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E140 - Raw Cannabis and Mitochondria Health Part 1

This episode of Reefer Medness - The Podcast features a discussion with a team of experts from BioSource Botanicals, including a pharmaceutical microbiologist, a cannabis clinician, and a pre-clinical research chemist. Kirk and Trevor discuss the importance of mitochondrial health and how the endocannabinoid system plays a crucial role in maintaining it. The experts explain the benefits of using whole raw plant extracts, including the “ensemble effect” where different compounds work synergistically, and how this can be more effective than isolated cannabinoids. Kirk brings a My Cannabis Story from local budtenders and how they provide guidance to customers seeking cannabis-based wellness products.

Episode Transcript

Trevor: Kirk, We're back.

Kirk: Hey, Trevor. How's it going?

Trevor: Good. You organized a little different. A little more voices, a little more video chat coming up today. In fact, you have organized a two parter. Tell us a little bit about what's going on this time around.

Kirk: Yeah, we're going back in time a little bit here, and people on our social media will see that we gave a little bit of a hint that this episode was going to be a group discussion with a team of experts from BioSource Botanicals.

Trevor: And how many people are we going to be talking all at once  Kirk? Yeah.

Kirk: How many people? Well, we had we had a zoom. We had a Brady Bunch Zoom call. We talked to we talked to Daniel Gana is a pharmaceutical microbiologist. We had same time Doctor Abe. And he is a cannabis clinician. So he is a practitioner prescriber of cannabis, an M.D., a doctor. And we also talked to Brent Ristow, and he is a pre-clinical research director for the BioSource Botanical Group, but he is a chemist lawyer. So this is the team working with BioSource  Botanicals. And Trevor, we're starting something brand spanking new. On our web, on our YouTube page, and also on our web page. We have the entire hour long interview on our YouTube channel. So this is the very first time that we've actually posted an entire interview. Now, the audio podcast that you're listening to right now is taking that that discussion into two parts because I think I think as listeners, there's some science we might want to explain.

Trevor: Yes. And but before we do that, just, you know, if you know who is your favorite guest, it's like picking your favorite child. I liked all of them. I really did. You know, like we said, Brent Ristow, a lawyer, Ph.D., biochemist. Yeah. Don't run into those every day. Daniel Gana was nice enough to jump on a call with us from Nigeria. We didn't even check, but it was evening there, so thank you for staying up late, Daniel. And aside from being a microbiologist, he's now a full fledged cannabis researcher and educator. And then I'm not picking favorites here, but I've got to say, Dr. Abe Benavidez, the M.D.. Wow, what a story. And he'll go into it from, you know, his grandmother being a herbalist and a healer in Costa Rica to, you know, him getting involved in sort of a student group promoting cannabis or at least looking into cannabis as a medical student. To him being denied a residency for some,  we'll let him tell you why. But then got into a better one. And then he's got Covid. He got Covid from a patient in the ICU. So he's now a Long Covid guy, you know, so he can't do what he was going to do because, you know, even talking.

Kirk: I think you're giving away his story here Trevor.

Trevor: No, no, there is lots more. But there is. You don't want to pick a favorite guest. They're all fascinating. But there's a doctor Abe, just, just listened to to him and yeah, that this was.

Kirk: He's in Costa Rica and he's in.

Trevor: And he's in Costa Rica but sort of kind of practicing the US and his medical. There's so much, so much there's so much to all their stories. But you know, because we have three guests now, listen carefully for all of their backgrounds because they're all really interesting.

Kirk: Yeah. And we're getting into a pretty heady subject here. We're getting back into mitochondrial health again. And basically how the endocannabinoid system is a huge part of keeping your mitochondria healthy. So we're getting back into the deep science.

Trevor: Yeah. So how about we'll start trying to introduce people for them and let them introduce them for them and then we'll come out and we'll talk a little bit about the science for Part one. But don't forget everybody, two parter, this one and then another one down the road. But for the moment, we listen to our guests from BioSource Botanical.

Brent Ristow: Yeah. My name's Brent Ristow. I'm a lawyer with a PhD in organic chemistry. I have for many years in education, found myself in the pharmaceutical industry, testing, developing, validating, and testing for release, pharmaceuticals and testing medical devices Class one, two, three, four.  Potential extractable that might be present. And in that process, you see a lot of, how the pharmaceutical industry generally works. It's not that there are no impurities in these products. It's not that there are no compounds that will leach out of the device into your system. It's just that there are acceptable levels of impurities within these compounds that are then distributed throughout the pharmaceutical industry. And that level was determined by, you know, a very complex mathematical formula and some scientific standards after leaving that wanting to take away from that type of environment in industry. I ended up running into Bob. Bob reached out to me on LinkedIn and we had a number of conversations about the type of work that it was doing, how he got into it, what his philosophy was in the space and his experiences in the hemp space. And it was really just kind of an inflection point for me on my perception of overall health. And I've been working with Bob very closely since to try to help develop the robust science around these types of products and the space within the market.

Kirk: And where are you today, Brent?

Brent Ristow: I'm currently in West Saint Paul, Minnesota.

Kirk: Right on. And Daniel.

Daniel Gana Yeah, I did. My name is Daniel Gana. Now I am a pharmaceutical microbiologist. I do most of my research on plant medicine, trying to test out antimicrobial activities against several diseases such as tubercularly, I happen to come across the BioSource Botanicals and Bob  in 2020 when he was talking about the benefits of CBD. And at that particular time the industry was quite new to CBG. We had a lot of people talking about CBD, talking about THC. Then I met this wonderful person who was trying to talk about CBG, and it was a coincidence because I was trying to educate people about the benefits of all the cannabinoids, which was called nano-cannabinoids at that time. I discovered the industry was turning into something that was CBD and THC centric where you have people slapping a lot of numbers depending on trying to  describes the THC percentage. While we have other cannabinoids like CBG, CBGA, THCV, THCA and others relegated to the background. So I met Bob on LinkedIn and then we got talking and then I told him about my work and he keeps impressing me and since then we've been together all this very long time. I work mostly as a cannabis researcher now. I tend to do more of education content.  I teach people about the hemp plant, its benefits on how best to activate our cells with the endocannabinoid system. Thank you.

Kirk: Fantastic. And Daniel, where are you this afternoon?

Daniel Gana Well, I'm in Nigeria.

Kirk: Okay. Good. Good evening. And Dr. Abe, you are where and how do you fit into this team?

Dr. Abe Benavides: Yeah, I'm great. I have a very long story, but I'll keep it very brief. So my story actually starts here long ago in this sleepy, dusty town called Hart, I've been rural Guanacaste, Costa Rica. So my great grandmother was actually a tropical remedy healer in this town and one of the original dozen settlers. She her memory is what inspired me to start studying medical cannabis in the first place. When I got to medical school, so I actually was born and raised in the States. GW made me an offer I couldn't refuse, so I went to medical school there in DC. When I was there, I realized we weren't learning anything about medical cannabis in medical school. All I was hearing were negative things and nothing positive, so I figured we weren't learning the whole story. I figured we weren't getting a full picture. So that's when I in 2016, I became the first medical student at a medical school to stand up and say, Wait a minute, there's something to this cannabis plant. Our patients are using it. There's a lot of research coming out on it. And I don't think it's all just bad things and we should be learning about it. And so I banded together with other medical students. I led the charge on the cannabis as a medicine interest group, the first of its kind in the United States. And then with them, I also did some research that also a survey study that showed that most medical students are encountering patients who have questions about medical cannabis, but the same proportion are equally feel totally unprepared to counsel patients about medical cannabis. So that showed a big problem. And then so that study has been cited at least 20 something plus times since then, since I was one of the first ones that got into this in medical school. So then since then, I got into the industry in terms of like medical writing, editing and doing literature review. And so when I first got, I actually went to residency, my first residency program, I became a disproportionate racial victim of the war on drugs. I was not allowed to start my program over an initial positive UTSA pre-employment, even though they I went and got another retest that was negative. They refused me to start working there, even though other residents told me that other residents test positive for this stuff all the time. And it's no problem because it was in Colorado. And so the Colorado board thought that this was clearly racism. They saw my attorney, but I had to choose whether I had to pursue justice, which I couldn't afford or move on with my life. So I eventually moved on to a different a better residency program in Seattle, Washington. So we did family medicine. And then so but unfortunately, this was at the start of the pandemic. So I moved into Seattle in mid 2020, and then six months later in December, I caught a severe Covid from an ICU patient that I was caring for. And so you see me a little bit short of breath today is because I am actually still recovering. It's been about four years now or three and a half years of Long Covid, Sorry, it was 2020. So yeah, over four years with long Covid and I was still having some vocal cord dysfunction. But as long as I'm seated, I'm fine, no problem. But this did forced me out of my residency program, which was very unfortunate because it's everything I've fought for my entire life. But since then, I continued my work in the medical cannabis industry with my disability. It enabled me to find work that is meaningful to me and also something that was already in my repertoire. And, you know, since then, since I moved on from residency, I went on to educate millions of people around the world. I have over one and half million reads on Veriheal alone, where I had our medical review and our medical education based like everything on our blog. I've written e-books for them, courses for them that train the Veriheal doctors, too. And I'm also CannaKeys, number one, physician focus cannabis decision making tool in the world. I am the medical editor there. I help update and review Uwe Blesching work. I'm also at CBD Oracle and about a dozen other websites. So I've been reading cannabis literature for eight years, reviewing it for the last five years and writing, educating millions of people. And then I joined LinkedIn about a year ago at the request of a client, and then that's where Bob found me. And he reached out and he liked the work I was doing because he noticed that I was working with whole plant extracts in my clinical practice. So I did actually join the GW Center for Integrative Medicine, where I'm still doing cannabis health coaching remotely. Been there almost three years now. I work with medical director who's also my friend and colleague, Dr. Michael Kogan. He is the author of that book you see sitting on the shelf right there. And so he, you know, he inspired me to start was sorry. He gave me the materials to start learning about cannabis in medical school. And now it's great to be his right hand cannabis guy. So I do split my time between research, writing, and clinical work. I do. I see patients at the Center for Integrative medicine on Tuesdays and Thursdays, and then I do medical writing and research the other three days of the week. It's really good because I find that in cannabis, not everything is well written down. There are certain practical things that people need to learn and need someone to help guide them with. And so I'd say about, you know, I have like hour long consults. It can be a short half hour, but really, like at least half of it is just solid patient education, getting them up to speed on what hemp and cannabis are, what are each of the components that we're trying to use. And then I'll come up with a plan for them. And so I only take on our most severe or complex cases. So I've helped patients with everything from Alzheimer's to advanced metastatic cancer to chronic intractable pain. I helped heal someone's 40 years of insomnia using medical cannabis when nothing else had worked. So I know this is something that, you know, the medical industry is behind on. But I have been on the vanguard of this, you know, pioneering this since medical school. And it's something I've always been asked about. And I'm excited to be part of BioSource Botanicals.

Kirk: Fantastic. I just want to explore a couple of things with you, Dr. Abe. You were on the Vanguard as a medical student, so without giving your age away, when was that? When were you in medical school?

Dr. Abe Benavides: When I was in 2016, when I started the club. I started medical school 2015, so it was my first year of medical school that I started sticking my neck out for patients.

Kirk: Well, I see you're in pretty much a brand new M.D., I guess. And are you are you practicing down south now? Is that your practice in Costa Rica?

Dr. Abe Benavides: No, I do not. And I don't have patients here. All my client consults are through the GW Center for Integrative Medicine. So that's at the George Washington University in Washington, DC. So we a small clinic and I also do cannabis coaching at Veriheal, which is the largest prescriber of medical cannabis cards in the US. And I head up their medical review. So I do both things there.

Kirk: Okay. Thank you. That's wonderful. That gives us the background that we obviously have had group of experts and such a wide variety of knowledge. We can dig really deep. The focus of this episode was going to be mitochondrial health. Before we get into the mitochondrial health, Is there is there anything else you want to add to that comment? Because the understanding was we're going to take Bob's episode and stretch it and get down to the science of it. Is that sort of where you guys are at, too? We're going to go into mitochondrial health. Got consensus. Okay. So who would like to start about the mitochondria? I've done a lot of reading and I got to compliment Bob. And we also had another episode from Hunter Lamb in Episode 128. He also got into mitochondria. So all three of these episodes are going to blend together. So who wants to talk about the mitochondria and tell us how cannabis is related to that?

Daniel Gana I think I'll go first. Okay. Questions. So from basic knowledge of biology to understand the mitochondria is the powerhouse of cell. It goes with a lot of activities such as providing energy to the cell and then making sure to cell up to par with these activities. Now, we recently discovered from our research that this mitochondria has its own membrane, which houses a CB1 receptor. And this CB1 receptor is responsible for, as we all know, modulating a lot of activities and then sending signals and other activities, one of which is talking about the vacuum of free radicals and then also talking about oxidation, trying to keep the cells free from oxidation and helping them metabolize and then produce the energy needed by the step. Now, we discovered that if we can have products that can target this CB1 receptor or target this unique endocannabinoid system, and the softest of the mitochondria cell. We can get the cells to do what we want them to do. It's more or less like introducing the program into the cell and then instructing it on just what we want. This is what you are meant to do and we want you to do that. So we discovered that the best way to do this is to actually have our own plant compounds. When we talk about plant compounds, we're not talking about just a product with a few cannabinoids, maybe like CBD, THC, and then if you are talking about preserving the plants in its entirety. That's what BioSource is all about. We're talking about the active spectrum extract. Where we try to preserve the plants in its entirety. Why you need to know about this and why its activates the mitochondria. It's because we discovered that having the plant in its entirety, having them their unique and natural ratio. The way nature intended them to be, we can have them delivered to them. The endocannabinoid system at the mitochondrial level. Now by having the cannabinoids, terpenes, and then the flavonoids forming a symphony coming together to form a synergy, we can guide the right substances to go to the mitochondria and then activating it. And by activating it, instructing it to carry out its design. By so doing, we tend to have cells, yes, we would tend to have cells that are free from free radicals and then cells that are open green and then making sure that we are doing what they ought to do. So that's basically a summary of the work on mitochondria. But I'm sure Brent has a unique story about the mitochondria. So we would like to hear this.

Trevor: We've heard a lot about the Entourage effect. Different cannabinoids and terpenoids working together. But, you know, since we're talking about a whole plant extract, you also talk about an Ensemble Effect, about things happening in the right order and how that's important in a whole plant. Extract Do you want to touch on what the Ensemble Effect is a little bit before we go to Brent and more about mitochondrial stuff?

Daniel Gana Okay. Thank you very much for that question. And just as I said, I'm about to Entourage effect into some work that somebody is bringing together the different activities of these compounds and coming together to form a whole and then giving us definitely activity. So that's what most people are very familiar with, the Entourage effect and the attempt to limit it to just CBD acting on THC, to reduce these psycho-activities. So they are some who most times is confused with the Entourage effect, but in most cases they do tend to work hand-in-hand because you find those two things coming and modulating the cannabinoids and the more the mixing, the flavonoids and all the more they tend to find a meeting place like a meeting point. When you go to our website, we have this unique triangle we created that stand for the Entourage effect and ensemble effect where you have the cannabinoids having the meeting points with them with the flavonoids, and then they come together and become what we call the therapeutic potential of the cannabis plant. So as somebody describes the combined effect of this plant, when the compounds when the raw and the same plants, I think that's what you asked me about.

Trevor: Yes. Thank you, Daniel. Sorry, Brent. I'll. I'll stop jumping in. Brent, please keep, continue about mitochondria.

Brent Ristow: Yeah, no worries. Please feel free to interrupt at any time. Great questions. So just kind of the paradigm shifts that occurred when I started working with Bio Source was the oxidative stress theory of aging. And it really kind of struck me. And when you talked about the mitochondria and mitochondria health, you really have to just first establish two kind, of and why the work at BioSource Botanicals is important. Not only, as Daniel said, are we working to maintain the entire chemical profile of the hemp plant so you get those native cannabinoids, flavonoids, Terpenes from the native plant itself. Unlike what's happening in the marketplace now, where isolates are being added together in some Frankenstein concoction. You get the native profile of the plant. So just establishing two facts. Fact one would be that, you know, you ingest the CBD, the CBG, it becomes ubiquitous in the system, right? It permeates the system. It's lipid soluble. You look at flavonoids, flavonoids are less so they are like, I calculated when they enter the pass the liver into the system. But terpenes are ubiquitous in the system as well. They're lipid soluble. So you ingest this stuff over regular periods of time. You eventually get permeation through the system. Flavonoids get broad exposure in the formulation. But again, they're not as ubiquitous in the system because they're not as easily soluble. So that's fact one. Second fact that the current research is everywhere. It's out there that these cannabidiols have very strong antioxidant characteristics on par and exceeding vitamin E in some studies. So we know that they are ubiquitous in the system. They permeate the system broadly and they have strong antioxidant properties. So why is that important when you're talking about mitochondrial health, as was mentioned in Daniel, the mitochondria, the theory Endocytosis, where our cells see this bacterium out there and it absorbs it because that bacterium is really good at producing energy and that is now our what we refer to as our mitochondria. You have to take the perspective that we're still in the process of evolving. We're not fully evolved. Humans a million years ago look different than we look today, and humans a million years from now will look different than we look today as well. So these processes, once our cells absorb the by the bacterium that becomes mitochondria. Over the millennium, our cells have adapted processes to maintain the balance of the chemical reactions taking place inside the mitochondria. And because we are still evolving, those chemical reactions are complex. They are not 100% perfectly efficient. The mitochondria itself, as it is the powerhouse of the solid, generates a lot of ATP. That's where all of your energy comes from. If you think about metabolism, in my mind at least, that is your metabolism, that efficiency at generating that ATP. A consequence of that ATP generation is the electron transport chain in the mitochondria. And again, these chemical reactions can get out of balance when you're under stress and these chemical reactions generate things called reactive oxygen species, primarily superoxide. And when these chemical reactions get out of balance and the mechanisms that are inherent in the cell are unable to maintain their balance, you get excess of superoxide present in the cell. What happens at that point? You get signaling proteins get damaged. Cellular DNA, RNA damage. Hopefully eventually it leads to cell death. But you know, nothing is 100% efficient in any system like this. So you will get damage. And that is the oxidative stress theory of aging, that that damage happens incrementally over time. Like a good analogy is here in Minnesota, you get into a car accident, you notice. It immediately. But your car rusts gradually over time. You don't see it in an instant. So that's an apt analogy for people that live in areas where cars rust. That oxidative damage can build up when there is excess superoxide in the cellular system causing that damage, causing arthritis, causing heart disease, causing a lot of cognitive decline. So imagine if you were able to introduce broadly into the system compounds that had that had demonstrated high antioxidant effectiveness in the presence of that superoxide. Our working theory is that the ubiquitousness of the compounds, their antioxidant nature and the effects on superoxide and oxidative stress will help the cells maintain the balance of those reactive oxygen species, reducing cellular stress and damage. And in the long term, you know, helping prevent a lot of these cognitive declines, these oxidative stress related aging issues that people are experiencing. In the short term, that the evidence is very broad for its analgesic effects, etc., but that that is the working idea around maintaining mitochondrial health is helping the mitochondria when it comes out of balance, providing it a system where it can help maintain that superoxide concentration within the cell and maintain a healthy homeostasis.

Kirk: Am I correct? Am I correct in saying that the mitochondria is unique in the human body, in that it is from the mother's DNA. And not the father's DNA. Is that a correct statement? So mitochondrial health is based on the mother's DNA.

Brent Ristow: Yeah. If you're doing genetic. Yeah. The mitochondria contains a full set of the mother's DNA.

Kirk: Okay. Yeah, that's. That's. So now what We also learned from Hunter Land and Bob is that it has something to do with the calcium channels. Correct. And in the mitochondria and how the endocannabinoid system works with that. Can you explain a little bit about how the endocannabinoid system cannabinoids and the and the calcium channels all work within the mitochondria?

Daniel Gana Well, I think by calcium channels, he was referring to TRP channels, which is the movement of compounds in a lot of cells. So I think Bob was trying to talk about how this endocannabinoids or cannabinoids or endocannabinoid system tends to form gated ions where it allows the passage of selective compounds by way the passengers certain compounds into the mitochondria and in order to stop them from passing into that. So I think we're talking TRP channel. Dr. Abe go on now.

Dr. Abe Benavides: Yeah, I think Daniel was really great at explaining it and Brent too by explaining like the micro level of detail. I think my expertise is more on like the macro level and what this means for practicality for a patient. So the evidence for this stuff is still in preclinical stages, of course, but I would expect that these kinds of things would mean I mean, we're already showing hope our extracts are better for things like pain relief, controlling seizures, neurogenic symptoms. And so I just think that by introducing the flavonoids, which we're doing is basically introducing a whole new therapeutic class or substance to the oil that we will get. I would expect that we'd probably see things like lower dosing being needed. This means less oil in a vehicle by the mouth. Less bitter taste would probably also mean better control of the symptoms. Better cost effectiveness. Better shelf life. I see a lot of patients have increased energy and mobility, better sleep, less inflammation and pain. So these are the things that I would expect to see being improved by it. And as soon as they're out, I'm excited to switch my patients to them.

Brent Ristow: Just a comment about the calcium channels. There is evidence that suggests that the TRPV1 channel is activated or interacts with components of cannabis. That's a lot like my understanding of it is it's a lot like how capsaicin interacts with the same channel. It essentially opens the channel, creates an imbalance and then prevents the firing of the nerve. And that is really the result of the analgesic. That's what results in the analgesic effect of the CBD. So it opens ion channels and allows an imbalance there for them not to fire.  The work that we're currently doing in studies Kirk and Trevor, we have chemical studies currently taking place that are looking at the free radical scavenging capabilities of BioSource Botanicals Extracts. They are raw extracts in their finished products. We also have some cellular studies that are progressing. They're a little bit more complicated because we are taking kind of a new approach to how we're examining and testing these types of cells. So that is ongoing. But that is that work is progressing. One of the things that Trevor, you asked Daniel about this and I'm just kind of elaborate on it a little bit, is that the entourage effect is typically referred to as a CBD, THC, where they can in fact affect the experience of the THC experience. So there's no THC in any of the products at BioSource Botanicals. So we're trying to move away from that kind of vernacular and we're trying to make sure that we're treating the industry with the respect that the medicine that it provides really deserves. So with the components, what you see typically in the industry are people formulating compounds out of isolates, and you can get massive doses, you can get some toxicity. There's absolutely no real regulation in the industry when you're putting these products on the market in regards to their quality. So you see people trying to do research with a lot of these products and they are so inconsistent that it makes the research a lot more difficult. At BioSource Botanicals I didn't even start the research until we got the CofA on all of the products that we're going to test. And the CofA show just really an incredible composition based up Peter Vermeul's decades in the industry developing these plant varieties, this proprietary extraction process that really allows instead of taking individual isolates, taking them all out of the one plant product and having that kind of holistic medicine present there. So it maintains that chemical profile of the native plant itself, it does provide CBG, CBGA in just really incredible amounts. The CofA are on the website BioSourcebotanicals.com. You can check those out and flavonoids and terpenes all in the same tincture from the same source. So that's kind of when we talk about the entourage effect these chemicals, this plant has been outside since the dawn of time. Way before us and it develops over the millennia these chemical processes to help defend itself and make sure that its processes are stable. They all work synergistically together. It only makes sense if you're being serious about botanicals to try to maintain the chemical profile of the plant itself instead of bastardize it and stripping away and taking out a component. And then you have to go through all the industrial process of that component. That industrial processing is just like what's happening in the pharmaceutical industry. There are residual solvents. There are impurities that will be present. It's moving away from really the maintaining the native health of the plant and allowing those cannabinoids, those terpenes flavonoids to work synergistically together. It's just bastardized and it's creating a worse product than what I believe is BioSource Botanicals.

Kirk: This is a great segway because what I've been wrestling with and I've tried to do the research, I just can't find it to satisfy my brain. But yeah, that's the critical component of, of BioSource Botanical. Is that your products are raw cannabis so heavily CBGA THCA, a CBDA is a so you've got these acid form molecules. Once they enter the body, do they convert within the body into and drop the acid? And like how does a acid form THC molecule lodge into a CB1 receptor? Like that's what I'm really wrestling with. Can you explain the science behind that?

Daniel Gana Yes, I would do that. Well, that's quite an interesting questions. You see most people are confuse when it comes to the acid form of the plants. Because most of them are stable. Talk about like CBDA, which is very unstable, that can easily convert to CBD even at room temperature or just exposing it to air. But that's not the case in biology you'll find out that's in metabolism the potential for a different a completely different result. They don't get converted to, or drop the acid when they're in the body. They actually act like a completely different compound in the body. Now, what we've discovered with CBGA to be precise because it's one of the most researched acid from some of the plants for now. Then the second should be CBGA, followed by THCA which is quite not really used that much. Now what I discovered is that CBGA, once it gets into the body has an advantage over CBG because it carries an extra carboxyl group COOH group, which assists it in interacting differently with receptors. One thing we come to understand is that this acidic form of the compound interact or binds to the receptors differently. And that's they adhere or reach the receptor as a completely different compound. That is why they tend to have different effects entirely. You'll find CBDA having one time, 1000 times more effective, binding to the receptors and then reducing nausea and vomiting compared to CBD. So if they don't really convert to the natural form or drop the acid. For this acid plays a critical role in how they interact with the binding pocket, because at the receptor level we have the binding site and then we have the binding pocket. Now the binding pocket is what the examine the effects that we produce. That's why you have CB1, you have that Delta8 and Delta9. Delta8 and Delta9 binding to CB1 will produce a different difference because they are interacting differently by different pockets. That's why you have CBG and CBD products for different use. So no, they don't combust to the natural form. or drop the acidic form. That acidic group gives them an edge over the neutral counterparts.

Brent Ristow: Yeah, I just wanted to get a parlay of that. I mean, if you look at how the cell itself functions, it might make sense that the acidic version might be more functional within the cell. When you know, you see drugs, think of multidrug resistance. You see drugs enter the body. Enter the cell and they get oxidized. They get oxidized by cellular enzymes to have hydroxyl in carboxyl groups, acid groups on them so they can be more water soluble. That's that is the state that the cell wants these things in because then it is more easily manipulated for the cell. So it's just easier for the cells to deal with. That's what the cell wants to Daniel's point and that's. Thank you for the excellent summary, Daniel.

Trevor: Well, jump in real quick. And because I'm going to have to leave probably before this excellent. Put it on the spot a little bit. How clinically have you noticed differences when you treat patients with what I assume, right now, you have been doing a lot of, you know, using extracts, THC extracts, CBD extracts. Have you noticed any differences between that form and whole plant extracts or extracts with the with the acid form? Like clinically, have you noticed any of that yet or is that still sort of to come?

Dr. Abe Benavides: Yeah, absolutely. And thanks for asking that. So whenever I'm working with a patient, I'm always recommending the acidic versions. I never recommend CBD oil by itself anymore. I always recommend CBDA or at least an equal portion with the CBD if it's possible to find. But I've definitely you know, I have patients. When patients come to me, they generally are grasping at straws. They're very desperate because usually, I mean, people have been to all kinds of specialist pain specialists, neurologists, all kinds of things before they are like, okay, well, maybe I'll try this cannabis thing. And they come to me and sometimes they've been on, you know, 25, 50, 100 milligrams of CBD isolate that somebody else suggested and they had no idea. So they just chose the cheapest product, which is a CBD isolate. And it had maybe had some effect for them but not ideal or maybe it had no effect. And then when I switch them to whole plant extracts, I do always choose try to choose the raw, acidic cannabinoids first and then we they are surprised that I want to start them on. I always use self-titrated approach. Week by week. I have them increase the dose because I want to find the smallest possible dose that's going to help them in the long term without causing side effects. And so they're always surprised that they're like, well, I was on 100mg of CBD isolate, it wasn't doing anything. And then my protocol will bring them through ten, 20, 30, 40mg week by week. And then by week four, we meet up again. And then I have, you know, I see the benefits already within the first month. So I usually follow up with patients one month after because I try to set expectations appropriately where, you know, I tell them that THC is really good at working right away and that's because of the receptors working on CB1 CB2 right away. So people notice that difference. With CBD, it's CBG. You're working on 65 other molecular targets in the background. And these are things like serotonin receptors, dopamine receptors, GR55, TNLalpha, tons of other receptors that I tell them are mostly important for involving mood and pain processing. And those receptors are generally slow to change. And so in the same vein that you would, you know, tell a patient to expect 4 to 6 weeks of trying an antidepressant before they judge whether or not it's working for them, I tell them it's kind of pretty much the same with CBD. You got to give it at least a good trial, at least 4 to 6 weeks. I expect you see some benefit within the first few weeks or the first month and then you will once we find your what I call your therapeutic dose, that's when you'll see maximal benefits 1 to 3 months out. Using that dose. And that's what I see in my job, is to to heal people, make them healthy. It's not to keep them coming back. I have to put myself out of business because I have to teach patients how to drive the cannabis boat for themselves, like how to actually listen to your body, what you want to be dosing when, how much and how often. And then once I see that they're comfortable with this plan, I'll see them, you know, maybe once a month and then depending on if it's a really bad chronic issue, I might see them in three months or six months, but at least see them in a year when it's time for their cannabis card renewal. Or I'll just read in their notes that they're just doing better from their other providers. And, you know, like yesterday I helped somebody get 90, 95% better on their cervical alga, bilateral nerve pain burning down both arms. And it was a combination of CBD, CBV, CBG, and they were already seeing tons of pain specialists out of West Virginia University Medical Center. They tried all kind.  They were at a pain clinic. They had tried everything else before they come to me and this is usually what I see. People are usually pretty desperate and they're pretty surprised that the results that they get. And so, yeah, with, with whole plant products, I see much less need for dosing than with isolates where I would see hundreds of milligrams. I get people down to reasonably, you know, less than 50mg. I'd say people usually do better on less than 50mg twice daily rather. I mean, and then so I just expect that when we introduce a whole new class of therapeutic substances like flavonoids to it, I would only expect that the ethically would improve. And so hopefully we could even get that dosing down. It also means better taste for the patients, better cost effectiveness. These are things that matter to people. Cannabis is expensive and so people want their medicine to go far. So I think with whole like whole plant products, that's going to go farther than you do with the isolates, even though they're kind of cheaper and more available. But it's just going to be better for for their health. And that's in the end, the bottom line, that's what people really want.

Kirk: I was just going to say, Dr. Abe, what is your typical patient? What is the what type of how do you help them to wellness?

Dr. Abe Benavides: Great point. My typical patient is pretty desperate. They are pretty like they have seen other specialists like I mentioned they have tried lots of other medications. My best example is an 80, 82 year old patient with 40 years of insomnia, nothing else had worked for them. They've tried everything under the sun. And when people come to me, oftentimes they're understandably skeptical because they've tried everything. So of course they're probably like, Well, this is probably isn't going to work. And then I educate them on why it's going to work and that I have helped lots of people in their position. And then and then they're surprised when we do. And I really enjoy it. But my approach is generally always to say half my visit is just solid patient education. Most of my patients know absolutely nothing about it. I would also say most of my patients are middle aged or older, and they preferably don't want to get high. Not necessarily for like religious reason or political reason, like some people might think. Really for practical reasons, they want to be present with their family. They want to be able to take care of their dogs or their children or their parents in case of an emergency. They need to work. They need to drive. They need to go grocery shopping. They can't be high all the time. And so what's really good is that with whole plant hemp extracts, you don't have to be, but you can still get the relief that you need to be able to function, clean your house, move across the country, do things that you previously weren't able to do. And I help people do those things. And it's part of the beauty of my work in a way. I really enjoy it. And then it also informed my research writing and my research writing informs my clinical work. So it's a really great blend because when you're in a new field like this and you're on the forefront, you kind of need both to make progress with people and really understand what you're doing and what people actually want and what's important to them.

Kirk: So. So you said you said pain, insomnia. Are there any other types? Is it primarily people with long term pain and insomnia, or do you have people who are nauseated? I mean, we know that cannabis, the Western world, does recognize cannabis for its insomnia, helping with insomnia. It helps people with nausea from cancer treatments. And some clinicians are looking at it to help with pain. So your classic patient is insomnia. Pain.

Dr. Abe Benavides: Insomnia, pain, and metastatic cancer. So the pain can be from several things, I see a lot of metastatic cancer patients or patients with metastatic breast cancer or prostate cancer, lung cancer, things like that. And so they do often need help with their pain, but also their nausea, also their appetite, also their sleep, also their energy levels mood, their anxiety, their depression. And so the patients will ask me if this is going to help with those things as well. And so I reassure them that, yes, and that's because of the, you know, the 65 molecular targets that I've talked about using the other parts of the hemp plant rather than just THC, which activates CB1 and CB2. And they really should probably just be called THC receptors because nothing else was really working well on them. And so and I also do a lot of work with Terpenes as well, so I make sure that they have the right Terpene blend and profile. I go, I explained through what Terpenes are, what each of them are doing and then which ones I think they should be looking for in their products.

Kirk: This is great. This, this just again naturally turns me to My next question is, in our research with cannabinoids and mitochondria, there is some talk about cannabis actually killing cells and shrinking cells and helping people who have cancer. So is that and is that again, to mitochondrial health, is that can you explain that?

Daniel Gana Talking about cannabis and mitochondrial health and stuff, you see the major thing is what message does this particular cannabinoid sending to the CB1 receptor on the surface of the mitochondrial. Now, if this mitochondria is found within the cancer cells, which we've be able to write something about in Bloom magazine, should be coming out soon enough by February we should have that out in print and we can give that a read. We discovered that cancer cells tend to hijack the endocannabinoid system and then they use the CB1 receptor to their advantage in the sense that they use it to grow bigger and then they tend to spread all over the place. Now when we introduce cannabinoids medicine, what it does, is it regulate this activity and then bring it back to normal. Now it recognizes that this CB1 receptor, is sending their own signals to these cells, causing them to grow and then a lot and spread all over the place. And then what it does is it begins to work with ion channels we about in another question and then the ion channels begins to shrink down these cells. Now when it finds the mitochondria not working or that is working outside the normalcy of what is supposed to do. It begins to shrink down the cells. But when he find the mitochondria are not working the way you ought to do, it's best to give it a particular boost. So I usually describe this as a endocannabinoid attack. Think of an agent comes to crime scene and then is strictly able to identify the criminals and then lock them up and then to find the good guys. So that's basically what happened. So, yes, when it shrinks the cancer cells it is part of mitochondria activation. And when test these mitochondria to reduce the production of these cells making the cells free from free agents is part of mitochondria. So it depends on what the cell bring before the cannabinoids introduced. So I hope I answer your question.

Trevor: So of course I loved that one. We talked. We talked the science. I'm you know, I'm always into the science. I want to talk about you. Just it might pass people by, but we talked about capsaicin. Capsaicin is the stuff in, like Zostrix cream. It's the stuff that comes out of ground up hot peppers. And we over the years, we've taken that. We put it in a painkilling cream. And what fascinates me about it and pharmacy school is you rub it on a sore limb and it actually makes it hurt more. When you say, Well, why would I want that? If you rub it on 4 or 5 times a day, the capsaicin actually makes the substance in the capsaicin makes the pain receptors, basically give up. Tires them out, they can no longer send pain signals to your brain. So now it doesn't work. So it sort of over over uses some of the stuff in there like overstimulating the calcium channels. And I really like that Brent was talking about. It's not exactly the same thing, but it's analogous, we think, to maybe how some of the cannabinoids are making the cannabis, the calcium channels work in mitochondria. Kind of. So I like that. So I want to throw that one out.

Kirk: Yeah, it's, it's deep, dark science about the mitochondria. What I, what I find, what I like about the story about the BioSource Botanical fellows is that they're going after the raw plant. And a couple days ago I took a walk around Dauphin and I walk into the Tokyo Smoke shop and and meet up with Allie. And I remember I remember talking to Allie and they were talking about raw milkshakes with using whole flower and raw flowers and making shakes. And I went in and said, you know, you're going to want to listen to this next episode because it's all about raw cannabis. And this is what I find fascinating about this science. And and this isn't the first time we've ran into scientists and practitioners that are looking at the raw plant, the Flavonoids and the Terpenes and the CBD and how it all relates. I mean, I did do a little self promotion. I asked people, you know, go back to Episode 134. We talk about mitochondrial health in there and in Episode 117, Solventless Cannabinoid extraction with Richard, I'm talking about the whole and Brent was discussing it in his conversation about how a lot of the industry right now are using toxic substances to extract the cannabinoids and how that is not good for Wellness medication. We also talked to Akeem Gardner. He was the fella that with the basketball star, nephew or son?

Trevor: Nephew , he just hopes. But but he but Akeem does have a whole company Canurta that is one of their main focus is is canaflavins and how they can do stuff like treat ALS. And when we and when we're talking about mitochondrial health previously sorry I don't know if anyone else noticed. When we talked about Hunter Dr. PhD Hunter his last name is Land like as opposed to Sea it sound an awful lot like Lamb, like a small sheep. But anyway, Dr. Hunter Land was talking about mitochondria in previous episodes. This is stuff that we've talked about a lot, but I like the the twist that the BioSource Botanical guys put on it. One of the mitochondria stuff that Brent talked about was oxidation. So we've talked, you know, you've heard we've all heard of antioxidants forever and ever and ever and they're good. But I liked his analogy said So oxidation to aging is like a car crash, you know, boom, it happens all at once. Oxidation is more like a car rusting over time, which in my mind was really cool because rusting literally is an oxidative process. So if you can stop that rusting, you can have the car live longer. So yes, it's it stretches the metaphor a little bit. But yeah, if we can slow down the the oxidative stress, we might be able to slow down the aging process. And since the mitochondria are where oxidation happens that we want it to happen in the body and some of the oxidative bad stuff pops out into the cell, it makes sense. I had a sudden revelation that it makes sense why, if we make the mitochondria healthier, it might reduce oxidative stress, reduce aging. You know, it's all just ideas at this point. But they that that rusting car analogy, I really liked it to sort of make that sound a little better.

Kirk: Yeah. Yeah. That that explains the whole process of reactive oxygen species and, and that was I had to go deep into the books on that one. And basically, yeah, it all made sense to me. And it's, that's what I like about talking to people that are experts that know content so well that they're able to give you analogies that make sense. So yeah, this was an interesting episode and I hope it makes people smile and enjoy and enjoy the science of it, you know, because there's there's good people. Cannabis as a plant, you know, I guess I guess what I'm sort of thinking about is the green culture has been talking about cannabis whole cannabis forever. And it's funny how science is now examining that and again anecdotally we believe these things are true. And we've just spoken to a group of scientists that are actually going to prove that through recognized method of of of research. I guess that's what we're seeing here. Right? And we're talking to them as Reefer Medness. And it's just bringing it's just bringing the knowledge of cannabis to other people. And I hope people see the importance of knowing this and making cannabis more useful in Western medicine. Right? Because this is the only way cannabis is going to be used in Western medicine is when this type of research is done. And I like the fact that BioSource Botanicals are are using their certification of analysis before they do their research. Yeah. That I found good too.

Trevor: And we will definitely hit the more on that in part two. Nice segway. But before we leave this this and and speaking of bringing knowledge to the people, you're going to bring some knowledge to me because I have no idea about anything of this coming up. Kirk, are you going to spring my cannabis story on us? Because I have no pre knowledge of this one at all.

Kirk: You haven't heard this one at all. This is good because we namedrop in you.

Trevor: Oh good.

Kirk: Yeah, we do. Well, we have three cannabis stores in Dauphin, and I just decided one day this week past week to go visit them and take our poster and make sure they have the poster up. Spoke to Allie about the whole raw cannabis stuff that we're now researching at Reefer Medness - The Podcast. I went to Delta9 and gave them the poster. Chatted with those guys. And you remember that Destree my cannabis story a couple episodes ago came from the Delta9 store. This, my cannabis story comes from Payson's Joint, and we did an episode on Payson's Joint a few episodes ago where I talked to the the owner and I walked in to talk to Kimberly, the manager, and Brady. And getting back to that whole concept of people going into the store looking for medicine.

Trevor: Right.

Kirk: And and I asked them, so what happens? What's your strategy? So we get into this conversation. This is a conversation how Bud Tenders direct people, how they direct people to uses as medicine. So I leave it at that and your name gets dropped in it.

Trevor: oh good.

Kirk: So introduce yourselves.

Kimmie: Kimmie and Brady.

Kirk: You're Kimmy and you're Brady.

Brady: I'm Brady.

Kirk: And you guys had questions for me about about people coming in. Can you tell me some stories what type of clients you have to come in here?

Kimmie: Older patients, older people, I should say, that are looking for stuff to help them sleep, to help them relax, maybe even cancer patients looking for some relief. But yeah, that propaganda that they were fed back then and trying to get them over the hump on their knowledge, I guess.

Kirk: But they walk in the door, right? So they've taken, they've taken they've had to get the nerve to walk in the door. So when they walk in the door, walk me through it. Do you see them go ah?

Brady: Not necessarily. No,.

Kirk: No.

Kimmie: No. They walk in and they just look lost. They're so overwhelmed. But yeah, we greet them and nine times out of ten, they're looking for oils, gel caps or edibles.

Brady: They're too scared to try smoking it.

Kimmie: Yeah.

Kirk: But they come in and tell you, what do they tell you? How do they how do they introduce themselves?

Brady: They're usually like, hey, a friend recommended me to come try this out. I've got a lot of pain and I want something to help that. And we're not supposed to give medical advice.

Kirk: not supposed to? You cannot give your cannabis.

Brady: We cannot

Kirk: No, no that's alright

Brady: And and we're like, well, you know, we could try something, but you'd have to talk to your doctor first.

Kirk: Okay. So you recommend him to go to the doctor?

Brady: I do.

Kirk: Okay and that's fair. And I'm not challenging you. I'm just asking because I'm very curious. But you also have products here. Like you have a product called Sleepese, right?

Kimmie: Endonight, I think it's called now.

Kirk: Okay endonight so if someone if an elderly person came in and said they're having difficulty sleeping, you could go and say this product.

Kimmie: And we have like we definitely have. It's just if they have more medical directed questions for sure.

Kirk: Right.

Kimmie: but yeah, like it's just a lot of them just want CBD and just trying to get them to realize that sometimes just CBD isn't going to work and you might need a little bit of THC to help.

Kirk: Right, For the pain.

Kimmie: Yeah.

Kirk: Okay.

Kimmie: And then they're like dead set on the no THC things so.

Kirk: Right they need education. Yeah. And but you're, you're you're employer Payson's Joint to give it a little plug he he has you go through a orientation program right so you guys have information about cannabis. So what what do you feel comfortable sharing?

Brady: I would say if they're looking for sleep, I would say try CBN. It's slightly psychoactive, but not nearly as THC is.

Kirk: Right.

Brady: And it's studies have said that there is drowsy and effects to it.

Kirk: What don't they advertise it right on it by saying, sleep?

Kimmie: Some of them do. Yeah. Yeah.

Brady: Not necessarily all,.

Kirk: But that would make it easier for you, right?

Kimmie: Yeah. And, but a lot of customers don't know what the CBN, CBG CBD, any of those things are, so.

Kirk: But you know that. You can. I can give them that.

Kimmie: We guide them like through what a better product would be for them if they they wanted something like with this because it's it has CBG but just because it had like strawberry in the flavor you know what I mean?

Kirk: Right.

Kimmie: You would explain to them, okay, well, yeah, it's got the name Strawberry, the flavor, but the CBG isn't necessarily going to help pain wise, it get you happy for sure

Kirk: Bubble wrap for your brain.

Kimmie: yeah so it'll it's definitely a good morning daytime keep going thing. But if you're looking for it for bedtime, then.

Kirk: Don't stay away from it. Yeah. So you're able. You're able to give that kind of advice. Yes. You're able to save THC is psychotropic, CBN's are for sleep you can give people that kind of guidance.

Kimmie: Yes.

Brady: Yeah.

Kirk: So. So. So you do you do you do that?

Kimmie: Yes.

Kirk: Okay. I think that's fair. But when does it become prickly? When does it become difficult? Like what would be a typical question that would be difficult.

Kimmie: I have cancer. What do you recommend? We can't do that.

Kirk: So what do you do?

Kimmie: We just go over the options. Like. Like, hey, like sort of like CBD does this CBG does this. THC does this. Are you looking for pills or you're looking for oil or It's looking for smoke? Are you looking for edibles? Like if they're a first time user like dosage, maybe questions, but again, with dosage questions and elderly, I do still recommend them to go to Trevor because I don't know what medications they're taking. I don't know their age nothing.

Kirk: Which is. Which is which is, I think, a practical thing to do. Direct them, give them the insight to what the individual cannabinoids do and they can choose. And then if I guess, if they're on meds, they should talk to Trevor.

Kimmie: They should talk to a doctor or pharmacist before. Like,.

Brady: and a lot of them don't.

Kimmie: No.

Kirk: Right. And but but from an ethical perspective, you're here to sell weed, so you will sell the weed to them with the caveat. Please. If you have an issue.

Kimmie: To please notify. And we do go over them to like, hey, this is if you do feel this and this and this, this is a side effect that you are. You took too much. So to go see medical attention or.

Kirk: Cool. Yeah. Your name was dropped.

Trevor: Well, you know what is it all All publicity is good publicity.

Kirk: Well, let's. Let's just say. Let's just say that you are known to be the cannabis pharmacist in Dauphin.

Trevor: Yeah, that that that part is definitely come up before. So, Kirk, to kind of wrap up part one first one, remind everyone, this is part one of BioSource Botanicals. Come back and listen to part two. We get much more into the actual products that BioSource has, but anything else we need to tell them about part one before we wrap this one up?

Kirk: Well, we could say I'm Kirk Nyquist. I'm the registered nurse

Trevor: Trevor Shewfelt,  I'm the pharmacist.

Kirk: Our Web page is growing. It's growing. It's growing. You will find on the Web page the full the full YouTube video of this conversation without us interrupting. It's the full conversation unedited from the perspective of us adding more to it. You'll also find our CannaBits or a Cannabites page is growing. Trevor and I are learning to use A.I. and trying to ensure that we we can give you guys.

Trevor: make us, make us younger and grow hair.

Kirk: Is that what we're doing? thats what you do?

Trevor: I'm sure that's. I'm sure that's what I ask AI to do for me.

Kirk: I don't need to grow hair anymore. It's already growing in the wrong spots. Anyways, I digress. So, no, our web page is growing and we're trying to provide you as as as it says in the description Cannabites of information. So if you want to go and learn about cannabis as medicine, there's a couple of episodes there, two minute listening, two minute listenings, little hits on cannabis information. You can check that out.

Trevor: Okay, For the last time, this was part one. Don't forget to come back for part two. I'm Trevor Shewfelt and he’s Kirk Nyquist was another good one.