Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Neurotherapeutics
Published in: Neurotherapeutics 4/2015

01-10-2015 | Review

Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis

Author: William G. Notcutt

Published in: Neurotherapeutics | Issue 4/2015

Login to get access

Abstract

The endocannabinoid system was discovered in 1988 but has received little attention for its potential therapeutic possibilities. That has started to change, and since 2000, a significant number of clinical trials of cannabinoids, principally for the control of spasticity in multiple sclerosis, have been undertaken. These studies have been difficult because of the nature of the disease and have involved patients for whom other therapies have failed or proved inadequate. This paper outlines the background to the use of cannabinoids available and discusses the principles of practice associated with their safe use. The focus has been on nabiximols, being the most studied and the only cannabinoid that has been both adequately researched for use in multiple sclerosis and granted a license by the regulators. However, what has emerged is that the effect for many patients can be much wider than just control of spasticity. Within and outside of neurology there seems to be an expanding range of possibilities for the therapeutic use of cannabinoids.
Appendix
Available only for authorised users
Literature
1.
2.
3.
Pertwee RG. Targeting the endocannabinoid system with cannabinoid receptor agonists: pharmacological strategies and therapeutic possibilities. Philos Trans R Soc Lond B Biol Sci 2012;367:3353-3363PubMedCentralCrossRefPubMed
4.
Skaper RD, Di Marzo V. Why do cannabinoid receptors have more than one endogenous ligand? Philos Trans R Soc Lond B Biol Sci 2012;367:3216-3228.CrossRef
5.
Notcutt W, Clarke E. Cannabinoids in clinical practice: A UK perspective. In: Pertwee R (ed.) Handbook of cannabis, Oxford University Press, Oxford, 2014; p. 415-432
6.
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;16, 707-714.CrossRefPubMed
7.
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;18:1122-1131.CrossRefPubMed
8.
Vermersch P. Sativex® (Tetrahydrocannabinol + Cannabidiol), an endocannabinoid system modulator: basic features and main clinical data. Exp Rev Neurother 2011;11:15-19.CrossRef
9.
Collin C, Ehler E, Waberzinek G, 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;32:451-459.CrossRefPubMed
10.
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.CrossRefPubMed
11.
Brady CM, DasGupta R, Dalton C, et alAn open-label pilot study of cannabis-based extracts for bladder dysfunction in advanced multiple sclerosis. Mult Scler 2004;10:425-433.CrossRefPubMed
12.
Zajicek J, Fox P, Sanders H, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet 2003;362:1517-1526.CrossRefPubMed
13.
Zajicek JP, Hobart JC, Slade A, Barnes D, Mattison PG. Multiple sclerosis and extract of cannabis: results of the MUSEC trial. J Neurol Neurosurg Psychiatry 2012;83:1125-1132.CrossRefPubMed
14.
Serpell M, Notcutt W, Collin C. Sativex long-term use: an open-label trial in patients with spasticity due to multiple sclerosis. J Neurol 2013;260:285-295.CrossRefPubMed
15.
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;18:219-228.CrossRefPubMed
16.
Notcutt WG. A questionnaire survey of patients and carers of patients prescribed Sativex as an unlicensed medicine. Prim Health Care Res Dev 2012;12:1-8.
17.
Nurmikko TJ, Serpell MG, Hoggart B, et al. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain 2007;133:210-220.CrossRefPubMed
18.
Abrams DI, Jay CA, Shade SB, et al. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology 2007;68:515-21.CrossRefPubMed
19.
Ellis RJ, Toperoff W, Vaida F, et al. Smoked medicinal cannabis for neuropathic pain in HIV: a randomized, crossover clinical trial. Neuropsychopharmacology 2009;34:672-680.PubMedCentralCrossRefPubMed
20.
Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol 2011;72:735-744.PubMedCentralCrossRefPubMed
21.
Cichewicz DL, Martin ZL, Smith FL, Welch SP. Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. J Pharmacol Exp Ther 1999;289:859-67.PubMed
22.
Karst M, Wippermann S, Ahrens J. Role of cannabinoids in the treatment of pain and (painful) spasticity. Drugs 2010;70:2409-2438.CrossRefPubMed
23.
Russo E. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuroendocrinol Lett 2004;25:31-39.PubMed
24.
Devinsky O, Cilio M, Cross H, et al. Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 2014;55:791-802.CrossRefPubMed
25.
Ware MA, Fitzcharles MA, Joseph L, Shir Y. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesth Analg 2010;110(2):604-10.
26.
27.
28.
29.
Flynn J, Hanif N. Nabilone for the management of intractable nausea and vomiting in terminally staged AIDS. J Palliat Care 1992;8:46-47.PubMed
30.
Notcutt W, Phillip C, Hughe J, LacouX P, Vijayakulasingam V, Baldock L. A retrospective description of the use of nabilone in uk clinical practice – extension study. British Pain Society Annual Scientific Meeting 2015, Glasgow: Poster Presentation; 2015.
31.
Russo E, Guy GW. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and Cannaidiol. Med Hypotheses 2006;66:234-246.CrossRefPubMed
32.
Notcutt W, Price M, Chapman G. Clinical experience with nabilone for chronic pain. Pharm Sci 1997;3:551-555.
33.
34.
Johnson JR, Burnell-Nugent M, Lossignol D, et al. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC: CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manag 2010;39:167-179.CrossRef
35.
Strasser F, Luftner D, Possinger K, et al. Comparison of orally administered cannabis 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 Cannabis-In-Cachexia-Study-Group. J Clin Oncol 2006;24:3394-3400CrossRefPubMed
36.
Nutt DJ, King LA, Phillips LD. Independent Scientific Committee on Drugs. Drug harms in the UK: a multicriteria decision analysis. Lancet 2010;376:1558-1565.CrossRefPubMed
37.
Schoedel KA, Chen N, Hilliard A, et al. A randomized, double blind, placebo controlled, crossover study to evaluate the subjective abuse potential and cognitive effects of nabiximols oromucosal spray in subjects with a history of recreational cannabis use. Hum Psychopharmacol 2011;26:224-236.PubMed
38.
Calhoun SR, Galloway GP, Smith DE. Abuse potential of dronabinol (Marinol). J Psychoactive Drugs 1998;30:187-196.CrossRefPubMed
39.
Ware MA, St Arnaud-Trempe E. The abuse potential of the synthetic cannabinoid nabilone. Addiction 2010;105:494-503.CrossRefPubMed
40.
Wade D. Evaluation of the safety and tolerability profile of Sativex: is it reassuring enough? Exp Rev Neurother 2012;12:9-14.CrossRef
41.
Robson P. Abuse potential and psychoactive effects of d-9-tetrahydrocannabinol and Cannabidiol oromucosal spray (Sativex), a new cannabinoid medicine. Exp Opin Drug Saf 2011;10:675-685.CrossRef
42.
Henquet C, Krabbendam L, Spauwen J, et al. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ 2005;330:11.PubMedCentralCrossRefPubMed
43.
44.
Aragona M, Onesti E, Tomassini V, et al. Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study. Clin Neuropharmacol 2009;32:41-47.PubMed
45.
46.
47.
Asbridge M, Hayden JA, Cartwright JL. Acute cannabis consumption and motor vehicle collision risk: systematic review of observational studies and meta-analysis. BMJ 2012;344:e536.PubMedCentralCrossRefPubMed
48.
49.
Slof J, Gras A. Sativex® in multiple sclerosis spasticity: a cost-effectiveness model. Expert Rev Pharmacoecon Outcomes Res 2012;12:525-538.CrossRef
50.
Flachenecker P. A new multiple sclerosis spasticity treatment option: effect in everyday clinical practice and cost-effectiveness in Germany. Exp Rev Neurother 2013;13(3 Suppl. 1):15-19.CrossRef
51.
AWMSG Secretariat Assessment Report. Delta-9-tetrahydrocannabinol/ Cannabidiol (Sativex®). All Wales Therapeutics and Toxicology Centre. Reference number: 644. July 2014.
52.
Shakespeare DT, Boggild M, Young C. Anti-spasticity agents for multiple sclerosis. Cochrane Database Syst Rev 2003;(4):CD001332.PubMed
Metadata
Title
Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis
Author
William G. Notcutt
Publication date
01-10-2015
Publisher
Springer US
Published in
Neurotherapeutics / Issue 4/2015
Print ISSN: 1933-7213
Electronic ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-015-0383-5

Other articles of this Issue 4/2015

Neurotherapeutics 4/2015 Go to the issue

Editorial

Cannabinoids in the Treatment of Neurological Disorders

Review

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

Review

Cannabinoids and Schizophrenia: Risks and Therapeutic Potential

Review

The Endocannabinoid System and its Modulation by Phytocannabinoids

Review

Molecular Targets of Cannabidiol in Neurological Disorders

Erratum

Erratum to: Parsing Physiological Functions of Erythropoietin One Domain at a Time