In 1988, researchers studied the effect of synthetic THC in the human body. During their study, they discovered the cannabinoid receptor called CB1.

The study showed that the receptor is found in the central nervous system (CNS). But they were not contented with the research output. Researchers knew that something was missing in their study.

As the scientists continued the research, they discovered the second cannabinoid receptor. The second receptor is CB2, found in the immune system.

Afterward, they found the ligand where these two cannabinoid receptors attached.

And after failing many times, the researchers discovered the “anandamide.”

Anandamide is a natural endocannabinoid produced in the CNS. It stimulates a sense of happiness and well-being. 

At present, researchers discover new enzymes, receptors, and cannabinoid-related molecules every year. But these new discoveries are unclear on how they work and tie together.

Understanding ECS

What comes into your mind when you hear the word “endocannabinoid”? You might think it has a connection with cannabis. Yes! You are right.

Long ago, people have used cannabis for medical and recreational activities. The ECS remained undiscovered until the mid-1990s.

From then on, ECS intrigued many researchers. They also learned that the ECS has lots to offer in medicine.

You may not be in the mood for a science lesson but hold your breath as we tour you about this complex system. 

As we go along, we will learn about the following:

• What is ECS?
• How is ECS connected to cannabis?
• What is the impact of ECS in medicine in the future?

WHAT IS THE ECS?

The ECS is a complex cell-signaling system. It exists and is active in our body even without consuming cannabis.

It has three parts: cannabinoid receptors, endocannabinoids, and enzymes. They help our body system in balance in some aspects.

Despite many studies, there are many mysteries about the ECS yet to be uncovered. 

How does the ECS work?

The ECS is located all over the body with a balancing negative feedback loop.

It activates the release and production of endocannabinoids that target specific receptors. Afterward, enzymes break down the endocannabinoids.

Part 1: The Endocannabinoid Receptors

The two most researched ECS receptors are CB1 and CB2. They have the most impact on the human body.

The third receptor is called GPR55, which has a unique signaling system

Cannabinoids interact with these receptors in different ways:

• Agonists – bind the receptor and activates it
• Antagonists – bind the receptor but block its activation

CB1 Receptors

They are found in the following:

• Neocortex, hippocampus, and cerebellum of our brain
• Basal ganglia in the SNr and segments of the globus pallidus
• Reproductive system, endocrine glands, white blood cells, and spleen

The activation of CB1 receptors hinders the excitability and transmission of neurons.

But, too much activation of CB receptors is harmful. It can change the body’s perception, emotion, balance, and brain function.

CB2 Receptors

The CB2 receptors found in our human body are the following:

• Central Nervous System
• Mast cells
• Microglial
• B and T lymphocytes
• Natural killer cells
• Monocytes
• Macrophages

Part 2: The Endocannabinoids

Endocannabinoids are in tissues, organs, and fluids in our body. They also act as agonists of both CB1 and CB2.

Some research shows that endocannabinoids affect the following:

• Transmitter release 
• Neuronal signaling 
• Actions involving complex cognitive functions and processes.

There are two kinds of cannabinoids:

1. Endocannabinoids- made by the ECS
2. Phytocannabinoids- made by plants

The two main endogenous cannabinoids are:

1. N-anandamide (AEA)
2. 2-arachidonoyglycerol (2-AG)

Anandamide (AEA) is the first endocannabinoid discovered. The primary role of AEA is regulating feeding behavior and neural generation of motivation and pleasure.

2-Arachidonoyglycerol (2-AG) is an endogenous ligand of the cannabinoid receptors. It is best for mediating the effects of the active components of marijuana.

AEA and 2-AG have similar roles, but each has a specific job. They have both arachidonic acid but with different enzymes.

What are Vanilloids?

Vanilloids bind to the TRPV receptors. They also serve as ion channels that respond to noxious stimuli.

Noxious stimuli are something that can damage the tissues.

The two most common vanilloids are:

1. Vanillin- a primary component of the vanilla bean
2. Capsaicin- an ingredient that makes the chili pepper hot

These two vanilloids are opposite but come from the same family.

Why is TRPV1 special?

The TRPV1 receptors are located in the following parts of our human body:

• Nerve fibers
• Smooth muscle cells
• Vascular cells
• Digestive system
• Cardiovascular system
• Respiratory system

TRVP1’s primary role is significant and has a domino effect. Its role is:

1. Transmits signal to the nerve center
2. Activates signaling pathway in the cell
3. It causes a large-scale cellular response that regulates various related functions

TRPV1 reacts fast to high temperatures to acid that causes tissue damage.

An example of this is the intense pain after getting sprayed with pepper spray. The vanilloid binding causes extreme discomfort with the TRPV1 receptor.

Part 3: ECS Enzymes

The enzymes with their functions:

1. Fatty acid amide hydrolase (FAAH)- takes care of AEA
2. Monoacylglycerol Acid lipase (MAGL)- deals with 2-AG
3. Cyclooxygenase-2 (COX-2)- degrades FAAH and MAGL through oxidation

The Effects of ECS on our health

The ECS helps maintain and balance our essential body systems, which includes:

• Central nervous system
• Cardiovascular system
• Gastrointestinal system
• Reproductive system
• Skeletal system
• Immune system
• Metabolic processes
• Temperature regulation
• Memory
• Learning
• Appetite
• Stress response
• Pain sensation
• Mood
• Sleep
• Inflammation
• Pleasure and reward
• Motor control

The ECS has a high impact on our bodies. Endocannabinoids could cause problems whether they’re too high or too low.

There are many health problems connected to the ECS, like:

• Clinical Endocannabinoid Deficiency (CED)
• ECS Hyperactivity

Scientists believe that the ECS holds the key to finding the cure for various illnesses, including:

• Neurodegenerative Diseases
• Epilepsy
• Traumatic Brain Injury
• Obesity
• Sclerosis
• Psychiatric Disorders
• Drug and Alcohol addiction
• Parkinson’s Disease
• Huntington’s Disease
• Spinal Cord Injury
• Stroke
• Hypertension
• Glaucoma
• Osteoporosis 
• Metabolic Syndrome

Cancer

The ECS can treat cancer in two ways.

First, endocannabinoids slow or stop the cancer cells and tumors is increasing.

Second, studies show high CB receptors and ligands in tumor tissue. The CB activation can counteract the formation of tumors.

Brain protection

Cannabinoid receptor activation can help protect brain functions in many ways.

The endocannabinoids can prevent microglial cell activation.

The endocannabinoids can also decrease nitric oxide produced in the cells.

The ECS can help treat Traumatic Brain Injury (TBI).

ECS can also treat learning and memory issues, motor impairment, and seizures.

Pain

If you involve yourself in exercises, there’s a point where it makes you feel good. Your pain during the activity seems to subside. Athletes know this as “runner’s high.”

The ECS turns out to be responsible for it. Exercise boosts the level of endocannabinoids which produces a pain-relieving sensation.

Mental Disorders

The primary role of ECS is to balance things in our bodies. It includes emotional, cognitive, and neuropsychiatric functions.

Too much cannabinoid receptor activation can lead to schizophrenia, anxiety, and depression.

Stress adaptation is one of the ways the ECS affects our mental health. It also helps in regulating emotional memories.

Obesity

The ECS handles our food preferences and controls our metabolism. So, ECS can help treat obesity and metabolic diseases.

What is the relation between Phytocannabinoids and the ECS?

Before ECS was discovered, many used cannabis for recreational and medical purposes.

Phytocannabinoids are found in cannabis plants. And endocannabinoids are in mammal bodies.

But research shows that cannabinoids are also found in: 

• Rhododendron species
• Certain legumes 
• Radula marginata
• Some fungi

Cannabinoids affect the nervous system and regulate our immune system.

The following are the most popular phytocannabinoids:

Delta 9 THC and ECS

Tetrahydrocannabinol (THC) is the most common and popular cannabinoid in cannabis.

Delta 9 THC is the primary active ingredient in marijuana with psychoactive effects.

It is famous for its medicinal use.

There are other types of THC found in cannabis like Delta 8, 10, and 7. These are less potent versions of Delta 9. Though, they still get users high.

THC is a partial agonist that binds with the CB1 and CB2 receptors, but its bond is much tighter with CB1.

CBD (Cannabidiol) and ECS

The CBD is the first cannabinoid to be the main component of Epidiolex. It is a medicine that reduces seizures in rare forms of epilepsy.

Moreover, CBD does not bind to CB1 and CB2 and has no psychoactive properties. It tends to have calming effects and is primarily used for its therapeutic properties. 

CBC (Cannabichromene) and ECS

CBC is a significant cannabinoid that binds to both receptors. But it has no psychoactive properties.

It also regulates the TRPV1 receptors. Most people use this cannabinoid to lessen the pain and swelling.

Summary

Despite many studies about ECS, some aspects of it remain a mystery. 

We know that ECS affects our immune system, cardiovascular system, emotion, hunger, and so on.

It consists of three parts:

• CB1 and CB2 receptors
• AEA and 2-AG endocannabinoids
• Enzymes

The most exciting part is that substances extracted from cannabis plants bind with the ECS. Scientists can use this in further studies on the medical properties of cannabinoids.