Broadly speaking, we all tend to agree that eating well, staying hydrated, keeping physically and mentally active, and managing stress are solid building blocks for overall health. Many of us add in vitamins and supplements, and make other tweaks, too, to perform better in different ways. But even with all of our healthy-lifestyle bases covered, aging and other factors mean that our health can still deteriorate.

With the discovery of the endocannabinoid system (ECS) and the proliferation of a number of common diseases, some researchers are now citing the possibility of an ECS deficiency as responsible for some of today’s most common health problems. Readers might find it somewhat surprising to learn that there are in fact cannabinoids present in human breast milk, which tells us that these compounds are essential for optimal vitality in infants. As we mature, our bodies continue to produce endocannabinoids. If this process is deficient in some way, our ECS cannot work properly, leading to a host of imbalances.

The ECS is one of the largest neural signaling systems in the body. In 2004, Dr. Ethan Russo suggested that a compromised ECS can lead to what he coined Clinical Endocannabinoid Deficiency (CED), a condition characterized by a group of symptoms that occur when there isn’t sufficient ECS signaling, or signaling is out of balance. Russo, an esteemed neurologist who is also now the medical research director at Phytecs (a biotech firm specializing in potential ECS therapies), hypothesized that all humans have an ECS “tone” that reflects their levels of endocannabinoids anandamide and 2-AG, their metabolism, and their proportions with respect to each other. If these levels are deficient or heightened, or if there are problems with the ECS receptors, diseases marked by chronic pain, immune system dysfunction, fatigue, mood imbalances, and digestive/GI issues can manifest. Russo looked at a decade’s worth of objective evidence to arrive at his hypothesis. His abstract states:

“Medicine continues to struggle in its approaches to numerous common subjective pain syndromes that lack objective signs and remain treatment resistant. Foremost among these are migraine, fibromyalgia, and irritable bowel syndrome, disorders that may overlap in their affected populations and whose sufferers have all endured the stigma of a psychosomatic label, as well as the failure of endless pharmacotherapeutic interventions with substandard benefit. The commonality in symptomatology in these conditions displaying hyperalgesia [meaning heightened sensitivity to pain] and central sensitization with possible common underlying pathophysiology suggests that a clinical endocannabinoid deficiency might characterize their origin.”

It’s worth noting that an excess of endocannabinoids can also be harmful, and has been linked to obesity, metabolic syndrome, and liver fibrosis. But for the purposes of this article, we are focused more on deficiency as it marks the cluster of CED symptoms. The most concrete evidence of CED has been found in migraine patients. By assessing endocannabinoid levels in their cerebrospinal fluid as part of an Italian study that took place after Russo’s CED review paper was published, a deficiency was indeed confirmed. In addition, it has been shown that ECS receptors are directly affected by low endocannabinoid levels in the body, with many anandamide receptors located in the periaqueductal gray matter locus in the brain, which is sometimes referred to as the “migraine generator.” This partly explains why CED can be so closely linked to migraines.

Why do imbalances and deficiencies in the ECS develop? Unfortunately, the Western lifestyle seems to have a lot to do with it, and genetics can play a key role as well (this is still being studied). But people who deal with the CED cluster of conditions can be proactive in rectifying ECS signaling and homeostasis. They can eat more foods that help to improve the “tone” of the ECS, like omega-3 rich fish, or by taking omega-3 supplements. They can also consume phytocannabinoids, which can help to restore balance to the ECS. There are new discoveries around plant-based foods that can help to boost the ECS, but the most abundant source of cannabinoids is, of course, cannabis. Because of the unique way in which CBD interacts with the ECS receptors, it is now thought that regular CBD supplementation can have a corrective effect on the ECS in people suffering from the CED “cluster” of diseases. In an interview with Project CBD Ethan Russo explains this in a bit more detail:

“Cannabidiol is an endocannabinoid modulator, in other words, when given chronically it actually increases the gain of system [sic], which is, at its core, a homeostatic regulator. To explain that: homeostasis is a state of balance. Many diseases interfere with a balance in a given system and if we can bring that balance back to where it should be there’ll be improvement in the overall condition. This is one reason that cannabidiol is such a versatile medicine because so many disorders operate on that kind of level. So, if there’s too much activity in a system homeostasis requires that it be brought back down. If there’s too little, it’s got to come up. And that’s what cannabidiol can do as a promoter of endocannabinoid tone, we call it.”

A 2014 review by scientists S.C. Smith and M.S. Wagner backs up Russo’s theories, and concludes: “Subsequent research has confirmed that underlying endocannabinoid deficiencies indeed play a role in migraine, fibromyalgia, irritable bowel syndrome and a growing list of other medical conditions. Clinical experience is bearing this out. Further research and especially clinical trials will further demonstrate the usefulness of medical cannabis. As legal barriers fall and scientific bias fades this will become more apparent.” Russo also wrote a follow-up to his original review, in 2016.

New screening techniques are being developed to detect ECS issues and evaluate for CED. What’s becoming increasingly clear is that the proper balance of endocannabinoids and the ECS, and the discovery of CED, might hold innovative solutions to many hard-to-treat chronic health problems where neurotransmitters and homeostasis are implicated.



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