Can Cannabinoids be an effective treatment for disordered sensorimotor control

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SPASTICITY ASSOCIATED WITH MULTIPLE SCLEROSIS OR SPINAL CORD INJURY
Spasticity is defined as disordered sensorimotor control resulting from an upper motor neuron lesion, presenting as intermittent or sustained involuntary activation of muscles (Pandyan et al., 2005). It occurs in some patients with chronic neurological conditions such as multiple sclerosis (MS) and paraplegia due to spinal cord injury. Recent studies have shown that some individuals with MS are seeking alternative therapies, including cannabis, to treat symptoms associated with MS (Zajicek et al., 2012).

Are Cannabis or Cannabinoids an Effective Treatment for Spasticity Associated with Multiple Sclerosis or Spinal Cord Injury?

Research identified two recent systematic reviews that assessed the efficacy of cannabis or cannabinoids in treating muscle spasticity in patients with MS or paraplegia due to spinal cord injury—the systematic review by Whiting et al. (2015) that examined evidence for a broad range of medical uses of cannabis or cannabinoids and the systematic review by Koppel et al. (2014) that focused more narrowly on neurologic conditions. Both systematic reviews examined only randomized, placebo-controlled trials. Whiting et al. (2015) excluded from their primary analysis trials that did not use a parallel group design (i.e., they excluded crossover trials) and performed a quantitative pooling of results. In contrast, Koppel et al. (2014) included crossover trials but did not perform a quantitative pooling of results.

Whiting et al. (2015) searched for studies examining the efficacy of cannabinoids for spasticity due to MS or paraplegia. They identified 11 studies that included patients with MS and 3 that included patients with paraplegia caused by spinal cord injury. None of the studies in patients with paraplegia caused by spinal cord injury were reported as full papers or included sufficient data to allow them to be included in pooled estimates. Whiting et al. (2015) reported that in their pooled analysis of three trials in patients with MS, nabiximols and nabilone were associated with an average change (i.e., improvement) in spasticity rating assessed by a patient-reported numeric rating scale of −0.76 (95% CI = −1.38 to −0.14) on a 0 to 10 scale that was statistically greater than for the placebo. They further reported finding no evidence for a difference according to type of cannabinoid (i.e., nabiximols versus nabilone). Whiting et al. (2015) also reported that the pooled odds of patient-reported improvement on a global impression-of-change score was greater with nabiximols than with the placebo (OR, 1.44, 95% CI = 1.07–1.94).

The review by Koppel et al. (2014) restricted its focus on spasticity to that due to MS. Their conclusions were broadly in agreement with corresponding conclusions from the review by Whiting et al. (2015). In particular, Koppel et al. (2014) concluded that in patients with MS, nabiximols and orally administered THC are “probably effective” for reducing patient-reported spasticity scores and that oral cannabis extract is “established as effective for reducing patient-reported scores” for spasticity (Koppel et al., 2014, p. 1558).

A commonly used scale for rating spasticity is the Ashworth scale (Ashworth, 1964). However, this scale has been criticized as unreliable, insensitive to therapeutic benefit, and reflective only of passive resistance to movement and not of other features of spasticity (Pandyan et al., 1999; Wade et al., 2010). Furthermore, no minimally important difference in the Ashworth scale has been established. Whiting et al. (2015) calculated a pooled measure of improvement on the Ashworth scale versus placebo based on five parallel-group-design trials. They reported that nabiximols, dronabinol, and oral THC/CBD were associated with a numerically greater average improvement on the Ashworth scale than with a placebo but that this difference was not statistically significant. This conclusion is in broad agreement with corresponding conclusions reached by Koppel et al. (2014), who concluded in particular that nabiximols, oral cannabis extract and orally administered THC are “probably ineffective” for reducing objective measures of spasticity in the short term (6–15 weeks), although oral cannabis extract and orally administered THC are “possibly effective” for objective measures at 1 year.

Discussion of Findings
Based on evidence from randomized controlled trials included in systematic reviews, an oral cannabis extract, nabiximols, and orally administered THC are probably effective for reducing patient-reported spasticity scores in patients with MS. The effect appears to be modest, as reflected by an average reduction of 0.76 units on a 0 to 10 scale. These agents have not consistently demonstrated a benefit on clinician-measured spasticity indices such as the modified Ashworth scale in patients with MS. Given the lack of published papers reporting the results of trials conducted in patients with spasticity due to spinal cord injury, there is insufficient evidence to conclude that cannabinoids are effective for treating spasticity in this population.

CONCLUSION 4-7

4-7(a) There is substantial evidence that oral cannabinoids are an effective treatment for improving patient-reported multiple sclerosis spasticity symptoms, but limited evidence for an effect on clinician-measured spasticity.
4-7(b) There is insufficient evidence to support or refute the conclusion that cannabinoids are an effective treatment for spasticity in patients with paralysis due to spinal cord injury.

Source: www.ncbi.nlm.nih.gov

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