A healthy endocannabinoid system is integral to innate stress response, immune regulation and inflammatory homeostasis
Rick: Good afternoon and welcome to the Tuesday webinar series, “Chiropractics Webinar for Doctors of Chiropractic.” I’m Rick Vach, editor-in-chief of “Chiropractic Economics.” Today’s webinar, “Harnessing the Endocannabinoid System Immune Competence and Inflammation Control,” is sponsored by TrueGen3. And as always, our program is being recorded and will be archived at Chiropractic Economics website, chiroeco.com/webinar for one year. Our expert is onboard here today to speak with you and when this presentation is complete, it’ll follow with the Q&A period. You can submit questions throughout the presentation by clicking on the appropriate icon on the right side of the screen.
Our presenter today is Dr. Chris Meletis, whose personal mission is changing the world’s health one person at a time. He is an expert on CBD and believes that when people become educated about their body, that is the moment when the change begin. Dr. Meletis, thank you for taking the time to participate in our webinar and for sharing your expertise regarding the endocannabinoid system and immunity. And before we get started, we have a slide with some background information on Dr. Meletis as you can see. And at this point, we will hand it off to Dr. Meletis. Thank you.
Dr. Meletis: This discussion will be “Harnessing the Endocannabinoid System Immune Competence and Inflammation Control.” I’ve written several national and international articles on the endocannabinoid system, CBD, including in the peer review literature. I’m currently finishing a book on CBD and the endocannabinoid system that’s available for free at trugen3.com. So, why am I so interested in the endocannabinoid system? The same reason I’m interested in the mitochondria, the same reason I’m interested in plasmalogens as well, naturally occurring substances and processes within our body or as a naturopathic physician and a holistic providers, we know the term, “vis medicatrix naturae,” the healing power of nature, what’s been instilled and created within us.
So, the goal is to support what our processes are within our body and then we supplement that aspects that are not already covered with a good diet and lifestyle. So, the format platform for our conversation today is that this is a clinician to clinician conversation, where we discuss the clinical research, what’s coming out, what’s currently known, some application…so, the format platform for our conversation today is that this is a clinician to clinician conversations, where we discuss the clinical research, what’s coming out, what’s currently known, from applications, and some hypotheses as well.
What we will not be discussing and the integrated link is directly to COVID topic as right now, there’s some FDA and FTC issues relative to what can and cannot be said about that and I think we’re all very familiar with this as functional medicine providers and clinicians in general. So, what about the endocannabinoidome? Yes, I did pronounce that correctly, the endocannabinoidome. So, this is the endocannabinoid system and the microbiome working in synergy in the biome. This is one of my peer reviewed journal articles discussing very important aspects of how our probiotics, aka in our microbiome, or diubiosis, and potentially our dysbiosis, interact with our CBD receptors.
So, when we look at the literature, it’s quite clear that we’re far beyond now appreciate just CB1 and CB2 receptors, even though of course they play an integral role in the bioavailability and bioactivity of, of course, the endocannabinoid system as well as the role of CBD within the body and some of the terpenes. But the endocannabinoidome, aka the ecology of the microbiome and its interface with the cannabinoid pathways, extend to systems that include other receptors such as TRPV1, PPAR alpha, GPR55, and 5-HT 1A. There’s fascinating mechanisms that include the endocannabinoid receptor expression in the gut and that it interplay with the intestinal microbiota.
So, once again, we know about the microbiome, we know about the mitobiome, which is the mitochondrial linked with, of course, microbiome, and now we’re seeing, of course, there’s the endocannabinoidome as well. So, are we surprised? No, we just humbled as practitioners realizing we know so much and we know so little. I’ve been very fortunate to write extensively in both peer reviewed journals as well as “Townsend Letter.” And in the “Townsend letter,” I’ve written on attention deficit and autism and then we think about the endocannabinoid system and the microbiome and now hearing about the endocannabinoidome, it comes to no surprise as we work with autism and attention deficit that there’s a link there and a correlation and potential of therapeutic synergy, let alone if we go to the extent of leaky gut, leaky brain, or even the microbiome or the mitochondrial aspect in the microbiome.
We also have the endocannabinoids, the phytocannabinoids , and palmitoylethanolamide, and palmitoylethanolamide…I know it’s a mouthful, but it’s abbreviated PEA. has some fascinating roles for a synergy or pain management, and particularly for neurological pain. So, if you Google palmitoylethanolamide, you will actually find that it has been studied in neuropathies, which were otherwise recalcitrant to treatment. Then we have, of course, the roles of the cannabinoid system and stress pain management and inflammation. So, once again, a penny saved is a penny earned.
We need to conserve our energy, whether it be brain chemistry, adrenal support, downward stream of the thyroid or genesis pathway, we need to, once again, support and confer a degree of protection or as I share with my pieces, squirrel away a little bit for winter because winter does come. And then we look at the role in the gut-brain axis and cannabinoid-rich hemp oil, including things beyond just CBD. Once again, we have a tendency just to fall in love with a one substance. So, when we fell in love with vitamin D, we forgot about vitamin K and, “Whoops, our bad,” and now we’re doing vitamin D and vitamin K. But what about A and B?
So, once again, we need to look at whole plant or at least a whole spectrum than just CBD because there is some synergy as provided by nature. And then we also look at muscle and visceral pain and this can also apply to endometriosis and more deep, no pun intended, visceral issues. Yet to the fact that we are one stressed out nation, we are worn out, we’re tired, and if we weren’t already worn out and tired in 2019, I think 2020 spend a lot more people. We see our patients are stressed out, they’re tired, they’re not feeling well, and they’re having exacerbations of all kinds of symptoms that often they’ve had under control and now they’re not so well-controlled because once again, there’s additional obstacles to the cure, there’s additional allostatic load that’s impacting homeostasis and leave you closer to rapid entropy.
So, Dr. Russo did lots of research and has been a pioneer in this area, and he speaks about the clinical endocannabinoid deficiency. So, we in the clinical practice work on hypothyroidism, so it’s officially not maybe full hypothyroid, maybe they’re not full Hashi’s but they’re going that way, so we call it subclinical. So, whether we’re fully worn out on endocannabinoid system or just moving in that direction, can it have an impact on migraines, fibromyalgia, irritable bowel syndrome, onwards and onwards? Is it a straw on the camel’s back? And this is where CBD and other terpenes in cannabinoids come into play to nurture and support this, and also as we’re going to find out, regulate multiple pathways at enzymatic receptors in the body.
2020 in review, okay? If COVID-19 as a standalone and historical event wasn’t enough to add another straw on the camel’s back, our human physiology has taken a licking and hopefully like a Timex watch, it keeps on ticking. However, the quarantine, the masks, the economic stressors, childcare and education have been added to the plate. So, a bad cold or flu season, challenging enough. Quarantine and loss of jobs, another challenge. Wearing a mask and having the little fibers going up your nose and potentially consuming this tiny sight is another thing, challenging. And some parents and grandparents have became the mandatory school teachers and childcare itself has become very elusive, impacting the work.
And in my clinical practice here in Oregon, I basically from March all the way…still for the state to the large part, I’m not able to see the patients as I typically did in my clinical practice. Obviously, we’re masked up, we’re having all those challenges but I’ve now moved to a large Zoom platform, which doesn’t have the same satisfaction, for me at least, as sitting in a room communing, communicating, and collaborating with our patients. Decrease the opportunity to gather to de-stress and sustain comradery…and why am I going through this lift? I thought this was an endocannabinoid CBD presentation. Ah, but I was just sharing Russo’s work on the endocannabinoid deficiency.
So, just like we have adrenal burnout, adrenal fatigue, I look at my clinical practice at adrenal insufficiency and that process have led to that status and that state of being deplete. And doesn’t it make sense, where probably at the same time, though we don’t have a way to overtly measure it, also experiencing an endocannabinoid insufficiency and deficiency? They’re both going down, the water level is lowering, our resilience is diminishing, and I think as we look at adrenal insufficiency, we really have to start looking at could there be some endocannabinoid deficiency as well? Hence the list that I’m going through.
So, we have mental health challenges, lots more anxiety, a lot more depression, but I think Endocannabinoid deficiency, if we think about adrenal issues, obviously…let alone the neuroendocrine system. And then, of course, we have a very interesting year where it’s 2020, it’s political, there’s lots of strife and division, and, of course, a constant stream of negative news that’s been going on for well over a decade-plus now. And we’ve had wildfires up here in Oregon, lots of wildfires, Colorado, California, Washington, it’s not limited just to the west, but that also puts another allostatic load. The benzene burden, the polycyclic hydrocarbons, all of these things challenging, lots of heartache, lots of suffering within humanity.
And so, the greater our susceptibility, of course, the more likely we are to get ill. And actually there’s quite a bit of evidence and there’s actually a quotable quote from a Stanford researcher, that where there are more forest fires, there’s actually greater risk of contracting COVID-19. And, of course, actions such as lung inflammation as well as an altered biota within our GI tract inhaling smoke, having the alveoli also have that absorption of the particulate matter at 2.5 actually will alter the microbiome per the peer review literature, another presentation I just recently have given. So, we need to work on addressing these homeostatic disruptors and CBD and the phytocannabinoids have a role here in my clinical opinion.
So, from an endogenous gatekeeper perspective, the endocannabinoid system plays a very important role in regulating immunity and scientists consider it a gatekeeper of the immune system. And they say the gatekeeper, I think that may be overstating it but it’s definitely a gatekeeper because once again, there’s a wisdom of the body. We don’t spend energy physiologically or genetically sustaining a pathway as in the case of the endocannabinoid system for millennia has serves us and serve us well. So, the endocannabinoid system includes receptors, of course, we know that the CB1 and CB2 receptors, and of course, we know of anandamide, and for those novices to the CBD conversation, anata in Sanskrit means to live.
And interesting enough, when a mom breastfeeds, not only we confer immunity and oxytocin, but also we’re conferring anandamide to baby. And on a piece of random trivia, you’re also conferring PQQ, pyrroloquinoline quinone, to baby through breast milk helping with neurogenesis and mitogenesis. Scientific evidence had showed that the immune system expressed CB1 and CB1 receptors, although CB2 receptor seem to be higher than the CB1. When we come to what I call CBD 101, beyond the CB1 and CB2 receptors, I’m going to tease you…of course, if you’re already an expert in this field, you already know about the TRPV2 receptor, the transient receptor potential vanilloid 2.
I want to talk about other ones as we go along here but once again, there’s a lot of things happening here. I can tell you when I graduated in 1992 from the Naturopathic University up here in Portland, it was a college back then, we didn’t know any of it. It was not even barely being discovered, Devane and Mechoulam were just coming up with some of these observations of the endocannabinoid system and we’re still humbled and we need to realize there’s still a lot more to go when it comes to appreciate all the nuances. The next 5 or 10 years are very fascinating, to say the least.
Then we get to, “Could we have a polymorphism?” So, my goal today is to bring two or three pearls to you that even if you are an expert and well-versed in this, do we know it all? None of us know it all. So, I went through the literacy saying, “I wonder if there’s any cool stuff out there that we might not know?” So, they looked at the cumulative evidence of the endocannabinoid system as a role of half the physiological processes and severity of disease and they look at respiratory syncytial virus.
So, thinking of childhood illness here, well, why does some children get sicker than others? We could argue maybe they’re overweight, maybe they’re malnourished, maybe they have low vitamin D, maybe they have poor iodine or zinc. Of course, all variables but could they have a polymorphism, a SNP that also alters their ability to respond optimally? Well, that’s what the study kind of looked at. They look at whether or not there could be a contributing factor. And so, voila, if you see where the yellow just popped in, children who carrying the QQ genotype were more prone to developing severe acute respiratory tract infection. Okay, well, we know vitamin D plays a role there, we know zinc plays a role there, like, “Hmm, so if you’re a QQ type for CBD2 receptor, that can be enrolled.”
So, some people respond better to CBD and phytocannabinoids than others based on their genetics, it only makes sense much like if we were doing methylenetetrahydrofolate or any of the other addresses of the SNPs in our body genetically. And then once again, more yellow popping in here. The acute respiratory tract infections following respiratory syncytial virus infections increase more than twofold in children carrying the QQ allele. So, we’re familiar with catecholamine methyltransferase, COMT, once again, alleles, whether it be met/met or val/val, all these little nuances, but once again, the concept, taking away all that knowledge is saying, “Might a person genetically have susceptibilities and if one person responds well in the family, there might be increased chance of another?”
Today alone, I had a patient which was not responding to therapies for blood pressure, so I asked, “Which other family members had this condition of hypertension and what have they found successful?” Lo and behold, I called up the parents, which they were not getting along with, and said, “Hey, do either of you have high blood pressure?” And then, “No,” and they tell me, “Yes, and this is what helped.” Today, we put this person on the thing that one of the parents was using and voila, they’re already doing better within 24 hours.
Genetics plays a role. Epigenetics, of course, plays a role in how our genes manifests but those genes are there and if we can figure out what were our susceptibilities are and what works and what doesn’t work, voila, clinical practice and that’s, of course, the art of medicine. So, increasing natural killer cell. In animal studies investigating autoimmune health, CBD oil from hemp has been shown to balance the immune system by reducing the activity of T cells, B cells, and both T helper and T cytotoxic lymphocytes subsets. However, outside of an autoimmune arena, CBD supports the activity of natural killer cells, a type of white blood cell as we know.
I call them the Green Berets, Army Rangers, Navy SEALs of our immune system and the natural killer cells are major players in the body’s response. We know this. What else do we know about viruses? We know that IgG, which is activated and part of the complement pathway also kill the virus. This is why avoiding food sensitivities that are IgG-driven is important, otherwise, we have a distracted immune system. And CBD also supports the activity of natural killer cells, which share properties of both natural killer and T cells. In vitro studies have shown CBD has actions of interest to people want to maintain immune health in their liver and when we get to the liver, of course, we think peroxisomes and then we go into the concept which we’re not going to go into today of plasmalogens.
Where do we find plasmalogens? It’s another endogenous process within our body, naturally pretty much like anandamide, another endocannabinoid, that it diminishes with age. And where do we find a lot of plasmalogens? The brain and the heart, an area which I’ve just wrote in another peer reviewed journal article and once again, listening to the body, nourishing the body with what it already naturally makes. This is why CBD and the phytocannabinoids come into play because they’re supporting the endocannabinoid system and as we just learned, the endocannabinoidome as well.
When it comes to lung health, we know that CBD can play a role because it’s supporting overall immune function but we also know that secretory IgA is majorly contributory to how well our mucous membranes are doing. The more stressed you are, all things being equal, the lower your secretory IgA. The more food sensitivities or gut irritation you have put in, the higher your secretory IgA localize and point towards the inflammation, but a nice amount of secretory IgA is important to coat the mucous membranes, as I share with my patients, it’s like waterproofing or scotch guard on the immune system without, of course, that toxicity.
So, now we’re stressed and we can minimize some of that stress and if CBD can help with that and supporting the endocannabinoid system can help with that, doesn’t it make a great sense? So, let’s continue looking at clinical practice. So, in animals, CBD supports healthy inflammatory response in the lungs. It also improves lung function in mice exposed to lung irritants. And in one study, CBD enhanced markers of healthy lung such as decreased total lung resistance, elastance, as well as leukocyte migration into the lungs, as well as several other factors as well for maintaining cytokines tumor necrosis factor, Interleukin 6, and chemokine as well.
So, once again, what are we concerned about in 2020? And what are we concerned about in every fall and winter? Cytokines, cytokines that run away and we get excess inflammation. We already know that, particularly in North America and the westernized world, inflamm-aging are a very real factor. So, we already have too much c-reactive protein, too many cytokines in the westernized world just because of diet, lifestyle, stress, and who knows other contributing factors, we have all of us a long list. So, once again, wouldn’t it be great to nurture support pathways which have supported humanity for millennia? The answer is yes.
So, the potential for respiratory health is important. And if we look at a hierarchal set of things, all day in our clinical practices, we talk about healthy eating, keeping your body in motion, staying hydrated, but we can live weeks without food, we can live about three days without water, but we can only moments without air. And if we think about our toxicity, we inhale a lot of indoor and outdoor air pollutants, so, once again, controlling that inflammation, of course is vitally important. So, when it comes to maintaining a healthy gut microbiota, we also know we’re maintaining our immune system.
The human body is argued between 50 and 100 trillion cells in composition and it’s also said that we have about 100 trillion visitors in our microbiome of our GI tract. So, a large portion of our immune system is in our GI tract, as we already know, but we educate our patients on that routinely. And also the gut microbiota, the collection of organisms good and bad down in our GI tract play a critical role in how well we’re doing. And I asked my patients all the time, “When you’re eating, who are you feeding?” And invariably, they think it’s a trick question, “Well, I’m feeding myself.” Yes, of course, you’re feeding yourself but what else are you doing? You’re feeding your microbiome.
And so, as a result, they eat and they create either short chain fatty acids like butyrate, which are good, maybe an imbalance of acetate, or propionate, maybe not so good and imbalance. So, once again, looking at it as we are feeding the little critters our ecology, the microbiome that also as we’re seeing here with the endocannabinoid system, we’re also potentially causing a shift in that pathway as well. Excessive inflammation in the gut can lead to intestinal permeability, gut microbiota dysbiosis, and, of course, impaired intestinal immune response.
And, of course, we know the leaky gut, leaky brain, and as we found out in the peer review literature, we’re finding out leaky lung, leaky gut, and leaky brain and systemic inflammation within the wildfire studies as well as air pollution that are very pervasive in that areas. So, once again, inflammation and integrity in that buffer state. So, whether we have adrenal buffer, immune buffer, inflammatory buffer, we need to, of course, support those pathways and the endocannabinoid system is one of the ways in which we can do it and we don’t know all the mechanisms yet, but we know it confers a degree of what I will term Kumbaya or Anata, to live.
One way the body counteracts this process is, of course, in the endocannabinoid system, and like endogenous cannabinoids, CBD also has been found to support a healthy GI tract and once again, critical for a healthy overall inflammatory and immune system. Healthy gut, healthy us. We know Hippocrates has many quotable quotes, the father of Western medicine, often conferred as, and what’s interesting, he says, “All disease begins in the gut,” a common quote of his. “Made your food be your medicine and your medicine be your food,” but the other one, “In excess, one fights with nature.”
So, we all find that to be the case as well, you can do too much of a good thing. So, finding that balance is absolutely critical, including with CBD and the phytocannabinoid. So, many of my patients well before 2020 struggled with just the daily burden of life. After all, we’re all grown up little kids. Somehow along the way with a kick of hormones during the teen years, then we, of course, get older, we learn life skills, but the reality is we all have a child within us that’s worn out tired, that if we knew how challenging adulthood would be, we might not have signed up for it or we might have wanted to stay at 12 years old.
But realizing how do we nurture the inner us, which of course is a progression of life, but we have to have the ability to handle psychological stress. And now we’re finding that the endocannabinoid system plays a role in that as well in maintaining that healthy immune response and I often think of endocannabinoid system and endocannabinoid deficiency and adrenal insufficiency as probably going hand in hand. So, unlike endogenous cannabinoids, which work on the CB1 receptor, CBD supplementation has a direct activation on the 5-HT1A receptor. So, once again, there are other receptors including serotonin receptors playing a role here.
CBD stress relieving properties have also been attributable to modulation through blood flow. Right now as I’m sitting here, 20% of my oxygen is going into my brain, pretty impressive considering my brain doesn’t weigh nearly as much percentage-wise as the rest of my body. So, blood flow, interesting, huh? And then we see here, brain regions involved in anxiety includes amygdala, hippocampus, hypothalamus, and cingulate cortex. So, once again, healthier brain, calm, once again, a little bit more Zen like a little bit of CBD, some L-theanine, and we’re starting to feel a little bit better about things.
The fact is we were not born properly or designed to have the amount of stress that we do in this new millennia. We have too many things coming to us. In 1990s, we had the “Can you hear me now?” commercials when it came to cellular connection. Now we have our text, our phones, our messages, our constant stream, once again, a lot of things coming at us and once again, we have never experienced this level of stress for such a prolonged period of time. We hear a ringer on a phone, we said, “Oh, is that on my phone?” And once again, too much information.
So, how do we de-stress to avoid distress? So, once again, if we’re not de-stressing, we’re going to be distressed. And so, we look at human clinical trials and CBD was found to reduce mild stress in people giving a speech. Researchers observed that the effects of CBD dose or placebo in 57 healthy male participants performing in a simulated public speaking. And usually, public speaking for any of us can kind of get us going, it can get into our heads, right? So, in this double-blind study, they gave very large doses, in my opinion, of CBD, 150 milligrams, 300 milligrams, or 600 milligrams or a placebo prior to the public speaking.
Compared with placebo, 300 milligrams led to the subjects being more calm and relaxed. So, that’s intriguing, right? But 300 milligrams, A, you would think expensive, but why do they have to give so much? But this is a very tangible part of our conversation later on about bioavailability of CBD. So, if you have a CBD and it’s not very bioavailable, you might need a lot of it. And of course, when they’re doing clinical trials, we also know the other flaw, just like with drug trials, is to give big doses of things because they don’t want to do so many of these studies and they need to have an impact and if they do 57 people and they don’t have the right dose, then guess what? It’s a failed study. So, they go higher than necessary.
But I really want to point out, in my opinion, if you go super physiological, you have to wonder, “Why am I going so high?” Just like why are you going so high if you’re doing an anabolic steroid or estrogen or progesterone? You shouldn’t and wouldn’t. And if you do, much like a sea anemone and if you live along the coastline, you’ve seen these little sea anemone that you see in the right hand upper corner, they’re like little receptors. If you put your little finger gently in a tidal pool and touch the sea anemone, the little tentacles move, you poke it with a finger ever so gently and it starts closing down because it’s thinking, “Okay, this is potentially a prey.”
And, of course, if you poke your finger aggressively, which of course, we will not want to do because, after all, we shouldn’t even interacted with the sea anemone, it’s going to close, it’s going to miss potentially its next lunch. So, once again, receptors, we have to be aware of nudging and not shoving and, of course, we know that it’s blocked up philosophical functional medicine providers but that’s generally our approach, nurture the body. Susceptibility and immune modulation.
Recently, the endocannabinoid system has lots of attention, lots of space on the immune system and modulation. And once again, modulation, that’s a nebulous word. The cannabinoids act in the system to help with the T and B cells and to bring up balance, so we’re not over regulating it, generally, when dosed properly. And so, cannabinoids also support the health of people living in a world where viruses and bacteria are prevalent. In vivo and cell culture studies shows that cannabinoids modulates the production and function of immune cytokines as well as support activity and other immune-related cells such as macrophages and T helper cells, Th1 and Th2. Once again, nudging, not shoving.
Unfortunately, there’s a dearth of human trials. I would love to see more human trials, have to get them past the Institutional Review Board, have to get them funded. So, once again, I would love to see more and more clinical trials and I’m hoping that will come over the course of time. This one, of course, way back in 1998. So, all of us are quite familiar with the CB1 and CB2 receptors. They were the first things that were really described in the medical literature, whether it be with THC or when the endocannabinoid systems became much more elucidated because of Mechoulam and Devane and their colleagues.
But what about the TRPV1, the PPAR alpha and gamma, and the orphan G protein-coupled receptor, the GPR55? Again, these receptors also exist in our body and, of course, if you use like an organ-grade berberine on the PPAR pathways, you’re working on sugar regulation or inflammatory pathways. We know about these pathways but it seems that, once again, the endocannabinoid system and CBD can play a role here and it gives us a head scratching moment of like, “I wonder if there’s some innate synergy here in some of the therapeutic protocols we’re using?”
All of these receptors are widely expressed in our immune system, and in addition to the ability of the endocannabinoid system to regulate immunity is important, particularly due to their actions on PPAR alpha and PPAR gamma, but GPR55 receptors also specifically expressed on immune cells such as the monocytes and natural killer cells. So, once again, we’ve seen that one, we have these pathways in our body. So, I’m using a lot of CBD in my clinical practice, not only for conferred immunity, now I support sleep and decreased stress and by decreasing the stress, I’m helping with the immune system as well, but I’m also using it for my GI patients, my patients with irritable bowel syndrome, my patients with autoimmune conditions, as well as, of course, immunocompromised circumstances as well.
So, the endocannabinoid system expressed in immunity. So, we know about the receptors, we’ve discussed them, they’re hemp-based CBD. And so, what we want to do is we want to look at how do we have the long-term effects. So, what they did was, they looked at the long term effects of space flight on stress and immunity in cosmonauts and the study found that space flight does not elevate cortisol levels. That’s interesting, I know it would for me but good for them, they’re conditioned. Blood levels of the endocannabinoid system spikes during space flight, suggesting that biological stress response.
At the same time, space flight altered the immune system. So, let’s pause here for a moment. Remember my conjecture that when the body gets stressed like adrenal burnout or adrenal fatigue that’s protracted, eventually we’re gonna get adrenal insufficiency? Here we’re seeing that what they had was a spike in the endocannabinoid system during the flight, so a stress response via the endocannabinoid system. So, you can say, “Well, maybe if we continue hitting that,” and luckily, these folks were conditioned so they did not have an elevation of cortisol levels, for most but for the average person, probably both of them would have taken a hit. So, it’s very interesting, but at the same time, space flight alter the immune system.
There was a significant increase in white blood cells in the cosmonauts. Immune cells such as neutrophils, monocytes, and B cells increased by 50% while natural killer cells levels developed by nearly 60% shortly after landing. Lymphocyte percentages did not change before and after flight but were high in-flight. So once again, showing a physiological response to stress. So, what would be our cosmonaut-like experience in life? It might be merely showing up, it might be a tough patient case and likewise, for our patients, it might be the 2020 COVID events, it might be some other challenge that occurs with them or to them over the course of time.
So, the allostatic load and impact on homeostasis, I want to reiterate that. You already had this slide, I’m not gonna go over this slide but once again, what happens if we have an endocannabinoid deficiency? We might want to support with phytocannabinoids and CBD and see whether or not we have some clinical efforts to see on both subjective and objective level for the patient and as observing clinician. So, supporting the immune system with cannabidiol is important.
And so, what we have here is there’s lots of aspects to, once again, immune function. And remember all those lovely little macrophage we have in our biome, we have the dust cell, remember, the lungs macrofage? We have the Kupffer cell. But once again, we have to maintain immune function and remember all that blood from our GI tracts went where? It start with the liver, the first task, right? Animal studies also suggest that CBD oil may help with overall healthy immune response.
And then we look at inflammation and immune system and in a mouse model of asthma, CBD reduce inflammation and lung fibrosis but also makes you wonder, “Well, what about pulmonary fibrosis?” And for those that are not familiar, pulmonary fibrosis is one of those dreaded diseases that can occur and what’s interesting is if you have a patient with GERD, you really want to be warning them that we need to get that under control, not because of esophagitis or Barrett’s esophagus, not because, once again, a gastric issue, but that acid coming up into your lungs can contribute and trigger pulmonary fibrosis and I’ve had patients that come to that over the course of the years.
So, in animal model, a similar animal model for the mouse model, they triggered asthma and they later injected CBD into the animal’s abdominal areas cavity and CBD reduce the levels of the inflammatory cytokines interleukin 4, interleukin 5, interleukin 13, interleukin 6, and tumor necrosis factor alpha. It did not reduce the anti-inflammatory cytokines, interleukin 10. So, once again, is it natural to be injecting the CBD into abdomen? No, but that’s, of course, once again, the animal model and they had their procedure.
The hemptourage effect, a term that’s often used to describe the application of the entourage effect, which we know relative to Cannabis sativa or Cannabis indica marijuana side of things with the high THC. But the hemptourage effect, or the entourage effect, is about the other cannabinoids, the terpenes, and seeing that, once again, a unison, plants have a wide variety of things, we know that. When was the last time we found a pile of white ascorbic acid just laying around out in nature? We do not, we find it, it’s with bioflavonoids.
Once again, whole plant medicine, a concept we have to remember, not to lose as functional medicine providers because, otherwise, we’ll just be, once again, practicing quasi pharmaceutical medicine but on the phyto side of things. So, the alpha-pinene significantly MRSA and other bacteria according to one study that I came across. Beta-amyrin in another setting, it’s an example of a terpene, has antimicrobial effects. And the entourage or hemptourage effect kicks in the immune system and offers a synergy again. Just like we need vitamins and minerals, we need certain phytonutrients to confer protection to the body.
So, once again, as designed by nature, as provided, as we were created. So, not all hemp and CBD products are created equal. Just like on any other supplement, we know this. This is an article that I contributed to “Marijuana Ventures” about taming the Wild Wild West. When CBD first came out, everybody and their brother was producing a CBD product and still, there’s a lot of dysregulation in the industry and if we don’t regulate and we don’t vote with our dollar, of course, FDA and other regulatory bodies will.
So, we’d have to, once again, support the people that are doing the research and conferring a higher level of quality for public safety purposes as well as clinical efficacy. If we had the ability to offer a highly absorbable CBD, would we choose that or we continue using the CBD we have in our practices already? Well, there was a study done that looked at the randomized aspects of absorption. And so, in this study, they did a randomized double-blind, cross-over design with 16 healthy volunteers under fasted conditions and they gave them 25 milligrams.
So, that’s a massive dose but again, 25 milligrams but highly bioavailable, and after a single oral dose, it led to a 4.4 higher level of CBD under the curve max. So, once again, here’s a better glimpse of that. So, once again, 2019 article, showing that we had a CBD dose standardized at 25 milligrams, it looks at the pharmacokinetics, single oral dose, lead to 4.4-fold higher c max. So, once again, 25 milligrams but how much more efficacy were we getting for a single dose?
You know, one of the things when it comes to my patients compliance is they say, “Dr. Meletis, how many more pills do you want me to take?” Of course, we’re already working on food, we’re already working on diet, we’re already working on sleep hygiene, we’re already doing all of that first and it’s like there is a point of non-compliance. Plus, once again, we want to have the efficacy because even 100 milligrams of poorly absorbed CBD wouldn’t necessarily get the same job done as, once again, a cannabinoids like CBD in this particular study and with other phytocannabinoids for the synergy of the hemptourage factor.
So, the technology is called VESIsorb and it is a naturally self-absorbing colloid droplet delivery system that has been clinically proven to increase absorption of bioactives used in nutritional supplements, foods and beverages, cosmetics, and pharmaceutical products. VESIsorb, a lipid-based formulation that naturally self-assembles on contact with an aqueous phase into a colloidal system, called an association colloid, mimics the physiological mixed-micellar absorption pathway of nutritional lipids.
So, once again, mirroring what can naturally occur. And so, CBD absorption matters as does hemptourage synergy. So, TrueGen offers TrueEase, a 25 milligram CBD along with the other phytocannabinoid with this VESIsorb ability, so they get a known efficacy. This was a 2019 article. So, we want to look at that but we also want to have non-detectable level of THC. If you have patients that are concerned with driving, commercial licenses, onwards and onwards, they don’t want to mess around with THC.
One of my sons works at a manufacturing plant where they do work for Intel. And once again, they have federal dollars and federal projects, so they test for THC. He can’t afford to have that problem of potentially having something above that 0.3% level and we don’t want to have that risk in our clinical practices. We’ve worked too hard for our licenses to potentially be a marijuana dispensary of 0.35% or whatever it might be. So, once again, safety of our licenses, safety of our practices, and trying to minimize concerns with our patients that they will not have that psychoactive effect.
It is so hard, even after 29 years of clinical practice almost, to actually convince my patients where sometimes they’re pretty straight and narrow and those that, “I don’t think they are very straight and narrow,” it’s like, “It’s okay to do, you won’t have a trip,” and it’s like, “Hmm.” So, once again, having that confidence can confer and it’s very, very important, we all know that. So, this one is researchers are curious about CBD applications. I’m not going to say a lot about this, the title speaks very clearly in the 2020 June edition of the “British Journal of Pharmacology” on the topic of the potential CBD in COVID-19.
I’m not saying anything more about it but the literature is there, you can just go to pubmed.gov and you can see the literature. The reason I’m not saying anything, right now the FDA and FTC are really, regulatory-wise, looking at coming down hard on anybody that say anything about that and we already know our boards also have warned us about saying anything. But just realize you support the gut, you support the immune system, you support the innate capacity of the body, guess what? Our susceptibility will be lower, our resilience will be higher, all things being equal.
So, TruEase Phytocannabinoid-rich oil, you’ll see 334 milligrams, and once again, it is pure oil, it got some caryophyllene in there, it got some limonene in there, and a cannabinoids blend. So, once again, it’s offering that blend along with that 25 milligrams of CBD per capsule of, once again, with the VESIsorb absorption, so it’s going to be doing something a little different than a regular 25 milligram dose and that’s what I found in my clinical practice and also my own personal use.
And if you’re looking for some more additional…that’s the word, more additional. If you’re looking for additional benefits, TruEase and Curcumin, which again offering that Curcumin benefit with the VESIsorb technology, so once again, some additional anti-inflammatory effects. And TruEase also has an immune support that I helped formulate, and it’s vitamin C, zinc, Astragalus, EpiCor, which we’ll talk about more in a moment, olive leaf, Berberian, N-acetyl-L-cysteine, think of mucolytics, they’re called glutathione production, garlic, citrus bioflavonoids.
But what’s interesting is the EpiCor. If you’re not famliar with the EpiCor, lots of research done on it, they did some epidemiological research when it was discovered that it’s conferred protection ability to help with Secretory IgA. And if you go to embryo research or you just do a search in PubMed, you can find that it offers a really nice, what I call the scotch guard immune system to the immune capacity of the mucous membranes so it’s a little firmer. I’m personally taken, of course, I had my kids on it as well and I was very honored and privileged to have been invited to help with that formulation.
So, Monday morning clinical pearls. The endocannabinoid system has been working behind the scenes for millennia. And as we know, the subclinical deficiency of the endocannabinoid system seems like a very viable theory, the literature is pointing to this. And we each know that it seems like every year, which is a little bit more challenging, a little bit more daunting, we have more facts and factoids to deal with, more regulatory considerations in our clinical practices, our patients have their own challenges, and we live in a very challenged environment at this juncture. So, why wouldn’t we want to support our bodies at a natural way, which has been working for millennia for humanity?
Immune competence involves a healthy endocannabinoid system. Remember, it also involves endocannabinoidome, so, once again, tying back to that microbiome, which I think we’re all big fans of. And CBD and other phytocannabinoids are tools for our clinical toolbox and, once again, if you do a CBD as a standalone, you do with other phytocannabinoids, which is a more natural way of doing it. And once again, our bodies are designed with multiple receptors and enzyme pathways, including FAAH and MAGL, which are pathways which break down anandamide to AG.
So, all these amazing things, which once again a longer lecture, I have multiple other lectures that I give on these topics. The endocannabinoidome is very significant. Once again, healthy gut, healthy us. If you’re doing a probiotic and supporting your probiotics, well, you want to necessarily maybe give some CBD and phytocannabinoids that support that, also realizing that some of the literatures point toward leaky gut and, once again, the inflammatory processes that’s within the GI tract. And dosing is about efficacy, not the size of the dose alone.
Delivery mechanism and bioavailability is key and this is why I like VESIsorb technology and why I’m giving this presentation. Access to research article, my CBD book for free, and educational resources in general all available at truegen3.com. So, I have a couple of minutes for questions and it looks like we have some already. And the first one is, “What’s your typical dose of the TrueEase, which is the full CBD product?” Well, I usually just do one capsule per day and see how a person does, I’m going to diagnose, so one capsule.
If I need to go up to two capsules short term to get some regulatory control, I will, but often one capsule alone will do the trick. Again, I start low, I nudge, once again, like the sea anemone, I’m gonna want to gently work with those receptors and support multiple pathways at one time. So, give it a little time to do its effect. It takes a while for us to get broke and it takes a little while for us to gently finesse it and I don’t believe in overshooting on dosing of any supplements including CBD.
So, next question, “So would you do the TrueEase or the TrueEase Curcumin and when do you use it?” Well, that question is a good one. If I have a person with a lot of inflammation, I’ve measured them, they have elevated c-reactive protein, maybe interleukin 6, and their quality of life is really low. I’m going to look for some synergy beyond just putting all my energy on just one approach. So, we know that CBD has multiple pathways in which it can work and other pathways which we’re not even fully elucidated.
We know it’s going to help with potential to endocannabinoidome, help with the GI tract. But now let’s say we know Curcumin, lots of research there too, so that’s what I’m going to do, a synergy. So, they have arthritis or they got some inflammatory process going on, they’re cooking in their own juices in their own stool, then I’m going to add a Curcumin along with a CBD and, once again, maybe even a probiotic. “So, when would you use an immune product? And would you use it for the autoimmune?”
Well, that’s a tricky question. So, do I use immune stimulation product with autoimmune patients? It depends on where they are in their journey. I’m usually big on vitamin C and zinc and I’m going to have a person that’s marginally controlled on autoimmunity and they’re thinking about going on biologic drug that hopefully control, am I just going to throw all immunity stimulation at them? No. If they’re a Hashimoto’s patient, everything’s good, they’re doing the therapies you and I do in our clinical practices.
Yeah, I would definitely consider doing an immune support product, especially short term, in and out, get the job done. But once again, I find that CBD, in particular, is very important to just support that pathway, as well as making sure that it gets working and making sure what I call the babbling brook. If you’re not having every two to three bowel movements a day, first thing you want to do is get your bowels moving. If you’re not urinating near clear, as I tell my patients, you’re going to get that going. If you’re not sleeping, you’re going to get that going.
And then, of course, we’re gonna do the fish oils and the Curcumin and the CBD and then as needed, an immune product to kind of get in there and get the job done. So, next question was, “On the immune product you designed, Dr. Meletis, would you take that ongoing during a cold or flu season?” I’m personally am, I’m seeing sick patients. Both of my kids come over routinely and they have, of course, their wife, right? Their own personal exposures, and I am very prone towards bronchitis and in this COVID environment, I’m going to play very safe.
So, I’m doing a daily regime and at the first sign of a problem, I’ll go from a couple of capsules a day to four capsules or if I’m really feel like I’m coming down, then I’ll crank it up a little bit more. But every night, I’m also doing my CBD allowing that to work with my endocannabinoid system. And it looks like we have several other questions, you can actually go ahead and email TrueGen3 or you can email me at email@example.com on the bottom of the slide and I’ll be more than glad to field your questions.
Thank you all, it’s great to see such an international community and it’s just great to be part of the team. It’s part of what we all do together, we learn from one another and I look forward to your feedback, your insights, and your questions. I’m here to assist. Take care and blessings and may everything you touch and everything you pursue be blessed abundantly.
Rich: Thank you, Dr. Meletis. Our time is up but we also want to mention a special offer and the special offer is from TrueGen3. For participants, you can receive a free bottle when purchasing 6 and 3 free when you purchase 12, you’ll receive details via email. And we’ll also email you the video on the VESIsorb technology that unfortunately didn’t play, an excellent video.
At this time, we’d like to thank our sponsor, TrueGen3, and Dr. Chris Meletis for today’s webinar, and thank you all for attending. Remember, this webinar including our speaker’s PowerPoint presentation has been recorded, we’ll alert you via email when the webinar is available online. Thank you again for attending and we look forward to seeing you next time. Have a great day.