Delta-9-tetrahydrocannabinolcannabidiol (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 11 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. THCCBD 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 THCCBD regimen in this population, 12 weeks double-blind treatment with THCCBD significantly reduced spasticity severity (primary endpoint) compared with placebo in patients who achieved a clinically significant improvement in spasticity after 4 weeks single-blind THCCBD treatment, as assessed by a patient-rated numerical rating scale. A significantly greater proportion of THCCBD than placebo recipients achieved a ≥ 30% reduction (a clinically relevant reduction) in spasticity severity. The efficacy of THCCBD has been also shown in at least one everyday clinical practice study (MOVE 2). THCCBD 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 THCCBD is a useful symptomatic treatment option for its approved indication.