COPENHAGEN — A cannabis extract reduces spasticity and is safe in patients with motor neuron diseases (MND), including amyotrophic lateral sclerosis (ALS), results of the phase 2 randomized multicenter CANALS trial suggest.
A major symptom for patients with MND, spasticity can lead to functional loss, affect joints, and cause pain, Nilo Riva, MD, PhD, San Raffaele Hospital, Milan, Italy, told delegates here at the Congress of the European Academy of Neurology (EAN) 2016.
Currently available antispastic therapies are often not satisfactory, and no randomized clinical trials have evaluated antispastic drugs specifically in patients with MND.
A cannabinoid-based treatment for spasticity makes some sense, according to Dr Riva. Cannabinoid receptors are expressed in the central nervous system, so such therapies could have some therapeutic effects, he said.
Such potential effects might include muscle relaxation, analgesia, appetite stimulation, nausea control, anticonvulsion, antioxidation, and possibly neuroprotection.
Dr Riva noted that several clinical trials have tested the efficacy of cannabinoids on spasticity in patients with multiple sclerosis (MS). Such drugs, he said, are first-line treatments for central neuropathic pain and are a valuable alternative in non-neuropathic pain.
And Dr Riva pointed out that cannabinoids have shown improved survival and delayed functional impairment in ALS animal models.
The new study included 60 adult patients with ALS or primary lateral sclerosis with spasticity symptoms that they deemed to cause impairment. The mean age of study patients was about 58 years, and their disease duration was about 57 months.
After screening, study patients entered a 7-day baseline evaluation stage during which they recorded their symptoms on the numeric rating scale (NRS), scored from 0 to 10.
Half of the patients were then randomly assigned to receive placebo and the other half to take a combination tetrahydrocannabinol (THC) and cannabidiol (CBD) oral mucosal spray.
The CBD and THC act synergistically, with the spray "optimized" to reduce the psychoactive and sedative effects of THC, said Dr Riva.
The two groups were well balanced, Dr Riva said. In the first 2 weeks, the treatment dose was titrated, after which a stable dose was maintained for 4 weeks. One patient dropped out of the active treatment group.
The study showed a "significant effect" on the primary outcome of change in the mean score on the modified Ashworth scale (P = .013).
Secondary endpoints included symptoms of spasticity and pain on the NRS; various measures of function, including the timed 10-meter walk; patient reported Global Impression of Change (GIC); and adverse effects (AEs).
The researchers observed a "general improvement" on the NRS scale, which reached a "significant threshold" for pain (P = .013), Dr Riva reported.
As well, he said, there was "a significant subjective improvement" on the GIC in about 55% of the patients receiving the active treatment.
Other secondary outcome measures were not significant, although there was a trend in favor of the cannabinoid intervention in most of these measures, said Dr Riva.
No serious AEs occurred. A "substantial number" of patients in the active group experienced potentially treatment-related AEs (70% vs 13.8% in the placebo group), but these were mild to moderate in severity and "were in line with what we expected form previous experience, particularly in MS patients," said Dr Riva.
The AEs included asthenia, somnolence, vertigo and nausea.
Given the safety profile of this agent and the clinical data in a mouse model of ALS, it would be "interesting" to "explore a potential neuro protective effect of cannabinoids in these patients," said Dr Riva.
Asked by co-chair Orla Hardiman, Dublin, Ireland, if the outcome for spasticity in patients with ALS is similar to that in patients with MS, Dr Riva said that the current study used the same outcome measures, "so it's comparable."
Although the message from the current study is "positive," Dr Riva stressed that it's important to keep in mind that it's a phase 2 clinical trial, "so the results should be confirmed in larger studies." He said he hopes to carry out a larger phase 3 study.
The study also includes an open-label extension phase.
The study was funded by Fondazione Italiana di Ricerca per la Sclerosi Laterale Amiotrofica (AriSLA, CANALS Project).
Congress of the European Academy of Neurology (EAN) 2016. Abstract O1213. Presented May 28, 2016.
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Cite this: Cannabis Extract Spray Reduces Spasticity in Patients With MND - Medscape - May 31, 2016.