The Endocannabinoid System

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The Endocannabinoid System

To begin with, some key definitions are outlined below:

Cannabinoid - any of a group of closely related compounds which include cannabinol and the active constituents of cannabis.

Endocannabinoid - endogenous cannabinoids (the cannabinoids that your body makes naturally).

The Endocannabinoid System - includes endocannabinoids, the enzymes that help make them and break them down, and the receptors that (endo)cannabinoids bind to.

The Endocannabinoid System helps modulate the regulation of homeostasis across all major systems within the body, ensuring all systems operate in concert with one another. The Endocannabinoid System assists with fine tuning most of our physiological functions, promoting homeostasis which affects the physiological functions listed below;

  • Sleep
  • Appetite
  • Pain
  • Inflammation
  • Memory
  • Mood
  • Reproduction

Although the function of the endocannabinoid system remains mysterious in healthy tissues outside the brain and gut, diseases reveal clues. In obesity, both CB1 and CB2 receptors are upregulated throughout the body, including in the liver and in adipose tissue. The activation of CB1 receptors increases food intake and affects energy metabolism in peripheral tissues and the peripheral nervous system. In type 2 diabetes, endocannabinoids and their receptors are upregulated in circulating macrophages and contribute to the loss of pancreatic beta cells, which store and release insulin.

Cannabis users have no documented increased incidence of diabetes or obesity. It is speculated that this is because chronic use results in downregulation of CB1 receptors, a form of pharmacological tolerance. Another possibility, is that chronic THC exposure alters the gut microbiome, affecting food intake and preventing weight increase.

Yet there remains debate as to whether endocannabinoid receptors are always a harmful factor in disease. In some cases, endocannabinoid signalling even appears to be therapeutic. Animal studies suggest endocannabinoids are effective pain relievers, and the system has anti-inflammatory properties in certain contexts.

The function of a cell can be changed by receiving a message. The message can be sent by the cell itself, or from another cell. This message is typically in the form of chemicals contained within administered drugs, or chemicals produced within the body, neurons, or even mechanical stimuli. This message will be received by something called a receptor and will cause the cell to respond in a certain manner. There are various types of receptors, their existence can vary by cell type and other cellular activity.

The location of the receptors and the specificity of that message to that receptor will greatly impact the function of the message.

What are endocannabinoids?

Endocannabinoids, also called endogenous cannabinoids, are molecules made by your body. They’re similar to cannabinoids, but they’re produced by the body.

Experts have identified two key endocannabinoids so far:

  • anandamide (AEA)
  • 2-arachidonoylglyerol (2-AG)

The two endocannabinoids maintain internal functions and ensure they operate effectively. The body produces them as needed, making it difficult to know what typical levels are for each.

What are endocannabinoid receptors?

These receptors are found throughout your body. Endocannabinoids bind to them in order to signal that the ECS needs to take action.

There are two main endocannabinoid receptors:

  • CB1 receptors, which are mostly found in the central nervous system
  • CB2 receptors, which are mostly found in your peripheral nervous system, especially immune cells

Endocannabinoids can bind to either receptor. The subsequent effects depend on where the receptor is located and which endocannabinoid it binds to.

An instance of this would be endocannabinoids targeting CB1 receptors in a spinal nerve to relieve pain. Others might bind to a CB2 receptor in immune cells to signal that the body’s experiencing inflammation, a common sign of autoimmune disorders.

How are endocannabinoids broken down?

Enzymes are responsible for breaking down endocannabinoids once they’ve carried out their function. There are two main enzymes responsible for this:

  • fatty acid amide hydrolase, which breaks down AEA
  • monoacylglycerol acid lipase, which typically breaks down 2-AG

Cannabinoid receptors (CB receptors)

Cannabinoid receptors sit on cell surfaces, waiting for specific neurotransmitters to bind to them. Depending on the type of cell the receptor is on, the downstream effect will rapidly impact immunity, sensation, mood, and even consciousness. 

CB receptors are present throughout the body, guarding a wide variety of cell types & responses. Different cell types have different receptors, which are sensitive to different types of endocannabinoids. The two main receptors of the endocannabinoid system are CB1 and CB2.

CB1 receptors are essential for a healthy functioning brain and are one of the most common receptors in the entire nervous system. Depending on what region of the brain they are located in, they can be moderators of your memory, mood, motor function, or your perception of pain. These brain receptors are also responsible for the psychoactive properties of cannabis when THC binds to them.

 CB2 receptors are most often found on the cells of our immune system. They help moderate inflammation and our immune response to pathogens. If you use CBD products to combat conditions of an overactive immune system (i.e. arthritis, asthma, allergies, autoimmune disorders or digestive issues like inflammatory bowel disease).

How does CBD interact with the Endocannabinoid System?

Unlike THC, CBD doesn’t make you “high” and typically doesn’t have any negative effects.

Experts aren’t completely sure how CBD interacts with the Endocannabinoid System. But they do know that CBD doesn’t bind to CB1 or CB2 receptors in the way that THC does. Many believe CBD works by preventing endocannabinoids from being broken down. This allows them to have more of an effect on your body. Others believe that CBD binds to a receptor that hasn’t been discovered yet.

While the details of how CBD works are still under debate, research suggests that CBD can help with pain, nausea, and other symptoms associated with multiple conditions.

The endocannabinoid system explains why natural cannabinoids in hemp and other plants have therapeutic effects. Hemp and Cannabis had been used for thousands of years to treat a number of ailments, including epilepsy, headaches, arthritis, pain, depression, and nausea. Traditional healers may not have known why the plant was effective, but their experience demonstrated its effectiveness and provided the basis for more recent scientific research. The discovery of the endocannabinoid system revealed a biological basis for the therapeutic effects of plant cannabinoids and has sparked renewed interest in cannabis as medicine.

Research has shown that small doses of natural cannabinoids from hemp and other plants help support the endocannabinoid system and enhance its signalling. This suggests that small, regular doses of naturally occurring cannabinoids from hemp and other plants might act as a tonic to our most central physiologic healing system.

Exercise and diet can also help boost the endocannabinoid system. Scientists have found that prolonged aerobic exercise increases levels of anandamide, the endocannabinoid that has been found to make you feel good. Diet is also a useful target. Increasing your intake of the essential fatty acid, omega 3, found in oily fish or healthy seeds like flax or hemp, can help support endocannabinoid brain signalling.

While a tremendous amount of research has been conducted into the endocannabinoid system, there is still a great deal that remains beyond the comprehension of scientists. The majority of medical doctors are not trained on the endocannabinoid system so can therefore not advise patients on treatments targeted to treat ailments using the science behind the endocannabinoid system. Certain diseases could simply be an aspect of clinical endocannabinoid deficiency.

However, the future looks bright. With an increasing amount of research into the endocannabinoid system, Cannabis, CBD oil tinctures and other cannabinoids being undertaken, humanity’s understanding of these topics shall improve and ultimately result in medicines that can best treat conditions that involved the endocannabinoid system.