title: Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis.
abstract: 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.
authors.affiliation: Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore, 0754, Auckland, New Zealand, demail@springer.com.
authors.forename: Yahiya Y
authors.initials: YY
authors.lastname: Syed
authors.forename: Kate
authors.initials: K
authors.lastname: McKeage
authors.forename: Lesley J
authors.initials: LJ
authors.lastname: Scott
mesh_terms: D000328:Adult; D002185:Cannabidiol; D063386:Cannabinoid Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D013759:Dronabinol; D004338:Drug Combinations; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D009128:Muscle Spasticity / Q000188:drug therapy* / Q000209:etiology; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists; D012720:Severity of Illness Index
chemical_list: D063386:Cannabinoid Receptor Agonists; D004338:Drug Combinations; D010936:Plant Extracts; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D002185:Cannabidiol; D013759:Dronabinol; C587251:nabiximols