In the late 1980s and into the early 1990s researchers running studies on THC discovered part of the human body which they later named the endocannabinoid system, or ECS. Although researchers have been studying the ECS for decades, it is still a relatively new system and there is much that remains unknown about it. However, using genetic and pharmacological methods, researchers have concluded that the ECS is a vital part of human biology and essential to health and over well-being as a powerful regulator of various systems within the body. The studies have shown the endocannabinoid system to control processes in motor learning, appetite, and pain sensation among others.
What the Endocannabinoid System Does
In simple terms, the endocannabinoid system maintains homeostasis within the body. If one or more systems experience some sort of disruption, the ECS will step in and work to correct the imbalance and bring back equilibrium to the affected system. Human bodies are complex and changes can happen at any time. Conditions need to be kept stable in order for cells to maintain optimal performance. The endocannabinoid system is not limited to humans, however. All vertebrate species have their own ECS that is also used for homeostasis.
The Core Components
There are three main components on the endocannabinoid system that can be found in almost every major system of the body and are responsible for homeostasis when called upon after a disruptive element is introduced to the environment.
Endocannabinoids
Endocannabinoids are small molecules that bind to receptors and active them. These molecules are also very similar to the cannabinoid compounds produced by cannabis plants. The two major endocannabinoids are anandamide and 2-AG. These compounds are made up of fat-like molecules within cell membranes and the body is able to produce them on demand. Because the body can synthesize them immediately, these endocannabinoids are made and used exactly when they are needed, rather than stored away for later like other molecules in the body. Let’s discuss these two compounds in further detail:
- Anandamide (AEA): Anandamide was first discovered and named in 1992 and has since been the subject of many scientific studies trying to determine its exact effects on humans. The name for this molecule comes from the Sanskrit word “ananda” which means “bliss” and it’s sometimes referred to as the “bliss molecule” because of its ability to produce a calming or blissful feeling in humans [1]. High levels of anandamide have also been shown to contribute to a successful pregnancy when used during ovulation [2]. Overall the anandamide molecule acts as a binding agent, connecting the body’s CB receptors to communicate signals throughout the body to other receptors in a variety of systems.
- 2-arachidonoylglyerol (2-AG): This molecule was first described in detail in 1994-1995, but had previously been known as a chemical compound in the human body. After it was properly described, scientists became aware of its distinct relationship with cannabinoid receptors. 2-AG is found in high levels within the central nervous system and has been identified in human milk as well.
Receptors
Found on the surface of cells, cannabinoid receptors monitor conditions outside the cell and transmit any information about changes happening in the environment surrounding it. If a big enough change is reported, the ECS will receive the message communicated by the receptors and initiate the proper response to balance the system and maintain homeostasis. Endocannabinoids are able to bind to either of the two main receptors, but the result will depend on where the receptor is located and which endocannabinoid it binds to. There are two major cannabinoid receptors:
- CB1: These are the most plentiful receptors in the brain and central nervous system and are also the receptors that most commonly interact with cannabinoids.
- CB2: These receptors are most abundant in other systems outside the nervous system, especially in the immune system.
Enzymes
Metabolic enzymes are used to destroy endocannabinoids within the ECS systems once they have been used to reestablish homeostasis within the body. This helps ensure no overcorrection will be able to occur after the need for the endocannabinoid has ended. The two biggest enzymes are:
- FAAH: Fatty acid amide hydrolase is the enzyme used specifically to break down the endocannabinoid anandamide.
- MAGL: Monoacylglycerol lipase is the enzyme that is used to break down the endocannabinoid 2-AG.
What it Controls
While research is still ongoing, studies have so far found the endocannabinoid system to be linked to the following processes [3]:
- Appetite: Studies have shown the cannabinoid THC to interact with the CB1 receptor in the ECS to directly increase appetite [4]. A related study also showed that endocannabinoids have the ability to alter the taste perception in taste cells, specifically sweet tastes [5].
- Metabolism: The ECS controls several metabolic functions, including energy storage and the transportation of nutrients. Connecting to the gastrointestinal tract, the skeletal muscles, and the pancreas, it helps regulate insulin sensitivity and may play a role in conditions such as obesity and diabetes [6].
- Pain: The endocannabinoid system regulates the systems around the spinal cord, suppressing neural responses as needed at the dorsal horn. This process is hypothesized to work by controlling the noradrenaline coming directly from the brainstem [7].
- Immune system: Activation of cannabinoid receptors has been shown to have a direct effect on several processes within the immune system, including in the bone marrow cells, white blood cells, and immunity enzymes [8].
- Mood: The receptors on the endocannabinoid system are connected to various forms of depressant neurotransmitters. A recent study found that the CB1 receptor had the ability to mediate short-term depression and long-term depression [9].
- Memory: While THC has been shown to decrease long-term memory [10], research has also shown that mice without the CB1 receptor had enhanced memory and neural growth in the hippocampus [11]. This indicates that the endocannabinoid system plays an important part in memory.
- Sleep: When the central nervous system experiences increased endocannabinoid signaling, sleep-inducing effects can be felt. The endocannabinoids within the ECS have been shown to increase sleepiness, slow-wave sleep, and REM sleep [12].
- Reproductive function: Research has shown that developing embryos produce cannabinoid receptors early in the development process. These receptors are quickly responsive to CS-specific enzymes produced in the uterus. Human studies have shown that the maintained balance of this enzyme in the uterus reduces the likelihood of miscarriage [13].
- Stress: The CB1 receptor in the ECS is responsible for stress reactions. Research has indicated that some of the endocannabinoid enzymes can experience different synthesis after being exposed to repeated stress. This suggests that stress is endocannabinoid receptor dependent [14].
- Anxiety: Like stress, researchers have found that the ECS is directly related to anxiety reactions and exposure. By controlling the endocannabinoid system, studies have shown anxious behavior to be effected and reduced in mice, suggesting again that ECS receptors are important for controlling anxiety [15].
- Nerve function: Within the nervous system, research has found that cannabinoids play an important role in synapses of neurons. This includes regulation of the intestines, digestive, urinary, and reproductive systems [16].
All of the above functions require a state of homeostasis for proper function, therefore the ECS is important to each of them for its ability to maintain equilibrium.
Endocannabinoid Deficiency
Experts are currently researching the possibility of something called clinical endocannabinoid deficiency (CECD). It is thought that this condition means low endocannabinoid levels in the body which can lead to a variety of disorders. A recent study suggested this condition could be why some people develop migraines, fibromyalgia, and irritable bowel syndrome [17]. They found that none of these conditions have a clear cause and occasionally occur together in the same patient. This type of research is still very new, but finding out more about the ECS and possible endocannabinoid disorders will likely become more important as we also learn more about ECS and cannabinoid.
How ECS Interacts with Cannabinoids
Because cannabinoids are so molecularly similar to naturally produced endocannabinoids, the ECS is able to more easily interact with them, which provides humans with the psychoactive and medicinal properties cannabinoids are now known for. For example, the cannabinoid THC is able to attach itself to the CB1 receptor in the brain. The endocannabinoid anandamide is also able to activate the CB1 receptor, however because enzymes will break it down quickly, the effect is not as prolonged as with THC, in which the enzymes are unable to break down as quickly as anandamide. THC is also able to bind to the CB2 receptor, which opens up the possibility of THC having wide ranging effects.
CBD is actually able to affect the levels of endocannabinoids in the brain. Specifically, CBD inhibits the FAAH enzyme which is used to break down the anandamide molecule. As mentioned earlier, anandamide has a naturally occurring blissful effect, however is normally broken down very quickly by enzymes, stifling this effect. As a result of CBD keeping the FAAH enzyme from breaking down anandamide, humans can experience less anxiety after ingesting CBD [18].
Disclaimer
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