Homeostasis is the concept that all biological systems have to be maintained within a narrow range for cells to perform their roles optimally. Vital physiological parameters such as body temperature, blood sugar, etc. have to be kept within a specific field that is unique to each of them. The human endocannabinoid system (ES) plays a critical role in maintaining this balance.
What is the endocannabinoid system?
It consists of three parts:
i. Cannabinoid receptors
iii. Metabolic enzymes
We shall discuss these in more details later but first;
How does it work?
The endocannabinoid system was discovered in 1990, making it one of the most recent anatomical discoveries. Its recent discovery means that there is still much about it that is yet to be understood. There are, however, somethings we know about the role of the endocannabinoid system and how it works. The following section is your endocannabinoid system for dummies; it explains how each of its parts works.
Endocannabinoid receptors are found throughout the body. Their locations all over the body enable them to control the internal environment of the entire body in situ. There are two primary endocannabinoid receptors:
CB1 receptors: These are found in the central nervous system and the brain
CB2 receptors: They are found in the immune system
When you introduce cannabinoids into the system, they can connect to either CB1 or CB2 receptors. The cannabinoids that attach to CB1 receptors affect motor learning, pain, coordination, and metabolism.
The cannabinoids that attach to CB2 receptors, on the other hand, play a more protective role, reducing inflammation, fever, among others.
The word endocannabinoid is short for endogenous cannabinoid. These molecules are cannabinoids manufactured by the body. Typical levels of endocannabinoids in the body are not known since the body produces them as and when needed.
It is endocannabinoids that bind and activate cannabinoid receptors, and they are of two types.
- 2 – arachidonoylglyerol (2-AG)
- Anandamide (AEA)
Anandamide connects with CB1 receptors, while 2-AG connects with CB2 connectors. Both of these endocannabinoids are made up of fatty molecules, and they are typically found on the cell membrane.
As earlier mentioned, the body doesn’t keep endocannabinoids in reserve; it just produces them when needed. So what happens to them when they have been used? Once endocannabinoids have restored the homeostatic balance, metabolic hormones destroy it.
The fact that they are only produced when needed distinguishes endocannabinoids from other molecular signals in the body. Common neurotransmitters and hormones either remain in the body long after they have accomplished their purpose or the body manufactures and keeps them in stock to be used when the need arises.
A different hormone synthesizes each of the two endocannabinoids;
- Fatty acid amide hydrolase (FAAH). This one breaks down Anandamide (AEA)
- Monoacylglycerol acid lipase (MAGL) typically breaks down 2 – arachidonoylglyerol (2-AG)
Fig 1: Endocannabinoid System Diagram
Working in Retrograde
The endocannabinoid system is said to work in retrograde. Working in retrograde means that its signals move opposite other neurotransmitters in the body.
The nervous system is made up of chains of neurons. These neurons are found in every part of the body. They connect in a string to the central nervous system and ultimately to the brain. Between every two neurons, there is a tiny gap known as a synapse. The neuron that comes after the synapse is referred to as a postsynaptic neuron.
Common neurotransmitters move through synapses from the rest of the body towards the brain. Every neuron receives the signal, reacts to it (for example, if the neuron is transmitting a pain signal, it ‘feels’ the pain and passes it on to the next (postsynaptic) neuron — the more intense the pain, the more frequently the neurons fire.
The endocannabinoid signaling moves in the opposite direction, towards the pre-synaptic neuron. Let us use the pain signal as an example. When the neurons send pain signals to the brain, the brain sends endocannabinoids to bind with it. This binding keeps the neurons busy, reducing the frequency with which it sends the pain signals, when the rate at which neurons send pain signals reduces, the intensity of pain as felt by the body decreases.
Functions of the Endocannabinoid System
The endocannabinoid system is made up of the most versatile signaling molecules in the bodies of vertebrates. Seeing that endocannabinoids are found throughout the body, they play many diverse roles. The following are some specific homeostasis actions to which the ES is associated.
- It regulates metabolism
- Appetite and digestion
- It makes chronic pain more bearable
- It reduces inflammation and other adverse responses by the immune system
- It governs a person’s moods
- It controls memory and learning
- Stress reduction
- It keeps the cardiovascular system within the right system function
- It regulates liver function
- It monitors the internal environment of the reproductive system
- It regulates nerves and skin functions
- Regulates sleep patterns
Research is still ongoing to establish whether the ECS has more features.
Interaction of the Endocannabinoid System with CBD and THC
Earlier in this article, we observed that endocannabinoids are simply cannabinoids that the body produces internally for its use. The similarity between endocannabinoids and plant cannabinoids, i.e., THC and CBD, means that THC and CBD connect with Cannabinoid receptors in the EC system the same way endocannabinoids would. CBD, the non-psychoactive plant cannabinoid, can, therefore, be used as a supplement in case there is an endocannabinoid system deficiency.
Some conditions for which CBD is used to manage such as Irritable Bowel Syndrome are said to be caused by a clinical endocannabinoid deficiency.
THC connects with CB1 connectors in the Central Nervous System and CB2 connectors in the rest of the body. On connecting, its psychoactive properties manifest, thus causing the high a person experiences when they use marijuana.
You might wonder why we don’t get high every time our bodies synthesize anandamide, which also connects with the CB1 connectors. THC connection is slightly different from the way endocannabinoids connect.
The other reason why the high occurs is that THC lingers in the system for too long. Ordinarily, when endocannabinoids complete their work, they are synthesized by the enzyme, Fatty acid amide hydrolase (FAAH). FAAH doesn’t break down THC the same way it breaks down anandamide, and it, therefore, its effects remain in the body for long periods.
The relationship between the endocannabinoid system and CBD is a fascinating one. CBD interacts with both CB1 and CB2 receptors. Its ability to connect with both is unlike endocannabinoids, which interact with a specific type of receptor. CBD’s versatility gives it a unique effect on the body by reinforcing the endocannabinoid system in its function.
One of the most notable effects that CBD has in the body is increasing its endocannabinoid tone. It does this by inhibiting the FAAH enzyme preventing it from breaking down anandamide, causing it to linger and build up in the system. One consequence of increased anandamide levels is the reduction of anxiety.
There is information on how CBD connects with the ECS that is still unknown. Some experts believe that CBD connects with a receptor that it is yet unknown, and endocannabinoid system research is ongoing with regards to this proposition.