Delta-9-Tetrahydrocannabinol/Cannabidiol (Sativex®): A Review of Its Use in Patients with Moderate to Severe Spasticity Due to Multiple Sclerosis


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.

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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.

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Corresponding author

Correspondence to Yahiya Y. Syed.

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The manuscript was reviewed by: D. Baker, Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, London, UK; E. Bernitsas, Department of Neurology, Wayne State University, Detroit, MI, USA; A. Chaudhuri, Department of Neurology, Queen’s Hospital, Romford, UK; T. Menge, Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany; G. Pryce, Centre for Neuroscience and Trauma, Blizard Institute, Queen Mary University of London, London, UK; F. Piehl, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; W.A. Sheremata, Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.

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Syed, Y.Y., McKeage, K. & Scott, L.J. Delta-9-Tetrahydrocannabinol/Cannabidiol (Sativex®): A Review of Its Use in Patients with Moderate to Severe Spasticity Due to Multiple Sclerosis. Drugs 74, 563–578 (2014).

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  • Baclofen
  • Numerical Rating Scale
  • Tizanidine
  • Cannabidiol
  • Numerical Rating Scale Score