Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study
In the per-protocol population, significant improvement in spasm frequency and mobility, but no statistically significant effects in the ITT set.
Summary
n=50 MS patients with poorly controlled spasticity (ITT analysis); Cannabis sativa extract vs. placebo; per-protocol (n=37): significant reduction in spasm frequency (p=0,013) and improved mobility (p=0,01); ITT analysis shows only trends. Tolerability good; mild adverse events more frequent during the active phase.
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PopulationMS patients with poorly controlled spasticity during inpatient rehabilitation, n=57 (ITT: n=50, per-protocol: n=37)
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InterventionOral cannabis extract (capsules), standardized to 2,5 mg THC + 0,9 mg CBD per capsule, dose titration 15–30 mg THC/day over 14 days
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ControlPlacebo capsules (double-blind, crossover)
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OutcomeNo significant differences in the ITT set; in the per-protocol set significant reduction of spasm frequency (p=0,013) and improved mobility (p=0,01) under active treatment vs. placebo
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
<h4>Objective</h4>Cannabis may alleviate some symptoms associated with multiple sclerosis (MS). This study investigated the effect of an orally administered standardized Cannabis sativa plant extract in MS patients with poorly controlled spasticity.<h4>Methods</h4>During their inpatient rehabilitation programme, 57 patients were enrolled in a prospective, randomized, double-blind, placebo-controlled crossover study of cannabis-extract capsules standardized to 2.5 mg tetrahydrocannabinol (THC) and 0.9 mg cannabidiol (CBD) each. Patients in group A started with a drug escalation phase from 15 to maximally 30 mg THC by 5 mg per day if well tolerated, being on active medication for 14 days before starting placebo. Patients in group B started with placebo for seven days, crossed to the active period (14 days) and closed with a three-day placebo period (active drug dose escalation and placebo sham escalation as in group A). Measures used included daily self-report of spasm frequency and symptoms, Ashworth Scale, Rivermead Mobility Index, 10-m timed walk, nine-hole peg test, paced auditory serial addition test (PASAT), and the digit span test.<h4>Results</h4>In the 50 patients included into the intention-to-treat analysis set, there were no statistically significant differences associated with active treatment compared to placebo, but trends in favour of active treatment were seen for spasm frequency, mobility and getting to sleep. In the 37 patients (per-protocol set) who received at least 90% of their prescribed dose, improvements in spasm frequency (P = 0.013) and mobility after excluding a patient who fell and stopped walking were seen (P = 0.01). Minor adverse events were slightly more frequent and severe during active treatment, and toxicity symptoms, which were generally mild, were more pronounced in the active phase.<h4>Conclusion</h4>A standardized Cannabis sativa plant extract might lower spasm frequency and increase mobility with tolerable side effects in MS patients with persistent spasticity not responding to other drugs.