#127 – Researching CBD Bioavailability and Absorption with Tiffany Weir of Colorado State University

cbd bioavailability study
April 14, 2021 • 47:28 minutes

#127 – Researching CBD Bioavailability and Absorption Rates with Tiffany Weir of Colorado State University

Dr. Tiffany Weir is an Associate Professor of Food Science and Human Nutrition at Colorado State University. Her research focuses on understanding the role of microbes in ecosystem functioning, ranging from soils to processed food products to the human gut. Dr. Weir currently conduct studies examining how fermentation of plant foods affects composition and bioavailability of phytochemicals beneficial for human health. Focus plants include rice bran and fermented Chinese tea, both of which have been used traditionally as medicines in Asian cultures and have shown activity in a number of chronic and infectious disease models. Another area of study is how dietary phytochemicals affect the composition of gut microbes. She was recently involved in a study with Caliper CBD on the bioavailability of CBD in water-soluble vs oil-soluble forms. 

Show Notes

Dr. Tiffany Weir was part of a team of researchers at Colorado State University who recently conducted a groundbreaking study on the bioavailability and absorption rates of CBD in water and oil-soluble forms. We discuss the results of the study, and its implications for further research into CBD's potential to positively impact the human gut microbiome and reduce symptoms of inflammatory gut diseases. 

Highlights

  • Phytochemical and plant-based medicines
  • Impact on absorption of water-soluble vs oil-soluble forms
  • Potential impacts of research results
  • CBD's initial promise as a anti-inflammatory

Links of Interest

Connect with Dr. Tiffany Weir on ResearchGate
Dr. Tiffany Weir's Bio Page at Colorado State University
The Caliper CBD pilot study: Evaluation of Pharmacokinetics and Acute Anti‐Inflammatory Potential of Two Oral Cannabidiol Preparations in Healthy Adults
Summary of Caliper CBD Bioavailability Study

Summary Keywords

study, bioavailability, absorption, microbiomes, people, cbd, cannabinoids, gut, health, thc, plants, phytochemicals, humans, compounds, called, research, class, formulation, lab, fermentation, microbes, tiffany, weir, inflammation

Speakers

Vadim Fedorovsky, Host, CBD School Podcast
Tiffany Weir, Associate Professor, Colorado State University

Podcast Transcript

Introduction

Vadim  00:10

All right. And we are back in class. This is Vadim, the CBD professor from cbdschool.com: Your school to learn all about cannabidiol. On today's episode of the CBD School Podcast, get ready to learn a lot because I'm here with Tiffany Weir, who is an associate professor at Colorado State University and her specialty is in food science and human nutrition and we're going to be getting all into how that relates to CBD. But the main goal of her research is to understand the role of microbes in ecosystem functioning and with ecosystems ranging from soil to processed food products to the human gut. So let's talk about there, especially with the cannabinoid receptors that are in the human gut. So Tiffany, welcome to the show.

 

Tiffany  01:04

Thanks for having me this morning, Vadim.

 

Vadim  01:06

Yes, it's a pleasure. And you are in Colorado?

 

Tiffany  01:08

Yes, I am in Colorado, and it's finally starting to warm up a little bit here.

 

Vadim  01:13

I used to live there, but I live in Mexico now.

 

Tiffany  01:16

Oh, in Mexico. So you've missed the recent cold spell then.

 

Vadim  01:21

Yeah. But I love Colorado. I mean, I loved living there. I would probably move back there. I forget where CSU is. I don't know if I've been there.

 

Tiffany  01:28

We are in Fort Collins. So right up near the Wyoming border.

 

Vadim  01:32

Oh, yeah. I used to work in Birchwood, which was not that far from there.

 

Tiffany  01:36

Yeah. 30 minutes or so away. 

 

Vadim  01:38

I know Fort Collins. I knew a bunch of people that lived there. I remember that. Great. Well, are you a Colorado native?

 

Tiffany  01:44

I am not. I am originally from the east. I lived in Pennsylvania, New York, Maryland. But I've been out in Colorado now for 20 years.

 

Vadim  01:53

Cool. Okay. I'm from Pennsylvania. Just to get into what you do, what made you — obviously a lot of years of school to become a professor. I actually wanted to be a professor, but I quit. You have to really want to do it. So I'm curious. What drove you to dedicate yourself to this?

 

Tiffany  02:12

Yeah. My path has not been very straight. I started out as a biology major. I went to Penn State and studied biology and then I went on and got a graduate degree master's level in plant pathology, which is the study of plant diseases. And after that, I got hired by the USDA and worked for the USDA in New York doing quarantines. I got to like tramp around Amityville, New York looking for Asian long-horned beetles and other invasive species and things like that. It was an interesting and fun job. And then my husband, who I met at Penn State, ended up getting a professor job out here in Colorado. So we moved out here. And I worked for the USDA out here for several years before I decided that I wanted to go back to school. And I think when I worked for the USDA, a lot of the decisions that I saw being made about quarantines weren't necessarily the most scientific and it just made me miss science and want to get back to science. 

 

I've always loved microbes. A lot of the study of plant diseases was, you know, studying plant and microbe interactions. And right about this time, we started to be able to have the technologies to study the human gut microbiome. And I heard a story on NPR and you know, they were talking about how the microbes in your gut can contribute to obesity. And I was just completely fascinated by that and decided that that was really the area that I wanted to study. And everything's history. Beyond that, I focused for the last, I'd say 15 years or so, on looking at interactions between the diet and the gut microbiome and how the gut microbiome can influence disease in humans.

 

What are Phytochemicals?

 

Vadim  03:50

Wow. Yeah. It's one of the most fascinating new developments, I think, in medicine and biology is like the second brain thesis. And not that it's like that new, right? It's been researched for a while, and there's some like old wives’ wisdom or whatever you would call it to it too. Because people would use their stomach kind of to make decisions for, I think, thousands of years. It's really fascinating. Because it's also like the food, the frankenfoods, how are they messing with us and everything. So what are phytochemicals? So let's maybe start with defining some stuff that we're going to talk about. So I know you work a lot with bioavailability and phytochemicals. What are those things? For people, we can define that.

 

Tiffany  04:32

Yeah. So phytochemicals are basically metabolites that are produced by plants that aren't necessary for their day to day functioning. If the plants didn't make them and they were in a perfect environment, they can survive, but a lot of them are made for attracting pollinators or inhibiting insect predation and herbivory and things like that. And these compounds have, you know, these specific defense functions in the plants, but they also have important functions in human health when we consume those compounds. And so some of the more common ones, you know, obviously, cannabidiol, which we're going to be talking a lot more about, is one of the phytochemicals. But some other ones people might be familiar with are the beneficial green tea catechins. Because you can buy this as purified supplements and things like that, and they have antioxidants. I know several years ago there was this big push by the nutrition industry to eat your colors. And that whole eat your colors thing was basically to try to encourage people to get a diversity of these different types of phytochemicals because they are also pigments in plants. And so a lot of them are responsible for the bright colors. Berries, you know, and the different brightly colored foods.

 

Vadim  05:48

Okay, okay. So CBD is a phytochemical, right?

 

Tiffany  05:52

Yes, CBD is a phytochemical. It's in a class that's called terpenes. 

 

Vadim  05:57

Okay. So CBD actually is a terpene. Are all cannabinoids terpenes then? 

 

Tiffany  06:00

Yes. 

 

Vadim  06:01

Oh, wow. Okay, okay. And they are very volatile, right? Or I thought I remember that, like they don't last long in certain environments.

 

Tiffany  06:10

Yeah. So typically, terpenes are going to be volatile. But again, so this kind of comes back to the function of a lot of these compounds in the plants. They connect these volatile molecules with sugar molecules so that they become less volatile and their plants can then store them and basically only have them available when they're needed. And so, you know, in order for them to become volatile, sometimes they need to go through a little bit of processing.

 

Vadim  06:36

Okay. Yeah. I think that's something a lot of people don't know is that the cannabinoids are actually a terpene. And the idea is that the plant produces them as a deterrent for pests, right?

 

Tiffany  06:48

Yes. For defense. 

 

Vadim  06:51

It's funny. It deters pests, but attracts humans.

 

Tiffany  06:53

Right. Yeah. 

 

Vadim  06:55

What's the reason that people should be, you know, eating their colors? What is it that phytochemicals do? Is it that they fight cancer? Is that the theory?

 

Tiffany  07:04

Yeah. I mean, there's some evidence. Again, you know, there are a lot of different classes of phytochemicals. And the different types of phytochemicals are found in different plants. And so eating your colors is sort of encouraging you to get a range of them. So in addition to the terpenoids, you have things like the glucosinolates and you have polyphenols and you have the alkaloids. And each one of these is going to have different types of functions in humans. But basically, you know, the fiber, to kind of broadly state what they do, they are anti inflammatory. So they have antioxidant capacity. Some of them are able to stop the growth of cancer cells. Because their function role in the plant was to stop the growth of fungal pathogens and so they can basically inhibit cell replication. They have antimicrobial properties.

 

Vadim  07:54

Well, yes, I remember there was some studies being done on a certain cannabinoid and MRSA. I think it was CBG. But yeah, that makes sense. They benefit the plant and they can benefit us as well just in a different way. So from your research, what's like the strongest link you found between these phytochemicals? What's the strongest evidence of it treating a disease or a condition? Which one do you think?

 

Tiffany  08:19

Oh, boy, that's a tough one.

 

Vadim  08:21

Is there one that there's like conclusiveness on? Or is it more just we think these are good for you. 

 

Tiffany  08:27

Well, when we think about the foods that, you know, I mean, you're not going to cure cancer by all of a sudden drinking a bunch of wine, and resveratrol is a chemical in wine and it got a lot of attention. And that's one of the reasons for people saying health benefits of wine. It's not going to stop you from aging. In fact, they've come up with, I think, it's somewhere around 200 liters of wine a day you'd have to drink for the benefits that they see in laboratory studies. But a lot of the drugs that we use, a lot of the pharmaceutical compounds actually are derived from phytochemicals. Now, they found ways to recreate them in the laboratory or to grow them up in bioreactors and have microorganisms produce them in order to make it more efficient to extract them. So you know, you don't necessarily think of these as phytochemicals. But Taxol is a great example. It comes from a yew tree, and the drug, I think, it's called Paclitaxel that was derived from Taxol. They can now make this synthetically in a lab, but it's one of the primary treatments against certain types of cancers.

 

Vadim  09:30

 Wow. Well, no, I never heard of that. And I've never heard of yew trees either. Are those native to America?

 

Tiffany  09:35

Yeah. I think that they grow up in the north. I know Canada. They grow a lot in Canada.

 

Vadim  09:41

Okay. I never heard of that. And the one I thought of was the Aspirin. What's the source of that? S, right?

 

Tiffany  09:47

Yeah. Salicylic.

 

Vadim  09:49

That comes from a tree, right?

 

Tiffany  09:51

Yeah. That comes from the bark of birch trees.

 

Vadim  09:53

Wow. And it really worked. It was like an ancient painkiller, right? And then it was synthesized to make Aspirin.

 

Tiffany  09:59

Right. Yeah. I think like Native Americans stuck with that too on the little piece sticks or pieces of the bark for pain relief. And, you know, obviously like a lot of these things, we don't derive it directly now from the tree. We don't go out and harvest trees and extract that they found ways to make it in the laboratory.

 

Vadim  10:17

And I guess the other one that people would probably know is like dark chocolate has these compounds in it?

 

Tiffany  10:23

It does. And honestly, myself, I love any scientific paper story that comes up and says that eating dark chocolate is good for you. Yeah. So those are the flavonols. And those are a lot of the same compounds that you find in the teas and things. And so really, widespread belief that there are benefits. But I think that there's still a long way to go in terms of showing the scientific efficacy of some of those compounds. But you know, again, anything that says eating chocolate is good for you, I'm all on board.

 

Vadim  10:53

It seems like people are really excited about some of these studies because it justifies their love of wine and chocolate.

 

Tiffany  11:01

Absolutely.

 

Caliper CBD Bioavailability Study

 

Vadim  11:02

I mean, the resveratrol people, they're always studying the fasting and stuff. And I like that. I mean, I think there's a lot of applications to this stuff, you know, and it's still experimental, like resveratrol, obviously. But I think this is probably one of the most interesting areas, I think, in biology right now. Especially if they can solve some major issues like cancers and things like that. I wanted to pivot to your study with Caliper foods. We were talking about that a little bit before we started. Could you give us a little background on that, what you did there?

 

Tiffany  11:36

Yeah. So Caliper is a local company here. When I started working with them, they had a different name, which I can't recall right now. And they became Caliper sort of over the course of the time I've known them. But the research director contacted me about another issue. And, you know, we got to talking about some of the capabilities that we have in our lab. And he said, “We're really interested. We've got this new formulation and we want to test and see the bioavailability of this formulation compared to some other formulations. Would you be willing to do that study in your lab?” And it's interesting because of the legal issues right now with cannabis and the university for a while wasn't allowed to do these types of studies. 

 

Now with kind of widespread legalization, CBD is primarily allowed. We still have to go through a few extra regulatory hoops where our legal and ethnic people have to look at our study protocols and things like that before we go forward. THC is another story. We have to have, I think, Schedule I drug administration approval and things like that to be able to do THC. But, you know, it's interesting, because I feel like I'm sort of on the forefront of being able to do these. Because a lot of universities kind of had a broad ban on doing any kind of studies with cannabis, which is unfortunate, because it's a plant that produces phytochemicals, like all these other plants that we work with. And so I honestly don't understand why,there was sort of this ban on researching it. 

 

But anyway, getting off track a little. You know, we're able to get a study approved to do this in CBD and it was a really small pilot study. But basically, we had 10 people that came in. We had two formulations. We had their new formulation that was a water-soluble formulation and then we had a lipid-soluble formulation that I guess is how the cannabinoids or the CBD comes to them. So sort of pre their processing. And the goal of the company is to produce a product that comes in a powder packet that you would buy in the store, open up and pour into whatever your favorite beverage is and then drink it. Something like a crystal light packet. 

 

So that's how we administered it. We had people put it in water, drink it. And then we had them hooked up to IVs. And we collected blood over a six-hour period. And we took blood pressure and we did a couple other measures as well. And basically just looked to see how much of the CBD we were able to detect in their blood over this period of time. So, you know, what point did it reach its highest level, when did it start going down back to baseline levels. We did have people abstain from any kind of cannabis use for several days before they came in for their clinic visit. And we did take extra blood collections at certain time points and we collected these cells that are inside the blood. They're called peripheral blood mononuclear cells. So they're basically immune cells that are in the blood. And we grew those in a petri dish and we stimulated them with something that causes inflammation and then we measured to see how much inflammation was generated. So, you know, kind of two goals. One was to look at whether we could demonstrate anti inflammatory properties of the CBD and then the other goal was just to kind of look at the kinetics of this in the blood of humans and compare it with this other formulation.

 

Vadim  15:07

Wow. And the results were that — let me see if I'm saying it right. It's water-soluble, right?

 

Tiffany  15:12

Yeah. The water-soluble. Right.

 

Vadim  15:14

That was the one that had significantly more bioavailability, right? And it was faster absorbed, right?

 

Tiffany  15:21

Yeah. We were able to detect it in the blood sooner and it reached much higher levels in the blood than the lipid-soluble CBD that we administered.

 

Vadim  15:31

And do you know what they're doing to make it water-soluble?

 

Tiffany  15:34

I don't. That's one of their commercial trade secrets.

 

Vadim  15:39

Okay, okay. So a lot of people have heard of — to quote what it’s being called now “micronized CBD”.

 

Tiffany  15:45

Yeah. Some sort of seal. I'm sure that they're encapsulating it into some sort of a nanoparticle.

 

Vadim  15:51

Okay. So this has been a trend for some time now. But this study is fascinating because you're actually –I haven't seen a lot this straightforward shown that you're getting more of it and you're getting it faster. So people who took it not only got it faster, did it stay in the blood longer? Or did it leave faster because it got in earlier?

 

Tiffany  16:12

It's hard to say. We with the lipid-soluble really barely got above baseline levels. And so, you know, it's hard to say if it was there longer because the lipid-soluble was hardly detectable. 

 

Vadim  16:25

Really?

 

Tiffany  16:25

I do want to add. So we were blinded. We were just given these two different powders and, you know, they had codes on them. So we didn't know which was which. We randomized our participants. So that, you know, we didn't necessarily give one to a certain type of person and one to another type of person. And we did all of the analyses blinded. And so it wasn't until I had the data analyzed that we went back and matched up our codes with what the actual formulations were. And personally I enter every study with a degree of skepticism. You're like, oh, this isn't gonna work. I was really astounded that there was such a big difference and it was very clear cut in terms of the absorption and bioavailability differences between these formulas.

 

Vadim  17:11

That's really interesting to hear you say. So you went into it kind of thinking like, yeah, this is all kind of maybe like a gimmick or something, right? Or not as big a deal as they make it sound.

 

Tiffany  17:20

Right. 

 

Vadim  17:21

Do you yourself use CBD or ever have used it for any reason?

 

Tiffany  17:26

Yeah. My husband uses it religiously, saying he can't sleep at night without it. I get joint pain occasionally. And we'll use CBD creams and I, at least anecdotally, for me, it seems to work really well.

 

Absorption Rates of CBD in Water vs Oil

 

Vadim  17:40

I mean, the creams are another interesting story from a scientist point of view. Because how is it getting in there, right? That's the big debate with the creams. And a lot of these companies are fighting to be the one that gets the most absorption. It’s gotta go through the skin, right? And then into the area of pain. That's been one of the big debates in the space. But I mean, studies like this that you did is like that’s amazing. I've never seen either and I'm a skeptic like you with these products. I always think like, yeah, it’s probably just a gimmick. It's all the same CBD. But this is, I mean, it's amazing. These results. Do you plan to do another one like a follow up?

 

Tiffany  18:17

We actually have. It's published in the Journal Pharmaceuticals. I didn't run this study. One of my colleagues did because he's got a bigger clinical space and it was a little bit bigger study. They did six different formulations including the one that we tested — this water-soluble formulation. And we found one that actually consistently was more bioavailable than the formulation that I report in the study that you're talking about. That just came out, I think, at the beginning of the year. So in January, brand new study.

 

Vadim  18:49

Okay. Is that public that people can find?

 

Tiffany  18:52

It is public. Yeah. And it's open access. So it's free for anybody to be able to read the entire study.

 

Vadim  18:59

Okay. I'll get that from you afterwards so I can put in the show notes for people. And are you saying that in that study, they did six different CBDs and there was one that actually did better than the Caliper one?

 

Tiffany  19:09

Yes, there was one that — well, so Caliper supplied all of these. And again, the differences in these formulations is to some degree their private trade secrets, but they have a new formulation that they're working on that performed even better than the one that we tested in that first study.

 

Vadim  19:26

Wow. And what was better about it?

 

Tiffany  19:28

I mean, just better in terms of absorption. Much higher levels were absorbed in that particular study, and more consistently. So this is something else I wanted to talk about. We saw even with the water-soluble, there was a lot of variability from person to person in the total CBD that we were able to detect in the blood. And that's an area of interest to me that I'd like to follow up on. Because why? Does it have to do with body weight? That's one of the things that we explored in this second study. My colleague has what's called a DEXA scan and it can look at lean and fat mass. And so we report correlations between the amount of lean and fat mass that individuals have and their absorption. 

 

The other thing about the study that we just wrapped up and got published is that it was what's called a crossover study. So instead of having two groups of people taking two different treatments, we had one group of people that took all of the treatments at different time periods. And then they'd have a washout period where they clean out all the cannabinoids, and then they come back into the lab and they take a second treatment, and they'd go through the process again. And so they continue to do that until they've been through the round of all of the different treatments that we had. And so really, you're comparing absorption of different formulas within a single individual. So you can see a little bit better if there were ones that were really truly better absorbed, or if that was just individual differences.

 

Vadim  20:58

Wow. Yeah, that's interesting. I think our listeners would love to see that study. So they didn't tell you after the study what about that formulation made it the best, like the one that did better the second time?

 

Tiffany  21:12

I don't think so. Again, you know, a colleague of mine was the lead on that study. And so he might have a better idea. He might have had more conversations with them about what the difference was between that one and the lipid-soluble, the water-soluble one that I tested in this first study.

 

Vadim  21:28

Oh, okay. And it was all powders that you did all the products?

 

Tiffany  21:32

Yes, they were all powders, I believe. The ones that I tested in my study were all powders. And I think that they were in the second study although there may have been some liquid ones, but they were all delivered in the same manner. So they were all mixed with water and consumed as part of an eight-ounce glass of water.

 

Vadim  21:48

So it sounds like it was very professional, the collaboration with them was very set up. Because you hear about these studies where you get like a one pager out of it but you don't really know the details. It sounds like this was done very top notch with your collaboration with them.

 

Tiffany  22:02

Yeah, I mean, you know, we're not affiliated with the company in any way. We're scientists at the university and this is kind of what we do on a regular basis. It’s to design and run these different types of studies. And so we just applied the same principles that we would to any of the studies that we were designing and incorporated their products into our study designs.

 

Vadim  22:23

Yes, yes. Are you working on any other CBD studies right now?

 
 

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.

 

 

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