Delta-9-tetrahydrocannabinol/cannabidiol (Sativex®): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis

Drugs. 2014 Apr;74(5):563-78. doi: 10.1007/s40265-014-0197-5.

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.

Publication types

  • Review

MeSH terms

  • Adult
  • Cannabidiol
  • Cannabinoid Receptor Agonists / adverse effects
  • Cannabinoid Receptor Agonists / pharmacology
  • Cannabinoid Receptor Agonists / therapeutic use
  • Dronabinol
  • Drug Combinations
  • Humans
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / physiopathology
  • Muscle Spasticity / drug therapy*
  • Muscle Spasticity / etiology
  • Plant Extracts / adverse effects
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB2 / agonists
  • Severity of Illness Index

Substances

  • Cannabinoid Receptor Agonists
  • Drug Combinations
  • Plant Extracts
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Cannabidiol
  • Dronabinol
  • nabiximols