Episode Transcript

Trevor: Kirk, we're back. 

Kirk: Hey, Trevor, How's it going?  

Trevor: Good. I saw some pictures on the Facebook with you and Michelle and some kind of watercraft. 

Kirk: We bought ourselves a Nova Craft Prospector 16-foot canoe. Yes, we have. We went out on Moon Lake and went paddling for the first time in a couple of years. Pre-pandemic, and our canoe got bashed up in that hailstorm a few years ago, and for whatever reason I just never got around to replacing it. I bought a kayak and I used to kayak a lot and I went out and bought a canoe. And we're spending the weekend out in Moon Lake. This weekend we're going to go out there and do some fishing and hang out with the bears and the stars and paddle around. 

Trevor: Sounds like an excellent weekend. And it's supposed to it's supposed to be hot. So, you know, that's good or bad, but that's what it's going to be. 

Kirk: I may end up doing some swimming. And what have you been up to? 

Trevor: A work? 

Kirk: You've been working a lot. 

Trevor: Yeah, well, I was in Winnipegosis today, so, you know, a change of scenery, so that was okay. But this isn't about, you know, what we're doing with our time. We I don't think I'm being immodest and saying, I think we have a legend of the cannabis industry who agreed to chat with us. So that was super cool. So we've got Dr. Ethan Russo and I was just I've been telling everybody who will listen that, you know, we got to talk to him. And like I was, I was at a completely unrelated cannabis talk and one of the speakers said, Yeah, you know, there's this effect here and it works really well. You know, it's just like that paper by Russo. Yeah, that Russo, that's the one. 

Kirk: Well, it's interesting. I googled him and I was looking for his wiki page. Well, he doesn't have a wiki page. So I went to, I went to Google Scholar and Googled them on Google Scholar. Came up 600 times. So like, he's been involved with or been cited by people involved with the cannabis industry a lot. He has some of the most groundbreaking papers that other people cite. So he's definitely the, the modern day researcher on cannabis and he talks about it and he got into it first about 1997. 

Trevor: My notes because I made a couple of notes on that. Yeah, he neurologist then decided to go back to an earlier passion of his of medicinal plants. Hung out in the Amazon with a few of the tribes there for a few months. And then I got 1998 paper on cannabis in the journal Pain. 

Kirk: And then the rest is history. 

Trevor: Well, yeah, then GW Pharmaceuticals, which honestly I didn't, I guess maybe I wasn't paying attention. I didn't realize sort of how groundbreaking GW Pharmaceuticals were because they they've been sort of one of the people to start groups to successfully sort of bring cannabinoid medicine to the mainstream. So they are Sativex, which is an under the tongue spray for MS. And the one that's made all the news lately is Epidiolex they're CBD one for like seizures in young kids. So they've been huge, we'll call it taking cannabis medicine and bring it into pharmaceutical medicine. Whether you like that or hate that they've been. And anyway, of course he was a big part of that as well. So. And then Credo Science, his current company. Yeah, no, he's been there, done that. 

Kirk: So before we get into listening to the interview you had with him, I'd like you to explain a couple of things for me. 

Trevor: Oh, good. 

Kirk: Enigmatic illness and biphasic response curves. 

Trevor: Okay, well. 

Kirk: Well. And I ask because these are the phrases that come up and he sort of skirts over it. So I thought maybe we should get our audience ready for those terms. 

Trevor: So. Well, I'll get back to the biphasic because I think that one makes a little more sense. I think what he was trying to say with cannabis hyperemesis, I'm saying it wrong again. He corrected me. Cannabinoid hyperemesis syndrome, it was one of these things that no one really kind of knew what it was like. He talked about it being coined in about 2004 by an Australian group, but they were still referencing stuff that had happened back in 1996. So it was a thing. No one was really sure what this thing was. There was people who use a lot of cannabis who puked. But you know, sometimes people use cannabis puke. You know, it was one of these things that happened that there it took a little while for people to sort of see the pattern. So I think that's the whole big enigmatic part. But the biphasic. This I'm hearing more and more while it happens in pharmacy world too, but in cannabis world where low doses of something have a different effect, that high dose of something. So he is specifically talking about THC where it's been known, accepted, and one of actually the I think it's five accepted uses of THC in medical world and that's to treat nausea and vomiting due to chemotherapy. But it's a low dose of THC that that makes you want to vomit less. So call it antiemetic but high doses of THC can make you want to vomit. So if you take a you know a lot of dried flower or probably more likely if you've got an extract of some kind, you know, dabs and vapes and synthetic K2 and that sort of thing. But you get a high amount of THC that can absolutely make you want to vomit and actually vomit. But well, he gets into it more and better. But the cannabinoid hyperemesis syndrome isn't just I took way too much of that dab and puked. It's I seem to be puking a lot all the time. Kind of whether I would just overdoing it last night or not. So that's my 2 cents on a enigmatic disease biphasic. 

Kirk: Okay, yeah, I was. I was trying to think of it. Is it like sort of like dopamine? When you give dopamine at lower doses, it has an effect on the vessels. You give it a higher doses has effects someplace else. It's not, it's not really biphasic. It's just the drug at different doses does have different effects. 

Trevor: Yeah but that's not, that's not wrong. Like just sort of different, different effects. The different strengths. The top of my head, I can't think of. 

Kirk: So that's when the fact that the fact that cannabis helps some people like in cancer care it helps you with your nausea vomiting but. 

Trevor: But at a low-ish dose. Yeah, but in a big-ish dose, whether cannabinoid hyperemesis syndrome or not, a big dose could make just about anybody vomit. 

Kirk: Well, it's it's I, you know, I guess I guess I'd like to come out of this because. Because there's a lot of stuff I want to talk about CHS. Cannabinoid, hyperemesis syndrome after we come out of the interview, because there's a few things I find fascinating, what he's saying. I don't know if I want to give it away. I think let let people, let people hear the surprise, because I am I think there's a lot to this that we're missing in our frontline care for this syndrome. 

Trevor: Yeah. No, it's a dense one folks. I'm not going to apologize. So there's lots of really cool stuff in there. So enjoy with Doctor Russo and Kirk and I will come out at the end. Dr. Russo probably, I should just, I know it's really long, but for those of you out there who haven't heard of you, can you just tell us a little bit about who you are and what you sort of do in the cannabis space? 

Dr. Ethan Russo: Sure. Be glad to. So I'm a neurologist by training, but after I was in practice for seven years circa 1990, I was increasingly disappointed with the kind of results that I was getting from conventional medicine and treating my patients. So I turned back to an interest in medicinal plants I'd had as a teenager. Very quickly I got involved in research in Amazonia, particularly in migraine and psychoactive. That led to a nontraditional sabbatical in the rainforest in 1995, working with Machiguenga tribe in Parque Nacional del Manu, for about two and a half months. When I got back, it was then 1996, and I quickly became embroiled in the cannabis controversy with Proposition 215 in California and began a deep dive into cannabis and cannabinoids. That, in turn led to writing and publishing on my first paper on cannabis was in 1998 in the journal Pain that caught the notice of Jeffrey Guy, the chairman and founder of GW Pharmaceuticals, the British pharmaceutical company that had a license from the British Home Office to develop cannabis based pharmaceuticals. So I was a consultant for them for the next five years and then came on full time as senior medical advisor and pharmacovigilance officer, study physician, etc. for that company as they developed the prescription pharmaceuticals from cannabis: Sativex and Epidiolex. Subsequently I have work for a couple of private companies, culminating in 2020 at the beginning of the pandemic with the founding of my own company, Credo-Science, which is dedicated to making cannabis safer and better. So we have a number of patents pending related to cannabis, cannabinoids, diagnostics, a variety of areas, and also do formulation work which extends from herbal cannabis to supplements and pharmaceuticals. So that's it in a nutshell showing my involvement in cannabis R&D. 

Trevor: That is quite the summary. So the first thing I want to try and get into in today is cannabis hyperemesis syndrome and a test that you have helped develop. So first, although it seems like everybody has run into it one way or the other, in case no one has heard of it before, what is cannabis hyper animas syndrome? 

Dr. Ethan Russo: So actually the proper title would be Cannabinoid Hyperemesis Syndrome. The reason being that was the name that was coined in 2004 when a group in Australia identified eight patients who had this strange syndrome. Also is the better title because the same thing can happen with high potency cannabinoid agonists such as K2, Spice or the various other synthetics that work on the CB1 receptor. But going back to 2004, they reported an index case from 1996 and then seven other individuals who had in common the following scenario. There were high volume users of cannabis. They all had a constellation of symptoms, including abdominal pain, nausea, vomiting and then pathognomonic added feature, which was they all seemingly got relief from hot water bathing. Either prolonged showers or baths that temporarily reduced symptoms. Gradually, this came to the attention of more people and has been identified around the world, but it seems to cluster to some extent in certain areas that also happen to be areas of high availability of high potency cannabis. So this would include the North American West Coast. So I'd include B.C. States of Washington, Oregon and California, certainly Colorado and some places on the East Coast, such as New York and Massachusetts, where there's a greater availability of products, particularly by potency products, dabs, vape pens, etc.. What this is, is an enigmatic condition that affects certain individuals that use cannabis but not others. And this is where some real distinctions come into play. So I was aware of this way back when and like everyone else was interested in this unusual condition that is one of the few but definitely red flags in cannabis usage. So what's different about people who are affected versus those who are not? Well, there's been various theories that people have advanced that really don't hold water such as that this was related to pesticide use or had something to do with synthetic fertilizers that might produce toxicity in the brain and nausea from hyperanemia, ammonia from residual fertilizers, etc.. However, those symptoms really don't match up with the phenomenology of CHS (cannabinoid hyperemesis syndrome). They really don't fit. My supposition, and this had been suggested in a couple of papers but without investigation, was that there might be a genetic susceptibility of people to develop CHS as compared to high volume users of cannabis that were never affected in this way. Now it's complicated by a couple of things. THC and other cannabinoids are subject to what's called a biphasic dose response curve. At down for a less technical folks in the audience. It means that at a low dose there are certain effects which may be opposite at a higher dose. Okay. People are very familiar with the idea that THC is an antiemetic and helps reduce nausea and vomiting associated with chemotherapy, for example. And that was the first indication for synthetic THC Marinol, which is approved by the U.S. FDA in 1985. However, what people may be less familiar with, if you have too much THC, it's not unusual at all to become nauseated and vomit. And that can happen to anyone. The distinction here is in cannabinoid hyperemesis syndrome. This is an ongoing thing. It's not that, oh, you know, I over did it with that huge spliff and now I feel sick. Rather, this is protracted nausea and vomiting. People may go days or weeks spending hours in the shower, ending up in an emergency department, spending upwards of $100,000 in diagnostics and interventions. Another thing about it is that the standard drugs used to treat nausea and vomiting don't work so well. But things like Ondansetron and Granisetron rather Haloperidol works a major tranquilizer used to treat schizophrenia. And also another funny thing, which is application of Capsaicin Ointment on the skin. Capsaicin is the active ingredient in chili peppers that make it very piquant. Hot, if you will. So there was a common thread there too. Hot showers help. The capsaicin on the skin helps. So something to do with heat. That implied to to us that it had to do with what's called the TRP-V1 receptor, a heat receptor that where capsaicin works on. It also responds to low ph and ethanol. A couple of other things. So bottom line was we were presented with a situation of this unusual flagrant syndrome that affected certain individuals that use cannabis but not others. Again, my theory was that this is related to a genetic susceptibility. Fortunately, we have the tools to investigate that. So Credo-Science, we partnered with Endocanna Health, a company that does genomic testing. Testing of people's DNA to look for mutations in the genetic code that might indicate a susceptibility to disease. Okay. But when we did that, we had a number of things in mind. I thought, gee this might have something to do with the CNR1 gene that codes for the CB1 receptor where THC works. That turned out not to be the case in this instance. However, two other theories were borne out. One was that there might be a problem with the genes that encode cytochrome I'm sorry CYP2C9, which is in the liver that breaks down THC also anandamide, an endogenous cannabinoid. That turned out to be the case. The third hypothesis was that it had to do with this TRP-V1 receptor that we just discussed that also turned out to be the case. So already we had two genes that helped explain why people with CHS, there were people who got CHS that use cannabis and those who didn't. What we did was put out a survey with over 500 respondents asking questions related to CHS and cannabis usage. We were very, very strict in our criteria for entry, meaning that to enter the study someone needed to have a diagnosis of CHS by a professional and they needed to have ongoing symptoms. So in other words, they had to have this pattern of cannabis usage associated with nausea, vomiting, abdominal pain, and the hot water bathing behavior. We also in the survey had high volume users of cannabis, both for averaging about four grams of herbal cannabis a day. 

Trevor: That's a lot. 

Dr. Ethan Russo: Yeah, it is, definitely. But for entry is controls. People who didn't have CHS they had to lack the symptoms of CHS. So it was apparent these were high volume users over a period of time. They've never gotten sick from cannabis and so they were comparators. What we ultimately found was five genes with statistically significant differences mutations on these specific genes in the CHS patients as compared to the controls. So besides the CYP2C9  and the TRPV1, we found others and these were more of a surprise. There were two genes affecting dopamine metabolism. Dopamine, of course, is one of the neurotransmitters in the brain on it's important a number of disease conditions, including Parkinsonism, also addiction and schizophrenia. So one was for the gene that encodes DRD2, which is a target of antipsychotic drugs. 

Trevor: Okay.

Dr. Ethan Russo: And the other was COMT, the enzyme that breaks down dopamine. So with mutations in these two genes, we noted a susceptibility to a couple of things. If there were problem with breaking down dopamine, it would lead to its excess. We know that when dopamine is present in too great an amount, it produces nausea. It also produces addictive behaviors. And this was very much in keeping with the sort of compulsive use we saw in the CHS patients. I should mention that folks that have this syndrome typically have difficulty believing that cannabis is responsible for their problem, and most often they might stop for a while. Abstinence is really the only definitive way to prevent further attacks of CHS. But almost invariably they would return to cannabis usage and go through another cycle of nausea, vomiting, abdominal pain. And it's just unfortunately, a story we've seen repeatedly over time. Well, well-meaning people tried to edge back into cannabis usage and would be hit again with the same flagrant symptoms. The fifth gene had to do with cholesterol metabolism. And again, this was a surprise. But mutations on this gene, unfortunately, would show a susceptibility later in life. And again, I use the word susceptibility, not guarantee, but susceptibility to the possible development of type two diabetes and dementia. So ultimately, this was an important epidemiological red flag, meaning that this is a public health concern in that people with CHS may be at risk for these other disorders. So overall, we felt that there was a compelling case to support that this is a disorder that arises out of a genetic susceptibility. There is now a commercial test available. People could find the information at what-is-CHS.com. Similarly, the publication of this was a couple of years ago in the Journal Cannabis and Cannabinoid Research and that's available free online at my web site which is EthanRusso.org. There's a library tab. And then if people just look through for cannabinoid hyperemesis syndrome, they'll find the article. 

Trevor: So I just got the test. So when I was first talking to you about this at a conference we were at, we happened to be surrounded by a bunch of cannabis nurses. And so let's talk about maybe the practical application. So let's say someone presents at an E.R. and, you know, they've been vomiting for three days. And the only thing that seems to make that better is when they sit in the hot tub. Let's say we have nurses listening and they have access to this test. What would you hope would be happening next? 

Dr. Ethan Russo: Right. Well, there are a couple of different uses potentially for the test. One is we hope that this might be applied earlier in the course of investigation. In other words, if a young person comes to an emergency department with this kind of syndrome, the proper questions need be asked about the nausea and vomiting and whether they have get relief from hot water. What is their cannabis usage? Because we've seen ascertainment bias associated with this that moves in both directions. What I mean by that is this was a poorly recognized syndrome for a long time on people invariably ended up with invasive tests, barium enemas, scans, tremendous associated expense. On the American side of the border, one study showed costs of $96,000 per patient before a diagnosis was put in place. 

Trevor: That's a lot. 

Dr. Ethan Russo: That's terrible. But now it can go the other way if people know about this. You've got emergency room physician that is overworked and doesn't have enough time. And a young person who comes in with nausea and vomiting might be asked the question, do you use cannabis? If the answer is yes, they might be falsely pegged with a label of CHS when they have a gallbladder problem or something else. And this is an indictment of American medicine that because of insufficient time, little care has been taken to really talk to people and ferret out the true reasons for their problems. Bottom line, to answer your question. 

Trevor: ya no. 

Dr. Ethan Russo: Would be that we hope that this test could be applied noninvasive. It's a swab in the mouth that's sent off for genomic testing. And in about ten days, people could see if they have one or more of these genes that seem to be markers of a susceptibility to CHS. Another scenario would be, let's suppose that you were a 15 year old and you have an older brother who has CHS. All your friends are using cannabis and you're wondering about whether you should do it. It might be helpful to have the test and know whether you've got the same susceptibility that your brother does. 

Trevor: Sure.

Dr. Ethan Russo: But no. So we feel that this could be just another tool to save money, unnecessary interventions, and act as a screening device for people that might be at risk. It clear that's the case. There's some people that shouldn't use cannabis. So people with CHS would be one. 

Trevor: Well, I was going to ask that I get to the second one in a second. But, you know. All right. So I have CHS. I've suffered. I know. And now it's definitively shown. Genetically, I had. But, you know, either I really like cannabis, all my friends use it or even, let's say I have another medical condition and arthritis or something and the cannabis is helping. Am I, am I banned from all cannabinoids or what can I do? 

Dr. Ethan Russo: Oh, it's a great question. There do seem to be threshold for this. It is possible that someone who has a medical condition that requires cannabis, they might get away with low level use of THC. However, it's really risky. Fortunately, we do not is CHS that commonly in medical users. It really is more common in people who are using high, high doses, so-called recreational users, or people who have developed tolerance to high amounts of THC. The question remains are there other components of cannabis that don't trigger this? The answer right now is we suspect, but don't know. One of the things that we asked a number of the patients with CHS was, have you ever used pure cannabidiol CBD? And if so, what happened? Some people found that they could. Others triggered more episodes. The problem is most CBD preparations aren't pure. And maybe in this instance we use the word contaminated with THC content that could trigger it. And there's another possibility, and that is that nausea and vomiting is very subject to conditioned responses. People may know about Pavlov's dog or during ringing of the bell with food reward, and eventually when the bell goes off, the dog will salivate, even if there is no reward. A lot of people with CHS will know triggers, even if they don't partake of cannabis. So smelling it or hearing about it, things like this can get people nauseated again. 

Trevor: So more like a nocebo effect instead of a placebo effect. 

Dr. Ethan Russo: Sure, exactly. To use the proper technical term. But again, we're sensitive beats, humans. And so there can be these things that trigger a physiologic reaction in the absence of the actual toxicological trigger, if you will. 

Trevor: So unfortunately, if you have CHS, you know, all cannabis products might be off-the-table. But you know, you could try low dose things and or high CBD things and see, but even that might not be good for you. 

Dr. Ethan Russo: And you know, there'd be other possibilities. There are some very pure Cannabigerol products now. If someone had used cannabis previously to treat anxiety, CBG does that very well. We have no indication currently that CBG would trigger cannabinoid hyperemesis syndrome. Its profile is quite different to THC, so that would be possible. And then there are things like both THCA and CBDA are antiemetics. Help prevent vomiting. I think THCA would be problematic because if it's exposed to heat or light, it breaks down into THC. But for example, CBD may be a possibility, although very few people likely have good access to it at this point. And so there are important open questions to whether cannabis could be the treatment as well as the trigger. 

Trevor: Okay. And that and because I don't want run a time, I thought that was excellent, but I wanted to try and fit a second thing in while I have you on the line and want to talk about THCV. So some people might have heard of it, some not. You know, usually if they've heard of it. They've heard of something about diabetes or obesity, because, frankly, everybody in North America is worried about those things. But can you tell us a little bit about what THCV is, some of the potentials and then potential good sides and potential downsides to it? 

Dr. Ethan Russo: Sure THCV is tetrahydrocannabivarin, this is present in Chemovars, chemical varieties of cannabis in low amounts. Very interesting substance, first described in 1970, but not really actively researched until some 30 years plus later. So it has a three carbons side chain as opposed to THC with five carbon side chain and its pharmacology is very interesting. At a low or moderate dose, it's what's called a neutral antagonist at the CB1 receptor. That means that it acts a little bit opposite to THC. So as opposed to the munchies from THC, THCV allays hunger and in testing in both animals and humans, it's shown the ability to positively treat symptoms of type two diabetes and metabolic syndrome. So it may have a role in people with those conditions. Additionally, interesting medical properties as a anticonvulsant and possible treatment for neuropathic nerve based pain. So this is now appearing in some areas mixed with THC. When people use this type of preparation, they tend to tolerate the effects of THC better. So this sort of push pull we see in a lot of pharmacological preparations. So you have something that stimulates CB1 and something that antagonizes it. That may not be really logical, but sometimes that improves the safety profile of the drug. So we see parallels in pharma, same idea being pursued. 

Trevor: And so in a talk I went to of yours. You're also talking about things like anticonvulsant and anti-hyperalgesia effects. So there's it sounds like there's lots of things that the THCV might do. 

Dr. Ethan Russo: Right now there are again chemovars that are predominantly THCV at this point. They're not widespread or available in most areas, but certainly this is a type of selective breeding that we'd like to see pursued in more areas. I really highlights the versatility and therapeutic possibilities for cannabis far beyond THC. 

Trevor: And just because I was an interesting side note and I'd heard you mentioned it a couple of times. So you talked about there being lack of adverse effects because of the inverse agonists of CB1. Now if I'm getting my story straight, one of the drug companies had a anti CB, a an inverse agonist that they thought was going to be fantastic for weight loss and things went badly. Can you talk about what happened there? 

Dr. Ethan Russo: Sure. So the drug was called Rimonabant by Sanofi. Its original name was SR141716A, which is a mouthful. So this was an inverse agonist. This means that it works on the CB1 receptor and actually lowers the gain of the system. Now the endocannabinoid system is a vital homeostatic regulator of physiology. So yes, if you took rimonabant, it would decrease hunger, but it had a tremendous number of unwanted side effects. Specifically, I could increase pain. It provoked anxiety and depression. There was some suicidality associated. It would lower seizure threshold. It could produce nausea. So this is briefly on the market in Europe before it was yanked and it was never approved by the U.S. FDA. However, when this happened, there was a tremendous blowback. There were probably five other companies that had similar drugs in development. That all stopped. It turned off big Pharma to the whole area of cannabinoids, when in fact this was a synthetic agent with a bad rationale from my point of view. In contrast, THCV being a neutral antagonist has none of these liabilities. It doesn't produce nausea, doesn't make him more susceptible to seizures. It doesn't make people anxious. So a very, very different profile, a much more promising drug for therapeutic use. 

Trevor: And then last to wrap up, I'm a little bit over what I promised, but not by a lot. So I thought I really thought the thing on THCV was interesting. So I really hadn't heard a lot about it. But at a recent conference we were both that there seemed to be generally two groups of people. There were people who wanted to go into cannabis, find a cannabinoid, extract it and use it for like we do pharma pharmacies, like we do for all pharma drugs. We take one drug and we take it on one indication. And that's what it does. And then there was, I will call them the whole plant people said, No, no, cannabis has to be used as a whole plant because, you know, things work in concert and the term we usually use is Entourage effect. Do you want to talk just since we just spent time talking about the individual cannabinoid THCV, do you want to talk about the pluses and minuses of extracting in a single cannabinoid versus using multiple cannabinoids as a as in the entourage effect? 

Dr. Ethan Russo: Right. Well, there's a third possibility. I definitely have been a proponent of the entourage effect, the idea that different components of cannabis, the cannabinoids and terpenoids work in concert to create the therapeutic index and a more versatile medicine. For the most part, I feel that while individual components can be helpful, they lack the full panoply of effects that might be desirable in treating a complex medical condition. But the third way is to isolate various components and creatively recombine them, a sort of a deconstruction reconstruction. And this is a way that at Credo-science, we're doing a lot of our formulation work. So it would be the case in a crude extract of cannabis. There'll be some stuff that you don't really need and certainly for pharmaceutical development that complicates things because you still have to show a tremendous degree of consistency in the right ingredients over time. So it is the case if you had different components from different plants, as long as they were all from one species - cannabis sativa. Regulatory bodies like Health Canada, like the US. FDA accept that as a unitary formulation. What you can't do is use THC from the plant and a Linalool from lavender or a different species. That's a combination product and it's a much, much more complicated and extensive approach to drug development. 

Trevor: No, thank you. And there are, you know, at least 100 other things I wanted to ask you, but, you know, I don't have you all day. 

Dr. Ethan Russo: I really appreciate that. 

Trevor: I will absolutely take you up on that. Kirk? So you have gone and grabbed the study and read through it. And what did you think of the actual paper he was sort of describing there? 

Kirk: You know, it's an interesting paper. He talked about a little bit, of course, like like most cannabis studies, they always say we need more, we need more. The survey yielded 585 responders, 205 of those respondents were eligible for the genomic testing that he talks about. Right. So I think the study I mean, I think the study is good. He has 200 people, you know, so he's gone through 200 people to do these studies. 

Trevor: And if I remember, cannabis, cannabinoid CHS, we are going with CHC now because I keep want to say cannabis, not cannabinoid, it is not that common, you know, so the fact he got to 500 people who thought they had it and, you know, he used released and got 200 plus who met all the criteria they're looking for. I don't think that's terrible. You know, 20,000 would be better, but maybe there just aren't that many. 

Kirk: You know what's interesting. It's what do they say? I mean, the two big the two big downfalls of cannabis is cannabinoid hyperemesis syndrome. Right. That's a big one. The other one is that you're going to have a really bad day. And I've never quite understood what that means. People that take too much, they just, you know, they go to sleep. They have a very agitated, very anxious day. But it does not kill you. Now, there is some research that, you know, when you take it as a young person, that's one of the reasons we want to save the developing brains. But again, again, they're the research on that is is depends on how you read it. Right. That is, those are the acceptable risks of cannabis. Right. CHS, having a really bad day and underage children developing brains. What is another risk of cannabis? What am I missing? 

Trevor: I'm sure there is one, but those are the ones I would have come up with. To just circle back to. They found five genes. Now, like you said, this might not be the end all, be all. But I, I think I am not a geneticist by any stretch, but the fact that they, they seem to have five genes they found that seem to be relatively definitively related to CHS. So I thought was just phenomenal. So the first one as a pharmacist made me excited. It was one of the cytochrome P450 is because we like those the CYP2C19, which we've talked about before, because it is involved in in a lot of drug metabolism. And in this case you're genetically predisposed to break down THC or anandamide differently. So that was that was cool. And the other pharmacy one that leapt out at me was I don't know if you he was sort of listing antiemetics or anti-nausea vomiting drugs that didn't work like Ondansetron. Now ondancsetron is a heavy duty stop you from puking drug that we use frankly in, cancer, chemo, cancer patients and other people who won't stop puking. And it's not working on this. But one of the ones that did work was Haloperidol and I like that because it made sense in my little mind. Because Haloperidol, we don't use them that much anymore. But it's an older drug for treating schizophrenia, i.e. it hits dopamine. And he found genes that affected dopamine were related to CHS. 1, a dopamine receptor, and the other a an enzyme that breaks down dopamine. So they just they hit a couple of things that, you know, as a pharmacy go, oh, that makes sense. Now, that makes sense doesn't necessarily mean it's the end all be all but it just it hit those that that that makes so much sense. 

Kirk: Yeah. And what I find fascinating about this study is that it was done in 2021. It was published it was published in 2022 in the Cannabis and Cannabinoid Research magazine. And when you start reading, you know, you go to the Web page of Medical News Today or you go to a Web page from Cedars Sinai. So these are respected medical online medical places. And you look at what are the symptoms of cannabinoid hyperemesis syndrome, and you look at how is it how does this how is it diagnosed and then how is it treated? It's funny to read these papers now these online references. And I think a lot of us in the health care field would go to these online references. And after reading his paper, these online references are dated like they're out of touch. It's like his research for me is it's an epiphany because I've been working. I've been working well, we both have been working on cannabis for the last five, six years of this podcast and researching it. And and this is one of the one of the risks of cannabis. Are you always say, you know, be careful if you take too much. But you know, also as I think I said a few episodes back, I had a contract with Nunavut of it and I was a cannabis consultant for about three or four months. And with my with talking to the people up there, the health workers up there also talking to itinerant doctors. I'm involved with I'm involved with CPAR as well. And I think some of our listeners will remember when I went off to Ethiopia. Well, one of the doctors that's affiliated with that organization, we were talking also one day about his experiences and Nunavut. And he and and when I explained to him that I'm doing this podcast, he says, you know, in Nunavut, I have never, ever dealt with so much CHS, so much cannabinoid hyperemesis. Like he said, it was every day people coming in and I'm thinking to myself, you know, Nunavut and small communities, small family trees, you know, I mean, I'm sure if you go back 100 years, the you know, people are uncles and aunties everywhere. I'm wondering if this paper is not a paper practitioners who work and none of it should not be reading, you know that that this is genetics. If it's in your genome to be susceptible to this. This could explain when communities of people seem to be ravaged by this, by this syndrome. Does that make sense? 

Trevor: Or at very least if we get some, you know, geneticist or, you know, frankly, what with all of the genetic testing available right now, it would be very interesting to do sort of genetic sampling across various communities and Nunavut and go, you know, see if, you know, these five genes being out-of-whack is sort of more common in Nunavut than it is other places. And you know, that that might be a very in the grand scheme of things, in medical testing, a relatively noninvasive, inexpensive way to possibly save a bunch of suffering. 

Kirk: Well, you know, if I was if I was doing a master's, and I was interested in cannabis, this would be an interesting master's paper to the find communities of people through the genome to see if they're more susceptible. The plant's Fascinating.

Trevor: And he explained it better but just yeah, sorry. I did want to mention that that Sanofi drug, it was just cool because it came up a couple of times was this artificial cannabinoid synthetic. I know, I try not, but anyway that was, was working against the CB1 receptor to you know, help people lose weight and they did, which is great. But you know, then they, they start getting depressed, they start having suicidal ideation, they started having more pain, they started having seizures. So it was just a really powerful reminder of all the things the endocannabinoid system touches on and muck around with it at your peril. Or at least think about it a little bit more. So, you know, just I guess a point for the plant people is the you know, the cannabis, the cannabinoids that come out of the plant seem to do a better job of fine tuning the endocannabinoid system. Whereas if sometimes if we just take one receptor blocker we can, you know throw the endocannabinoid system into a tailspin. 

Kirk: Couple of things I want to just quickly go over here and this is from his study. So these are the appendix to the study and the questions, the yes and no questions he was asking people. Now, these are people that have been diagnosed as having cannabinoid hyperemesis syndrome. And the question is, if you have suffered severe nausea, vomiting and abdominal pain, were the conditions improved by taking a hot bath or shower? 100% said yes. So, you know, have you ever been diagnosed with cannabinoid? 100% said yes. Now, how long did you have the symptoms before you were diagnosed? A year. 60% of them had these symptoms for a year before they're diagnosed. 

Trevor: Yeah and just throw it in there. Just talking to him off camera on a different thing. He was just saying, yeah, sometimes it was things like, you know, that the spouse, the significant other said we spend more on our hot water than we do on rent. Go get yourself checked out. Yeah. What, You spend a three hour shower every day? No, I don't. Yes, you do. So it's denial is not quite the right word, but, you know, there seems to be something going on that there's not a lot of self-awareness of this condition for quite a while. 

Kirk: Well, what do we call cannabis? The the great the demotivator. The great distractor. Right.

Trevor: The great distractor, for sure. 

Kirk: Yeah. But I just find these fascinating numbers. Right. How long how long does symptoms last? 6% for over a year. And I think I think for Mount Sinai or Cedars Sinai. They also say one of the criteria is you've had this for over a year, but in that year, a lot of these people spend a whole lot of money on treatments. Yeah. You know, and then they say, how long do the episodes last? Several days. 70%. 69%. Several days. 

Trevor: Yeah. Can you imagine if you've got something that that's causing you to puke for several days at a time. 

Kirk: No. 

Trevor: And it's taking over a year to figure out what that was. 

Kirk: Yeah, well, but then, then the other one did they. And did the condition improve after you stopped using cannabis. 89%. Yes. 

Trevor: Yeah. Yeah. 

Kirk: You know, so sometimes people, sometimes cannabis just isn't for you, right. You know, so and again, if this is something you suffer from, go get, go get the test. Now, did he talk any more about the test at all. The, the. Yeah. 

Trevor: He mentioned it in there. The easiest way if to go to what-is-chs.com and that's sort of where that I didn't probe into you know how much it costs you can you get in Canada or all of those kind of things. No I didn't I didn't get into that. 

Kirk: Okay. Because I'm wondering because I say, you know, if someone's interesting doing a study on this, this would be very cool. I good interview. And I found it fascinating. And I hope I listeners did too. It was one of your real dense ones that yeah. You have to listen to it very closely and it's nothing like talking through a bright person that just goes on about something like intuitively and you're going, Whoa, whoa, whoa, whoa, whoa. Slow down, slow down. Let me catch that. What did you say? What you say. 

Trevor: Well, it's one of the good things about podcasts. We got the rewind button. 

Kirk: Yeah, yeah, yeah, yeah. Press rewind. Anyways, thank you for that. Is there anything else we got to add? Like, do we have anything else to add? 

Trevor: I don't have anything else that. Oh, I'm Trevor Shewfelt I'm the pharmacist. 

Kirk: Right. We have to introduce ourselves. I'm Kirk Nyquist. I'm the registered nurse, and we are Reefer Medness - The Podcast. 

Trevor: We are. 

Kirk: We are. We still remain to be Reefer Medness to podcast. 

Trevor: All right,. 

Kirk: All right, man, that was a good one. Another good one

Trevor: Yeah. Talk to everyone later. 

Rene: Okay. It's Rene back here in the studio. That was another good one. I'm just here to wrap a few things up. One thing we like to do, of course, is in as many podcasts as possible to acknowledge that we produced the shows on Treaty two territory, which is the homeland of the Metis. And we pay our respects to the First Nations in Metis ancestors of this land and consequently reaffirm our relationships. One interesting thing over the summer here was the Dauphin’s CountryFest Festival, which happened recently. It's always such a great time and so many stand out acts, and it's always nice when Dauphin local or Parkland, Manitoba, acts perform. And one of them that performed this year that Kirk took in was Nelson Little. And so that's with this song we're going to go out with. The song is High Road by Nelson Little. Thanks for listening. Make sure to check out the website.