What Is Clinical Endocannabinoid Deficiency (CECD)?

The endocannabinoid system exists to monitor several of our body's vital biological systems. Its primary role is to help restore balance to the human body and keep it in optimal condition. Some researchers believe that a defective endocannabinoid system could be the underlying cause of medical conditions such as migraine, fibromyalgia, and irritable bowel syndrome. While the concept is not unanimously accepted among medical bodies, there is a growing volume of research to support the theory.

Endocannabinoid deficiency starts with the endocannabinoid system

Before reviewing the research into clinical endocannabinoid deficiency (CECD), it is worth recapping the role^[1] of the ECS and its primary parts. Throughout our immune and central nervous systems, major organs, and parts of our brain, are receptors. These receptors typically fall into two categories, CB1 and CB2. Their role is to act as access points for cannabinoids (both internal and external) to interact with the ECS. This allows the endocannabinoid system to support the body in maintaining homeostasis through a range of chemical reactions. You can read more about the role of the endocannabinoid system here.

Endocannabinoid deficiency is the belief that conditions can occur as a result of problems with the ECS. That could either be through a lack of endocannabinoids being produced by the body, or missing or defective receptors. If the body is not able to maintain the balance of its physiological systems, diseases can occur. In the cases studied so far, these diseases are usually linked to our immune system.

What research is there to support the theory of “endocannabinoid deficiency”?

Leading cannabinoid researcher Dr. Ethan Russo first proposed the concept of endocannabinoid deficiency. In a study^[2] published in 2004, Dr. Russo suggests a lack of cannabinoids may be the underlying cause of several conditions.

• Migraine

Migraine is a highly complex condition that involves signalling between different areas of the brain and several neurochemicals. The exact cause of migraine is not fully understood, although genetic predisposition is considered to be a pivotal contributor to its development. Dr. Russo’s review found examples of AEA (anandamide) being involved in serotonin production and pain modulation. High levels of serotonin are believed to contribute to migraine, which could potentially be counteracted by greater concentrations of AEA. The presumption is that a deficiency in the production of anandamide could contribute to migraine because of a lack of serotonin regulation.

• Fibromyalgia

Fibromyalgia is a chronic, long term condition that can leave sufferers in constant pain. There is currently no cure for the disease, and thus far, traditional medicine has only been able to ease symptoms. The research Dr. Russo collated suggests that “the endocannabinoid system regulates nociceptive thresholds”. Nociceptors are responsible for detecting pain and transmitting the signal to the brain to be processed.

The study went on to add that an absence of such regulation could contribute to chronic pain conditions. Much like the findings of the investigations into migraine, serotonin was again considered to have significant involvement in fibromyalgia, as did various cannabinoids. The results of the review found that “cannabinoids have demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain”.

• Irritable bowel syndrome

IBS or irritable bowel syndrome was the final condition considered to be affected by endocannabinoid deficiency as part of Dr. Russo’s review. The involvement of cannabinoids in the onset of IBS was believed to be along the same lines as both migraine and fibromyalgia. Serotonin was thought to play a part, as IBS sufferers have been shown to have increased levels of serotonin in their blood. However, this wasn’t the case for all forms of IBS.

All three conditions come back to the assumption that serotonin plays a crucial role in their development. Therefore, by controlling or manipulating levels of serotonin, it would be possible to develop treatments. Cannabinoids would naturally form a key part of this treatment because of the influence they have on critical endocannabinoids like anandamide.

Dr. Russo concluded that “underlying clinical endocannabinoid deficiency may be suitably treated with cannabinoids medicines”. The investigation also clarified that far more research needed to be conducted to understand the concept of endocannabinoid deficiency fully.

How could CBD help tackle endocannabinoid deficiency?

While the theory of endocannabinoid deficiency may be grounded in scientific studies, none of them pinpoints how the condition (if proven to be legitimate) could be treated. The exact role that cannabinoids would play has yet to be determined. Based on current research, there are some assumptions we can make, using the idea that anandamide production is fundamental to reducing CECD-based diseases.

In the case of CBD, it has shown the ability to inhibit the FAAH enzyme^[3]. Fatty acid amide hydrolase (FAAH) supports the breakdown of anandamide, and is part of the reason that AEA doesn’t exist within the body for very long. If specific mechanisms or triggers could be identified, then it is possible that CBD could support treatment into the conditions outlined above. CBD has also been found to directly affect specific serotonin (5-HT1A) receptors in the brain.

The implications, if proven, are significant, but more research is needed

Although the concept of endocannabinoid deficiency was first considered in 2004, research into the topic is still lacking. The characteristics of each condition do seem to suggest an underlying link between migraine, fibromyalgia, and irritable bowel syndrome. The evidence Dr. Russo presents points to a complication with specific neurotransmitter systems to which the ECS is linked. Since the initial review took place, the theory^[4] has widened to include Alzheimer's and Parkinson's as two conditions potentially related to CECD.

If the existence of CECD were proven, it would allow researchers to develop targeted therapies, rather than relying on the information of several preclinical studies. Although a pattern may be emerging, relying on individual reviews presents many issues. Each study will have its own unique variables, and this makes pinpointing conclusive outcomes incredibly challenging. The complexity of the endocannabinoid system, and the hundreds of cannabinoids that exist, make studying CECD a problematic task requiring large-scale focus. For the millions of people living with a chronic disease like IBS or fibromyalgia, a possible treatment using cannabinoids could be part of the solution. But for now, we will have to wait for more definitive results.