5 Things You Need To Know About the Endocannabinoid System

WRITTEN BY SHALINI RANA AND DR. SWATHI

If you use CBD or are CBD curious, you may be wondering how it works. How does your body produce an effect after the topical application or ingestion of your product? Well, the effects of CBD are largely dependent on a system in our bodies called the endocannabinoid system (ECS). If you are new to learning about this system and what things affect it, then you are in the right place. Here are five things you need to know about the endocannabinoid system.

#1

What exactly is the endocannabinoid system (ECS)? It’s a collection of receptors, endocannabinoids, and enzymes that regulates different processes in the body. The two receptors found in this system are CB1 and CB2. The CB1 receptor is found primarily in the brain but also occupies areas like the liver, adipose tissue, and the digestive system. The CB2 receptor is mainly found in the immune system and peripheral tissues. These receptors can bind cannabinoids from the cannabis plant like THC and CBD, but there are also molecules produced in our bodies that can bind to these receptors called endocannabinoids [1].

#2

What processes do the endocannabinoid system regulate? The ECS is important because it helps our body maintain homeostasis in various processes like appetite, pain, mood, hunger, and sleep. I’m sure you’ve heard of cannabis being associated with “getting the munchies.” This is because activation of the CB1 receptor can stimulate hunger. In turn, blocking this receptor can help reduce signals of hunger; however, the caveat with doing so includes potential reductions in mood [1].

The ECS also plays a role in memory, which can be seen when looking at the association between cannabis use and short-term memory loss. Research has shown that cannabinoid THC can affect both learning and short term memory by binding to the cannabinoid receptors and activating the ECS. Moreover, the ECS plays a role in many processes in the body [1].

#3

What are the different cannabinoids and endocannabinoids? Anandamide and 2-Arachidonoylglycerol (2-AG) were the first discovered endocannabinoids. They help to regulate many different processes in the body. Anandamide, for example, is typically known as the “bliss molecule” because increased levels of this endocannabinoid can produce euphoria and relaxation. 2-AG, on the other hand, plays important roles in our emotions, thinking, and pain sensation [2]. As for phytocannabinoids (also known plainly as cannabinoids), there are over 100 different cannabinoids, but the most well known include THC and CBD, which are found in the cannabis plant. THC is responsible for producing the psychoactive feeling of being “high.” CBD does not produce the same effect, but both THC and CBD affect pain, mood, and inflammation.

#4

What external factors can affect the endocannabinoid system? Many external factors can affect the ECS, including:

1. Diet: Eating a diet high in dietary fatty acids and saturated fats could overstimulate the CB1 Receptor and therefore cause weight changes [3].
2. Exercise: More physical activity can increase the sensitivity of CB1 receptors in the body and increase anandamide levels–aka the underlying cause of the “runner’s high” [4].
3. Stress: The ECS has been found to be an essential and complex regulator of the stress response. Chronic stress can downregulate the number of CB1 receptors available to bind to cannabinoids, as well as reduce anandamide levels–therefore increased stress = decreased bliss[5].
4. Medications: Antidepressants and antipsychotics may have an effect on the expression of CB1 receptors and may decrease the levels of endocannabinoids in the body [6].
5. CBD Use: CBD is a cannabinoid that modulates the CB1 and CB2 receptors and activates the ECS to produce feelings of relaxation, a potential reduction in pain, and effects on learning and memory.

#5

The endocannabinoid system is a potential target for many medications and therapies. Due to its role in processes like pain-regulation and hunger, the ECS has been the target of research for several disorders. One study looked at the degradation of the endocannabinoid anandamide by an enzyme called fatty acid amide hydrolase (FAAH), and it found that by removing FAAH , a 10-fold elevation was seen in the levels of anandamide in certain areas of the brain [2]. This has potential application in mood disorders. Another study looked at the potential for anandamide to reinforce behavior for drug abuse in animals, so further research on the ECS may help us discover solutions to drug addiction in the future [2]. Finally, as mentioned before, the ECS can regulate hunger. With the increasing prevalence of obesity and metabolic disorders, the ECS is being increasingly looked at as a potential target for an anti-obesity drug [7].

Conclusion

In conclusion, the endocannabinoid system is a complex network that regulates many important processes in the body such as appetite, memory, and hunger. Most people know it as the system that allows cannabis to take effect, but it is truly so much more than that. Understanding this system and its role in our health is crucial for future development of therapies that can potentially treat a wide range of disorders.

References

1. Grinspoon P. The endocannabinoid system: Essential and mysterious. Harvard Health Publishing. August 11, 2021. Accessed Jan 2023.
2. Scherma M, Masia P, Satta V, et al. Brain activity of anandamide: a rewarding bliss? Acta Pharmacol. Sin. 2019 Mar;40(3):309-323.
3. Clark TM, Jones JM, Hall AG, et al. Theoretical Explanation for Reduced Body Mass Index and Obesity Rates in Cannabis Users. Cannabis Cannabinoid Res. 2018;3.1:259-271.
4. Loprinzi PD, Zou L, Li H. The Endocannabinoid System as a Potential Mechanism through which Exercise Influences Episodic Memory Function. Brain Sci. 2019 May;9(5):112.
5. Morena M, Patel S, Bains JS, et al. Neurological Interactions Between Stress and the Endocannabinoid System. Neuropsychopharmacol. Rep. 2016 Jan;41(1):80-102.
6. Weston-Green K, Huang X, han M, et al. The effects of antipsychotics on the density of cannabinoid receptors in the dorsal vagal complex of rats: implications for olanzapine-induced weight gain. IJNP. 2008 Sep;11(6):827-835.
7. Vasquez NA, Nielsen DE. The Endocannabinoid System and Eating Behaviours: a Review of the Current State of the Evidence. Curr. Nutr. Rep. 2022 Aug;11;665-674.

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This article was edited by Dr. Swathi and was written by Element Apothec Scientific Communications Intern, Shalini Rana. She is a Doctor of Pharmacy (PharmD) candidate at Rutgers University Ernest Mario School of Pharmacy in Piscataway, New Jersey.