Cannabinoids have been shown to treat a variety of neurodegenerative disorders such as Alzheimer’s Disease, Parkinson’s Disease, Multiple Sclerosis, and ALS through several different neuroprotective mechanisms (Cristino et al., 2020). 

To understand how cannabis can treat such a wide range of neurodegenerative disorders, it helps to understand how cannabis interacts with the endocannabinoid system. The endocannabinoid system is complex, playing a role in many functions ranging from emotional processing and sleep to memory and learning. It also involved many receptors such as CB1, CB2, and TRPV1. (Mechoulam & Parker, 2013). Substances that bind to these receptors that are made naturally by the body are called endocannabinoids while those that are found in nature or made in a lab are known as cannabinoids. 

Cannabinoids like THC and CBD bind to many different receptors in the endocannabinoid system, although much research has focused on their effects on CB1 and CB2 receptors. CB1 receptors are found throughout the brain and spinal cord. These receptors are thought to be responsible for the psychoactive and intoxicating effects of weed.

CB2 receptors are concentrated in the cells and tissues of the immune system like T cells, and macrophages. They are also found in the brain but are concentrated mainly on microglial cells and astrocytes which act as immune cells in the brain. Microglia are important modulators of neuroinflammation and are the first line of defense from infection and injury in the brain. When microglia are activated they increase in number and they produce proinflammatory signals that lead to neuroinflammation, neurodegeneration, and the inhibition of the growth of new neurons. CB2 receptors are upregulated in all neurodegenerative disorders particularly on glial cells and are most intense in reactive microglial cells (Fernández-Ruiz et al., 2008). 

Cannabis is used to treat such a wide range of neurodegenerative disorders because many of these disorders are associated with increases in neuroinflammation and decreases in neurogenesis. Cannabinoids protect neural cells from neuroinflammation by helping to maintain immune system balance. Cannabinoids influence whether microglial cells will release signals that are neurotoxic or neuroprotective (Mecha et al., 2019). Downregulation of pro-inflammatory signals and glial activation alleviates the effects of neurodegenerative diseases like Alzheimer’s Disease and Parkinson’s Disease (Mee-Inta et al., 2019).

Cannabinoids offer hope for disorders such as Huntington’s Disease that have no cure. Huntington’s Disease affects motor control causes cognitive deficits and is associated with negative psychiatric outcomes such as depression. Using a mouse model of Huntington’s, the role of CB2 receptors in the progression of the disorder has been explored. Researchers used mice breed to have genetic mutations that reduced the amount of CB2 receptors. These mice had worse motor control. Additionally, their conditions progressed faster leading to earlier deaths. Finally, the mice without CB2 receptors had increased microglial activation and inflammation.

Cannabinoids hold great potential for treating neurodegenerative diseases, as both normal and pathological aging is associated with increases in neuroinflammation. Because cannabis is a schedule I drug, meaning it has no medical use, it is difficult to conduct research with cannabinoids especially in humans. Clearly this legislation should be revisited as cannabis may hold the key to curing devastating conditions like Alzheimer’s Disease.

Sources

Cristino, L., Bisogno, T., & Di Marzo, V. (2020). Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nature Reviews Neurology, 16(1), 9-29.

Fernández-Ruiz, J., Pazos, M. R., García-Arencibia, M., Sagredo, O., & Ramos, J. A. (2008). Role of CB2 receptors in neuroprotective effects of cannabinoids. Molecular and cellular endocrinology, 286(1-2), S91-S96.

Mee-Inta, O., Zhao, Z. W., & Kuo, Y. M. (2019). Physical exercise inhibits inflammation and microglial activation. Cells, 8(7), 691.

Mecha, M., Feliú, A., Carrillo-Salinas, F. J., Rueda-Zubiaurre, A., Ortega-Gutiérrez, S., de Sola, R. G., & Guaza, C. (2015). Endocannabinoids drive the acquisition of an alternative phenotype in microglia. Brain, behavior, and immunity, 49, 233-245.

Mechoulam, R., & Parker, L. A. (2013). The endocannabinoid system and the brain. Annual review of psychology, 64, 21-47.

Palazuelos, J., Aguado, T., Pazos, M. R., Julien, B., Carrasco, C., Resel, E., … & Galve-Roperh, I. (2009). Microglial CB2 cannabinoid receptors are neuroprotective in Huntington’s disease excitotoxicity. Brain, 132(11), 3152-3164.