Understanding Clinical Endocannabinoid Deficiency (CECD)


In this article we’ll cover Clinical Endocannabinoid System Deficiency (CECD) background, conditions, symptoms and more.

Here’s an overview in case you’d like to jump ahead:

What is Clinical Endocannabinoid Deficiency?

Clinical Endocannabinoid Deficiency (CECD) is a term coined by Dr Ethan Russo, a neuropharmacologist, in the early 2000s. The theory behind CECD is that many disease states are related to a deficiency of various neurotransmitters. For example, depression might be related to low serotonin, Alzheimer’s disease might be related to low acetylcholine, and Parkinson’s disease might be related to low dopamine levels.

In the same way, there are likely diseases or syndromes related to a low functioning endocannabinoid system (ECS)

The endocannabinoid system is involved in various processes within the body, including regulation of pain, sleep, stress, mood, digestion, and immune function. So, if someone has a deficiency or dysfunction of the ECS, they would start manifesting symptoms related to these core pillars of the endocannabinoid function.

The hypothesis was that patients with CECD would have a syndrome of specific symptoms that were not better diagnosed by pathogenic markers, tests or lab studies and did not have a clear diagnosis. They would also often have an overlap between comorbid states.

What conditions are related to CEDC and why?

The following conditions are related to CECD:

  • Irritable bowel syndrome
  • Fibromyalgia
  • Chronic migraines
  • Endometriosis
  • Anxiety
  • Depression
  • PTSD

The first conditions were IBS, fibromyalgia and chronic migraines because, at the time, we didn’t have a clearly defined understanding of why the conditions existed, and they have similar symptoms. Each of them has stress as a significant trigger. There is a pain element out of proportion to any tissue damage or pathological process. They came in clusters and often co-existed in the same patients. Other conditions such as Parkinson’s disease, multiple sclerosis, Huntington’s disease and motor neuron disease all have an implication of the endocannabinoid system in the development and worsening and progression of their disease status.

Since then, the other conditions have been added to the list of potential CECD conditions. But, whether these chronic diseases are triggered by CECD or cause ECS deficiency is yet to be determined.

However, the upregulation of the ECS in these disease states makes a significant difference to the health and wellbeing of patients with these conditions.   

Research related to CECD and related conditions:

Patients with chronic migraines have markedly lower levels of anandamide in cerebrospinal fluid.

Women with endometriosis display lower levels of CB1 receptors in endometrial tissue. Impaired ECS functioning has been suggested to lead to unregulated growth of endometriosis tissue and significant levels of severe pain.

In children with Autism Spectrum Disorder, there are notable deficiencies of anandamide, palmitoylethanolamide, and oleoylethanolamide compared to neurotypical controls.

Fluctuations in ECS tone have been observed in patients with inflammatory bowel disease and irritable bowel syndrome. One study found a genetic variation associated with colonic transit time affecting ECS metabolism in diarrhoea-predominant IBS patients. 
Research on CECD in humans is still in its early days. However, numerous studies demonstrated that rodents with a deficiency of 2-AG are more likely to display low-stress resilience and behavioural alterations analogous to mood disorders, such as increased anxiety, impaired reward pathway activation, compromised fear extinction and changes in structural plasticity.

What causes Endocannabinoid Deficiency?

There is no clear answer to what causes CECD. While research has gotten us closer to understanding CECD and related conditions, the two main factors that contribute to CECD are genetic and environmental.

Some of the genetic factors include:

  • Expression and density of CB1 and CB2 receptors in the body
  • An individual’s genetics in relation to the production of certain enzymes (ie FAAH)

The likelihood is that CECD can arise in two ways. One is with people predisposed to having an endocannabinoid deficiency and then are exposed to a stressor or trauma and develop a related condition. The second is where an individual develops a medical condition and can’t manage the condition well enough. As a result, there is a decline in the ECS’s ability to keep up with demand and the patient may then be diagnosed with CECD.

What are the signs and symptoms of endocannabinoid deficiency?

The ECS is involved in many different regulatory processes within the body. However, it’s widely known that the main role of the ECS is managing:

  • Eat
  • Sleep
  • Relax
  • Forget
  • Protect

This means that the ECS is involved in the regulation of stress, pain, and mood regulation as well as cognition, memory, digestion, inflammation, immune function and motor function.

When people develop issues with sleep, unmanageable stress, an increase in pain, IBS type symptoms, reflux or problems in any of those areas directly related to those functions, it may be a sign of a declining ECS.

How do you test for endocannabinoid deficiency?

Unfortunately, there is no test or specific way to diagnose CECD.

There is no endocannabinoid gland. Instead, the cell wall releases endocannabinoids. They act locally and are taken back inside that cell and broken down locally. And, there is no endocannabinoid deficiency blood test. So, measuring levels of endocannabinoids in the blood is difficult.

The best indicator of endocannabinoid dysfunction is increase of cell receptors. An increase of receptors shows that the body is trying to hold on to as many of the endocannabinoids that are being produced.

Without doing invasive testing such as tissue biopsies or lumbar punctures, it’s impossible to discern an endocannabinoid deficiency from pathological or laboratory processes.

Diagnosing an endocannabinoid deficiency, it will boil down to patient history more than anything else. Dr Jim Connell said:

When patients are getting health issues in multiple areas that may seem unrelated but may have a common link through the ECS processes, this is where you may begin to suspect CECD.

Let’s take an example. When treating someone with chronic pain, you’re often not just treating pain. You’re treating their pain, sleep, anxiety and aiming to improve their overall wellbeing.

The ability to potentially manage all of this with one medicine, cannabis, is what makes it such a valuable tool for you and these patients.

How do you treat endocannabinoid deficiency?

When treating the ECS, the goal is to upregulate and tonify the system to help get balance back to the body. The two main ways to do this are:

  1. Lifestyle and nutrition
  2. Cannabis

Lifestyle and nutrition

Nutrition

It’s crucial to maintain a healthy gut microbiome. Fatty acid precursors produce endocannabinoids, so it’s essential to have the right balance of omega-3 to omega-6. 

The standard Australian or American diet has the ratio of omega-3 to omega-6 at around 1:20 and up to 1:40. The ideal ratio is 1:2.

Most omega-6 fatty acids come from our vegetable oils, fried foods and pre-packaged products. Minimise packaged and processed foods and maximise fresh foods. The goal is to increase omega-3 rich products. Omega-3 rich foods include:

  • Wild-caught fish
  • Gamey wild-caught meats
  • Pasture-raised eggs
  • Nuts and seeds (chia, flax, hemp)

The gut microbiome has a strong interaction with the body’s endocannabinoid system. So, we want to care for this critical ecosystem within our body.

Dr Jim Connell

The best way to care for your gut is to have a diverse microbiota. And, the best way to maintain a diverse microbiota is to eat a wide range of fruits and vegetables. This is because fruits and veggies contain prebiotics, the food for the microbacteria. 

Plants and spices with Beta-caryophyllene (BCP) are very good for you. BCP is a terpene that activates the CB2 receptor and can help support the ECS. Some examples of spices with BCP are:

  • Basil
  • Black pepper
  • Cinnamon
  • Cloves
  • Rosemary

Lifestyle changes

It’s best to take a holistic approach the health and lifestyle.

Research has shown that exercise can have significant benefits in supporting the ECS. However, the goal of an exercise regime should be to engage the patient in something they enjoy. 

Moderate aerobic exercise has a more substantial impact on endocannabinoid signalling than light or intense exercise. And part of the benefit of exercise is the enjoyable nature of it. So, if you’re working with a patient on an exercise regime, it’s better to create a plan with exercise that they enjoy than to ask them to do exercise they don’t really like but should be doing. 

Connection to nature, friends, and loved ones are also very beneficial in maintaining a healthy ECS. In line with connection and touch, other treatments that can be beneficial are

  • Osteopathic treatments
  • Acupuncture
  • Massage

Things where you get physical touching and connection, can help rebalance the endocannabinoid system as well. The beauty of the endocannabinoid system is that generally, the things that support it are the things that make you feel good.

Dr Jim Connell

Cannabis

Cannabis is a complex herbal medicine. While the TGA and many health professionals in Australia often focus on CBD, cannabis is so much more. And, it’s not just CBD and THC. Cannabis has minor cannabinoids such as CBC, CBG and CBN and contains terpenes, an important part of the medicine. 

Here’s a short overview of some of the parts of cannabis.

THC works similarly to the body’s anandamide as a partial agonist. So, if a patient has a CECD state which lacks endocannabinoids, adding this phytocannabinoid can help supplement the system. It’s important to note that patients don’t need to consume THC to the point where they are intoxicated. The goal is to support the system. 

People who don’t have significant ECS dysfunction and overuse THC can start suppressing or down-regulating the endocannabinoid system. So, it’s really a fine balance.

Dr Jim Connell

CBD is another very safe tool for supporting that system. CBD can reduce the breakdown of the body’s anandamide. It competes with the fatty acid-binding proteins that carry around our endocannabinoids. This means that our endocannabinoids will last in the body for longer.

Terpenes are also beneficial, as mentioned briefly in the nutrition section. Terpenes are found in abundance in cannabis. Whether from cannabis or other plants, terpenes can positively impact the ECS. Different terpenes can help improve mood, boost energy or relax people. When prescribing cannabis, it’s essential to know the dominant terpenes in the medicine to understand how the drug will affect the patient.

Conclusion

The endocannabinoid system is a biochemical feedback machine. It helps to translate external experiences into internal responses that keep our body in balance.

Nurse Cameron Roisin

When we have dysfunction or deficiencies in our biochemical messengers, the signals sent to maintain homeostasis are inhibited or cut off.  

Various tools can supplement or enhance the ECS and mitigate those potential effects. For example, making changes to diet and lifestyle can positively impact the ECS. And, there are supplements such as cannabis (phytocannabinoids), PEA or OEA.

The most important thing to remember is that it’s important to find balance in everything a patient does and the supplements and medications they may take.

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