CBD and the Endocannabinoid System

CBD is the hottest nutritional supplement to hit the market in recent years. You’ve probably heard about the potential benefits of CBD oil, but if you’re like most people, you probably don’t quite understand how it works. That’s not surprising since the science behind how cannabinoids like CBD and THC work is a relatively recent discovery.

Meet the Endocannabinoid System

CBD and other cannabinoids, such as THC, CBG, and CBN, are among the hundreds of active compounds in cannabis plants. These plant cannabinoids, called phytocannabinoids, stimulate receptors in the body’s endocannabinoid system (ECS).

The ECS is comprised of a series of receptors designed to receive molecules called endocannabinoids. The brain and central nervous system has one type of receptor, referred to as CB1. The second kind of endocannabinoid receptor, CB2, can be found in abundance in the organs of the immune system. Human skin also has cannabinoid receptors, making cannabis topicals particularly effective.

The human endocannabinoid system is involved in regulating the balance of many essential bodily systems, including:

  • Anxiety
  • Pain-response
  • Mood-regulation
  • Inflammation
  • Sensation of pleasure
  • Motor control
  • Sleep cycles
  • Temperature control
  • Immunity

By modulating these functions, the endocannabinoid system helps the body maintain homeostasis. Homeostasis is the process by which organisms can maintain proper functioning despite the fluctuation of outward conditions. Homeostasis allows us to maintain a consistent body temperature and heart rate despite changing circumstances.

CBD and the Endocannabinoid System

Endocannabinoids: The Body’s Natural Feel-Good Molecules

In 1992, a group of researchers found the first endocannabinoid, anandamide. The scientists named the compound after the Sanskrit word, “ananda,” which means bliss. The name is particularly appropriate because biologists suspect that anandamide plays a role in the euphoric feelings athletes get after a session of strenuous exercise. Anandamide also affects memory, appetite, and reproductive functions.

The second endocannabinoid discovered, 2-arachidonoylglycerol (2-AG), imparts an equally euphoric feeling and is involved in emotional states, cardiovascular regulation, and prevention of seizures. Together these two feel-good molecules play the most significant roles in the endocannabinoid system.

Endocannabinoids and Neurotransmitters

Endocannabinoids work in a similar way as neurotransmitters. Neurotransmitters send messages between neurons in the nervous system. Similarly, endocannabinoids transmit information between the receptors in the ECS.

However, endocannabinoids work in the opposite direction as neurotransmitters like dopamine and serotonin. When a synapse is stimulated, a neurotransmitter leaves the cell from an axon. The neurotransmitter travels to a postsynaptic site on another cell, causing activation. Conversely, endocannabinoids depart from these postsynaptic sites and travel to the axon sites of nearby cells. In effect, endocannabinoids and neurons create a feedback loop.

Clinical Endocannabinoid Deficiency Syndrome (CECD)

When patients don’t produce enough natural endocannabinoids, they may develop Clinical Endocannabinoid Deficiency Syndrome (CECD). CECD may be responsible for many of the adverse effects of a variety of conditions, including:

  • Anxiety disorders
  • Chronic Pain
  • Irritable bowel syndrome
  • Psoriasis
  • Migraines
  • Fibromyalgia
  • Depression
  • Parkinson’s
  • Schizophrenia’

Although more investigation is needed, phytocannabinoids like CBD may hold incredible therapeutic potential for patients suffering from these illnesses.

How Phytocannabinoids in Cannabis Work

Naturally-produced endocannabinoids act like keys. They fit into the cannabinoid receptors and unlock a mechanism which causes the receptor to make changes in the body’s regulatory systems.

Phytocannabinoids like tetrahydrocannabinol (THC) and cannabinol (CBN) function in the same way as endocannabinoids do. THC acts in a lock-and-key fashion with the CB1 receptors in the brain and nervous system, which explains the psychoactive properties of cannabis. CBN, a cannabinoid produced when THC oxidizes, seems to prefer the CB2 receptors in the immune system.

Unlike other cannabinoids, CBD doesn’t usually bind to receptors in a lock-and-key manner. Instead, CBD modulates the receptors to affect how other cannabinoids bind with the receptor sites. For example, CBD inhibits the action of THC, which makes it a perfect companion to soften some of the more intense effects of THC. The CBD in high-CBD cannabis strains keeps some of the THC from binding to CB1 receptors, reducing unwanted effects like anxiety or paranoia.

Together these phytocannabinoids create a synergistic phenomenon known as the “entourage effect”. The entourage effect happens when cannabinoids and other cannabis compounds called terpenes work together to create balance in the body. Full-spectrum CBD oils and CBD products that contain some THC take advantage of the entourage effect to produce better results.

Ways Cannabinoids Affect Receptors

When cannabinoids stimulate endocannabinoid receptors, they work in one of four ways:

1. Agonists:

When a cannabinoid attaches and stimulates a receptor to transmit a signal, it is called an agonist. An agonist acts like an “on” switch. CBD is called a “weak agonist” of some receptors. A weak agonist doesn’t easily bond to the receptor, but when it does, it flips the “on” switch.

2. Antagonist:

A cannabinoid which doesn’t attach to a receptor, but actively blocks other substances from binding is referred to as an antagonist. CBD is a weak antagonist of CB1 receptors, which may contribute to its painkilling effects.

3. Inverse Agonist:

An inverse agonist is a cannabinoid that binds to the receptor, but blocks signal transmission. An inverse agonist is equivalent to an “off” switch. CBD is a weak inverse agonist of CB2 receptors. This action is one of the ways CBD reduces inflammation and pain.

4. Allosteric modulators:

Allosteric modulation occurs when a cannabinoid changes the way a receptor works without stimulating it directly. Allosteric modulators may cause the receptor to speed up or slow down the transmission of electrical signals. CBD is a strong allosteric modulator of the CB1 receptor. In this way, CBD lessens some of the effects of THC.

How CBD Affects the Endocannabinoid System

As we’ve learned earlier, CBD doesn’t easily bind to endocannabinoid receptors in the typical lock-and-key manner. The primary influence of CBD on the ECS is to help the body maintain endocannabinoids. CBD does this by using up enzymes that are involved in the breakdown of endocannabinoids.

Since anandamide and 2-AG are the most abundant endocannabinoids in the human body, scientists know more about the enzymes involved in metabolizing them. Monoacylglycerol lipase (MAGL) breaks down 2-AG. Fatty Acid Amide Hydrolase (FAAH) is the enzyme responsible for breaking down anandamide.

CBD’s anti-anxiety effects can be traced to its ability to help the body conserve anandamide. CBD does this by inhibiting FAAH and keeping the enzyme from metabolizing anandamide. A certain percentage of the human population has a genetic propensity to produce smaller amounts of FAAH. As a result, this segment of the population is less susceptible to anxiety disorders. CBD works in the same fashion that Selective Serotonin Reuptake Inhibitors (SSRIs) function to allow more serotonin to remain in the system. But instead of serotonin, CBD increases levels of anandamide and is called an “anandamide reuptake inhibitor.”
FAAH and MAGL enzymes are less-effective in breaking down phytocannabinoids from cannabis. This property is one of the main reasons for the long-lasting effects of THC and CBD.

CBD and Transport Proteins

Human bodies are comprised mainly of water, while cannabinoids are made of fats. For this reason, endocannabinoids need help traveling through the body. They do this by enlisting the aid of transport proteins. CBD modulates these transport proteins to facilitate the distribution of endocannabinoids throughout the body.

Other Ways CBD Affects the Body

Besides interacting with enzymes and transport proteins, CBD affects a host of additional receptors, including:


CBD binds to Dopamine D2 receptors, which are involved in the treatment of schizophrenia.


CBD and other phytocannabinoids activate TRP1 receptors, which may contribute to their analgesic effects.

PPAR Gamma

CBD activates PPAR receptors, which is involved in conditions like diabetes and Alzheimer’s disease.


CBD stimulates 5-ht1A receptors, which play a role in a variety of vital systems.

CBD and Other Animals

Although biologists believe that the endocannabinoid system evolved over 500 million years ago, the ECS wasn’t discovered until the 1990s. All vertebrate organisms have an ECS, including mammals, birds, reptiles, and fish. Even some invertebrates, such as mussels, leeches, and sea urchins, have endocannabinoid systems. Insects lack an endocannabinoid system, which is why cannabis doesn’t seem to affect bees and other pollinators.

CBD has a similar effect on other mammals as it does on humans. Pet-owners are increasingly turning to CBD products to help their dogs and cats with common problems, such as anxiety and chronic pain.

As you can see, CBD has a complex range of effects on human bodies. Researchers are just beginning to understand the whole range of therapeutic possibilities for CBD. If you would like to know more about our range of high-quality CBD products, contact us at CBD Oil Canada.