Cannabis-based drug may help to relieve symptoms of motor neuron disease
A multicenter study published today on Lancet Neurology suggests, for the first time, that chemical compounds derived from the cannabis sativa plant may help ease symptoms of spasticity – tight or stiff muscles – in patients with moto neuron diseases. The therapy, a THC-CBD mouth spray, has been recently approved also for symptomatic treatment of spasticity in multiple sclerosis. The study, possible thanks to the support of the Italian Research Foundation for Amyotrophic Lateral Sclerosis (AriSLA), was conducted by a group of physician-scientists of IRCCS Ospedale San Raffaele and Università Vita-Salute San Raffaele, led by Professor Giancarlo Comi, director of the Institute of Experimental Neurology.
Spasticity is a common symptom in motor neuron disease, a rapidly progressive, fatal neurodegenerative disorder affecting the nerve cells that control muscle movement (motor neurons). It occurs to a variable degree in people with amyotrophic lateral sclerosis (ALS), the most common and severe form of motor neuron disease, and is a defining characteristic of primary lateral sclerosis (PLS), that is rarer and progresses more slowly. While there are several drugs to relieve spasticity, evidence for their effectiveness is scant and they do not sufficiently improve symptoms in all patients. Moreover, they can have undesirable side effects, such as increasing muscle weakness and fatigue.
Previous research has found possible therapeutic benefits of cannabinoids (components of the cannabis plant) to include muscle relaxation, appetite stimulation, and pain-relieving, anticonvulsant, and anti-inflammatory effects in patients with other neurological conditions. Cannabinoids have been licensed in several countries for symptomatic treatment of spasticity in multiple sclerosis, and are increasingly recognized as a valuable option for the management of pain.
To investigate whether cannabinoids might also reduce spasticity in motor neuron disease, Italian researchers recruited 60 adults (aged 18-80 years) with ALS or PLS from four tertiary motor neuron disease centers in Italy. To participate in the study, patients had to have experienced spasticity symptoms for at least 3 months and be taking a stable dose of any anti-spasticity medication for 30 days before enrolment and throughout the study.
Participants were randomized to receive a THC-CBD mouth spray (29 participants) or placebo (30) for 6 weeks. The number of sprays was gradually increased for the first 2 weeks of treatment until the optimum dose was reached, and then that dose was maintained for 4 weeks. Change in spasticity was assessed by a physician who rated the spasticity of each participant’s joints on the Modified Ashworth Scale (MAS) – an objective tool to evaluate intensity of muscle tone. Participants were also asked to keep a daily symptom diary on spasticity levels, pain, spasm frequency, and sleep disruption.
At the end of treatment (6 weeks), spasticity was significantly improved in the THC-CBD spray group compared with the placebo group. Additionally, the number of participants treated with THC-CBD spray reporting an improvement was significantly higher compared with participants receiving placebo. Finally, pain scores were significantly improved in the THC-CBD spray group compared with placebo.
Overall, THC-CBD spray was well tolerated and adverse events were mild to moderate and typical of cannabinoids: asthenia (loss of energy and fatigue), somnolence (sleepiness), vertigo and nausea. There were no serious adverse events and no participants permanently discontinued treatment.
“There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” says dr Nilo Riva, first author of the study. “Our proof-of-concept trial showed a beneficial effect of THC-CBD spray in people on treatment-resistant spasticity and pain. Despite these encouraging findings, we must first confirm that THC-CBD spray is effective and safe in larger, longer term phase 3 trials.”
Nilo Riva, Gabriele Mora, Gianni Sorarù, Christian Lunetta, Ottavia E. Ferraro Yuri Falzone, Letizia Leocani, Raffaella Fazio, Mauro Comola, Giancarlo Comi for the CANALS Study Group, Safety and Efficacy on Spasticity Symptoms of a Cannabis Sativa Extract in Motor Neuron Disease Patients (CANALS): a Multicentre, Randomized, Double-Blind, Placebo-Controlled phase 2 trial, The Lancet Neurology, Dec 2018.