Endocannabinoid Deficiency Syndrome

Illustration of endocannabinoid system
Written by Nina Julia | Last updated: October 31, 2023

Is endocannabinoid deficiency syndrome a real thing? If yes, we would gain completely new insight into the pathophysiology of many civilizational diseases, such as migraines, fibromyalgia, irritable bowel syndrome, and more.

Although modern medicine has come a long way when it comes to treating various medical conditions or providing means of intervention for life-threatening situations, many diseases still remain a mystery.

Let’s not be afraid to say this: modern medicine hasn’t found a solution to a whole range of chronic conditions, and there’s nothing to be ashamed of.

And, when you consider cannabinoids like CBD and THC as part of that modern medicine, it turns out cannabis can revolutionize it and help overcome the current obstacles.

In recent years, hypotheses have emerged that the aforementioned diseases may stem from a dysfunctional endocannabinoid system, or to be more precise, endocannabinoid deficiencies (ECD).

Could ECD explain why certain diseases form in the first place? According to Dr. Ethan Russo, an esteemed neuroscientist and cannabis expert, this can be the case.

Let’s dive deeper into the endocannabinoid system and its importance for our biological balance (homeostasis).

What Is the Endocannabinoid System (ECS)?

Everyone has an endocannabinoid system (ECS). It’s present in every other system and organ in the body.

Through a complex — and not fully understood — the network of endocannabinoids, receptors, and enzymes that communicate with your brain, the ECS controls a broad range of biological processes.

It’s basically everything from your immune reaction and sensitivity to pain to gut motility, appetite, metabolism, mood, memory, and sleep.

When you use and consume CBD, it facilitates communication between the ECS and the brain. It helps regulate neurological signaling and protect your body against environmental damage.

It’s through this interaction that CBD provides diverse and numerous physical and mental health benefits.

However, like every other system in the body, the ECS has its limitations and is prone to dysfunctions.

What Is Endocannabinoid Deficiency (ECD)?

Now that we’ve covered the basics of ECS, we can explore its dysfunctions also known as endocannabinoid deficiency syndrome.

Endocannabinoid deficiency is a relatively common term that describes a condition where the ECS can’t produce enough of its natural endocannabinoids on a daily basis. Medically speaking, it’s called clinical endocannabinoid deficiency syndrome (CECD).

Although CECD isn’t currently an officially accepted medical condition — it’s just a theory — there’s a significant body of evidence supporting its occurrence and connection to other illnesses. It was first proposed in 2001 and reviewed in 2016 after more than 10 years of collecting clinical data.

Long story short, endocannabinoid deficiency is when the ECS falls out of homeostasis, or a state of balance and peak performance. When your body becomes deficient in endocannabinoids, this may be due to the following triggers:

  1. It isn’t properly producing endocannabinoids so there are insufficient amounts of them in the body.
  2. There aren’t enough cannabinoid receptors to connect the calls between the ECS and the brain.
  3. There are too many enzymes in your ECS. Enzymes are made to metabolize (break down) other substances. Too much is never good.
  4. Communication between the endocannabinoids and receptors is flawed. These interactions must be correct in order for the ECS to function; otherwise, the brain can struggle with processing the signals from neurotransmitters.

The above causes a decrease in your endocannabinoid levels, creating dysfunctions.

With the compromised ECS, the usual brain signaling that relies on the ECS is weakened or distorted. As a result, the body may experience a range of health issues because it’s getting false messages and instructions from the navigation center, which is your brain.

Symptoms of Clinical Endocannabinoid Deficiency (CECD)

CECD is difficult to diagnose because there are no standard tests that would measure the levels of endocannabinoids in your body. I mean, there are such tests, but they’re not subject to official medical procedures because, as I said, CECD is a theory for now — although a well-backed one.

That being said, here are some commonly mentioned symptoms of endocannabinoid deficiency:

  • Increased sensitivity to pain (hyperalgesia)
  • Having anxiety, depression, or trouble regulating mood
  • Irregular sleep patterns or insufficient sleep
  • Metabolic health issues
  • Having fibromyalgia, irritable bowel syndrome, and/or migraines

If you believe you might have CECD, consult your doctor. They might be able to test you for this disorder.

Causes of Endocannabinoid Deficiency

Researchers have yet to fully understand the causes of endocannabinoid deficiency syndrome. However, it’s likely a combination of factors including:

  • Alcohol consumption
  • Diet and nutrition
  • Environment
  • Genetics
  • Sedentary lifestyle
  • Stress
  • Having other health conditions

The medical community doesn’t really know how common CECD is, but what they do know is that other diseases related to this condition are quite prevalent today.

Diseases Caused By Endocannabinoid Deficiency

A poorly functioning ECS may give rise to a whole host of other health problems because it’s a key system in the human body, responsible for maintaining internal homeostasis.

Therefore, if your endocannabinoid function is lower than it should be, you’re more likely to have your pain threshold lowered and digestion disrupted. Moreover, you may suffer from mood and sleep disorders; that’s why we suspect ECD may pave the way for conditions such as migraine, irritable bowel syndrome, and IBS.

Here’s what Dr. Russo said on the Cannabis Enigma podcast about investigating ECD in the diagnosis of contemporary diseases:

“These disorders actually have a lot in common in that they’re all what are called diagnoses of exclusion, which is a way of saying that there are no specific tests for them, you can’t scan for them, you can’t do blood tests for them, but they all involve a sort of hypersensitivity to pain. In the case of migraine, it’s headaches, but also painful stimuli such as noise and bright light. For irritable bowel it’s an acute awareness of the gut and phenomena that normally don’t hurt are quite painful to people with that condition. And with fibromyalgia, you’ve got a generalized often increase in pain sensitivity on certain muscles or fibrous tissues that may hurt to a great extent, but examining the tissues reveals no specific problem to explain.

These three conditions also involve a higher probability of anxiety, depression, sleep disorders, and headaches. While this profile of symptoms is the starting point for considering these health issues, there’s compelling evidence for each suggesting it’s probably caused by a dysfunctional ECS.


Migraines are severe headaches that affect about 15% of Americans and are three times more likely to appear in women than men. Associated with sensitivity to light and sound, hormonal and environmental triggers, and nausea and vomiting, migraine headaches are debilitating and difficult to live with.

So why do neuroscientists believe migraines might be connected to endocannabinoid deficiencies?

Well, the first indicator is that migraine sufferers seem to benefit from cannabis treatments. It’s been used historically as a remedy for migraines, and modern surveys have shown that cannabis can significantly curb migraine frequency. For example, one survey found that 85.1% of those who used cannabis for migraines reported lower migraine frequency, from 10.4 to 4.6 attacks per month on average.

Migraine sufferers’ response to light and sound is also another hint. It suggests an abnormal sensitivity to external stimuli in the central nervous system. That’s exactly the thing that the ECS would usually balance.

Moreover, the endocannabinoid anandamide is capable of inducing serotonin receptor responses that align with the profile of drugs that have been effective in reducing the frequency and severity of migraines.

And studies are now showing that anandamide plays an important role in stimulating the trigeminovascular system — a network in the human body whose activation and sensitization occur once migraines are triggered. It could be that lower levels of natural anandamide would result in migraines by allowing for excess activation of the trigeminovascular system.

Other studies discovered that anandamide triggered dose-dependent vascular phenomena similar to those observed in migraine patients, including vasoconstriction and vasodilation (both observed in different studies). Since these two processes are present in migraine, this suggests anandamide plays a significant role in this aspect of the disease.

Scientists have also reported high levels of fatty acid amidohydrolase (FAAH) in the platelets of migraine sufferers. These enzymes break down anandamide, helping the body clear it from the system. With less anandamide active in migraine sufferers’ bloodstream, patients become more sensitive to pain signals.


Fibromyalgia is a condition whose symptoms involve pain throughout the body, which is deteriorated by exertion. This persistent pain is also associated with depression, anxiety, and sleep disorders. Researchers are still trying to pinpoint the physical signs to diagnose this misunderstood yet common condition. In fact, there’s no specific test to diagnose fibromyalgia. However, many believe that the oversensitivity to pain in the central nervous system could stem from endocannabinoid deficiencies.

Russo covers several different studies related to fibromyalgia and endocannabinoid deficiencies. Similar to other conditions caused by a dysfunctional ECS, fibromyalgia is associated with hypersensitivity to pain. This phenomenon has been observed in patients with weak endocannabinoid function in the spinal cord.

Interestingly, both CBD and THC can alter pain transmission between the spinal cord and the brain. And given that plant-derived cannabinoids have similar molecular makeup to endocannabinoids, reduced endocannabinoid function is a good guess when trying to rule out the cause of fibromyalgia.

Studies on fibromyalgia patients treated with cannabis show that those who well-tolerated the psychoactive effects of THC experienced significant reductions in pain and stiffness. They also reported improved relaxation and sleep, and better well-being overall.

One study analyzed endocannabinoid levels in fibromyalgia patients and found increased concentrations of certain cannabinoids. The authors noted that the elevated levels reflected some form of metabolic asymmetry taking place. This adds more evidence to the theory that fibromyalgia may occur due to an imbalance in the endocannabinoid system.

Related: Best CBD Oil for Fibromyalgia

Irritable Bowel Syndrome (IBS)

Also known as IBS or spastic colon, irritable bowel syndrome involves gastrointestinal pain, discomfort, spasms, and abnormal bowel movements — usually accompanied by constipation, diarrhea, or co-occurrence of the two. While sometimes caused by certain food allergies of behavior such as overeating, IBS is also associated with anxiety. It’s a common condition in the western world, affecting up to 15% of the population. Still, there are no physical indicators that would point researchers to a potential cause.

Cannabis has long been used for gastrointestinal issues. In fact, it was one of the first effective treatments in the 19th century for cholera-induced diarrhea. Today, research supports its effectiveness. Today, many people with IBS use cannabis to ease their symptoms and swear by its effectiveness. Nevertheless, clinical research is in its infancy, so it’s too early to say for sure that cannabis cures IBS.

The scientific literature provides additional evidence to link IBS with ECD. One study examining muscle fibers from colonoscopy biopsies found that anandamide modulated colon movements. The research team suggested that the ECS was an important therapeutic target for relieving inflammation associated with the disease.

Another study found increased TRPV1 nerve fibers in IBS patients, which could cause hypersensitivity to pain. Since endocannabinoids such as anandamide or phytocannabinoids like CBD may desensitize TRPV1; this is a receptor involved in pain signaling and also relates to ECS function.

Moreover, genetic differences in endocannabinoid metabolism can occur in patients with IBS and diarrhea. The activation of CB1 receptors with cannabinoids like THC has been proven to slow colonic transit time and improve the quality of life of patients.

In obese mice, THC has also been shown to positively affect the gut microbiome — restoring it to a similar state to healthy mice.

Other Conditions Related to Endocannabinoid Deficiency

Aside from fibromyalgia, migraines, and IBS, there are other conditions that Russo proposes may be related to ECD. The syndrome has been implicated in conditions such as:

  • Diabetic neuropathy
  • Huntington’s disease
  • Autism
  • Anxiety
  • Anorexia
  • Schizophrenia
  • Parkinson‘s disease
  • Brachial plexopathy
  • Infantile colic
  • Glaucoma
  • Dysmenorrhea
  • Bipolar disease
  • Post Traumatic Stress Disorder (PTSD)
  • Phantom limb pain
  • Multiple Sclerosis
  • Hyperemesis gravidarum
  • Repetitive miscarriages

For example, if you experience nausea from motion sickness, you may have reduced levels of endocannabinoids. The same goes for impaired ECS functioning in MS, Huntington’s disease, and major depression. On the other hand, higher levels of anandamide were found in people suffering from schizophrenia and Parkinson’s disease.

Not only that, but the ECS also controls fear extinction mechanisms that allow patients with PTSD to recover from traumatic experiences. Researchers theorize that lower levels of anandamide may impede this process — hence the prevalence of self-medication with cannabis among PTSD sufferers.

For people with autism, CBD and other cannabinoids can also help regulate ECS functioning. Recent studies have found that children with autism have lower levels of endocannabinoids circulating in their system.

All these conditions share one common thing: their underlying causes remain relatively unknown. And endocannabinoid deficiency syndrome is one of the possible explanations for their development.

How to Treat Endocannabinoid Deficiency

According to a 2014 study, endocannabinoid deficiency can be treated with a variety of methods, including:

  • Cannabis
  • Other herbal medicines and remedies
  • Food supplements
  • Acupuncture
  • Stress-management techniques
  • Lifestyle modifications (including more exercise, and eating nutrient-dense food)
  • Moderate use of coffee
  • Massage and manipulation

You may also consume functional foods that contain high levels of therapeutic compounds, such as antioxidants, phytocannabinoids, vitamins, and trace minerals. Taking care of an anti-inflammatory diet may also improve your endocannabinoid system.

Speaking of cannabis, let’s take a look at how CBD can help with endocannabinoid deficiency.

CBD for Endocannabinoid Deficiency: Can It Help?

CBD oil, gummies, and hemp leaves

This shouldn’t sound surprising by now; after all, cannabis is a plant chock-full of cannabinoids that can address deficiencies in the ECS and potentially help restore your body’s homeostasis.

It makes sense, without a single doubt.

Cannabidiol products are a good option to consider because they contain the whole spectrum of cannabinoids and terpenes (including trace amounts of THC); altogether, these compounds work synergistically to amplify their health benefits and mitigate potential side effects.

This phenomenon is known as the entourage effect.

When it comes to CBD, it may balance endocannabinoid deficiency by signaling the ECS to produce more of its endocannabinoids while slowing down their breakdown by blocking the FAAH enzyme.

CBD’s effects are less direct than what people experience after using high-THC cannabis (marijuana). THC activates the CB1 receptor in the brain, resulting in a range of euphoric reactions known as the “high.” This effect is therapeutic but not all people can tolerate it in higher doses.

CBD, on the other hand, doesn’t have any affinity to the CB1 receptor, so its effects are more subliminal. It can improve your mood, help you focus, and regulate your circadian rhythm, it won’t get you high in the way THC does.

Using Medical Cannabis for Endocannabinoid Deficiency

Medical cannabis usually refers to high-THC weed strains and their extracts. While CBD modulates the activity of the endocannabinoid system, THC is the agonist of both receptors, meaning it activates them.

Therefore, consuming marijuana for conditions potentially stemming from endocannabinoid deficiencies may help you address the pesky symptoms, contributing to better life quality overall.

That said, you should use medical cannabis responsibly and strive to form only positive patterns around it. While clinically insignificant, behavioral addiction to marijuana is a real thing and may hinder some of its therapeutic qualities. Self-control above all, remember.

Final Thoughts on Endocannabinoid Deficiency & Possible Treatment Options

Endocannabinoid deficiency is gaining popularity as a potential explanation for the development of many modern diseases, such as migraines, ADHD, fibromyalgia, irritable bowel syndrome, neuropathy, and more.

Research is ongoing but the clinical evidence is piling up, suggesting that endocannabinoid deficiency may play an important role in establishing the right treatment for the said diseases.

You can choose from a broad range of treatment options to bring your ECS back to balance, including natural supplementation, lifestyle modifications, herbal remedies, and cannabis products such as CBD oil.

As more resources are fueled into the research on endocannabinoid deficiencies, scientists may soon come to bolder conclusions on cannabis as a possible first-line treatment.

Nina created CFAH.org following the birth of her second child. She was a science and math teacher for 6 years prior to becoming a parent — teaching in schools in White Plains, New York and later in Paterson, New Jersey.