Cannabis extract in the treatment of muscle stiffness and other symptoms in multiple sclerosis - results of the musec study

BACKGROUND: The 'Cannabinoids in Multiple Sclerosis' (CAMS) study assessed the value of cannabinoids in the treatment of MS symptoms such as spasticity, pain, and sleep quality. Although in the primary analysis the Ashworth score did not show a significant benefit, the patients themselves rated cannabinoids clearly helpful. Here we report the results of the 'Multiple Sclerosis and Extract of Cannabis' (MUSEC) study conducted from 06/2006 to 09/2008, aiming at confirming the patient-based findings of the CAMS study. METHODS: Across 22 UK centres 279 patients were randomised to oral cannabis extract or placebo. The study consisted of a 1- to 2-week screening period, a 2-week dose titration phase from 5 to 25 mg THC daily (final dose based on tolerability), and a 10-week maintenance phase. Main in-/exclusion criteria were definite MS disease stable for the previous 6 months, troublesome muscle stiffness, with stable antispastic medication and physiotherapy. Primary outcome measure was the patients' assessment of change from baseline regarding muscle stiffness. Beneficial response ('relief') was defined as marking categories 0 to 3 on an 11-point category rating scale (CRS). Further measures included CRS for body pain, spasms and sleep quality, and the MS Spasticity Scale (MSSS-88), MS Impact Scale (MSIS-29), and MS Walking Scale (MSWS-12). At an interim analysis an Independent Data Review Board recommended reducing the final sample size for statistical and ethical reasons. RESULTS: The rate of relief in muscle stiffness after 12 weeks was almost twice as large under cannabis extract compared to placebo (29.4% vs 15.7%, p=0.004 one-sided). Equivalent results were found in sensitivity analyses, after 4 and 8 weeks, and also in rates of relief for body pain, spasms and sleep quality at all time points. Corresponding scales of the questionnaires corroborated these findings. Most frequent AEs were urinary tract infections, dizziness, dry mouth, and headache. Pronounced differences in the frequency of adverse drug reactions were mainly seen during the 2-week dose escalation phase. Conclusion The study met its primary objective to show superiority of cannabis extract over placebo in the treatment of muscle stiffness in MS. Secondary efficacy parameters corroborated these results. The profile of AEs in patients treated with cannabis extract was consistent with the known side effects of cannabinoids. No new safety concerns were raised.