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Fibromyalgia, Migraines & The Science Of Clinical Endocannabinoid Deficiency

First proposed by Dr. Ethan Russo, Clinical Endocannabinoid Deficiency could contribute to numerous painful conditions from fibromyalgia to IBS to migraine. This would help explain why cannabis and hemp help so many people with these conditions.

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.

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.

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.

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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CBD In The Brain: The Neurological Effects Of CBD Oil

The unique neurological effects of CBD are key to this supplement’s growing popularity. CBD is notably different from other cannabinoids, or chemicals which are found in hemp and cannabis. In this article, we take a look at how CBD works to heal.

The unique neurological effects of CBD are key to this supplement’s growing popularity.

Cannabidiol (CBD) is a chemical compound that is present in hemp, a close relative of marijuana. It is nonpsychoactive—meaning, it doesn’t make people feel stoned. CBD is also known to have various medical benefits that can help relieve patients from pain, inflammation, anxiety, lethargy, and other conditions. When taken, CBD allows a person to feel relaxed without the intoxication.


CBD is notably different from other cannabinoids, or chemicals which are found in hemp and cannabis. While all other cannabinoids interact with two significant receptors in the nervous system, CB1 and CB2, CBD has very little effect on both of them. CB1 receptors are found in different parts of the brain, including those concerned with emotion, sensory perception, memory, and cognition. CBD does not induce a mind-altering state.

The unique effects of CBD in the brain lead to a host of healing benefits from this popular supplement.

An illustration of neurons firing in a human head. The unique effects of CBD in the brain lead to a host of healing benefits from this popular supplement.

Tetrahydrocannabinol (THC), on the other hand, is another story. It is the chemical responsible for majority of cannabis’s psychological effects, sending you on a cerebral adventure. It is found mainly in the resin secreted by the glands of the marijuana plant. THC attaches itself to both CB1 and CB2 receptors. This activates them and affects a person’s thinking, perception, memory, pleasure, and concentration, making the person feel high.

CBD may also moderate the effects of THC. While some people report anxiety from consuming marijuana, strains which are high in CBD tend to cause less of these effects. CBD itself may be beneficial in the treatment of anxiety.


CBD is known to have several medicinal properties, but because the field of marijuana studies is fairly young, more research is needed to explore the properties of marijuana’s compounds. Here are some of the possible medical benefits of CBD. More research is needed to determine whether CBD can effectively be used to treat all these conditions.

  • Neuroprotective Effects

CBD could be useful when treating neurological diseases because it protects neurons from degeneration. In a study about Alzheimer’s, CBD was seen to hinder and the development of Alzheimer’s symptoms.

  • Analgesic Effects

CBD has proven itself useful in suppressing pain. It is able to inhibit neuronal transmission without causing analgesic tolerance. Because of this, researchers suggest that CBD and other nonpsychoactive components can be used as a foundation to the treatment of chronic pain.

  • Antitumor Effects

Studies have shown that very high doses of CBD no toxic effects in humans and that it might be used to inhibit the growth of cancer cells due to its antitumor properties. This could even help treat leukemia and similar diseases.

  • Antianxiety Effects

CBD has been shown to reduce anxiety in patients. Researchers have also suggested that it can be used on patients with a variety of related conditions including Post Traumatic Stress Disorder.

In a 2011 study, a test was administered to 24 patients with social anxiety disorder. 1.5 hours before the test, the patients were given CBD or placebo. It was found out that the anxiety, cognitive impairment, and discomfort in patients who were pretreated with CBD had significantly reduced, compared to those in the placebo group.


CBD produces effects through various molecular pathways. Although CBD does not really bind with two of the cannabinoid receptors, CB1 and CB2, it acts through several different receptor-independent channels. CBD enhances and inhibits the binding action of certain protein-coupled receptors.

Listed below are some of the receptor systems and their relationship with CBD.

  • Serotonin System

CBD targets a specific serotonin receptor, the serotonin 1A receptor. Its affinity with this receptor is associated with a lot of CBD’s therapeutic properties.

The unique neurological effects of CBD offers relief without the feeling of being “high.”

THC & CBD, two chemicals found in cannabis and hemp, have distinct effects. The unique neurological effects of CBD offers relief without the feeling of being “high.”

Take note that serotonin receptors regulate the release of hormones like cortisol, which is responsible for metabolism and reactions to stress, and oxytocin, which affects social behavior. Serotonin receptors also affect a person’s mood, cognition, and appetite.

Enhancing the activation of serotonin 1A receptors supports the theory of how CBD impedes certain problems and disorders such as neuropathic pain, anxiety, depression, schizophrenia, and nausea from chemotherapy.

    • Vanilloid Receptors

CBD binds to TRPV1 receptors, which are also called vanilloid receptors, to achieve a therapeutic effect. As an ion channel, TRPV1 plays a role in thermoregulation (temperature regulation), inflammation, and the perception of pain.

    • Orphan Receptors

GPR55 is called the orphan receptor because researchers are still not sure if it belongs to a larger receptor family tree. It is involved in the process of modulating blood pressure, bone reabsorption, and bone density.

When it is overactive, GPR55 may cause osteoporosis. GPR55 also contributes to the multiplication and migration of cancer cells. CBD blocks GPR55 signaling. This could affect the likelihood of cancer cells proliferating under the right conditions.

    • Nuclear Receptors

Peroxisome proliferator activated receptors (PPARs), also known as “nuclear receptors,” are activated by CBDs to produce an anticancer effect. They are found on the surface of the cell’s nucleus. When activating a receptor known as PPAR-gamma, an antiproliferative effect begins. Its activation also causes tumors to regress in lung cancer cell lines.


According to a study, CBD in the brain inhibits anandamide reuptake and breakdown, which increases endocannabinoid levels in the brain’s synapses. Anandamide is an extremely powerful, cannabis-like chemical in the brain. This, in turn, has neuroprotective effects against seizures and other problems.

A row of vials of CBD oil, a nutritional extract made from hemp. Only in recent years has science begun to rediscover the benefits of medicinal hemp and cannabis.

Since it is a plant compound, CBD has to pass through the cell membrane to get inside a human cell and bind with a nuclear receptor. It does this by attaching itself with a fatty acid binding protein (FABP), which takes it into the cell’s interior. The same intracellular molecules also transport THC and the brain’s cannabis-like molecules, the endocannabinoids anandamide and 2AG, to different parts inside the cell.

CBD has a strong attraction to three kinds of FABPs. This causes CBD to compete with endocannabinoids. Once endocannabinoids are inside the cell, anandamide is broken down by fatty acid amide hydrolase, a metabolic enzyme. CBD interferes with endocannabinoids’ process by reducing anandamide’s access to transport FABP and delaying it from entering the cell.


CBD has therapeutic properties that can aid individuals facing both physically and psychologically related problems.

    • Anxiety, Stress, and Depression

While THC can amplify the anxiety in some people, a study done by Neurotherapeutics suggests that CBD can help lessen the anxiety felt by people with particular anxiety disorder. The neurological effects of CBD could lead to it being used as a supplement to existing treatments like pharmaceutical drugs.

    • Epilepsy

A study posted in Epilepsia suggested that CBD is able to treat epilepsy and neuropsychiatric disorders. Since CBD has antiseizure properties, it has a low risk of adverse side effects on people who already have epilepsy. Because of this, there are more and more studies being conducted with the focus to treat many of the disorders linked to epilepsy, such as neuronal injury, neurodegeneration, and psychiatric diseases.

    • Sleep Quality

Since CBD can help reduce anxiety, this, in turn, can help out with sleep difficulties. It may increase the overall amount spent sleeping by subduing chronic pain and insomnia. At a small dosage, CBD induces wakefulness and reduces daytime sleepiness, but heavy doses taken a few hours before bedtime have a balancing effect that often leads to a good night’s sleep.


While most of the studies have put their focus on understanding THC, cannabidiol has been consistently showing great potential with regard to its medical uses. It is important to understand all the properties of cannabis and hemp so that people can use it to help benefit the human body.

As they understand this chemical more, scientists may find newer ways to improve human health and healing, without having the fear of the stigma that comes with cannabis.

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