The EndoCannabinoid System By Jillian Thayer

September 09 2020 0 Comment(s)

In a new cultural shift, many people have become more familiar with cannabis terminology such as cannabinoid, endocannabinoid, and terpene. This has been helped by the recent federal legalization of hemp and its derivatives. This “green rush” has been spurred by the CBD industry. This change in rhetoric for cannabis is owed mainly to this once unheard of cannabinoid and now it is helping to revitalize the humble cannabis plant. As more people become increasingly aware of the cannabinoid CBD along with full-spectrum extracts, this elucidates the importance of understanding how it is able to work within our bodies.

The endocannabinoid system is an internal balancing system that resides within all mammals. This once unknown physiological system has begun to be enthusiastically researched because of its profound role within the body. Consuming cannabis products (with high THC or high CBD) directly affects this system, although it’s important to note that cannabis-derived compounds are just one example of compounds that interact with this system.

Defining the endocannabinoid system

The endocannabinoid system (ECS) is an innate system that resides inside all mammals which helps regulate physiological and cognitive processes in order to maintain homeostasis, or in other words, to remain in balance. Our bodies are constantly adapting to many minute changes in our environment to function optimally. The endocannabinoid system helps regulate and modulate many bodily functions, such as sleeping, eating, thinking, remembering, forgetting, moving, and our pain response; additionally it plays a role in immune system functioning. It supports all physiological functions within many different systems, including the neurological, endocrine, digestive, and immune systems.

It reacts and adapts to many environmental factors that could be external or internal stimuli like stress, anxiety, and pain. It is a very intuitive system that is constantly learning and adapting from positive and negative events that occur in our lives in order to maintain optimal health. These positive and negative events could include exercise and social connection as well as feeling stressed or anxious. There are many components that make up this system such as endogenous cannabinoids, receptors, and enzymes. The following breakdown in the terminology exhibits a minimal deconstruction of this system. It is highly suggested that one does a deep dive into this newly recognized system in order to educate themselves further.

Endocannabinoids

The two most prolific and well-researched naturally occurring endogenous compounds are termed anandamide (AEA or N-arachidonoyl-ethanolamine), also known as the “bliss” molecule, and 2-AG (2-arachidonoylglycerol). They are specifically derived from arachidonic acid. These compounds operate on the cellular level and work in a retrograde fashion. This means they are produced on the post-synaptic neurons and bind to specific receptors (most notably the cannabinoid variety) on the pre-synaptic neurons, therefore they are able to modulate other neurotransmitters, such as GABA (gamma-Aminobutyric acid), a crucial inhibitory neurotransmitter. These modulations create the effect that the body requires.

Our bodies make these compounds on-demand, where they are needed, as a way of responding to the environment. They can help with slowing down an overstimulated system or ease pain symptoms. It’s significant to note that researchers have found that endocannabinoids do not exclusively bind to their cannabinoid receptors; they can also bind to other receptors such as TRPV1. There is potential for uncovering more interactions between other receptors with more research. These compounds are considered “promiscuous” because they will bind with other receptors, illustrating the complexity of the system.

Asset 3

Receptors

The two main cannabinoid receptors are called “Cannabinoid Type 1” and “Cannabinoid type 2” receptors (CB1 & CB2). Both can be found in the same location within the body such as the neurological system but at varying concentrations. For example, within the central nervous system (CNS) and peripheral nervous system (PNS), the CB1 receptor is more abundantly concentrated than the CB2 receptor. Furthermore these receptors “are differentiated by their physiological actions and locations within the body,” thereby modulating certain functions and offering different pathways of relief (Fine, P. & Rosenfeld, M.. 2013). It is important to note that much of the research on the endocannabinoid system has focused on the Cannabinoid Type 1 receptor, so there is still more to uncover about the second type in order to elucidate the full scope of its role in the body.

The CB1 is found primarily in the brain, specifically in regions like the hippocampus and cerebellum, but is also present throughout the body. CB1 receptors are not found in the brain stem, which is why cannabis cannot suppress the vital respiratory functions the way other substances such as opioids can. This receptor is involved with many physiological functions like pain, appetite, and cognition. Activation of the CB1 receptor is what elicits a psychoactive response in humans. THC readily binds to and activates the CB1 receptor, whereas CBD does not. This is why CBD products do not get consumers “high.”

The CB2 receptor is found in parts of the brain and peripheral tissues like the cardiovascular system, liver, fat tissue, and bone. It is especially present in the immune system. It plays a significant role in influencing immune function by regulating immune cell migration as well as cytokine production, which are the chemical messengers of the immune system that regulate the immune response. This receptor plays a role in pain perception as well, which offers analgesic effects. As more time passes and regulatory hurdles are eased, we will see more attention placed on CB2 in addition to uncovering more about these unique receptors.

Asset 2

Enzymes

There are enzymes needed to synthesize and degrade endocannabinoids. Endocannabinoids are tightly controlled by these enzymes for a reason. Our ECS is highly sensitive because it is designed to maintain balance. There are more degradative enzymes compared to ones that create endocannabinoids. This is important because endocannabinoids don’t need to stay in the system for prolonged periods of time since the receptors are highly sensitive and don’t like to be overstimulated. Studies show that our endocannabinoid system will downregulate itself by closing off the receptor from receiving any further stimuli or activity.

The Relevance of This System

It is important to understand this system as it can potentially help us to understand how to maintain balance and how to remain in optimal health. Using cannabis products is just one tool for this goal. It’s not solely about using classical cannabinoids in order to have an effect on our endocannabinoid system, but rather it is one piece of the puzzle. Cannabis products contain phytochemicals other than cannabinoids, like terpenes and flavonoids, which can help a deficient or hyperactive ECS. It is well known that this plant contains constituents that bind to or modulate cannabinoid receptors, and also to regulate or modulate enzymes which control endocannabinoid levels. There are well over 120 different cannabinoids alone. With more time and clinical research, more mechanisms of action, and how we can find other ways of utilizing this plant will be discovered.

There are other plants that can exert effects on the ECS due to cannabimimetic properties. This means that some plants have similar pharmacological effects to that of cannabis and can interact with cannabinoid receptors, non-cannabinoid receptors, enzymes, and more. Due to endocannabinoids being able to interact with many non-cannabinoid receptors and enzymes, cannabimimetic compounds can be applied to our endocannabinoid system. For example, beta-caryophyllene, a sesquiterpene found in cannabis and other aromatic plants is a great example of a terpene functioning as a cannabinoid since it binds to CB2 receptors. Another example is echinacea, which contains alkamides that can bind to CB2 receptors aiding the immune system’s function. As mentioned before, exercising and maintaining strong, positive relationships are just some ways we can help boost this system’s healthy functioning.

It is an exciting time to be able to research a once unheard of physiological system. There is so much potential to unlock more information about the ECS and also to discover more cannabimimetic plants besides cannabis.

References

Bosch-Bouju, C., & Layé, S. (2016). Dietary Omega-6/Omega-3 and Endocannabinoids: Implications for Brain Health and Diseases. In Cannabinoids in Health and Disease. doi: 10.5772/62498

Chianese, R., & Meccariello, R. (2016). The Endocannabinoid System in Human Physiology. In Cannabinoids in Health and Disease. DOI: 10.5772/63818.

ElSohly, M., & Gul, W. (2014). Constituents of Cannabis Sativa. In Handbook of Cannabis (pp. 3–22). Oxford University Press. doi: 10.1093/acprof:oso/9780199662685.003.0001

De Petrocellis, L., Grazia-Cascio, M., Di Marzo, V. (2009). The endocannabinoid system: a general view and latest additions. British Journal of Pharmacology, 141(5), 765-774. (Original work published 2004). https://doi.org/10.1038/sj.bjp.0705666

Fine, P. G., & Rosenfeld, M. J. (2013). The Endocannabinoid System, Cannabinoids, and Pain. Rambam Maimonides Medical Journal, 4(4). doi:10.5041/rmmj.10129

Gertsch, J., Pertwee, R. G., & Di Marzo, V. (2010). Phytocannabinoids beyond the Cannabis plant - do they exist?. British journal of pharmacology, 160(3), 523–529. https://doi.org/10.1111/j.1476-5381.2010.00745.x

Kreitzer, F. R., & Stella, N. (2009). The therapeutic potential of novel cannabinoid receptors. Pharmacology & Therapeutics, 122(2), 83-96. doi:10.1016/j.pharmthera.2009.01.005

McPartland, J. M., Guy, G. W., & Di Marzo, V. (2014). Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system. PloS one, 9(3), e89566. https://doi.org/10.1371/journal.pone.0089566

National Academies of Sciences, Engineering, and Medicine. (2017). Cannabis. In The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research (pp. 43–60). Washington DC: The National Academies Press.

Russo E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British journal of pharmacology, 163(7), 1344–1364. https://doi.org/10.1111/j.1476-5381.2011.01238.x

Zou, S., & Kumar, U. (2018). Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International journal of molecular sciences, 19(3), 833. https://doi.org/10.3390/ijms19030833

Leave your thoughts