Behind the Science: Introducing CV Defense w/ Dr. Jamie Corroon
Mar 16, 2021
CV Defense was created with specific intent — fortify your daily immune health. Dr. Jamie Corroon, ND, MPH, Founder & Medical Director of the Center for Medical Cannabis Education and CV Sciences Medical Advisor, presents an overview of the science behind CV Defense, the latest addition to CV Sciences’ new line of Immunity products. A published clinical researcher and endocannabinoid expert, Dr. Corroon discusses the interplay between the endocannabinoid system (ECS) and the immune system and gives us a glimpse into the hundreds of scientific studies backing the active ingredients in CV Defense for daily support of barrier, innate and adaptive immunity. The information presented in this webinar is for educational purposes only.
Dr. Jamie Corroon, ND, MPH:
My name is Dr. Jamie Corroon, and in this video we are going to look at a new product from CV Sciences called CV Defense. I am the medical director at the Center for Medical Cannabis Education in San Diego, California, where I have a specialty clinical practice. I help patients use phytocannabinoids like THC and CBD to treat their symptoms and medical conditions. I also do clinical research there and consult for a variety of cannabis companies both marijuana and hemp companies. I'm also on the medical advisory board of CV Sciences.
Our objectives for today are to introduce CV Defense, to discuss the interplay between the endocannabinoid system and the immune system, and to review the ingredients in CV Defense, and just look at some of the scientific literature that supports their inclusion in this formula.
This product emerged from a crisis, the crisis we're actually facing during this moment, which is a global pandemic caused by a novel coronavirus. The immune system is front and center in the news and in scientific research. Immune support is a catchy slogan but what does that actually mean? And we'll talk a little bit about that. CV Sciences as well as some other manufacturers of dietary supplements saw a need to create a product to help consumers support their immune systems. But to be clear this product is not designed to diagnose treat cure or prevent disease including viral infections and especially COVID-19. The ingredients of CV Defense may alter the structure and or the function of important aspects of the immune system particularly as it relates to infection, but these ingredients are not approved by the FDA as disease fighting medications.
Before we delve into the product, let's quickly review the endocannabinoid system and talk about how it interacts with the immune system. A simplified description of the ECS includes three basic components: cannabinoid receptors, the endocannabinoids themselves, and the enzymes which both biosynthesize and hydrolyze or degrade them. Cannabinoid receptors are g-protein-coupled receptors, there are two of them that have been identified to date: the CB1 and the CB2 receptor. To simplify the distribution of these two types of receptors in the body, it's often said that CB1 receptors are most often found in the central and peripheral nervous systems, while CB2 receptors are mostly found in the periphery on tissues of the immune system and on immune cells, white blood cells in particular. This is obviously a simplified explanation, but it is somewhat helpful.
Endocannabinoids are lipid signaling molecules that are derived from arachidonic acid: anandamide, or AEA, and 2-AG are the two endocannabinoids that have been identified and described to date. They were discovered in the early to mid- 1990s. PEA, which we will talk about, is technically not an endocannabinoid. But if you look at the chemical structure, it sure looks like one. It modulates the interaction between endocannabinoids and cannabinoid receptors, as well as mediating other immune supportive effects, and we'll look at this.
When talking about the endocannabinoid system, we typically talk about the central nervous system, and we're referring to endo or phytocannabinoids interacting with receptors in the brain and spinal cord mostly CB1 receptors. But the endocannabinoid system is more than a neuroregulatory system, it's also an immunoregulatory system. In this diagram we have a cross section of the gut. Up here is the lumen, where food and water and some bacteria are. There is inflammation here in the wall of the gut as indicated by these white blood cells, a mast cell, and a macrophage here. And inflammatory mediators are released by these white blood cells as is anandamide. And, to be clear, the endocannabinoid anandamide is released here as a result of the inflammation with a goal so to speak of restoring homeostasis. Anandamide diffuses and activates CB1 and CB2 receptors on these white blood cells and this causes a decrease in the production and secretion of these inflammatory chemicals. Now this is an example of innate or non-specific immunity. In this model supplementing with compounds that act like anandamide could be considered immune support. And by the way this is not how CBD exerts its anti-inflammatory effects, scientists are still trying to figure that out. But there are a variety of different mechanisms, some of which we'll talk about.
Today, stepping back for a minute, the immune system is extraordinarily complex, and I'm going to attempt to provide a basic outline here on one slide. So, the immune system is primarily composed of white blood cells and the tissues that produce these white blood cells, including bone marrow. And these white blood cells have specific names in specific systems in the body. So, for example, glial cells are type of white blood cell in the nervous system functionally. White blood cells are divided into two broad categories: those that mediate the innate or non-specific immune response, and those that mediate the acquired or adaptive or specific immune response which is also called humeral immunity.
So, I'm going to try for simplicity to stick to adaptive and innate or specific and non-specific. Adaptive immunity here on the left is mediated by antibodies, which are produced by B-lymphocytes. These are the B-lymphocytes here and these are the antibodies in blue and red. While innate immunity is mediated by T-lymphocytes: here's a helper T-cell, here's an antigen presenting cell, here are other T-cells. Cytokines, which are chemical signals produced by and responded to by white blood cells, are an important part of both types of immunity. You could see cytokines here on the right with innate immunity being released from this T-helper cell. Innate immunity on the right is non-specific, meaning the response is the same regardless of the individual pathogen whether it's a virus, whether it's a coronavirus, or the human immunodeficiency virus, or a herpes virus or a bacteria.
The example that we looked at in the previous slide with the diagram of the cross section of the gut was an example of immune regulation that was innate or non specific. Typically, there is a breach in a physical barrier, like the skin or a mucosal surface, and mucosal surfaces line the inside of the nasal passages and the lungs and the gut etc. And proteins on the surface of a pathogen are presented to T-helper cells, and that's happening right here. This white blood cell is presenting the pathogen to a t-helper cell it's an antigen presenting cell taking this pathogen from this infected cell, which is a virus in this example, and presenting it to this T-helper cell.
This stimulates cytotoxic T -cells, and natural killer cells to attack infected cells and this is known as cell mediated immunity. This is what we're seeing here. This infected cell that started up here is now being destroyed. On the left acquired or specific immunity is a slower process and more specific to the invading pathogen. So, this process is mediated by B-lymphocytes, depicted here, whereas cell-mediated immunity is mediated by T-lymphocytes. B-lymphocytes or B-cells produce antibodies, as seen here, which are specific to the proteins found on the surface of the pathogen. These antibodies circulate in the blood eventually binding to and neutralizing the pathogen, which is what we can see here in the diagram. The production and secretion of antibodies is triggered by cytokines. Some of these antibodies remain in the body long after the infection has been resolved, and they may provide immunity if the person encounters the same pathogen in the future. Acquired immunity is often referred to as the immune system's memory. Here on the left, the complex of the antigen, which is the protein on the surface of the pathogen, and the antibody mark this pathogen for white blood cells. So here is a phagocytic white blood cell called a macrophage that is engulfing this pathogen and destroying it.
I recently contributed to a paper published by Michelle Sexton that does a great job with explaining the interplay between the endocannabinoid system and the immune system. And Michelle writes that the ECS acts as a gatekeeper in immune homeostasis, which we saw before in the diagram in the gut. Immunosuppression is a term you'll often hear related to the role of the endocannabinoid system and it can be loosely thought of as taming the immune response, which can sometimes become overactive like in the presence of an autoimmune disease, or perhaps a chronic infection, or organ transplantation for example.
There are four basic immunosuppressive functions which are mediated by the endocannabinoid system. The first is the inhibition of the proliferation of immune cells. And so immune cells are part of the immune response as we've seen. The endocannabinoid system can inhibit that proliferation which can be helpful. Second is the production and the migration of antibodies. Third is the induction of apoptosis. Apoptosis is programmed cell death. We want cells that have been infected by a pathogen to die, and so the endocannabinoid system can induce that process. And four, it can suppress cytokines. Now cytokines are obviously very important as we've seen, they're signaling molecules. But sometimes their production can be excessive, and perhaps you've heard the term cytokine storm during the COVID era. And so, the endocannabinoid system can help suppress cytokine production and secretion.
Here are the ingredients in the new product CV Defense. I'm going to go through each one of these briefly: PEA, Vitamin A, Vitamin D, Zinc, Selenium, and reishi mushroom extract. So, two vitamins, two minerals, a mushroom extract, and PEA. Most people think about CV Sciences as a CBD company, we should start there. You may recall that CBD does not activate cannabinoid receptors directly, does not work like THC, it does not work like anandamide or 2-AG. CBD acts at a variety of different receptors, which are not traditionally considered part of the endocannabinoid system. It also interacts with enzymes and other molecular targets like transport proteins. And because CBD has so many different targets in the body, we're still really trying to figure out how it does what it does.
PEA, palmitoyl ethanolamine, acts in a similar fashion. It is technically not an endocannabinoid because it also does not activate cannabinoid receptors, however it is chemically and structurally very similar to endocannabinoids. The earliest reports of PEA's immune modulating properties date back to 1957, when scientists discovered that it had anti-inflammatory effects. In the 1970s, it was used as an approved medicinal product called impulsin in the former Czechoslovakia. It was especially used for the treatment and prevention of the flu and other respiratory infections. Interest in PEA declined until around the mid-90s, when the discovery of the endocannabinoid system revived interest in this compound. In the 90’s, Italian Nobel Prize laureate Dr Ritalevi Multichini showed that PEA may control overactive inflammatory cells in several different disease models. More recently, PEA has been investigated as an anti-inflammatory and an analgesic, which means a pain reliever.
Here is a diagram that helps to explain how PEA may exert its anti-inflammatory effects. In the lower left-hand corner we have PEA molecules diffusing into a mast cell, which is a type of white blood cell, and inducing the enzyme DAGL-Beta to synthesize 2-AG, an endocannabinoid. 2-AG then diffuses and binds to a CB2 receptor on the cellular membrane of the mast cell, which leads to a decrease in the production and secretion of histamine and other inflammatory mediators. You'll notice that this mechanism looks a lot like the gut example that we discussed a moment ago. In addition to reducing inflammation pea also is an analgesic, and it also offers neuroprotective and anti-epileptic effects. Sources of PEA are soy lecithin in peanut meal and egg yolk. Historically, it has been used to prevent respiratory viral infections, as I mentioned, and it possesses a broad range of activities given the fact that it interacts with so many different types of receptors. This is a review from 2013, it was published in the International Journal of Information. The authors state that it has been shown that PEA can decrease the intensity of several inflammatory and immunological processes. Table one from this paper shows six randomized controlled trials with nearly 4, 000 participants that investigated PEA as a treatment for or prevention for respiratory infections. The fourth column shows protection in the form of a percentage, as you can see here. The range of protection goes from 16 to 59, and according to the authors PEA has clear treatment effects in respiratory infections.
Vitamin A is also an ingredient in CV Defense. It is a fat-soluble vitamin, it’s an antioxidant, it is derived in plants like carrots and spinach as well as animal products like liver egg yolks and dairy fat. It has an essential role in a variety of different processes in the body including functioning of the retina growth and differentiation of different tissues, and modulation of the immune system. And Vitamin A consists of three different molecules, retinol, retinal or retinaldehyde, and retinoic acid. The authors of this 2018 narrative review of the role of Vitamin A in the immune system state that Vitamin A has demonstrated a therapeutic effect in the treatment of various infectious diseases. They also call it the anti-inflammation vitamin because it can enhance the anti-inflammatory response. The authors of a different publication looking at the barrier protection in the gut state that vitamin a has been well known for its protective roles against infections, specifically with regard to IgA antibodies in mucosal tissues and these barriers are often mucosal tissues as well as the skin.
Vitamin D is a third ingredient in CV Defense. It Is often referred to as a steroid hormone because of the way it interacts with vitamin D receptors in the body. The skin can produce Vitamin D, you can also take it in supplemental form and get it from a variety of different dietary sources. Vitamin D plays a very important role in maintaining bone mineralization by regulating calcium and phosphorus levels in the blood. And as I mentioned before, it activates Vitamin D receptors and can modulate gene expression. The authors of a 2010 publication on Vitamin D as a modulator of the immune system state that Vitamin d targets various immune cells and enhances the modulation of both the innate and adaptive immune responses. Two years later in a different paper, the authors concluded that Vitamin D regulates both innate and adaptive immune responses in humans and that it can bolster clinical responses to infection when it's supplemented.
Zinc is a fourth ingredient in CV Defense. It has a wide number of roles in the body, it also has anti-inflammatory and antiviral activity. Zinc deficiency in humans predisposes them to infections, fungal, viral and bacterial. It can reduce the production of certain cytokines, which can be harmful or in some circumstances it can be helpful. Zinc is a cofactor in more than 300 enzymes in the body influencing a variety of different organ functions, many of which influence the immune system. The authors of this 2002 narrative review of zinc and the immune function state that it's clear that this trace element has a broad impact on key immunity mediators, including the regulation of lymphoid cell activation proliferation and apoptosis. The authors of a different publication state that the activity of virtually all immune cells is modulated by zinc.
Selenium is the fifth ingredient in CV Defense. It’s a mineral, it’s a micronutrient that also has a variety of different roles in the body, it’s found in nuts and meat and eggs. A deficiency of selenium like zinc may decrease immune function and predispose humans to infections. It is also a cofactor for a very important antioxidant enzyme called glutathione peroxide. Selenium can enhance immune function, it has anti-viral activity, and when supplemented in people with deficiencies, it can help reduce the risk of infection. The authors of this 2008 publication state that the notion that zinc boosts the immune system has been supported by studies. They also say that limited data from studies in humans suggests that selenium supplementation may enhance immunity both humoral or adaptive and cell mediated or innate responses. And then a different publication from 1990 reports that supplementation in the presence of a deficiency has a positive effect upon humeral or adaptive responses this is that antibody response.
And finally, reishi mushroom extract. Reishi mushroom is also called Ganoderma lucidum, that is the scientific name. There are over 400 compounds in this mushroom that are biologically active. It looks as though the triterpenoids and the polysaccharides are the compounds that have the most pharmacologically active effects. Reishi has been used in Chinese medicine for a long period of time, and it also shows antimicrobial anti-inflammatory antioxidant and anti-tumor responses. It's also anti-fungal and antiviral. In this 2019 pre-clinical study in human macrophages, the majority of mushroom extracts and the formulas were found to be highly potent immuno-stimulators according to the author. And finally, in this narrative review from 2018, research has now confirmed that Ganoderma lucidum induces a self-triggered immune response and is a very powerful antioxidant.
So, in summary, CV Defense is a new immune support product from CV Sciences. It contains individual nutrients which play a role in the immune response both the innate and the adaptive immune responses. PEA is an endocannabinoid-like compound with anti-inflammatory analgesic and immune supportive effects. And the endocannabinoid system is a gatekeeper in immune homeostasis. It communicates with the immune systemin order to restore homeostasis when there has been some sort of disruption to that homeostasis.
Quick disclaimer this was not systematic or comprehensive review of all of the evidence supporting the ingredients in this product. There are the citations if you want to learn more. With t
hat, I'd like to thank you for your time and your attention. I'm happy to answer any questions please reach out to me directly at the information below.
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