Your Body’s Natural High…..

The endocannabinoid system (ECS) is mainly found in the central nervous system (CNS) and plays important roles to modulate plasticity and homeostasis in the brain. When we talk ECS, the major receptors for binding are CB1 and CB2 receptors and the two main endocannabinoids are 2-AG  and anandimide   [1]

The CB1 receptor is known to be the most abundant GPCRs in the CNS and does the function of inhibiting the release of both excitatory and inhibitory neurotransmitters. The CB1 receptor also binds the many ligands, including the notable THC, AEA, and 2-AG. THC is an active ingredient in marijuana and can elicit feelings of calm, just like endocannabinoids. However, endocannabinoids are naturally produced by the body.

While CB1 receptors are abundant in areas like the hippocampus and neocortex, CB2 receptors are found in areas such as cells and tissues of the immune system. CB2 receptors are also localized to the microglia, which relates to neuroinflammation in the CNS. Neuroinflammation also relates to diseases such as Alzheimer’s disease (AD), which is a huge area of research today. [2]

Now endocannabinoids. These are natural chemicals that are produced by the body. They interact with the cannabinoid receptors in the CNS, and affect process relating mood, memory, appetite, and pain sensation. These molecules are similar to the compounds found in the cannabis plant, which is they are called “endocannabinoids” meaning cannabinoids produced inside our bodies.

Societal stereotypes have taught us to associate cannabis with words like addiction, failure, druggie, crazy, and many other negative words. It is agreeable that the feelings of calmness induced by cannabis may lead to high risks of addiction, but did you know that cannabis may also hold some potential in increasing the quality of health when used appropriately? Currently, only the University of Mississippi is allowed to conduct research with cannabis. This confirms the existing research gaps in this area.

Relating this to AD, preclinical studies in animal studies have shown that modulating the endocannabinoid system can have neuroprotective effects, reducing inflammation and oxidative stress which are implicated in AD. Researchers also believe that the endocannabinoid system may serve as a  therapeutic target to provide pharmacological benefits for AD. The neuroprotective effects of endocannabinoids may be due to interference with several cellular and molecular mechanisms, including apoptosis and inflammation. The progression of AD is related to the changes in the endocannabinoid system. Both cannabinoid receptor agonists and endocannabinoids, such as AEA, can reduce the neurotoxicity caused by Aβ-peptide in a mitogen-activated protein kinase (MAPK) pathway. [3]

Figure 1. Diagram showing the binding action for the two main endocannabinoids in the body, 2-AG and AEA. [4]

Figure 2. Diagram explaining the binding action for CB1 and CB2 receptors. [5]

Figure 3. Artstract by student depicting how stereotypes and uncertainties around cannabis hold back research on how cannabis might improve human health.

References.

[1] Zou, S., & Kumar, U. (2018, March 13). Cannabinoid receptors and the endocannabinoid system: Signaling and function in the central nervous system. International journal of molecular sciences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/#:~:text=As%20the%20two%20major%20endocannabinoids,D%20(NAPE%2DPLD).

[2] Kendall, D. A., & Yudowski, G. A. (2017, January 4). Cannabinoid receptors in the central nervous system: Their signaling and roles in disease. Frontiers in cellular neuroscience. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209363/