What is the endocannabinoid system? Simply put, the endocannabinoid system (ECS) is a complex system of receptors, ligands, and enzymes that work together in regulating important functions in the human body.
The exact mechanisms the ECS uses to regulate fundamental processes, in both central nervous and peripheral systems, are still under investigation.
However, even with a limited amount of research, the endocannabinoid system has become a synonym for “internal balance”, as it is believed that it plays a vital role in maintaining the body’s homeostasis.
Several decades of research resulted in the recent discovery of the way cannabis works in the brain, which is through this unique communication system that plays a role in the way a person feels, moves, and reacts.
But before we get deeper into the role of the endocannabinoid system, let’s take a look at the term “endocannabinoid.”
The first part of the term “endocannabinoid” is “endo”, which is short for “endogenous” that refers to something produced naturally in the body.
Cannabinoids derived from the cannabis plant—such as CBD and THC—are also known as phytocannabinoids, as they come from a plant. Phytocannabinoids are exogenous, which means they originate outside the human body.
What Comprises the Endocannabinoid System?
The endocannabinoid system is made up of numerous parts, including:
The endocannabinoid receptors are located on the surface of cells, organs, tissues, and glands, and provide different reactions when stimulated. The endocannabinoid receptors interact with endocannabinoids and phytocannabinoids, and receive messages that produce certain effects in the body. The most studied receptors are CB1 and CB2. “Cannabinoids used in cancer are best-known for their palliative effects, including reducing nausea and vomiting, alleviating cancer pain, and stimulating appetite” 
The CB1 Receptors
According to anatomical studies, the CB1 receptor is mainly present in the central nervous system and the brain. 
The CB2 Receptors
According to anatomical studies, CB2 receptors are mainly found in peripheral, organ and immune cells. 
Another vital element of the ECS is the endocannabinoids. As explained—endocannabinoids are naturally produced in the body.
“Endocannabinoids (eCBs) are lipid mediators, isolated from brain and peripheral tissues that include amides, esters, and ethers of long-chain polyunsaturated fatty acids; they mimic the action of Δ9-tetrahydrocannabinol (THC) in different biological processes.” 
The first endocannabinoid to be discovered was anandamide (AEA) in 1992—also known as the bliss molecule—that is a high-affinity, partial agonist (or a chemical that binds to a receptor and activates it to produce a response) of the CB1 receptor. Another endocannabinoid involved with the endocannabinoid system is 2-arachidonoylglycerol (2-AG). 
Another major part of the endocannabinoid system are the metabolic enzymes. These enzymes are involved with cannabinoid signaling and in the process of degrading endocannabinoids. Metabolic enzymes include FAAH (fatty acid amide hydrolase)—an enzyme that is “primarily found in postsynaptic terminals and is responsible for degrading AEA.” 
The Relationship Between Cannabis and The Endocannabinoid System
After decades of research, scientists have finally made important discoveries regarding the relationship between cannabis and the endocannabinoid system.
The two most well-researched compounds of cannabis are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is known for its effect to make a person feel “stoned,” while CBD is the non-psychotropic cannabinoid that is widely used for its health benefits.
The exact mechanism of action of THC in the brain is still not clear, but it is believed that THC is a CB1 receptor agonist, meaning that it activates these receptors in the brain. CB1 receptors are associated with states of intoxication. A study conducted in people who had their CB1 receptors blocked by a different drug showed no reaction to the THC in the cannabis. 
The mechanisms of action (MOA) of CBD in the endocannabinoid system is completely different compared to THC’s. CBD doesn’t bind directly to CB1 and CB2 receptors. It is, in fact, an antagonist of these receptors. Instead, CBD inhibits FAAH that is responsible for breaking down anandamide, which makes anandamide available longer in the body.
As mentioned previously, anandamide is known as the bliss molecule and affects sleep patterns, the immune system, pain, anxiety and more. Although further research is needed, it is clear that the endocannabinoid system and CBD share a very important connection.
Potential Health Effects of The Endocannabinoid System
A 2015 review that looked into the safety, toxicology, potency, and therapeutic potential of cannabis, concluded that while it appears safe for use in preliminary studies, a lot of research is still necessary before it can be declared 100 percent safe for use. 
Another study also mentions that “[t]he endocannabinoid system has been recently recognized as an important modulatory system in the function of the brain, endocrine, and immune tissues. It appears to play a very important regulatory role in the secretion of hormones related to reproductive functions and response to stress.” 
The CB1 and CB2 receptors have the following physiologic and pathophysiological roles in the body: 
- Chronic stress. The endocannabinoid system is the central mediator of the stress response in the human body. The endocannabinoid system regulates the release of norepinephrine—a chemical released from the sympathetic nervous system in response to stress and cortisol. The ECS helps regulate metabolism and reduce inflammation.
- Pain. Many studies show the effect of the endocannabinoid system on pain, which is an important therapeutic target for the endocannabinoids.
- Nervous system. The endocannabinoid system plays a significant role in the normal functioning of the brain, peripheral nervous system, and the spinal cord.
- Cancer. The endocannabinoids have an anti-inflammatory, anti-invasive, antimetastatic, and antiproliferative effect in most cancer, as tested on animals.
The endocannabinoid system also: 
- Regulates Appetite. Since ancient times, people have known that the use of cannabis in various forms increases appetite. As a result, the person might experience significant weight gain.
- Regulates Weight in Cancer Patients. A couple of studies have reported that THC in cannabis stimulates appetite and weight gain in patients with cancer. However, these beneficial effects have been documented more extensively in AIDS patients.
- Helps with Movement Disorders – Parkinson’s, Tourette’s, Huntington’s Disease. There are multiple lines of evidence showing that the endocannabinoid system is involved in the central regulation of motor functions and movement disorders.
- Epilepsy. Although further research is needed, the first CBD medicine in the U.S. has been approved for the use of children with severe forms of epilepsy.
- Mental health Disorders – anxiety, depression, schizophrenia. The combination of the psychoactive and psychotropic effects of cannabinoids and the fact that cannabinoid receptors are distributed across various emotional circuits in the brain indicates to a possible involvement of the endocannabinoid system in various mental health disorders as well as mood disorders.
According to studies, the endocannabinoid system is important in regulating brain and endocrine functions and immune responses in our bodies. Cannabinoids such as CBD and THC, appear to hold promise as effective remedies in treating a range of ailments, but a lot more research on human subjects is needed.
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303140/ [Under: Physiological and Pathological Roles of the CB1R; Under: Endocannabinoid system: metabolism and targets of endocannabinoids]
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5877694/ [Under: Endocannabinoid System; Under: Figure1]
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2241751/ [Under: The Endocannabinoid System as Therapeutic Target in Pathophysiological Conditions]