What is Clinical Endocannabinoid Deficiency?

woman suffering from clinical endocannabinoid syndrome

Could it be too little or too much action within the endocannabinoid system is an underlying cause of illness? Could increasing action in the endocannabinoid system, then, be an effective treatment for conditions such as migraines, fibromyalgia, irritable bowel syndrome (IBS), among others? Such an idea is the basis of Clinical Endocannabinoid Deficiency. Here is what you need to know:

Emerging Evidence Supports The Theory

From our current understanding, the endocannabinoid system aids various organs, bodily systems, and internal processes to remain in working order, contributing to homeostasis and healthy living. As a unique condition, Clinical Endocannabinoid Deficiency was first proposed in 2001 by Dr. Ethan Russo.
In 2004, Dr. Russo published an expanded, formal report on his studies and scientific findings, purporting it may be possible to remedy various conditions in which current treatments are ineffective in a portion of individuals.

In the years since it’s publication, other notable research has been conducted, many with data seeming to overlap with several of Russo's works. In 2016, Dr. Russo released an update to his findings, which incorporated such new findings.

The idea of Clinical Endocannabinoid Deficiency has far-reaching implications, opening a wide variety of possible treatments. Research on the endocannabinoid system has gained momentum as an increasing number of US states revise their marijuana laws. Many questions and mysteries still exist, likely a result of friction between state and federal marijuana laws.

Research funding, of course, is another barrier.

The Feds Undermine Research on Cannabis

Cannabis is a Schedule I narcotic under the Controlled Substances Act – the same tier as heroin. Oddly, however, methamphetamine and cocaine are Schedule II.

The federal restriction remaining fully in place on marijuana cultivation, possession, and use undermines the ability of researchers in the US to access grants and other funding typically available to researchers and pharmaceutical manufacturers. With limited research capabilities, large studies on the plant have not been conducted in the volume necessary to get a uniform scientific understanding. It is this writer's opinion such action is largely against the benefit of society.

In 2017, the National Academy of Sciences released a 300+ page meta-analysis of research evidence highlighting the various conditions marijuana is suggested to have therapeutic value in treating. Compounded by the legal aversion to cannabis in the US for the majority of the last century, many of the 10,000 studies included in the analysis were found to be flawed, misleading or unable to be replicated.

There is good evidence marijuana can help treat a number of illnesses, though further research needs to be conducted.

Clinical Endocannabinoid Deficiency (CED) Basics

That is not to say we are unable to make data-based decisions using research and experimentation; our understanding of how cannabis interacts with the body is fairly in-depth. For instance:

Expanding upon the opening of this article, the endocannabinoid system (ECS) is a network of neuronal connections throughout the brain, central, and peripheral nervous systems. Everywhere from the skull to the feet. The ECS has unique connection sites in the body where cannabinoids from marijuana use can readily attach. This is how cannabis produces its many psychoactive and/or therapeutic effects on the mind and body.

The endocannabinoid system also responds to several neurotransmitters – the electrochemical messengers of the body. Two in particular: anandamide and 2-arachidonoylglycerol (2-AG for short) are what is known as endogenous cannabinoids, but may also be referred to as endocannabinoids themselves. Both anandamide and 2-AG bind easily to receptors within the endocannabinoid system.

Receptors within the ECS are broken into two groupings: CB1 and CB2 receptors.

In those suffering from Clinical Endocannabinoid Deficiency, as defined by Dr. Russo's work, a lack of endogenous cannabinoids such as anandamide or 2-AG may contribute to the development of a number of medical conditions, often capable of reducing an individual's quality of life.

Dr. Russo focused his research of Clinical Endocannabinoid Deficiency on three conditions. Dr. Russo notes utilizing cannabinoids from cannabis and endogenous cannabinoids could possibly be the answer to many treatment-resistant conditions. It is thought, if functioning at optimum levels, the healthy function of the ECS may hold numerous other medical answers and benefits.

Dr. Russo studied fibromyalgia, migraines, and irritable bowel syndrome, given to a somewhat similar basis of mechanism among all. Here is what was observed in the data:


Fibromyalgia affects millions of people, causing pain, tenderness, fatigue, and a variety of other less favorable symptoms. The idea of Clinical Endocannabinoid Deficiency being a contributing factor to the cause of fibromyalgia stems from Dr. Russo's 2004 paper. Russo explains:

"Cannabinoids have… demonstrated the ability to block spinal, peripheral and gastrointestinal mechanisms that promote pain in headaches, fibromyalgia, IBS and related disorders."

Put simply, there is good evidence the ability of cannabinoids from cannabis such as anandamide, which is produced internally, may be an effective treatment of Clinical Endocannabinoid Deficiency. Anandamide, among other cannabinoids, therefore may have the potential to lessen the symptoms of fibromyalgia and the frequency the condition manifests.

Irritable Bowel Syndrome (IBS)

As mentioned above, cannabinoids such as THC, CBD, and endocannabinoids may block spinal, peripheral and gastrointestinal mechanisms promoting pain.

Good news for those suffering from IBS.

"To summarize, GI propulsion, secretion, and inflammation in the gut are all modulated by the ECS, providing a rationale for cannabinoids as treatment candidates for IBS," writes Dr. Russo, referring to the wide influence the endocannabinoid system has on motility in the GI tract.

It could, therefore, be logical to assess a person suffering from Clinical Endocannabinoid Deficiency and IBS may receive significant relief by utilizing cannabis medicines.


The relationship between Clinical Endocannabinoid Deficiency and migraines, as noted by Dr. Russo, reflects a relationship between the endocannabinoid system and serotonin release.

"The possible relationship of migraine with the ECS is highlighted by numerous findings. Anandamide produced serotonin receptor responses consisting of 89% potentiation of 5-HT1A and 36% inhibition of 5-HT2A,41. [These] findings… have been associated with profiles of effective pharmacological migraine interventions that would seem to support respective activity in acute and chronic migraine (CM), respectively."

If reduced, Dr. Russo suggests anandamide, one of the two primary endogenous cannabinoids, is a potent activator of specific serotonin receptors, while also blocking action at others. As a result, using a cannabis product may be effective in the treatment of migraines. Such action is thought to be effective by interrupting the hypersensitivity to light and sound associated with migraines, while slowing the anxiety and pain signaling.


  • Clinical Endocannabinoid Deficiency (CED) affects everything from the brain to the nervous and gastrointestinal systems. 
  • More research is needed on CED, particularly as a means of lowering the risk of other medical conditions.
  • Both endocannabinoids such as anandamide and 2-AG and cannabinoids introduced into the body from cannabis use have the potential to treat Clinical Endocannabinoid Deficiency.
  • The receptor sites and basis of action of each cannabinoid, endogenous or from the cannabis plant, vary. 
  • Different neurotransmitter pathways are activated with anandamide than with THC, making some cannabinoids better for pain and others for GI disorders. 
  • Interaction of cannabinoids at serotonin receptors may help interrupt signals producing light and sound sensitivity in people with migraines.  
  • Cannabinoids can help restore the endocannabinoid system to normal regulation – a state known as homeostasis.

Clinical Endocannabinoid Deficiency is potentially more common than we know. As Dr. Russo has demonstrated, cannabinoids may be an effective therapy in conditions like migraine, IBS, and fibromyalgia. By contributing to homeostasis, normal functioning of the endocannabinoid system can set in motion is a number of biological processes. Many may help lessen symptoms of numerous chronic, acute illness or conditions.