Amyotrophic lateral sclerosis (ALS), also known as Charcot’s disease, is a fatal neurodegenerative disease characterized by progressive muscle paralysis of the muscles involved in muscle movement such as the legs, arms, in breathing, swallowing and speaking. However, cognitive and sensory functions are not affected.

This disease, which is mainly sporadic (a disease that affects individuals in isolation), generally manifests itself between the ages of 50 and 70. The prevalence of this rare disease is 2.16 patients per 100 000 people in Europe, with slightly more frequent cases in men (3 per 100 000) than in women (2.14).  The average life expectancy from diagnosis is 3 to 5 years, although in rare cases patients may live longer (e.g. Stephen Hawking).

Amyotrophic lateral sclerosis: symptoms and origin

During ALS, degeneration of the motor neurons (nerve cells that control the body’s movements) in the spinal cord, brain stem, and motor cortex occurs. The progressive death of the upper and lower motor neurons causes the muscles to weaken and atrophy due to inactivity, resulting in complete paralysis. [1]

Although the reasons for this degeneration are not yet known exactly, several hypotheses have been put forward by scientists. One study theorises that an extremely high level of glutamate (a neurotransmitter), due to reduced absorption, could be responsible for neuronal exhaustion and lead to excitotoxicity (neuronal alteration), oxidative stress (cell aggression), mitochondrial dysfunction (disorder of the respiratory cellular chain), neuroinflammation and dysregulation of cellular metabolism. [2]

Cannabis therapy: an alternative for ALS?

The growing scientific interest in cannabis and its therapeutic potential has encouraged researchers to look into its possible use in the treatment of amyotrophic lateral sclerosis. Although it is still too early to draw conclusions due to the lack of clinical studies on the subject, preclinical studies conducted on animals have shown encouraging results.

The Role of the Endocannabinoid System in ALS

Discovered rather late (1990s), the endocannabinoid system (ECS) is a neurotransmission system essential to the functioning of our body. It ensures homeostasis, i.e. the maintenance of the body’s internal balance, and regulates various physiological processes such as pain, inflammation, appetite, emotions, and so on.

Preclinical studies in animals (mice) have demonstrated the role of the endocannabinoid system in the pathophysiology of ALS.  Indeed, they suggest that a failure in the homeostatic functioning of the neuromuscular system – potentially due to a deficiency in endocannabinoids (cannabinoids produced by the body) – could be the cause of the disruption of physiological processes observed in people with ALS. [3]

Activation of the ECS has been shown to reduce excitotoxicity, neuro-inflammation and oxidative cell damage. Endocannabinoids are used to activate it and have an important role in protecting the nervous system. A deficiency of these would explain the pathophysiology of ALS.  Thus, exogenous cannabinoids (external to the body) present in the cannabis plant, such as Cannabidiol (CBD) and Tetrahydrocannabinol (THC), may activate the ECS and slow the progression of the disease.  [4]

Promising preclinical studies

The primary source of evidence for the potential role of endocannabinoids and cannabinoids in the treatment of amyotrophic lateral sclerosis comes from studies in mice.

In vivo studies in murine mice suggest that THC may act as a neuroprotective agent, improving motor skills and increasing survival time by up to 5% due to their potential anti-glutamatergic and anti-oxidant effects. [5]

About ten preclinical studies in ALS transgenic mice have been conducted. Seven of these studies showed an increase in survival in mice following cannabinoid-based treatment.

The results of the studies suggest that treatment with cannabinoids may slow the progression of the disease, although further studies are needed.  [6]

The effects of therapeutic cannabis on humans

At present, there are no real clinical studies on the effects of therapeutic cannabis on amyotrophic lateral sclerosis that can confirm its effectiveness.

The only experimental data are anecdotal reports from patients describing the effects of cannabis on their symptoms.  These include improvement of pain, muscle spasms, spasticity, depression, appetite and saliva management. A randomized, double-blind, crossover study in people with amyotrophic lateral sclerosis showed that oral THC was safe and overdose resistant. [7]

Recently, the Gold Coast University Hospital (Australia) is conducting a randomized, double-blind, placebo-controlled clinical trial in people with ALS to determine the effectiveness of medical cannabis in slowing the progression of the disease.  Thirty people between the ages of 25 and 75 will participate in the six-month study, the results will be published in a journal soon. [8]

In general, the situation with cannabis and amyotrophic lateral sclerosis is similar to that at the beginning of this century, with anecdotal patient reports of potential efficacy to be followed by well-designed randomized clinical trials that can properly examine the therapeutic benefit of cannabis or endocannabinoids in the treatment of symptoms or their potential for disease modification.

[1] Pryce, G., & Baker, D. (2015). Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis. Endocannabinoids, 213–231. doi:10.1007/978-3-319-20825-1_7

[2] Turner, M. R., et alt. (2013). Mechanisms, models and biomarkers in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 14(sup1), 19–32. doi:10.3109/21678421.2013.778554

[3] Bedlack, R. S., et alt. (2015). Complementary and Alternative Therapies in Amyotrophic Lateral Sclerosis. Neurologic Clinics, 33(4), 909–936. doi:10.1016/j.ncl.2015.07.008

[4] Urbi, B., et alt. (2019). Study protocol for a randomised, double-blind, placebo-controlled study evaluating the Efficacy of cannabis-based Medicine Extract in slowing the disease progression of Amyotrophic Lateral sclerosis or motor neurone Disease: the EMERALD trial, doi: 10.1136/bmjopen-2019-029449.

[5] Giacoppo S, Mazzon E. Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?. Neural Regen Res 2016;11:1896-9 , DOI: 10.4103/1673-5374.197125

[6] Urbi, B., et alt. (2018). Effects of cannabinoids in Amyotrophic Lateral Sclerosis (ALS) murine models: A systematic review and meta-analysis. Journal of Neurochemistry. doi:10.1111/jnc.14639

[7] Giacoppo S, Mazzon E. Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?. Neural Regen Res 2016;11:1896-9 , DOI: 10.4103/1673-5374.197125

[8] Urbi, B., et alt. (2019). Study protocol for a randomised, double-blind, placebo-controlled study evaluating the Efficacy of cannabis-based Medicine Extract in slowing the disease progression of Amyotrophic Lateral sclerosis or motor neurone Disease: the EMERALD trial, doi: 10.1136/bmjopen-2019-029449.