Episode Transcript

Trevor: Kirk. We're back.

Kirk: Hey.

Trevor: We're back with my favorite type of episode with so much science that it whacks the other side of the head and makes you semi-comatose. So now I'll fully admit this is this is a geeky science episode. I love it if you hate the geeky science episodes, try it anyway. But you are, you know, they do, trigger warnings. This is a trigger warning if geeky stuff is not your thing.

Kirk: Yeah. What? We're reaching back to Episode 123, with Bob Hill and the electric High, and we talked about mitochondrial health. This is taking us a little deeper into the the rabbit hole of mitochondria and, we will remind people that mitochondria organelles found inside the cell. Biology 11 for me was the cell life. When I got into nursing school, we learned a little bit more about cells. And back in 40, 45 years ago. Not that I'm giving away anything here. Mitochondria were known as the powerhouse. The furnace they were. It is what fed and kept the cell going. In this episode, we learned a little bit more that mitochondria, mitochondria might be the answer to a lot of things. If we start paying attention to the receptor cells.

Trevor: Receptors on the organelle.

Kirk: Right. Just receptors. Correct. But hey, you know what? I think what the listeners need to understand is that cannabis, you know, might be, or CBD might be the fountain of youth for nematodes.

Trevor: Yep. If so, if you if you want a tiny little worm to live forever, CBD might be the answer. Might be good for us, too. But, you know, definitely for tiny little worms.

Kirk: So. So according to the pre-clinical trials, CBDs might be the answer. So that's tease should we go into that might keep people listening.

Trevor: I think that's a really good, really good intro. Let's, let's get into Hunter Land PhD and mitochondrial, have more stuff that you ever want to know about mitochondria. I love this one.

Hunter Land My name is Hunter Land. My background is, I have a Master's in Nutrition. I also have a PhD in neuro-biochemistry. And I've been, accidentally fell into the cannabinoid space about 13 years ago. So kind of your normal run of the mill scientist. And, was the, first official U.S hire for GW Pharma, although, Ethan Russo was the first consultant. And there's me.  Started my work there. A lot of the work, done there didn't get published, for obvious reasons, and a lot of it did, which resulted in the FDA approval of Epidiolex and, quite a bit of work in Sativex. I later went to Canopy Growth. And now I am, leading the research, Biopharmaceutical Research Company, which is a schedule one, DEA, approved manufacturer and producer of cannabinoids, where we do, research and development. I also act as the chief scientific officer for the NHL alumni.

Trevor: And it's too bad we don't have lots of time because we'd love to talk about the NHL is up here in Canada.

Hunter Land But it may be related. You know, as we dive in, there's some interesting stuff around concussion and traumatic brain injury in the space as well. So lots to discuss.

Trevor: Lots to discuss. So let's start with mitochondria. So way back when I took microbiology. So mitochondria were these tiny little things that we thought a billion and a half years ago, one small micro cell animal swallowed another one that the little one mitochondria, why it was special is it could it could use oxygen to change things like sugars and fats into energy. And for reasons we don't know, that little thing ended up staying inside the bigger thing. Those turned into eukaryotic cells, turned into animals. And the last thing I remember, the last two things I remember from microbiology was the, you know, these were the powerhouses of the cell. And then from CSI, I learned that, though they're only passed, they've got their own DNA, and they're only passed down from mothers. So, you know, you can track who someone's mother is through the mitochondria, and that's about all I know about mitochondria. And then a few months ago, we were hearing about mitochondria having cannabinoid receptors, which kind of blew my mind about why they were there and what they were doing. And that's when we called you. So tell us a little bit more about mitochondria and cannabinoid receptors, starting with wherever kind of makes sense.

Hunter Land Sure. Well I think your general overviews is fairly accurate, right? It depends on how you dive, how much you dive into the nuance. But generally speaking, known to be the powerhouse of the cell. And we talk about this as and converting, things like glucose into energy or ATP, which is the, the well known energy molecule. The other thing that I don't think is discussed as much is they don't only convert to ATP, they also, play a pivotal role in producing things like neurotransmitters such as serotonin. They're also involved in genetic regulation, and produce production of hormones. So there's a lot of different things that they do outside of that space. And the importance of mitochondrial health has been broadly implicated. So, there are things like the brain energy theory where it's connected to mental health disorders, and larger health concerns, in the community currently. And that's all under investigation. Now, your point about, the cannabinoid one receptor being, expressed on mitochondria is relatively new and not well known, but certainly interesting. I do have to ask, how did you come about receiving this information? I'm just curious. Did you did you dive into some sort of publication or.

Trevor: No, it was. Well, yes and no. We were we were interviewing a lawyer because, you know, that comes up with lawyers. But, he has a company that, does a lot of work with, acidic cannabinoids. And they put out a paper where they were talking about, you know, all the things that acidic cannabinoids did. And one of the parts of the paper was, what does this on the mitochondria. And I said, does what on the what it does. Do mitochondria have receptors? Why do they have receptors? You know, how does something from the outside of that cell get all the way into an organelle inside the cell? And that was sort of the beginning of where that happened.

Hunter Land Yeah, well, I think that's a good place to start. Interestingly enough, if you go back to 1970, around 1970, they did know that cannabinoids, THC and endocannabinoids played some role with mitochondria. They didn't actually know that there was a receptor. Obviously, Allen (Huillet) that was the first to find the binding site of the brain and wasn't looking for it on mitochondria. And that was, what, 1990, 1988, I think so long before that they thought that disruption, so they saw negative impacts on mitochondria at that time. And they thought it was because the lipophilic nature was that was disrupting the membrane. It was until much later we found that there was the CB1 receptor, that can be on mitochondria. Now, I think it's very important for the listeners to understand that what happens in a dish. So in invitro studies, it's very, very different than what happens in humans. So oftentimes when you see negative data, what they've done is they've they basically left mitochondria cells and looked at mitochondria from being essentially soaked in very, very high levels of cannabinoids, whether those are synthetic that we use in modeling, endocannabinoids, which has been done very little because they're not particularly stable, or phytocannabinoids like THC. So, for example, a lot of the studies that show some negative impacts are 5 to 10 micromolar of THC. And that's a exceedingly high level that you'll probably never get to, in the brain. And then secondly, that's not something they don't just sit like, if you were to use cannabis, you don't just, your neurons aren't just sitting in cannabis, hopefully not for 48 hours at that level, because that would be a toxic. Now, on the flip side of toxicity, you may want it to be toxic for things like cancer. So we did some work with Glioblastoma, and there's some preclinical evidence that THC and other cannabinoids can be toxic to cancer cells. They have a higher energy demand. Right. So we may want to investigate that further to say, hey, you know, if you've got this high demand, can we impact, this kind of the Krebs cycle and other components of the mitochondria to result in apoptosis of cancer cells. So this can be twofold where these high thing.

Trevor: Is it too simplistic to say that like a cancer cell literally has more mitochondria in it. So that's where the THC is targeting.

Hunter Land Oftentimes they do. But also I would say that they're probably more sensitive due to energy demands. Right. So you've got these cells that are, you know, hard wired to just produce and replicate rapidly. So, it's kind of like the straw that breaks the camel's back. Now again, these are early pre-clinical studies. So I don't know that there's really strong evidence in humans that there's a true benefit at physiological relevant levels. Right. So, so using a small amount of THC or CBD that doesn't I'm not saying that it couldn't be a benefit for cancer treatments or in conjunction with other treatments. I don't think we know the answer to that. We know some about the side effects that it can counteract. But all on its own, at the levels most people received, probably not, however super high doses it does seem to be beneficial. For me personally, my interest lies further and and areas of where we would say mental health disorders and, and things like cellular energetics, where small amounts and acute amounts may produce long lasting effects. And same thing with, same thing with conditions like Alzheimer's disease.

Trevor: Okay. And we were talking a little bit before, we started recording and this might be a place to jump into it, but in case anyone missed it. So CB1, we generally talk about that being like that, the quote unquote THC receptor. Obviously other endocannabinoids do stuff there too. But and we talked about CB1 receptors being on mitochondria and that might have something to do with so THC hits that. Does the mitochondria not work as well, like does it reduce how much energy it puts out or do we know that yet.

Hunter Land Yeah. Most of the data again, invitro, does seem to relate to reduction in energy production. So you do seem to impede some energy production at the level studied in conjunction with THC. It also tends to result in something called fusion where your mitochondria actually come together and they're fused together as one. And it can also, decrease at least in short term, decrease the turnover rate. Again, this is the continual dosage with something like THC. Now there is a theory and it's not so much a theory, but there is something known as Formsis. Do you have you heard of Formsis?  A really interesting theory.

Trevor: No what's that?

Hunter Land There is some good data to support for Formsis. And basically the idea is that sometimes acute stress or small amounts of toxins can actually be beneficial. And some of the best, examples of that are exercise, right? In theory, tearing down your muscles and being exhausted doesn't seem like something that would be good for you in theory. And what happens is it, and you actually increase things like what we see with THC, increase in reactive oxygen species within the mitochondria that's ROS. We also see that same thing with exercise, right? We see, kind of profound effects, that also result in cascades around, translation, transcription of different hormones and even cellular turnover. Right. So just because something could be in a dish could be acutely toxic or not so something that's positive, that doesn't mean that you're not stimulating something very positive on the back end. Now, CBD, is actually quite a bit different. So there's quite a bit of evidence that CBD does have a pretty profound interaction with mitochondria. There's a different receptor called VDAC1. It is located on mitochondria and it's involved with calcium regulation. So this is of critical importance to epilepsy. But also I think to mitochondrial health. Essentially what happens is when CBD binds to this receptor, more calcium becomes available and goes within this, it goes into the mitochondria. At high doses this could be a mitochondrial toxin, but at low to medium doses it seems to increase biogenesis. So resulting in even resulting in death of the mitochondria is not, or turnover so to speak, of a mitochondria is not a negative thing. Right. It can be a very positive thing if you have old mitochondria that aren't actually working that well, stimulating this biogenesis, so providing a signal, to the nucleus to produce more mitochondria or to produce more, replicate mitochondria can actually be a quite beneficial thing because now you've kind of gotten rid of the old mitochondria that aren't functioning well, and now you're producing these new mitochondria that are hopefully, functioning at about optimum rate.

Trevor: Okay. And maybe it'll be too complicated, but I'll try anyway. So I kind of understand, quote unquote, the powerhouse of the cell and energy level and maybe even the whole, stretching something a little bit can be good, aka things like exercise. That all sort of makes sense. What do mitochondria have to do with epilepsy and why, why does CBD, how do CBD mitochondria and epilepsy go together?

Hunter Land Glad you brought that up. So typically, epilepsy, I think most people are familiar. Most, epilepsy is result in seizures, especially if you're not well controlled and, in part that's due to hyper excitability of the brain. So, we know that you get these massive spikes and a lot electronic depolarization that result in seizures. Some methods to modify this, the availability for this change of electronic transmission is to modulate ions. And one of those methods would be modulating calcium. Right. So if we can soak up some calcium in mitochondria and in endoplasmic reticulum, which is another organelle within cells. Then you've got less calcium available and we don't see these big drastic spikes. That is one of the potential mechanisms for reduction in seizures. There's also, TRPV4 receptors or channels on mitochondria that are also thought to to play a role around calcium modulation. So this is just in hyper excitability. There's been some studies that show that when we see some of these acute stressors, both with THC and CBD in these envitro models, it not only depends on the type of cell being used. So you might get something very different in the hippocampus than maybe another region of the brain. But it also depends on the state of that particular cell. So if they're in a state of hyper excitability, then you tend to see more of a beneficial effect. At a state of resting we don't see the same sort of impacts. So it gets even further complicated on, you know, what are the state of the mitochondria and the cells that we're looking at, especially neurons. And where are they coming from in the body? So again, a lot of nuance to where we are right now with mitochondria and mental health, especially seizures.

Trevor: Though that is fascinating. I say that too far too often, but it really is, especially the the soaking up calcium to make, say, a neuron less hyper excitable. And the fact that soaking up extra calcium in a hyper excitable neuron more than if I have a resting neuron, that's that's really cool that we're doing different things in, sort of a part of the body where things aren't going. Well, we're changing that and leaving parts of the body where things are going well alone, it's very, very interesting.

Hunter Land Right. And you know, some of the, the interest around brain energy theory, which says that a lot of conditions can be related to mitochondria and that includes things like depression, anxiety, even other more broad disorders like Alzheimer's dementia, can be impacted about by faulty mitochondria. And this is where cannabinoids may play a really good role, right? It may be that by, increasing biogenesis, so by saying hey, we want to go through my myopathy, which is killing the bad, the bad mitochondria, that aren't functioning well, that we may increase, the effect of the good ones, if that makes sense. So, we may increase the we may double the production, and then all of a sudden we have a very healthy set of mitochondria to move forward. There's some evidence in things like ketogenic diet, which focuses which is a big focus of mitochondrial health, that where we get this biogenesis and you get the turnover of these positive, or replacements for the, the nonfunctioning or poor functioning mitochondria that you see long term effects. There have been patients that have been on ketogenic diet to control seizures that after two years stop, and, and no longer need, no longer need to be on epileptic medication or stay on that ketogenic diet. So.

Trevor: So I just going to stop you there because that is interesting that I have read, for other reasons, about ketogenic diet. But just to remind people. So a ketogenic diet is usually very low carbohydrate, very low sugar. And the whole idea is that your body breaks down fats and produces ketones as the ketogenic part. And whether you believe in ketogenic diet for weight loss and all the other things has become very popular for one of the original uses for ketogenic diet was epilepsy. So and I read that and said okay that's probably true. There seems to be studies behind it, but I had no idea the why.

Hunter Land That's one theory of why. That's one theory. You know, like everything else there are theories. But yes, it does appear to play a very significant role in mitochondrial health. As do other things, you know, polyphenols, which cannabinoids are, within that class. Do seem to have impacts on mitochondrial health. One example is resveratrol, which is, you know, found in red wine. And, and it made a lot of press years ago. Seems to work really well in rodents. Not necessarily as well in humans. So I'm not going to dive into the, the reasons there. But what we do see is resveratrol is actually a mild mitochondrial toxin. By essentially kind of pushing that mitochondria to get into a shape, it leads to things like, tautology and even, apoptosis. So cell death. Right. So if you've got cells that aren't functioning well, then it may be a benefit to, to more or less get them out of the way and have proper cellular turnover. So, but where we see this with polyphenol is we may see that same thing with cannabinoids and they may be doing it through different ways. So just, I'll get on my high horse for a minute and, and just give a short description of why the term cannabinoid is so bizarre. You know, it was originally made by chemist. You know, they named, essentially a scaffold, whereas you as a pharmacist, I suspect that many drugs, if I say it's, SSRI or, or something, tricyclic you think about mechanism. Right. And, and if you're a chemist, you think about a scaffolding. Well, you know, we've got all these cannabinoids and, whether they're endocannabinoids, you know, the ones produced by your brain, synthetic ones designed to work on cannabinoid receptors or the phyto the phytocannabinoids, where actually, most of them don't seem to have direct interaction at CB1 receptors. So, when we say cannabinoids and mitochondrial health, you've got two different things going on. So they may be, there's I think a strong potential that, you know, something like THC or some of these other cannabinoids could do one thing in terms of like, give it, impact the mitochondria in such a way where you'll need to have proper turnover in the long term or, CBD, where it may, it may actually work, effectively, acutely by soaking up calcium and controlling things like seizures.

Trevor: That's really interesting. Now, I know, and I think we've touched on it a little bit, but I know you've done some work and done a lot of reading on we'll call it cannabinoids and anti-aging, does that sort of fit into the mitochondria story as well?

Hunter Land It may, you know, the work. I would say the primary reason for the work that I've done in aging wasn't necessarily to say, you know, use cannabinoids and live forever. That wasn't the intention. We've used quite a few seal against models. So there are nematodes out there and certainly not humans. Despite, getting some, some questions afterwards about how much cannabinoid X should I take to live forever? I don't think that's what the main goal is. It's again preliminary research. But what we, what we did find, and this is, let me just take a step back. The FDA had a lot of concerns, initially with CBD, about what happens if you take CBD all day, every day. What if it's in foods? What if it's, you know, candy bars and drinks and you've got this constant exposure? What happens in ten years or 20 years? Right. And and nobody knows. It's a really hard study to do. Lifelong toxicity. Right. And it's even harder in rodents. It's a that's a long study. So kind of the canary in the coal mine approach is using C-elegans because the lifespan is usually around two weeks, 14 to 21 days, depending on the specific nematode in the conditions. And so you can give them something even if you don't know what it is. And if they die early, chances are it's toxic. And you can look at different levels. So the EPA likes this water, this model for like water, and certain soils and stuff. So, you know, if they're not sure what's to test on the water and they put C-elegans in and they die, then you probably shouldn't play in the water. It's a good indicator. NASA use the same model in space. We use that, to see, you know, if there's any sort of long term toxicity concerns. And actually, with CBD, the first thing we found was it extended lifespan. And not only did extend lifespan by about 200%, it included, excuse me, by 18%. It extended health span by over 200%. Meaning as they got older, they moved more, they had more activity level. So that was that was a surprising finding for all of us that we're primarily looking at at long term toxicity, not anti-aging.

Trevor: No. And that's cool. And just, health span. In case people haven't heard that term before, it's a cool term. I think I've only run into the last year or so. So picture you're going to die at 80. Well, do you want to be sick and in bed? You know, between 65 and 80 like the last 15 years in your life? Or do you want to be running marathons up to, you know, age 79 and then die at 80? So how long during your regular life span are you able to do the things you want to do? So you're saying that these worms were still wiggling right up until the their last day?

Hunter Land Yeah. It would be akin to, you know, the 80 year old worm acted more like a 50 year old worm. So, that was exciting. We saw this also with cannabigerol, which is, you know, the acid form would be the mother of THC and CBD. So, again, primarily looking for toxicity and then had this surprising effect. We later kind of move past that a little bit. I was interested in the impacts on in disease states. There's a model called Tau. Are you familiar with the Tau protein?

Trevor: I'm just going to say it's that one of the Alzheimer's proteins. Yes.

Hunter Land It's associated with Alzheimer's as well as many other things. So, these Tau proteins seem to accumulate within neurons, and they, they wreak havoc. It's in many different neurological diseases as well as cancer. And one of the things that Tau does is it actually affects mitochondrial migration. So if you look within neurons, these mitochondria, they move around pretty much continuously. And in less healthy neurons and less healthy cells, they move less. Right. And this may be a problem. And if you've got these Tau tangles, these proteins that are all in the way, then then they don't move very well. So that's a, that's one of the questions is you know, is Tau we know it's kind of a marker, but what is it actually doing. Why is it causing these negative effects? Tau also implicated in things like concussion and traumatic brain injury. If you think about the brain and an impact, your neurons can be essentially stretched, right? And when they get stretched, that's a stressor. And as an impact of that, either impact or that stretching, you get the buildup of these Tau tangles. And, and so we decided we would look at a botanical drug substance and not just CBD alone. We use that as a positive control. But we also looked at a combination with CBD, THC and CBG together, at different concentrations. And what we found was significant improvement, in longevity. No change in activity level. So no change in health span. But we did see significant improvement in longevity. We also added Cannflavins to that by themselves and alone. And Cannflavins seem to work better than CBD alone. Didn't really have much effect or like a super additive effect or entourage effect with the botanical drug substance of cannabinoids. But did better than CBD alone. So interesting. Certainly must be implicated in different mechanisms there.

Trevor: So do we think they're actually breaking up the tau protein, getting the cell to get rid of it faster? Do we know?

Hunter Land Yeah, so the next step is actually to look to see what we've done to those tau concentrations and also the mitochondrial health. Right. So we may find that we get better mitochondrial turnover. They are turnover. They're very quick turnover. In many of these models. And what we may see is that which leads to better cellular functioning. So that's the next step. Which could also be implicated in many diseases like, depression and anxiety where we see, these mitochondrial dysfunctions. If they're treated, if you do certain things like ketogenic diet or exercise, it appears now, preliminary data that you have much better outcomes on mental health disorders. So, the same may be true for Alzheimer's and dementia.

Trevor: Do we know why the mitochondria move around? I was just thinking, you know, in a microscopic cell, it probably doesn't matter. But then, on the other hand, like, some nerve cells are literally centimeters to a meter long if they're stretching down to your leg, so are they moving around just to different parts of the cell that need energy, or are they just out for a walk? Or why do they move around? Do we know that?

Hunter Land That's my understanding, is that they tend to be more densely located in areas with higher demand. And remember these are involved in hormone production. Cellular DNA translation. Excuse me, transcription. So they provide a lot of useful tools for proper functioning of the cell in the neuron. So it's, they're critical, their movements critical, and their energy production is critical. Their role in cell death because we don't want all cells to live. So their role in cell death is important. And their role in creating more mitochondria is important. So these are all areas where cannabinoids, whether through CBD1 activation may be important. Or where we actually don't need to activate that. We need to activate some other thing like VDAC or H-Type1, to result in some sort of positive effect like control of seizures.

Trevor: This has been fascinating and I, I could go on forever, but I promised we'd wrap it up around half an hour or so. We'll start the beginning of the wrap up. Did I miss anything? Should I have asked anything about cannabinoids and mitochondria or anything else you really think the listeners need to know?

Hunter Land I think I've covered most things. I just I would be, if you look at the preclinical models, where they where they show impacts of on mitochondria, they typically tend to be at very high levels. And they typically occurs for a very long period of time. So just remember, you know, the way that our endocannabinoid system functions and the way that, people actually take cannabinoids, it's not this prolonged duration of exposure. So usually things like to 2AG and anandamide or endocannabinoids are metabolized very quickly. You know, usually within five minutes. So you're not getting this prolonged high amount. So that very well may be like the homeostatic regulation that we see with neurons. Where does we get too much signaling. We get too much activity. So just as in low mitochondria activity can be bad. You can also get overactivity. So so actually using this kind of archaic rest, relax, restore system to say, hey, don't be so active for a minute may be very beneficial. And that's that may not be very well illustrated by looking at, you know, some of the, the data saying that, you know, cannabinoids could be bad for mitochondrial health. The last thing that I would say is it doesn't appear that, that things like THC would be good for metabolic syndrome. So if you have, if you have, if your mitochondria is not functioning well already, and even if you go through something like biogenesis, where you start with my myopathy, where you're killing those, basically mitochondria are replaced by newer, better mitochondria. If you have that metabolic disease, you're probably not going to replace them with healthy ones. Right. Because it may very well be related to other factors such as genetics. So I would say that right now the evidence doesn't look strong for true mitochondrial disease, especially around THC. You may cause further impairment in those individuals. But again this is preliminary studies. We don't know very much. Just as in we, with the negative modulation by CBD and CB1, originally people said, oh, well, that would be great. We can counter effect the effects of THC by giving CBD. And actually, Doctor Brian Thomas recently published and colleagues where you by negatively impacting that CB1 receptor. You impact betarestin. And so the part that internalizes CB1, so you actually get more expression of CB1. And that may also be the case in mitochondria. So if you reduce the binding, do you actually increase expression of CB1? And that could be mitochondria or on presynaptic neurons. So a lot to be done in this space for sure.

Trevor: Okay. Last little one because he touched on metabolic disease in Canada and, well, all of North America, we're in like a type two diabetes crisis, which is, you know, metabolic disease after it's carried on a little ways. Are any of the cannabinoids interacting with mitochondria showing any promise that they might help with things like metabolic disease, or is that just we don't know enough yet?

Hunter Land I don't know if it's the question would be how much of it's mitochondrial mediated. I think there's some evidence to suggest that, something like, TCV which, which unfortunately wasn't positive in the clinical study for metabolic syndrome, but pre-clinically, I think there's evidence and that may be effective in that it depends on the for those that don't know THCV is an antagonist at about, human equivalent of 100mg or less. So it's not an inverse agonist, which Rimonabant was so led to suicidal ideation. I think there could be some evidence to look into that. And it may be not due to mitochondria, or it could be playing a role in mitochondria by blocking or antagonizing that CB1 receptor. So, more to come on that certainly. But yeah, I think there's a lot of promise. And I think we need to we certainly should be looking more into mitochondrial health. And how these things impact everyday diseases, especially mental health disorders.

Kirk: You know what I found interesting about this this fella. He's a nutritionist. With a biochemical, chemist. Biochemist. So. And then 13 years, he's been involved with cannabis and had had his hands in the development of synthetic cannabinoids. So he's been around a while.

Trevor: Well, and, because GW Pharma will jump up and down and say they weren't really synthetic like they were, so Sativex. It's a spray. And it really is a THC/CBD combo spray. For that you spray under your tongue for, for MS. And they are also involved in Epidiolex, which really is a very for a pure form of CBD used for epilepsy at the moment, I think mostly in children. So I think they would.

Kirk: Okay, so correct me. Correct me if I'm wrong. Are these not chemicals that were developed in the lab? Were these actual chemicals that were drawn from a cannabis plant and created as medicine?

Trevor: Good question. I don't know the answer to that, but I would argue that as long as it's THC or CBD doesn't matter. Yeah, that's an angry E-mail.

Kirk: Spoken as a pharmacist but as a gardener.

Trevor: But but but when I think when I think synthetic cannabinoid, I think, you know, cannabinoids not found in nature.

Kirk: Correct.

Trevor: That we can definitely make in the lab, but, you know, you can't go to any particular plant and and find. So, yes, send an email my way. But, as a pharmacist, I don't really care if they took it from a plant or or, or made in a lab. My guess is they probably started with the plant because it just has so much of that in it. But again, I don't know, I will admit right now I don't know which way they went on that, but yeah, these are two, arguably two of the first cannabis medicines out there, GW Pharma and and Dr. Land and, and Ethan Russo were, were both involved.

Kirk: Yeah. I what I liked about this is again, it forced me to go back to studying biology that I haven't thought about in ages. And, and the irony, you know, the irony is that I'm now teaching. I was back teaching health care aids in the last few months. And, you know, I'm sitting there with 44 years experience, someone who didn't necessarily enjoy the biology classes as a student back in the day. But now, after 44 years of practicing, how important that foundational knowledge is to your practice. I mean, I osmosis diffusion happens throughout the whole body and is a big part of your diagnostics. So understanding the mitochondria today. Boy, I wish I had this knowledge back in the day because I would have been a much better practitioner if I had paid attention to some of those chemistry lessons a little bit better. But trying to tell my students today, using my, you know, experience, please, when you go into nursing school, could you please pay attention to those chemistry classes because they're important and so what do you think? Do you think CBDs is going to make us live longer?

Trevor: Yes. Sure. Absolutely. Everybody, go, go take. No, everything we learn about CBDs sure sounds like, it's good for us. Now, you know, there's obviously going to be reasons why it isn't, but, yes, they sure seem to be doing a lot of good things. But one of the things that that made me think of, sort of related was the whole, ketogenic diet. And so ketogenic means we, we don't, no sugar, no carbs. Try to keep the, the amount of carbohydrate to the absolute minimum, and then you burn fat and forms ketone bodies.

Kirk: Yeah.

Trevor: So many people probably heard about that in relation to weight loss.

Kirk: It was a big diet ten years ago.

Trevor: Well and it comes and goes now too. But the part that fascinated me is this is a legit treatment for types of epilepsy. For types of seizure disorders. If you and it's really hard to do, but you know, if and it's often kids and if you basically as a parent completely cut out all carbohydrate from your kid's diet, many kids seizures or some kid's seizures went away altogether. So a legit proven treatment. I said, okay, so I read that, but I had no idea why. Like what would sugar have to do with or carbohydrate have to do with seizures? Kind of blew my mind. So many things blew my mind. But I'll jump on this one. Mitochondria you know, the whole, affecting the mitochondria, affecting seizures. Wow. I that yeah, really kind of, blew my mind again, you know, right up there. What do you mean that that mitochondria have receptors for CB1 receptors.

Kirk: Yeah. Yeah. But again working it backwards, deconstructing the knowledge that we have there Trevor. It makes sense because when you, when you, when you consider the mitochondria is the is the furnace, is the powerhouse, the engine of a of a cell. If you want to tune up the cell you would tune up the mitochondria. So if the cell is overreacting and the cell is causing spasticity called seizures, then if you were to tune up the mitochondria you might settle that cell down. So again it working backwards. It makes sense to me. I what I found fascinating is how the mitochondria, how he kept calling it mitochondrial health. Mitochondrial health. If you have a healthy mitochondria you have healthy mental health. You have healthy. And I'm thinking, wow, well, we're now we're now going to depend on our mental health by how we treat our mitochondria. That fascinates me in the sense that, okay, so, you know, Shelley Turner, when we met Shelley Turner, a friend of the show from S3E5, she talked about CBD being vitamin CBD. Everyone should take the vitamin D tablet. All Canadians should take vitamin D. Now all Canadians should take vitamin CBD because it helps with mental health. It's it's I find it absolutely fascinating how all these all these stories we get Reefer Medness - The Podcast kind of connect you know.

Trevor: They do and I like and again we got to be very careful. A lot of what Hunter Land was talking about is pre-clinical. In the lab. Not necessarily proven in people.

Kirk: But making nematodes happy.

Trevor: Making very happy nematodes. But yeah, but having some potential mechanisms for how this works, like, you know, having a mitochondrial suck up some calcium and making a nerve cell less likely to pass along a seizure. So having some actual not just motherhood and apple pie statements like this is good for you. This is how this might work. And you know what might be, mitochondrial related. Yeah. I love that part.

Kirk: Yeah.

Trevor: And, exercise now just because we're, we're in the time of year where I'm trying to get ready for charity bike tour in September. So I go out for long bike rides and often come home at the end of the day and say, exercise is terrible, no one should do it because, you know, it hurts. My legs hurt. My butt hurts. I look like a 100 year old man climbing up stairs. Exercise doesn't make a lot of sense when you think about how immediately afterwards, or sometimes the next day, you don't feel great, you know the of why the hell am I doing this comes up a lot. But you know, back to some of the mitochondrial health stuff when Hunter Land talks about, there's a theory that says if you stress the mitochondria a little bit, not a ton, don't blow it up. But if you stress it a little bit, it makes them more healthy. And how that sort of broadly links to, you know, an analogy is exercise. So exercise, you know, you tear up your muscles a little bit and then they repair stronger and able to do more next time. So having a little bit of stress and, and maybe cannabinoids involved in that little bit of stress on mitochondria and that making them better down the road and like you said might be involved in pairing off the bad mitochondria. Like, you know, the old ones get rid of those. And having cannabinoids involved in all of that craziness. I loved it.

Kirk: Well, hey, we've often talked about this, but not in a while. Is that the runner's high? When I was when I was running back in the day and I was running marathons and running long distances, my goal was always run to the runner's high to run through the wall. And I would get this what we call the endorphin rush, right? And it's a it's an incredible rush for those that have done it. Get it? It's it's probably one of the best rushes I've ever had is just by running at 26, 26.4 mile race

Trevor: 26 and a bit miles.

Kirk: Yeah, 26 and a bit miles. Now we know that it is, endocannabinoid rush that you're getting. And I can remember back in the day saying to people that I just felt like I just smoked a great big reefer because I feel so calm and mild. So when you are stressing muscles and you do get to the point of the endocannabinoid rush, maybe that's all part of mitochondria repair. Maybe that's the anandamide in your and in your body that's doing it naturally. So another connection I think, you know I don't know maybe I'm reaching. But it could all be part of that.

Trevor: Maybe reaching. But, but. But it's still a good analogy.

Kirk: Yeah it's it. Well but  I think in the chemistry if we, if we're listen to what Hunter says is that the mitochondria has receptors for cannabinoids. Then if your body is naturally producing cannabinoids to, you know, when you when you stress it, then it could be your body's way of just kind of getting down and taking care of the mitochondria. That's how I'm relating this. And I can I could be out to lunch, but I'm putting it, you know, trying to take a little bit of knowledge and build something with it. Anyways, that that's another connection.

Trevor: And then the last thing because you tease with it on the way in cannabinoids, mitochondria and cancer.

Kirk: Yeah. Yeah. That's the other thing that's kind of cool. We learned about that. We learned about that with Dr. Daeninck. Back back when we, we did E71 - Why cancers come to pot? And he talked about it right at the end of that interview. He talked about how cannabis might actually decrease cancer in people. So, yeah, Hunter touched on that.

Trevor: And then we also had Doctor Goldstrich, who wrote an entire book on curing cancer with cannabis, which, again, we're not saying it's the end all be all, but certainly might be a important part.

Kirk: Episode 116. Yeah, I know there's again, there's lots of connections here. And what I like about this episode is it it all gets down to that little mitochondria that's inside a cell that when we were kids studying chemistry, we said, oh yeah, okay. It's the engine of the it's the engine of the cell. I'll get that when they well, in the test, when they draw a cell and say point out the mitochondria, what does it do? It's the engine. Well, if I was to do that test now, I could write an essay on it.

Trevor: Yes. And, you know, probably like everything else more complicated than we think. But cannabis cure in cancer, cannabis treating cancer, cannabis and being involved in cannabinoids, being involved in cancer and the mitochondria. Probably part of the story. There's probably a bazillion other little bits of the story. But again, it just, kind of blows my mind. Again, this might be another mechanism, another why or how that that cannabinoids do what we've been other people have been saying they do for a while. And mitochondria might be part of that link of the how or why they do what they do.

Kirk: Okay. So what Reefer Medness - The Podcast founded ReeferMed.ca. I am Kirk Nyquist, I am the registered nurse.

Trevor: I'm Trevor Shewfield, I'm the pharmacist. And I'll say it again, I love this episode. Sorry. Sorry for all the people who are triggered by all the science, but it was very cool.

Kirk: Yeah. So music.

Trevor: You know, all the, all the, the sort of, you know, something powerhouse related or maybe science related or she blinded me with science or or one of those would, would be fine, but I'll leave it up to you guys.