November 6, 2003
Laurie Barclay, MD
Reviewed by Gary D. Vogin, MD
Lancet. 2003;362:1513, 1517-1526
The first large-scale randomized trial of cannabis for treatment of symptoms of multiple sclerosis, reported in the Nov. 8 issue of The Lancet, had mixed results. The objective measure of spasticity was not improved, but patients subjectively reported less pain and improved mobility. The commentator hopes that this study will stimulate further research on alternative formulations.
"Spasticity is a highly complex phenomenon, composed of both signs observable to assessors and symptoms reported by patients," lead author John Zajicek, from the University of Plymouth in the U.K., says in a news release. "Our results, using the Ashworth score as the primary outcome measure, exclude any major effect of treatment of spasticity with cannabinoids, but the effect of spasticity and pain as assessed by patients indicates a symptomatic subjective clinical effect."
At 33 U.K. centers, 630 patients with multiple sclerosis were randomized to receive oral cannabis extract, D9-tetrahydrocannabinol (THC), or placebo. After 15 weeks, spasticity scores on the objectively assessed Ashworth scale were similar in all three groups. Walking time for 10 meters decreased by 12% in the THC group compared with 4% in both the cannabis extract and placebo groups. Subjective improvements in spasticity occurred in 60% of patients in the cannabinoid treatment groups and in 46% of the placebo group, and pain decreased in 54% of patients in the cannabinoid groups and in 37% of patients in the placebo group (P = .003).
Study limitations include those associated with the Ashworth score, possible failure to achieve adequate systemic medication concentrations, large placebo effect, and unmasking in the active treatment groups explains some of these subjective ratings. "Our findings therefore provide some evidence that cannabinoids could be clinically useful in treatment of symptoms related to multiple sclerosis, but more work is necessary, using outcome measures that more adequately assess the effect of symptoms in chronic disease," Dr. Zajicek says.
The U.K. Medical Research Council funded this study. The authors report no potential financial conflicts of interest.
In an accompanying commentary, Luanne Metz and Stacey Page, from the University of Calgary in Alberta, Canada, note that many standard therapies for spasticity, including baclofen, have comparable evidence to support their use in ambulatory patients with multiple sclerosis.
"Because we do not know how these cannabinoids compare to other anti-spasticity
treatments, they should generally only be considered when other therapy
has failed," Drs. Metz and Page write. "We still have no data to compare
the risks and benefits of smoked cannabis. Hopefully, this study will stimulate
further research to develop and evaluate safe, effective formulations of
cannabis, and will inform debate over the social and legal restrictions
that limit its use. In the meantime, when other treatment inadequately
controls spasticity, oral cannabinoids should be considered where law permits
their possession and use."
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