medwireNews: The oromucosal cannabinoid spray nabiximols has had a positive effect on spasticity symptoms in patients with motor neuron disease in a proof-of-concept trial.
The phase II trial – safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS) – showed a significant 6-week difference in Modified Ashworth Scale (MAS) scores between 29 patients with amyotrophic lateral sclerosis randomly assigned to nabiximols, which contains a defined combination of delta-9-tetrahydrocannabinol and cannabidiol, and 30 patients assigned to placebo.
The two groups were taking similar levels of first-line anti-spasticity medications at baseline and the average MAS scores at this point were 2.3 among the patients given nabiximols and 2.4 in those given placebo. At the end of a 6-week double-blind treatment phase, the score among patients taking nabiximols had improved by a mean of 0.11, whereas it deteriorated by 0.16 among placebo-treated patients.
After 6 weeks patients were given the opportunity to participate in an open-label treatment phase, and those originally given placebo experienced a mean 0.28 improvement in MAS score.
Nabiximols was also associated with a superior reduction in numeric rating scale pain scores of 0.97 versus 0.06 with placebo; and 55% of patients receiving nabiximols rated their global impression of change as improved, compared with just 13% of the placebo group.
“Improvement in patients’ global impressions of change might reflect the multiple symptomatic effects of cannabinoids that could be beneficial to patients with amyotrophic lateral sclerosis”, say Giancarlo Comi (San Raffaele Scientific Institute, Milan, Italy) and colleagues.
By contrast, there were no significant differences between the two groups for other secondary endpoints, including sleep quality, spasms, spasticity numeric rating scale score, strength, upper and lower motor neuron tests and scores on the Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised, although the researchers note that “the direction of change was consistently in favour of the active treatment”.
They acknowledge in The Lancet Neurology that “the small sample size and short duration of the study provided little opportunity for the detection of a potential neuroprotective effect of cannabinoids in slowing disease progression”.
Nabiximols was generally well tolerated with no patient withdrawing from the blinded phase of the study. At least one potentially treatment-related adverse event was reported in 72% of patients given nabiximols and 13% of those given placebo, all of which were mild to moderate. The most common adverse events were asthenia, somnolence, vertigo and nausea.
In a related comment, Marianne de Visser, from Amsterdam University Medical Centre, the Netherlands, describes the results as “promising” and “encouraging”. But she points out a couple of limitations, namely that 16 of the patients given nabiximols had overt or predominant involvement of upper motor neurons, the prevailing symptom of which is spasticity, and the use of change in MAS score as the primary endpoint, given the measure has lacked sensitivity in similar studies in patients with multiple sclerosis.
She therefore agrees with the researchers’ sentiment: “[B]efore we can confidently recommend the routine use of cannabinoids for symptomatic management of spasticity in patients with motor neuron disease, further studies are warranted to confirm our results.”
By Lucy Piper
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