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This is an unaltered image from the following: Int J Mol Sci. 2018 Mar; 19(3): 833.
What is CBD?
CBD stands for Cannabidiol which is one of the two most abundant cannabinoids found in the Cannabis plant from which CBD can be extracted. The other abundant cannabinoid from this plant is Tetrahydrocannabinol (THC) which is the psychoactive substance found in marijuana. It is important to note that cannabidiol is not the same thing as marijuana.
Marijuana is a cannabis plant called Cannabis indica and contains THC as well as CBD. Hemp is a cannabis plant called Cannabis sativa and contains only small amounts of THC. Therein lies the controversy surrounding those that support medicinal marijuana versus those that support CBD and full spectrum hemp oils. Those in the marijuana camp believe that CBD can only reach its full potential by being exposed to THC in a synergistic relationship. Those in the hemp camp believe in the full power of hemp even with the reduced amounts of THC it contains. Hemp products have 0.3% THC or less in order to be sold legally.
To understand the possible therapeutic effects of CBD, it is important to understand that CBD is part of the endocannainoid system (ECS). Since it became legal to grow hemp with the 2018 Farm Bill, there has been an explosion of information from studies looking at this system.
What is the Endocannabinoid System (ECS)?
The ECS is present as a normal system within the body involved in lipid signaling. Contained within the ECS are cannabinoids, cannabinoid receptors and enzymes. The system is present in the Central and Peripheral Nervous system, the heart, intestines, and is involved in immunity, autonomic nervous system function and microcirculation.
The ECS has two main cannabinoid receptors simply known as Type 1 (CB1) and Type 2 (CB2). The receptors are regulated by the endocannabinoids of the ECS involving numerous physiologic functions. Type 1 receptors are found in the brain and regulate emotional responses, sexuality, reproduction and maintenance of homeostasis (the normal “balance” of the body). Type 2 receptors are mainly found in immune cells but are also expressed in the heart, gastrointestinal tract, liver, fat tissue and the reproductive system.
CBD and THC are just two of the cannabinoids identified. Research on the plant has identified over 100 cannabinoids contained within Cannabis. Collectively they are known as phytocannabinoids. The target receptors for modulation of the endocannabinoid system are CB1 and CB2. Two other common endocannabinoids are amantadine (AEA) and 2-arachidonoyl glycerol (2-AG). Endocannabinoids are produced on demand, are not stored in a cell, and degrade rapidly after exerting their influence on tissues. They don’t just “hang around”.
The CB1 and CB2 receptors are involved in numerous normal body functions as well as pathology which result in disease. Therefore, a significant amount of research is being done on the effects of CBD on improving disease and maintaining health.
For ease, I will refer to CBD while discussing the numerous ways in which use of phytocannabinoids may improve health. What I’m talking about is all 100 of them.
Conditions that CBD may improve (with references)
Research continues on modifying the ECS using CBD and how they may improve various disorders. The ECS and receptor activity appears to be altered in disease states. Pathology can inhibit or prolong the actions of endocannabinoids and therefore modulation of the ECS can lead to therapeutic benefits.
The following health conditions are currently being studied:
Cancer- especially regarding management of treatment side effects
High blood pressure
Heart attack
Heart disease or “hardening of the arteries”
Emotional issues such as depression and anxiety
Multiple sclerosis
Chronic pain syndrome
Seizure disorders
Peripheral neuropathy pain
Insulin resistance and abnormal weight gain
Parkinson’s disease
Let’s look at each in more detail.
CBD and Cancer
The research data on the use of CBD in cancer patients with pain and nausea seem to be solid. The data on the anticancer benefits of CBD is inconsistent.
THC has been shown to help with cancer pain as well as the nausea associated with chemotherapy. It also has anti-inflammatory properties. Inflammation is a process of significance in patients with cancer. It is important to note that full spectrum hemp products contain a small amount of THC which can work together with the rest of the endocannabinoids.
As for anticancer effects of CBD, some studies show an up regulation of the CBD receptors in some cancers. Other reports indicate that activating CBD receptors can keep cancer from developing. The main effects of CBD on tumors seems to be inhibition of cancer cell growth and causing cancer cells to “commit suicide” by a process called apoptosis. Apoptosis results in death of these cells. These effects have been observed in cancers of the lung, prostate, pancreas, breast, cervix and gliomas of the brain.
Research is also being done on the effects of CBD on the immune system response to cancers. This may involve the CB2 receptor found in immune cells that may enhance their activation in response to tumor invasion. The immune system appears to modulate the growth and development of many types of cancer. If the immune system response is weakened, that may be the spark to let cancer cells proliferate.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852356/
CBD and Seizure Disorders
The use of Cannabis in the treatment of epileptic seizures dates back 4000 years. The first studies were done in China about 2700 B.C. There has been an explosion of research in the use of CBD oil and THC in the management of this condition.
There is finally evidence for CBD use in double blinded, randomized and controlled studies. Three studies have now been done showing a reduction in seizure activity in patients treated with low dose CBD oil. Interestingly, the most beneficial dose for CBD oil treatment of seizures was only 10mg daily. It appears this may lead to an evidence based recommendation for the use of Cannabis in the management of epilepsy.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767492/
CBD in Chronic Pain Syndrome
In light of the opioid use epidemic, the search for an effective alternative for chronic pain management that does not create dependence or addiction is a priority in this country. An ABC News poll indicated that 19% of Americans have chronic pain and 6% have used Cannabis to treat it.
Chronic pain syndrome is defined as persistent pain that lasts three months in duration or pain that lasts past the normal time of tissue healing. Approximately 25% of people who have acute pain will go on to have chronic pain syndrome. In the past twenty years, the use of opiate pain medication has increased significantly for management of chronic pain syndrome and leads to dependence.
It is important to distinguish between opiate dependence and opiate addiction. All chronic pain syndrome patients on long term opiates are dependent. That does not mean they are addicts. All opiate addicts are dependent but addicts are compulsive in their use of narcotic pain medications. Addicts do not stop taking opiates until they have none left. An opiate dependent chronic pain syndrome patient will take their medication as prescribed.
Research indicates that in treatment resistant pain conditions, there appears to be an endocannabinoid deficiency at work. If stimulated, the ECS has been shown to reduce pain in migraines, fibromyalgia, irritable bowel syndrome and intestinal pain.
CBD also appears to reduce inflammation which contributes to chronic pain syndrome. The cannabinoids have been shown to be 10 times more potent than morphine in the neurons that mediate pain from the thalamus of the brain.
Non cancer pain patients have self reported using cannabis for a variety of chronic pain locations including the lower back, neck, head, abdomen, and knee. It has also been used for multiple sclerosis, myofascial pain, infection, arthritis, stroke and trauma/postoperative pain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2503660/
CBD and Heart Disease
Despite the focus on the role of cholesterol levels in heart disease, the abundance of evidence points to chronic inflammation as the major risk factor for heart disease and heart attacks. Inflammation of the inner lining of cardiac arteries begins the cracking and damage that leads to plaque buildup and arterial narrowing. Eventually a clot forms in the damaged vessel and you get a myocardial infarction (heart attack). Fifty percent of the risk of heart attack is from chronic inflammation, with cholesterol and family history each providing 25% of the risk.
Functional Medicine looks at the causes of disease and how to prevent them. You cannot control your heart disease family history. You can control your chronic inflammation and cholesterol levels. The point is to avoid treating the symptoms of the disease by preventing the disease in the first place.
CBD positively influences the response of the cardiovascular system to stress. It also influences the life cycle of white blood cells and platelet aggregation, two hallmarks of inflammation that can lead to arterial damage.
Very recently, CBD was found to cause relaxation in blood vessels. This may be due to increased availability of nitric oxide which dilates and relaxes blood vessels. This, in turn, should lower blood pressure and reduce hypertension related risks of stroke and heart attack.
CBD is now known to mediate the effects of heart attack, atherosclerosis and heart disease. CBD appears to limit damage of heart muscle brought on by heart attack through improved reperfusion and reduction in ischemic (lack of oxygen) injury to the heart.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579247/
CBD and Anxiety/Depression
There are imaging studies that can be done on the brain which show altered blood flow in patients who suffer from anxiety and/or depression. The fear response that can be so debilitating to those with anxiety and post traumatic stress disorder (PTSD) resides in the amygdala. Depressive symptoms and emotions in general are controlled in the cingulate cortex, amygdala, hippocampus and hypothalamus.
THC use in those with anxiety is dose dependent. Low doses seem to relieve anxiety whereas higher doses may actually make anxiety symptoms worse. However, the combination of THC with CBD, which is found in full spectrum hemp, has a synergistic effect on anxiety symptoms. Imaging studies on the brain show that CBD induces significant reduction in anxiety symptoms. Also, CBD allows the extinction of fear memories associated with PTSD by acting on the amygdala and cingulate cortex.
Studies in patients with depression have demonstrated a significant reduction in the endocannabinoid known as 2-AG and is worsened the longer major depression symptoms are present. Exposure to social stressors in these individuals increases the serum levels of this endocannabinoid in response to the associated anxiety.
There are seven studies that show CBD to be effective in reducing depressed mood. Other studies show an increase in depression symptoms with heavy cannabis use and one study that shows an increase in manic episodes in patients with bipolar disorder. As with any intervention, people are not all alike and management needs to be individualized. However, for most, low dose CBD appears to be effective in several mental health disorders.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313625/
CBD and Diabetes/Insulin Resistance
The CDC estimates that 30 million Americans have Diabetes which translates to 1 in 10 people. 90–95% of them have Type 2 diabetes. Type 1 diabetes is generally found in childhood and is a lifelong illness. Type 2 diabetes is usually found in adults and is preventable as well as reversible.
Metabolic syndrome is a state of insulin resistance that is considered pre-diabetic. The CDC estimates that 80 million Americans have pre-diabetes bringing the total number of Americans having insulin issues to over 100 million.
The development of Type 2 Diabetes and insulin resistance involves oxidative stress and chronic inflammation. Eventually, insulin resistance leads to the actual diagnosis of diabetes with all the tissue complications of this disease. Deterioration continues from oxidative stress and inflammation leading to heart disease, kidney failure, stroke, blindness, amputations and premature death. Complications of diabetes is the seventh leading cause of death in Americans.
Several studies show that CBD can reduce oxidative stress, chronic inflammation and cell death in those with diabetes. This appears to be related to CB2 receptor activation while activation of the CB1 receptor can make diabetes complications worse. Specifically, the search is on for a way to down regulate the CB1 receptor and up regulate the CB2 receptor in diabetes. The natural endocannabinoids found in full spectrum hemp appear to do just that and have tremendous therapeutic implications in the management of this dangerous disease.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349875/
CBD and Abnormal Weight Gain
On the world spectrum, it is estimated that almost 2 billion people on earth are overweight with 600 million of them considered obese. Based on Body Mass Index, a level of 26 kg/square meter is considered overweight and at 30kg/square meter is termed obesity. The goal for BMI is 19–25kg/square meter.
The CB1 receptors for endocannabinoids are found mainly in the central nervous system. However, in obese individuals, these receptors proliferate throughout the body and are more numerous. The endocannabinoids are significantly involved in metabolism, food intake and energy utilization.
Fat is located in two types of adipose tissue. Brown Adipose Tissue cells have several small lipid droplets and a high concentration of mitochondria which is the energy producer within cells. Mitochondria give this tissue a brown appearance and is involved in heat production and caloric expenditure. Brown Adipose Tissue is thus more involved in metabolism. White Adipose Tissue has a single lipid droplet and appears either white or beige in appearance. This tissue is involved in fat storage and secretes hormones.
Activation of Brown Adipose Tissue has significant implications in weight loss as well as lipid and glucose metabolism. White Adipose Tissue is activated into beige by exercise, being cold or by thyroid hormone. The beige tissue is an intermediate that occurs when White Adipose Tissue transforms into metabolically active Brown Adipose Tissue via “browning”. The CB2 receptor has been found to trigger enhanced browning which produces thermal energy. Blocking the CB1 receptor induces the same change.
THC has a strong affinity and binding to the CB1 receptor increasing appetite and fat storage by activating the receptor. CBD has no binding or affinity for CB1 or CB2 receptors and influences their activation indirectly to get the appropriate ECS response. Activation of CB2 by CBD provides a higher safety profile with no side effects for management of obesity.
There are six FDA approved medications for weight management all of which have a host of side effects. Only Orlistat is approved for weight management in children. Its list of side effects include oily stools, flatulence, GI discomfort, fecal incontinence, vitamin deficiency as well as damage to the liver, pancreas and kidneys. Activating the CB2 receptor with CBD enhances the conversion of White Adipose Tissue to Brown Adipose Tissue in a safe and effective manner.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163475/
CBD Guidelines for Use
Although the research for therapeutic use of CBD is very promising, it is still in its infancy. It has only been legal to grow hemp in the United States since 2018. It is important to keep several things in mind when considering or starting CBD.
1. Start with low doses and work up in increments. Note that low doses of CBD work very well when dealing with mental health and seizure disorders. Chronic pain syndromes may require higher dosing but there will be a “sweet spot” that is individualized for each person.
2. Make sure to read labels so you know how much CBD you are taking. A typical starting dose is 10 mg in 1cc of oil. There are many different strengths of CBD oils on the market. Look, compare and increment up based on the CBD strength in the oil, cream or edible you are using.
3. You are probably better off using full spectrum products to obtain the best “bang for your buck” and take advantage of all the endocannabinoids. There are full spectrum hemp products and CBD only extract products. Hemp products will contain less than 0.3% THC while CBD extracts have only cannabidiol. There is an “entourage effect” with full spectrum hemp which takes advantage of the synergy that occurs between the various cannabinoids.
4. There are many medications that involve the Cytochrome P450 system of the liver which brings up the possibility of CBD interaction. You must consider any medications and supplements that use that system and watch for interactions that could occur.
5. Make sure of the quality of the CBD products you are considering for use. Buying CBD products from the convenience store or gas station may help your wallet, but may not be of good quality. There are reputable companies that produce hemp products and have a certificate of analysis, frequently from an independent lab. While a higher price does not guarantee quality, a low priced hemp product is probably cheaper for a reason.[/vc_column_text][/vc_column][/vc_row]
