TY - JOUR
T1 - Multiple Sclerosis and Extract of Cannabis (MUSEC) – 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 multiple sclerosis
AU - Zajicek, John Peter
AU - Hobart, Jeremy C.
AU - Slade, Anita
AU - Barnes, David
AU - Rickards, C
AU - Mattison, Paul G.
PY - 2012/7/12
Y1 - 2012/7/12
N2 - SUMMARY
Background. Multiple sclerosis (MS) is associated with chronic symptoms including muscle stiffness, spasms, pain, and insomnia. In the 'Cannabinoids in Multiple Sclerosis' (CAMS) study that assessed the value of cannabinoids in the treatment of spasticity, the Ashworth score did not show significant benefit. Nevertheless, the patients themselves rated cannabinoids as clearly helpful. Here we report on the results of the 'Multiple Sclerosis and Extract of Cannabis' (MUSEC) study that aimed to confirm the patient-based findings of the CAMS study.
Methods. Patients with stable MS at 22 UK centres were evenly randomised to oral cannabis extract (N=144) or placebo (N=135), stratified by centre, walking ability and use of antispastic medicaton. 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 tetrahydrocannabinol (THC) 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 CRS's assessed body pain, spasms, and sleep quality. Three validated MS-specific patient rating scales measured aspects of spasticity, physical and psychological impact, and walking ability. The study is registered at www.clinicaltrials.gov, NCT00552604.
Findings. The rate of relief from muscle stiffness after 12 weeks was almost twice as high with cannabis extract than with placebo (29.4% vs 15.7%; OR 2.26; 95% CI 1.24-4.13; p=0.004, one-sided). Similar results were found after 4 and 8 weeks, and also for all further CRS's. The results for the MS scales supported these findings.
Interpretation. The study met its primary objective to clearly show superiority of cannabis extract over placebo in the treatment of muscle stiffness in MS. This was supported by the results for secondary efficacy variables. The adverse events in patients treated with cannabis extract were consistent with the known side effects of cannabinoids. No new safety concerns were observed.
Funding. Funded by the Society for Clinical Research, Berlin, Germany, and Weleda AG, Arlesheim, Switzerland.
AB - SUMMARY
Background. Multiple sclerosis (MS) is associated with chronic symptoms including muscle stiffness, spasms, pain, and insomnia. In the 'Cannabinoids in Multiple Sclerosis' (CAMS) study that assessed the value of cannabinoids in the treatment of spasticity, the Ashworth score did not show significant benefit. Nevertheless, the patients themselves rated cannabinoids as clearly helpful. Here we report on the results of the 'Multiple Sclerosis and Extract of Cannabis' (MUSEC) study that aimed to confirm the patient-based findings of the CAMS study.
Methods. Patients with stable MS at 22 UK centres were evenly randomised to oral cannabis extract (N=144) or placebo (N=135), stratified by centre, walking ability and use of antispastic medicaton. 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 tetrahydrocannabinol (THC) 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 CRS's assessed body pain, spasms, and sleep quality. Three validated MS-specific patient rating scales measured aspects of spasticity, physical and psychological impact, and walking ability. The study is registered at www.clinicaltrials.gov, NCT00552604.
Findings. The rate of relief from muscle stiffness after 12 weeks was almost twice as high with cannabis extract than with placebo (29.4% vs 15.7%; OR 2.26; 95% CI 1.24-4.13; p=0.004, one-sided). Similar results were found after 4 and 8 weeks, and also for all further CRS's. The results for the MS scales supported these findings.
Interpretation. The study met its primary objective to clearly show superiority of cannabis extract over placebo in the treatment of muscle stiffness in MS. This was supported by the results for secondary efficacy variables. The adverse events in patients treated with cannabis extract were consistent with the known side effects of cannabinoids. No new safety concerns were observed.
Funding. Funded by the Society for Clinical Research, Berlin, Germany, and Weleda AG, Arlesheim, Switzerland.
KW - Multiple Sclerosis
KW - Cannibis
U2 - 10.1136/jnnp-2012-302468
DO - 10.1136/jnnp-2012-302468
M3 - Article
SN - 0022-3050
VL - 83
SP - 1125
EP - 1132
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 0
ER -