Bowel Moments
Real talk about the realities of IBD...On the rocks! Hosts Robin and Alicia interview people living with Crohn's disease, ulcerative colitis, or indeterminate colitis (collectively knows as Inflammatory Bowel Diseases or IBD) and the medical providers who care for our community. Join us to meet people affected by IBD- we laugh, we cry, we learn new things, we hear inspiring stories, and we share a drink.
Bowel Moments
Meet Dr. Colm Collins!
This week we spoke to Dr. Colm Collins! Dr. Collins is an Associate Professor at the Conway Institute of Biomolecular and Biomedical Research at University College Dublin. He shares his journey from the world of pharmacology to pioneering research in inflammatory bowel disease (IBD). You'll learn about the innovative approaches his team is exploring to revolutionize treatment options for IBD patients. With a blend of humor and expertise, Dr. Collins offers a rare glimpse into the challenges and triumphs of translating scientific breakthroughs into real-world health solutions.
Our conversation unravels the intricate relationship between the immune system and gut bacteria, as Dr. Collins explains how retinoic acid and microRNAs play crucial roles in managing IBD. We delve into the promising possibilities of replacing lost proteins and the therapeutic potential of cannabinoids, exploring their implications on both the immune system and the digestive tract. Amidst the science, we tackle the ethical and legal complexities of cannabis research, particularly in adolescents, as Dr. Collins shares his experiences navigating these challenges with integrity and humor.
Join us for an enlightening discussion that balances serious scientific inquiry with light-hearted anecdotes, as Dr. Collins recounts his experiences in Colorado and discusses the future of IBD treatment. From the nuances of cannabis use in managing IBD symptoms to the exciting potential of selective human receptor-modifying peptides, this episode promises to expand your understanding and offer hope for more effective therapies on the horizon. Plus, enjoy a humorous account of altitude adaptation and its quirky effects on newcomers and the unexpected twists in cannabis research funding.
Links:
- Journal article: Manipulation of the Endocannabinoid System in Colitis: A Comprehensive Review
- Journal article: Adherence, Safety, and Effectiveness of Medical Cannabis and Epidemiological Characteristics of the Patient Population: A Prospective Study
- Information on medical cannabis and IBD: Crohn's & Colitis Foundation- USA
- Research funding opportunities- Crohn's & Colitis Foundation- USA
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Hi, I'm Alicia and I'm Robin and you're listening to Bowel Moments, the podcast sharing real talk about the realities of IBD Serve on the rocks. This week we talked to Dr Colm Collins.
Speaker 1:Dr Collins has a PhD in intestinal immunology and is currently an assistant professor at the Conway Institute of Biomolecular and Biomedical Research at the University College Dublin. Prior to that, he was an assistant professor at the University of Colorado. He is a research scientist working on finding new treatments for inflammatory bowel disease and has a special interest in cannabis. That started with his time in Colorado, so we talked to him about doing research in cannabis. We talked to him about getting research funding and the challenges there and the support he received from the Crohn's and Colitis Foundation. We talked to him about translating science for lay people and patients to help educate them on all the exciting things that are happening. We talked to him about what's on the horizon and what might be new in inflammatory bowel disease treatments, and we talked to him about what it's like working with animal models of inflammatory bowel disease. Dr Collins is a laugh riot, so we really enjoyed our time with him. We know you will too, cheers.
Speaker 2:Hi, everybody Welcome to Bowel Moments.
Speaker 1:This is Robin. Hey guys, this is Alicia, and we are absolutely delighted to be joined by yet another international guest. I am very excited to talk to this person, Dr Colm Collins. Welcome to the show.
Speaker 3:How's it going? Nice to meet you.
Speaker 1:Nice to have you on the show. So we are going to get to you and who you are and get to know all about you very, very soon. But our first very unprofessional question for you is what are you drinking?
Speaker 3:Well, despite the fact that I'm Irish and I didn't want to push the racial stereotype too far, I'm actually coming down with a bit of a cold, so I figured hot whiskey is the way forward. So I've got a whiskey with some lemon. Lemon's obviously full of vitamin C and that's very good for boosting your immunity, fighting infection. And then it's got cloves studded into it and again the cloves provide that analgesic effect but also help clear my throat a little bit so I can talk to you guys more comfortably, and obviously it's mostly hot water. Then, after that, we had a small dash of cooking jams.
Speaker 1:All right, that sounds good here's all. Yes, robin, maybe you need that, maybe I do, maybe I do.
Speaker 2:I am having coffee, but while we were doing the setup, I had my husband, matt, swing in here and put a splash of bourbon in it, so I'm having a little coffee with bourbon.
Speaker 1:I am also having bourbon Robin. Hey, here's a bourbon cinnamon simple syrup, old-fashioned.
Speaker 3:I love that you should stick a couple of slices of apple in there. A couple of slices of apple in there.
Speaker 1:you're away there you go, I might have to run downstairs real fast and put some apple in there. But well, cheers guys.
Speaker 3:Cheers.
Speaker 1:Dr Collins thank you so much for being on the show. Next question for you Tell us your IBD story. What made you become part of this community?
Speaker 3:Well. So it obviously started when I went to college. So someone suggested to me they're like you know, if you're going to go to college, you really should experiment with drugs. And so I said, okay, fair enough, makes sense. Studied pharmacology and absolutely just loved it. You know, I was fascinated by. You know how complex it was making drugs and how to get them to where they need to go and then how to make them do what you want them to do. So I did that and I loved it so much that I stayed on and a PhD in GI diseases. So looking at it sounds pretty glamorous, but I was looking at cramping and diarrhea in chickens and at that point I thought, right, well, Wait, that's what makes it glamorous.
Speaker 2:It's specifically that it's chickens.
Speaker 3:I didn't mean to interrupt you, but I had to, like I mean so chickens are constantly infected with stuff like salmonella and campylobacter, bacteria that we would normally get really sick from, and yet they're somehow completely immune to it. So we really wanted to understand how they managed to do that. But, like I said, it sounds pretty glamorous. But then so at the time my then girlfriend she's now my ex-girlfriend, or my wife, as I like to call her so my wife she was working in Baylor College of Medicine and she said, oh, you should come out here and you should interview for a job. And cause she's like I really like it here and it's amazing, and you know it is, it's an amazing center for research. But I met with a very nice gentleman called James Rusalovich who's at Texas Children's and he said look. He said you know, it doesn't matter where you work in the in the U S, you're going to Texas and the only downside of living in Texas is you've got to go from your air-conditioned house to your air-conditioned car to your air-conditioned place of work. And I thought, brilliant, I'll go look at a job in Colorado, because that's kind of halfway between the two. And so I did. So I interviewed for a job in Colorado.
Speaker 3:I worked for a physician scientist called Jesus Rivera Nieves and he was amazing. He was working in the lab four days a week and then seeing patients on the fifth day, and it meant that he was really, really at the coalface in terms of looking after patients with pretty severe IBD. So you know it was a referral center and so they were getting all the worst possible cases. So, jesus, his enthusiasm just blew me away, like he couldn't help but get excited about it. To a certain extent it was like being locked in a room with a really bouncy ball. You know that you're constantly kept on your toes. You're kind of forced to get better, forced to move quicker. You know you're probably going to come away with some bruising, but yeah, generally I'd say it was easily one of the most enjoyable periods of my life. You know, working with people like Owen and Josh and Megan and Matt, it was just amazing.
Speaker 3:And I just got engaged with this IBD research process and then from there I got a research fellowship award. So that was from the Crohn's and Colitis Foundation and they're incredible. They can just kind of suck you in, so you get funding from them and then they say, okay, we gave you some money. We'd like you to spend that to come to a meeting that we're hosting. And so you go along to this meeting and it's amazing.
Speaker 3:It's like the Oscars for IBD research. It's like all the big names from clinical research, from translational research, you name it, and these people are just hanging out, having a couple of drinks, having a chat and they're saying, oh yeah, you're doing that experiment. Well, here's the 10 ways I've tried it and here's the way that might work best for you. And it just cuts down so much on the learning curve, it just makes it so much easier and it just really accelerated my research and it just I loved it. It was amazing. And then the other thing that's nice about the foundation is that they're so engaged in patient education and patient engagement that as soon as I got back to Colorado, having you know.
Speaker 3:I'd obviously been on someone's radar and I got a call from our Rocky Mountain chapter from a young gentleman called Jeremy Stern. So Jeremy was like he's like five foot five, ginger hair, but he's got his personality. That's like the size of the mile high stadium. Like I don't mean ego, I mean personality. This guy was just insane. He would, he would have you doing stuff and you kind of felt like you know he was doing, you were doing him a favor, even though you were coming away with way more than what you put into it. You know, like he'd say, hey, colm, you know we'd like to host a lab tour, so we'll have people come around your lab, is that okay? And the next thing he'd show up with 30 people, he'd be fully catered, he'd be all organized, everything done. And you know we'd give a little bit of a tour and explanation. And you know that doesn't fail. When I do it it'll fail by the time it gets to the clinic pretty much 90%, but anyway. So realistically I'm looking at this going. I don't know if I want to see the faces of the people who I'm constantly disappointing. You know I get enough of that at home. So even still, I was like okay, I'll do this. And I was blown away because I met people who had lived with this disease and they didn't need sympathy or support or they were just rocking it Like every day was a new day and they were super excited. They were like, oh cool, you know, it's great to see people working on this. And you're like, wow, I'm really bad at it. And they're like, no, no, that's fine, like at least you're trying. So you know, for me were like, oh yeah, I've tried this, I've tried this, I've tried this. This kind of worked, this only kind of worked sometimes. But it also gave me this which I never thought I would get, and I was like, wow, geez, I'm like a taken notes going. This is immense. Like you know, the books don't tell you all of these patient experiences and how these drugs actually make you feel, as opposed to just, this is a percentage drug in this context. So for me that was huge, all right.
Speaker 3:So then research, fellowship that went really well. I was happy enough. Like I said, it was probably the most productive time of my career. I had no kids, it was easy, things were nice. But then again, where the foundation really kind of steps up is, so they supported me for what's called a career development award, so that was about 2012.
Speaker 3:And we're talking big money now, right, so this is like $300,000 for a three-year research grant and in and of itself, that seems like a huge investment for relatively little return in terms of I'm a one scientist, one-stop shop. But actually the way it works is it's much smarter than that. So what they do is they have you apply for this funding and then you get feedback, and the feedback's coming from people who are absolute experts in the field, right, and so they can tell you here's all the things you're doing right, here's all the things you're doing wrong, here's the reasons why it's good, here's what's bad about it, here's how you can make it better. And so the feedback you get it's not like oh yeah, we're not giving you the money. End of story, best of luck, goodbye. Instead you get then is you know, it makes you way more competitive at a kind of national level, because you've had this kind of incubator system where you're being coached and corrected and prodded and poked and got into the right kind of areas, which meant that when I went to look for NIH funding you know that was I mean I don't want to say it was easy, right. So the funding rate's probably about 20%, but still I had a huge advantage going into that because I'd already gotten the support from the Crohn's and Colitis Foundation. So I walked in, got that and now all of a sudden their $300,000 investment turned into three quarters of a million of federal dollars to spend on the same problem. Right, we're still dealing with treating IBD, but now all of a sudden we're getting federal dollars to do it instead of just foundation bonding. So you're basically looking at taking every dollar that the Crohn's Colitis Foundation invests and that converts to $3.50 if you include the federal funding. Except that I was even able to give back some of the money that the foundation sponsored into the final year because of overlap with the new grant. So that was huge. That's not just great from an IBD community perspective, that's just great business end up and through that, because I was involved in that stage.
Speaker 3:Then I got involved with people within the foundation who were really keen to kind of help progress careers of junior investigators, help to disseminate knowledge and break down barriers to communicating or collaborating with people within our field. Like that's normally a difficult thing to do to walk up to someone who you idolize and say, hey, can I get you to come to my lab and help you with my research? Whereas, because the foundation just cuts through all that kind of hierarchy and says we just want this to happen, we want the results, we want it now, we want you to focus on getting this done. It just breaks down all that kind of resistance and it makes the process so much simpler. So I remember that there was a VP of research at the time called Marjorie Merrick, and Marjorie was just this incredible person to watch. So it was like watching this majestic lion just parading through the savannah, right, on the one hand, she's incredible to watch. Right, she's incredibly efficient. She just cuts through all the nonsense, gets things done, breaks it all down, but at the same time, in the background, in the back of your mind, you're thinking I never, ever want to be on her bad side. You know what I mean. So through that process then I had, you know, people coming out to our lab. You know, meet someone who's at the foundation meeting, and they go oh yeah, no, we're doing this experiment all the time. You know, don't waste your time learning how to do it. Why don't you just fly out to North Carolina We'll show you how to six months and this kept happening the whole way through and it was all because the foundation just put us together.
Speaker 3:I wouldn't say that's their only job, because obviously they do a lot in terms of patient support and patient education. And we see that and they do a ton of work in terms of physician education right, because things are changing so fast within the field. New drugs come out, but also the drugs that we already have. We're changing the way they get used. We change the order in which you use them and who gets what. Then that's all changing all the time and they really make sure that physicians who are on the ground you know PCPs and you know referral centers and stuff all have the same level of knowledge when it comes to what the best kind of case scenario is. And actually I saw you had Alan Moss on your show last week, so I obviously want to mention that because Alan's actually an alumnus of the Conway Institute, where I work in UCD. So clearly you know he was trained in the Conway so he knows how to operate with a fairly constrained budget.
Speaker 3:So I would say, if you're feeling being supportive, especially this holiday season, if I was putting smart money, I would invest in that foundation, not just because you know, I think it's a great effort, but also because I think it's where the smart money goes, like, even if you hate, if you absolutely hated people who had inflammatory bowel disease, right, and all you cared about was this is the most expensive disease there is and I want my insurance premiums to go down I'd stick my money on the foundation simply because you know that when the time comes that a cure is found, they'll have their fingerprints all over it.
Speaker 1:Wow, I'm pretty sure that anybody who hates Maybe they hate listening, maybe they're trolling us, I mean a download Alicia.
Speaker 2:a stream is a stream. We need the numbers, that's right.
Speaker 1:We'll take it. So funding is limited. So how do you prioritize what you're going to research? I mean you started out with chickens. Obviously that involved it. How do you prioritize what's going to be the best way to use limited resources?
Speaker 3:So for me there's always been a theme right. So intestinal disease is a really tough target because there's no all or nothing, right, you can't shut it down completely, your intestinal immune system, because there's a kilogram of bacteria in there. They're just waiting to break down the barrier and invade and cause damage and cause infection and stuff like that. So you can't shut it off. You know, like if you've got an infection in the eye you can quite easily say, right, let's just blow this wide open, kill every single living thing. That's not eukaryotic and it'll be fine. But you really can't do that in the gut because then it affects digestion and it affects everything else. So for me I've always looked at ways to just modify existing pathways. So know, we started with retinoic acid, looking at how vitamin a can in effect immune activation and immune and immune cells traveling into the gut. You know, as a way to say, right, well, if we can shut that down or turn it down a bit, we'll still have natural immunity present in the gut. But now all of a sudden it's not quite as rapid and so then that's spread into. You know, targeting microRNAs. So microRNAs are just really short RNA sequences and they're perfectly designed. I mean, this is literally what they're designed for. They're not on-off switches, they're just dimmers on an existing system, right? So they're just designed to tweak things up and down in a very kind of controlled manner.
Speaker 3:And so we did a study a few years ago where we looked at a specific micro RNA called Mira106A. They're all named for reasons I don't know, but it was a perfect target in that we know it's increased with IBD patients, it's increased in the gut of an IBD patient. We know it responds to TNF. So TNF, or tumor necrosis factor, which is what, like Remicade and Humira and Simsia, they're all designed to target TNF. So we know that's important. And also we know that it suppresses natural or anti-inflammatory cytokine called IL-10 or interleukin-10. And so the idea was okay. Well, if it goes turned on during inflammation and it suppresses anti-inflammatory signaling, then all we have to do is silence it and we can hopefully develop a treatment. And it worked really well in mice. Now those mice never thanked us for curing them, but we did all the time. So we cured it a couple of different ways. We cured it, we knocked it out, we deleted it genetically and then we also used a lentiviral vector to silence that specific microRNAs or microRNA. Problem in reality is that the delivery of those drugs is very difficult, so it's not certainly ready for clinical use, unfortunately.
Speaker 3:But like again, the theme kind of stuck with me that I liked this notion of taking endogenous systems and making turning them up or turning them down, rather than turning anything on or off. So from there then I switched to looking at excuse me, alpha-1 antitrypsin. So this is another protein that you find a lot in your bloodstream and we saw that patients were losing a lot of it. You know. Same with lactoferrin. So lactoferrin is another one where you know this was used as kind of a biomarker is oh, you know, we can measure lactoferrin in your stool and see how much you're losing and that tells us how much bleeding internally you are or you have going on within the gut and how absorptive your, your colon is and how you're covered, how you're coping really with your inflammation. But that's all people thought it was. They were like oh yeah, this is a good biomarker, but that's it. And I kind of went well, hang on, if you're losing a ton of it and it's kind of important, what about we put it back? Would that be helpful? And so again, that's what we did. We said, right, well, we made with a friend of your drug, but we stuck that into mice. And again same thing. We made them totally better. Again, we've patented that. We haven't moved it into clinical trials yet, but the hope is that at some point we'll get there.
Speaker 3:And then, most recently, I switched gears a little bit and I started working on a drug you've probably not heard of, called cannabis. And so cannabis actually the reason why cannabis does anything is because our body has a natural what we call endocannabinoid system, right? So there's a system within our body that responds to chemicals that our body produces, called endocannabinoids, like anandamide and 2-AG, and these are natural signaling molecules within your body and they can turn stuff on and off and they can affect your nerves and they can affect stuff on and off and they can affect your nerves and they can affect your immune cells and they can affect a whole range of different aspects of your body. And that's kind of what cannabis plant hijacks. It kind of hijacks that system. So anandamide, for example, it comes from the Sanskrit for blissfulness, because it gives you that like warm, kind of fuzzy feeling.
Speaker 3:So they often say that people who runners, runners who like go running for whatever. I don't know why. It just blows my mind. But if you're into that sort of thing, runners get this weird high from running. I think I don't think it's just like a sanctimonious I'm better than you kind of thing. I think it's a.
Speaker 1:It is a physiological response and that response might be a little bit of sanctimony in there too probably a little bit of both, I would have to say yes right?
Speaker 3:well, basically they, they produce increased levels of anandamide and that's what gives them that blissful feeling, that's what makes them feel good. And so we were interested in cannabis because I was working in Colorado, which you may or may not know is one of the founder states when it comes to the green, the green rush, but we were. I was working specifically in children's hospital in Colorado and we had, I think, a third of our adolescent patients. So there was a study by a colleague of mine, ed Hofberg, and he showed that a third of patients who are kind of 13 and up were using marijuana. And we were like, oh, that's huge. So we wanted to understand, first of all, why, why on earth would you use this? And, second of all, what's beneficial, because if it is great, we can certainly engage that. But really we just wanted initially to understand what's happening. And so it turns out there's a lot of good reasons why you might want to use marijuana, right?
Speaker 3:So for people who have intestinal disease, which is often associated with gut pain or visceral pain, in fact, it's the number two cause of intestinal pain there is, after gastroenteritis, where you've got an infection. Ibd is the second most common cause of visceral pain right and that's pretty severe. And the problem with pain for patients with IBD is that you can't treat it. You can't treat it with aspirin or ibuprofen because those drugs cause more tissue damage. They prevent that protective mucus within your gut from forming and that makes disease worse, and so that's a no-no. At the same time, opioids not really a great option either, because you've got, you know, that affects bowel motility, so you're susceptible to getting things like toxic megacolon, which sounds like a transformer but it's actually. It's actually pretty severe. Definitely want to avoid that. But overall, you know, and it's addictive and you know there's and you're at risk of getting this kind of hyperalgesia where basically the more more opioids you use, the more pain you feel, and so there's a lot of reasons why you want to avoid that.
Speaker 3:And we know from studies by a guy called Daniele Piemelli. He showed a few years ago that if you prevent the breakdown of natural cannabinoids within the body, that you get a decrease in this visceral pain. So you can actually suppress pain with cannabis-like compounds, and so the same is true if you use marijuana. It looks like you can certainly suppress that visceral pain to a certain extent, which is totally understandable. And if that's all it did, I would advocate wholeheartedly for people to use it, but it's not all it does.
Speaker 3:So another nice feature for cannabis, if you're interested, is it increases your appetite, right? So we know this. You know people go for the munchies and think this is a great thing, and to a certain extent, for IBD patients, I want to say I don't want to say it's true, but they're not wrong. So there's a big issue with people who have IBD that they don't want to eat. Because if you're having bowel movements 10 times a day and everything you eat comes with a side order of visceral pain, then you're inclined to eat less often. That sounds like a pretty poor deal. The flip side of that is, if you can eat more and improve your appetite, then that helps you boost your immune system, it helps you fight infection, it helps you control your disease a bit better, it helps to manage your stress levels. There's a whole load of benefits from eating more and from recognizing that you've got a decrease in nutrient absorption. So, if anything, you need to eat even more than a person who's not suffering from intestinal disease.
Speaker 3:There was a paper, actually a guy called Mark Garrick, who's a former colleague of mine and he's not the only author on the paper, but anyway, mark's the first author on this paper, but it's basically a clinical. It was from the Red Journal. It was a clinical paper looking specifically at how cannabis is beneficial or not for IBD patients, all right. So they talked about it in the paper. They talked about the pain issue, they talked about appetite, but what they didn't really talk about was intestinal inflammation, right, and how it affects that. And so for me that was obviously that's super important because you know, yay, great, if you can get rid of the visceral pain, that'd be brilliant, so long as it's not doing more harm than good.
Speaker 3:And so a few years ago there was a couple of studies by a really talented scientist called Timna Naftali, and so Timna showed that she did two different studies now quite small studies, but in two studies using either cbd or cannabidiol or thc, which is one of the other active ingredients of cannabis that patients who use marijuana for two weeks and had crohn's disease saw a significant reduction in pain, a significant decrease in motility and bowel movements, but what they didn't see was any kind of improvement in their uh, what we call kind of empirical measures of disease right. So whether it was in the blood or in their stool or you know anything empirical measures of disease, right? So, whether it was in the blood or in their stool or anything where there was no question about it, and so that was kind of a red flag to us that it didn't seem to be having a protective effect. But again, that's fine as long as it's not doing any damage.
Speaker 3:Except that a couple of years later there was a paper by a Canadian group, by a guy called Martin Storr, and what Martin showed was actually that for patients who were using cannabis for six months or more, their likelihood of having surgery went up five times, five fold, like five times higher. And that's huge. Now you'd argue that, okay, maybe this. It's skewed in that people with probably more painful and more severe disease might be more likely to use cannabis. And this wasn't a prospective trial, wasn't like hey, if you're, you want to, you know, enroll. This was just kind of a retrospective study, looking at people who use cannabis and looking at whether or not they went on to need surgery. But even still, a five-fold increase in surgical risk is huge, right. So that's a big deal. We always think of surgery as being kind of the worst case scenario. So anything that inflects the results, that much it's got to be very-.
Speaker 2:Wait, I have to stop you right there. I have to stop you, surgery is not a worst case scenario. It is a treatment option. I just want to put that out there. We always say that on the show. We've had several surgeons on here, so surgery is not a worst case. Last resort.
Speaker 3:Actually there was a paper from a group in the UK who recently said that actually, especially for ulcerative colitis, that surgical intervention early, like almost immediately, was probably the best outcome for patients. But sorry, I'm specifically talking about Crohn's disease in this case. But yeah, so avoiding surgery seems like a good option. And so that made us kind of work on what's the cannabis doing at a cellular level that's changing this disease susceptibility, right. So we started looking at T cells, which are a subset of immune cells within the gut that are known to not only make the disease worse but they persist and they last a long time, and they're the ones that kind of cause the chronic nature of the disease. And so, even if the disease goes away and those t-cells move out of the gut and they move off somewhere else, they'll go to the, to the joints, and they'll cause all right, you know, arthritis type pain. Or they'll go to the eyes and they'll cause inflammation of the eyes, like uveitis, or they'll cause skin diseases like pyoderma gangrenosum or erythema nodosum, diseases that we always associate with IBD but are kind of triggered by the intestinal disease. They're secondary or what we call extraintestinal manifestations, right, and so that's all driven by T-cells and a kind of memory that the T-cells maintain. And so what's all driven by T-cells and that kind of memory that the T-cells maintain? And so what we found is that if we take cells just in isolation and we stimulate that cannabis pathway within those cells, then our cells develop the munchies effectively, right? They start sucking in sugar like they can't stop. They just take on a load of sugar and it completely changes their outlook, right? So instead of doing what they're supposed to do during infection, which is they proliferate a load, they get loads of T-cells, they kill off the infection and then they die.
Speaker 3:Right, that's what you want. You want a system where, if anything goes wrong, the response is really fast. You get this massive immune cell activation, those immune cells totally engulf whatever infection arrives and resolve it, but then they die. And the last part's just as important, right? You still want them to die because you don't want them to survive, because they'll only go somewhere else and do more damage, right? They're like English soccer fans. So really, what you want to have happen instead is you want them to divide and proliferate but then die off, and unfortunately, because of the cannabis, because they take on so much sugar and they start reducing proteins that will allow them to survive much better and much longer.
Speaker 3:Now, all of a sudden, you've got this immune system that can last and last and last, and so if it's triggered inappropriately, like we see with patients who have IBD, it will persist and it will reoccur, and so those patients might feel fine initially, but when their next flare comes they've got more T-cells on board already that are primed and ready to go, and they will just trigger this much more severe flare up when the second infection comes, and that's already part of it. So it turns out your T-cells also have signals that send it to different locations, right. And so we've seen drugs like vedalizumab, which is a drug that targets T-cells from trafficking into the gut, and it does so by blocking this integrin or surface protein called alpha-4-beta-7. And so we know that's really important for gut homing, because if that, elizabeth works and it works in about 20% of patients then that pathway has got to be important, right. And so one of those kind of side effects that we saw when we started stimulating ourselves with cannabis-like compounds is that now, all of a sudden, that integrin, that alpha-4-beta-7, starts coming up a lot, much higher than normal than you would see on normal immune cells, and that's a problem too, because that means now you're shifting more cells into the gut.
Speaker 3:It's a double-edged sword, because in one way it helps us to understand how is it that in other diseases it looks like cannabis might be anti-inflammatory, right? So if you've got arthritis or you've got MS or you've got something else, it looks like it's protective and it's anti-inflammatory. But it could be. What's actually happening is it's driving your cells into the gut and once they're in the gut then your other diseases might calm down. But now your intestinal disease is primed for when the next infection comes.
Speaker 3:And certainly there's evidence that we've seen from monkeys.
Speaker 3:So there was a study looking at kind of a monkey version of HIV and what they found is if they gave monkeys marijuana and it meant that their disease went way down, so their viral and viral loads dropped off significant, because what was happening was all those t-cells were being forced into the gut and, as a result, were controlling the virus much better, because that's generally where hiv lives. So yeah, so basically there's we think we see the same thing, that we can and, more importantly, we can now start blocking that pathway. Right now that we know kind of the cannabinoid pathway is important in the immune system. What my lab is working on now with our collaborator, a guy called Dave O'Connell. We've developed what Dave, for reasons I don't understand, calls SHRIMP. These are selective human receptor-modifying peptides, or SHRIMP. But the point is, the plan is that they will target the cannabis system and they will start to reverse those kind of symptoms and stop T-cells from going to the gut and stop them from persisting. So that's kind of where we're at.
Speaker 1:So out of curiosity for the other disease states like, say, you have multiple sclerosis and you're using cannabinoids to control your MS, but it's driving all the T-cells into the gut. Do we then see people who end up with GI issues?
Speaker 3:Not necessarily, because if you think about inflammatory bowel disease, you've got to have a whole bunch of risk factors combined together to actually develop the disease. So, for example, it's not enough that you've got the right genetics to develop disease, because we know that twins, they're only about 40% likelihood of them both having it. It's not enough that you live in a developed country, because obviously there's a whole bunch of people living in developed countries who don't develop it. But equally we know that if you live in sub-Saharan Africa, the chances of you developing IBD are also pretty low. So it's obviously there is an environmental factor. We just don't fully understand what it is. And then we know that there's a trigger. So it doesn't matter what the trigger is, whether it's butt chugging, alcohol or a viral infection or whatever it is. Any of those things can trigger disruption of the intestinal barrier, which allows bacteria to get across that barrier, and that triggers an immune reaction.
Speaker 3:So there was an amazing study by a scientist in the UK called Fiona Perry a few years ago and she tested every single T cell that patients and control individuals had within their gut and the idea was that they expected to see that people who had IBD would have this group of immune cells that were recognizing a specific thing right, so that they'd had one particular infection that all the IBD patients had all been exposed to, and it was what triggered their disease and that's what made them different from regular people.
Speaker 3:And it turned out that that's not true at all, that the things that an IBD patient's immune system sees are exactly the same things as someone who doesn't have IBD they see exactly the same things, their T-cells are identical and the only difference is how they respond, where they could respond and say I see this, it's fine, I'm not going to freak out, it's not like a peanut allergy that I need to lose my mind over it. Instead, ibd patients automatically see something and think oh my God, this is terrible, it shouldn't be here. I've got to trigger this huge inflammatory response and I've got to clear out this is something that's totally safe and normal. But yeah, so driving cells into the gut alone is not enough. To trigger intestinal disease is the long-winded way of saying that.
Speaker 1:Thank you. I appreciate the long-winded explanation. Right, thank you, I appreciate the long-winded explanation. I definitely have questions about the butt-chugging alcohol comment. We're going to come back to that, I think. Yes, we're going to come back to that one. When you've been doing this research, have there been any differences in how it's consumed Smoking versus edibles, versus? Is there a difference? Because obviously we know that cigarette smoking is not good for people with Crohn's disease, but yet some people with ulcerative colitis it can be somewhat helpful for them. So how does that work?
Speaker 3:Yeah, so it's a really tough one, right? So first and foremost, we'll talk about the cigarette smoking issue. So this was done with adolescents or kids in children's hospital and so we very much discouraged them to smoke. But that said, there are yeah, so there's huge difference. So we were struggling in that we couldn't power studies big enough to look at the difference specifically between, let's say, oil and edibles and vaping, which would be the three options I think that we would probably reach for.
Speaker 3:I do have a fun anecdotal story about a patient who was vaping marijuana. Although it turns out so, it's not advisable, it turns out again, not having known this, it's not advisable, if you're immunosuppressed, to vape your homegrown marijuana, which is a very specific problem to have. So the reason I say this is because we had a patient who was vaping his marijuana and obviously vaping doesn't heat up marijuana as high as, say, smoking would, right, so you're not burning anything, so you're heating it to a much lower temperature and actually the temperature that you heat it at changes the phytocannabinoids or the chemicals that come out of the cannabis, and so some of those are anti-inflammatory and some of those are probably pro-inflammatory and some of those are kind of inhibitory and some of those are stimulatory. So it gets really tricky. Like there's 106, I think different active ingredients in a regular cannabis plant, which is another reason why medicinal marijuana is a bit of a nightmare, right, because it's not really practical. It's not just that, say, some of the components are pushing one way and some of them are pushing the other way. There's what we call allosteric modulators, so there's drugs within the cannabis plant that don't even target the receptor that triggers cannabis responses, but it binds somewhere else and it changes the kind of structure of the cannabis receptor. And now more else, and it changes the kind of structure of the cannabis receptor and now, all of a sudden, drugs bind better or they bind less, more weakly, like it's. It's way too complicated to find any real therapeutic benefit from a plant like that. When there's you know, there's 106 different things pushing in different directions, it's very hard to find which one is being beneficial, which one's not.
Speaker 3:But yeah, so he was immunosuppressed, which is fair enough, right? If you had a, you had a recent flare, you're automatically put on steroids and they always say with your steroids or with your anti-TNFs or whichever medication you're on, you're at risk of infection because we're deliberately suppressing your immune response. And so in an average healthy individual, if they were exposed to aspergillus or an aspergillus fungal infection and they'd be able to fight it off right, your immune system can just deal with it, kill it, problem solved. But because this individual was immunosuppressed and vaping and also growing his own marijuana because obviously, at least in the state of colorado, if you buy marijuana it'll be screened for aspergillus and you won't get fungally infected marijuana on sale as a kind of a they recognize it's bad for business. So so this individual, because he was growing his own, managed to get a fungal infection in his marijuana and so the combination of vaping and immunosuppression and fungal infection ended up he had to go to hospital because he couldn't breathe because he had this huge pedunculated is the word they use pedunculated growth in his throat which was basically at the point it was almost cutting off his airways. So the answer is don't do that.
Speaker 3:But after that then, in terms of vaping, is probably better than edibles, just because edibles are very difficult to track right. So different people respond very differently and at very different rates, whether it's, you know, some people are very high metabolizers of it and it'll clear their system quite quickly. Other people, they might take eight or six, you know, six or eight hours before they'll even feel any kind of response to cannabis edibles. And it depends on what you've eaten, it depends on what's in your stomach. So, in terms of dosing deliberately or consistently, it's definitely not a good way to go, whereas vaping at least, you know pretty quickly how much you're getting. People tend to be good about stopping at a reasonable cutoff point.
Speaker 3:There was a study by Ken Hutchison and Cinnamon Bidwell, two scientists working in CU Boulder. They were amazing, right, so there was loads of regulations about bringing cannabis on campus right, because we're talking federally funded university campuses who were like, yeah, we don't want to be anywhere near this. Like, federal dollars and cannabis do not mix. So these guys came up with this incredible solution of they developed a bus, right, so the bus would drive to your house. You smoke whatever you want to smoke, get in the bus, they do blood samples, they do psychological testing, you name it and they could have you jump in and out of the bus four or five times over the course of whatever you were doing. And it was amazing because it meant they generated a whole load of data and actually for cannabis research.
Speaker 3:That's a major problem, right. Access to patient information is a huge problem when it's a federal crime, most of you know in most parts of the. But what they were to show was that we were really concerned, right, because people were using things like wax and shatter and what we call very high concentration THC type products. But it turns out that people only there's only a certain amount that they want, anybody wants, and then they just shut off and they ended up reaching, even though they'd get there a lot quicker because they're using a much more high potency cannabis. They'd still reach the same levels overall, but I digress.
Speaker 1:Listen, I'm a social worker, so I'm going to preface my question because I would imagine working within a children's hospital system. You learn that a child is using a drug that is legal in the state but not federally legal. What are the reporting requirements of that? And like and truly that means, like when you're designing research using cannabis, like you can't necessarily recruit children right, like how does that work?
Speaker 3:You, can you just wait outside the school? No, I'm just kidding, you definitely don't do it.
Speaker 1:Take this lollipop, kiddo, come join me.
Speaker 3:No, so, right, well, yeah, so when we started, so actually, it gets worse, right. So the money we were investing in our research in cannabis was actually state-sponsored funding. So when Colorado brought in the legalization of marijuana, they said, right, we'll cap the tax revenue that we earn. And they really underestimated what the tax revenue was going to be. Right, they didn't realize just how popular it would be. So they ended up generating so much extra revenue and they realized they couldn't keep it. They'd already agreed in advance that they wouldn't keep the excess. So they asked people okay, well, what do we spend the money on? And the consensus was, well, we want more research, right, we want to understand what the cannabis does. And so I was lucky to be part of a clinical trial that was based off that kind of state tax windfall. But it was a major issue in advance, like we talked about. Like, one of the studies that was proposed was to look at transfer of cannabinoids from the mother to the fetus in utero right, and, yeah, you know, hugely important. But you now put that mother on a list of federal criminals who are subjecting an unborn child to cannabis, right? So that's not okay, and so that was definitely panned.
Speaker 3:We were lucky in that we were able to get a dispensation. We certainly weren't advocating for cannabis use, but equally we weren't trusting people to tell us if they were or were not using cannabis. So we tested them. We tested serums or their bloodstream and we looked for there's a number of cannabinoids that can last quite a long time within your body, within your blood, so we could test those. We confirmed that anybody who said they were using cannabis was actually using cannabis fairly regularly and likewise we didn't have any cases of people who denied using it but actually were. So that was fortuitous. But yeah, we had to get a special dispensation to say, right, we're putting together a list of federal criminals, is that okay? And in all cases, the parents were also actually part of the medicaid, part of the I don't want to say treatment decision, but they're part of the process, right? So the parents were all aware and they were providing the cannabis for their children, so they were fully aware of what was going on.
Speaker 2:So there was nothing shady about it everybody who listens knows I'm from louisiana and I know at one point, working with the family, like they had considered like just moving their whole life to colorado after it became legal because their child was so sick. They were like at wit's end. They did not know what to do and so they were willing to do anything, and moving to Colorado so that their child would have access to this was one of the things that they had discussed. So I feel like you know you can't make these parents villains, because they really just want to be better.
Speaker 3:Yeah, if you do anything if you think about even the, even the best treatments only work in kind of 20 to 40 percent of patients. So you're kind of rolling a dice already. And if they do work, some of them take, you know, three or four months to get work to start working effectively and consistently right. So you know, in the meantime, absolutely right, a patient parents are. You know, we, we spend our whole lives trying to protect our kids and trying to make sure they're never in pain or never discomfort, or never unhappy or, you know, never wanting for anything, and so, yes, you can totally see why that would be a port of call and there's no question that it makes people feel better. The concern is that in reality, it's making your disease worse and so when it comes around again, you're going to flare much worse and you're going to have a much more severe disease.
Speaker 3:But, yeah, no, it's a tough call and, like I will say so, we had another study running in the hospital that was looking at seizures and this was a huge component of it. Right, people moving to Colorado so that they could be part of the study, and unfortunately, what they found actually is that moving to Colorado had a much bigger impact on seizure frequency reporting than the actual cannabis did. Because if you change your whole life and you uproot everything and you move to a different state, then yeah, that's going to be a you're going to want to see and you're going to have confirmation bias in that scenario. So you want to see, you want to see it being worthwhile, but I mean, there's always kratom. You know I'm joking, don't ever do that.
Speaker 1:Well, I guess what I was curious, like, if part of it is just moving, is it? You know, like, how do you take out some of the factors of like, does altitude or the you know the lack of oxygen? You know it's like, how does that play into this? Like, how do you sort of control the variables if, yeah, that is part of it where you get somebody who's entirely uprooted their life and completely changed?
Speaker 3:And there's no doubt so like there's a. There's a scientist in Colorado called Sean Colgan, and Sean is just like. He has built a career looking at hypoxia and how hypoxia regulates intestinal inflammation, and there's no question that it's really important. And so if you live somewhere high altitude, then obviously you know that increases expression of those proteins, it changes your bloodstream, it changes a lot of your physiology, and so there's no doubt that it affects your disease, not to mention you're also moving somewhere that's incredibly high, also incredibly dry, right. So National Jewish Hospital in Colorado, in Denver, was a respiratory center, and the reason they were so successful is partly because people move into Colorado to seek medical treatment for respiratory diseases. We're also getting 10% humidity at most, and that completely changes what you're breathing Like. You come live in Dublin where it's 90% humidity on a good day and that's barely getting above 10 degrees Celsius or 40 something Fahrenheit. You know we're breathing in moisture all the time. That's probably full of God knows what else, whereas in Colorado there wasn't any of that. He says.
Speaker 2:I can relate to that being from Louisiana also.
Speaker 1:Well, yeah. And Houston, right, he says I can relate to that, being from louisiana also. Well, yeah, in houston, right same thing. It's like the inside of an armpit. It's awful right. Sorry, houston, love you. But I'm curious, like, does that level off over time? Like does staying in one place like so? Yeah, sure, when you first move there it's like this big, drastic change. Does that then increase over time, because your body gets used to it, like that's? I just like what's the?
Speaker 3:no, you mean you stay, you stay. Uh, evolved to live in that altitude, like so much so that I'd fly down to sea level and I'd be like running around going crazy. I used to have a sister who's she's nearly six foot tall. We go for walks every now and again. Uh, when I came home I should be like, yeah, let's go for a walk, and like I'm five foot six, so every step I take sorry, every step she takes, I taking two steps. But I remember when I moved back from Denver, walking along which I was chatting, and she eventually was like, can you just stop talking? But I was like, well, yeah, I'm not used to this low altitude. It's amazing. Babies born in Colorado have a much longer umbilical cord because they need. There's just not enough oxygen going around, so they need extra oxygenation just to survive. There you are now. Useful fact.
Speaker 1:I mean I'm going to definitely pull this out at a party someday.
Speaker 3:Right, when I moved out there I joined a group of people who we were called the Mucosal Inflammation Program, or MIP, but everybody used to refer to us as mostly Irish people, because there was like 11 Irish postdocs working together. And so my very first day I was told we were on the 10th floor, this high rise, and I was told hey, colin, we've got a meeting upstairs, we've got to go with it, we've got to go, we've got to hurry, we're already late, we've got to go. So I was like, oh shit, by first day this is not a good start. So I went tumbling up the stairs behind, opened the door to find a circle of my colleagues standing there in hysterics.
Speaker 3:Because when I got to the top I realized not only was I out of breath but I wasn't getting any oxygen to recover. So I thought I was dying, like I could not breathe. I couldn't. The more I breathed, you know, the worse I was doing. I was absolutely horrified and they thought this was hilarious. Apparently, this is like rite of passage for Irish people moving to Colorado. That hilarious. Apparently, this is like right of passage for irish people moving to colorado. They are, they were horrible people horrible people listen.
Speaker 1:If you're listening to the show, you know who you are. Has there been any research about how the microbiome may change with butt chugging alcohol?
Speaker 3:uh, so why? I should preface this by saying the reason I brought up that is because, yes and no, we do it all the time. I, honestly, we do it all the time in mice. I should start with that. I should really have started with that. So, in mice, if you give them an enema of, so actually, no, I'll be a bit more scientific about it.
Speaker 3:So we were interested in human disease. We don't really care about curing mice, we're really good at that. We do it all the time. We wanted to be able to cure human disease, but there's rules about right, there's a bunch of drugs you can't just give to humans, right, it's not safe. So our compromise was okay, we'll take mice, we'll give them a human immune system and then we'll test our treatments on those, because we're sort of testing human immune responses, albeit still in a mouse, right, and so that's actually pretty straightforward.
Speaker 3:So you take patient blood from IBD patients, you spin out the immune cells that you want, you inject them into a genetically modified mouse strain that can tolerate a foreign immune system. You basically wipe out their own immune system, but it takes three or four weeks, right, and then they establish this immune system. That's all human and, even better than that, it's individual to the patient. You got it from right. So your patient, mary, whatever, this is Mary's immune system, but now it's in six different mice. So we can tell Mary, this drug works in your immune system. But the last part of the process is you need to actually trigger intestinal inflammation in those mice, and the way we do that is with erectile enema of ethanol or alcohol. And so what alcohol does is it just breaks up the barrier between intestinal epithelial cells. It just kind of separates that barrier out and it allows the bacteria to get across the gut and into the underlying tissue and that triggers immune activation and it triggers intestinal inflammation. And now, all of a sudden, you know my friend Mary, I can test all the treatments that are currently available to Mary and I can say Mary, at least in mice, this drug worked best for your immune system.
Speaker 3:And the hope is that at some point we'll be able to transfer that into standard clinical practice, right, the idea being that we could tell everybody in advance this is the drug that's going to work best for you, because right now the way it works is patients get out, you know, put on Remicade. All right, we'll try that for three months. If it doesn't work, we'll stick you on Vedalizumab. If that doesn't work, we'll wait another three months, we'll stick you on something else. If that doesn't work, we're gone. And the problem is the longer you leave it, the worse the disease gets, the more uncomfortable it is for patients, but also the more difficult it becomes to treat. Patients become recalcitrant or resistant to treatment because they've failed on multiple different treatments. So the idea is that if we can identify what works best right off the bat or before, ideally, you get treatment, then we can streamline that whole process and we can get you on the right treatment right away. But that's somewhere in the future, I think. Hopefully.
Speaker 1:Hopefully not too far in the future, though that gives me a little bit of hope. Do you have to give the mice colonoscopies?
Speaker 3:We can do. It's actually really tricky. It's tricky. So I worked with a clinician called Ed DeZotenoten who was an expert in doing colonoscopies on children, which are like really big mice, so he was brilliant at showing us how to do the colonoscopy part of it. But it turns out children and mice are not the same, because children they toot, whereas mice don't.
Speaker 3:So if you fill a child full of air, then you can ask them to just blow it back out again, and they might even find that quite funny. But if you ask a mouse to do it, it can't, and so there's always a risk that you'll over-inflate the mouse and you'll be left with a balloon-shaped mouse. So for that reason we don't do it. It's also not super helpful, right? So at the end of our studies we tend to have to euthanize the mice anyway, because they're treatment and we really want to know if it works. So what we end up doing is euthanizing the animals and then removing their gut, their intestinal tissue, and looking at that without having to do the whole colonoscopy part. But yeah, they don't like being over-inflated.
Speaker 1:No, I assume that was probably the case, but also I just was thinking of like a Barbie colonoscopy scope. To like go in the tiny mouth.
Speaker 3:We've got one, and so actually my wife my wife's an ibd researcher as well and so she's more interested in the intestinal epithelium, like how that barrier works and how it breaks down and how it recovers and how it heals, and so what they were looking at when they were using those scope for was to to generate a little injury, so to generate like a small pinch, pinch the biopsy out and that leaves a little hole behind, and it means that then you can go back in a week later and see where the hole is and see how much it's healed and actually they're doing that in patients as well, and they can even tattoo around the hole, so you know exactly where the hole was, and so you can be able to go back in and be like, oh yeah, that's where the damage was and now it's all better.
Speaker 1:When you're doing something like a lab tour and or patient education, because you are literally like bench research mice not necessarily a scientist, that who also treats patients. Tell me how, taking what you do and sort of breaking it down in a way that makes sense for for the lay people of the world, how like, how easy is that when you're sitting and doing like educational pieces?
Speaker 3:Yeah, it's really tough. And actually now, now that I run a lab and I have students working with me, it's one of the things I kind of teach them early on is to have it. You know, there's no point in doing research if nobody hears about it, and there's no point in trying to help patients if they don't know you're doing it like if they don't get the benefit. Right. And so we do a lot of work on how to get rid of jargon out of what we're saying and how to simplify communications, but at the same time, you know, if you really want to understand what you're doing, the best way to do that is to not rely on scientific terminology, to break it down into its simplest form and say, right, it's doing this or it's doing that. Scientists are constantly working towards improving our communication skills because, you know, we recognize that it's becoming an increasingly important part of our job. Right, there's no point in doing research if you can't share it with people. If I can find something that you need to know and I don't share it with you, then I might as well not have found it in the first place. But when it comes to lab tours, it's actually it's really refreshingly simple. So we bring people in and we show them. Here's our microscope here. These are tissue slides. We've got a tissue on there that looks like it's from a gut. It is, but it's not a human gut, it's a mouse gut, but it looks, you know, very similar, like so much so that we work. We work with pathologists who spends most of his time looking at humans and when he looks at mouse stuff he's like, yeah, it's the same, like it's similar, sort of sort of appearance. But it's funny.
Speaker 3:Like things like a centrifuge. Right, we would use centrifuge 40, 50 times a day and we don't even think about it. And we've got people come in the lab and they're watching us doing stuff, doing, you know, setting stuff up, and they see us drop something in the centrifuge, stick it on, walk away, come back and we've separated out blood from serum or we've, you know, something like that. And they're like, oh, my God, that's amazing. And you're like, wait what? It's a centrifuge. You know we use liquid nitrogen a lot. And again they're like, oh, wow, that's so cool. And you're like, wow, you know, the stuff that we take for granted all the time, was this stuff that the patient's already interested in? And really they don't. They've never been overly like oh, why are you doing your experiment this way? Or why are you doing this Because they recognize that that's not their expertise.
Speaker 3:So really what they want to know is are you excited about it? And when they see how excited I get and they see how excited my students get, that's enough for them. They're like okay, you know you really care about our disease and you know you don't have to, but you do and that's that's kind of a win-win. And then for us, obviously in the back of our mind, we're always thinking like I am failing you all of the time, like every time I put my iPad in the wrong place, or every time I press too hard on something and it breaks, or like you name it, the stuff I do wrong is just, the list is endless. But every time I do that I'm like you know, that was an option for me to be helpful and I've failed, and it's hard not to forget that.
Speaker 3:But then you meet these people. They're like, yeah, we don't need your help, like we're doing really well. I mean they're as a patient group. Ibd patients are incredibly resilient and, you know, positive, overwhelmingly positive. You know I remember a patient saying to me one day. She was like oh yeah, you know I've failed Remicade, I've failed Adalimumab, I've failed something. You know listing off all the drugs that haven't worked. And I've had you know this number of centimeters in my intestine removed and you know how are you doing and it was like you know it. Just they just take a kick and keep on ticking, like they just do not stop, like these people don't need your sympathy, they just need you to be working hard and you know that's they're happy enough and that worked, like for us. That was really tremendously reinforcing to know that you know at least we care and we're doing the right thing and that's all you can hope for.
Speaker 1:In looking at your research or research or the other people like that, are kind of working in the field with you.
Speaker 3:Is there anything that seems really exciting, really like hopeful, at the moment? It is tough. For a good period recently it's been the opposite. So we've gone from a stage where you know there were new drugs coming on the market all the time, right so 10 years ago, when we had like Eustekinumab and all these other new drugs that were coming out in rapid succession and basically every clinical trial or a whole load of clinical trials. We're looking at all these new medications and that was really really exciting time.
Speaker 3:And I think with the advent of biosimilars, that's really killed off a lot of that investment in new therapies for IBD, because so much of the clinical trial work is had to focus on. You know, is this biosimilar the same as the other one? Is it an equally effective? Is it doing this, that and the other? And I think that's really sucked up a huge amount of resources in terms of patients who are enrolled and in terms of investment that was available into a field that doesn't offer a huge benefit. So, yeah, it's hard not to be negative about that. Is their future going to be brighter? Yeah, I think this, you know, if you look at the cancer field and the developments they've made with CAR T-cells, where they basically take your T-cells, re-educate them and modify them and re-inject them. I think that's probably where we're going to see IBD therapies go in the future. I think the technology to do that is very much available. So I think that's not far away. Right, that's going to come quick enough.
Speaker 3:But, yeah, no-transcript able to get to that point and it's probably more of an insurance problem than the biology and the science tells us that it's better to use multiple different treatment options. And that's one of the things where right now, there's a huge hope. Right, we've got anti-TNF drugs, we've got integrin blocking drugs, we've got IL-12, il-23 blocking drugs, we've got S1P inhibitors, we've got JAK inhibitors. We've got way more different types of medications than we've ever had, but we're not doing enough to combine them together and seeing if we give you a drug that has all of those things combined, would that be effective on everybody and wouldn't that be worth having, because insurance companies won't pay for that. So even if it's lower concentrations of all the drugs and it's less side effects, there's a bunch of upsides.
Speaker 2:Colm, it has been so entertaining to talk to you and informational, but we've been talking for a long time and it's time for us to ask the last question. So what is the one thing you want the IBD community to know?
Speaker 3:The one thing I think is please, even though cannabis might make you feel better, be aware that it's making your disease worse and don't do it. And I appreciate that's coming from a place where I don't suffer from a chronic disease and so I do have the luxury of saying you know, even that's something that makes you feel better, you shouldn't be doing it, but really it will make your disease worse. We have a lot of evidence that says that it is going to make your disease worse, so please don't do it. And if you don't have IBD, don't do it till you're over 25.
Speaker 2:I will add for the cannabis part don't do it. But if you're going to do it, make sure that you talk to your doctor about it or at least let them everything that you're taking, drinking, eating, whatever because it's going to affect your disease course. So if you're going to do it, make sure that your doctor knows you're doing it For sure.
Speaker 1:Collin, thank you so much for being on the show. This was, like Robin said, so much fun to talk to you and this is also where sometimes I wish like we weren't on mute and we use the video because we were laughing a lot and you can't actually hear it. So for those of you who think we don't have a sense of humor, I promise we were laughing, just we were muted. So thank you so much for coming on the show and spending your Friday night with us. We really appreciate that. And thank you so much to everybody else for listening and cheers guys, Cheers everybody.
