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The endocannabinoid system, explained.

Learn about the role of the endocannabinoid system, how to regulate it and the unique way cannabis interacts with the human body.

Author

Emily Osborne – Polln

medically reviewed by

published

December 19, 2022

table of contents

8

min read

What is the endocannabinoid system?

Each of us – whether we consume cannabis (aka marijuana) or not – has an endocannabinoid system. The endocannabinoid system (ECS) is a molecular system made up of a vast network of chemical signals and cellular receptors located throughout our brain and body. These help regulate and balance many processes in the body – including immune responses, communication between cells, sleep, pain, appetite, hormone levels, metabolism, memory, and more. 

The endocannabinoid system is made up of:

  1. Endogenous cannabinoids (endocannabinoids)
  2. Cannabinoid receptors
  3. Enzymes responsible for the synthesis and degradation of the endocannabinoids (we’ll unpack all of these terms below!)

Unlike the nervous system or cardiovascular system, the endocannabinoid system is not an isolated structural system located in a specific region of the body. Instead, the ECS is a receptor system broadly distributed throughout the body which is acted upon by cannabinoids and enzymes. Endocannabinoids and cannabinoid receptors can be found throughout the brain, organs, connective tissues, glands, and immune cells.

Let’s unpack the endocannabinoid system further.

What is the role of the endocannabinoid system?

The ECS plays a vital role in our central nervous system and immune systems. Researchers have linked the endocannabinoid system to at least 15 internal processes in the body.1

These include:

  • appetite and digestion
  • bone remodelling and growth
  • cardiovascular system function
  • chronic pain
  • inflammation and other immune responses
  • learning and memory
  • liver function
  • metabolism
  • mood
  • motor control
  • muscle formation
  • reproductive system function
  • skin and nerve function
  • sleep
  • stress

All of these functions contribute to the stability and balance of your internal environment. The role of the endocannabinoid system is to ensure that when external force – such as an injury, illness or stressor – throws the body off balance, your ECS can kick in to help return your body to a state of homeostasis.  

The endocannabinoid system is made up of those three core components mentioned above: endocannabinoids, cannabinoid receptors and enzymes. Each of these components play an important role in helping our internal functions run smoothly, and are constantly working together to keep a wide range of bodily processes in balance. Let’s look at each component individually:

1. Endogenous cannabinoids (endocannabinoids) 

Endocannabinoids are naturally occurring molecules found in the body. They exist to mediate our normal physiological functions, and appear to have evolved in the brain to maintain biological harmony while also playing a role in neuronal plasticity (how the brain adapts to change).

The two major endocannabinoids that have been discovered are:

  • Anandamide (AEA) (ananda is the Sanskrit word for bliss)
  • 2-Arachidonoyl glycerol (2-AG)

Both of these endocannabinoids help our internal functions run smoothly, and a healthy human body produces them as needed. When there is a deficiency or imbalance in our endocannabinoid production, then we may need to look at external ways to upregulate our endocannabinoid system (more on this below).

Endogenous cannabinoids (endocannabinoids) are not to be confused with Phytocannabinoids which are found in plants. Phytocannabinoids naturally occur in a range of plant species, but are most commonly associated with the cannabis plant. You’ve probably heard of the popular cannabinoids, CBD and THC, however there are hundreds of cannabinoids. 

2. Cannabinoid receptors

Cannabinoid receptors are found on the surface of cells throughout the body. When endocannabinoids bind to these receptors, this signals to the ECS to kick-start a response.  Researchers have identified two primary cannabinoid receptors within the body:1 

  • CB1 receptor (cannabinoid receptor type 1) – predominantly found in the central nervous system, brain, connective tissues, gonads, glands, and organs. CB1 receptors can also be considered a THC receptor due to the way THC directly binds to CB1 receptors (more about this later).
  • CB2 receptor (cannabinoid receptor type 2) – predominantly found in the immune system, specifically within organs and cells responsible for some sort of response.

Many tissues contain both CB1 receptors and CB2 receptors, and each is linked to a different action. Both endocannabinoids (like Anandamide (AEA) and 2-arachidonoyl glycerol (2-AG)) and phytocannabinoids (like THC and CBD) interact with our two primary cannabinoid receptors to produce varying effects on the mind and body. More about how cannabis interacts with our CB1 receptors and CB2 receptors below.

3. Enzymes

Enzymes are molecules that accelerate chemical reactions in the body. Enzymes in the ECS are responsible for the synthesis and degradation of endocannabinoids.2 This means that certain enzymes will help produce endocannabinoids on demand, and once they have carried out their functions in the body, other enzymes will then just as quickly break the endocannabinoids down again.

There are two main enzymes responsible for this:

  • fatty acid amide hydrolase (FAAH) – which breaks down the endocannabinoid anandamide (AEA)
  • monoacylglycerol acid lipase (MAGL) – which typically breaks down the endocannabinoid 2-arachidonoyl glycerol (2-AG)

Modulation of these two enzymes can up-regulate or down-regulate the endocannabinoid system by increasing or decreasing endocannabinoid levels within the body.

How does the endocannabinoid system work?

The endocannabinoid system works by relying on each of its components – endocannabinoids, cannabinoid receptors and enzymes – to create balance within the body

A typical endocannabinoid system function works when the body’s naturally produced endocannabinoids (which are present in various organs and tissues) become active by binding with a cannabinoid receptor (also located all throughout the body) to regulate a bodily function, such as digestion or sleep. Essentially, when a system or function in the body is out of balance, receptors bind to cannabinoids to help correct the problem. Once the endocannabinoid system brings the body back into balance, enzymes will break down the cannabinoids to prevent overcorrecting the problem.

Let’s look at an example: if your body is experiencing pain, then a signal may be sent to enzymes to synthesise (produce) the endocannabinoid 2-AG. The 2-AG may then bind with and activate the CB1 receptors and/or the CB2 receptors3 to relieve the sensation of pain4 without interrupting other important bodily functions, such as temperature regulation, digestion and more. Once the body has been brought back into balance, the enzyme MAGL will then rapidly degrade the endocannabinoid 2-AG to avoid overcorrecting the problem and creating an imbalance in the body. It is this process that helps other functions of the body run smoothly even when the body is experiencing disruptions such as pain, inflammation or a fever.

When it comes to conditions like chronic pain, anxiety, or inflammatory diseases where the endocannabinoid system has not managed to bring the body back into balance and reduce symptoms, then it may be worth investigating whether an endocannabinoid deficiency or ECS dysregulation is contributing to these symptoms and looking at ways to upregulate the ECS to provide relief (more on this below).

How does cannabis interact with the endocannabinoid system?

There are hundreds of cannabinoids found in cannabis. The most popular and well-known are CBD and THC, followed by CBN, CBC and CBG. Because these phytocannabinoids have a similar chemical structure to our endocannabinoids, they have the potential to aid internal processes and mediate physiological functions when taken correctly and responsibly – especially under the guidance of a prescribing doctor

Phytocannabinoids like THC, CBD and CBN interact with our endocannabinoid system in varying ways:

THC and the endocannabinoid system

THC has been shown to work directly with the ECS by activating the CB1 receptors in the brain, producing a psychoactive effect. This may help relieve symptoms of pain, reduce nausea and vomiting, increase appetite, improve sleep, and more in some patients. It’s important to note that because THC works so directly upon the endocannabinoid system via the CB1 receptor, using too much THC can actually flood the CB1 receptors, potentially leading to increased anxiety, impaired memory and slow reaction times. This is why it’s so valuable to undergo cannabis treatment with the support of a prescribing doctor who can tailor a cannabis treatment plan to your exact needs, symptoms and individual circumstances. Learn more about THC tolerance and how THC interacts with the endocannabinoid system by heading to our Tolerance Breaks article.

CBD and the endocannabinoid system

CBD works indirectly with the ECS to interact with our opioid, dopamine, and serotonin receptors, giving it the potential to reduce pain, depression and anxiety while boosting the immune system and helping with addiction. CBD is more likely to bind to the CB2 receptor, but it does not bind to the CB1 receptor like THC does. Because the stimulation of the CB1 receptors is what causes the ‘high’ associated with cannabis (an unwanted side effect for some), CBD taken without THC does not cause this effect. CBD may also work by preventing endocannabinoids from being broken down, allowing them to have a greater effect on your body. For example, CBD has been found to inhibit the activity of the fatty acid amide hydrolase enzyme,5 which breaks down the endocannabinoid anandamide (AEA). Because anandamide levels play a key role in memory, mood, appetite, sleep, and pain relief, CBD’s inhibition of the enzyme that breaks it down may aid these functions while stimulating a sense of happiness and mental wellness.

CBN and the endocannabinoid system

One of the lesser known (but no less important) cannabinoids found in the cannabis plant is CBN, short for ‘cannabinol.’ CBN is known to have anticonvulsant, sedative, and other pharmacological activities6 that are still being explored. CBN is created during the breakdown of the psychoactive cannabinoid THC.

Like THC, CBN also binds to the CB1 receptor, but at a much lower strength than THC.7 This technically makes it a psychoactive compound, but it doesn’t produce much of a ‘high’ sensation that some patients may experience with THC. CBN has a stronger affinity towards the CB2 receptors, which are mostly associated with immune system regulation.7

What about endocannabinoid deficiency? 

Clinical Endocannabinoid Deficiency8 (CECD) is a term coined by neuropharmacologist Dr Ethan Russo in the early 2000s in an attempt to explain the potential therapeutic effects of cannabis in treating certain treatment-resistant conditions. The theory suggests that a low functioning endocannabinoid system – which may look like low endocannabinoid levels, an overabundance of metabolic enzymes or some other ECS dysfunction – could contribute to the development of certain chronic conditions such as:

  • Irritable bowel syndrome9
  • Fibromyalgia9
  • Chronic migraines9
  • Endometriosis10
  • Anxiety11
  • Depression12
  • PTSD13
  • Autism spectrum disorder14

A 2016 article reviewing over 10 years of research on the endocannabinoid system and its relationship with IBS, fibromyalgia and chronic migraines, suggests that endocannabinoid deficiency may explain why some people develop some of these conditions.9 However, much more research is needed before we can come to a definitive conclusion.

Possible signs of endocannabinoid deficiency:

If you develop issues with sleep, chronic pain, menstrual pain, unmanageable stress, IBS symptoms, migraine, depression or any other issues relating to bodily functions that are regulated by the endocannabinoid system, this may be a sign of endocannabinoid deficiency or dysregulation. Unfortunately, there is no definitive cause of CECD and the concept is still very much a theory which requires more robust research to be better understood. If you’re ever unsure, always speak with a qualified healthcare professional about your conditions and symptoms.

Is medicinal cannabis right for me and my condition/s?

If you have a chronic condition with symptoms that are resistant to other types of treatment, such as pain or anxiety, you may want to explore medicinal cannabis as a potential treatment option with a prescribing doctor. Medicinal cannabis may be beneficial for patients who have some kind of endocannabinoid dysfunction, which has been seen in endometriosis patients, fibromyalgia patients and more.

Medicinal cannabis is legal in Australia with a valid prescription. To be eligible for medicinal cannabis, you’ll need to:

  1. Have a chronic condition with symptoms lasting 3 months or more, and
  2. Have tried other conventional treatments which were ineffective or caused you unwanted side effects.

Take our free eligibility quiz to see if you might be eligible for medical cannabis access.

Ultimately it will be up to a prescribing doctor to determine whether cannabis may be right for you and your condition. A cannabis clinician with experience in cannabinoid medicines is your best bet for getting specialised advice and a treatment plan that meets your therapeutic needs. An experienced cannabis clinician should be able to determine which cannabinoids and other cannabis compounds would benefit you and your symptoms, as well as your ideal type of cannabis treatment, the method you use to take it and at what dose.

6 ways to balance your endocannabinoid system

There are a number of ways we can naturally regulate our endocannabinoid system to achieve balance in the body and treat potential endocannabinoid deficiencies. Some of these methods include:

  1. Eating more omega-3 fatty acids: fatty acid precursors – like those found in omega-3 – are known to produce endocannabinoids.15 Try consuming omega-3 rich foods like wild-caught fish, nuts and seeds and pasture-raised eggs.
  2. Diversifying your gut microbiome: eating a wide range of fruits and vegetables (all of which contain microbacteria feeding prebiotics) can boost endocannabinoid levels.16
  3. Trying terpenes: terpenes are the aromatic compounds found in plants – including cannabis. The terpene Beta-caryophyllene (BCP) which is found not only in cannabis but in basil, black pepper, cloves, cinnamon and more activates the CB2 receptor17 and has anti-inflammatory, anxiety and pain reducing and neuroprotective effects.
  4. Moving your body: exercise has been shown to increase endocannabinoids18 to help maintain homeostasis within the body, with moderate aerobic activity19 having a greater benefit than light or intense exercise. Importantly, the exercise should be something you enjoy and take pleasure in to really benefit your endocannabinoid system.  
  5. Reducing stress: prolonged periods of stress can impair the development of new cannabinoid receptors, and increased amounts of the stress hormone cortisol interfere with the function of our CB1 cannabinoid receptors, finding ways to reduce stress is another good way to regulate the ECS.20
  6. Consuming cannabinoids: When there is a potential endocannabinoid deficiency,9 or a condition like chronic pain that is resistant to standard treatments (such as medications, therapies and lifestyle changes), phytocannabinoids in medicinal cannabis treatments can potentially help boost our endocannabinoid system function.

The bottom line

Although there is still much research to be done, studies to date strongly suggest that the endocannabinoid system plays a vital role in our central nervous system and immune systems. This means that maintaining a balanced and functioning endocannabinoid system is essential for good health. Lifestyle changes like diet, exercise, stress reduction techniques and herbal medicines can be used to help upregulate the endocannabinoid system and drive a range of health benefits, while cannabinoids like THC and CBD can be useful in helping to correct potential endocannabinoid deficiencies where other treatments have failed.

At Polln, all of our doctors are experts in cannabinoid medicines who understand the therapeutic implications of medicinal cannabis. They can determine your suitability for medical cannabis and tailor a treatment plan with your individual needs, symptoms and potential endocannabinoid deficiencies in mind.

To talk to an expert in medicinal cannabis, sign up as a Polln patient today.

References
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