Outline
- What is the endocannabinoid system?
- Cannabinoid receptors
- Endo-cannabinoids
- Enzymes
- ECS system out of balance
- Cancer
What is the endocannabinoid system?
The endogenous cannabinoid system (ECS), plays an important role in regulating many biological processes of the human body, including: pain sensations, movements, digestion, metabolism, immune system, memory, reproduction, cell cycle, bone growth, etc. ECS activity was summed up in 1998 by Professor Di Marzo as “Relax, Eat, Sleep, Forget and Protect.” [1]
There are three main components that make up the ECS:
- Receptors
- Cannabinoids
- Enzymes
Read more:
Cannabinoids - THC, CBD and more
What are terpenes? Why does cannabis smell?
Cannabinoid receptors
The cannabinoid receptors are the first piece of the complex endocannabinoid system. First, we need to understand what a receptor is. Receptors are protein molecules located on the surface or within a cell, that receive biological signals and thereby induce the appropriate cellular response to that signal.
Imagine you're a random person in a company, with those biosignals like letters, emails, or phone calls from your boss. So, what is a receptor? They are mailboxes, computers or phones. The receptor is responsible for receiving, decoding, and transmitting information, telling you what you need to do. Without them, you won't be able to get a signal about the work your boss gives you. Similarly, the body cannot produce a response to cannabinoids without the right receptor, or will respond incorrectly if the receptor is malfunctioned.
In the ECS system, there are two main types of receptors: cannabinoid type 1 receptors (CB1) and cannabinoid type 2 receptors (CB2). The signaling molecules acting on them are cannabinoids. These cannabinoids can be endogenous cannabinoids, produced by the body, or plant-derived cannabinoids, also known as phyto-cannabinoids, in which “phyto-” is a prefix that means “related to plants”.
Cannabinoid receptors 1 (CB1)
CB1 is most abundantly present in the brain and is best known for its role in regulating and influencing the nervous system. Activating this receptor is the cause of the cannabis high. When you consume cannabis, time may feel slow. You may laugh endlessly, or become extremely creative and enjoy musical or artistic experiences, or simply may just want to sit back and relax.
Simply put, this phenomenon is a change in one's perception of the world around them, as well as their “inner world”. When THC acts on CB1, it produces psychoactive effects that alter one’s cognition, sensation, and short-term memory. However, this state of change is not permanent, meaning things will return to normal once the effects of the cannabis wear off.
In addition to the nervous system, CB1 is also widely present in other systems as well. It regulates so many other processes beyond just cognitive/mood changes. For example, in the spinal cord and peripheral nerves, CB1 regulates pain, itchiness, and muscle. CB1 receptors in the digestive system play a role in the passage of food through the intestinal tract by regulating intestinal contractility, and also regulates the secretions of digestive enzymes.
Cannabinoid receptors 2 (CB2)
Unlike type 1 cannabinoid receptors, activating CB2 receptors does not lead to psychoactive effects. These receptors play key roles in immune regulation, including pain and inflammation, and are mostly abundant in the immune system.
Cannabinoid receptors 3 (CB3)
Do you know that every time you eat spicy food, you also trigger a response related to the endogenous cannabinoid system?
TRPV1 (transient receptor potential channel, vanilloid subfamily member 1), is a receptor that can also be considered part of the ECS system. This is a receptor that makes you feel the spiciness of chili peppers, caused by the protein capsaicin which presents in the chili. When consuming cannabis, cannabinoids acting on this receptor can reduce pain and inflammation, and for some magical reason, it doesn’t lead to the spicy taste like when eating chilies.
Read more: Does CBD have side effects?
Endo-cannabinoids
These cannabinoids are not from cannabis, but are made by you!
Our bodies are capable of producing compounds that act on our own cannabinoid receptors, called endogenous cannabinoids, or endocannabinoids. “Endo” means “inside”, and endocannabinoids means cannabinoids produced inside/by the body. In contrast, plant-derived cannabinoids are known as phyto-cannabinoids, in which “phyto-” means “related to plants”.
There are two main endogenous cannabinoids, arachidonylethanolamide (AEA), or can be called “anandamide”, and the second one is 2-arachidonylglycerol (2-AG). The name 'anandamide' is taken from the Sanskrit word “ananda”, which means "joy, bliss, delight". When necessary, our body automatically produces endogenous cannabinoids in response to the environment and directs the body's activities. These endogenous cannabinoids travel to the cell where the cannabinoid receptor is present and from there, they regulate the cell’s functions. So, even if you don't smoke cannabis, anandamide and 2-AG will activate your ECS on their own.
In addition to cannabis, a number of other plants also produce cannabinoids, but only very little, in trace amounts. Today, there are more than 113 different cannabinoids found in cannabis and hemp. Tetrahydrocannabinol (THC), Cannabidiol (CBD), Cannabinol (CBN), Cannabigerol (CBG)… are the main phyto-cannabinoids.
Enzymes
Enzymes are biological molecules, usually a protein, that cuts, breaks down, or modifies another protein molecule.
In this case, enzymes are responsible for destroying endogenous cannabinoids (AEA and 2-AG). Without these enzymes, the cannabinoids would continuously act on the cannabinoid receptors. causing excessive responses. Our body depends on this breakdown process, along with synthesizing new cannabinoids when needed to maintain a balance of the endogenous cannabinoid level in the body, depending on how much of them our body needs.
Read more: How does CBD work in skincare?
Balance/ homeostasis is an extremely important concept of the ECS system and when it comes to cannabinoid therapy. Under or over activation of the cannabinoid system can cause many health problems. Similarly, dosage is extremely important when it comes to using medical cannabis. Too little of a dose is not enough to relieve symptoms, while too much of a dose can potentially produce many undesired side effects, or even cause the exact opposite effects of a sufficient dose of cannabinoid, thus worsening the condition.
ECS system out of balance
The ideal, most healthy state of our body is when the ECS system is functioning at a sufficient level, which means that the amount of endogenous cannabinoids synthesized as well as broken down is balanced.
As mentioned, the ECS system will either enhance or inhibit the release and actions of cannabinoids accordingly, depending on the current body needs. The system is often overactive when there is increased inflammation, decreased insulin sensitivity[3], or in the case of liver diseases.[4]
Read more: Cannabinoid Delivery Systems
On the other hand, what if endocannabinoid levels are too low? Meaning not enough endocannabinoids are produced? There have been many studies and theories suggesting that there are various illnesses that fall under the category of “Clinical Endogenous Cannabinoid Deficiency,” or CECD, where the body fails to maintain a certain level of endocannabinoids for various reasons. These conditions include migraines, fibromyalgia, and irritable bowel syndrome (IBS). All three of these conditions can be effectively relieved when taking in phytocannabinoids from the cannabis plant.[5]
Cancer
There are also many forms of cancer associated with CB1 and/or CB2 receptor overexpression.[6] This is thought to be a way for the body to try to fight off the disease on its own. Interestingly, phyto-cannabinoids have also been shown to destroy cancer cells at high doses without harming healthy cells in the body.
Cancer develops when mutations occur, causing problems with cell division, so that the cells will divide rapidly and uncontrollably. Or maybe, they somehow become immortal, not dying on their own when ordered, or can be killed by our own immune system. As such, they multiply and grow, infiltrate surrounding tissues, stimulate blood vessel formation of their own, and even metastasize (spread to other distant regions of the body). Endogenous and plant cannabinoids, such as THC and CBD, have the ability to reverse and prevent many of the above effects, according to some invitro and invivo studies.
In addition, when done properly, medical cannabis therapy can also have a tremendous effect on reducing the symptoms of cancer, or side effects of cancer treatments, such as pain, nausea, insomnia, depression and anxiety.
However, until now, research on cannabinoids and cancer is very limited, largely due to the illegal status of the cannabis plant in many parts of the world. Most studies are only limited to animal experiments or in cell culture. Despite the positive results, we still cannot come to a definitive conclusion as to whether cannabinoids can kill cancer or not, and if it can, then at what dosage and form.
References
[1] Di Marzo et al., “Endocannabinoids: Endogenous Cannabinoid Receptor Ligands with Neuromodulatory Action.”
[2] Bisogno et al., “Molecular Targets for Cannabidiol and Its Synthetic Analogues: Effect on Vanilloid VR1 Receptors and on the Cellular Uptake and Enzymatic Hydrolysis of Anandamide.”
[3] Jourdan, Godlewski, and Kunos, “Endocannabinoid Regulation of β-Cell Functions: Implications for Glycaemic Control and Diabetes.”
[4] Bazwinsky-Wutschke, Zipprich, and Dehghani, “Endocannabinoid System in Hepatic Glucose Metabolism, Fatty Liver Disease, and Cirrhosis.”
[5] Russo, “Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes.”
[6] Pyszniak, Tabarkiewicz, and Łuszczki, “Endocannabinoid System as a Regulator of Tumor Cell Malignancy – Biological Pathways and Clinical Significance.”