 The inflammatory process is designed to help us with the function and repair of injury. However, inflammation that is out of control and chronic can lead to diseases such as metabolic syndrome or arthritis. Acute inflammation can be downright painful. It is no wonder we have developed anti-inflammatory medications to control these effects and have now turned to a more natural relief, cannabidiol.
What is Inflammation? nflammation is the body’s response to injury. It is the body’s way of telling the immune system that it needs to heal itself, repair damaged tissue, and defend against pathological invaders such as bacteria and viruses. For example, in acute injury, inflammation is usually short, and it is designed to remove the harmful agent. This is a positive inflammatory response. Our job is to prevent the inflammation from getting out of control by taking anti-inflammatory measures. Short-term measures for acute inflammation might include rest, ice, compression, elevation, and topical CBD. When inflammation is prolonged past the critical stage and becomes chronic, tissue damage can occur, and pain can become relentless. What happens when inflammation sets in? Your body increases its production of white blood cells and cytokines to help fight infection. Cytokines are small messenger proteins that can stimulate inflammation. Cytokines can be pro-inflammatory and cause swelling and heat in the tissues as an inflammatory response. Cytokines are also involved in the sensation of pain. CBD has been shown to downregulate cytokines. The primary problem with inflammation is the increased production of free radicals, causing oxidative stress. Oxidative stress is the balance between the production of free radicals and the presence of antioxidants. When there are more free radicals than antioxidants, the body becomes stressed and out of balance, and tissue damage occurs in general. When oxidative stress operates, total speed damage occurs to proteins, fats, and genetic material, specifically. CBD has been shown to have potent antioxidant activity. Signs of inflammation include:
If inflammation is necessary for our body to heal, what types of inflammation do we need to control to feel well and still be in balance and healthy? Acute inflammation Inflammation can be divided into acute and chronic. There is local vasodilation, increased capillary perfusion, accumulation of fluid, and pain from increased cytokine production in acute inflammation.” If these processes are not halted, such as by the use of CBD, and whatever caused the inflammation is not removed, progression to chronic inflammation will occur, which is characterized by a maladaptive immune system and the overexpression of pro-inflammatory genes, the dysregulation of cellular signaling and the loss of barrier function. Examples of acute inflammation:
A reaction to an acute injury will begin within two hours of the injury, and anti-inflammatory measures are generally begun to prevent the inflammation from causing tissue damage or pain from the resulting swelling. Acute inflammation can serve a positive role if it stops an infection from causing tissue damage or cushions an injured joint from further harm. Chronic inflammation is a maladapted immune system response of the immune, nervous, endocrine, and reproductive systems to a perceived threat or injury. This maladaptation leads to such diseases as:
Can CBD be Used for Inflammation? Some of these chronic conditions do not have acceptable treatments for the pain associated with them, such as osteoarthritis. Opioids and non-steroidal anti-inflammatories often do not adequately control the pain and/or are not acceptable as a treatment option. In a landscape of opioid addiction, other viable pain relievers must be found. This is where CBD can be safely used topically or orally to control the pain from the inflammatory process. CBD as a Safe Alternative Anti-inflammatory Current therapies for inflammation involve pharmaceutical drugs with well-known and mostly adverse side-effect risk profiles not only on the cardiovascular system but also on the gastrointestinal tract. Drugs such as diclofenac sodium or ibuprofen are common pharmaceutical answers to inflammation, but they come at a price that may put your heart or gut at risk. CBD has few to no adverse side effects making it a perfect alternative to more dangerous therapies. Does CBD Help With Inflammation? CBD is well known for its anti-inflammatory effects, and CBD limits the formation of free radicals and modulates the function of the immune system. How does it do this? CBD is known to: ● Increase cellular apoptosis (cellular death). Cell death refers to leakage of cell contents into the adjacent tissues, resulting in the transfer of white blood cells to the injured tissue. The accumulation of white blood cells and enzymes and oxygen radicals release enhances the inflammatory reaction. ● Inhibit cell proliferation. The cellular division increases rapidly during the inflammatory process, and CBD slows down the growth of unruly cells. ● Inhibit cytokine production. Cytokines are signaling molecules released from immune cells that cause inflammation. ● Stimulates induction of T-regulatory cells. T-regulatory cells prevent auto-immune disease, are immunosuppressive, and promote wound healing. ● IL-6 suppression IL-6 has pro-inflammatory characteristics and plays a pathological role in autoimmunity and chronic inflammation. CBD amplifies CB2 receptor signaling, which regulates inflammation and immune cell activity. It does this without actually binding to the CB2 receptor, and CBD can down-regulate the CB1 receptor while up-regulating the CB2 receptor. It does this through a myriad of parallel metabolic pathways involving other receptor sites and enzymatic actions. Its actions are often termed the “entourage effect” since CBD works in concert with terpenes, flavonoids and other synergistic molecules to achieve its anti-inflammatory effect. CBD is also known to inhibit a specific enzyme (FAAH) that breaks down the body’s own endocannabinoid, Anandamide, causing these levels to be elevated exerting another synergistic anti-inflammatory effect. CBD Dosage for Inflammation Clinical trials are fervently underway to answer the myriad of questions the new legal status of CBD has ushered in. With CBD status now primarily legal in the US and Europe and the rest of the world taking a renewed interest in it pharmacologically, studies that can accurately answer CBD dosage questions are underway. For now, we have a plethora of animal studies that cannot be extrapolated to humans and small, poorly designed human trials from which to glean some information on dosages for inflammation. Topical doses of CBD for inflammation Animal studies have shown us that low doses of CBD do not exert an anti-inflammatory effect that we must turn to higher doses to achieve local effects. This could be because CBD will interact with cannabinoid receptors in the epidermis (the outer layer of skin tissue) but not enter the endocannabinoid system itself. The epidermis has cannabinoid receptors, but the effect is local, not systemic, which is why topicals can be used without the CBD getting into the bloodstream and, thus, the entire endocannabinoid system. Transdermal applications have shown a dose-dependent response, with the higher doses giving greater pain relief. Animal studies showed a wide range of effective doses from 6.2 – 62 mg/day. Transdermal applications enter the endocannabinoid system. Oral doses of CBD for inflammation Oral bioavailability is quite low – about 13%-19% of the ingested amount. According to one study, suggested oral amounts are 5-25 mg/kg/day. To get an idea how much CBD oil this would be for anti-inflammation for this woman, calculate: for a 60 kg woman, take 60 kg and multiply by 5mg = 300 mg of CBD. The low oral bioavailability is due to the excretion of metabolites via the kidneys and the multiple metabolic pathways CBD undergoes in the transition from the gastrointestinal tract through the liver and then undergoing elimination. Oral CBD bioavailability can be increased if taken sublingually and held under the tongue putting the oil in direct contact with the blood vessel located on the underside of the tongue. Hold the oil there for 60-90 seconds. CBD doses based on weight Other resources based on body weight suggest a dose range of 1-6 mg of CBD per 10 lbs. Of body weight. The weight guideline is unclear on whether these dosage recommendations are for inhaled or oil-based products. For example, starting at the lowest dose of 1 mg per 10 lbs., a 100 lb. woman would need 100 lbs. divided by 10 = 10 x 1 mg = 10 mg to start. Dosages will vary according to several variables, including sex, genetics, environment, presence of food, the form of CBD, age, and others. A scientific basis for the weight guidelines is not found and varies from website to website. What about CBD vaping for inflammation? Doses by inhalation would theoretically be lower as you don’t have to deal with the first pass metabolism associated with digestion and the CBD would pass into the bloodstream within minutes. Clinical data on inhalation doses for inflammation are currently lacking, although a proposal for an aerosol delivery system of 4 mg -200 mg of CBD has been proposed. Is CBD legal for athletes to take for their injuries? All cannabinoids except for CBD are prohibited from the World Anti-Doping Agency (WADA), so CBD is in the clear for using topically or orally to treat inflammatory conditions resulting from sports trauma or injuries. Topical ointments and creams packed with CBD are widely available in doses up to 3500 mg for application on injured areas to subdue pain and reduce swelling in the injured athlete. These may be used in conjunction with CBD oils for a synergistic effect. Application We know CBD works for inflammation, and it offers a safer alternative than opioids or NSAIDs. Many products for CBD treatment exist, and more are being put on the patent market every day. The literature supports using both topical and oral CBD for inflammation, with dosages yet to be determined. Acute inflammation would benefit from topical use of the creams and lotions with supportive oral use as prevention for a few days. More chronic conditions might want to consider oral or aerosol/inhalation devices for use every day to prevent the persistent discomfort prevalent with the pain these inflammatory dysfunctions often bring. And, always, if in doubt, consult your physician or health provider for guidance.
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 The endocannabinoid system, or ECS, is a complex system of cellular signaling present in all vertebrate animals and necessary for our very survival. Discovered in the 1990s while researchers were exploring THC, a well-known cannabinoid present in marijuana, the ECS is now known to be involved in several other physiological systems related to mood, stress, appetite, memory, reproduction, inflammation, sleep, pain, thermogenesis, heart function, and anxiety. Endo, meaning “in” is an important deviation from the word cannabinoid because It implies that these cannabinoids are made within the body and not obtained exogenously from a plant. Essentially, the ECS keeps everything in balance. If you start to sweat on a hot day, it is the ECS that kicks in monitoring your internal environmental temperature and stimulates the sweating or cooling down process. It is responsible for homeostasis in the body. The endocannabinoid system, with its complex actions in our nervous system, immune system and various biological and behavioral systems, it is literally a bridge between body and mind. By understanding this system, we can begin to explore how states of consciousness can affect health or disease. Furthermore, recent research shows that endocannabinoids, phytocannabinoids and the ECS induce widespread or gene specific changes with the possibility of genetic transferability of changes from one generation to the next. This puts a sense of permanency to changes that occur because of the ECS. The ECS Tone The ECS operates in a continuous cascade of enzymatically orchestrated pathways of which the endocannabinoids flow, attach to receptors, are degraded and synthesized as needed. This may all happen congruently in a multi-system fashion. This is called the ECS tone. ECS tone is an indication of the overall state of your ECS. Obesity, for example, represents an elevated hypothalamic endocannabinoid tone. Diabetes is another example of a dysregulated tone. The tone is the overall action generated by the receptors, endocannabinoids, and enzymes all working in sync throughout the body, creating a rhythmic flow that leads to balance in the body. A lack of balance often involves a dysfunctional ECS. How Does the ECS Work?The ECS system is a vibrant and alive system whether you are aware of its processes or not. Endocannabinoids are produced within the body which is why we have receptors for them located in all our major organ systems. Cannabinoid receptors sit on the outside of cell monitoring for conditions both inside and outside the cellular wall to observe changes in cellular activity. Enzymes then respond to changes in cellular activity by degrading the endocannabinoids no longer needed. When signals are received at the receptor that an endocannabinoid is needed, it is made immediately and secreted to attach to the cannabinoid receptor where it is then taken up into the cell and tells the cell how to secrete other substances like hormones or neurotransmitters such as serotonin. They affect how other messages are sent, received and processed by other cells. There are three major components to the ECS system.
Taken together, these three components of the ECS regulatory system ensure that the body remains in homeostasis with neither deficiency nor excess of activity. What Are the Two Main Cannabinoid Receptors?Scientists estimate that the endocannabinoid system evolved over 600 million years ago. Cannabinoid receptors are present throughout the body and are considered to be the most numerous receptor system. Endocannabinoids are cannabinoids our body makes that bind to these receptors, and phytocannabinoids are plant cannabinoids that also bind to these receptors. The two main cannabinoid receptors most studied are CB1 and CB2. CB1 is the most abundant receptor in the brain, while CB2 receptors are found outside of the nervous system, such as in immune cells. The receptors act as a doorway for the cannabinoids to enter the cell. Both endocannabinoids and cannabinoids from plants can bind to the CB1 and CB2 receptors. Receptors are like locks, and THC is like a key that unlocks the door and allows metabolic processes to occur. Both endocannabinoids bind to these receptors like THC does to CB1 but are produced on demand in nerve cells and travel backward to inhibit the release of various neurotransmitters. For example, glutamate is one of the stimulatory neurotransmitters, but when present in excessive concentrations, such as after a stroke or head injury, it can cause neuropathic pain. The endocannabinoids are naturally secreted after such an injury and act to inhibit glutamate release, thus alleviating neuropathic pain. A third receptor, TRPV1 or transient receptor potential vanilloid-one, is also considered part of the ECS and targets the body’s two main endocannabinoids but not THC. Growing evidence shows that non-retrograde communication exists within the ECS. Multiple points of interaction have been identified in the ECS involving the TRPV1 receptor. Evidence points to CBD acting via the TRPV1 receptor in mediating some of its effects in potentially alleviating the inflammation of arthritis. What Are the Two Major Endocannabinoids? Unlike THC, endocannabinoids are produced within the body and bind to the CB1 and CB2 receptors. These two endocannabinoids are: · Anandamide (from Sanskrit meaning “eternal bliss”) · 2-arachidonoylglycerol (2-AG) A unique and striking feature of these endocannabinoids is that their precursors are present in fatty membranes. Upon demand, endocannabinoids are liberated in one or two rapid enzymatic steps and released into the extracellular space. This is in direct contrast to typical neurotransmitters like serotonin which are secreted ahead of time. The routes of synthesis and degradation of anandamide and 2-AG are distinctly different from each other. Relationship Between THC and Endocannabinoids These endocannabinoids are not mind-altering, addictive chemicals such as THC. That is where so much of the public confusion comes in. THC may be similar in structure to anandamide; however, it is not the only plant-based cannabinoid being studied as having effects in the ECS system. Relationship Between THC and CBD Cannabidiol, or CBD, is another cannabinoid under study that does not have the psychoactive effects associated with the plant-based cannabinoid THC. Cannabinoids are compounds found in the cannabis Sativa plant, of which THC and CBD are the most actively studied cannabinoids to date. CBD is the second most abundant cannabinoid after THC in the cannabis plant. In addition, a total of 8 other major ones have been identified, with a total of over 100 confirmed to date. How Do Endocannabinoids Work?Endocannabinoid release occurs immediately after bodily biosynthesis with no intermediate storage for “later use,” making them ideal homeostatic modulators in real-time. This is seen, for example, in appetite regulation. Endocannabinoids regulate appetite and food intake through stimulation of the CB1 receptors, which stimulate the release of hunger/satiety hormones. This all happens relatively rapidly with little thought; it is just an occurrence of “balance” between hunger and satiety. Homeostasis. Balance. The role of enzymes Metabolic enzymes that break down the endocannabinoids after they are used are important for maintaining homeostasis. Two primary enzymes have been isolated that are charged with this duty: · Fatty acid amide hydrolase or FAAH · Monoacylglycerol acid lipase (MAGL) FAAH breaks down anandamide, and MAGL breaks down 2-AG. These enzymes guarantee that endocannabinoids are used for as long as needed and no longer. This is a distinguishing factor of these enzymes from the actions of hormones or other regulating signals like neurotransmitters, which can persist for seconds or minutes or be packaged and stored for later use. These enzymes cannot break down plant-based cannabinoids, a limiting factor in cannabinoid research relative to disease treatment. This means that if an active dose of cannabinoids is found for an illness, the exact dosage must be determined because the natural homeostatic mechanisms of the ECS will not be able to regulate cannabinoids administered from the plant. Endocannabinoid Deficiency As we learn more about the ECS, we discover diseases that may be classified as endocannabinoid deficiency diseases. Medical science has termed these clinical endocannabinoid deficiency dysregulation diseases, or CECD for short. The available evidence seems to indicate that the ECS systems suffer from a deficiency of anandamide, thus suggesting that treatment of the ECS to upregulate the tone might benefit these disorders. These conditions include:
The conditions listed frequently involve more than one physiological system and effective treatment for them has been difficult to unearth. It is only logical that science would look to multisystem treatment modalities such as cannabis to treat multisystem disorders such as the ones just mentioned. How Does THC Interact With the ECS? THC interacts with ECS in the same manner as the endocannabinoids do. It can bind to either CB1 or CB2 receptors and is not subject to enzymatic regulation, thus the problem with addiction and mind alteration. On the other hand, it may help with pain and stimulate the appetite of those who have lost theirs, as in cases of anorexia. How Does CBD Interact With the ECS? CBD is a different story. CBD doesn’t make you “high” and doesn’t carry any negative side effects such as paranoia or delusions. Experts don’t exactly agree on how CBD works or even exactly what it does, but they hypothesize that it prevents endocannabinoids from being broken down through the effects of the enzymes. Scientists do know that CBD doesn’t bind to the CB1 or CB2 receptors in the same manner as THC. Science has proven that CBD prevents the enzyme FAAH from breaking down cannabinoids, unlike THC, where enzymes have no effect. The ECS is the key to maintaining homeostasis in our body. It may one day hold the answers to treatments for diseases that affect multiple organ systems for which we have no treatments. The ECS offers a rich landmine of untapped research and potential therapeutic applications. Concluding Remarks We need to further educate others on the important role of the ECS on cannabinoids and the differences between THC and CBD. Along with more research, we need to keep an open mind as to the application of cannabinoids to therapeutic treatments of multi-system disorders for which we currently have no well-defined treatment protocols. And keep in mind that lifestyle activities can alter endocannabinoid tone and, thus, ECS activity. Research has shown that diet, supplements, herbs, weight control, and exercise also modulate the ECS tone. Clinical trials investigating these modalities are sorely lacking and in need of attention. In conclusion, the ECS may be a newly discovered system, but it is old in its presence and seemingly imperative to our existence. Furthermore, the field of pharmacology is now considering all members of the ECS as potential novel therapeutic targets for the modulation of problematic diseases. The discovery of the ECS opened a doorway to the discovery of possible novel therapeutic agents that can be utilized in the form of cannabinoids or related chemical structures to modulate health and disease without the adverse side effects so often associated with the psychoactive cannabinoid THC. Keywords: endocannabinoid system, anandamide, 2-AG, ECS, endocannabinoid deficiency, cannabinoid receptors |
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