by Seshata on 25/03/2013

What is clinical endocannabinoid deficiency?

Clinical endocannabinoid deficiency (CEDC) is a proposed spectrum disorder that has been implicated in a range of illnesses, including fibromyalgia, migraine and irritable bowel syndrome. So far, very little research has been conducted on this speculative disorder, but if it is found to exist, it could be responsible for these very common conditions as well as many related ones.

Clinical endocannabinoid deficiency (CEDC) is a proposed spectrum disorder that has been implicated in a range of illnesses, including fibromyalgia, migraine and irritable bowel syndrome. So far, very little research has been conducted on this speculative disorder, but if it is found to exist, it could be responsible for these very common conditions as well as many related ones.

Migraine, serotonin and the blood plasma platelets

Migraine is a debilitating and very common condition that affects millions worldwide

The three conditions feature common clinical and biochemical patterns that may point to underlying CEDC. Migraine is thought to be influenced by endocannabinoid function, as areas suspected to be involved with generation of migraines are also affected by cannabinoid activity; furthermore, the endocannabinoid anandamide, with its role in pain modulation and serotonin transmission, is believed to positively affect sufferers of the condition.

The biochemistry of migraine is highly complex and poorly understood, but it is known that high levels of serotonin are present during attacks. THC and its endogenous ligand, anandamide, have been shown to inhibit serotonin in high doses (although low doses may increase its production), particularly in the platelets of the blood plasma. The platelets contain the body’s highest reserves of serotonin, which is also present in the ENS as well as throughout the brain. Serotonin release from the platelets is thought to be crucial to generation of migraines, and migraine is often thought to be a disease of the blood on this basis.

Fibromyalgia and serotonin deficiency

Fibromyalgia, a pain disorder which is widely considered to be neuropsychiatric in nature, is treated with cannabis in approximately 10% of patients in the USA (either through self-medication or prescription), and has been shown to respond favourably to the synthetic THC-mimic nabilone. In a study which documented the effect of nabilone on fibromyalgia sufferers, subjects experienced significant improvement of symptoms when administered the cannabinoid. Another study demonstrated that quality of life was markedly improved in fibromyalgia sufferers that self-administered oral or smoked cannabis.

Points of hypersensitivity found in fibromyalgia

Serotonin levels in the platelets are also known to be affected in fibromyalgia, although it is thought that deficiency of serotonin, rather than over-abundance, is responsible for the sufferer’s aberrant perception of pain. This disparity is not fully understood, and is somewhat surprising given the high degree of comorbidity between the diseases: in one study, up to 63% of primary fibromyalgia sufferers also reported symptoms of migraine, in another, 22.2% of primary migraine sufferers were also found to have fibromyalgia. This disparity may be partly explained by gender differences, as none of the male migraine sufferers reported symptoms of fibromyalgia, and the latter disease is overwhelmingly experienced by women, who comprise 90% of sufferers.

IBS and the link between the brain and gut

Irritable bowel syndrome (IBS) is a common gastroenteric condition that presents as bloating, abdominal cramps and diarrhoea. It is long been suspected that there is a link between IBS and neuropsychiatric dysfunction, as the condition is often comorbid with psychiatric conditions such as anxiety, depression and PTSD; acute symptoms often arise in times of mental distress. However, as endocannabinoids are expressed in the enteric nervous system (ENS), as well as the areas of the brain affected by such psychiatric disorders, their effect may be independent.

Serotonin also plays a part in IBS, influencing gut motility (the peristaltic actions of the colon, which become “spastic” or uncontrolled during bouts of IBS), sensitivity and secretion of fluid. Interestingly, IBS-D (characterised by diarrhoea) sufferers have been shown to have increased blood serotonin levels, while sufferers of IBS-C (characterised by constipation) experience reduced levels of serotonin.

Cannabinoid receptors in the enteric nervous system

It has been demonstrated that activation of the cannabinoid receptors in the ENS decreases hypersensitivity of the gut, as well as reducing gut motility  and inflammation. Many sufferers of IBS use cannabis to alleviate their symptoms, although some report that symptoms worsened subsequent to commencing use; some even postulate cannabis as a trigger for IBS in certain individuals.

The overlap between instances of these conditions has led to the hypothesis that they are all expressions of the same underlying somatic disorder. Many sufferers of IBS also report symptoms of migraine, and up to 70% of fibromyalgia sufferers also present IBS symptoms. Many have all three, but it is not strictly necessary for all three to be present for an underlying condition to be the cause, as many spectrum disorders manifest markedly different symptoms from patient to patient, and other related conditions may be involved.

Is an underlying condition responsible?

A diagram showing the postulated causes of IBS
A diagram showing the postulated causes of IBS

The idea that a dysfunctional endocannabinoid system is responsible for this postulated somatic disorder first arose within the last few years. In 2004, the condition CECD was first proposed; researchers suggested that the high degree of comorbidity, along with the common feature of unusual cannabinoid receptor activity, pointed to an underlying disorder of the endocannabinoid system. Many known conditions can be attributed to dysfunction of a specific neurotransmitter system: Alzheimer’s is caused by deficiency of the acetylcholine neurotransmitter, and Parkinson’s by age-related dopamine deficiency. It is therefore logical to assume that deficiency of the cannabinoid neurotransmitters would also cause a specific disorder, or set of related disorders.

The relationship with the serotonin signalling system cannot be ignored when researching the possibility of CECD’s existence. Behavioural studies suggest that the effects of endocannabinoid signalling are mediated by regulation of the serotonin system: THC has been shown to inhibit serotonin release from the platelets in migraine sufferers, as well as increasing synthesis of serotonin in the brain; 2-AG and cannabidiol have demonstrated similar effects. However, the independent effects of cannabinoids on the cannabinoid receptors are thought to be the underlying cause of CECD, despite this possibly fundamental relationship with serotonin signalling.

If the existence of CECD is proven, targeted therapies can be investigated, which would pinpoint the precise nature of the deficiency and determine the appropriate ration and dosage of supplemental exogenous cannabinoids. At present, treatment of these conditions is usually through ingestion of crude cannabis extract, or through smoking, which may involve wildly different cannabinoid ratios between cannabis strains. Due to the dose-dependent effect of many cannabinoids, relief of symptoms may not be adequate with some varieties.

Comment Section

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Seth McCaslin

This is very interesting stuff, please let me know when you have more information/articles I would like to follow this story.



please send or post anything you find about the cannabinoid system and Schizophrenia. I have studied all I can and I know it can be used as an anti-psychotic with those properties in CBD. thank you.



I used raw cannabis after suffering from chronic thromboses hemorrhoids (internal and external) for 7 years. I have had multiple operations, tried many home remedies and finally got fed up and ate raw cannabis (3/4 oz w/juice) and my golf ball sized tumor shrank to nothing, only taking three days to heal. Since it is still illegal I did not get anymore and after a month it came back to its golf ball size and pain. I'm 22 and a healthy person. These symptoms (fluid, colon spasms and others) is what I experience. It's not cancer and my doctor wants to send me to another state hospital. Why can't my doctors locate the issue? They are not looking at the right system in my body, the endocannabinoid system. I would drive to CO and get enough oil to heal, if I had the resources.



Nicely done Seshata,
In my view this explanation seem to key into one of the reasons it helps halt cancer growth and heal on so many levels. Are the studies based on ingesting or vapour?


Kathy D.

I proved to the court my long list of health issues is completely related to my having a dysfunctional endocannabinoid system. I have Celiac, 2 types of Arthritis, IBS, hypokalemia, a constant state of fever, and more. Without cannabis I am bed ridden and need medication that makes everything worse and turns me into a non-functioning person. With the miracle of cannabis I can live a normal life and all my health issues become so minor as long as I eat right I have no problems. Without it I will die and nearly have everytime I have had to quit. The court watched me, it took over 2 years but the hell and damage to my body is something I am still healing from. Cannabis must be available nationwide. There are so many people like me. Please encourage your lawmakers to reverse cannabis prohibition. Educate Everyone. Lives depend on it.


Kathy D.

Thank you for writing this article!


Ronald Samudio

Several conditions may present themselves as IBS, including coeliac disease, fructose malabsorption,[5] mild infections, parasitic infections like giardiasis,several inflammatory bowel diseases, bile acid malabsorption, functional chronic constipation, small intestinal bacterial overgrowth, and chronic functional abdominal pain....--



Face book has a couple of good sites on there hemp Australia hemp Sunshine Coast
Have a look they have CBd charts n info on what's going on with hemp study's and findings
I hope you find what ur looking for.
Kindest regards


Mimi Weil

Been looking for someone that is on the same page as me. Thanks!


Anthony Pottinger

I know of several persons who suffer from IBS, regular headaches, joints & muscle pain. These are all worse or initiated by times of increased stress, anxiety, depression. This article is very interesting, these could all be one illness, namely CECD.



Sounds plausible to me. I have all three, plus PTSD, arthritis, neuropathy, diabetes, and several other diagnoses that just seem to go along with rest. I notice that smoking helps about 80 to 85% of the time, there are those times that even cannabis doesn't work.



This caught my attention!! I have every one of those problems and the pain chart for fibromyalgia was very spot on!! Please everyone help us fight for legalization/decriminalize and medicinal use!!! God Bless!!



I suffer from Crohn's, RA, Fibro, and Migraines....and major depression. If we could just get the medical community and government together to understand just a small part of the pain that we go through on a daily basis. All we want is pain relief without all of the side effects of narcotics destroying our organs.


Regina Nelson

Excellent article! This has been my hypothesis for about 2 years--but being a PhD in Ethics and Social Justice vs. Medicine made my argument fall on many deaf's good to see some validation coming forward. The key is in listening to patients and understanding how cannabis effects their symptoms--if our medical profession would stop and listen to cannabis patients the knowledge gained could lead research in many new and interesting areas!! www.CPNInstitute.Org


Marti Parsons

Kathy D. I agree 100%-although it would be even better if our government would stop trying to legislate morality-and telling adults what to do-and let us choose for ourselves. The drug war has been fought for 40 years-and we are further behind than ever-it will never be won, and it is not being fought for our benefit. As usual the government does what will benefit them, not the people who elected them and pay their salaries.



legalization is necessary in all aspects with response to social and healthy life.
no any more doubts.....



I would like to read more articles like.this related to back pain & illneses and conditions to backrelated pain, I have horrible back problems & I know this miracle serum/ plant could help myself among many others who have similar problems



Clinical endocannabinoid deficiency (C... [Neuro Endocrinol Lett. 2008] - PubMed - NCBI


joan shapiro

Lyrica is helping me with fibromyalagia. I wonder if there is any relationship between lyrica and some form of marijuana. So far I haven't found it.

Also, chronic depression can result from being in pain almost all the time, and I wonder about the link between EXCESS serotonin and the above conditions. However I did find that when I started taking Lyrica, I could stop taking Zoloft (a Serotonin re-uptake inhibitor) and still not suffer from depression. I had taken Zoloft for about 20 years.



What are CBD's?



Kathy D. can you tell us more about going to court. My son is executive Producer on a new movie and i am curious to know more about your statement. also, for everyone, the first documentary he made is free and can help you talk with Doctors and family members and you can watch it for free at


Nancy Anderson

This information just dropped into my lap! Legal in all 50 states 32000 people enrolled for free until 3/31/2014 CBD /Hemp Salve and Hemp oil Vap pen more products to come. No medical claims guys. Check it out for me I have IBS , back issues etc tried and feel relaxed and better. Just sharing with y'all


Chris C

Where do I sign up for this hemp vap pen thing your speaking of?



@Debbie: CBD is cannabidiol, which is a plant cannabinoid found in cannabis. THC is the other main component, tetrahydrocannabinol, which, when paired with CBD produces the psychotropic effect or high. There are also other cannabinoids, such as CBN, and terpenoids which are not cannabinoids but have some anti-inflammatory effects. You have to have both for not only the high but for many of the treatments in this article. CBD alone won't do the job, you have to have whole plant cannabinoids in a plant form, either smokeable or vaporizeable or edible. You can even make tinctures. Unfortunately politicians in a number of states (Utah, Wisconsin, Missouri, etc) have enacted CBD-only legislation and are trying to pass it off as "medical marijuana", which it is not. They intend to extract the CBD and throw away the THC (which, incidentally, is marketed in tablet form as Marinol). The only honestly-passed medical marijuana bills are for "charlotte's web" strain which is high in CBD and low in THC. The politicians won't admit this came from a dispensary in Colorado! Then there are the 22 states which have passed real medical marijuana bills, in which the whole plant and edibles are sold.



Not true about Marinol. It is a synthetic product.


my back hurts all the time upper back exercises

Howdy! This post couldn't be written any better! Reading through this article reminds me of my previous roommate!
He always kept talking about this. I'll send this article to him.
Pretty sure he's going to have a good read. I appreciate you
for sharing!


Tim rene

In most causes and cases,where distortion of neurotransmitters-especially seretonin,is involved-there is present a fungal and/or mold overload/infection.
The mycelium (vegetative filaments) of the fungus/mold,have taken over,grown alongside the nerve "threads",stopping and messing with the normal flow of signals.
Causing auto immune disorders,drying of the joints,penetrating the stomach wall, and mucous membranes,etc.
The phosphor in the cannabis crystal glands,renew the cells-as this is there fuel.



This could explain strokes are related to cannabis, people with migraines/RCVS are self medicating because they have an endocannabinoid deficiency. Otherwise we should be hearing deaths everyday from dabs, and see it in marinol and sativex studies since its concentrated cannabinoids.


Carlene brown

Seriously now we are saying there is a deficiency of pot in people? This is taking advantage of people with severe pain many disorders like Fibromyalgia. Pot may help some but this takes it a bit far! And you wonder why we are not taken serious by the doctors!



No, that's not what this article is saying. This article is saying that the endocannabinoid system appears to be dysfunctional in certain individuals suffering from a range of diseases that have a high rate of co-morbidity (ie they often occur simultaneously in patients). The endocannabinoid system is the system of protein receptors and their endogenous ligands (compounds that bind to the receptors and are produced by the body) that is found in humans and most other animal species. Compounds in cannabis closely resemble some of these endogenous ligands, such as anandamide and 2-AG - so closely, in fact, that they do a very good job of binding to the cannabinoid receptors. In individuals whose endogenous ligands are not produced in sufficient quantities, and who experience the above-mentioned illnesses as a result, treatment with exogenous cannabinoids (ie, those from cannabis) may help to restore the inherent imbalance and improve the symptoms of the disease.

Please, if there's anything else you don't understand, don't hesitate to ask more questions.


Jennifer Batchelder

Charlene: Actually ALL mammals produce their own cannabinoids. Cannabinoids are found in breast milk because it helps to calm the baby as well as make them hungrier so they will drink more, and allow them to gain the necessary weight they need to gain to grow and develop. We have CB receptors in the brain and in the genitalia. It has been proven that when we don't produce enough of our own cannabinoids, we must turn to plant cannabinoids. Marijuana actually lessens pains felt by the user and has been proven in many lab tests. While YOU personally may not agree with the methodology, many users of marijuana suffer from many different issues, depression, anxiety, physical pains and the usage of marijuana allows them to feel like most people do on their good days. The timber industry is the reason for the criminalization of hemp. You should really do some research before making blanket statements as you have done.


Amy Black

Was wondering if there have been any studies pertaining to this deficiency and drug addiction, in the way the receptors work. From my own experience with addiction of one of my son's, it seems that when he is sober he does not feel comfortable in his own skin.



That is an interesting question and not one that I have had the chance to research in detail. I am planning to publish and update to this article soon; if I discover anything relevant I shall include it. Make sure to check back in a month or so!




Mary K Fox

A lot of factitious somatoform disorders being mentioned here


Paula Williams

I was just reading that serotonin is used to regenerate nerve cells in the spinal cord and brain. If cannabis is capable of this it would definitely help a wide variety of conditions and injuries. As a Multiple Sclerosis sufferer who also has Fibromyalgia and Migraines I've been seriously researching cannabis and the implications of it's prohibition on the rise in autoimmune disorders. There is definitely a correlation with the removal of cannabis from society and the rise in neurological/psychiatric diseases. Great article!


Ras Ible

Very helpful article thank you!


Ethan Russo

This material is not original, and is not properly referenced or attributed. A hidden link inside the text is inadequate. Please rectify.



I'm sorry, but what on earth are you talking about? I have provided no less than 20 sources for my arguments in this article. And whatever you believe about the adequacy of links within the text (which are "hidden" how exactly?), that is the way we link to sources in articles on the Sensi blog.



I have to agree on this article and thank god science is relating the connection....I suffer from migraines,IBS and stress pain and fybromalsia....cannabis helps all three...there are even days I can wake up without one bowl attack, when its usually so swallow instead of spiting out the stuff in my mouth in the morning would set it off.


iliana bayona

please let me know if cannabidiol oil can help with my carcinoid tumor.



Without knowing more about your specific case I can't comment.


Camilla Illa Illa

Marijuana is the only thing that HAS controlled my pain related to migraine's and fibromyalgia. I'm on no pain meds other than Excedrin migraine, as needed. And this is after suffering for about 30 years, going through conventional doctor's and treatments. Cannabis should be available to everyone, to keep it illegal or unavailable, is doing a disservice to everyone. I have 2 personal friends that were cured of inoperable, terminal brain cancer, thanks to what most know as "Rick Simpson Oil."


José Sousa

A erva é cura para algumas doenças e só por isso deveria ser legalizada-: -)



Hello Seshata I have a situation that is for me very troubling. I'm a medical mmj patient and I smoke and vape. However I'd prefer to consume edibles. After several months trying every dispensary edible known to man (have not tried transdermal) the edibles have absolutely no effect on me. Regardless of quantity and method of preparation/extraction. Is it possible that I'm endocannabinoid deficient and therefore that's the reason I cannot absorb oral thc?

Also @ Karhy B do you medicate with edibles?



As a chronic migraineur for 25+ years, I found this article interesting. One point in your article that confused me though is the statement, "The biochemistry of migraine is highly complex and poorly understood, but it known that high levels of serotonin are present during attacks." In all the literature that I have ever read regarding migraine and serotonin levels, it states just the opposite; that migraines are correlated with LOW levels of serotonin, even during attacks. In an article from the American Headache Society on the subject of serotonin and headache, this is stated, "Migraine and in particular, chronic headache sufferers, tend to have low levels of serotonin, and their serotonin level goes even lower during a headache."


Can you please clarify this discrepancy? Thank you.


Charles Waller

Excellent article on the subject, but I noticed one significant lack. Cramping and constantly spastic muscles are also serious symptoms of fibromyalgia which are relieved with cannabinoid replacement therapy. When diagnosed in 1996, I was fortunate to be loaned the first edition of this book: Fibromyalgia and Chronic Myofascial Pain: A Survival Manual (2nd Edition) Devin Starlanyl & Mary Ellen Copeland. The biochemical mechanics occurring with FMS/CPS are well known, the "neuropsychiatric" description is promoted by certain interests offering compounds such as Lyrica for treatment, referring to "overactive" nerves in their advertising.
You make an important point about cannabinoid content determining therapeutic benefits. Prohibition restricts access to the enormous variety of cannabis cultivars, many of which offer enormous therapeutic benefits for chronic conditions which "mainstream medicine" fails to offer significant relief. Imagine the progress which could have been made with cannabis in the past 40 years alone, if not for federal prohibition.



Eating food high in salt and fat also trigger our bodies to produce our own endocannabinoids. What I would like to know is what would be better for our systems? Smoking actual weed, or just eating a bag of potato chips. Which method would produce the most beneficial amount of endocannabinoids in our bodies?



I have never used cannabis, but I do find it interesting that there is possibly another system in our body and that a plant exist that directly relates to that. God did create us, the heavens and the Earth. I do know that if you listen to your bodies cravings if may help. My niece craved butter and bacon fat when she was little. She has seizures, one of the dietary recommendations was to increase her fat intake. The comment I read about salt, made me think of my mom, who has muscle aches. I think if medical society focused more on foods and plants and balance of systems, we would be better off. I think we could be on to something with the Endocannibanoid system. Hope more research can be done and less restrictions can be given on a plant that may do more good than harm. I am sure, as always, it may be a fine line but we need openess to be able to address it.


Angela M

I have Fibromyalgia, Ankylosing spondylitis, gastroparesis, Hereditary Hemochromatosis, Chronic Fatigue Syndrome, PTSD, Depression, arthritis in several joints, chronic severe headaches that will go on for a month or more without relief. The more my conditions progress, the more the my body seems to add to the list. With the right strain of cannabis, I can hault the symptoms altogether while under its affects. With the right strain, I am a functional member of society. If I go without it, my body starts going back to the way it was before I started it, I can barely function. I am too nauseous for water to remain in my stomach. My pain level is unbearable. Before it, and without it, I literally don't have the energy to sit, I have to remain laying down. Some aren't right and only lessen my agony.



Very interesting reading, I have Crohns disease, fibro, ehlers Danlos syndrome, arthritis, Raynaud's, hyperthyroidism and have smoked cannabis for a few years now, I find it helps with nausea, helps me to relax more and helps with my sleep. I will continue to take cannabis as long as it keeps working for me, some agree some don't but each to their own x hugs to all you chronic illness warriors all around the world



Is there any blood test I could ask my Doctor to test for CEDC?
Thank you so much for all you help



I wonder something I have been a daily smoker for many years and reciently due to moving and knowing no one have been with out for almost a month a few days ago while working I started getting foot pain and it's progressed from mild to pretty much constant resembling neuropathy or gout .
im now after testing my sugar and finding it to be normal trying a Apple cider vinegar, vit C , kewi , low acid high alkaline flush. And just replaced poor foot ware for much better footwear.
I have no visible swelling but my nerves are painfully tender and my big toe is sensitive.
Trying this flush for a few days started today so no results yet but wonder if the lack of canabnoids is an issue.


Suzi Best

Please tell me there is a way to be tested for CEDC! This was written with me in mind, totally! When I'm out of my "meds" (stopped big-pharma years ago) I can only go a few days before the issues (all above) start kicking in. After 2 weeks without I'm bedridden from the fibro and migraines.
Fibro, migraines, periphial neuropathy, IBS and autoammune rashes. I live in a state that is still illegal to medicate (sad). Whomever wrote this, please help me find the doctors testing for this so I can help get more info to build our case for legalization.


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