Cannabis as a symptomatic treatment for MS: Clinically meaningful MUSEC to the stiffness and walking problems of people with MS

Background: The Multiple Sclerosis and Extract of Cannabis (MUSEC) study was a randomised, double-blind, placebo-controlled phase III trial to determine the efficacy and safety of a standardised oral extract of Cannabis sativa for the symptomatic relief of muscle stiffness and pain in MS. The primary outcome measure was a category rating scale (CRS) measuring patient-reported change in muscle stiffness from baseline. The study met its primary objective to demonstrate superiority of cannabis extract over placebo in treatment of muscle stiffness in MS, and no new safety concerns were observed. We now report results from the secondary patient-reported outcomes measures: the MS Spasticity Scale (MSSS-88), MS Walking Scale (MSWS-12), and the MS Impact Scale (MSIS-29) Methods: Patients with stable MS at 22 UK centres were randomised to oral cannabis extract (N=144) or placebo (N=135), stratified by centre, walking ability and use of antispastic medication. There was a screening period, a 2-week dose titration phase from 5mg to a maximum of 25mg tetrahydrocannabinol (THC) daily, and a 10-week maintenance phase. Rating scale data were analysed using Rasch measurement methods. We report impact above and beyond placebo using widely accepted approximate thresholds for clinical meaningful effect sizes (ES; small=0.20; moderate=0.50; large = 0.8). Results: There were differential effects across the different outcomes. Essentially, people reported: clinically moderate benefits on muscle stiffness (ES= 0.44) and walking ability (ES=0.46); clinically mildto- moderate benefits on body movements (ES=0.36); clinically small benefits on pain/discomfort and physical impact (both ES=0.20). No clinically meaningful benefits were demonstrated on muscle spasms (ES=0.13) and activities of daily living (ES = 0.01). Of note there were no effects above placebo on people’s feelings (ES=0.01), psychological impact (ES=-0.03), and social functioning (ES=0.01). Conclusions: Results imply cannabis in MS reduces muscle stiffness and improves walking ability, and to a lesser extent improves body movements and reduces pain and physical impact. The lack of a psychosocial effect, coupled with the differential effects across outcomes appears to dispel the myth that the benefit of cannabis in MS is simply because it makes people feel better.