MUltiple Sclerosis and Extract of Cannabis: results of the MUSEC trial

Abstract

Objective Multiple sclerosis (MS) is associated with chronic symptoms, including muscle stiffness, spasms, pain and insomnia. Here we report the results of the Multiple Sclerosis and Extract of Cannabis (MUSEC) study that aimed to substantiate the patient based findings of previous studies. Patients and methods Patients with stable MS at 22 UK centres were randomised to oral cannabis extract (CE) (N¼144) or placebo (N¼135), stratified by centre, walking ability and use of antispastic medication. This double blind, placebo controlled, phase III study had a screening period, a 2 week dose titration phase from 5 mg to a maximum of 25 mg of tetrahydrocannabinol daily and a 10 week maintenance phase. The primary outcome measure was a category rating scale (CRS) measuring patient reported change in muscle stiffness from baseline. Further CRSs assessed body pain, spasms and sleep quality. Three validated MS specific patient reported outcome measures assessed aspects of spasticity, physical and psychological impact, and walking ability. Results The rate of relief from muscle stiffness after 12 weeks was almost twice as high with CE than with placebo (29.4% vs 15.7%; OR 2.26; 95% CI 1.24 to 4.13; p¼0.004, one sided). Similar results were found after 4 weeks and 8 weeks, and also for all further CRSs. Results from the MS scales supported these findings. Conclusion The study met its primary objective to demonstrate the superiority of CE over placebo in the treatment of muscle stiffness in MS. This was supported by results for secondary efficacy variables. Adverse events in participants treated with CE were consistent with the known side effects of cannabinoids. No new safety concerns were observed. Trial registration number NCT00552604.

The Cannabinoid Use in Progressive Inflammatory brain Disease (CUPID) trial: a randomised double-blind placebo-controlled parallel-group multicentre trial and economic evaluation of cannabinoids to slow progression in multiple sclerosis

“…Conversely, dronabinol might have a slight potentially negative effect in patients with higher EDSS scores. One possible explanation for these findings is that cannabinoids have been shown to reduce muscle stiffness 2,26,27 and, although an antispasticity effect might improve function at lower levels of disability, if walking is compromised by weakness, dronabinol might reduce muscle tone to the point where muscle power becomes affected and walking is more difficult. This side effect is well known with agents such as baclofen.…”

“…(15) 162 (2) 248 (27) 129 (9) 216 (36) 119 (10) 193 (42) 108 (12) 172 (46) 95 (13) 147 (52) 87 (14) 3 (88) 8 (176) Placebo FIGURE 3 Kaplan-Meier estimates of the probability of progression on the EDSS in the two treatment groups, confirmed after 6 months within the study period. The numbers at risk (cumulative number of censored observations) are given.…”

“…The data set was imputed 50 times and the ICE program uses the 50 data sets simultaneously for statistical analysis, thereby accounting for both within-and between-data set variability. (1) 4.5-month follow-up 71 (22) 28 (17) 9-month follow-up 73 (22) 33 (20) 15-month follow-up 84 (26) 38 (23) 21-month follow-up 95 (29) 48 (29) 27-month follow-up 109 (33) 44 (27) (12) 9 (5) 6-month follow-up 40 (12) 16 (10) 12-month follow-up 44 (13) 17 (10) 18-month follow-up 58 (18) 23 (14) 24-month follow-up 62 (19) 24 (15) 30-month follow-up 68 (21) 30 (18) 36-month follow-up 79 (24) 25 (15) Completed all questionnaires 217 (66) 118 (72)…”

Cannabinoids in neurology – Brazilian Academy of Neurology

“…Os naxibimols, os preparados com THC/CBD e o extrato de cannabis apresentaram resultados conflitantes, e embora não seja possível concluir de forma definitiva quanto à sua eficácia, os dados sugerem que esta pode ser uma opção terapêutica em pacientes que não responderam aos tratamentos convencionais 7,8,9,10,11 .…”

Clinical Use of Cannabinoids for Symptom Control in Multiple Sclerosis

“…They concluded that while there was no improvement shown when assessing spasticity on the Ashworth scale, there was an improvement in subjective perception of spasticity and also other secondary outcomes. In 2012, the Multiple Sclerosis and Extract of Cannabis trial concluded that the rate of relief of muscle stiffness in patients with MS patients after 12 weeks of therapy was doubled with the same cannabis extract compared with placebo [13].…”