Cannabis Mouth Spray Sativex May Help Reduce Spasticity in ALS Patients, Phase 2 Trial Shows

Sativex, a mixture of two active compounds of cannabis, may help control symptoms of spasticity (stiff muscles) in people with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis, a Phase 2 trial shows.

The study “Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial” was published in the journal The Lancet Neurology.

Cannabinoids are pharmacologically active compounds found in the cannabis plant, with the most studied compounds being the tetrahydrocannabinol (THC) and cannabidiol (CBD).

Spasticity, a condition where the muscles are stiff, heavy and difficult to move, is a major factor contributing to disability and decline in quality of life in patients with ALS and other motor neuron disease, such as multiple sclerosis or cerebral palsy. Previous studies in MS patients have shown that treatment with cannabinoid-based medicines reduced pain and muscle spasticity.

A team of researchers in Italy investigated whether cannabinoids might also reduce spasticity in patients with motor neuron disease, including ALS. The Phase 2 CANALS trial (NCT01776970), which took place at four centers in Italy, enrolled 59 patients diagnosed with ALS or primary lateral sclerosis.

At the time of enrollment, the participants had spasticity for a minimum of three months that was not completely controlled by therapy, with scores of 1 or greater in the Modified Ashworth Scale (the primary clinical measure of muscle spasticity in patients with neurological conditions). All were on anti-spasticity therapy for 30 days before enrolling in the trial and during its course.

Patients were randomized to receive a mix of cannabinoids — specifically THC and compounds called nabiximols (sold under the trade name Sativex by UK-based GW Pharmaceuticals in some European countries and a request for U.S. approval is being considered) — or a placebo for six weeks. Sativex is a mouth (oromucosal) spray.

During the first 14 days of treatment, the participants self-titrated the dose up to their optimal dose, following a predefined escalation scheme, with a maximum 12 actuations per 24 hours. They maintained that dose through the remaining four weeks.

The study’s primary objective was to determine any changes in the score on the Modified Ashworth Scale, from the trial’s beginning to its end. Sativex’s safety and tolerability were also assessed.

In total, 29 patients were randomized to Sativex and 30 to the placebo. The results showed that six weeks of treatment with Sativex significantly improved patients’ scores in the Modified Ashworth Scale, by a mean of 0.11 points, compared with those in the placebo group, who saw their condition deteriorate by a mean of 0.16 points.

Sixteen (55%) of 29 treatment patients rated their “global impression of change as improved, compared with four (13%) of 30 in the placebo group,” the researchers wrote.

Moreover, Sativex was well-tolerated, with no serious side effects reported, and no participants withdrawing from the study.

The trial results suggest that “the study drug . . . provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease,” the researchers said. However, they cautioned that “before 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.”