Signs of Endocannabinoid Deficiency

Understanding Endocannabinoid Deficiency requires a basic knowledge of human body’s endocannabinoid system (ECS).

ECS is a cell communication mechanism within the human body. It is a complex system responsible for regulating a range of major body functions, including sleep, memory, reproduction, hunger and mood.

Endocannabinoid Deficiency occurs when the efficiency of the ECS is affected. The theory of CED or Clinical Endocannabinoid Deficiency was first put forth by Dr. Ethan Russo.

According to Dr. Russo, many medical conditions are a result of deficiencies in the body’s neurotransmitter systems (messaging systems that help the nervous systems communicate with the rest of the body). Dr. Russo suggests that increasing the activity of the ECS through the use of cannabinoid agonists can help address many health issues.

What Happens when there is Endocannabinoid Deficiency

The ECS has 3 key components: cannabinoid receptors, enzymes and endocannabinoids.

  • Endocannabinoids are molecules of natural chemicals produced within the body. They are similar to chemical compounds called cannabinoids produced by cannabis sativa plant. THC (tetrahydrocannabinol) and CBD (cannabidiol) are the most prevalent and popular forms of cannabinoids found in cannabis sativa.

Two key types of ECS endocannabinoids are 2-AG or 2-arachidonoylglycerol and Anandamide (AEA).

  • The body has cannabinoid receptors throughout. Receptors serve as a binding site for endocannabinoids. Binding of endocannabinoids to these receptors transmits relevant signals to the ECS and appropriate action is taken by the system.

CB1 and CB2 are key receptors. When endocannabinoids attach themselves to these receptors, signals for functions such as pain reduction, mood improvement, and appetite are triggered. CB1 receptors are located in the CNS or the Central Nervous System. CB2 receptors are found in the peripheral nervous system.

  • Enzymes clear endocannabinoids that have completed their purpose, from the body. The two key enzymes in the ECS are fatty acid amide hydrolase, responsible for clearing AEA, and monoacylglycerol, which targets 2-AG.

The ECS is responsible for several key functions in the human body. While ECS is present in all humans, the degree of efficiency varies for each. Every individual has his/ her unique ECS tone. This tone is responsible for the endocannabinoid deficiency experienced by an individual. In such people, the ECS remains less activated.

An individual may experience endocannabinoid deficiency due to multiple reasons; Genetic issues, medical conditions, and injury, can result in deficiency.

How Does Endocannabinoid Deficiency Manifest?

This deficiency can express itself internally in many ways:

  • Endocannabinoids may be high or low in quantity
  • Metabolites may occur in low or high levels
  • Excessive or inadequate cannabinoid receptors
  • Desensitization of cannabinoid receptors (receptors become less responsive)

External Signs of Endocannabinoid Deficiency

There are some key body signs that could indicate CED. Dr. Ross explains that there are no specific tests to diagnose CED. But he associates CED to a hyper-sensitivity to pain. People with the conditions explained below experience them in the first place because of a heightened sensitivity to pain. Pain that is normal for others tends to become extreme for people with CED.

Irritable Bowel Syndrome (IBS)

IBS is characterized by irregular and uncomfortable bowel movements, pain in the gastrointestinal region, and spasms. Diarrhea and constipation are common symptoms of IBS. Food allergies, overeating and anxiety are some known reasons of IBS.

But IBS could be a reason for CED. ECS is closely associated with certain gastrointestinal (GI) tract functions. ECS regulates gut inflammation, GI secretion and GI propulsion. This close association is an indication that CED could be a possible reason for IBS.

study involving the examination of muscle fibers from colonoscopic biopsy reports supports the association of CED with IBS. This study showed that anandamide (AEA) influenced colon contractions. The study authors opined that the role and function of the ECS was especially significant when the gut gets inflamed or suffers a disease.


Headache, nausea, and heightened sensitivity to light and sound, are some symptoms of migraine. There are multiple factors that connect migraine with CED:

  • Hypersensitivity to sound and light is an indication of ECS association. Sensory control is a function of the ECS. A diminished capability could possibly be due to an impaired ECS.
  • Anandamide, the endocannabinoid in the ECS, can produce serotonin receptor response. This enzyme function aligns with the drug profile usually recommended for migraine patients.


  • Anandamide is also known to produce an inhibitory action against trigeminovascular system. This system is activated during migraine attacks. Reduced levels of anandamide in the body could be encouraging the activation of the trigeminovascular system.
  • A study by scientists at Italy’s University of Perugia showed that anandamide levels in migraine patients were significantly lower than in others.
  • People with migraine respond positively to the use of cannabis. In a study of migraine patients, those (85.1%) that used cannabis witnessed a decrease in migraine frequency (from 10.4 to 4.6 monthly attacks).
  • Higher quantity of FAAH or fatty amidohydrolase were seen in the platelets of migraine patients. These enzymes clear anandamide after it serves its purpose. So, high levels of this enzyme could denote reduced action of anandamide, leading to lower pain-withstanding capability in patients.
  • Genetic effects such as those where the trigeminovascular function is altered.


People with this condition suffer from chronic pain of the entire body. Exertion increases the pain. Currently, there are no specific tests to diagnose this condition.

The lower threshold to pain is what associates this condition to CED. In patients whose spinal cord showed lowered endocannabinoid function, a heightened sensitivity to pain was observed. Since the role of endocannabinoids is to decrease pain sensitivity, a lack could indicate reduced ECS function.

study of endocannabinoid levels in people with fibromyalgia showed increased levels of specific endocannabinoids. Study authors attributed the increased levels to metabolic asymmetry. Thus, fibromyalgia could be associated with an imbalance in the ECS.

Preliminary studies show that use of cannabinoids from cannabis improved symptom management in fibromyalgia patients.

Other Signs of CED

There are other conditions that Dr. Russo associates with CED:

  • Nausea caused due to motion sickness has been associated with reduced levels of anandamide.
  • Impaired functioning of the ECS has been associated with anxiety, multiple sclerosis, major depression, PTSD and Huntington’s disease. In patients with schizophrenia and Parkinson’s disease, it was found that the levels of anandamide were low.
  • In PTSD patients, levels of anandamide are lower. This can reduce a patient’s ability to recover from PTSD because ECS’ role in fear extinction mechanism is reduced.
  • CED could also be associated with autism. The genes linked to the condition have also been linked to ECS function. In addition, it has been found that autistic children have lower levels of endocannabinoids in their bodies.

In Conclusion

Dr. Ross’ findings came out in 2004, but more research is needed to reach conclusive results regarding CED. Cannabis treatment may work in certain cases as cannabinoids such as THC and CBD in the plant help activate the ECS. It is important to consult a doctor specializing in cannabinoid medicine to understand the next step in case you feel you have CED.















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