Cannabidiol and Amyotrophic Lateral Sclerosis: A Disease-Modifying Treatment Volume 3 - Issue 5

Marco Orsini¹*, Acary Souza Bulle Oliveira², Adriana Leico Oda², Carlos Henrique Melo Reis¹, Victor Hugo Bastos³, Bruna Velasques⁴ and Marcos RG de Freitas¹

• ¹Medicine Department, Iguacu University, Brazil
• ²Neurology Department, Sao Paulo Federal University, Brazil
• ³Fellow Programa em Mapeamento Cerebral e Funcionalidade, Federal University Piaui, Brazil
• ⁴Rio de Janeiro Federal University, Brazil

Received: October 13, 2019;   Published: October 16, 2019

*Corresponding author: Marco Orsini, Department of Neurology, Fluminense Federal University, Brazil

DOI: 10.32474/LOJMS.2019.03.000174

Abstract PDF

Amyotrophic Lateral Sclerosis can be defined as a progressive, degenerative and inexorable disease that leads to the depletion of upper and lower motor neurons. With the evolution of the disease, the patients present several damages regarding their daily activities. Muscle weakness is undoubtedly the leading cause of functional disability, swallowing, speech and breathing problems [1,2].

A drug approved to “contain” the natural history of the disease is Riluzole (a drug that slows dependence on mechanical ventilation for an average of 3-6 months). Other proposed treatments such as intramuscular use of Methyl cobalamin, oral use of l-serine at high doses, Tauroursodeoxycholic acid up to 2 grams/day, among others, have a certain link with the pathophysiological structure of the disease. Studies on novel therapies are warranted based from the emerging molecular discoveries on the pathogenesis of neuronal cell death in ALS. Edaravone, an antioxidant drug, has recently received approval by Food Drug Administration (FDA). However, more recent studies, while proving to be safe, Edaravone did not provide increased longevity [3-8].

Currently, there have been studies that “seek” to associate the use of medicinal cannabis (cannabidiol - CBD) with Amyotrophic Lateral Sclerosis, as these components have antioxidant, antiinflammatory and neuroprotective characteristics. Authors “believe” that its use could lead to “relief” in neuronal death. We emphasize, with all our expertise, not only for the great care of this clientele, but based on current scientific articles, that CBD alone or associated with THC (Tetrahydrocannabinol) is not a diseasemodifying drug, but it can be used (with parsimony), in some associated clinical situations (spasticity, sleep disturbance, anxiety, depression and pain) [9,10].

Although some media information brings hope to patients, it also generates psychological distress, as many believe in solving the problem altogether. Rare disease groups are extremely beneficial by sharing experiences, helping families, and especially in creating a positive and fierce current of disease control. It is worth mentioning that, every drug, whether controlled or not, ought to be first discussed with the specialist/prescribing physician [10].

Some colleagues or scholars on the subject (CBD) will question about the binding of THC to the CB1 receptor in glutamate receptor inhibition activity in the remaining motor neurons, and even through the antegrade and retrograde axoplasmic flows. It is a fact that glutamate (neurotransmitter) in excess causes damage to cells of the central nervous system and contributes to neurodegeneration. Once again, we are aware of these mechanisms, however current studies need more emphatic to “advertise” cannabidiol as a diseasemodifying drug [11,12].

We will be asked again about studies that conclude that CBD when used in genetically modified animal models (rat) has proved to be a neuroprotective drug. We ought to call attention to the fact that results in animals may not translate success when research is directed to humans. We believe that further experiments may conclude that CBD is indeed a disease-modifying drug. However, at the present time we cannot “validate” such statement [13].

Can CBD be prescribed or not for patients with ALS? Certainly, as long as the prescriber knows exactly what its purpose is in the prescription and it is not considered a disease-modifying drug. Many of us have already prescribed or will prescribe CBD with or without THC in ALS patients; always aware, obviously, of our goals.

1. Chazot Balcon M, Dumazeaud M, Bouchard JP (2019) Neuropsychopathology of amyotrophic lateral sclerosis]. Rev Infirm 68(254): 36-38.
2. Stopford MJ, Allen SP, Ferraiuolo LA (2019) High-throughput and Pathophysiologically Relevant Astrocyte-motor Neuron Co-culture Assay for Amyotrophic Lateral Sclerosis Therapeutic Discovery. Bio Protoc 9(17): pii: e3353.
3. Thakore NJ, Lapin BR, Pioro EP (2019) Pooled Resource Open-Access Als Clinical Trials Consortium. Stage-specific riluzole effect in amyotrophic lateral sclerosis: a retrospective study. Amyotroph Lateral Scler Frontotemporal Degener 27: 1-4.
4. Kaji R, Imai T, Iwasaki Y, Okamoto K, Nakagawa M, et al. (2019) Ultrahigh- dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study. J Neurol Neurosurg Psychiatry 90(4): 451-457.
5. Angiopoietin-1 and ανβ3 integrin peptide promote the therapeutic effects of L-serine in an amyotrophic lateral sclerosis/Parkinsonism dementia complex model.
6. Cai HY, Tian KW, Zhang YY, Jiang H, Han S (2018) Angiopoietin-1 and ανβ3 integrin peptide promote the therapeutic effects of L-serine in an amyotrophic lateral sclerosis/Parkinsonism dementia complex model Aging (Albany NY) 10(11): 3507-3527.
7. Michaud M, Gauchet C, Dray C (2015) Tauroursodeoxycholic acid in the treatment of patients with amyotrophic lateral sclerosis. Eur J Neurol 22(9): e77.
8. Ludolph AC (2016) The TUDCA trial--innovative trial designs for amyotrophic lateral sclerosis drugs? Eur J Neurol 23(1): 11-12.
9. Lim K, See YM, Lee J (2017) A Systematic Review of the Effectiveness of Medical Cannabis for Psychiatric, Movement and Neurodegenerative Disorders. Clin Psychopharmacol Neurosci 15(4): 301-312.
10. Giacoppo S, Mazzon E (2016) Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis? Neural Regen Res 11(12): 1896-1899.
11. Suryadevara U, Bruijnzeel DM, Nuthi M, Jagnarine DA, Tandon R, et al. (2017) Pros and Cons of Medical Cannabis use by People with Chronic Brain Disorders. Curr Neuropharmacol 15(6): 800-814.
12. Bedlack RS, Joyce N, Carter GT, Paganoni S, Karam C (2015) Complementary and Alternative Therapies in Amyotrophic Lateral Sclerosis. Neurol Clin 33(4): 909-936.
13. Weydt P, Hong S, Witting A, Möller T, Stella N, et al. (2005) Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival. Amyotroph Lateral Scler Other Motor Neuron Disord. 6(3): 182-184.