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What Is Clinical Endocannabinoid Deficiency?

Researchers believe some illnesses may be explained by changes in the endocannabinoid system.

The endocannabinoid system is a wide-reaching biological system with many effects in the body. It responds to the cannabinoids in marijuana, as well as the body’s own cannabinoids, known as endocannabinoids.

The two most well-studied endocannabinoids are anandamide and 2-AG. These endocannabinoids are responsible for regulating many systems in the body, playing a crucial role in appetite, metabolism, pain, and sleep, among other functions.

The endocannabinoid system is thought to play an important role in many illnesses. Researchers have proposed that a lack of endocannabinoid system activity could play a part in certain diseases, including fibromyalgia, migraine, irritable bowel syndrome (IBS), and posttraumatic stress disorder (PTSD).

This theory is called clinical endocannabinoid deficiency theory, and it is supported by current research.

Clinical Endocannabinoid Deficiency (CECD)

Clinical Endocannabinoid Deficiency (CECD)
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Clinical endocannabinoid deficiency theory is the theory that some illnesses may be caused by an underlying deficiency in the body’s endocannabinoids.

Theories like this are not uncommon in medicine. Illnesses such as Alzheimer’s and Parkinson’s are both explained by a deficiency in specific neurotransmitters.

What is endocannabinoid deficiency?

Dr. Ethan Russo, a well-known researcher in the marijuana sphere, first proposed the theory in a 2004 publication.

He presents an argument that an endocannabinoid deficiency, or lack of endogenous cannabinoids, could explain several diseases that currently perplex doctors.

In particular, he argues that the theory could explain fibromyalgia, migraine headaches, and irritable bowel syndrome. These illnesses are linked in that they all produce pain sensitivity as a symptom, and are also “comorbid” or tend to occur in the same people.

He takes the theory one step farther by arguing that cannabinoid medicines — including marijuana — could potentially treat these illnesses.

For each of the three illnesses mentioned, Dr. Russo compiled evidence suggesting that medical marijuana was an effective treatment, further backing up his theory.

Dr. Russo published an update in 2016 which concluded that “additional studies have provided a firmer foundation for the theory, while clinical data have also produced evidence for decreased pain, improved sleep, and other benefits to cannabinoid treatment.”

What causes endocannabinoid deficiency?

A key question is how a clinical endocannabinoid deficiency would arise in the first place. Dr. Russo suggests two non-mutually exclusive alternatives.

Some people could be genetically predisposed to having a less active endocannabinoid system, leaving them vulnerable to developing certain illnesses.

On the other hand, exposure to different environmental conditions such as injury or infection could also potentially contribute.

However, there is still not a lot of research available on the topic. Dr. Russo hopes that more research will be conducted in the coming years.

Medical Conditions

Medical marijuana to help with fibromyalgia
(Photo: Shutterstock)

Studies suggest that an endocannabinoid deficiency could help explain several illnesses, including fibromyalgia, migraine headaches, irritable bowel syndrome, and PTSD.


Fibromyalgia is a painful condition affecting mostly women. While doctors don’t know much about the condition, some researchers believe it could be related to an endocannabinoid deficiency.

Studies suggest that cannabinoids can reduce pain that is similar to the pain of fibromyalgia. Other studies have shown that blocking cannabinoid receptors results in pain — meaning that an endocannabinoid deficiency could potentially cause pain like in fibromyalgia.

Additionally, many people report that the cannabinoids in marijuana are helpful as a treatment for fibromyalgia.


Migraine headaches are extremely painful and can often disable a patient for days at a time.

Migraines are associated with changes in the neurotransmitter serotonin. The endocannabinoid system and the serotonin system are strongly linked, leading researchers to propose that migraines result from an endocannabinoid deficiency.

Researchers believe cannabis could be an effective treatment for migraine, because it has a unique set of effects on the brain that make it an “ideal treatment” for the condition.

Irritable Bowel Syndrome

IBS is a condition that causes diarrhea, constipation, and abdominal pain. It is surprisingly common, with estimates that it affects around 15% of the population.

Cannabinoid receptors are expressed in the gut, and function to regulate gastrointestinal motility, or how fast food moves through the intestines. Symptoms of IBS are related to motility that is either too fast in the case of diarrhea, or too slow in the case of constipation.

Marijuana is often used as a treatment for IBS symptoms, and has been used to treat diarrheal illness such as cholera in the past.

While there are not many studies on the link between the endocannabinoid system and IBS, researchers believe endocannabinoid deficiency theory could help explain the disorder.


A 2013 study found that endocannabinoid levels were reduced in PTSD patients, but not controls.

The researchers measured blood levels of 2-AG and anandamide in people closely affected by the 9/11 attacks on the World Trade Center. They found that 2-AG levels were significantly reduced in those who met diagnostic criteria for PTSD, but not in those who did not.

This supports the theory that PTSD could be related to a clinical endocannabinoid deficiency.