Fibromyalgia, Migraines & The Science Of Clinical Endocannabinoid Deficiency

A theoretical syndrome, clinical endocannabinoid deficiency, could provide new insight into painful conditions suffered by millions.

Scientific advancements have helped us to find working treatments for countless debilitating conditions. However, there are some illnesses that continue to prove notorious and mysterious, with no known causes or cures. Research into the endocannabinoid system (ECS), a network in the body influenced by plant-derived cannabinoids, has provided medical experts with a fresh perspective on ailments such as fibromyalgia, irritable bowel syndrome (IBS) and migraines.

Dr Ethan Russo, a professional neurologist and cannabis researcher, first published the concept of a spectrum disorder in 2004. He first began working on the idea of dysregulation in the ECS in 2001. Both doctors and patients have noticed that cannabis and CBD oil seem to benefit people with these conditions. Russo has proposed that the effectiveness of cannabinoid medicine in the trio of aforementioned conditions can be explained by Clinical Endocannabinoid Deficiency (CECD).

A white paper cutout of a human head, missing a puzzle piece shaped hole, sits on a wooden surface. The puzzle piece, colored red, sits nearby. Though still theoretical, clinical endocannabinoid deficiency could be a common contributor to numerous conditions, from fibromyalgia to migraines.
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Though still theoretical, clinical endocannabinoid deficiency could be a common contributor to numerous conditions, from fibromyalgia to migraines.


For the ECS to function efficiently, the body must produce endocannabinoids (naturally occurring, cannabis-like chemicals) such as anandamide (AEA) and 2-Arachidonoylglycerol (2-AG).

However, studies have found that some people have lower endocannabinoid levels than others, which brings about health complications. There is an increasing body of clinical research which shows anxiety to be associated with reduced anandamide levels, and major depression to be linked with reduced 2-AG levels. When the body is unable to produce endocannabinoids in the concentrations required, chemical imbalances occur, which leads to illness.

Cannabinoid receptors interact with both endocannabinoids and cannabinoids, with the plant-derived compounds able to mimic endocannabinoids or otherwise influence them for ECS regulation. Therefore, it is logical that a cannabinoid treatment could effectively remedy CECD.

Russo’s latest significant update on his CECD research came in 2016, with a paper that continued to build on the concept, incorporating available clinical evidence. This followed an earlier 2008 release.


Medical researchers have been unable to come up with a definite cause for fibromyalgia. Patients suffer from an array of debilitating symptoms that have a significant effect on quality of life. These symptoms include chronic deep muscle and tender point pain, impaired cognitive function (or “fibro fog”), headaches, sleeping difficulties and restless leg syndrome. According to the Anxiety and Depression Association of America, 20 percent of fibromyalgia patients experience one of or both of these mental health disorders. Typically, this is a result of the pain and fatigue caused by the condition. In 2011, a study found that CBD could reduce anxiety beyond placebo levels, with patients given a 600mg dose administered via CBD capsules.

Moreover, several symptoms of fibromyalgia are indicative of ECS dysregulation — for instance, inflammatory conditions occur due to problems with immune system response, which is modulated by the ECS and specifically the CB2 receptor. Studies have also found that serotonin levels are affected in fibromyalgia patients, which may be noteworthy considering CBD is an agonist of the 5-HT1A receptor.


Around 39 million Americans are affected by migraines, according to the Migraine Research Foundation. Migraines can cause dizziness, nausea, numbness or tingling in the face and other unpleasant symptoms. Research has shown that migraine sufferers have “statistically significant” differences in anandamide levels in cerebrospinal fluid, which is found in the brain and spinal cord.

A woman clutches her head in pain, as if suffering from a migraine. Migraine sufferers have been shown to have lower levels of anandamide, a naturally occurring chemical found in all people that's similar to those found in cannabis and hemp.
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Migraine sufferers have been shown to have lower levels of anandamide, a naturally occurring chemical found in all people that’s similar to those found in cannabis and hemp.

Russo found that endocannabinoid system changes could help to alleviate migraines in his 2004 research. The main finding was that anandamide, a key neurotransmitter in the ECS, heightens the effectiveness of the 5-HT1A receptor while inhibiting the 5-HT2A receptor. This could help with treating acute migraines and as a preventative treatment. Furthermore, the results showed that several cannabinoids exhibited anti-inflammatory properties and dopamine-blocking effects.

The light and sound sensitivity that results from migraines may be due to an overactive nervous system. The ECS is renowned for regulating such imbalances (Russo, 2016). Some have suggested that the root cause of migraines can be traced back to the trigeminovascular system, which brings blood to the brain. Studies have shown that endocannabinoids can influence this system. Migraines and cluster headaches may be best managed with a treatment that is an agonist of the CB1 receptor.

In the case of migraines, one study found that while a CBD and THC treatment was not necessarily more effective than existing anti-migraine treatments, the side effects were significantly reduced.

Fascinatingly, cannabis was a common treatment for migraines in Europe and North America from the mid-1800s until the 1940s, a time when the herb was being prohibited around the globe.


As governments all over the world look into the benefits of medical cannabis, the number of high-quality studies being carried out in clinical settings is sure to increase.

With time, we should get an in-depth look at the potential of cannabinoids as a treatment for fibromyalgia, migraines and other illnesses. As our understanding of the ECS deepens, we may learn more about the wide-scale implications of dysfunction in the system.

A gloved scientist with a vial of CBD and a hemp leaf. 'Full spectrum' extracts contain more cannabinoids, terpenes, and other beneficial chemicals found in hemp & cannabis.
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A gloved scientist with a vial of CBD and a hemp leaf. ‘Full spectrum’ extracts contain more cannabinoids, terpenes, and other beneficial chemicals found in hemp & cannabis.

Furthermore, more research needs to be done on the possible interactions cannabinoids have with receptors outside of the ECS and the effects this may have on the body.


It’s essential to bear in mind that the work of Dr Russo and others on CECD is at the forefront of cannabis science, and we still have plenty to learn about the endocannabinoid system, the effects of its dysregulation, and the genuine potential of cannabinoid-based medicines for treating notoriously complicated conditions such as fibromyalgia.

However, the theory has certainly fleshed out since 2004. There are studies that suggest medical cannabis and CBD can have a therapeutic effect for certain conditions. But in his 2016 paper, Russo noted that contradictions in CECD research were common. He reported that excessive levels of endocannabinoids could also be damaging for health, potentially leading to obesity and hepatic fibrosis.

Regulation of the endocannabinoid system is probably not be as simple as taking a dose of CBD or THC. There are dozens of cannabinoids in hemp and cannabis. Research indicates that whole-plant tinctures can be preferable to isolates of just one chemical. Given that endocannabinoid imbalances differ from patient to patient, the ideal medication for these imbalances may vary too. Perhaps someday, these treatments may be more be tailored to fit a person’s exact illness.

It’s clear we still have a lot more to learn about the endocannabinoid system before we can fully understand how it contributes to our health and well-being.


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  • Cora huges says:

    Fibromyalgia attacked my mother body more than 3 years ago after her knee surgery. She has been in a wheelchair for about six months, and she used a cane for another six months. She  did not even know how to walk anymore. We fought the fibromyalgia with a lot of pain pills and tears not until we had to give a try on natural formulas, we purchased a herbal treatment from  which help her a lot and bring her back to normal again, the herbal formula reverse the symptoms dramatically and she’s totally free from the Fibromyalgia that cost her pains for ages .

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