Endocannabinoid Tone and Crohn's Disease

Crohn's disease is a condition where parts of the digestive system become inflamed, causing several severe symptoms. It is a lifelong inflammatory bowel disease (IBD) with no cure; however, some treatments can control the symptoms.

According to NHS Inform, there are at least 115,000 people in the UK with Crohn's disease. It can affect men and women equally and symptoms are usually first noticed in childhood or before the age of 30.

The common symptoms of Crohn's disease include:

• Sudden bouts of diarrhoea 
• Stomach-ache
• Stomach cramps 
• Bloating
• Blood in your poo
• Extreme fatigue
• Weight loss

Some people experience these symptoms continuously, but others have them in flare-ups separated by periods of remission.

It's not yet clear what causes Crohn's disease, but there may be a hereditary component, and immune system problems may also be involved. In addition, other factors like smoking and non-steroidal anti-inflammatory medications have been found to contribute to flare-ups and intensify symptoms.

There is no cure for Crohn's disease, but it can be improved by diet and medication. Steroids and immunosuppressants are sometimes used together to relieve symptoms. 

CBD and Your Endocannabinoid Tone

CBD works in your body in many different ways, but one of the most vital interactions is how it stimulates the endocannabinoid system (ECS) and raises your endocannabinoid tone:

What is the endocannabinoid system?

The endocannabinoid system is a collection of signal molecules (endocannabinoids), receptors and enzymes.

It's active throughout the body, particularly in the central and peripheral nervous systems. 

When the ECS is activated, it makes tiny chemical adjustments that enhance the signalling capacity of cells within your body.

This allows your body systems to communicate effectively and quickly restore a healthy balance following damage or illness.

What is your endocannabinoid tone?

Endocannabinoid tone refers to the level of potential endocannabinoid activity in your body and the ability of your endocannabinoid system to respond to any problems.

This can be affected by a range of factors, including genetics, diet, stress and disease.

If your endocannabinoid tone is low, your endocannabinoid system is unlikely to be able to restore your body systems to a state of healthy balance. As a result, you may feel unwell or experience symptoms related to anxiety. 

Regular consumption of CBD can stimulate the action of your endocannabinoid system (ECS) and raise your tone. 

To learn more about how CBD raises your endocannabinoid tone, you can read our article: Endocannabinoid Tone and CBD.

Key terms:

CB1 and CB2 – These are the most common endocannabinoid receptors.

• CB1 is found in the central nervous system.
• CB2 is present in the central nervous system, the peripheral nervous system and in immune cells throughout the body.

Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) – These are endocannabinoid signalling molecules present in humans and animals. They can interact with a range of chemical receptors, including CB1 and CB2.

Endocannabinoid Tone and Crohn's Disease

The endocannabinoid system (ECS) plays a crucial role in adjusting the signalling systems that connect the gut-brain axis.

Research indicates that when the endocannabinoid receptors in the gut are activated, they regulate the signals sent between nerve cells in the same way they do in the brain and central nervous system.

The role of endocannabinoids in people with Crohn's disease has been broadly explored in several studies.

On the whole, they demonstrated that a high endocannabinoid tone allows the body to modulate relevant gut actions better and reduce the symptoms of Crohn's. 

However, due to differences between patients and modes of study, much of the information on exactly how the endocannabinoids, receptors and enzymes behave during flare-ups is conflicting.

Consequently, the current understanding of how endocannabinoid tone may benefit people with Crohn's disease is still relatively broad and more detailed investigations are still necessary. 

The endocannabinoid system is essential to various functions that play a role in Crohn's disease. The two that we know most about are immune system homeostasis and pain sensitivity.

Immune System Homeostasis

The endocannabinoid system is vital to maintaining a correctly balanced immune system.

CB1 and CB2 receptors are present in almost all immune cells, including T cells, B cells, NK cells, dendritic cells, macrophages, neutrophils and mast cells.

In someone with a medium to high endocannabinoid tone, these receptors are activated by endocannabinoids to regulate the correct immune response and prevent too low or too high levels of cell activity.

In experiments with mice, researchers found that the number of CB1 and CB2 receptors around the intestine increased when Crohn's-like intestinal inflammation was modelled.

Further investigation demonstrated that mice without CB1 or CB2 receptors experienced worse inflammation than those with the receptors. 

Scientists concluded that in people with a naturally high endocannabinoid tone, the ECS might be able to regulate and inhibit inflammation in the colon, which is found in some types of Crohn's disease.

When activated, both CB1 and CB2 receptors produce a range of effects that restore immune system homeostasis and reduce inflammation.

These actions include changing the polarization of macrophages, preventing T-cells from releasing proinflammatory cytokines and inhibiting leukocyte adhesion and activation.

Pain Sensitivity



Another key element of Crohn's disease is pain and discomfort. Some scientists suggest that the pain experienced by people with Crohn's disease is linked to visceral hypersensitivity.

This involves nerves becoming sensitised to pain signals. As a result, low-level pain stimulus that would typically only cause minor discomfort can result in excruciating pain. 

In people with a medium or high endocannabinoid tone, this type of pain sensitisation causes an automatic balancing response from the endocannabinoid system.

Therefore, when CB1 receptors are activated, they reduce sensitisation, making the pain receptor less likely to fire. 

Also, when CB1 and CB2 receptors are activated, they stimulate several actions that modulate the proper control of the pain signals.

CB1 receptors activate channels that alter the electrical and chemical activity of the neuron.

CB2 receptors inhibit and control the release of cytokines which may be linked to uncontrolled inflammation and pain.

However, if the endocannabinoid tone is low, the sensitisation and uncontrolled pain signals continue, resulting in the chronic pain associated with Crohn's disease and other digestive system conditions like IBS.