27. Charlie Piermarini, PA-C: The Science on CBD, THC, and the Endocannabinoid System

Hello everyone, I'm Dr. Darsha, and I'm Dr. Altamash Raja, and welcome to Medicine Redefined. A podcast where we will explore the often overlooked but necessary components of health, what we consider to be the fundamentals. We will investigate topics and practices that can give you and your patients the best chance to optimize a healthy lifestyle. It's time to move the needle forward and put the health back in health care. Before we get into the show, let's talk about this week's sponsor, Deputy. At your practice, what happens when staff call out sick? How much time does it take to find a replacement who can fill in? If you need to cancel appointments because you're short staffed, what does that cost your practice? Deputy is a simple app that's helped more than 250,000 workplaces tackle this problem. Deputy makes it easy to schedule staff in line with patient demand, communicate schedules with your team and instantly find a replacement when someone calls out sick. To learn more and try deputy app for free, go to drapotcastnetwork.com slash deputy. Charlie Pyramarini is our guest today, and he is a physician assistant in pain management. Now while obviously his patients are suffering in pain, he started to notice a trend that CBD would take care of their pain. And so he decided to become an expert in cannabis, and he started his own company called restorative CBD, which not only provides CBD to consumers, but also provides education to patients and healthcare providers. As we all know, CBD, medical marijuana, the use of it is being used in so many different ailments from sleep to anxiety to cancer patients. And so in this episode, we delve into all of those different things. We first touch on the history. Where did cannabis first come from? Why would there so many limits on it? Why is it a schedule one drug? And why is it now becoming legalized? We then touch on the differences between the molecules, I think a lot of you have heard of CBD. Well how was that different than hemp or what is hemp? How is that different from THC? It can definitely become confusing, but we lay it all out. We then talk about the cannabinoid system, this inherent system that we all have. And it's the same system that will actually give you that runners high. Well, we talk about why it's so important and essentially how CBD and THC affect the receptors. We then go into all the different benefits of cannabis in different ailments such as sleep, nausea and cancer patients, appetite and definitely pain and inflammation. So this is definitely an awesome, awesome episode. I highly recommend you stick through it all because you guys will come out as almost cannabis experts. And again, check out restorative CBD if you truly, truly want to become an expert. All right. Hello, everyone. Welcome back to another fantastic episode of medicine redefined today. We got a special guest, Charlie, who is an expert in all things cannabis. And I'm really excited to delve into this topic, obviously it's a hot topic. We're seeing cannabis get legalized across the country. But we're also seeing maybe its benefits in healthcare and how patients can use it. So Charlie, how are you doing, man? Good. Thanks for having me, guys. I really appreciate it. Yeah, absolutely. So, Charlie, if we can just start off, how do you even get into cannabis? Yeah, great question. Kind of like most medical professionals, right, very, very limited knowledge about anything cannabis or CBD and been last six years in pain management and just seeing a lot of patients coming in. And patients are taking it upon themselves to find anything that will give them any type of relief. So I had a lot of people coming in with bottles of CBD and I had, I mean, I had no idea what it is. I thought it was THC, honestly. And so it wasn't until I had a few patients come in with some life-changing results. Some of them coming in, handing back their bottles of medication, opioids and some of them asking to be reduced. Some of them going from central pain syndrome, they're very difficult to treat to walking and talking and just, you know, life-changing results. And I started taking the serious, started researching in PubMed and a little behold, there's, as of right now, there's over 4,000 articles on PubMed with, you know, cannabis dials one of the headers. So, you know, I've just really made it my mission now to really educate our patients and the medical professionals about this amazing plant. That's awesome, man. That's a scene to see, you know, patients giving back their opioids because CBD is working. I mean, plus an iron, PMR, one of the things we often prescribe are, you know, opioids, oxycodone, all these things. Right. And I'll give it to a lot of patients, they don't want to end up taking it, but to hand back a bottle of this is pretty cool. Right. So, I want to get into the history of cannabis because I think it's such a cool topic that I think there's a lot of misinformation out there. And I think I first heard it on Joe Rogan that has something to do with paper and the paper industry. Is that correct? I don't know. So, if you really want to go, like, really far back, yeah, hemp has been, I mean, there's pictures of some of the first money ever printed was printed on hemp. And also, there's pictures of farmers farming hemp on some of the very first actual dollar bills, maybe $2 bills that were printed, I mean, all the way, way, way back then, you know, Thomas Jefferson, all these guys, some of the, there's rumors that some of the copies in some of the, of the Declaration of Independence was actually written on hemp paper. And hemp's been around, you know, longer than we have. And it's, it's just gotten such a bad rap and it's all because if you really trace this back to, really 1900s, there's prescription paper pads of physicians writing marijuana and THC tinctures for anything from nausea. I mean, the Queen of England was one of the first people ever reported to use it for her endometrial and nausea pain related to her periods. And so she, you know, fast forward to what really killed the industry to things was the taxes that they imposed on it and a little company called Bayer invested a pill called aspirin. And, you know, and so patients like to take a pill rather than, you know, dosing a tincture. So it was way easier to take one or two pills and then, you know, come in the morning rather than hear doses tincture by this and try that. So that really killed it. And then, you know, the whole war on drugs with the 80s that just really put the, you know, put the knife into the heart, but it's have a very convoluted history from the start. I mean, even from Dr. McCollum, who is from Israel, where all of the research is done. I would say most of the research is he actually stole one of the plants that was confiscated to actually study the cannabinoids. So even the legitimate research is kind of founded in illegitimacy. And so it's just a very interesting field. You know, it's interesting. I heard Dr. Andrew Wilde talk about this, I think, because he's one of the, you know, few that in the 70s and 80s was trying to look at marijuana, but he was saying the government would only let you study marijuana if you found negative side effects of it. That I can't speak to that, but it only makes sense because they have the marijuana actual, the patients that were getting marijuana is coming from a single farm in Mississippi. And it was highly regulated, highly controlled. And you know, it doesn't represent what the plant is today. But yeah, I mean, the government just had, so Nixon, when he did his war on drugs and all of those, you know, all the previous presidents and all of them leading up to him, they actually commissioned the drug task force. And actually, if you look at what they said, they said actually marijuana doesn't really have that many negative side effects to it, but they still banned it. You know, they still put it as a controlled one, you know, basically no medicinal benefit, just like heroin, cocaine, math, all these things. So we're slowly seeing it turn the tide since, you know, in the early 90s, the government actually owns two US patents on cannabis die off for anti-inflammatory and I think neural pathocaine, they own the two patents on it. So what do they know that we don't know, I guess? And so cats out of the bag, it's changing, especially states are not becoming legal. It's a matter of time before it's federally legal, I still think that's got some hurdles, but I mean, candidates legal, Mexico just made it legal, so it's just a matter of time. Charlie, I want to stay on this thread of the legality of it, right? I mean, you kind of just alluded to the fact that federally it's different and then state to state there might be some different aspects that we're looking at. But I think it's, let's take a step back really quickly and kind of just make sure that the terminology is all ironed out and so we're not using a management interchangeably. You mentioned hemp, we're talking about cannabis, we're going to touch on CBD, THC, are these terms interchangeable, if not, then what are the differences? Do great, great question. So cannabis is an overarching term and so cannabis is the umbrella term. So hemp and marijuana are brothers, they're both, they're both considered cannabis. The only thing that differentiates them is the federal government labels industrial hemp, they think containing 0.3% of CBD by volume or less, that's hemp. And hemp typically has higher volumes of CBD in it, which is the more medicinal part of the plant. And so cannabis can both be marijuana or hemp, but you know, I, as full disclosure, I own a CBD company, so all the CBD products are derived from hemp, but I also coach patients on cannabis. So that's a good point. They're not one of the same, but they're very similar, they're related, but marijuana is basically the two-manager cannabinoids or CBD and THC in both of marijuana and hemp. It's just how much the percentage for each of them is. Yeah, no, thank you so much, I think that's super important for us to kind of appreciate. And then with respect to the legality of it, again, as I understand, at the federal level it's illegal, but then obviously certain states have recently passed the law that at least the recreational use is legal, talk a little bit about that. Right, so that makes it super challenging as medical providers for us, right? You know, I've worked in pain management similar to you guys for the last five, six years. And you know, we tell our patients that our DEA number is a federal number, right? So we're regulated by the federal government, even though in the state of Arizona, it's with recreational and medicinal here. So you can walk in as an adult and get marijuana if you want, and you can have a card and have it too. And you have some paid different prices and there's some different protections. But basically what I tell patients is legally, if you're getting opioids, which is a controlled narcotic, you shouldn't be having any THC in your system, even though there are studies that show that concurrent use of cannabis with THC with opioids uses, patients use less opioids. You know, we're stuck in a rock in a hard place, especially someone like me who is a big believer in cannabis and coaches patients on it. I can't, you know, legally be writing you've kind of opioids if you're having THC in your system. There is a loophole, so my, the pain docs I work with and how I practice is, I see, we see a lot of cancer patients, you know, terminal cancer diagnoses sometimes are, you know, there's a little bit of a, a little bit of leeway if someone's got, you know, pancreatic cancer. And they got six months left to live and the only way to eat is smoking some cannabis you know, that's a whole different story. It's just I think in the next couple of years it's going to change for sure. That's it. So are you allowed to prescribe full spectrum CBD then to people who take these pain meds? Yeah. Okay. And if you can, can you just explain the difference between, oh, God. Yeah. So still full spectrum, no, because full spectrum has 0.3% THC in it. Okay. So it'll show up in your urine and so I tell all of my patients, all my coaching patients, everywhere I lecture, I said, if you are worried about pop and positive for THC either for your job, for religious reasons or for your pain clinic, you should avoid any CBD products. So we use a 99% pure CBD isolate for some of my products. But what does that leave another 1% right potentially with THC? It's non detectable THC, but if you're using higher dosages for longer periods of time, there are reports that people are popping positive for THC. So full spectrum products, I tell my patients, if you're on opioids, you got to avoid full spectrum. And if you're coming to me and you're on a CBD isolate, if you do pop positive for THC, we have to either stop the CBD or you've stopped the opioids, you can't have one or the other. I can't have both the same time. It's one or the other. So it's kind of put in difficult situations here. And I know you guys understand it too. And it's just sad because some of these patients get such great relief. You know, I've got a guy that's getting CBD. He was using creatum until we started, you know, the urine drug screens are now starting to pick up the creatum. And we don't know what creatum is, right? The opioid properties of creatum and, you know, plus his perk is said plus this CBD. So he's kind of, you know, these patients get into kind of a bind. So what's the difference then between full spectrum CBD, broad spectrum, and then that is good. Yeah. Good question. So full spectrum is basically if you took the butt of the plant and you crushed it and you got the oil out, that is the full spectrum. The full spectrum contains all of the over 700 active ingredients within cannabis. There are over 120, I think, active cannabinoids are finding more every year. And so the other thing that people don't realize is the full spectrum products contained all the terpenes. And terpenes are becoming very, very important across the bloodline barrier. They have a lot of properties, pain relieving, anxiety, sleep, depression. And so when you have a full spectrum product, you have the most real and the most natural product. And then the step down to it would be a broad spectrum is basically when they remove THC, keep trying to keep as much of the other cannabinoids in it. And then an isolate is basically isolating any one of those molecules. We can isolate THC. We can isolate CBD. You can isolate CBG, CBN, all these types of molecules. And that's kind of the hierarchy of how this works. Now, Charlie, obviously, this is a pretty complex system as we're just kind of scratching the surface and early in this conversation. But I think that it has a tremendous value in lots of different properties. But I think for our purposes and our conversation, we're looking at the medicinal aspect, right? And trying to keep this conversation as scientific as possible. And I think no conversation in science can truly be appreciated unless we understand the mechanisms behind things. So, right, I'd love for you to kind of explain what the endocannabinoid system is. And then also, how are these different formulations affecting that system, whether either up regularly or down regularly, talk a little bit about that. So we have an idea. That's a great question. Endocannabinoid system is a very, very complex system. A lot of people have a tough time relating to it because cardiovascular system, heart and lungs, people know what those are. But the endocannabinoid system is a loose collection of receptors, neurotransmitters and enzymes very similar to the endocrine system, right? And so it's a lot harder for lay people to kind of wrap their head around it. But basically, the endocannabinoid system, endometing within, cannabinoid meaning relating to cannabis-like products. So we have a whole system in our body that basically binds products exogenously from the outside. We also produce two carbon copies of CBD and THC naturally in our body that bind as receptors. And so the endocannabinoid system is charged with what they call homeostasis. And so homeostasis is basically just keeping you in a specific regulatory environment. Our body keeps our blood, our gas levels, our pH levels, our respirations, everything in a very tight window. And the endocannabinoid system is charged with being the super computer. It's basically the brake pedal to the gas pedal to all these other systems that are kind of making things go. This kind of slows things down. And so it gets overrun with our, you know, Western diet or lack of sleep or lack of exercise or bad diet. And there's clinical endocannabinoid deficiencies that Dr. Ethan Russo talks about. But the system is incredibly complex. We're just really learning about it. We've only really discovered it in the 90s. Basically we radioactivated, tagged THC when someone took it. We saw all these various receptors. And so the endocannabinoid system is comprised of two main receptors, CB1, which is primarily found in the brain. And the reason they named CB1 is because the first one that was found, CB2, is on mostly in organs and immune system, mostly in the immune system. And there's a new one that they're called CB3. It's the GP55, I think. It's an orphan receptor. They think is a cannabinoid receptor. But basically what also complicates this issue is when you take exogenous or an outside product, CBD, THC, cannabis, hemp, whatever it may be, these products don't just bind within the endocannabinoid system. They're hitting serotonin receptors. They're hitting open receptors. They're hitting trip V receptors, which are big, the vanilla receptors, which are big and pain management. They're hitting camsacin. They're hitting the PPR gamma receptors, which actually upregulate and downregulate gene expression, is an extremely, extremely complex system. Then you start layering on the fact that there's specific enzymes breaking down. These endogenous are naturally produced CBD and THC. And those sometimes become over-regulated, kind of similar to what I tell patients when you take CBD. It's very similar to lexapro or SSRI, downregulating some of the enzymes that are maybe overworking too much. And then the beautiful thing about the endocannabinoid system is one is, it's a, it takes signals out and it puts signals back in too. So it's an affair, e-fairing system. And also one of the only systems in that we know in the bar that actually does retrograde inhibition in the nervous system, and that's why it's very big in seizures. And that's why Epidilox got approved by the FDA for seizures. It's a beautiful drug for seizures. There's a whole litany of stuff on that. There's shows and movies. But the system is extremely complex. There's set enzymes that actually break down endocannabinoids, which are made on demand from the lipid bilayer, and then there's specific enzymes that are breaking it down on the other side. But I mean, now you're talking about not just one system, they're talking about something that's hitting multiple systems, right? And it's extremely complex. It's charged with a lot of stuff. We're still just relearning about what this is doing, and it just makes it so fascinating. So with the exception of CB1, did you, I'm sorry, if I missed this, the rest of them in their peripheral, are they're all central nervous system? So mainly, CB1 is central. CB2 is mostly peripheral, but it doesn't mean you can't find them in the same places. But there's even CB3 receptors that are finding out more at sites of injury, like a broken bone. A lot of endogenous endocabinids are released out of bone reformation. And so it's an extremely complex system. So that would kind of explain the concept of why you have the, you know, the psychoactive component of THC. Because my understanding, at least just from doing a little bit of homework, is that THC will primarily affect the CB1 system, right? Whereas CBD will affect all the other systems, kind of, as you already mentioned. Now, what I found interesting was, and please verify this, that CBD actually opposes the action of THC at the CB1 receptor as well. And so that's why it can help counteract some of those, you know, you have the effects of cognition, memory, psychosis, that stuff, is that true? Yeah, that's a, that's a great, that's an amazing point. And there's so many things I can go off of that, but basically, THC preferentially does bind the CB1 receptor. And so what I tell patients is in my lectures that I give is basically, you know, site of receptors determine function, right? CB1 receptors are found in the amygdala, hippocampus, prefrontal cortex, all areas for memory, emotion, and your cognition, right? So if anyone's ever smoked any marijuana in their life, understands that you get either happier, sad, you get hungry, right, and your judgment's a little bit off. It's because receptors are located specifically in these parts of the brain, and THC, like you said, preferentially bind CB1. Now the, when you start throwing in CBD into the mixes, CBD is what they call an allosteric modulator. So it doesn't bind specifically in the receptor site that THC does, it binds off of it, changing the complex a little bit, and kicking THC off, so it's not binding as fully. And so a lot of patients that get too high, they'll call me, I said, you know what, it's going to sound counter-intuitive, take some CBD drops, and give it about a half an hour, and they'll be holding it like, oh yeah, it's way better, yeah, because it's changing the confirmation in your brain. And that's what's the problem with these, with these, not to digress, I'm sure we'll get into this, but a lot of my patients that go to the spentry, they're 75-year-old grandma, they're looking for stuff for their back pain, and they go to the spentry, they're getting stuff that's super high THC, and there's no opposing CBD, and they're on the moon, right? And they're like, well, that sucks, I'm never using that again, I'm like, well, just give it a shot, you got to use this low and slow type of approach, but yeah, it's, I mean, just explaining that whole process, right, it's super complex, and then you can get into the fact of THC binding beta receptors, right, and that's why there's heart rate elevation when people smoke. I mean, it's extremely complex. Right, and I mean, the best part about it is, and the other thing I will say, we don't have a, even a fully grasped, I mean, we haven't grasped all these concepts, right? I mean, we don't have a clear understanding, and we're still learning, I mean, you mentioned there are several thousand papers out there, but I think, I, please correct me if I'm wrong in this, a lot of those studies aren't randomized control trials, and they're not human trials, is that correct? Right, right, you're 100% correct, and that's what I fight against a lot of my medical colleagues that are, you know, we're the randomized controlled studies, we're the randomized controlled studies, because that's what medicine is, right, randomized controlled, yeah, and for crossover studies, right, and unfortunately, but it's getting there. I mean, look at where we've come from five years ago, right, cannabis, dispensaries, and CBD, so we're deemed essential during the pandemic. I mean, you would have thought, you never thought that five years ago, so the randomized control studies are coming, and they're being done right now, and unfortunately, the people that can afford it are a big pharma, and so, you know, companies such as myself and the other CBD companies, I just don't have the money to run a randomized controlled study and donate thousands of bottles of CBD, so it's coming, it's just going to take some time. Yeah, I mean, change always does, and I think you don't, I mean, nobody wants the rest of the process. Well, some people do, right, I think that maybe if you feel like it, I know when you're sure you talked about the bad actors who are, have the, have the, have the wrong intentions at heart, you know, and, and, and they're doing their own, they're not doing it for the science reason, they're, they're looking at it from a business perspective, and understandable. But I think that you just need a few bad apples, which we've talked about at Lentz on this show. You mentioned earlier that large doses, you know, even if you're taking a CBD isolate, can give you a false positive, right? What kind of doses are we talking? Are we talking milligrams, you know, micrograms, what are we talking? Milligrams. So it'll most likely be anything, I mean, consistently over times, cannabis and THC are fat soluble. So it'll be stored in your fat. And so, and basically everyone's endocaminate system processes, things different. We can get into the gut biome and the, and that absorption properties. But I, I saw a paper once I wish I would have printed out about people taking CBD and they got bacteria, you know, synthesizing CBD A, which is the un, uncarboxylated portion of CBD. And you can sometimes be positive for THC, but also we know as medical professionals that, you know, point of care cups are not, you know, are they're not PCR tests. And so it's looking for anything that is similar as a cannabinoid rate THC and CBD are similar enough, right? And so there's different isomers of THC. There's Delta 8, Delta 9, Delta 10, THC, zero THC V. So sometimes it could be, you're not even taking TH Delta 9, but you're taking something as a full spectrum product that maybe just says THC A, which is non-psychoactive, trips off it, you know, but usually patients that are taking 100 milligrams or more consistently will have a chance of, of testing positive. So again, I tell patients like even topical products, you, I mean, I've seen patients come in that I trust and I'm like, I'm only using this topical product. So it works. Yeah, you're positive for THC. Like what the bottle says is no THC and I'm like, well, there's THC somewhere. And so, you know, you got to stop it, but you've got same conversations, I'm sure you guys have that. Yeah. Yeah. No, no, it's important. And I mean, as many times as it takes to kind of continue educating the masses, I think that's what it's all about. Before we switch gears from the mechanism, you know, understanding that just to further develop that, talk a little bit about the, if you don't mind, about the pharmacokinetics. So you mentioned topical. That's, that's one mode, right? I mean, there's, I mean, there's edibles, there's, there's a tincture and all that kind of stuff. I think that you touched on how, how quickly does it act and what are the differences? Yeah, great question. So the best, best way to deliver cannabis is inhalation, right? It's the quickest and it's the most absorbed. I have a tough time being a medical professional and telling patients to go smoke joints, just because or vapor, you know, especially other stuff that's going on with vaping and all that stuff. So I really avoid that. But I think it's 40 to 50 percent systemic absorption was smoking in the onset, like 10 to 20 minutes and the offsets, you know, an hour or two. The next level would probably be a tincture, a sublingual tincture, anything under the sublingual, you know, the tongue is full of that, the venous plexus, which is able to absorb it. That is anywhere from 20 to 30 to 40, I've seen some literature kind of all over the place. And that is going to be a little bit of a slower onset, 45 minutes to an hour. That's going to be a little bit of a longer, around kind of a couple hours. You know, they say, they say oral CBD can be dose anywhere from Q8 hours. So, you know, three times a day-ish. I tell patients every three to four, every three to four times a day depending on what you need. Topicals are absorbed, right? Systemical absorption is lower, but it's still there. And then gummies, like, the edibles are like 33% of the marker right now. Those are slowly absorbed. The absorption rate is much lower, and I don't recommend those for, like, pain patients who typically need a little bit higher doses. So, you know, even the research, even the literature, I've got textbooks here with, from Dr. Andrew Wile wrote the forward to cannabis pharmacy, right? And I've got his numbers from what they're saying for pharmacanetics is different than some of the stuff you find on PubMed. I mean, even published research is still kind of all over the place of what's the stomach absorption, what's the, you know, it's the pharmacanetics, and it's so variable. Yeah, Charlie, and, you know, the other thought that I have, you know, let's just take aside the whole vaping related language during that type of stuff. Right. But, you know, as a clinician, if I was thinking about it, you mentioned earlier, just if somebody is inexperienced and completely naive to this, and you want to just, again, you know, you know, start low, go slow kind of you mentioned, titrating the dose of something that's being smoked. I mean, that would be, how would one even go by doing that? Yeah. So, I've talked to some other cannabis clinicians, and a lot of times what they'll do is actually tell patients to smoke one puff, wait a half an hour, see how you feel, and go up or down from there, and then sometimes they transition them to an oil or a tincture. But, you know, that's what's, so that's what's beautiful about cannabis medicine is. It's very specific to the patient. And so, one puff for you may make you super high, one puff for me doesn't do anything. And so, low and slow, and basically this is why I think cannabis has a tough time catching a mainstream medicine is because a lot of practitioners are used to, you know, we can write a script for a purpose that 10 milligrams, take it three times a day, you know the dosages, you know how it's going to work. I tell you to take 10 milligrams of a tincture three times a day, it may not be enough for you, but it may put, you know, your friend on the, on their ass. So, it's, it's a very complex structure, and I think either vaping to start or tincture to start at a very low dose anywhere from five to 10 milligrams is kind of where patients should start. Yeah. And I guess, I mean, not all puffs are created equal, right? I mean, what are we talking about? Right. One second. So, yeah, I think that for me personally, just, you know, having some experience with this in dealing with a lot of patients with chronic pain in our world, I mean, this is kind of the part that I have a difficult time wrapping my head around, but it sounds like from what I'm getting from you is that's not your preferred method, because it's harder to kind of control. Is that right? It's harder to control, like you said, yeah, how long, how, what's your lung capacity, right? Your title body, how long are you holding it in, right? Like, and so with a tincture, even I've got the compliance with my tincture still very low, and I have written instructions, I tell the patients where the tincture bottles that I have have etched marks on it, you know, hold it for three to five minutes under your tongue, swallow it, you know, so it's, it's a little bit better, but I still think it's not, it's not perfect by any means. There's a few comments out there that have syringes full of, like CBD that you can kind of tick mark down to the back of your mouth. I don't know how perfect that is, but, you know, I don't know, it's, people, what we, what happens is we get away from the full spectrum products, which is the most beneficial part of this plant. And so I think that's why everyone's looking for the magic bullet, right? How do we, how do we take, put it into a pill, but that's, that's not what this thing is about. The things about using the most full spectrum product of possible. Right. And I mean, we can complicate it even further, right? I think people need to understand that there's different strains out there. There's indica, there's ativa, there's hybrids, right, and you can do an edible, which is going to last longer than, you know, maybe the smoke, right? So it's, like you said, I think it's individualized, for sure. Right. And to touch on the vaping, I mean, in the lab, my intern, you're last year, I think I had three patients that I saw with Ivali. So was that, yeah, E cigarette vaping, long associated injury. Oh, yeah, yeah, yeah, yeah, yeah. And I've, I've seen them with one girl who was smoking out of a, you know, a vape two times a week, only for three months and developed it. So you know, it's not necessarily people have this association with it thinking, oh, you have to be doing it for three, four, five years consistently and constantly. And well, it's apparently not the case, right? Because you don't, you might not know what you're getting out there if you're going black market or something. So it's definitely, right, and what people don't realize is the flavorings that they use for these, for these vapes are cut with random crap, right? And so even if it's cut with the vitamin E, it should be cut with, you know, terpenes and all the natural products. And then what I didn't even realize until I got this injury was the actual lighting elements inside of those things, the ceramic, are they ceramic, are they titanium, are they, you know, a whole litany of stuff that I don't even want to get into. So, you know, it's a shame that that whole market people, like the bad actors came into that and just made a crap ton of money putting out CBD vapes really quickly. But I mean, what do we left with people now? Does young girls got popcorn long or whatever they call it now? Yeah. Who knows what's her prognosis for us in her life, right? So, right. Exactly. Well, I want to get back to the endocannabinoid system because I know you mentioned your book Omega-3s, right, and how that also has a big role in the interaction with cannabis. How does that work? Yeah. So our natural endocannabinoids, two A.G. and ananamide, are actually byproducts of omega-3 and omega-6 breakdown. So obviously, as you guys know, a lot of patients are just deficient and good, you know, good healthy fats. We like to eat a lot of trans fats because it's nice and easy and quick and it tastes good. But so sometimes it adds to the endocannabinoid system deficiency that a lot of doctors are kind of finding out that it's playing to a lot of these hard-to-treat diseases, fibromyalgia, myagranes, all that stuff. You can look up Ethan Russo's stuff. But yeah, so supplementing with a good omega really makes sure that you're, it's also anti-inflammatory, right? But why are omega-3 anti-inflammatory? Maybe it's because part of it is because it's feeding the endocannabinoid system, right? I mean, no one's definitively showing omega-3 anti-inflammatory because it does block tumor in the closest factor or whatever it is, right? So you know, I think supplementing with a good omega just keeps your endocannabinoid system nice and healthy. Gotcha. I think I want to switch gears here now, talking kind of going back to the bad stigmas of things. You mentioned a little bit before about what cannabis is approved for. So what is it approved for by the FDA? So the FDA has approved CBD, the isolate, for the treatment of a salt-small subset of pediatric seizures with epidialox, which is extremely expensive. And I think they just got approval for seizures related to sclerosing, colongeitis, maybe there's some things, some other crazy salt-small subset of diseases. They're just going after what the orphan disease, right? Stuff that's really hard to treat, that's kind of like a Hail Mary. And they're using a CBD that's extremely expensive because it's regulated, right? And they did all the studies and they're trying to recruit their money. Same CBD that we make in my place for $10 a bottle, right? I mean, but very small subset of what is approved for cannabis on itself is state by state approved medicinally for certain diseases. Pain's usually one of them, right? Cancer, pain, you know, cacaxia related to cancer. I think even stuff like HIV, there's other issues that state by state determines what is medicinal cannabis, but still federally, it's still illegal, which is wild, right? These states are allowing cannabis to be written or recommended by physicians. But, you know, I think it's the Ogden memo that limits the federal oversight into arresting us for recommending cannabis, but, um, yes, so wild Westman. Gotcha. Now, Charlie, I'm curious to know what the conversation is that you have with patients who come in, right? And you say, hey, this doe, I think we should try some CBD for you. And, you know, they come from a generation possibly where schedule one, this is illegal, there's no way I would try this. You know, I thought this is what junkies do, right? What's the conversation you have with those patients? Yeah. Um, you know, I think by the time they come to see people like you and me, they're kind of, they'll try whatever, right? You know, and so, um, but the conversation is, listen, see, you've heard of CBD. It's not cannabis, it's cannabis, but it's not marijuana. It's hemp derived. Um, you know, we're going to start low and go slow, you know, it's kind of, it's a titration schedule. It's a personal dose. And I kind of talked to the patients, say, listen, are you ever tired of just come into the doctor's office and we write in prescriptions behind our computer, typing it up and sending it your way, this is your way to kind of take on this back onto yourself because you're able to take home a journal and really monitor your doses and how much did I take and how did I feel and did my pain go away and all these things. So, try and really tell them like, hey, this is a, this is your chance to really take, take control of some of your healthcare back into yourself instead of just me writing prescriptions where you left and right or doing shots or injections or whatever it is. So, the conversation is not as hard as you think it is. You do get pushed back, but literally just say, here's some, here's my pamphlet, here's some literature. If you have questions, I'm here, go home, I website, listen to my podcast. Um, but yeah, definitely that generation right, devil's lettuce, it's, you know, it's marijuana, it's going to get you high, you know, all that stuff, it's, it's there. But you can buy CBD in the gas stations now, I mean, so I think patients are getting just seeing it all over the place on TV. So it's, I think they're getting, they're open to it now. Absolutely. Yeah, no, I mean, even in the PM and R world, I know my attendings are starting to learn more about it so that they can have these conversations with patients. We do have patients coming in with spasticity. And I think there's actually a big study going on right now in Germany, I believe about CBD and spasticity. So yeah, I mean, it's, it's important for us healthcare practitioners to understand how to approach this conversation, right, it's becoming more and more popular. So, Oh, yeah. And that, but that's the biggest problem about this is like, we're never taught about any of this in medical or PA school or nursing school, right? Like, there's a whole body system that didn't even mention a cabinet system, right? You didn't even heard about that. What if the heck is that? So, just the fact that we can even just mention that word and people like the doctors at least have an idea what it is. That's kind of how the goal is, you know? Absolutely. Yeah. So last week on Instagram, do you know who the psychiatrist is, Dr. Daniel Aiman? He does a lot of like brain scan. I've heard of him. Yeah. So yeah, I've heard of him. Yeah, yeah, yeah. He kind of got popular talking about alcohol and like Alzheimer's and this is what your brain looks like now and he does a functional MRI. So recently, I think last week he went on impact theory with Tom Bilu and he talks about marijuana and how marijuana decreases blood flow to the brain and he talks about how he's not really a proponent for marijuana. Just kind of wanted to get your thoughts on that, you know? What do you? Yeah, I mean, I think that's, I think that's a, that's kind of a, I don't want to say a loaded question, but I think one, what, where the blood flow, what region of the brain is a decrease in blood flow, too, right? How do you quantify it? You know, I still think marijuana is marijuana doesn't come without any, there are still side effects, right? You have cannabis induced hyperemesis syndrome, which is skyrocketed in all the ERs, right? And if the listeners are familiar with that, it's when you consistently use too much cannabis. Basically, the receptors for your, you know, basically your emissive, or your throwing up, start to kind of switch off and you basically just continually throw up in the other way that you fix yourself is by sitting in a tub of hot water, shunts blood away from your stuff into your skin. So you don't feel nauseous, right? We don't have to go into the whole physiology of that, but basically there are side effects, right? And it's also they've done studies and they've shown that the one study that gets misrepresented I think is, most people say, oh, cannabis causes schizophrenia or causes bipolar. I think the data, if you look at the data, is it, if you have an underlying potential issue of developing schizophrenia or bipolar, it maybe kick starts it, right? I don't think it's causing it. I think it's maybe bringing that to the surface and, you know, in relation to the blood flow, I didn't see the study, I don't know, but, you know, come on, any of the drugs that we give, how come no one's ever published a study about opioids and the amount of testosterone that gets decreased after you take an opioid, right? Half an hour after with the increase in estrogen, I mean, there's bad to everything that we do. It's mitigating risk and it's the right drug for the right patient for the right condition, right? Is there, is there no evidence? I mean, I'm not familiar with it, but I'll tell you what, having recently taken my boards, I mean, that's, that's tested quite frequently. We talk about that all the time as a known side effect. So I would imagine that it's a document in the literature, I, I, I, I, I couldn't take it off the top of my head, which part, the testosterone stuff? Yeah, yeah, yeah, yeah, yeah, yeah, yeah, that's subsequent, yeah, huge, right? I mean, that's huge, but, so, you know, cannabis gets a, gets a bad name for potentially doing some of these things, but now we're decreasing people's, you know, testosterone people are addicted to this people are killing themselves because they can't get it. I mean, so there's always something bad with everything that we do and we just mitigate risk for providers, right? And, um, I think right treatment for right patient, for the right condition, I think cannabis is a good option. And I tell patients is, it's, you know, if you look at integrative medicine with Dr. Wow, right? It's one piece of the pie, right? And if I'm just, I, I can't give you, I can't give you enough CBD to overcome your bad diet, your lack of exercise, right? Are you meditating? What's your sleep pattern? Right? I tell patients like, if you take just CBD and expect this to be a miracle drug, it's, it's going to fail you, it's not going to work. This is in conjunction with other types of issues that you need to change in your life, right? Um, yeah. And so, you know, yeah, right, it's not the cure all, right? I think that's, we've been hitting that theme over and over, right? You got to get your lifestyle foundation correct first and these are all adjuncts, right? To kind of help you get over that hump and make you feel a little bit better, right? You mentioned Charlie's cyclical vomiting syndrome. Now, you're right. I've, I probably changed about five or six patients last year with that. And it's tough, right? Because what's going to help their nausea? They obviously think the cannabis, right? And then you fall into the cycle, what, what have you seen to work when you, when you treat it? Because I mean, we console gastroenterology all the time on these patients and it just goes back to using IBS medication, which does not help the patient. And then of course, insurance companies are like, well, we want you to try mirrorlacks before, you know, going on to this medication that we know will help. Right. Um, so I think with, you know, I don't have any clinical studies with this, I don't actually don't have any, you know, clinical, it's trying to think, I don't have any, I've never seen any patients with this because the patients that I deal with are not abusing it. They're using such lower doses. Sure. Um, but it also has to do with right, I mean, what's the nausea reflex? It's from, it's from stomach and also in the brain. So the receptors are, you know, are getting kind of messed up. And so I think absence or you're going to feel like you need it more. But, you know, I, I don't have a direct answer for you. But I think, I think people are remiss from, I mean, when, when a cannabis became legal in Colorado, wouldn't they say the, the amount of cyclical bombing they saw in the ER and Colorado was like, stupid, right? Right. But I think it gets back to the point, right? Every drug cannabis is a drug, every medicine that we prescribe has potential side effects, right? Aspirin has side effects, kind of, cell and has side effects. Doctors for the right patient, the right dose at the right time can have benefits. Yeah. So I think that this is kind of a perfect time to talk a little bit more about the therapeutic effects, right? I mean, you've talked about the end of kind of an ointment system, um, impacting so many facets of basic life. We talked about appetite, immune function, reproduction, all kinds of things. And so again, a bevy of possibilities for, for CBD, impacting health. But I think that the strongest evidence is probably for epilepsy. You touched on that. That's why the FDA has approved a drug for it. Would you, would you agree, is that fair? Yeah, I would say, you know, without being, you know, there's no, without being anecdotal, 100% clinical. Yeah. That's the only data that's been published, right? Gotcha. So could you, I'd love to kind of start and take a top down approach with the, with the strongest data. And then we can talk about more about pain and inflammation. I think that might be a close second with versus anxiety and sleep. And some, you know, obviously they kind of all go hand in hand. It's kind of this web that's tied together. But in terms of epilepsy, again, you touched on recalcitrant seizures, not, you know, not being treated and not successful in, with any other, right, occasions. And I know you've had several folks come on your show, talk about, um, their own personal stories, which have been powerful. So in terms of how is it, you know, affecting, you touched on the receptors before, but in terms of epidyleic, maybe we can talk about that medicine and how it's affecting and treating that specific disease. Yeah. Good question. So if you look at how, um, CBD works in the, so basically, right, for, for lay people that don't understand seizures is basically just a, uh, electrical storm in your brain. Right. I'm not a neurologist, but at the basic level, it's electrical storm in your brain, right? Um, the, the neurons are firing too quickly. They're not repolarizing and they're able just to continually fire signals causing a seizure. The endocabinine system has been charged with part of it is when a neuron sends a signal from the presynaptic to the postsynaptic, going upstream or retrograde, the endocabinine system will send a, a molecule, they're, A E A or an atomite or two A G up and it takes the presynaptic neuron and it makes it more hyperpolarized. So it can't fire another, another, um, another signal, right? So what happens is when you give somebody epidylox, one of the mechanisms that's proposed is basically the CBD and epidylox takes the enzymes that break down your natural endocabinines that you're making that make this process harder to happen again. It stops them from being as active. Like I told you, like I said earlier, like that is our eyes kind of similar in that fashion. Um, that's one of the reasons, one of the ways that they think and that's been proposed of how epidylox works procedures because the retrograde inhibition, which is a very powerful mechanism. Yeah. Now, I mean, that's, and I would even add it is not only is it an overdrive, but it's also the firing is asynchronous, right? And I think that kind of just messes up the electrical storm that you talked about. So right, switching on to talking more about pain, I mean, this is highly prevalent. I mean, even higher than epilepsy and we talked a lot about opioids, we've been back playing for the last maybe decade or two with opioids because we've kind of dug this hole. And so now everybody's on the opposite side of the spectrum where no, no, no, no, it's no, nothing. And we're trying to, we're reaching for everything, right? And so I want to talk about how the, you know, what the mechanism is, what, how, what the quantity of THC is required in CBD products in order to get a therapeutic effect with this. Good question. So start off in mechanism. So I'm obviously not, I don't know all of them, but I know the ones that I lecture on mostly are twofold, one inflammation, right, decreasing inflammation to help decrease pain for multiple reasons, right, decreasing nerve, nerve irritation. And also the second thing is the CB1 receptors are found in the dorsal root ganglion, right? They're also found in the amygdala and they're found in the hippocampus. So those two things, right? So pain is not just a perception, pain is also your memory attached to that perception of the pain, right? Step on another, like, oops, I know what that is. That's a nail, right? I've had that before, this sucks, this hurts, right? So if you're able to bind these receptors and decrease their activity in the dorsal root ganglion, which is where the pain is becoming afferent, right, into this phytoplank, into the midbrain, bologna, gets, gets, go to the prefrontal cortex, all these things, right? If you're able to cut it off, not only at the site, right, because there's CB1 receptors inside of your, in your skin, and on the inflammatory markers, like your white blood cells within your skin that are going to respond to any sites of injury, but also along the track of where these pain signals are going, if you're able to down-regulate that and decrease the ability for it to produce its pain signal, but now also you're decreasing, right, hippocampus, which is memory, decreasing amygdala, which is emotion, decreasing, you know, pain is perception. We all know this, right? Your pain is not my pain, and my pain is not your pain, but it's also the memory attached to this pain. If you're able to decrease that, it helps decrease some of the pain associated with that. So it's not a magic pill, there's actually physiology, and there's many papers published about where the CB1 and CB2 receptors are located in this fashion. And so regarding dosages? Yeah, sorry. Yeah, go ahead. No, no, that's what I was going to ask. Considering that this is the aspect that we're still refining, right? We don't have FDA kind of supporting that. So what type of dosages and which type of formulations would work? Great question. And the answer is always going to be low and slow, and it depends. And so if you follow Dr. Solac, Dustin Solac out of things out of Maryland, if you do the medical 401 courses, everything is about some people do weight-based, some people do a low and slow approach, because CBD is what they call bi-phasic. And so if you overshoot your course of where your natural pain relief is, it sometimes can make pain, anxiety, or sleep issues worse. And so you have to go very low and very slow to find your titration and to find your window. And so starting low, starting slow, a one to one CBD to THC is the most recommended thing because, again, we talked about, if you don't have, if you have unopposed THC, you're going to get super high. And so the CBD is really important to have and starting out a one-to-one ratio, starting very slow, starting anywhere from 10 to 25 milligrams a day, split up either at bedtime, split up a couple times a day, and doing that for five to seven days, taking note of how you feel, how you're sleeping, how you're anxiety, how you're pain, and then from there going up or down based on how you feel, but it has to be very slow, kind of like a gap of pet and titration is what I tell my patients. Now, when you say the one-to-one, can that only be achieved with full spectrum? Is that what we're talking about there? So a one-to-one is what you would find kind of if you go to a sensory and you're looking for a straight, just cannabis products, yeah. But full spectrum, it's not, full spectrum is not technically quite one-to-one because I have a 3,000 milligram full spectrum CBD oil. So a full dose is 100 milligrams CBD, but the THC, right, 0.3% that bottle's not a one-to-one, so. Okay. Yeah. So essentially, over the counter, when people are ordering it from different companies, getting it at the gas station, as you mentioned, assuming that putting aside the contamination purities, all the GMP, all that good stuff, that is in terms of what the data supports, that is not going to be efficacious for pain, that's what you're saying. What is not? In terms of pain control, like if you're just getting maybe a broad spectrum, a full spectrum or even a CBD, because obviously, you mentioned people for various reasons that might not feel comfortable taking a full spectrum because they're going to be tested, religious reasons, ethical, whatever it might be. So from what we do with the evidence. Yeah. CBD would still bind the CB1 and CB2 receptors, but you're going to be missing out what they call the entourage effect, which is very important to mention, right? It's the entourage effect is the parts, the some of the parts are greater than each of them individually. Kind of like what I tell people, it's, you know, it symphony sounds great if you listen to all of the parts together, but if you just have a violin and a saxophone, it doesn't sound that good, but as soon as you start adding all these other instruments or all these other kind of binoids, it creates bigger conformational changes around those receptors and it works better. And CBD, isolate is better than no CBD at all, you know, obviously within reason. But you know, full spectrum product works the best and then a broad spectrum and then isolate goes down from there. But low and slow, five to 10 milligrams, once a week, change your dose and just kind of got to figure out where you're sitting in with that. Awesome. All right. Let's keep going down, right? The next best thing to talk about is just mood related disorders. Again, you talked about the perception of pain and how that anxiety even building up, you know, how can amplify your experience of pain, right? So where are we with mood related stuff, depression, you know, anxiety and any of those? So again, no, I haven't seen any, you know, peer reviewed double blind crossover studies of CBD or cannabis for that. Just knowing where the receptors lie for the CB1 and CB2 receptors and CBD and THC binding to it, right? Obviously, you don't want too much THC because everyone that's smoked too much THC products will tell you they get more anxious. But you know, it helps decrease sympathetic tone. It decreases amygdala activation, decreasing some of your perception of the anxiety. A lot of anxiety also is you're perceiving the anxiety, it feeds into the anxiety and then you go into this whole circle. And so, you know, without going into any, I don't have any published data about it. I can just tell you where the receptors are located. And when the CBD binds it, you know, that's, you know, if you're going to paint me into a corner which a lot of physicians do, it's kind of, you know, where's the data? You know, I don't have concrete plus, you know, plus versus placebo data, but I can tell you anecdotally patient, it's helping patients. And you know, we use a lot of medications off label too that don't have all the published data that we have that we want for everything, right? So, I don't know. Yeah. No, I think we can certainly appreciate that. I think it all starts with, does a science make sense, which is kind of what we're talking a lot about, right? I mean, I think we've kind of beat that over and over and explaining it. And so, we have mechanistic understanding of how it makes sense. And then anecdotally, you're having good experiences and you're not the only one. Obviously, there are a lot of people who are doing it, just think about how popular it is. We've already touched upon. In your practice, what is the primary reason that your patients are using it? In terms of, you know, the volume of patients, is it more for anxiety? Is it sleep? Is it pain? What are you primarily seeing? Pain in sleep. Pain in sleep. Okay. Yeah. Yeah. Okay. Cool. And so, I think that makes sense as well. You know, we always talk about, you know, we had Patrick Feinen, you know, my friends here who's a psychiatrist by training, talking about this bi-directional relationship between pain and sleep and understanding now that, you know, impairments in sleep quality actually amplify the pain experience. And now, obviously, I think anybody who has a poor night's sleep, we're talking about how we're irritable. And again, you know, we're talking pain, sleep, mood, they're all kind of tied in together. Right. Now, the other thing, and this is kind of where it gets a little tricky as people start talking about, when we start talking about the effects of cancer, right? And again, I know that's just a overarching big term cancer, and we can talk about different types of cancers and what that even means, but I'm like, different types of cancer. But when people talk about, oh, this helped cure cancer, and I put that in quotes, or this has helped in cancer treatments, what are people even talking about? Is anything related to CBD, THC cannabis, anything that we know today, you don't have to answer the question if you're comfortable, because I know it gets a little tricky there. Yeah, that gets a little tricky. And so, you know, I think the biggest thing for cannabis that you can see, and not only anecdotally, but the evidence, is the nausea associated with the chemo therapy, right? You need to eat, and a lot of these patients are eating because they're nauseous, so the cannabis can help with that. Now, cannabis, in the term of treating and killing cancer, there are in vitro studies, right, in petri dishes, where they're able to replicate certain cannabinoids that are able to quote unquote kill cancer cells. Now that would be a great, that's a great finding, right? There's some merit to that, but we all know in vitro does not mean in vivo, right? So what happens in a petri dish is extremely a very, very far leap from what's going to happen when you ingest this, with all the different factors inside of your body. So to say cancer, see, I mean, and I'll probably get flacked from some of the people in the cannabis industry that, you know, I'm this representing it, it does cure cancer and all of this stuff, but you know what, I'm not going to go out and risk my professional reputation and my medical license on saying, you know, use cannabis to treat your cancer. I think that's a very, that's a very inappropriate and, you know, not, not a safe comment to make, but there are some, there are some instances that people have used it. I've seen it, you know, but I can't speak to any more about that. I don't know. I'm basically trying to overlay myself around that question. Yeah. No, absolutely. No, I mean, sorry, Dars, what I will say is, so actually, you know, kind of just learning a little bit more about, I came across a paper in Aqua Target in 2016 that talked about the potential of CBD being a pro to Mergenic, you know, and particularly for colon cancer. And mechanistically, they talked about how it activates the C, man, I hope I'm not getting this wrong, the CB2 receptors with sub-micromolar doses. And it, the, so it's the, the, it becomes an agonist for CB2 and induces cell proliferation and favors the acquisition of molecular features in colon cancer cells. And I forgot now, some of this, the biochemistry was beyond me and, you know, I think I could probably, we can find the paper and link it in the show notes. But I don't know. Have you heard anything about that? And so, you know, the flip side, the arguments there as well. So in terms of people trying to jump it down your throat, I mean, I, I think that would be kind of ridiculous because this kind of goes back to the idea that most of the stuff that we know in cancer treatments, I mean, Marinal, which is the synthetic CBD has been approved for a long time, we're, yeah, I mean, cancer-related pain, that's what we're treating. We're treating the symptoms, right, by cancer, not necessarily the actual pathology itself. Does that make sense? Right. Now, I get that. You know, it's, I think it's difficult because cannabis and CBD are under this microscope, right? I mean, there's a lot of time, there's anything good or bad, people, people elevate either one of those sides of the research, right? And I haven't seen that paper specific that you're talking about, but I have seen some stuff where people are like, oh, high dose of CBD can increase X or whatever hell it is. But, you know, I don't know about that specific paper increasing cancer, but, you know, it potentially could, right? We still need more research on this and it's still, you know, but anything in medicine still needs more research, right? I guarantee if you were to look at, I mean, what's the research on aspirin? The colon cancer, right? Doesn't go back and forth every year. Oh, it's preventative. Oh, it's not. It's going to bleed out. I don't know all that stuff. But I think, you know, I think if potentially could, I mean, I don't see any research that shows that it doesn't or the research that shows that it does definitively, right? I'm reading a whole paper right now about, you know, functional gut health disorders and how cannabis, health with IBD like colitis and the way it works in the mesentery and, you know, the mucosal cells and stuff like that, but just knowing how CBD works and preferentially decreasing the, the white blood cells that are kind of overactive and actually kind of old and retired helps actually create apoptosis in them, you know, but I don't know, are you killing too many, too many cancer-fighting cells? I don't, I don't know, you know, right, right, I don't have a direct answer for that. That's a good question. Sure. And this is, this is why we're young in the, in the subject, right? I mean, this is what all the research is having and, right, you know, with every single organ system. So it's super good stuff. I wanted to touch on marinal that ultimately I just brought up because I remember being in turn, just starting residency, a lot of the cancer patients at the Hemonc service, I'd see marinal and be like, wait, what? We have weed in the, in the hospital that we have, right? Right. Right. Right. Right. But little do we understand that it's actually just synthetic THC, correct? And it's not because it's a full agonist, which I read in your book, it's not going to work the same as your organic THC that you would otherwise get from. Right. Canvas lab. Right. Can you explain that a little bit? Yeah. So, marinal never caught on because one thing that we continue to lack understanding of is that this plan is extremely complex and that you need the entourage effect, right? And so marinal is a partial agonist of the CB one receptor. The problem is there's no opposing CBD, so a lot of patients, I've written it before and then the patients that take it, whenever you wrote it, they're high, right? And they're like, either it doesn't work for them, but they're like, man, I'm super stone and it's not achieving what I needed to achieve. So, screw this and never really caught on. But I was like, well, maybe I can write marinal because it's prescription and then I can just give them my CBD and then I created basically cannabis. But that's neither here nor there. But yeah, I mean, we try, right? We try to solve everything, you know, every, red yeast rice and lipitor, right? And we're at Willow Bark and Aspirin and we try to solve everything down to its active molecule. But what happens if cannabis works just because it's super complex? I don't know. Absolutely. Yeah. And I think the only times now I've really tried marinal for appetite, I've seen it work made slightly in some patients that need weight gain. But otherwise, yeah, it's not really doing much when I prescribed it. So, but I will have a lot of patients say, hey, can you, can you give me some marinal because, you know, I do take this cannabis at home and, you know, give in different hospitals, regulations, you got to, you can't really prescribe a THC, which now it's nice to think that at the institution that I work at, we're starting to allow patients to kind of bring in their own supplies if it, if it, if it shows the help. Oh, really? Yeah. Yeah. And so patients are for every patient for anyone. Yeah. As long as, as long as it's approved by the doctor or like, as, as, if it's approved by the physician, and there's a need for it. So like a lot of the IBD patients, like you said, all right, some like crazy pain that we can't really, you know, put a, put a pin on it will, will allow them to have their home supplies. So that's, that's super cool, man. That's for, you know, in Israel, they, they give cannabis to their patients in the hospital. So yeah. Awesome. Well, Charlie, I think it would be super important for us to, I mean, again, anytime in medicine, we all take a day for a category, we always start with do no harm, right? So we've talked a lot about the mechanisms, we talked about the therapeutic effects. This is, maybe we could have led with this, but let's talk about the safety concerns, right? And, and some of the adverse effects that people do tend to experience. We touched on them here and there, but what are common things that you'll see in your practice, but also reported, both common and also serious ones that people need to be on the look out for. Yeah. Good question. So the research shows that there are, there is a potential for liver enzyme elevation that is published data, but it is a couple thousand milligrams a day. And the people, the publisher that they have the LFTs that return a normal once the patient stopped the CBD, most commonly, and that's what I always worry about, right? If someone's already got Nash, or they're already on a statin and they're liver, potentially some liver issues, already kind of in the back of your head, you're like, all right, this guy starts taking higher doses, we should probably get a CMP real quick just to make, you know, make sure everyone's doing good. Most common reasons that people stop CBD and or cannabis is when they're like the feeling of it, too, sometimes the headache stomach and stomach upset is kind of kind of the biggest one, especially with higher doses and CBD, some patients get a little GI upset. And then, you know, sometimes people that increases their anxiety, which I've seen plenty of time. So like I said, CBD is a bi-phasic molecule, too much can make your symptoms worse. And so those are kind of common, but otherwise, you know, cannabis and CBD are pretty well tolerated. You know, if you're working with a knowledgeable medical professional, that's going to sit there and walk you through this, right? There are potential, I don't know if you're going to touch on, you know, drug interactions I touch on in my book and on my course, you know, anything that goes down the CYP 450, you know, a lineage of enzymes in your liver, right? It can only digest so many things at certain times, right? Some of the drugs that we write are pro drugs that need to be digested or are to be active, right? And some of them need to be digested to be excreted. And now, if you're putting a bunch of CBD down this pathway, it may, you know, get, get, you know, put a car accident down there and you may not be able to get all the stuff past it. So again, low and slow and, you know, sometimes if patients come in and their LFTs are elevated, is it due to the CBD? I don't know. But the two drugs that really concern me and that I always make sure that their prescribing physicians check with is any anticoagulant specifically warfin, twofold, right? Warfin is digested by the gut bacteria and vitamin K can alter warfin and CBD alters the gut bacteria and seizure medications, right? These are life sustaining medication, CBD is a life altering medication, it's not a life sustaining medication. So I, when I see those two medications on patients list, I say you're on warfin, who's writing it for your cardiologist? Make sure your cardiologist understands that we're taking CBD. We may get to higher doses and to maybe, you know, take an eye, take, take your iron arm maybe a little bit sooner than usual or whatever it may be. But those are the two ones that always in the back of my head, I'm like, alright, you need to really make sure you're doing this correctly. And then what about, you know, issues like contamination, right? I mean, at this stage of the game, I think for a lack of a better word, I mean, I would say that since most people can purchase it over the counter or, you know, at the grocery store, almost like a supplement, right? And so you always worry about different kinds of contaminations, we talked about the bad actors again, you know, you only want the product that you're getting. You don't want, you didn't sign up for the additional things that might have adverse effects. So how, I mean, what are common things that you've seen and we don't have to name any names here. But how do people sit that? So, yeah. So on the back of the bottles, on the back of the website, there's usually QR codes that link you right to the, right to the lab results. But in the beginning, it was a lot of solvents. Sometimes there's still a solvents depending on how these people are pulling out the products from cannabis. They're using either CO2 extraction, they're using ethanol, they're using other types of issues. Sometimes, you know, Delta 8, the big thing right now, Delta 8HC is not a natural occurring product, a cannabinoid, so they take CBD isolate, crush it with some type of chemicals, and they can Delta 8 full solvents. You know, so the contamination stuff is a little bit better than it was. But also, when you're smoking full flower, what people don't understand is the hemp plant actually recycles the earth and recycles the dirt. So if there's any contaminants in that soil that the hemp is growing in, it's going to suck it out and put it into the buds. And so it's very important when people are using smokeable flower that the labs show, pesticides, fungus, you know, all these other types of things that you don't need to be concerned about about an ice lid or a full spectrum product has already been kind of distilled out. But a lot of that and a lot of people that aren't putting the jam article, I think of 2017 showed, you know, how many people weren't actually putting CBD in their products, you know, poor labeling or some of them were putting, it said just CBD and they had doses of THC that would get you really high. But by now, it's pretty, it's pretty good, pretty reputable companies are, they're pretty spot on with what they're saying. Yeah. You know, I kind of want to transition here because a lot of our generation now is starting to get interested in becoming providers and licensed providers for cannabis, right? I, you know, the functional medicine doctor that I've worked with over the past year is doing the same. I know there's a process behind it. Can you kind of explain what the process was that you took to become a licensed provider? Yeah. So in the state of Arizona, PAs were left off the bill so I can't technically recommend cannabis. So I've kind of built it up where doctors write for it, recommend it and then the patients find me to coach on it. And so basically every state has its regulations based off of what you need to be competent in. And a few, the company that I recommend, I get no money from this is medical marijuana 4011. It's a, when you have the textbook on my desk, it's a extremely good course, like specifically for medical professionals, it's a thick textbook with online modules. And it meets certain states as criteria, right, that you have to do so many hours of studying or whatever. And that's basically it, right? It's almost like it's a box. So if you're an X waiver, you can just simply do the course for, what is it, 10 hours or five hours, whatever it is. But that's it, you know, and then kind of just really, but you got to think people that are finding this field really are interested in, so they're going to self educate you on top of the minimum requirements. And so I'm just trying to make sure that there's a lot of good information out there. Gotcha. And you, you have your own course. So speak on that. Yeah. Yeah. It doesn't certify anybody. It's just kind of during COVID, I was bored. And so I wrote my, I wrote my book and my wife is like, Oh, your board, why don't you make a course? And I was like, that's actually a really good idea. So I made the course one for, one for the like more lay people and one for more medical professionals, just to try and help people kind of make sure that they're getting, you know, even today, you still go on some of the websites of the CBD companies, some of the stuff they're saying. Like, you can't say it's going to cure your cancer, you can't say it's going to cure this, right? Like you're, they're just saying bad stuff, so I'm trying to make sure patients and other medical professionals get legitimate information. All my stuff is, I mean, you read my book, I have all the, the book notes for all the PubMed articles that I used for it. So yeah, my course is kind of just a combination of the book and I fill in some more gaps. Awesome. Well, I signed up for the course, can't wait to start that and your book is phenomenal. So providers out there, even patients, it's not a long read, right? I mean, it was engaging. I learned a lot from it. And if you guys are liking this podcast episode so far, it's definitely a book to have, so you don't have to keep rewinding this episode, you'll have it at your fingertips. So Charlie, future, future of cannabis, where is it heading? What are you excited about? Yeah. Great, great question. I, I foresee, so I'll break it down to two things. I foresee CBD becoming like the craft beer market. I think a lot of coalesceation of big companies are going to come in and kind of, you're going to have regional companies, you know, people maybe like my product are going to the Southwest, not much people in Maine or whatever like it. Cannabis is going to become, it's going to become legal. I mean, if you look at the popular pain, it shifted even more and more in favor of it. I think the federal government is trying to figure out how they're going to regulate it and tax the crap out of it, which is fine. At least people are getting legitimate products. And so I think the next five to 10 years are going to be super exciting and even, you know, we need, you know, this is coming from someone who believes in it, we need more research. We need more, you know, double blind placebo studied research in order to really validate what I'm seeing every day. And when I'm sure some of you guys seen some of your patients, but, you know, I always get pinned to the wall by other providers like, well, where's the data? I'm like, I don't have the data, right? It's still considered a leaps, you know, C1. So, but like you guys said, you know, we took an ult, you know, harm. And if it's a very, you know, there are some potential side effects. So this, but if it's on a relatively harmless plant, you know, right, like there is for alcohol, right? I mean, we've got control studies on alcohol, yeah, so. And is it, is it true? There's been zero deaths from marijuana, like solely from the plant itself, not in like, you know, driving a music bat. Yeah. So, you 100%, so there are no CB receptors on the brainstem, right? They control your respiratory drive. So there's, there's no reason, and when people, mostly the people who overdose rapids, right, they usually are aspirating or they just stop breathing. And so with cannabis, there's no receptor, you know, you have to smoke. I think I'm going to get the number wrong. It's like 40,000 joints and like 10,000, you basically passed out before you did it, right? And it just be some type of, yeah. So there's no deaths, but like, you know, I tell it, like we've, I want to hammer home, I don't want people to think, oh, there's a provider giving, cannabis is good for everybody. It needs to be the right dose for the right patient, for the right ailment, right? It needs to be done in a controlled manner as much as you can. Just don't go smoking weed until you get high. I think there's no ramifications, right? There are potential side effects of these medications, you know, of this plant. Awesome. Well, Charlie, I know people are going to want to learn more. Yeah. Where do they find you? What's your website? Yeah. So my company restorativecbd.com, you can purchase CBD products. I have some of my podcasts up there too. My podcast is medically assisted CBD. And then I have my cannabis coaching companies restorative cannabis coaching.com. Pretty similarly linked to each other. But yeah, you know, more than happy to help people out. If other medical providers, I get a lot of phone calls from doctors such as yourself. Like, hey, where do I start or what do I do or, you know, what it is? And always down to help, you know, other professionals make sure that this industry is getting a good, getting a good name and people are actually respecting it. Awesome. Well, Charlie, I want to thank you for your time for coming out and educating us. I think that this has been a highly informative conversation. And probably opens up a lot more questions for the inquisitive mind at least. And I think that's what any good scientific discussion is supposed to do. Right. I don't think that will convince anybody. And I don't, again, you know, I don't think that's the intention here. I think we want to inform people and then they make decisions on themselves. Also, there's nothing on here as medical advice. So just just remember that this is all for educational purposes only. But before we let you go, man, we do want to ask you this important question because that is kind of the mission of our our show here is how do we, how do we add the health back to healthcare? Go. God. How much time you got? And so you guys act, you guys obviously had my my mentor and you know, my good friend, Dr. Patel and here who has a very who has molded kind of my approach to medicine and how to get help in the back and health care man, it's, it's simple, right? If you follow Dr. Mark Hyman, food is medicine and movement is so important and putting this phone down and get talking to one another and having dinner with your family. I mean, I think they just came out with an article about having dinner with your family producers, right? So many benefits and it's not, we don't need gigantic hero medicine, right? We don't need to just put statins and steps and stents in everybody. If we actually talk to patients about, hey, why don't we move a little bit? What, you know, why do Italians eat, want, drink wine and eat a lot of pasta and pizza but they live healthier, longer lives, right? Look at the quality of their food, they walk more places, right? I'm talking, you know, old school, you know, in the hills and stuff. But we don't need, we don't need cons, it's not, it is a complex issue but start with simple issues, right? Low-hanging fruit, exercise more, sleep better, eat better food, you know, easier, easier to set than done, I guess. Simple, simple but not easy, yeah, I agree. Right. Right. Well, I love it. Thanks, Harley. Thanks for your time. Thank you. Yeah, thanks for having me, guys. Alright, thanks for tuning in to another episode of Medicine Redefined and this time with our guy, Charlie Pyramourini, expert in all things cannabis. What an awesome conversation for me. I mean, I thought I knew a lot about cannabis already but Charlie just took it to another level and I just came 10 times smarter understanding THC or CBD and it's effects and essentially the mechanism of action and I hope you guys all took away something as well. This is a very important conversation that we need to start having. I know a lot of us are probably already starting to talk about CBD and THC and it can be scary to bring up to our parents or to our kids or to our friends and, you know, a lot of us are afraid to be judged especially as it's starting to become legalized but it's still a schedule one. But hopefully this episode kind of clarified a lot of the things you were thinking about and I think the most important thing we can all do right now is to share this episode. Share it with your family, share it with your friends, share it to whoever you are having those conversations about cannabis with. Because we need to start understanding that CBD and THC and all these molecules might actually be helping us more so than the opioids that we are prescribing at a horrific rate. So go ahead, share this episode and let's provide education to everyone. Now before we end, here's a quick reminder, if you want to boost efficiency across your practice and make staff scheduling easier, try the deputy app. You can try this more technology for free by going to Drpodcastnetwork.com or slash deputy. That's Drpodcastnetwork.com or slash deputy. Disclaimer, everything in this podcast is for educational purposes only it does not constitute the practice of medicine and we are not providing medical advice. No physician, patient relationship is formed and anything discussed in this podcast does not represent the views of our employers. We recommend that you seek the guidance of your personal physician regarding any specific health related issues. And again, thanks for joining in, if there's one thing we can ask you to do please hit that subscribe button. If you are listening on Apple Podcast and the top right hand corner, you will see a plus sign. If you're on Spotify, I think it's pretty evident. But again, we are not only limited to those two platforms, you can hear medicine redefine across all different platforms. Until next time.