A Complete Guide To The Endocannabinoid System

11th October 2019

A Complete Guide To The Endocannabinoid System

Science class taught us about many different systems; a respiratory system that removes carbon dioxide, a urinary system that removes waste, and a distracted system where your eyes glaze over and ruin your chances of getting an ‘A’.

Regardless of your concentration levels in school, one system you would be forgiven for not knowing about the endocannabinoid system. The reason for this is: it was never in your school books as scientists only discovered it in the early 90s.

The Endocannabinoid System – What Is It?

The endocannabinoid system (ECS) is a molecular signalling system that is widely distributed throughout the bodies of humans and other vertebrate species. It is responsible for regulating all biological systems in a perfect balance known as homeostasis.

Endocannabinoid System

The ECS is comprised of endogenous cannabinoids, endocannabinoid receptors and enzymes. Together they are responsible for a whole host of functions such as:

  • Mood
  • Memory
  • Rest
  • Appetite
  • Sleep
  • Healing

Scientists are learning more and more every day regarding the intricacies at play in this elaborate system but thankfully we already have a good idea about how it works.

How Does The ECS Work?

Our body releases chemical messages (endocannabinoids) which attach to specific receptors located in cells throughout our body. This then produces a response or action depending on the stimuli involved.

For example, after exercise, your body releases an endocannabinoid known as anandamide which connects with receptors in the brain resulting in the euphoric feeling known as ‘runner's high’. In fact, it was once believed this was as a result of the endorphin hormone but recent studies suggest anandamide is the main instigator.

The endocannabinoid system is constantly at work in your body releasing endocannabinoids to make you feel hungry, or tired, or happy, or whatever feeling is required to move you or your body to act in order to achieve homeostasis (well being).


Our bodies naturally create endocannabinoids such as anandamide and 2AG which interact with receptors (namely CB1, CB2) located throughout the body. They either bind with them to perform a function or block them from performing said function.

Endocannabinoids can regulate the release of other neurotransmitters and hormones including glutamate, GABA, dopamine, serotonin, and acetylcholine. All of which have different effects on the body.

Endocannabinoid receptors

Every cell in your body has a receptor which is like a lock that only certain keys such as endocannabinoids or neurotransmitters can connect with and activate.

For example, when your adrenaline is pumping this is because it attached to the adrenergic receptor. Or when the feel-good hormone endorphin kicks in, it is because it attached to the opioid receptors in the brain.

In the endocannabinoid system, receptors such as CB1 and CB2 receive the chemical message and initiate the appropriate response. This might make us feel sleepy or hungry, or something may happen internally like a reduction in inflammation.

The endocannabinoid system is like an orchestra conductor that tells each part of the body what it needs to do in order to achieve what is necessary for survival.

Endocannabinoid Receptors

Metabolic Enzymes

The life of an endocannabinoid is short-lived because enzymes (fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) break the compound down very quickly thereby reducing its effect on the body.

Homeostasis and the ECS

The intelligence of the endocannabinoid system is too complicated for scientists to fully understand yet but we know from nearly 30 years of research that it is instrumental in our wellbeing or as a scientists like to call it ‘homeostasis’.

Endocannabinoids are instantly created in the body in response to threats such as high stress levels or low blood sugars. The aim is to achieve a balance between extremes. This is often referred to as the ‘goldilocks effect’ where too much or too little of something may not work, with a fine balance being the ultimate goal.

How Was the ECS discovered?

In 1988 the compound THC from the cannabis plant was shown to bind with neurotransmitter receptors in the brain of a rat. This led eminent Israeli scientist, and Nobel prize nominee, Dr Raphael Mechoulam to hypothesise that humans must produce their own endogenous cannabinoids to bind to these receptors which exist independently of cannabis consumption.

After nearly 2 years of extensive research, they finally found a tiny molecule that is produced in the human brain and named it anandamide meaning “pure bliss”.

Following this discovery, Dr Mechoulam identified other endocannabinoids including 2AG. Soon after, in 1995, more receptors were located throughout the human body; most notably in the immune system. These were named CB2 receptors. This started the ball rolling and what they learned next was astonishing.

Functions Of The ECS

The endocannabinoid system is incredibly complex and we are constantly learning new functions and roles that it carries out. There are, however, some day-to-day operations that we know the ECS is instrumental in, most notably:

  • Cerebrum functioning
  • Immune system regulation
  • Digestive system regulation
  • Other physiological functions

Cerebrum functioning

The central nervous system which includes the brain and the spinal cord are covered in CB1 receptors. Endocannabinoids have a binding affinity at these receptor sites facilitating the efficiency of communication within and between brain regions resulting in numerous functions such as sleep, pain modulation, memory, mood, and much more.

Immune system regulation

The immune system is covered primarily in CB2 receptors which endocannabinoids interact with to trigger a complex regulation and modulation of immune pathways which play a key role in immune homeostasis and most notably inflammation control.

Digestive System regulation

The ECS acts as an endogenous gastrointestinal defence system by affecting the regulation of endocannabinoids which interact with receptors located in the gastrointestinal tract, the liver, pancreas, and gallbladder.

CB1 receptors are expressed in the mucosa of the stomach and colon and their activation leads to a relaxation of smooth muscle and to decreased gut motility and gut secretion. Activation of CB2 receptors causes suppression of inflammation, resulting in improvement of mucosal healing leading scientists to believe it could potentially be a target for new therapies in irritable bowel syndrome and Crohn's disease.

Other physiological functions

The ECS has been implicated in a number of other physiological functions both in the central and peripheral nervous systems and in peripheral organs. These range from movement disorders such as Parkinson's and Huntington's disease, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, hypertension, glaucoma, myocardial infarction, stroke, obesity/metabolic syndrome, and osteoporosis.

Endocannabinoid Deficiency

Scientists believe that all humans have an endocannabinoid tone, a reflection of the levels of endocannabinoids, their production, metabolism, and the abundance and state of relevant receptors.

The theory is that, whether congenital or acquired, a deficiency in the ECS results in pathophysiological syndromes.

Unfortunately, we cannot add endocannabinoids to our diet, but incredibly we can add phytocannabinoids such as THC and CBD from the cannabis plant which mimic the activity of endocannabinoids perfectly.

The Endocannabinoid System and THC

THC binds to CB1 receptors in the brain in the same manner as the endocannabinoid anandamide does, only the effects last substantially longer.

This results in the now infamous euphoric high-like feeling typically associated with cannabis. Not only that but THC has been shown to reduce chronic pain, relieve muscle spasticity in MS patients and even kill cancer cells in vivo.

One potential negative effect of THC on its own is that it can produce negative feelings such as paranoia, but thankfully it's calming cousin cannabidiol (CBD) can help here.

The Endocannabinoid System And CBD

CBD does not bind very well with either the CB1 receptor or CB2 receptor in the ECS, rather it stimulates other compounds into action which is where we see its true effects.

It is believed that CBD interacts with 5-HT1A receptors which may drive its neuroprotective, antidepressive, and anxiolytic benefits. This results in a reduction of anxiety and inflammation as well as a reduction in the paranoia, potential psychosis, and poor memory often associated with high doses of THC.

CBD has also been shown to inhibit the enzyme FAAH thereby slowing down anandamide decomposition resulting in greater pain suppression.

Key Takeaways

The ECS is a communication system that facilitates the transference of messages throughout the body in order to instigate actions such as sleep, appetite, protection, and healing.

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