The endocannabinoid system

The endocannabinoid system

Intro/Background

You may have heard a person mention the endocannabinoid system (ECS) or have seen it mentioned in an article, but what does it mean?

Some believe that the ECS exists only to process phytocannabinoids (THC, CBD etc) due to containing the word “cannabinoid”, however, your body produces natural cannabinoids on a daily basis – known as endocannabinoids – endo meaning “within” the body.

The term endocannabinoid was coined when scientists were investigating how cannabis effects humans, when they discovered the ECS. They found that the ECS is present in every single human – infact every vertebrate has an endocannabinoid system.

One of the main purposes of the ECS is to maintain homeostasis –  controlling and regulating the internal environment of  the cells contained in your body.

What is homeostasis?

Homeostasis regulates levels of temperature, water, nutrients, blood flow, heart rate, neurological function and immune system responses. Our bodies homeostasis system is necessary for survival and adaptation, without it, the human body would not function correctly – our cells require specific environments in order to function at optimum levels.

The Endocannabinoid system (ECS)

First, let’s see what the ECS consists of before looking at an example of a role  which it plays within the human body.

The endocannabinoid system can be split into three categories, as below:

  • Receptors
  • Endocannabinoids
  • Enzymes

1. Receptors

Cannabinoid receptors are found on the surface of cells and control the internal response of the cell.

The two primary cannabinoid receptors are CB1 and CB2 and are both found throughout the human body.

CB1

CB1 receptors are found primarily in the brain and central nervous system. CB1 receptors are responsible for the psychoactive high experienced when using cannabis: THC has a high affinity for the CB1 receptor, meaning it bonds strongly to the receptor.

CB2

CB2 receptors are found in immune cells throughout the body. The CB2 receptor is responsible for neuroprotective responses and suppressing inflammation. It has been suggested that the CB2 receptor is responsible for the pain relieving effects of cannabis.

2. Endocannabinoids

You are probably familiar with the primary phytocannabinoids contained in cannabis; THC and CBD. Endocannabinoids are molecules which are produced naturally, on-demand, by cells in our bodies.

There are two primary endocannabinoids: Anandamide and 2-AG, which bind with the CB1 and CB2 receptors respectively.

3. Enzymes

There are two enzymes which break down the endocannabinoids:

Fatty acid amide hydrolase (FAAH) – responsible for breaking down Anandamide

Monoacylglycerol lipase (MAGL) – responsible for breaking down 2-AG

These two enzymes are responsible for degrading endocannabinoids to ensure that they are destroyed straight after use by the cells, so that they’re not used for longer than is necessary.

How the receptors, endocannabinoids and enzymes interact

The integration of the central and peripheral systems within the human body are achieved through hormonal and neuronal signalling.

For example, when your body requires food, endocannabinoids are triggered which send signals to the brain.

Endocannabinoids in the brain then trigger neuronal signalling by activating CB1 and CB2 receptors, which result in feelings of hunger and an increased appetite. The enzymes FAAH and MAGL will then destroy the endocannabinoids straight after use in order to stop the signals of increased hunger.

Figure 1 below depicts endocannabinoids, Anandamide and 2-AG, activating ECS receptors, CB1 and CB2 in a cell, and then being destroyed by enzymes FAAH and MAGL after use, in a cell.

Figure 1. The natural endocannabinoid system (ECS). The two endocannabinoids Anandamide and 2-AG activate the receptors CB1 and CB2 respectively. The enzyme FAAH breaks down anandamide, and the enzyme MAGL breaks down 2-AG. Both endocannabinoids are destroyed straight after use to ensure they are not used for longer than necessary.
endocannabinoid anandamide diagram
Figure 1.1. The natural endocannabinoid system (ECS). The endocannabinoid Anandamide activates the receptor CB1. The enzyme FAAH breaks down anandamide. Anandamide endocannabinoids are destroyed straight after use to ensure they are not used for longer than necessary.
Figure 1.2. The natural endocannabinoid system (ECS). The endocannabinoid 2-AG activates the receptor CB2. The enzyme MAGL breaks down 2-AG. 2-AG endocannabinoids are destroyed straight after use to ensure they are not used for longer than necessary.

The role of the ECS in the human body

The ECS influences many physiological processes through regulating the control of energy balances and metabolic processes of cells all throughout the body. The ECS works as a type of feedback loop.

Basic process example

When your body requires food, the ECS is stimulated; by hunger and fasting. This triggers endocannabinoids which send information to your brain which then produces signals that increase your appetite.

After you eat some food, endocannabinoids are activated and trigger signals which decreases ECS activity. This decrease in ECS activity increases a hormone known as leptin.

Leptin decreases endocannabinoid levels in the brain which in turn decreases your level of hunger/appetite.

Munchies

When ingesting cannabis, THC activates the CB1 receptors of the ECS, which makes you feel hungry.

Normally, after consuming food, the activity of the ECS is decreased due to enzymes breaking down the natural endocannabinoids produced by your body, which stop the feelings of hunger.

This is why you remain hungry after eating when high on cannabis – ECS activity does not decrease, as the ECS enzymes cannot breakdown THC, thus leaving CB1 receptors activated, until the THC wears off.

How cannabis interacts with the ECS

The cannabinoids contained in cannabis, namely THC, closely resemble the structure of anandamide, and activate the CB1 receptor, as shown in figure 2 below.

CB1 receptors affect certain signaling pathways found in the brain which are responsible for cognition and regulation of reward and mood systems – which is why THC causes the feelings of being high.

However, unlike the anandamide endocannabinoids, THC is not broken down by the enzymes FAAH or MAGL, which means the CB1 receptor remains activated until the THC is gradually used up.

Stress and cannabis

Research has found that people who are subjected to high levels of stress have a deficiency of endocannabinoids in their brain.

This is the reason that pretty much every cannabis strain can cure stress – THC takes the place of the “missing” endocannabinoids and activates the CB1 receptors, thus maintaining homeostasis in areas of the brain.

CBD and the ECS

CBD, the second most common phytocannabinoid found in cannabis indirectly activates the CB1 and CB2 receptors.

It has been found that CBD inhibits the enzyme FAAH – the enzyme which breaks down the endocannabinoid anandamide.

Since there is less FAAH enzyme present, the use of CBD results in an elevated level of naturally produced anandamide in the brain and body. For this reason, CBD is found to be effective in treating anxiety.

It should also be noted, cannabinoids from cannabis do not only activate CB1 and CB2 receptors: CBD has been found to indirectly affect other receptors in the brain such as opioid and dopamine receptors – these play important roles in cognition and behavior.

CBD also activates serotonin 1A receptors, which has shown promise to counteract opioid addiction, tobacco withdrawal, pain, depression, anxiety, nausea and symptoms of schizophrenia.

Figure 2. Phytocannabinoids activating CB1 receptors in the ECS system. THC directly activates CB1 receptors and is not broken down by the enzyme FAAH. CBD indirectly activates the CB1 receptors. CBD inhibits the enzyme FAAH: The enzyme responsible for breaking down the natural endocannabinoid Anandamide. Due to inhibiting the enzyme, there is excess anandamide within the ECS until CBD has been broken down.
phytocannabinoid THC interaction diagram
Figure 2.1. Phytocannabinoids activating CB1 receptors in the ECS system. THC directly activates CB1 receptors and is not broken down by the enzyme FAAH.
phytocannabinoid CBD interaction diagram
Figure 2.2. Phytocannabinoids activating CB1 receptors in the ECS system. CBD indirectly activates the CB1 receptors. CBD inhibits the enzyme FAAH: The enzyme responsible for breaking down the natural endocannabinoid Anandamide. Due to inhibiting the enzyme, there is excess anandamide within the ECS until CBD has been broken down.

Therapeutic/medical benefits of cannabis on the ECS

If you’re new to the cannabis world, you may be skeptical that cannabis can cure  such a vast range of diseases and conditions. The reason cannabis has so many therapeutic properties is down to the ECS.

The receptors of the ECS are found throughout the body; in the brain, nervous system and organs, and regulate virtually every process in the human body.

The feedback loop of the ECS in some people may not be working correctly/efficiently, which is why cannabis is able to aid the processes of the ECS.

We can deduce that cannabis treats a wide range of conditions and symptoms due to it’s interaction with the ECS – in other words, medical benefits of cannabis are not anecdotal.

The direct and indirect activation of the EC receptors by cannabis is therefore able to treat conditions such as:

Epilepsy, anxiety, depression and other mood disorders, pain, connective tissue diseases, chronic inflammation, arthritis, motion sickness, nausea caused by chemotherapy, multiple sclerosis, Huntington’s disease, Parkinson’s disease, schizophrenia, PTSD and autism.

Frequent cannabis use and the ECS

Frequent, extremely chronic cannabis use can alter the endocannabinoid system.

When phytocannabinoids from cannabis interact with the ECS during extended periods of use with no break, it can cause the natural endocannabinoids to “forget” how to work properly.

This is completely reversible – When you stop consuming cannabis after extremely chronic use, you may experience anxiety, hot/cold flushes, insomnia and not feel hungry. However the feelings will only last a couple of days to a week or so, and your ECS will be back into it’s normal “rythm” .

It should also be noted, fairly frequent use, with tolerance breaks every now and then will not have an adverse effect on the ECS processes.

Chronic ECS problems

Some people suffer from chronic ECS problems, where the feedback loop of the ECS does not work correctly, thus not maintaining homeostasis. Examples of ECS problems are:

  • Dyslipidemia (abnormal lipid (fat) levels in the blood)

    This occurs due to over-stimulated CB1 receptors, which leads to increased fat synthesis. An increased fat synthesis can result in high cholesterol and obesity.

  • Glucose homeostasis problems (Regulation of blood sugar level)

    The ECS triggers a hormone known as adiponectin, that regulates lipid and glucose metabolism in the muscles and liver, which improves insulin sensitivity. Over-stimulated CB1 receptors reduces adiponectin, which decreases insulin sensitivity.

Chronic ECS problems such as those above can result in metabolic dis-regulation, which leads to a number of symptoms such as obesity, hypertension, insulin resistance and inflammation.

Cannabis use is found to improve the symptoms of the above as it helps in regulating the processes through taking the place of the naturally produced endocannabinoids –  thus maintaining homeostasis.

Brain functions

CB1 receptors are found all throughout the body, with an abundance situated in the brain. The figure below indicates the areas of the brain which regulate various processes. Consuming cannabis activates the ECS in these areas which in turn affect certain conditions/processes within your body.

brain diagram
Figure 3. Approximate locations of various sections of the brain

Amygdala – Emotions

Basal Ganglia – Motor movements & Eye movements

Brain stem – Transmits brain signals to spinal cord and vice verse.

Cerebellum – Motor coordination and balance

Hippocampus – Learning

Hypothalamus – Eating/digestion & Sleep

Neocortex – Sensory perception, language, conscious thoughts

Nucleus accumbens – Reward processes

Spinal cord – Transmission of information

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