Future CBD Research

 

Tiffany  22:29

Not working on any right now. COVID has put a big damper on a lot of the lab work that we’re able to do at this point. And clinical work in particular is the most difficult because people are afraid to sign up for studies and come into the university. So the clinical studies that we had going prior to COVID, some of those we’re still working on finishing up and we’re restricted on the number of participants that we can have coming into the lab on any given day. And so it’s slowed down progress quite a bit. But we do have something here in Colorado that’s called the Cannabis Research Institute. And I’m not sure if you’re familiar with them, but it’s out of, I believe, Pueblo, Colorado, and they have funding that people researchers within the state can apply for to do cannabis related research. And that can be anything from  the horticulture side of it. So you know, better ways to grow it in the field and that kind of thing, to  looking at some of the human health effects of it. 

 

And I do have a couple proposals in there. One is looking at THC and glucose regulation. And the other one is looking at how the gut microbiota might actually be metabolizing different cannabinoids. And not just CBD but we also propose to look at CBG in that study as well. And what we want to do if this study gets funded is we have biobanks of human gut microbiota that are stored. We would put these in bioreactors in the lab and then add the cannabinoids to it, look and see one, how does the presence of the cannabinoid change the composition of the gut microbiota? But not just the composition, does it have an influence on the function of it? So we would take then some of the liquid from these bioreactors and we can put them in different intestinal cell models, and see, does it influence inflammation in these models? Does it influence gut barrier function and those types of things?

 

So this is work that I’m really, really excited about because it kind of brings me back more to the area that I’m interested in with gut microbiota and phytochemical regulation. And then we have a chemist on that project. And she would look at how the gut microbes might be processing and metabolizing the cannabinoids and what are some of the metabolites that result from that? And then do those metabolites have different bioactivities than the parent compound?

 

Vadim  24:53

Interesting. So with those studies, you’re not doing it in a person. It’s just like in a petri dish or something like that, right?

 

Tiffany  25:01

Yeah. Essentially, the first part, like I said, would be done in these sort of small microcosm bioreactors, but they’d be done using a consortium of human gut microbes. And then we would be taking liquids. It’s a really nice controlled process because then we can see specifically what are the effects of the cannabinoids on these microbial consortium? And how do the microbes then process the cannabinoids versus when you do this in humans, we all the time, right? You have to deal with all these things like, well, is that an influence of the cannabinoids that we added into the system or it has to do with the diet? And then of course, as I mentioned, that interindividual variability and absorption of cannabinoids. In this case, when we’re talking about how they’re affecting the gut, you want there to be a sort of lower absorption because you want it to reach the lower intestines where the microbes primarily live, so that you can see what those effects are. And we do know that a good bit of the cannabinoids that are consumed actually do make it to the areas where the microbes reside.

 

Vadim  26:11

Okay, okay. And what are some of the applications? Is it for an upset stomach or IBS type of thing or like Crohn’s?

 

Cannabinoid Receptors and Inflammatory Diseases

 

Tiffany  26:21

Yeah. You alluded to this. I think it was in our pre-recording discussion, but there are receptors in the gut and other cells in our body that are called the cannabinoid receptors. And they are basically compatible with compounds that our body makes that are called endocannabinoids. But these different phytocannabinoids can also bind to the receptors. And there is some research looking at CBD, I think, in particular, with regard to being able to bind to these receptors in the gut and having an impact on visceral pain or pain in the stomach. So people who have some of these inflammatory gut diseases, it can help with pain in those particular areas. It can help with motility and transit time of contents that are in the gut. So that’s one area. But also coming back to my real big area of research, my true passion here, the gut is the root of all these other things that we don’t always think about. And so if you have inflammation in the gut, and you have microbes and toxins and things like that, that are making their way out of the gut and getting into circulation, that’s the beginning of diabetes. That’s the beginning of arthritis. That’s the beginning of things like Parkinson’s disease and multiple sclerosis. So all of these diseases, they’re starting to find now have connections to disruptions in the gut.

 

Vadim  27:47

It’s honestly one of the most fascinating aspects, I think, of medicine right now is that they’re finding out all this stuff. And just to repeat for people, we were discussing how there’s cannabinoid receptors, as you probably, listeners, have heard of in the brain and the gut and throughout the whole body, right? I mean, it’s everywhere. 

 

Tiffany  28:04

Right. 

 

Vadim  27:47

But is there a higher concentration in the gut than other places? Isn’t it?

 

Tiffany  28:09

That’s a great question. I don’t know the answer to that. 

 

Vadim  28:13

Okay. I think there are.

 

Tiffany  28:14

Yeah. I couldn’t say. I don’t know if anybody’s actually quantified them at least in humans. But there is a significant amount in the gut because especially if things are taken orally. You know, you have to think that that’s going to be the first point of contact for a lot of these.

 

Vadim  28:28

Is there any theory on why we have an endocannabinoid system? I don’t remember. Is it thought of as something related to cannabis or just happens to be chemically similar?

 

Tiffany  28:38

Yeah. It just happens to be chemically similar. The fats actually that we eat. Some of them get converted into these other compounds that are called endocannabinoids. And those are the native compounds that bind to those receptors. And it really is kind of like our other systems, our nervous system and our muscular system and things. It helps regulate muscle tone and intestinal tone. And just, you know, kind of keeps the whole system in balance, basically. And these cannabinoids that are present in plants, it’s just a coincidence, I suppose, that they’re structurally similar enough that they can bind to those receptors.

 

Vadim  29:21

Yeah. It could be that we evolve with them or something, but we don’t know. But there could be that, you know, cause this plant has been around for so long and been a part of human history for so long. The history is really interesting. Yeah. The way I think of it as they happen to fit the lock, right? They have a key that works for the lock that we have and it just happens to be the same fit as some of our own internal things, chemicals that we produce.

 

Tiffany  29:48

Exactly. Yeah. That’s a great way to think of it too. Sort of this lock and the key. Yeah. And so if the receptors are the locks, we have keys that our body makes, but we have keys that are also in plants and other things that we consume that can fit that lock as well.

 

Fermentation Science and Gut Microbiome 

 

Vadim  30:06

Yeah. I can’t believe I didn’t ask you yet either. Do you teach or only do research?

 

Tiffany  30:10

I do teach. Yeah. We have a fermentation program at CSU. And so I teach fermentation microbiology to our undergrads, both the lab and our lecture class. And then for our graduate students, I teach a class on phytochemicals and probiotics as well as a class on personalized nutrition.

 

Vadim  30:29

Oh, cool. So the fermentation, is that for people that want to work in the beer industry and like fermented foods, like wine and yogurt?

 

Tiffany  30:37

Yeah. I would say probably 90% of maybe even higher percent of our students that graduate from that program end up going to work in the fermented food and beverage industry.

 

Vadim  30:47

And what’s big in that other than beer, like the dairy side?

 

Tiffany  30:51

No, I would say for us — and again, if you’ve lived up here, you know, Fort Collins, we’re pretty famous for our craft breweries. I can’t remember what the current number is right now. But I think, you know, we’re up in the 20. For a medium sized town that we are, I think we have over 20 craft breweries here. And so a big focus of the program is beer. But then because we’re housed in a nutrition program, I would say that the other part of our fermentation program has to do with what I’m doing, which is looking at the impact of both fermented foods, but regular foods as well, because they get fermented in the gut. And so sort of this humans as bioreactors fermentation and human health. And we have another fairly new professor that came on that’s also interested in looking at interactions between structure of food and function of food and how that can relate to intestinal inflammation in the gut. And so those would be the two main focuses of our fermentation program. But I have to admit that most of our students are here for the beer.

 

Vadim  31:53

Yeah. Well, it’s a popular industry and growing a lot. And also, yeah, and  Colorado kind of like started that actually. I know a guy there that was one of the pioneers of the craft beer world. A lot of people don’t know it. Colorado was one of the roots of that. So you said you have this other CBD thing that you were doing. Is that anything else on your list or bucket list of research that you’d like to do?

 

Tiffany  32:18

I think, you know, if we get this funding to do the study with the bioreactors, that that could lead to a lot more projects in terms of justifying taking it into humans and doing long term studies to see what the impacts might be on the gut microbiota and kind of alleviate intestinal inflammation in people who have specific conditions like IBS and IBD. So, you know, long term, I’d like to go there. But I’d like first to see, you know, what do we find out from our microcosm bioreactor experiments? And is it justified to move into these big clinical studies? Because obviously, you know, clinical studies are not cheap to conduct and we want to make sure that the evidence is there before we move in that direction.

 

Vadim  33:04

Absolutely. There’s a lot of, obviously, hoops and things to jump through before something can get out on the market. And that’s why I think people are excited about CBD being out there. And obviously, there’s not a lot of background on it. So we don’t know how safe it is, I mean, it seems pretty safe. But it’s good that people can use it if they want and not have to go through getting a prescription and all that stuff.

 

Tiffany  33:29

Yeah. So there’s something about the first study that I forgot to mention. I talked about we did two things and one was looking at the blood kinetics, basically. But the other was looking at this inflammatory profile. And what’s interesting is when we took the two different types of CBD and we analyzed for effects on inflammation separately, we didn’t see any significant differences. Now, again, it was a really small study. It wasn’t really powered to look at those differences. So we took the data from both groups and combined it. Because we said, well, they both had CBD. So we could say, you know, pre and post CBD, was there a difference in inflammation in these people? And we did that. When we did that, we did see that there were decreased inflammatory markers produced by these cell cultures that we’ve taken from blood. And I think that that’s really interesting and kind of justifies the idea of moving forward and looking at the effects of CBD in the gut. Because that one treatment didn’t really get absorbed, but it would have made its way through the digestive system and it would have come in contact with the intestines and the microbes in the intestines. And so that reduction that we saw in inflammation when we look at all of the data as a whole, I think is at least partly driven by the interaction with the CBD and the gut. And that’s, you know, for me, exciting because it kind of justifies that that’s an area that we need to do more research in.

 

Can CBD Help with Leaky Gut?

 

Vadim  35:00

Oh, yeah. I agree. When I first learned about CBD, that was one of the most exciting aspects of it as well as for helping people with anxiety and stress relief. But the gut aspect is really interesting. And one thing I wanted to ask you is because a lot of people hear about leaky gut, what does that mean? It’s kind of like a simple way of saying something more complex, right?

 

Tiffany  35:23

It is. Yeah. You know, it’s kind of a terrifying term when you think about it. Like I don’t know. A leaking pipe or something. Oh, God, that stuff from inside is getting outside. But really, that’s what it means. It means that the permeability of the intestines is more permeable than it should be. So things that normally should be contained within that gastrointestinal tract and move from one end to the other are actually escaping at some point and getting into circulation. And so it’s not like your intestines are degrading and completely falling apart, which that term always kind of brings that to mind for me. But it does mean that the integrity of that barrier is disrupted a little bit. And now, you know, things like maybe larger food particles that can elicit immune reactions and food allergies or things like bacterial toxins that are produced in the gut and would normally be detoxified can get into your bloodstream and into your circulation. And so really, it just means that there are more things that escape into circulation and then can have effects on your immune system and on different tissues and organs in your body.

 

Vadim  36:36

Is there some evidence or hope that CBD can help with that?

 

Tiffany  36:40

Well, I think, you know, that’s definitely one of the questions that we would like to address with the study. So the microcosm experiments, like I said, we’re going to take some of the liquid from the bioreactors after CBD and gut microbes have kind of been in contact with each other for a while. And we have this neat little system where you can grow intestinal cells to the point that they grow together and they function as a barrier. And you can do this in a dish. And then we can put the liquid from these bioreactors onto those cells and see how does that influence what can travel across that barrier. And so there are different ways that you can do that. You can add things to the barrier that are going to cause inflammation and cause disruption of the barrier. You can pretreat with CBD or the liquid from these bioreactors and then you can add these inflammatory challengers basically and see, does it prevent the barrier from leaking? Or does it still leak? And so those are some different ways that we can get to the answers to those questions. 

 

Vadim  37:44

That is something that I think is going to be very promising in the next decade or sooner hopefully with more cannabis research coming out. Would you say it’s easier for you to do studies on CBD, I think for sure, than on THC, right? 

 

Tiffany  37:57

Oh, absolutely. Yes, yes. 

 

Vadim  38:00

Okay. I figured. I mean, THC still has a federal illegality. Hopefully that changes soon. So there can be more research done on it because people have used that for stomach pain or like nausea. I mean, that’s obviously been well, well, well established with the pharmaceutical cannabinoid drugs that are out. I forget what it’s called. Marinol or something, Dronabinol. I mean, those are made for nausea. I don’t know how effective the synthetic versions are. By the way, the CBD that you used in those studies? Do you know if it was synthesized or plant-derived?

 

Impact of Federal Regulation of Cannabis Research 

 

Tiffany  38:35

It was plant-derived. Yeah. That was one of the legal hoops we had to jump through. We needed to show the certificates that it was derived from 100% hemp plants and the percentage of THC to CBD that was produced by the plant.

 

Vadim  38:50

There’s so many silly rules. It’s almost like there’s a system that’s kind of arbitrary, but you can’t get out of it. Because that’s the way it’s set up. So now there’s all these limitations put on science, which is really just hampering progress in this area.

 

Tiffany  39:06

Right. Yeah. And I mean, I think Europe and other countries haven’t had the same restrictions. And so a lot of the science that’s out there now, you know, other than what’s just come out in the last few years, has really been driven by other countries. And so it’s kind of unfortunate for the US that we’re really behind the curve on this. 

 

Vadim  39:27

Yeah. Israel and Europe definitely beat us to that. So I think that will change though. I mean, I’m sure the new president is more… I think they’re more lenient on the federal side, but I don’t know what will happen with them. I think as the time goes on we’ll have more ability to research this stuff.

 

Tiffany  39:47

And we found some unique ways around the regulations too. I mentioned that one of the studies that we’ve proposed to this Cannabis Research Institute is a THC study. So there have been models developed where we don’t provide the THC and we don’t give it to humans to consume but we recruit people who will buy it and take it and come into the lab and give us their blood. So that’s allowed. You can do that. You just can’t administer it to people right now without this Schedule I. And so that’s kind of how we’ve proposed to do these studies. And then, you know, if we want to look at the effects of THC on a particular outcome measure in a more controlled study, we can’t give it to people, but we can recruit people who normally use it and then take it away for a period of time. So a little bit sort of flipping it around instead of adding something into a system. You’re taking something away and seeing what are the effects of taking it away. 

 

And so for this study, looking at whether or not THC has beneficial effects on glucose regulation. The first part of that study would be that people will buy a particular type and dose of THC. They’ll take it, we’ll monitor, you know, we’ll do the glucose challenge and monitor that. And then the other part of that would be that we get habitual cannabis users and we get them to stop for a period of time and we do a glucose challenge prior to them stopping and then after they’ve stopped for a certain period. So there are still ways to answer the questions. There may be not the most direct ways and not the ways that we would prefer to do it but, you know, we can definitely still do it.

 

Vadim  41:27

I think some of the most interesting studies would be comparing THC and CBD, you know, and seeing which one works better for different applications or other cannabinoids.

 

Tiffany  41:36

Yeah. I think that those would be interesting, but they’re harder to get in completely purified forms. Well, the CBD, I guess not because that’s the only kind that we can research. We have to show that it doesn’t have the THC. But I think a lot of the THC preparations are sort of more synergistic. Am I correct in thinking that they actually have a range of cannabinoids typically?

 

Vadim  41:58

Like the products that people buy?

 

Tiffany  42:00

Yeah. They’re more full-spectrum.

 

Vadim  42:03

Well, no. I mean, there’s like half and half. Some are, some aren’t. That’s kind of the market right now. I wouldn’t say that it’s dominant full-spectrum. It used to be, for sure. It used to be. But now it’s all different kinds, where there’s pure THC products, there’s pure CBD. Like everything you can think of basically, they have. But I’m interested. When you do those studies with the people, the THC, how do you give it to them? Since you’re not allowed to administer it.

 

Tiffany  42:28

We would have to. And I haven’t done these yet. We’re just proposing to do them. But you know, it would be like go and buy this brand of gummy that has this particular concentration, right? And then take one and come in, take one in five minutes before you come into the lab.

 

Vadim  42:45

Okay, yeah. Well, that makes sense. I mean, that seems fairly reasonable if the person is — I don’t see anything unethical about it.

 

Tiffany  42:52

No. Yeah. And it’s been published. You know, I mean, it is now an acceptable model of study. But again, it’s not completely ideal, because, you know, the people are blinded to what they’re taking. They know what they’re taking. The researchers know what they’re taking. And so you know, when we think about trials, you think that the gold standard or these random double-blind placebo-controlled clinical trials. And it’s a lot harder to do that when you’re relying on the participant to kind of go buy what they need or what you need them to need to take it.

 

Vadim  43:24

Less control also. You don’t have control over the batch and the batchiness is a huge issue in this industry, like one batch can be hotter than the other as far as cannabinoids. Pennsylvania’s has done a phenomenal job, I think, of quality control, but I don’t know — like I’ve heard some places in Colorado, you can still find products that are kind of questionable consistency. So I think if doing that study, I’m sure if you find a brand that’s doing really good testing in quality control, that would be the good way to do it. And then to make sure that the person actually took that product and not a different one.

 

Tiffany  44:00

Right. Yeah. But you know, again, those are some of the challenges that we face right now without having the ability to do things the way we want to do them.

 

Vadim  44:09

Yeah. So are all your classes on Zoom now?

 

Tiffany  44:13

Right now? Yes, We have Teams. That’s the university sponsored program, so we have to use the Microsoft Teams’ program. But yeah, right now, I’m only teaching one class this semester. And it’s somewhat asynchronous. They listen to the lectures online and then we have live sessions virtually where the students can come and ask questions and we have discussions.

 

Vadim  44:37

Oh, ookay. It’s funny cause my brother is in a beer fermentation class. He goes to Villanova. It’s hard for me — it seems like something so hands-on to learn.

 

Tiffany  44:48

Is he taking that virtually? 

 

Vadim  44:49

Yeah. 

 

Tiffany  44:49

Oh, that’s unfortunate. Our brewing classes are still alive.

 

Vadim  44:53

Yeah, it’s virtual. But I think maybe the lab he goes to once a week or something, hopefully.

 

Tiffany  44:58

Okay. Yeah, that makes sense. I’ve taught my fermentation microbiology lab and we cut it down to one day a week. And we had to restrict the number of students who can take it. But you just can’t get the same level of experience if you’re not doing the hands-on.

 

Vadim  45:12

Yeah. Hopefully all this stuff just goes away soon.

 

Tiffany  45:15

I hope so.

 

Wrap-up and Contact Information

 

Vadim  45:16

Yeah. I think a lot of people are very sick of this virus. Well, thank you so much for being here and teaching us a bit about phytochemicals and how they interact with our gut. I think the research you’re doing is just absolutely fascinating. And I’m going to link to information about you in the show notes as well as this study. And I’ll have to grab that other one from you as well. So I can share that with people. The one where you did more, like the six different ones.

 

Tiffany  45:42

Yeah. I think I have your email. So I will send you the link to that study. And you know, the lead investigator on that was my colleague, Chris Bell. So you may want to find his web page on CSU site and link to him as well because he could definitely be a better resource to answer questions about that study.

 

Vadim  46:01

Very good. Tiffany, thank you so much again for being here and educating us. And you’re welcome back anytime.

 

Tiffany  46:07

Awesome. Well, thank you. It was good to talk to you. And I always get nervous doing these things. Thanks for making it not awkward.

 

Vadim  46:13

Yeah, no, you’re great. You’re doing a great job. Seems like you do these every day.

 

Tiffany  46:17

Well, thank you. I don’t. But thanks.

 

Vadim  46:20

Tiffany, where can people find you online if they want to connect with you?

 

Tiffany  46:24

So let’s see. My email is published and I usually respond to emails pretty well. And I also have a ResearchGate page, which is something that, you know, I guess it’s maybe more to connect academics in different areas. And then I have a LinkedIn page. Although I have to admit I’m not as good about checking my LinkedIn and following on LinkedIn. So I think just probably my university email would be the best way.

 

Vadim  46:53

Yes. And if there’s companies listening right now that want to — do you do any independent contracting for testing, if they want to contact you to do that?

 

Tiffany  47:02

I would be open to discussions.

 

Vadim  47:04

Okay. Very good. Well, you heard it there, folks. If you want to work with Tiffany or just connect with her, you can email her and we’ll include all that information in the show notes. Again, Tiffany, thank you so much for being here and stay on. After I stopped recording, we can talk for a little bit more.

 

Tiffany  47:19

Okay, great. Thanks.