Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial
Zajicek J, Fox P, Sanders H, Wright D, Vickery J, Nunn A and Thompson A;
Commented by , 30 Dec 2003
Background
Multiple sclerosis (MS) has many disabling features, which often are refractory to medical treatment. Among these symptoms are spasticity, ataxia, tremor and pain. Anecdotal evidence suggests that cannabis and its major components, the cannabinoids, provide relief for these symptoms. The cannabis stativa plant has more than 60 cannobinoids, and their action seem to be mediated through cannabinoid receptors.
Delta-9-tetrahydrocannabinol (THC) was the first isolated cannabinoid, and is suggested to be the most psychoactive component of the plant. Other cannabinoids might modulate the response to THC in a way that is still not understood. Essentially, it is not known which of the cannabinoids that has the largest therapeutic potential.
Aim
To determine if synthetic THC (sTHC) or an ethanol extract of whole cannabis is effective for the treatment of spasticity and other MS related symptoms.
Methods
The study was randomized and placebo controlled, although the authors were not able to make the sTHC and the cannabis extract looks identical. Therefore each of the two preparations had its own matched placebo.
Equivalent doses of the active ingredient were prepared, and medication was based on bodyweight, with a max dose of 25 mg pr. day. 667 MS patients with stable disease and an Ashworth spasticity score of >/= 2 were included in the study. 630 patients were allocated to treatment with sTHC (n=206), cannabis extract (n=211) or placebo (n=213).
The duration of the trial was 15 weeks. The primary outcome measure was change in Asworth spasticity score. Secondary outcome measures included the Rivermead mobility index and Kurtzke expanded disability status scale (EDSS). The primary outcome was compared using analysis of variance, with treatments as fixed effects. For further description of statistics, see original paper.
Results
Follow up data on the primary end point was obtained for 611 patients. There was no effect of cannabinoids on the primary outcome (p=0.40). Difference in mean reduction in Asworth score was estimated to 0.32 (95% CI –1.04 to 1.67) for cannabis extract and 0.94 (-0.44 to 2.31) for sTHC compared with placebo.
There was a treatment effect of self-reported spasticity (p=0.003) and pain (p=0.003) and sTHC improved mobility (10 m timed walk; p=0.015). There was no evidence of treatment effect in any other secondary outcome measure.
Discussion
The study showed no significant effect of THC on Asworth spasticity score, which was the primary end point. The Asworth scale is quite conservative, but still the most reliable and well validated measure of spasticity, which justifies its use. The authors found an effect on self-reported spasticity, which is a result that should be interpreted with caution.
Cannabinoids has the potential of affecting the perception of symptoms, which could lead to masking of negative symptoms. The pain assessment was not performed as a state of the art measure, and the positive result in this regard should therefore be considered as guiding.
The only objective measure that was significantly improved was mobility in the sTHS group, and the effect was weak to modest.
Generally the study show disappointing results for sTHC and cannabis extract, and it clearly states that these drugs has no major impact on spasticity in MS.