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| MS in focus Issue
12
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2008
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Paul Smith, PhD, Professor of Neuropharmacology, Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago Medical School, Dunedin, New Zealand |
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Many survey studies and anecdotal reports suggest that some people with MS self-medicate with marijuana (or cannabis, Latin name: Cannabis sativa) in order to relieve their spasticity.
Experimental pharmacological studies support the hypothesis that cannabinoid chemicals within cannabis, such as delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), exert muscle relaxant effects. While delta-9-THC does this via a specific cannabinoid receptor (the CB1 receptor) which was discovered in the central nervous system in the late 1980’s, CBD appears to have more complicated actions and may affect cytokines (proteins that are released by cells of the immune system and play a role in the generation of an immune response).
Initial clinical trial data did not support the efficacy of delta-9-THC in reducing spasticity. The first report from the “Cannabinoids in Multiple Sclerosis” (CAMS) trial, a blind and placebo-controlled trial in the UK, suggested that delta-9-THC had no statistically significant effect on spasticity when evaluated by the objective Ashworth scale.
However, in a 12-month follow-up study involving 630 patients, delta-9-THC was shown to have a small but significant effect. Nonetheless, in both studies the patients reported a subjective improvement in spasticity. It is a matter of some controversy whether the initial lack of effect using the Ashworth scale reflects the lack of sensitivity of that scale for quantifying spasticity.
The natural cannabis extract in the pharmaceutical product marketed as Sativex® has been reported to alleviate spasticity in a number of clinical trials.
Sativex is a 1:1 ratio of delta-9-THC and CBD and can be administered as a sublingual (under the tongue) or oromucosal (nasal) spray. Not all trials testing the efficacy of Sativex® have been blind or placebo-controlled, raising questions about the quality of the data collected. Most trials that have been well controlled have still found a significant improvement in spasticity, at least according to subjective rating scales, however there is also some contradictory evidence regarding this. The most common adverse side effects reported have been oral pain, dizziness, diarrhoea and nausea. Of the other cannabinoids that have been investigated, the synthetic cannabinoid, nabilone, has been reported to reduce pain related to spasticity in one recent study.
There have now been more than 12 clinical trials published on the effects of cannabinoids on spasticity and pain in MS. Although not all of these studies demonstrate a significant improvement in symptoms with delta-9-THC or CBD, evidence is accumulating that cannabinoid drugs may be useful in at least a subset of patients, and at least as an adjuvant therapy. Even where cannabinoids have failed to reduce spasticity according to the Ashworth scale, it has been pointed out that many commonly used anti-spasticity drugs have also failed to generate statistically significant results according to this scale.
Long-term studies suggest that cannabinoids are reasonably well tolerated by patients but there is still concern about potential long-term adverse effects, such as cognitive impairment, impaired foetal development and psychiatric side effects. However, it must be recognised that many conventional anti-spasticity drugs such as baclofen also have significant side effects. It should also be noted that in some countries cannabis is an illegal drug, which affects its accessibility.
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