CBD, Good for Your Gut or Marketing Hype?

So Alex, I guess I’ve put some pretty big shoes out here for you to fill, but I’m happy you’re here to help steward us through this conversation.

Dr. Alex Capano, DNP, CRNP, FNP-BC: Thanks, I hope I can meet that request.

DrMR:   Yeah, I have no doubt. Can you tell people about your background? It’s very relevant to this area, and I believe you are one of the first to graduate with a focus in cannabinoid research. I’m paraphrasing, but get us to speed on your background and your training.

DrAC:   Sure. So my original training was actually in neuroscience. Then went back to school, got a couple of degrees to become a family nurse practitioner. I practiced full-time seeing patients in primary care, and actually, in sexual medicine mostly. And then went back and got a doctoral degree that’s focused on cannabinoid science.

I have been recognized as the first person to focus on comprehensive cannabinoid science at the doctoral level, because no one else had the opportunity before me. The center didn’t exist. I was really in the right place at the right time and studied in what’s called the Lambert Center for the Study of Medicinal Cannabis and Hemp. That’s at Thomas Jefferson University in Philadelphia. So there maybe still needs to be credentialing around different programs for cannabis, but I was able to get through a couple of years ago.

DrMR:   Nice, well, congratulations to you on being in the right place at the right time. Certainly, it’s a booming field.

DrAC:   Serendipitous, absolutely.

DrMR:   One of the areas I wanted to start our conversation with was regarding the potential utility of either cannabis (meaning, smoking pot for lay parlance here) or marijuana—you don’t have to smoke it, you could use it as an edible or what have you, but it would be your complete cannabis that has THC, CBD, and the whole gamut—versus CBD only, which could be derived from hemp, it could be derived from cannabis.

These are typically legal over-the-counter depending on the source, and they have no psychoactivity, meaning they don’t get you high. I just want to give a brief primer on my understanding, certainly not an expert here, but I’ve done a little bit of poking around. So I want to throw these few ideas out there regarding applications to gut and then get your take. And then we can let the conversation evolve from there.

Defining Cannabis, Marijuana, Hemp, CBD

DrAC:   So if it’s okay, I just want to back up a little bit to make sure we’re all working with the right definitions.

There’s a lot of confusion in the space: what is cannabis, what is marijuana, what is hemp, what is CBD?

DrMR:   Yeah, please, let’s get our definitions straight.

DrAC:   So cannabis is either marijuana or hemp. That is the term for the family of plants, the Cannabis sativa plants. And then, inside of the flowers of those plants are molecules called cannabinoids. So CBD is a cannabinoid and THC is a cannabinoid. There are many others, but those are the two most abundant, most well-known and of the moment for a good reason.

THC is the cannabinoid that causes intoxication or gets you high. And a hemp plant is a cannabis plant with 0.3% THC or less. And a cannabis plant with more than 0.3% THC is considered marijuana, and that’s really just a U.S. law definition.

Even a cannabis plant, that at one part of its life cycle could have been considered hemp because of that low amount of THC, could mature and then we call it is “go hot” and could evolve into what’s considered marijuana. And that’s important for anyone looking to consume this and wanting to make sure that they stay in federal, legal regulations. So hemp grown in the U.S. and cannabis oils derived from hemp are federally legal. But at the federal level, no cannabis oils derived from what’s considered a marijuana plant are federally legal.

What’s also interesting is that plants that have higher THC tend to have very low CBD and vice versa. So a hemp plant, because it has such low THC, is a great source of CBD-rich oil.

DrMR:   So it’s not something that the industry is doing to try to get around legal restrictions. There’s actually some reason behind why hemp is so popular now?

DrAC:   Yes. So the 2014 Farm Bill created this pilot program of legality, and the 2018 Farm Bill made this permanently legal. So you can have a hemp-derived CBD oil that is only CBD and we call that isolate. You can have it where it’s called broad-spectrum, which means it has these other phytocompounds, these other cannabinoids and terpenes and flavonoids, but has eliminated all traces of THC. And then you can have what’s called full-spectrum, which has all of those compounds in it, plus 0.3% THC or less. So even with the hemp-derived, over-the-counter federally-legal CBD oil, you can have some THC in there. It’s just not considered high enough to cause euphoria and intoxication.

DrMR:   To get you high.

DrAC:   Yeah.

DrMR:   Because really, if you were to state it—maybe not fully technically accurately, but in the simple take-home message—it would be, if it has enough THC to get you high, it’s not able to be sold legally in a lot of states. If it has a minimal amount of THC, not enough to get you high and is derived from hemp, that’s going to be legal, is that a fair…

DrAC:   Yes, good summary.

Isolates, Full-Spectrum, Broad-Spectrum CBD

DrMR:   While we’re on this topic of isolates versus full-spectrum, for the consumer who’s saying, “This one is claiming to be full-spectrum CBD, this one is claiming to be full-spectrum,” meaning the whole plant and all the parts, “this other one is claiming to be an isolate,” is there any consensus in terms of what’s better to use?

DrAC:   Actually, yes. There’s something called the entourage effect, which I always say sounds like pseudoscience to me—the entourage effect—but it’s pretty well-established in the literature. And what that means is that CBD works better when it is surrounded by its constituents or its other compounds that exist naturally in the plant. So we know that when you add a little bit of THC to CBD, you get a more potent response at a lower dose.

And we know that certain terpenes, at least, also contribute to that effect. Beta-caryophyllene, for example, certainly has been demonstrated in the literature to help CBD’s efficacy. I always use this analogy that isolate CBD still works, but you might not get as much bang for your buck with it. It’s like putting a packet of vitamin C powder into a drink and that’s how you get those nutrients, versus eating an orange, which would be full-spectrum.

DrMR:   Great analogy. Okay, that makes sense. So I think that’s one valuable take-home for the audience. Look for a full-spectrum rather than some kind of isolate. And this is typically fairly prominently marketed when it’s full-spectrum, right? You’re going to see that usually displayed somewhere on the label pretty clearly. I feel like that’s a market differentiator many CBD companies are looking to use to show how their products are better than the others. And so it shouldn’t be too hard to find that, right?

DrAC:   That’s true. And then you’ll also see broad-spectrum, which has the other compounds, but no THC. Even a little bit of THC does pose the risk—it’s unlikely—of some of someone failing a drug test. So that’s the middle of the road, you get the other compounds that contribute to the entourage effect. Although THC is arguably the most important compound for that. But at least you’ll get some of it with a broad-spectrum, without the risk of having any THC in your system.

DrMR:   Oh, so the full-spectrum does run the risk of a small amount of THC?

DrAC:   Yes.

DrMR:   Not enough to get you high probably, but enough to potentially fail a drug test?

DrAC:   Yes. It’s unlikely that you could take enough, but the risk is there. So especially department transportation workers, certain people who are subject to drug screenings and really can’t risk that, should know what they’re getting into if they choose a full-spectrum. That there is that risk.

DrMR:   Gotcha, okay. That’s actually really helpful for people to know. Imagine the surprise if someone failed the drug test because of the CBD product they bought online, and they thought they all had all their bases covered.

DrAC:   Yeah, it’s happened. So I just think informed consent is important in this industry as well.

DrMR:   I’m making a note here for our audience for our Fast Fact notes. So remember, if you’re working in any profession where you might be drug-tested, use the broad-spectrum. You probably don’t want to use the full-spectrum, because that might contain a small amount of THC. Not enough to get you high, but enough to potentially fail a drug test.

DrAC:   Right.

DrMR:   Super important. See, already, you’ve given us what I think is worth the call here. Just those two tips right there. Obviously it has a lot of applicability and could have some nasty consequences for someone who didn’t realize those finer points.

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Gut Health & CBD

Okay, so let’s just go into a few of the points regarding gut health now, because that’s something our audience is very curious about. I’m sure we have a number of people listening here who might be struggling with IBS, IBD or general gut symptoms and might have gas, bloating, reflux, the inability to expand their diet. They may have to eat a very narrow cropping of foods to prevent symptoms.

When I looked at a few review papers, there was a paper on cannabis and autoimmunity. They cite two randomized controlled trials with cannabis here. This is a plant that would get you high. And essentially, they found positive results for Crohn’s. It was about a 50% response rate or higher. So in my opinion, this randomized controlled trial using cannabis in Crohn’s was pretty impressive. There’s also another randomized controlled trial —this is not GI—showing that pain, which I believe included also some abdominal pain, showed positive results. So that’s pretty encouraging.

Now, I’ll contrast that with Examine.com’s review on CBD. I found Examine.com to be a great source to get an evidence-based synopsis of what a body of literature shows. They review two randomized controlled trials (using the terms loosely here). One in Crohn’s, only using CBD. They found it was safe, but not effective for Crohn’s. And for ulcerative colitis, they found the CBD was also safe. They didn’t hit the threshold of showing effect, but there seems to be a trend that it might help and I’ll include Examine’s level of evidence table there .

So that gives me a little bit of pause with how quickly I rush to recommend CBD for patients with gut ailments. That’s not a ton of research, so we can’t draw too strong of a conclusion from four studies, but it does throttle my enthusiasm a little bit. How do you interpret these findings, Alex? And is there a greater context that we can examine and help people know whether this would be considered a great, an okay or a poor intervention for gut health?

DrAC:   I would say at this point, okay. That’s mostly based on looking at the mechanism of action and understanding its potential at a cellular level. And then also, it’s frustrating to use this word that’s often used in this space, but the reality is, anecdotal. For me, anecdotal is still an n of a thousand-plus patients that I observe every day. But that’s not a randomized control trial. And that’s obviously how we like to draw our conclusions when we’re using evidence-based practice. The problem is, there are a lot of barriers to researching cannabis, both CBD and THC, and utilizing them in a way where you can do a double-blind randomized control trial, where you can really control dosing, and where it can be plant-derived and full-spectrum oil.

There are a lot of barriers—in the U.S. especially, but also globally—to this type of research. And there are barriers to funding as well. It’s starting to open up a little bit, especially for CBD research, which is nice. But I say, it’s like ouroboros, where the snake is just eating its own tail.

We say, “Well, there’s no research, but we won’t let you do the research,” and “We won’t let you do the research, because there’s no research,” and then it just keeps going. But you really have to separate THC and CBD, and then also plant-derived versus synthetic cannabinoids. There are synthetic cannabinoids and they do act differently on these receptors.

But if we back up and just look at why we’re even investigating this, it’s because of endocannabinoid receptors and their abundance in GI tissue. We all have an endocannabinoid system. All of our pets have an endocannabinoid system. And it was discovered in the early 90s in Israel, but is unfortunately not really taught in most clinical schools. There’s a major knowledge gap across practitioners about what the endocannabinoid system is, what it does and how we can harness it for a potential across a variety of conditions and symptoms. It’s made up of two different types of receptors, your CB1 and your CB2 receptors.

CB1 receptors are the most abundant G-coupled protein in your brain. They are also in your central nervous system. CB2 receptors are pretty scarce in the central nervous system, but are abundant in the periphery. Particularly on immune cells and in the GI tract, you have these CB2 receptors. THC binds directly to these receptors and alters their function. CBD actually has a pretty low affinity for both of them and just alters functions within the cell. And both CB1 and CB2 receptors have a variety of functions.

They’re exceedingly complex, poorly understood, and we have a lot of discovering to do. But we know that they regulate homeostasis. So they are going to influence everything from your mood and breath and sleep/wake cycle to inflammation and immune response. I think that that’s the most important topic across, really, every chronic condition, but particularly, for GI issues like Crohn’s disease and IBD.

CBD particularly is a pretty potent immunomodulator and anti-inflammatory agent at the CB2 receptors in the gut. And that’s why so many researchers and practitioners are excited about the therapeutic potential for CBD in these conditions. That being said, you’re right, there are really not great randomized control trials that demonstrate that. It’s really case reports and observations anecdotally right now.

DrMR:   Right. It is a tough balance to strike. On the one hand, I believe we can learn a tremendous amount with these n of one experiments. This is what I do in the clinic every day, and this is how I’ve really come to develop the clinical model that I use. And it’s also, of course, by evidence. But it’s perhaps equally guided from the boots-on-the-ground clinician in the office treating patients and getting feedback from them.

On the other hand, placebo effect does influence the way one will report their response to a given treatment, and that’s one of the concerns that I have with anything that’s really rising to popularity. If everyone’s talking about how great it is, you’re going to go well beyond the 45% average placebo effect seen in randomized controlled trials and arguably maybe even up to 75-ish% could be influenced by placebo.

So it’s a challenge or it’s a challenging situation to be in, where I’m trying to get a read, but some patients seems so excited about CBD. I’m wondering, is this like other things patients have come in raving about? They rave for a few months, but then a few months later, the placebo effect wears off and they’re no longer raving about it.

So I just pose it as an open thought and question, I don’t have a great answer for it. I guess that’s what we’re struggling with, as the scientific community is trying to get a better consensus on what place cannabinoids or CBD should have in gut care. And I guess that’s something that you’re actually, obviously, trying to answer on a daily basis.

DrAC:   I always tell people, this is not a magic potion that is just going to cure everything for everyone. It really does help some people to live healthier lives and to be free or reduced of symptoms of chronic diseases. But it’s not this magic bullet, this snake oil. I think we need to get away from that thinking, because it actually increases the skepticism, and reasonably so.

DrMR:   Right, yeah. That’s actually an excellent point. I just want to underscore that really quickly for providers and for patients. If you want to kill the ability of something to permeate its way more into the medical and scientific system, be very excited about it. What that will do is make people skeptical of it. Yeah, I think that’s an excellent point.

DrAC:   But we do know that CBD is an anti-inflammatory agent in multiple mechanisms of action. It’s even a COX inhibitor, but it modulates mast cell activity and histamine release from mast cell. It reduces immunoreactive microglia, it decreases PLR responses, promotes adenosine receptor A2A, and the list goes on and on.

So we do know from a basic science perspective what some of these mechanisms are, and then we’re obviously trying to translate that into practice in the real world. Right now, it’s difficult with barriers to research. And also, that some of the research is using doses that are all over the place. Or maybe they say cannabis and they mean THC, or they mean CBD, or they mean both. So we have a long way to go until we have a lot of abundant human data on this.

THC Plus CBD in Gut Health?

DrMR:   Sure. And to the other point you made a few minutes ago, I have had patients come in who’ve sworn by either some type of cannabis containing THC or CBD, so those reports are there. Again, it’s a challenge trying to parse this. And I wonder, do you think—given some of the way the receptors are stimulated by THC vs CBD in the gut—it’s likely we’ll find that having some THC, maybe enough to get you high, getting over that threshold would be better for gut health? Or do you think there’s a probability that we’ll eventually come to learn that CBD alone could be just as effective as a combination of CBD and THC?

DrAC:   I think we’re going to find that you need some THC to get the best effect. I think CBD is a viable option for people who, for a number of reasons, cannot have any THC in their system. We see that CBD works better, but THC has therapeutic value. It has a few more risks that CBD doesn’t have, but at low doses, we see that you can certainly have a therapeutic response without those risks.