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).
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.