The Endocannabinoid Deficiency Syndrome (EDS) theory

In 2008, the Endo-cannabinoid deficiency theory was raised, claiming that three diseases: Migraine, fibromyalgia, and irritable bowel syndrome (IBS), have similar and/ or common clinical, biochemical and pathophysiological symptoms and patterns.

This theory links the symptoms of these diseases to the endocannabinoid system [ECS] and assumes that its dysfunction, resulting from a deficiency in the production of Endo-cannabinoids [eCBs] from an internal source in the body, can be solved by supplying exo-cannabinoids from the cannabis plant (phytocannabinoids [pCBs]).

CBD as a natural analgesic – A variety of benefits and medicinal properties

CBD has many properties that derive from its positive effect on many body systems and because of its variety of properties: CBD is an anti-inflammatory, antioxidant and fights infectious diseases, treats seizures and neurological disorders, relieves nausea, cures intestinal diseases, and improves cardiovascular health.

In addition, CBD’s ability to reduce anxiety is also well known, as mentioned above – sometimes a real part of the feeling of pain.

Before purchasing CBD products for solving pain problems, it is important to know: CBD is not effective in treating all types of pain but it can treat many types of pain, and most importantly: CBD is a natural analgesic especially suitable for inflammatory or neuropathic pain.

Nerve pain is usually caused by the glutaminergic system, which is a stimulating and primary nerve pathway in the brain & body. Glutamate is the neurotransmitter [NT] responsible for activating neurons. CBD suppresses the release of the neurotransmitter glutamate (Glu) and other pro-inflammatory compounds, making it a capable substance that protects the cells of the nervous system (neuroprotective) especially in the treatment of the combustion prickly sensations that characterize nerve pain. Along with other natural supplements like magnesium [Mg], CBD can also be a natural analgesic that also protects nervous system cells as a prophylactic treatment.

When the inflammatory cells accumulate due to chronic conditions, it is called inflammatory pain.

Pain as a result of inflammation is often associated with nerve pain except that it is not limited to nerve cells. An example of inflammatory pain in all types of arthritis, some immune diseases like Crohn’s disease, gastric ulcer, and simple situations like headaches, cramps, and muscle pain. A lot of problems arise when cells are damaged due to injury or as a result chronic illness. When the body feels the damage, it alerts the inflammatory cells to action.

CBD and the treatment of pain as a result of inflammation

The anti-inflammatory mechanism of cannabidiol is unique. It does not work like other anti-inflammatory drugs by suppressing the enzymes COX-1 and COX-2 – so there is no risk of developing gastrointestinal ulcers or heart attacks (as in many cases of current anti-inflammatory drugs). Numerous studies have found that the ability of CBD and THC to soothe inflammatory pain is twenty times higher than recognized anti-inflammatory drugs like ibuprofen (ibuprofen).

The virtues of CBD in treating the pain associated with gastrointestinal (GI) problems

When it comes to chronic gastrointestinal [GI] disorders, CBD is effective against many inflammatory & painful symptoms:

1. CBD suppresses the increased release of cytokines, monokines, and chemokines and in several laboratory models, it has been found to increase the production of T-regulatory cells in the immune system that function in suppressing inflammation, as a natural mechanism for suppressing the excessive inflammatory response.

2. CBD has been found to indirectly act on CB1 receptors by suppressing the enzyme FAAH that degrades AEA, allowing anandamide to act for a longer period and bind to the CB1 receptor.

3. CBD inhibits the mobilization of cells in the gut (lymphocytes & macrophages) to the inflammatory area of the intestines resulting in suppressing the release of TNFα that triggers an enhanced inflammatory response.

Most common questions about CBD for Pain Relief:

Is the pain relief after taking CBD immediately?

Although many consumers report immediate relief of pain from the first drop of CBD oil, it does not work like an analgesic pill whose function is to bind to one target protein in the human body. CBD acts simultaneously on about 60 target proteins in the body. Therefore, CBD’s effect on pain typically ranges from 4 hours to 5 days, depending on the intensity of the pain, the genetic background, the dose you are taking, and the quality of the product. The advantage of CBD over conventional pain killers is that once you have found the appropriate dosage, the body does not develop tolerance to CBD’s effects and therefore you will not need to increase the dose.

What is the recommended dose for chronic pain?

Finding the right dosage for solving pain problems consists of several factors: pain intensity, body weight, age, general health condition, sporting lifestyle, proper nutrition, and more. Since each person has an endocannabinoid system that responds to external cannabinoids differently – finding the appropriate dosage is completely individual. We recommend starting with taking two drops a day for two or three days and then going up to three drops for two days and so on – to the point where pain relief is clear. After reaching this point, there is no need for a dose increase.

Which is the best way to take CBD to treat chronic pain?

CBD can be consumed in a variety of ways. CBD oil is considered a way in which the absorption of the active substance is rapid. Utilizing the active substance by the body is considered very effective in taking CBD in the form of oil, and most importantly – it is possible to accurately measure how much CBD (mg) per day makes you feel pain relief. Ingestion of CBD using capsules or CBD-enriched foods & beverages is a way in which the absorption of the active substance is slower. Taking CBD by evaporation is considered especially suitable for relieving acute pain and allows mobility during the day in case of an “emergency”. Ointments, lotions, and creams applied to the skin and CBD transdermal patches are also considered a great way to relieve joint, muscle, and skin pain.

Should CBD be used regularly or before a pain attack?

We recommend taking CBD regularly, especially for people that suffer from chronic (persistent) pain. It takes between 36-72 hours to fully clean up CBD from the body and therefore even if you forgot to take your daily dose – usually, the body will utilize those CBD molecules that still flow throughout the bloodstream or are stored inside fat tissue. Some people who, for different considerations, choose to take CBD just before an acute seizure – it works very well for them as well. The decision and familiarity with CBD oil are all individuals.

Is there a fixed time of day for taking CBD or is it possible at any time?

We recommend taking CBD in the morning, and not drinking coffee for about 20 minutes before and after taking CBD oil. You can drink some water to wash out the flavour, but it is best to let the oil absorb in the mouth by itself. Some people have decided to take their daily dose at any other time of the day and this is entirely possible if it works for them.

Is it possible to disperse the dose of CBD oil drops throughout the day?

Daily doses can be dispersed (divided) throughout the day and night. If you take this approach, make sure you follow symptoms relief patterns and check carefully the amount of CBD you consume.

Are there any CBD overdoses?

As part of the FDA-approved safety trials conducted for a CBD-based drug called “Epidiolex”, doses of 600 – 1200 mg of pure CBD per day were given to children suffering from a rare epileptic syndrome called Dravet syndrome. At a dose of 600 mg per day, no significant side effects were observed and no liver toxicity developed, which may signal an “overdose” condition.

Is CBD safe to use?

In 2018, a World Health Organization (WHO) committee of experts on narcotic substances, reviewed the medicinal properties of the cannabinoid cannabidiol and published its recommendations report with the headline: “CBD is a substance with extensive and significant medical potential”. The report presented by the Experts Committee officially states: “No potential harm or addiction has been proven as a result of CBD use. Studies of experimental addiction models have found that CBD has no addictive effect.” In the model for the diagnosis between addictive drugs in animals, it has been discovered that CBD fails to be used as a substitute for THC, and as mentioned above, in light of the widespread use by patients all around the world, it can be determined that people do not develop any dependence on CBD and CBD cannot be abused [have no recreational value].

How do I define what pain is?

The experts of the International Association for the Study of Pain (IASP) defined pain as “a sensory and emotional experience, unpleasant, associated with real or potential tissue damage or described in terms of such damage”. In many cultures, pain is considered a physical injury, and since it can significantly impair the quality of life of the individual, it is the most common symptom that leads to a doctor’s appointment.

In many cases the feeling of physical pain also causes emotional suffering and the greater the intensity of the pain, the more the pain is accompanied by anxiety and the urge to stop ASAP the pain sensation. This defines pain as both a feeling and an emotion. Pain, especially acute pain, is a stress factor that leads to arousal and a characteristic physical reaction that manifests, for example, in the increase in blood pressure and heart rate. Pain that lasts over a long time directly causes mental and functional deterioration, sometimes to complete dependence on the medical system and strong painkillers, such as opioids.

Classification of pain according to the affected area of the neural transmission system

The feeling of pain is usually the result of the processing of the signals caused by changes in the tissues. These changes are felt by receptors found at the ends of peripheral nervous system [PNS] cells, also called nociceptive nerves.

These signals are transmitted along the nerve fibres to the spinal cord, which belongs to the central nervous system [CNS], and from the point of absorption in the spinal cord, the signals are transmitted along neural pathways to physical and emotional “data processing” centres in the brain. Here’s the classification:

A. Nociceptive pain is the “normal” pain, which originates from tissue damage. It’s transmitted through neural pathways.

B. Peripheral neuropathic pain: Pain resulting from damage to peripheral neural pathways.

C. Central neuropathic pain: Pain that results from damage to the neural pathways inside the CNS, spinal cord, or the brain tissue inside the skull.

Classification of pain by symptoms

There are several clinical syndromes, the main component of which is pain such as migraines or complex regional pain syndrome, Rheumatoid Arthritis (RA), and more.

Classification of pain according to mixed tissue

A. pain of muscular origin (Myofascial)

B. Joint pain

C. Bone pain

D. Visceral pain that originates from an internal organ (a type of abdominal pain)

E. Ischemic pain (lack of oxygen) resulting from insufficient blood supply to certain organs or tissues.

F. Neuropathic pain originates not from damage to the tissue or organ, but rather to damage to the neural pathways themselves that lead the pain sensation from the tissue and/ or the organ to the centre of sensation (the brain).

CBD is not effective in treating all types of pain but can treat many types of pain, Therefore, it is very important to understand the origin and nature of pain:

• Is it getting worse with weather changes?

• Does it have one focus or is it spread all over his body?

• Does it cause swelling?

• Is it stabbing or muffled?

• Does it develop and intensify throughout the day or begin in the evening?

• What symptoms are associated with the pain sensation?

It is important to share with your doctor when you are interested in starting to add CBD to treat chronic pain. Finding the right dosage and understanding the properties unique to CBD as a natural painkiller is important for the process.

Read more in studies on CBD and pain management:

• Cannabinoids in the management of difficult to treat pain

• A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of THC/CBD oromucosal Spray in Combination With the Existing Treatment Regimen, in the Relief of Central Neuropathic Pain in Patients With Multiple Sclerosis

• Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors

• Cannabidiol Inhibits Paclitaxel-Induced Neuropathic Pain Through 5-HT(1A) Receptors Without Diminishing Nervous System Function or Chemotherapy Efficacy

• Non-psychoactive Cannabinoids Modulate the Descending Pathway of Antinociception in Anaesthetized Rats Through Several Mechanisms of Action

• The Role of the Endocannabinoid System in Pain

• Meta-analysis of Cannabis-Based Treatments for Neuropathic and Multiple Sclerosis-Related Pain

• Sativex: Clinical Efficacy and Tolerability in the Treatment of Symptoms of Multiple Sclerosis and Neuropathic Pain

• The Non-Psychoactive Cannabis Constituent Cannabidiol Is an Orally Effective Therapeutic Agent in Rat Chronic Inflammatory and Neuropathic Pain

• Clinical Endocannabinoid Deficiency (CECD): Can This Concept Explain Therapeutic Benefits of Cannabis in Migraine, Fibromyalgia, Irritable Bowel Syndrome and Other Treatment-Resistant Conditions?

Mechanisms of action of CBD as a natural treatment of persistent (chronic) pain

1. Mechanism of action in pain relief of CBD as an agonist of GlyRs:

The stimulant neurotransmitter, glycine (Gly) is involved in transmitting the sensation of pain along the spinal cord. Recent studies have found that CBD binds to the amino acid Serine (Serine #296), which is part of the transmembrane component of the α3 Gly receptor. This implies that the CBD will change the structure of the α3 receptor in a way that will inhibit the sensation of pain that passes through the spine. The pain will be sent from the painful area through the spinal neurons but it will not reach the brain because CBD effect the Gly receptors. This way, CBD soothes a lot of types of chronic pain.

2. Activating cation channels that are involved in a feeling of pain

Cannabidiol causes activation and opening of the cation channel – TRANSIENT RECEPTOR POTENTIAL VANILLOID (TRPV-1) that is responsible for the recession of pain, also controlling body heat, and inflammation. The activation of this ion channel by CBD calms the feeling of pain, suppresses inflammatory processes, and lowers body temperature.

3. Allosteric inhibition of opiate receptors:

In our bodies, natural opioid substances like Endorphin and Enkephalin are found. Their job is to silence pain naturally. Most chronic pain sufferers are treated with external opioids and because CBD is an allosteric inhibitor of some opioid receptors, fewer internal opioids are needed to relieve pain.

4. Adenosine receptor binding:

Among the variety of mechanisms of action of the CBD, there is also its binding to adenosine receptors, which produce, among many other things (such as the sleep mechanism) also a significant anti-inflammatory reaction, which helps to calm many sources of the pain itself.

5. Activation of the serotonin receptor 5-HT1A:

Serotonin [5-HT] is a neurotransmitter in the nervous system which is involved in regulating a series of effects that include: nausea, appetite, anxiety, sleep, pain sensations, and addiction. CBD binds to the 5-HT1A receptor, activating it to produce pain-relieving sensations along with sedation of the digestive system.

More reading –

A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products

The effects of cannabidiol and analgesic expectancies on experimental pain reactivity in healthy adults: A balanced placebo design trial.

Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action

Cannabidiol prescription in clinical practice: an audit on the first 400 patients in New Zealand

A Review of the Use of CBD and Other Cannabinoids in Pain Management

The Effects of Cannabis Among Adults With Chronic Pain and an Overview of General Harms

Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

Cannabinoid Delivery Systems for Pain and Inflammation Treatment

Cannabinoids for neuropathic pain

Variations in the cannabinoid receptor 1 gene predispose to migraine

The endocannabinoid system and migraine

Cannabinoids and hallucinogens for headache

Effects of anandamide in migraine: data from an animal model

The Use of Cannabis for Headache Disorders

Experience of migraine, its severity, and perceived efficacy of treatments among cannabis users

Involvement of the endocannabinoid system in osteoarthritis pain