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Clinical Endocannabinoid Deficiency

By December 3, 2020 January 22nd, 2021 No Comments
EducationCBD Wellness
Danodan Hemp Flower CBD Shot for Clinical Endocannabinoid Deficiency

What do migraines, fibromyalgia, and irritable bowel syndrome have in common? Some researchers believe they could all be caused by clinical endocannabinoid deficiency.

What is Clinical Endocannabinoid Deficiency?

Clinical endocannabinoid deficiency (CED, also known as CECD) is a condition in which our endocannabinoid system (ECS) is not functioning properly. Typically, researchers believe that CED is the result of a reduced or imbalanced function of our ECS.

Think of CED as similar to an imbalance in our gut microbiota, or microbiome. Our microbiome is made up of trillions of beneficial bacteria cells that live in our large intestine, and they play a crucial role in our health. Sometimes the composition of our microbiome is thrown out of balance. This imbalance can affect us in many ways, from our digestion to our mental health.

This is similar to what happens in CED. Remember that our ECS is comprised of two main endocannabinoids – AEA and 2-AG – and two main receptors – CB1 and CB2. CB1 receptors are found mainly in our central nervous system (brain and spinal cord), while CB2 receptors are found throughout the rest of our body on organs and in our immune system.

AEA and 2-AG carry signals to receptors around the body. These signals regulate many functions throughout the body, from neurotransmitter production to digestion. If there is an imbalance between these different components of our ECS, it can affect our ability to remain in a state of homeostasis, or balance.

How can I support my body against CED?

Remember how we likened CED to an imbalance in our microbiome? Well, just like we eat foods rich in pre- and probiotics to help our microbiome, we can also support our ECS with plant-based cannabinoids and also through lifestyle.

Of course, one of the main sources of plant-based cannabinoids is from cannabis. Medicinal use of hemp and cannabis goes back thousands of years. Even in recent history, from 1843 until its illegalization in 1943, cannabis was perhaps the most common treatment for migraine in Europe and North America. (Russo 2016)

Now, researchers are investigating how hemp and cannabis may help support our ECS against developing CED. Cannabis compounds like THC and CBD are already well-researched and documented for their interaction with our ECS. In fact, it was in studying the effects of THC that the ECS was discovered in the first place!

THC is very similar in structure to our own endocannabinoids, and binds directly to CB1 receptors. CBD on the other hand works by supporting healthy levels of our own endocannabinoids.

So far, most studies related to CED have focused on THC. However, as Dr. Ethan Russo, one of the leading researchers in CED has made clear: “THC alone is poorly tolerated or appreciated by patients, and standardized whole cannabis extracts that contain additional synergistic and buffering components, such as CBD and cannabis terpenoids, are certainly preferable.” (Russo 2016)

In a 2015 interview, Russo gave further insight into effectively supporting a healthy ECS by including CBD along with small amounts of THC. CBD promotes natural AEA function and works to bring our own ECS into balance. Using CBD is also better-suited for symptom control because it can more easily be taken in lower quantities. CBD is also non-intoxicating, as many patients are simply seeking relief. Even more, CBD reduces the intoxicating effects of THC, especially when THC levels are low in the first place.

Danodan Hemp Flower CBD Shot for Clinical Endocannabinoid DeficiencyDanodan’s Hemp Flower CBD Shots contain the full spectrum of hemp compounds for real, whole support of your ECS. Yes, our products contain CBD and a trace amount of THC (well below the federal limit). They also contain other hemp cannabinoids, terpenes, flavonoids, and beneficial plant compounds.

In addition to cannabis, other plants contain different cannabinoids that can support your ECS. Check out this article or this article for more information.

Also, regularly doing low-impact aerobic exercises like brisk walking or jogging, and a diet rich in pre- and probiotics help support our ECS as well.

At this time, researchers are unsure about how CED develops in our bodies. The cause of CED is likely different with every condition, and even for every individual. That is why supporting a healthy ECS every day is so important.

How was CED discovered?

CED was first hypothesized in 2004 by Dr. Russo. He realized that certain diseases, like migraine, fibromyalgia, and irritable bowel syndrome, originate in places where our ECS is particularly active in healthy circumstances. Unfortunately, Dr. Russo theorized that if our ECS function becomes unbalanced,  conditions like these can develop.

In 2004, Dr. Russo published the first article on CED. This was the first time a researcher was suggesting the link between migraine, fibromyalgia, IBS, and CED, and how medical cannabis functions as a potential treatment by supporting our ECS.

Russo drew from the fact that cannabis had long been used in traditional and even modern medicine for conditions like migraine and fibromyalgia. That information, coupled with the recent discovery of the ECS, prompted Russo to propose and research a connection between the two.

How is CED diagnosed?

Researchers and scientists are working hard to develop better ways to measure and diagnose CED. Our endocannabinoid system is very active and complex. As a result, the level of endocannabinoids fluctuates throughout the day and varies greatly in different parts of the body, making it difficult to establish a baseline.

Many of the diseases associated with CED are what are known as “diagnoses of exclusion.” What this means is that people are diagnosed with, say, fibromyalgia or IBS only when their symptoms do not fit into any other number of diseases.

These diseases also share other common characteristics:

  • They have high comorbidity, meaning people often have more than one of the diseases at the same time
  • They have subjective criteria and symptoms and are nearly impossible to ‘measure’
  • They have a high incidence of anxiety and depression amongst patients
  • For decades they were labeled as ‘psychosomatic’ by doctors, with many doubting their prevalence or questioning the severity

What diseases might be related to CED?

According to Russo, here is a list of some of the diseases that are hypothesized to be related to CED, with a brief explanation of the theoretical relation:

  • Migraine: Anandamide (AEA, one of our endocannabinoids) prevents release of compounds that cause blood vessel dilation in the dura matter (brain); light and sound hypersensitivity are characteristic of an imbalance in the central nervous system, which is influenced by the ECS.
  • Fibromyalgia: hypersensitivity to pain that can wander around the body point to a decreased function in the central nervous system by way of the ECS; in studies, increased endocannabinoids reduced pain sensitivity.
  • IBS: Gastrointestinal propulsion (movement), secretion, and inflammation are all known to be moderated by the ECS.
  • Motion Sickness: Decreased levels of AEA and 2-AG were observed in the blood
  • Multiple sclerosis: Decreased levels of AEA and 2-AG were observed in the cerebrospinal fluid.
  • Huntington’s Disease: dramatic reduction in CB1 receptors in the brains of those who had died from HD; mouse models of HD have shown widespread impairment of ECS function.
  • Post-Traumatic Stress Disorder (PTSD): Very low 2-AG blood levels in survivors of the World Trade Center attacks, especially those with direct exposure. Also a negative relationship between AEA levels and PTSD symptoms.
  • Major Depression: No longer viewed as a failure of neurotransmitters, but a result of a diminished ability of the central nervous system to repair and heal, along with inflammation, all of which point to ECS deficiency.

Of course, all of this research and information is new and continually changing. In fact, these ideas have yet to be widely assimilated into modern medicine. Fortunately, with the ongoing research by Dr. Russo and others, we continue to learn more about the importance of supporting a healthy ECS.

Below we have the list of sources that were used in compiling this article. Please feel free to read the articles yourself and share them with your healthcare practitioner!


These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.

Russo EB. Clinical Endocannabinoid Deficiency Reconsidered: Current Research Supports the Theory in Migraine, Fibromyalgia, Irritable Bowel, and Other Treatment-Resistant Syndromes. Cannabis Cannabinoid Res. 2016 Jul 1;1(1):154-165. doi: 10.1089/can.2016.0009. PMID: 28861491; PMCID: PMC5576607.

Smith SC, Wagner MS. Clinical endocannabinoid deficiency (CECD) revisited: can this concept explain the therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2014;35(3):198-201. PMID: 24977967.

Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):31-9. PMID: 15159679.

Ethan Russo: Endocannabinoid Deficiency & Medical Cannabis. Interview. 2015 Jun 17. Available at: