Delta-9-Tetrahydrocannabinol/Cannabidiol (Sativex®): A Review of Its Use in Patients with Moderate to Severe Spasticity Due to Multiple Sclerosis
- 1.5k Downloads
Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) [Sativex®] is an oromucosal spray formulation that contains principally THC and CBD at an approximately 1:1 fixed ratio, derived from cloned Cannabis sativa L. plants. The main active substance, THC, acts as a partial agonist at human cannabinoid receptors (CB1 and CB2), and thus, may modulate the effects of excitatory (glutamate) and inhibitory (gamma-aminobutyric acid) neurotransmitters. THC/CBD is approved in a number of countries, including Germany and the UK, as an add-on treatment for symptom improvement in adult patients with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy. In the largest multinational clinical trial that evaluated the approved THC/CBD regimen in this population, 12 weeks’ double-blind treatment with THC/CBD significantly reduced spasticity severity (primary endpoint) compared with placebo in patients who achieved a clinically significant improvement in spasticity after 4 weeks’ single-blind THC/CBD treatment, as assessed by a patient-rated numerical rating scale. A significantly greater proportion of THC/CBD than placebo recipients achieved a ≥30 % reduction (a clinically relevant reduction) in spasticity severity. The efficacy of THC/CBD has been also shown in at least one everyday clinical practice study (MOVE 2). THC/CBD was generally well tolerated in clinical trials. Dizziness and fatigue were reported most frequently during the first 4 weeks of treatment and resolved within a few days even with continued treatment. Thus, add-on THC/CBD is a useful symptomatic treatment option for its approved indication.
KeywordsBaclofen Numerical Rating Scale Tizanidine Cannabidiol Numerical Rating Scale Score
The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author(s) on the basis of scientific and editorial merit.
- 3.Multiple Sclerosis Trust. Multiple sclerosis information for health and social care professionals. http://www.mstrust.org.uk/downloads/ms-info-health-professionals.pdf (2011). Accessed 8 Jul 2013.
- 6.National Collaborating Centre for Chronic Conditions (UK). Multiple sclerosis: national clinical guideline for diagnosis and management in primary and secondary care. NICE clinical guidelines, no 8. London: Royal College of Physicians (UK); 2004.Google Scholar
- 8.Walsh Z, Callaway R, Belle-Isle L, et al. Cannabis for therapeutic purposes: patient characteristics, access, and reasons for use. Int J Drug Policy. 2013;24(6):511–6.Google Scholar
- 14.GW Pharma Ltd. Sativex oromucosal spray: summary of product characteristics. http://www.medicines.org.uk/emc/medicine/23262/SPC/Sativex+Oromucosal+Spray/ (2012). Accessed 29 Jan 2014.
- 15.Hilliard A, Stott C, Wright S, et al. Evaluation of the effects of Sativex (THC BDS: CBD BDS) on inhibition of spasticity in a chronic relapsing experimental allergic autoimmune encephalomyelitis: a model of multiple sclerosis. ISRN Neurol. 2012. doi: 10.5402/2012/802649.PubMedCentralPubMedGoogle Scholar
- 16.Bayer Healthcare. Sativex® oromucosal spray: product specification. http://www.sativex.co.uk/data/file/Sativex%20Product%20SpecDocument.pdf (2010). Accessed 29 Jan 2014.
- 17.Medicines and Healthcare products Regulatory Agency. Public assessment report: Sativex oromucosal spray (decentralized procedure reference number UKH/2462/001/DC). http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con084961.pdf (2010). Accessed 28 May 2013.
- 20.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(3):224–36.PubMedGoogle Scholar
- 22.Wright S, Vachova MM, Novakova I. The effect of long-term treatment with a prescription cannabis-based THC: CBD oromucosal spray on cognitive function and mood: a 12 month double blind placebo-controlled study in people with spasticity due to multiple sclerosis (abstract no. P1206). Mult Scler. 2013;19(suppl 11):572.Google Scholar
- 23.Guy GW, Robson PJ. Phase I, open label, four-way crossover study to compare the pharmacokinetic profiles of a single dose of 20 mg of a cannabis based medicine extract (CBME) administered on 3 different areas of the buccal mucosa and to investigate the pharmacokinetics of CBME per oral in healthy male and female volunteers (GWPK0112). J Cannabis Ther. 2003;3(4):79–120.CrossRefGoogle Scholar
- 24.Stott C, White L, Wright S, et al. A phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of rifampicin, ketoconazole, and omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers. SpringerPlus. 2013;2(1):236.PubMedCentralPubMedCrossRefGoogle Scholar
- 31.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(9):1122–31.PubMedCrossRefGoogle Scholar
- 35.Farrell RA, Flisher L, Broome K, et al. Sativex: an alternative to intrathecal baclofen in patients with severe multiple sclerosis-related spasticity? (abstract no. P650). Mult Scler. 2013;19(suppl 11):284.Google Scholar
- 36.Arnal C, Carrion F. Structured diagnosis and management with THC:CBD oromucosal spray of patients with resistant multiple sclerosis spasticity (abstract no. P1110). Mult Scler. 2013;19(suppl 11):522.Google Scholar
- 37.Flachenecker P, Zettl U, Henze T. THC:CBD oromucosal spray (nabiximols) in the long term treatment of multiple sclerosis spasticity. The MOVE 2 long-term study (abstract no. P1121). Mult Scler. 2013;19(suppl 11):527.Google Scholar
- 38.Flachenecker P, Henze T, Zettl UK. Nabiximols (THC/CBD oromucosal spray, Sativex®) in clinical practice—results of a multicenter, non-interventional study (MOVE 2) in patients with multiple sclerosis spasticity. Eur Neurol. 2014;71(5–6):173–81.Google Scholar
- 43.Eltayb A, Etges T, Wright S. An observational post-approval registry study of patients prescribed Sativex®. Results from clinical practice (abstract no. P1041). Mult Scler. 2013;19(suppl 11):480.Google Scholar
- 44.Freidel M, Tiel-Wilck K, Schreiber H, et al. Resistant multiple sclerosis spasticity (MSS) treatment with THC:CBD spray and effects on driving ability (abstract no. P1111). Mult Scler. 2013;19(suppl 11):522.Google Scholar
- 45.Royal College of Physicians and Multiple Sclerosis Trust. The national audit of services for people with multiple sclerosis 2011. http://www.rcplondon.ac.uk/sites/default/files/ms_audit_national_report_2011_0.pdf (2011). Accessed 29 Jan 2014.
- 47.National Institute for Health and Care Excellence. Measuring effectiveness and cost effectiveness: the QALY. http://www.nice.org.uk/newsroom/features/measuringeffectivenessandcosteffectivenesstheqaly.jsp (2010). Accessed 7 Aug 2013.
- 48.GW Pharmaceuticals. GW pharmaceuticals files new regulatory application to expand Sativex® approval to France. http://www.gwpharm.com/GW%20Pharmaceuticals%20Files%20New%20Regulatory%20Application%20to%20Expand%20Sativex%20Approval%20to%20France.aspx (2013). Accessed 2 Aug 2013.
- 49.Multiple Sclerosis Trust. Sativex (nabiximols)—factsheet. http://www.mstrust.org.uk/information/publications/factsheets/sativex.jsp (2011). Accessed 2 Aug 2013.