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    Using phytocannabinoids to rebalance and prevent illness – How to treat endocannabinoid deficiency

    Clinical Endocannabinoid Deficiency is a term regularly used in the medical cannabis world and refers to a collection of illnesses where low levels of endocannabinoids and their receptors contribute to disease development in the human body. Source: Dr Ethan Russo – clinical endocannabinoid deficiency explained

    It is beyond any doubt that hemp and cannabinoids can be extremely beneficial in the case of many illnesses and symptoms.

    Even the fact that pharmaceutical companies are competing in discoveries of synthetic cannabinoids underlines that point. But could phytocannabinoids derived from the hemp plant also be used before we get ill, as a preventive measure to maintain our health? The answer is YES, and here I will explain how to use them to maintain health and nourish the endocannabinoid system. 

    The Endocannabinoid System Explained

    There is a broad debate around whether phytocannabinoids (the cannabinoids from the cannabis plant) could or even should be used as a means to prevent illness. There are many arguments for it and mostly just one against: the lack of long-term studies. In prevention and treatment a lot is dependent on dosing and routes of administration, similar as is also with all other substances. 

    When the complexity of the endocannabinoid system was slowly becoming evident and it became clear that describing it in a simple way was very hard, Prof. Mechoulam and Prof. Di Marzo proposed that we understand the endocannabinoid system as the one that regulates how we eat, sleep, relax, forget and protect.

    The life in modern society with all its demands and challenges turns on our Endocannabinoid System (ECS) many times during the span of a single day. If this is happening over a prolonged period of time, the ECS can start to dysfunction. It can happen that endocannabinoids are not being produced when we do need them. This dysfunction usually leads to something we know as ‘endocannabinoid deficiency’, meaning an overall lower level of endocannabinoids, which has been shown to be important in the development of many diseases. 

    The endocannabinoid system is essential to life and it relates messages that affect how we eat, sleep, relax, forget and protect.”

    Vincenzo Di Marzo, Ph.D. / Raphael Mechoulam, Ph.D.

    We all know we have an immune system that protects us from bacteria, viruses and parasites. Similarly we can think of the ECS as a system in our body that protects us from anything that can jeopardize our biochemical balance. It reacts to physical injury, breathing in toxins, or emotional trauma. We can imagine that when we do not have a well-functioning ECS, it’s like our body has its first line of defence turned off. We now know that this is usually one of the first steps in the development of chronic disease, the first domino piece in a complex domino structure to fall, leading to symptoms and disease development. And in such cases, where the ECS is malfunctioning, the use of exogenous cannabinoids, especially phytocannabinoids can be very beneficial.

    Physiological systems and conditions affected by cannabinoids (a partial list):

    • Anxiety
    • Inflammation
    • Appetite/feeding 
    • Memory
    • Blood pressure 
    • Mood
    • Bone formation 
    • Movement
    • Cerebral blood flow 
    • Neuroprotection
    • Digestive system 
    • Pain
    • Emesis and nausea 
    • Reproduction
    • Immune system 
    • Stress

    How to check if your endocannabinoid system is in good shape

    If you are wondering if your ECS is still in good shape, it’s best to look at the five areas that the ECS mostly affects. You can ask yourself the following questions: 

    1. Is your appetite well balanced? 
    2. Are you sleeping well, waking up rested and energized?
    3. Do you have enough strength in your muscles for your daily activities and do your muscles relax well in the evening?
    4. Do you remember the information you need and want and forget all the daily unvital informational chatter/noise?
    5. Does your immune system work well and you only seldomly get seasonal infections? 

    If you answered all these questions with yes, then your ECS is most likely functioning well and protecting your biochemistry. If one or more questions were answered with a no, then your ECS is not in top shape and it’s time to consider helping it out. First by ensuring enough building blocks for the ECS and second by cannabinoids from the cannabis plant. 

    Fats for health = Good fats – How to support our body’s endocannabinoid system

    One of the very important ways we can nourish and support our endocannabinoid system is by making sure we consume enough essential fatty acids. Besides all the health promoting benefits of the fatty acids that are well known, fatty acids are also the building blocks of our own endocannabinoids. And if we do not have enough fatty acids available when we need them for the production of endocannabinoids, it is like trying to build a house without bricks. So the focus on healthy fats is very important. We usually cannot totally avoid the bad ones, like trans and saturated fats, so it is even more important to balance that with good fats (unsaturated, omega-3/6). Not surprisingly, the dietary pattern with too many bad fats and too little good fats is associated with impaired function of the ECS. Two types of healthy fats are particularly important for the proper functioning of the ECS:

    1. Monounsaturated fats – usually found in olive oil 
    2. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) – usually derived from fish oils 

    Not surprisingly, hemp has a solution for this too. Hemp seeds and cold pressed oil are an exceptionally rich source of unsaturated fatty acids, linoleic acid, (alpha) linolenic acid and stearidonic acid. The alpha-linolenic acid and stearidonic acid get converted into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in our bodies, making seeds an indispensable part of a healthy diet, pronouncedly important for vegetarians and vegans to endure the EPA and DHA sources. The seeds and oils also contain other nutrients, phenols and antioxidants and have a perfect omega-6 to omega-3 ratio (3:1). 

    Bacteria for health = Good bacteria 

    The importance of a healthy gut is already well documented, but not only are cannabinoids important and beneficial in case of gut diseases, it is also the other way around. The gut is the place where not only most of our immune system is, but also where we produce endocannabinoids that to some degree determine the tonus of our endocannabinoid system. So it’s no surprise that a healthy gut is essential for a properly functioning ECS. If fatty acids are the bricks of the house blocks, then a healthy gut is the foundation. Probiotics are well known to the food supplement industry and are defined as live microorganisms that, when administered in proper amounts, improve host health. Of all the beneficial bacteria Lactobacillus acidophilus is best studied for its effects on the ECS. The effects on the ECS are: 

    1. The gut epithelial cells express more CB2 receptors if exposed to L. acidophilus
    2. The tone of ECS in the gut becomes more balanced and the gut cells also express more mu-opioid receptors leading to an analgesic function of L. acidophilus

    It was also shown that a 30 day regimen or oral intake of a mixture of Lactobacilli, Bifidobacteria, and Streptococcus thermophilus reestablished a balanced tone of the ECS in the gut, reduced inflammation and regulated the gut immune function. Pathologically obese people have an elevated tonus of ECS in the gut (more receptors and anandamide, less degrading enzymes) usually accompanied by low grade inflammation and dysbiosis. In such cases an intervention with probiotics might be especially important. 

    Prebiotics are compounds in food that induce the growth or activity of beneficial microorganisms. They also modulate our gut bacteria and the ECS tone. For example, when obese mice were fed prebiotics such as oligofructose they expressed less CB1 receptors, produced less AEA and gained less fat mass. 

    The relationship between the gut bacteria and the ECS is a complicated one, since bacteria affect the ECS and the ECS also affects the gut bacteria. It’s a ‘chicken or egg first’ causality dilemma here, if the altered profile of gut microbiota is responsible for changed ECS tone, or vice versa. However, adding fermented foods and foods rich in fibre to our diet is beneficial to both. 

    Also in this regard, hemp seeds can add their share to health. Whole hemp seeds are a good source of prebiotics, since they contain both soluble and insoluble fibre. Soluble fibre forms a gel-like substance in the gut and the insoluble fibre adds bulk to the stool and may help food and waste pass through your gut. Shelled hemp seeds contain less fibre because the fibre-rich shell has been removed. 

    Lifestyle effects on the endocannabinoid system

    Lifestyle can be beneficial or detrimental for our ECS. Many times, we are not even aware that the choices we are making on a daily basis affect the condition of our ECS. 

    The foods, supplements and medications we consume affect the enzymes responsible for building and degrading our endocannabinoids. Fasting and food intake affect it, as well as the ambiance of meals, like music, mood and alcohol consumption. 

    Massage and aerobic exercise have been shown to increase the levels of endocannabinoids. We’ve all heard about the “runner’s high”, a powerful good feeling when we exercise. It was long believed that endorphins are responsible for this state but as it turns out, exercise increases the sensitivity of cannabinoid receptors and production of anandamide in the part of the brain that is involved in pleasure and reward. In a way, it seems that the ECS is designed to reward exercise. 

    Even acupuncture and shamanic rituals modulate the ECS. Stress-reduction techniques, such as meditation, yoga, and deep breathing have a balancing effect on the ECS. It seems that the ECS is a vital and integral part of our perception of reality and surroundings. In a sense, it is an interface between the outside world and our responses at the biochemical and behavioural levels. Much like proposed by Dr. Lipton in his book The Biology of Perception.

    Cannabis-derived cannabinoids as prevention

    When we have done the above steps and have still not answered yes to all the 5 questions, then it is time to consider supporting the endocannabinoid system with plant-derived phytocannabinoids, especially CBD. For prevention, microdosing has gained much attention, since the threshold for medical benefits of cannabinoids is far lower than commonly assumed. Microdosing means that you take very small amounts of cannabinoids throughout the day. The definition of what a microdose constitutes is very individual. There is no magic bullet when it comes to dosing, but a starting dose of about 2 mg of CBD per day is usually a good place to begin with. Many people have reported that it helps them stay healthy, reduce stress, and stay sharp and focused at work. 

    Cannabinoid acids or juicing hemp

    Some experts argue strongly for the use of fresh hemp leaves and flowers for juicing, smoothies, salads. Dr. William Courtney is one of the advocates of this approach, believing that phytocannabinoids are essential nutrients. There is a vital difference in using the fresh plant as opposed to using already processed hemp products. The plant contains all the cannabinoids in an acid form, and they are called THCa (A standing for acid), CBDa, CBGa and so on. It was long believed that these are basically inactive forms of cannabinoids and that they have to be activated by heat to produce effects. We now know that this is not true, since the acid forms also have potent health promoting effects. What exactly these acid forms of cannabinoids do in our bodies is not 100% known. They do not bind to cannabinoid receptors and their mode of action has so far not been fully elucidated. THCa for example has completely different effects and, among others, lacks psychoactive effects completely. It is converted to THC by drying, light exposure, heating or smoking, in a process called decarboxylation. The molecule loses one CO₂ molecule and is converted to THC, with known effects.

    One could in fact ingest many THC-rich fresh plants and not get a ‘getting high’ effect at all, exactly because THC is in an acid form in the plant. It is a similar case with CBD. The fresh plant contains CBDa and depending on the processing methods, the end products can contain CBD, CBDa or a mixture. 

    Thus far we know that THCa and CBDa have the following effects:

    THCaCBDa
    anti-inflammatory 
    neuroprotective 
    antiemetic 
    antiproliferative 
    analgesic 
    antiepileptic
    antinausea
    decreased intestinal motility
    reduced stress
    antitumoral effect 
    anticonvulsant
    analgesic
    anti-inflammatory 
    antibacterial
    antioxidant
    cancer-preventing

    THCa and CBDa have been shown to have synergistic effects when combined, and when specific terpenes present in hemp are added, this combination is shown to significantly contribute to the effect of isolated acids in patients. This is called the Entourage Effect

    Cannabinoids as antioxidants

    Cannabinoids are very potent antioxidants and anti-inflammatory agents. These effects, observed with whole plant extracts, have been attributed mainly to non-psychoactive cannabinoids such as CBD, CBG and CBN. Cannabinoids were shown to be able to catch and neutralise free radicals in our body just like many other natural antioxidants. CBD was found to be as active as ascorbate (vitamin C) or tocopherol (vitamin E) and CBG was an even more potent antioxidant. The importance of antioxidative properties of food or food supplements is agreed on by the majority of nutritional experts. Also, anti-inflammatory effects are similarly gaining more and more importance. The search for the next best super food usually focuses on its antioxidative and anti-inflammatory effects and in our search for the most exotic roots or sprouts we fail to recognise the value of what is growing right in front of us. 

    Cannabinoids as neuroprotectants

    A consistent neuroprotective effect has been evident for cannabinoids. With CBD, it was shown to increase cerebral blood flow and provide neuroprotective effects. It was also shown to reduce the release of neurotransmitters and protect the neuronal mitochondria – the power plants of the cells. Interestingly, CBD had little effect on the neurons when they were in their normal state, but had a pronounced protective effect when the neurons were in an excited state. That would mean that it has little effect when all is ok, but when we are under stress or our neuronal system is challenged, then it will protect its functioning. This is in great coordinance with the overall protective function of cannabinoids. 

    It was also shown that low doses of THC can be very neuroprotective. This became evident in homes for the elderly in Israel, where the use of cannabinoids was approved for nausea, lack of appetite, insomnia, and pain, revealing with time that the use of cannabinoids also benefited the brain and cognitive functions. Animal and human studies later showed that very low doses of THC, well below the threshold of psychoactivity, (between 0.2 – 2 mg daily) actually reversed age-related decline in cognitive performance and also protected from alcohol-induced brain damage.

    It’s important to note that even small amounts of THC will interfere with the natural development of the brain, so treating conditions with THC isn’t recommended for people under 18.

    Cannabinoids as guardian molecules against diabetes and cardiovascular disease 

    Tetrahydrocannabivarin (THCv) is a very interesting cannabinoid, its name and structure are very closely related to THC, but it in fact has an almost opposite effect. Instead of activating CB1 receptors THCv seems to be an inhibitor, and it activates the CB2 and serotonin receptors. It was shown to restore insulin sensitivity in obese mice, reduce appetite and cause weight loss. It has also been tested in humans, where a single dose of 10 mg THCv changed the activity of brain regions involved in food intake. In patients with type 2 diabetes, 12 weeks of treatment with THCv (5 mg twice daily) decreased fasting blood sugars. It also has anti-inflammatory, antipsychotic, anti-seizure and neuroprotective effects. With this in mind, this phytocannabinoid holds much promise to prevent or treat type 2 diabetes and other metabolic disorders. 

    Cardiovascular diseases deserve special attention in the prevention chapter, since they are followed by stroke, representing the leading cause of mortality worldwide. Ischemia is a condition in which the blood flow (and thus oxygen) is restricted or reduced in a part of the body. The cause for this condition can vary from blood clots, hypertension, to injury and others. If this happens it can lead to a heart attack or stroke, but depending on where the blood vessels are blocked the symptoms can occur anywhere in the body. When discussing the effects of cannabinoids on cardiovascular health, we need to make a very strong distinction between different cannabinoids. As Pal Patcher said, we have the good, the bad and the ugly. 

    Synthetic cannabinoids are the ugly ones, they have caused severe health complications and even deaths. Usually they are mixed into cannabis sold on the black market and consumers do not even know what they are taking. 

    THC would be counted among the bad ones, since it affects blood pressure and heart rhythm. So for people with cardiovascular preconditions, like arrhythmia, hypertension or history of stroke, should be mindful of THC use. This is not to say THC is per se harmful for cardiovascular health, but as with any activity that raises the heart rate, caution is warranted, especially with dosing and contaminations. 

    CBD counts among the good ones, as it has been shown in many studies to be extremely beneficial for cardiovascular health. Ranging from positive effects on the blood vessels, blood clotting, blood pressure and heart function. Even intervention with CBD in cases of stroke or heart attack proved to be very beneficial. It was shown that if CBD is used as a prevention and a heart attack happens, the consequences for the heart muscle are less severe and the recovery period is shorter. And if CBD is used shortly (24h) after the heart attack, similar —but somewhat less potent— effects are observed. In the case of a stroke, observations were comparable. Both pre- and post-ischemic treatment with CBD resulted in potent and long-lasting neuroprotection. This all points to the fact that prevention with CBD would be extremely important for those who are predisposed for cardiovascular diseases.

    Cannabinoids as anti-age medicine

    Anti-age medicine has erroneously been perceived to consist of methods to reduce wrinkles by injecting botox to facial muscles, adding fillers to cheeks and tucking in excess skin. But the ageing we see on the outside happens due to processes on the inside, and much more important than the chronological age is our biological age. How old do our cells and organs really feel? Cannabinoids have many properties that put them in the front seat of inner anti-age medicine: from antioxidant, anti-inflammatory and neuroprotective effects on the cellular level; to cognitive functions, cardiovascular and gut health at the systemic level. In any anti-aging approach, stress management is vital, since too much cortisol is known to cause extensive cell damage. This is where cannabinoids have a vital role to contribute. 

    Cannabinoids also work at the level of DNA on the telomeres. Telomeres are the caps of DNA at the ends of our chromosomes that function like internal clocks, determining the rate at which we age. They shorten over time, as our cells divide, and when they become short enough, the chromosomes can no longer replicate and the cells die. Much of anti-age therapies, even gene-therapies, aim at telomeres, mostly by affecting the enzyme telomerase that degrades the telomeres. Interestingly, cannabinoids have been found to significantly decrease the activity of this enzyme. 

    It is clear that as the research mounts, there is solid and plentiful evidence of the positive impact cannabinoids can have through their interactions with the human body. Just as the human body is greater than the sum of its constituent parts, the hemp plant and its potential to improve people’s lives is far greater than some of its 1000+ elements. With this in mind, is it not logical that preparations that contain multiple compounds from this ingenious plant are better suited to medical applications than single isolated compounds? Only time, and more importantly, a dramatic increase in the amount, and scope, of research will tell.


    Tanja Bagar, Ph.D., Assistant Professor, CEO and Chairman, Expert Council of the International Institute for Cannabinoids
    AUTHOR

    Suggested product: Cerulean53 Broad-spectrum CBD oil. Cerulean53 is part of the Ardoa Organics S-drops range, and is our most potent CBD oil drops product with the broadest spectrum available. 

    Read more about how medical cannabis can aid chronic pain management: Science Digest – Clinical CBD Study: Adding medical cannabis to standard analgesic treatment for fibromyalgia


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