ALS

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Introduction

Amyotrophic Lateral Sclerosis or ALS is a degenerative disease of the motor neurons that control voluntary movement. Although some genes have been linked to ALS, the majority of cases have unknown environmental causes which may lead to overexcitation or excitotoxicity of motor neurons. Early signs of ALS include muscle weakness, muscle spasms, neuropathic pain or difficulty with eating or swallowing. At present there is no cure for ALS but several symptoms of ALS such as spasticity, cramps or pain can be treated with cannabis or cannabinoids. Also, cannabinoids can prevent neuronal excitotoxicity and degeneration and thus may help slow down the disease process and improve the patient’s quality of life. Overall there is evidence for the involvement of the Endocannabinoid system in ALS and for the therapeutic potential of cannabinoids in the treatment of ALS symptoms but more research is required.

Alternative Names

Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Lou Gehrig's Disease

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Prescription Advice

Preclinical data provides evidence for the therapeutic effect of THC and CBG. Clinical evidence suggests THC and CBD are therapeutic in ALS in a ratio of 1/1.

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Please note that, while based on preclinical and/or clinical research, this prescription advice is solely intended as a guideline to help physicians determine the right prescription. We intend to continuously update our prescription advice based on patient and/or expert feedback. If you have information that this prescription advice is inaccurate, incomplete or outdated please contact us here.

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Literature Discussion

In patients with ALS and reactive gliosis, spinal cord- and cortical motor neurons as well as astrocytes had elevated CB2 but no changes in CB1, MAGL or FAAH (Espejo-Porras et al., 2018a).

In the TDP-43 (A315T) mouse model of ALS, THC-like substances reduce reactive gliosis and improve motor performance via CB2 (Espejo-Porras et al., 2018b).

In the hSOD(G93A) mouse model of ALS, THC prevented neuronal excitotoxicity, improved motor performance and increased survival by 5% (Raman et al., 2004; Urbi et al., 2018).

In the hSOD(G93A) mouse model of ALS, elevating 2AG by  MAGL inhibition protected against inflammation and neurodegeneration (Pasquarelli et al., 2017).

In the hSOD(G93A) mouse model of ALS, a synthetic CBG-derivative was protective against reactive gliosis, preserved motor neurons and attenuated weight loss via PPARγ (Rodríguez-Cueto et al., 2018).

The SOD1 dog model of ALS also shows glial upregulation of CB2 and reactive gliosis (Fernández-Trapero et al., 2017).

Literature:

Espejo-Porras, F., Fernández-Ruiz, J., and de Lago, E. (2018a). Analysis of Endocannabinoid receptors and enzymes in the post-mortem motor cortex and spinal cord of amyotrophic lateral sclerosis patients. Amyotroph. Lateral Scler. Front. Degener. 1–10.

Espejo-Porras, F., García-Toscano, L., Rodríguez-Cueto, C., Santos-García, I., de Lago, E., and Fernández-Ruiz, J. (2018b). Targeting glial CB2receptors to delay the progression of the pathological phenotype in TDP-43 (A315T) transgenic mice, a model of amyotrophic lateral sclerosis. Br. J. Pharmacol.

Fernández-Trapero, M., Espejo-Porras, F., Rodríguez-Cueto, C., Coates, J.R., Pérez-Díaz, C., Lago, E. de, and Fernández-Ruiz, J. (2017). Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis. Dis. Model. Mech. 10, 551–558.

Pasquarelli, N., Engelskirchen, M., Hanselmann, J., Endres, S., Porazik, C., Bayer, H., Buck, E., Karsak, M., Weydt, P., Ferger, B., et al. (2017). Evaluation of monoacylglycerol lipase as a therapeutic target in a transgenic mouse model of ALS. Neuropharmacology.

Raman, C., McAllister, S.D., Rizvi, G., Patel, S.G., Moore, D.H., and Abood, M.E. (2004). Amyotrophic lateral sclerosis: delayed disease progression in mice by treatment with a cannabinoid. Amyotroph. Lateral Scler. Mot. Neuron Disord. Off. Publ. World Fed. Neurol. Res. Group Mot. Neuron Dis. 5, 33–39.

Rodríguez-Cueto, C., Santos-García, I., García-Toscano, L., Espejo-Porras, F., Bellido, Ml., Fernández-Ruiz, J., Muñoz, E., and de Lago, E. (2018). Neuroprotective effects of the cannabigerol quinone derivative VCE-003.2 in SOD1G93A transgenic mice, an experimental model of amyotrophic lateral sclerosis. Biochem. Pharmacol.

Urbi, B., Owusu, M.A., Hughes, I., Katz, M., Broadley, S., and Sabet, A. (2018). Effects of cannabinoids in Amyotrophic Lateral Sclerosis (ALS) murine models: A systematic review and meta-analysis. J. Neurochem.

Clinical Trials

Positive reports:

In a case report, 200-300 mg CBD twice daily transiently improved motor function and slowed down disease progression (Nahler).

In a clinical trial with 59 ALS patients a 1/1 mix of THC/CBD was tested as oromucosal spray. Each dose contained 2.7 mg THC and 2.5 mg CBD and patients were allowed to self-administer up to 12 doses per 24h. After 6 weeks patients who had received THC/CBD had improved on the Modified Ashworth Scale by 0.11 while patients who had received placebo had deteriorated by 0.16 (effect size 0.32, p=0.01) (Riva et al., 2018).

A cannabis user survey, with 13 ALS patients who were using cannabis, reported cannabis may be moderately effective at reducing symptoms of appetite loss, depression, pain, spasticity, and drooling (Amtmann et al., 2004).

Negative reports:

In one clinical trial with 27 ALS patients, 5 mg THC twice daily was well tolerated but did not reduce cramp occurrence or intensity (Weber et al., 2010).

Literature:

Amtmann, D., Weydt, P., Johnson, K.L., Jensen, M.P., and Carter, G.T. (2004). Survey of cannabis use in patients with amyotrophic lateral sclerosis. Am. J. Hosp. Palliat. Care 21, 95–104.

Nahler, G. Co-medication with Cannabidiol May Slow Down the Progression of Motor Neuron Disease: A Case Report | OMICS International.

Riva, N., Mora, G., Sorarù, G., Lunetta, C., Ferraro, O.E., Falzone, Y., Leocani, L., Fazio, R., Comola, M., Comi, G., et al. (2018). 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. Lancet Neurol.

Weber, M., Goldman, B., and Truniger, S. (2010). Tetrahydrocannabinol (THC) for cramps in amyotrophic lateral sclerosis: a randomised, double-blind crossover trial. J. Neurol. Neurosurg. Psychiatry 81, 1135–1140.