cbd motor neurone disease

Cbd motor neurone disease

Summary of study procedures. AE, adverse event; ALSFRS-R, ALS Functional Rating Scale-Revised; ALSSQOL, ALS specific quality of life-Revised; CBD, cannabidiol; ConMed, concomitant medication; C-SSRS, Columbia-Suicide Severity Rating Scale; ECAS, Edinburgh Cognitive and behavioural ALS Screen; FVC, forced vital capacity; pNRS, Numeric Rating Scale for pain; sNRS, Numeric Rating Scale for spasticity.

Exclusion criteria

The activation of the endocannabinoid system (ECS) has been demonstrated to reduce excitotoxicity, oxidative cell damage and neuroinflammation. 7 8 ECS is a vital physiological neuromodulatory system in human beings; it is involved in regulating homeostasis. ECS is widely expressed in different parts of the human body, particularly in the brain and spinal cord. ECS regulates physiological processes such as pain, emotions, stress, neural development, inflammation, appetite and sleep cycles. 9 ECS has two major cannabinoid (CB) receptors – CB1 and CB2. CB1 receptors are extremely abundant in the nervous system while CB2 receptors are more present in immune cells. 10

The Efficacy of cannabis-based Medicine Extract in slowing the disease pRogression of Amyotrophic Lateral sclerosis or motor neurone Disease (EMERALD) trial is a randomised, double-blind, placebo-controlled single centre study enrolling ALS patients with symptom onset within the last 2 years prior to randomisation. Patient recruitment will take place at Gold Coast University Hospital (GCUH), Australia. Recruitment of participants started in January 2019. All participants will be screened and if eligible will be enrolled in the trial. All participants are required to give written, informed consent prior to enrolment. Participants will take either the study drug or placebo for 6 months. They will be followed up by face-to-face visits 3 monthly and via phone call every month. It is anticipated that the study will take 2.5 years to complete (January 2019 to June 2021).

Sample size

The titration regimen for this study was based on the principle of ‘start low and go slow’. 37 Patients taking the approved CB nabiximols (Sativex) commence medication using a titration scheme for up to 2 weeks to determine the optimal drug dose. The pharmacokinetic variability of nabiximols is high between individuals, but low within individuals. 38

History of any psychiatric disorder other than depression associated with their underlying condition. including immediate family history of schizophrenia.

Additionally, the rationale for choosing a high-CBD-low-THC formulation relates to the entourage effect of CB. When administered together, the CB modulate or enhance the effects of the various components, and the reduction of psychoactive effects associated with cannabis can be seen. 31 THC and CBD are two well-understood CBs of the 60 constituents of the cannabis plant. 32 THC is the major psychoactive constituent in cannabis, while CBD is known to have neuroprotective effects and is non-intoxicating, but has antianxiety and antipsychotic activity. CBD modulates the activation of CB receptors 31 and may counteract the psychoactive effects of THC. 33 A high-CBD-low-THC ratio was chosen for this study not only to mitigate the psychoactive effects of THC but to leverage the neuroprotective potential of CBD.

Study intervention

Unwilling to stop driving and operate heavy machineries.

To ensure the blinding of investigators and participants to study treatment, the study drug or placebo will be provided in identical packaging and labelling. Due to some natural variability in the colour of the study drug, which is batch dependent, the colour of the placebo has been matched to be the same as the average colour of the study drug. Study drug and placebo will be labelled with a unique label letter that will be used to assign treatment to the patient but will not indicate treatment allocation to the investigators or participants. No member of the study team and their extended staff, except for the trial pharmacists and biostatistician, will have access to the randomisation scheme during the conduct of the study. In the event of a medical emergency, where breaking the blind is required to provide medical care to the participant, the investigator will obtain the treatment assignment from trial pharmacists.

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.

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.