What is the Endocannabinoid System and How Does It Work?

Introduction
Recently, marijuana has become a huge talking point for scientists, physicians, and politicians alike. Public support for medical marijuana is at an all-time high and research on therapeutic uses for the plant is rapidly progressing. Today’s modern view on the drug seems a far cry from the past, and much of this can be attributed to the breakthroughs in medicinal uses and applications of marijuana, one of the biggest and most radical of which was the discovery of the endocannabinoid system and its effects. In this article, we will look at what the system is, the effects it can have across the body, and where research on the system is going.
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What the Endocannabinoid System Is
At its most basic level, the endocannabinoid system is a combination of the endocannabinoids produced in the body and the cannabinoid receptors found throughout the nervous system. The receptors can be either CB1 receptors or CB2 receptors, and both are found in many different places. It was previously thought that CB1 receptors were only found in the brain, and CB2 receptors only in the immune system, but this has since been disproven. There are several endocannabinoids produced in the body, all with seemingly different affinities, or “preferences” for the cannabinoid receptors.
The cannabinoid receptors are a trans-membrane protein, meaning that the protein binds to molecules outside of the cell and send signals through the inside of the cell. Both CB1 and CB2 receptors have been linked to many important pathways in the body, and their effects can differ depending on which endocannabinoid is binding to which receptor.
What the Effects of the Endocannabinoid System are
The endocannabinoid system has been found to have numerous effects across the body, affecting both physical and mental processes. Some of these processes include effects on the immune system, neurodegenerative processes, and tumor growth.
The cannabinoid receptors’ location in the immune system has provoked extensive research. It has been shown that CB2 receptors are produced on many types of immune cells and can have a wide variety of effects on these cells (Galiègue et al., 1995). These effects have become clearer over time, and includes inducing movement of immune cells, suppressing the expression of immune cells, and causing immune cell death (Basu et al., 2011; Lombard et al., 2007). These discoveries have led to the proposal of targeting the endocannabinoid system for rheumatoid arthritis therapy and treatment of certain kinds of neuropathic pain (Lowin et al., 2019).
Cannabinoid receptors also have a profound effect on the mind. When activated, they can promote the development of cells in parts of the brain, regulate hunger, and induce sleep depending on the pathways they activate. These pathways can also oppose each other. Returning to the endocannabinoid system and hunger, for example, there is evidence that food intake can be increased or decreased depending on the chemical activating the receptor.
Where Research is Heading
Research on the endocannabinoid system has progressed hugely in just the past eighty years. THC was only just isolated in 1964 and the first cannabinoid receptor was discovered in 1988 in rats. In 1993 the second cannabinoid receptor was discovered, one year after uncovering the first endocannabinoid. From there, the locations and pathways of endocannabinoids have been identified. Researchers are continuing to bring new reactions and processes to light and are using the system to treat a wide range of disease.
Recent studies have shown promise in slowing growth of certain types of cancers, easing symptoms of MS, and combating Parkinson’s disease. A recent study in rats has shown that activation of the CB2 receptor can lead to a reduction in the plaque commonly found in Alzheimer’s patients (María Tolón et al., 2009).
In summary, the endocannabinoid system is a combination of the endocannabinoids produced in the body and the cannabinoid receptors. Its effects are far-reaching and varied and is a possible target for many different clinical and therapeutic processes. Researchers are currently working on the mechanisms and actions behind the effects and ways to modify and control it.
Cited Works
Galiegue, Sylvaine, Sophie Mary, Jean Marchand, Danielle Dussossoy, Dominique Carriere, Pierre Carayon, Monsif Bouaboula, David Shire, Gerard Fur, and Pierre Casellas. “Expression of Central and Peripheral Cannabinoid Receptors in Human Immune Tissues and Leukocyte Subpopulations.” European Journal of Biochemistry232, no. 1 (1995): 54-61. Accessed March 29, 2019. doi:10.1111/j.1432-1033.1995.tb20780.x.
Basu, S., A. Ray, and B. N. Dittel. “Cannabinoid Receptor 2 Is Critical for the Homing and Retention of Marginal Zone B Lineage Cells and for Efficient T-Independent Immune Responses.” The Journal of Immunology187, no. 11 (2011): 5720-732. Accessed March 29, 2019. doi:10.4049/jimmunol.1102195.
Lombard, Catherine, Mitzi Nagarkatti, and Prakash Nagarkatti. “CB2 Cannabinoid Receptor Agonist, JWH-015, Triggers Apoptosis in Immune Cells: Potential Role for CB2-selective Ligands as Immunosuppressive Agents.” Clinical Immunology122, no. 3 (2007): 259-70. Accessed March 29, 2019. doi:10.1016/j.clim.2006.11.002.
Lowin, T., M. Schneider, and G. Pongratz. “Lombard, Catherine, Mitzi Nagarkatti, and Prakash Nagarkatti. “CB2 Cannabinoid Receptor Agonist, JWH-015, Triggers Apoptosis in Immune Cells: Potential Role for CB2-selective Ligands as Immunosuppressive Agents.” Clinical Immunology 122, No. 3 (2007): 259-70. Accessed March 29, 2019. Doi:10.1016/j.clim.2006.11.002.” Current Opinion in Rheumatology31, no. 3 (May/June 2019): 271-78. Accessed March 29, 2019.
Tolón, Rosa María, Estefanía Núñez, María Ruth Pazos, Cristina Benito, Ana Isabel Castillo, José Antonio Martínez-Orgado, and Julián Romero. “The Activation of Cannabinoid CB2 Receptors Stimulates in Situ and in Vitro Beta-amyloid Removal by Human Macrophages.” Brain Research1283 (2009): 148-54. Accessed March 29, 2019. doi:10.1016/j.brainres.2009.05.098.

With over 25 years of specialty training in Internal Medicine, as well as fellowship training in Functional and Sexual medicine, Dr. Maginso added Plant Medicine (Medical Marijuana) to her niche practice as of 2017. She is licensed in the State of Florida and attended the University of the East (UERM) in Quezon City, Philippines as well as the University of Medicine and Dentistry in Newark, NJ.
She joined DocMJ in 2019 to align with a known group of compassionate physicians that empower their patients to be better versions of themselves. Her favorite hashtag is #powerpassionperformance, using the combination of optimized bioidentical hormones, medical marijuana, plasma therapies, and sexual wellness.
She is an author, speaker and community advocate for Medical Marijuana, Sexual Health, and the empowerment of mature women.