medicinal cannabis on spasticity in multiple sclerosis. Neurology. 2008;70(11 (suppl 1)):A86-A87. | Link |

Center for Medicinal Cannabis Research. Short-Term Effects of Medicinal Cannabis Therapy on Spasticity in Multiple Sclerosis. clinicaltrials.gov. 2001 | Link |

Centonze D, Mori F, Koch G, Buttari F, Codecà C, Rossi S, et al. Lack of effect of cannabis-based treatment on clinical and laboratory measures in multiple sclerosis. Neurol Sci. 2009 Dec;30(6):531-4 | CrossRef | PubMed |

Clifford DB. Tetrahydrocannabinol for tremor in multiple sclerosis. Ann Neurol. 1983 Jun;13(6):669-71 | PubMed |

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 Jun;32(5):451-9 | CrossRef | PubMed |

Collin C, Ambler Z, Kent R, McCalla R. A randomised controlled study of Sativex® in patients with symptoms of spasticity due to multiple sclerosis. 22nd Congress of the ECTRIMS. 2006 | Link |

GW Pharmaceuticals Ltd. A Study to Evaluate the Efficacy of Sativex in Relieving Symptoms of Spasticity Due to Multiple Sclerosis. clinicaltrials.gov. 2005 | Link |

Collin C, Davies P, Mutiboko IK, Ratcliffe S; Sativex Spasticity in MS Study Group. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol. 2007 Mar;14(3):290-6. | PubMed |

GW Pharmaceuticals Ltd. A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis. clinicaltrials.gov. 2002 | Link |

Conte A, Bettolo CM, Onesti E, Frasca V, Iacovelli E, Gilio F, et al. Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis. Eur J Pain. 2009 May;13(5):472-7 | CrossRef | PubMed |

Fox P, Bain PG, Glickman S, Carroll C, Zajicek J. The effect of cannabis on tremor in patients with multiple sclerosis. Neurology. 2004 Apr 13;62(7):1105-9. | PubMed |

Freeman RM, Adekanmi O, Waterfield MR, Waterfield AE, Wright D, Zajicek J. The effect of cannabis on urge incontinence in patients with multiple sclerosis: a multicentre, randomised placebo-controlled trial (CAMS-LUTS). Int Urogynecol J Pelvic Floor Dysfunct. 2006 Nov;17(6):636-41 | PubMed |

Katona S, Kaminski E, Sanders H, Zajicek J. Cannabinoid influence on cytokine profile in multiple sclerosis. Clin Exp Immunol. 2005 Jun;140(3):580-5 | PubMed |

Zajicek JP, Sanders HP, Wright DE, Vickery PJ, Ingram WM, Reilly SM, et al. Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J Neurol Neurosurg Psychiatry. 2005 Dec;76(12):1664-9 | PubMed |

Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A, et al; UK MS Research Group. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomized placebo-controlled trial. Lancet. 2003 Nov 8;362(9395):1517-26 | PubMed |

Medical Research Council (MRC) (UK). A multiple randomised controlled trial of cannabinoids on spasticity in multiple sclerosis (MS). ISRCTN.com. 2000 | Link |

Greenberg HS, Werness SA, Pugh JE, Andrus RO, Anderson DJ, Domino EF. Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers. Clin Pharmacol Ther. 1994 Mar;55(3):324-8. | PubMed |

Hamann W, di Vadi PP. Analgesic effect of the cannabinoid analogue nabilone is not mediated by opioid receptors. Lancet. 1999 Feb 13;353(9152):560 | PubMed |

Kavia R, De Ridder D, Sarantis N, Constantinescu C. Randomised controlled trial of cannabis based medicine (CBM, Stativex®) to treat detrusor overactivity in multiple sclerosis. Neurourology and Urodynamics. 2006;25:166-166. | Link |

Kavia RB, De Ridder D, Constantinescu CS, Stott CG, Fowler CJ. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler. 2010 Nov;16(11):1349-59 | CrossRef | PubMed |

Killestein J, Hoogervorst EL, Reif M, Blauw B, Smits M, Uitdehaag BM, et al. Immunomodulatory effects of orally administered cannabinoids in multiple sclerosis. J Neuroimmunol. 2003 Apr;137(1-2):140-3. | PubMed |

Killestein J, Hoogervorst EL, Reif M, Kalkers NF, Van Loenen AC, Staats PG, et al. Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Neurology. 2002 May 14;58(9):1404-7 | PubMed |

Killestein J, Hoogervorst ELJ, Kalkers NF, van Winsen LML, Uitdehaag BMJ, Linssen-Schuurmans CD, et al. The effects of orally administred cannabinoids in multiple sclerosis patients: a pilot study. Multiple Sclerosis. 2000;6(1 suppl 1):S27-S27 | CrossRef |

Langford RM, Mares J, Novotna A, Vachova M, Novakova I, Notcutt W, et al. 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. J Neurol. 2013 Apr;260(4):984-97 | CrossRef | PubMed |

GW Pharmaceuticals Ltd. Sativex Versus Placebo When Added to Existing Treatment for Central Neuropathic Pain in MS. clinicaltrials.gov. 2006 | Link |

Leocani L, Nuara A, Houdayer E, Del Carro U, Straffi L, Martinelli V, et al. Effect of THC-CBD oromucosal spray (Sativex) on measures of spasticity in multiple sclerosis: a double-blind, placebo-controlled, crossover study. Joint Americas Committee for Treatment and Research in Multiple Sclerosis ACTRIMS—European Committee for Treatment and Research in Multiple Sclerosis ECTRIMS Meeting. 2014 | Link |

Martyn CN, Illis LS, Thom J. Nabilone in the treatment of multiple sclerosis. Lancet. 1995 Mar 4;345(8949):579 | PubMed |

Meinck HM, Schönle PW, Conrad B. Effect of cannabinoids on spasticity and ataxia in multiple sclerosis. J Neurol. 1989 Feb;236(2):120-2 | PubMed |

Notcutt W, Price M, Miller R, Newport S, Phillips C, Simmons S, et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 'N of 1' studies. Anaesthesia. 2004 May;59(5):440-52 | PubMed |

GW Pharmaceuticals Ltd. A Study to Evaluate the Effects of Cannabis Based Medicine in Patients With Pain of Neurological Origin. clinicaltrials.gov. 2002 | Link |

Notcutt W, Langford R, Davies P, Ratcliffe S, Potts R. A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols). Mult Scler. 2012 Feb;18(2):219-28 | CrossRef | PubMed |

Novotna A, Mares J, Ratcliffe S, Novakova I, Vachova M, Zapletalova O, et al; Sativex Spasticity Study Group. 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 Sep;18(9):1122-31 | CrossRef | PubMed |

Petro DJ, Ellenberger C Jr. Treatment of human spasticity with delta 9-tetrahydrocannabinol. J Clin Pharmacol. 1981 Aug-Sep;21(8-9 Suppl):413S-416S. | PubMed |

Robson P, Wade D, Makela P, House H, Bateman C. Cannabis-based medicinal extract (Sativex) produced significant improvements in a subjective measure of spasticity which were maintained on long-term treatment with no evidence of tolerance. IACM 3rd Conference on Cannabinoids in Medicine. 2005 | Link |

Wade DT, Makela P, Robson P, House H, Bateman C. 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. Mult Scler. 2004 Aug;10(4):434-41 | PubMed |

GW Pharmaceuticals Ltd. An Investigation of Delta-9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) in Multiple Sclerosis Patients. clinicaltrials.gov. 2001 | Link |

Rog DJ, Nurmikko TJ, Young CA. Oromucosal delta9-tetrahydrocannabinol/cannabidiol for neuropathic pain associated with multiple sclerosis: an uncontrolled, open-label, 2-year extension trial. Clin Ther. 2007 Sep;29(9):2068-79 | PubMed |

Rog DJ, Nurmikko T, Young C, Sarantis NS. Randomized controlled trial of sativex, a cannabis based medicine (CBM), in central neuropathic pain due to multiple sclerosis, followed by an open-label extension. Neurology. 2006;66(5):A31-A31 | Link |

Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 2005 Sep 27;65(6):812-9 | PubMed |

Young CA, Rog DJ. Randomised controlled trial of cannabis based medicinal extracts (CBME) in central neuropathic pain due to multiple sclerosis. IV Congress of the European Federation of IASP Chapters (EFIC). 2003 | Link |

GW Pharmaceuticals Ltd. A Study of Sativex in the Treatment of Central Neuropathic Pain Due to Multiple Sclerosis. clinicaltrials.gov. 2002 | Link |

Serpell MG, Notcutt W, Collin C. Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. J Neurol. 2013 Jan;260(1):285-95 | CrossRef | PubMed |

Svendsen KB, Jensen TS, Bach FW. [Effect of the synthetic cannabinoid dronabinol on central pain in patients with multiple sclerosis—secondary publication]. Ugeskr Laeger. 2005 Jun 20;167(25-31):2772-4 | PubMed |

Svendsen KB, Jensen TS, Bach FW. Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ. 2004 Jul 31;329(7460):253 | PubMed |

Turcotte D, Doupe M, Torabi M, Gomori A, Ethans K, Esfahani F, et al. Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial. Pain Med. 2015 Jan;16(1):149-59. | CrossRef | PubMed |

Ungerleider JT, Andyrsiak T, Fairbanks L, Ellison GW, Myers LW. Delta-9-THC in the treatment of spasticity associated with multiple sclerosis. Adv Alcohol Subst Abuse. 1987;7(1):39-50 | PubMed |

Van Amerongen G, Beumer T, Killestein J, Groeneveld GJ. Individualized dosing of a novel oral DELTA9-THC formulation improves subjective spasticity and pain in patients with progressive multiple sclerosis. Joint Americas Committee for Treatment and Research in Multiple Sclerosis ACTRIMS—European Committee for Treatment and Research in Multiple Sclerosis ECTRIMS Meeting. 2014 | Link |

Vaney C, Heinzel-Gutenbrunner M, Jobin P, Tschopp F, Gattlen B, Hagen U, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult Scler. 2004 Aug;10(4):417-24. | PubMed |

Wade DT, Robson P, House H, Makela P, Aram J. A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil. 2003 Feb;17(1):21-9. | PubMed |

Wade DT, Makela PM, 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 Oct;12(5):639-45 | PubMed |

Wissel J, Haydn T, Müller J, Brenneis C, Berger T, Poewe W, et al. Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain: a double-blind placebo-controlled cross-over trial. J Neurol. 2006 Oct;253(10):1337-41 | PubMed |

Zajicek JP, Hobart JC, Slade A, Barnes D, Mattison PG; MUSEC Research Group. Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry. 2012 Nov;83(11):1125-32 | CrossRef | PubMed |

Hobart JC, Zajicek JP. Cannabis as a symptomatic treatment for MS: Clinically meaningful MUSEC to the stiffness and walking problems of people with MS. 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. 2012:247-247 | Link |

Zajicek J, Reif M, Schnelle M. UK MUSEC Study Investigators. Cannabis extract in the treatment of muscle stiffness and other symptoms in multiple sclerosis – results of the MUSEC study. IACM 5th Conference on Cannabinoids in Medicine. 2009 | Link |

Zajicek, J, Reif, M, Schnelle, M. Cannabis extract in the treatment of muscle stiffness and other symptoms in multiple sclerosis—Results of the MUSEC study. 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis. 2009 | Link |

Institut fur Klinische Forschung, Germany. Multiple Sclerosis and Extract of Cannabis (MUSEC) Study.clinicaltrials.gov. 2006 | Link |

Gesellschaft fuer klinische Forschung e.V. Multiple Sclerosis and Extract of Cannabis (MUSEC): a randomised, double-blind, placebo-controlled phase III trial to determine the efficacy and safety of a standardised oral extract of cannabis sativa for the symptomatic relief of muscle stiffness and pa. EU Clinical Trial. 2006. | Link |

FDA and Marijuana: Questions and Answers. Disponible en: http://www.fda.gov/newsevents/publichealthfocus/ucm421168.htm#notapproved). Accedido el 20 de Diciembre de 2016. | Link |

EMEA-000181-PIP02-13. Disponible en: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/pips/EMEA-000181-PIP02-13/pip_001257.jsp&mid=WC0b01ac058001d129. Accedido el 20 de Diciembre de 2016. | Link |

Scolding N, Barnes D, Cader S, Chataway J, Chaudhuri A, Coles A, et al. Association of British Neurologists: revised (2015) guidelines for prescribing disease-modifying treatments in multiple sclerosis. Pract Neurol. 2015 Aug;15(4):273-9 | CrossRef | PubMed |

Medical Marijuana (Cannabis). Disponible en: http://www.nationalmssociety.org/Treating-MS/Complementary-Alternative-Medicines/Marijuana. Accedido el 20 de Diciembre de 2016. | Link |

GW Pharmaceuticals Ltd. A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis. clinicaltrials.gov. 2002

Edición Julio 2022
icon Estudios originales
Caracterización clínica, psicológica y sociofamiliar de la conducta suicida en adolescentes chilenos: análisis de correspondencias múltiples

Asociación de biomarcadores y severidad de COVID-19: estudio transversal

Sistematización de iniciativas en salud sexual y reproductiva según criterios de buenas prácticas en repuesta a la pandemia COVID-19 en la atención primaria en Chile

NUEVO SISTEMA EDITORIAL
Autores
Abrir sesión
Registro
Recibir alertas
Politica de cobros
Políticas editoriales
Instrucciones para autores
Equipo editorial
Comité editorial
¿Desea ser revisor?
Contactos y soporte
rssFacebookTwitter
ISSN 0717-6384