Up in Smoke: Where Cannabis Meets the Immune System

Since the discovery of cannabinoid receptors in the mid-1990s, researchers have been trying to determine their role and how they affect the immune system. Barbara Kaplan, Mississippi State University, discusses research in this area with co-hosts Anne Chappelle and David Faulkner and also shares what scientists are discovering about CBD, vaping, THC, and more.

About the Guest
Barbara Kaplan, PhD, is an Associate Professor in the Center for Environmental Health Sciences in the College of Veterinary Medicine at Mississippi State University. She got her BS in environmental toxicology at University of California Davis and her PhD in pharmacology and toxicology from Michigan State University. Before starting her own lab at Mississippi State, she conducted postdoctoral research at the University of Chicago and worked as a Research Assistant Professor at Michigan State. Her transition from MSU to MSU was easy!

The focus of her lab is trying to understand effects and mechanisms by which drugs and chemicals affect the immune system. She has National Institutes of Health (NIH) funding to study aryl hydrocarbon receptor ligands on antibody signaling and also has been studying the immune effects of marijuana chemicals for more than 20 years. Her work was some of the first to suggest that cannabidiol (CBD) exhibited immune suppressive effects through a mechanism similar to other well-known drugs, such as cyclosporin.

With the passage of the Farm Bill that legalized CBD from hemp and US Food and Drug Administration approval of a CBD-containing therapy for epilepsy, information—and misinformation—about CBD and other marijuana chemicals has exploded. Therefore, she has been active in obtaining and practicing her science communication skills. She attended the Alan Alda Center for Communicating Science bootcamp at Stony Brook University in 2017 and got to meet with Mr. Alda when he gave a presentation at Mississippi State University in 2018. She has been involved with many workshops and other training sessions since then, including a recent interactive Continuing Education course for SOT in which attendees learned some basic science communication skills, presented an aspect of their science in small groups, and then received constructive feedback in real time.

Transcript

[00:00:00] Adverse Reactions “Decompose” Theme Music

[00:00:05] David Faulkner: Hello, and welcome to Adverse Reactions.

[00:00:08] Anne Chappelle: This season, our theme is intersections, where we see toxicology intersect with another science. 

[00:00:15] David Faulkner: Well, a lot of other sciences.

No person is an island, and no discipline has all the answers. But when scientific fields collide, some really interesting things happen. I’m David Faulkner,

[00:00:27] Anne Chappelle: and I’m Anne Chapelle. 

[00:00:28] David Faulkner: Welcome to Adverse Reactions Season 3: Intersections.

[00:00:32] Adverse Reactions “Decompose” Theme Music

[00:00:39] We’re excited to welcome you to today’s episode, “Up in Smoke: Where Cannabis Meets the Immune System.”

[00:00:45] Barb Kaplan: We actually found that a lot of the effects of the cannabinoid chemicals that we were using, although they exhibited affinity for these receptors, their effects were not being mediated through these receptors. And so that was a hard thing to sell to the field because everyone just assumed that since the receptors were there, they must be the reason that we have these effects. 

[00:00:06] Adverse Reactions “Decompose” Theme Music

[00:01:12] David Faulkner: Hello, and welcome to Adverse Reactions. Today we have an interview with the wonderful Dr. Barbara Kaplan. She is in the Center for Environmental Health Sciences at Mississippi State University as Associate Professor, and she studies cannabis. Doctor, it is wonderful to have you on the show.

[00:01:30] Barb Kaplan: Thank you very much for having me. I’m very excited to be here to talk about cannabis.

[00:01:35] David Faulkner: Yes, something near and dear to my heart.

[00:01:36] Anne Chappelle: I think we need to have some kind of explanation: it’s not like you do cannabis. Tell me what research you do with cannabis.

[00:01:46] Barb Kaplan: Yes. Fair. So, I am an immunotoxicologist. So, I have studied how drugs and chemicals affect the immune system, and so, one of the things that we’re really interested in is trying to understand how some of the chemicals from a marijuana plant might affect your immune responses.

[00:02:03] Anne Chappelle: Are you trying to show that it has a pharmacological effect, like quantify that effect? 

[00:02:10] Barb Kaplan: One of the things that we’re interested in is whether or not some of the chemicals from the marijuana plant affect the immune system to see whether or not there is a possibility of even developing them as potential drugs or drug-like therapies.

For instance, one of the things that we and others in this field have found over the last several years is that they seem to be, for the most part, immune suppressive and/or anti-inflammatory. So, in that regard, they might act like Tylenol, for instance. 

We’re trying to understand whether or not we can harness their effects for good. The other thing that we’re trying to understand is that if they do have these effects and people are using marijuana or cannabis recreationally or for therapeutic purposes, are there effects that maybe we don’t yet know about or we should be warning people about? What is the risk-to-benefit ratio of using these compounds or these extracts for either medical use or recreational use?

[00:03:09] David Faulkner: Before we go to far in, I think it’s worthwhile to establish a bit of terminology. Just, we use the words cannabis and marijuana interchangeably. Are they the same thing?

[00:03:18] Barb Kaplan: Marijuana is a loose term that’s given to the plant, which is Cannabis sativa, or, I suppose, Cannabis indica is another plant. So, that’s the group name that’s given to the plant. And then, in those plants, there are these various chemicals that are called cannabinoids, which is similar to the cannabis word, and these are all structurally similar. Some of them are the reason that you feel the high you get when you smoke marijuana. Some of them are not. There’s actually probably in the order of about a hundred of these different chemicals, and we know a lot about just a few of them.

[00:03:49] David Faulkner: My understanding is that one of the reasons why these cannabinoids have an effect in the body is because there is actually a system in the body that is built to be receptive to them. The endocannabinoid system?

[00:04:05] Barb Kaplan: Yes, that’s correct. So, this system is very similar to the opioid system if people are familiar with that, and what that means is that we have natural, endogenous—or in our body—opioids that combine to receptors that are on the outside of cells and change something in that cell, make you feel whatever you feel with opioids.

And then, the same thing happens with the cannabinoids. So, the endocannabinoid system is very similar. We have endogenous compounds that are made in our body that are called endocannabinoids, and those bind to at least two known cannabinoid receptors. So, we have CB1, which is the main receptor that’s found in the brain, and that is really the one that’s responsible for the high that you feel when you smoke pot. And then, CB2 is another receptor, and what’s interesting about CB2 is that it is found more peripherally, but it’s found at very high levels in cells of the immune system.

[00:05:02] David Faulkner: Ahh, interesting. But not just in the immune system, is it that these…

[00:05:06] Barb Kaplan: No, correct. 

[00:05:07] David Faulkner: So, these receptors: it seems like they do a lot of different things.

[00:05:11] Barb Kaplan: Yeah, they do. So, certainly, we didn’t develop these receptors because the world thought we were all gonna be smoking pot someday. So, they play a lot of different roles in just our normal physiology. For instance, one of the really cool things that cannabinoids can do in the brain—and I hope I get a little leeway here cuz I’m not a neuroscientist—but one of the things that they can do is they can control the amount of neurotransmitters that are released from neurons and really affect that communication in the brain.

And the other thing that the cannabinoid receptors have been shown to do is they can regulate appetite. They can regulate the immune system, so there is a normal physiological reason that we have endogenous cannabinoids. And then, any cannabinoids that we take into our body can act on that same system.

[00:05:57] David Faulkner: Wow. 

[00:05:58] Anne Chappelle: How did you choose pot? There’s lots of ways you can study the immune system, and so, why pot? 

[00:06:05] Barb Kaplan: When I started my PhD program at Michigan State, I did my first rotation in the lab of Dr. Norb Kaminski at Michigan State. And then, I went into another rotation, and I ended up really liking learning about immunotoxicology. And one of the things that he was starting at that time was trying to understand how these chemicals modulate the immune system. So, I was really attracted to the idea that you could combine immunology, pharmacology, and toxicology all in one system. So, I decided to stay with Dr. Kaminski and get my PhD there.

[00:06:39] David Faulkner: Was it just the system, the endocannabinoid system, that you were looking at, or was it actually the effects of the drug?

[00:06:45] Barb Kaplan: I guess it was probably both—although we may not have known it at the time. So, the early ‘90s was actually a huge turning point for cannabinoid research for, I think, a couple of reasons. 

So, from a society standpoint, there was the beginnings of the traction for legalizing marijuana, whether that be for medical use or recreational use, and that happened about the mid-’90s. The other thing that happened scientifically in the early ‘90s was that those two cannabinoid receptors that I talked about earlier they were cloned. So, scientifically, we really had a lot of good forward motion in the cannabinoid field because now we actually had receptors. We had a lot of ideas that the receptors probably existed, but then, they were cloned, so then, we knew they were there. So, that really allowed us to start investigating cannabinoid effects of the immune system. And I think we—and probably everyone in the field at the time, especially since that CB2 receptor was found at high levels in the immune cells—we thought, “Great, we’ve got this figured out. The cannabinoids are gonna act via the cannabinoid receptor, and we’re gonna understand the pharmacology.”

[00:07:55] Anne Chappelle: Nobel Prize. Here you go. 

[00:07:58] David Faulkner: There you go.

[00:07:59] Barb Kaplan: Yes. Not yet. But it was interesting over the next few years we actually found that a lot of the effects of the cannabinoid chemicals that we were using, although they exhibited affinity for these receptors, their effects were not being mediated through these receptors. And so that was a hard thing to sell to the field because everyone just assumed that since the receptors were there, they must be the reason that we have these effects. And I think that’s true for a lot of the effects, but I also think it’s true that there are other receptors through which these chemicals act. Some we know about, and some we don’t know yet.

[00:08:33] David Faulkner: That is very interesting. So then, you alluded to the fact that legalization started up in that period of time in the mid-’90s. In the most recent election, we actually saw two more states legalize it for recreational use, which is very exciting, but this creates kind of an interesting position for you, I would think, as federally it’s still illegal, still Schedule I.

[00:08:55] Barb Kaplan: Yes, correct. So, you’re absolutely right. Certainly, the number of people who are using these compounds in various forms has increased exponentially over the last 20 years or so, and the other thing that’s happened is that an entire industry has been built up around these things, especially after following the legalization of the Farm Bill in 2018, which legalized hemp—which is another layer of confusion, I suppose. But yes, from a research standpoint, these chemicals that I use from the marijuana plant are still Schedule I because they come from marijuana, including THC, so we have to certainly comply with all the regulations in order to do this research.

[00:09:35] David Faulkner: So, this is to say that there are regulations. There are ways you can do this and be within the bounds of federal law.

[00:09:42] Barb Kaplan: Yes, correct. There are ways. So, you have to have a state and federal Schedule I research license, and then, you have to have identified where you’re gonna get the compounds and what you’re gonna use and justify how much you’re gonna use. 

[00:09:55] Anne Chappelle: In the medical marijuana world, you hear a lot about the different strains and the different kinds of marijuana and “This one’s really good for two things, and this one’s really good for that.” And that’s gotta come up—either with the potency, the binding—that’s a very complicated messy place right now.

[00:10:15] Barb Kaplan: Indeed. It’s just gotten more messy over the last few years as this industry has grown up because it’s grown up without any really regulations in place. People are selling these different cultivars, as they call them. They aren’t really called strains; they’re cultivars. And they may or may not have more CBD or be CBD-rich versus more THC or what have you. And then hemp itself, as defined, is the plant that has less than 0.3% THC. So, typically, hemp is very CBD-rich. So, especially once the Farm Bill passed and made hemp legal, that’s when we really saw the explosion of CBD products hit the market because now CBD from hemp was legal. And so, now, you can see that CBD has infiltrated almost everything—whether they be edibles or vaping products or pillows or stuff for your pets or lotions or what have you. So, that really has changed since the Farm Bill passed.

[00:11:14] David Faulkner: Pillows is a new one. I’ve not heard of pillows.

I’m so curious cause we were talking about all these different like cultivars and these different things that they are purportedly able to do. Is it just the THC and CBD? And you mentioned there are other cannabinoids, or I’ve heard a lot about terpenes in recent years.

[00:11:32] Barb Kaplan: Yes. Terpenes are a big one. So, as I indicated, there’s probably about a hundred cannabinoids in the marijuana plant. And that is in addition to any of these other compounds like terpenes, which in part are responsible for the characteristic smell of marijuana. So, I think that’s a really interesting pharmacology question because when you’re studying a crude preparation of marijuana, that’s very different than vaping THC because of course you’re being exposed to these hundreds of compounds, and we know a lot about some. We know a lot obviously about THC and CBD. We know a fair bit about cannabinol; we know a fair bit about cannabigerol. And then there’s, like I said, tens of others that we really don’t know that much about—not to mention the terpenes, which can also have effects. So, they actually call that an entourage effect, meaning that all the chemicals come together and they are what mediates the effect when you’re using crude marijuana as opposed to just going and getting your CBD-rich hemp although the CBD rich hemp I suppose would also have other things in it as well, just not so much THC.

[00:12:42] David Faulkner: So, if you were trying to formulate a drug, wouldn’t you have to contemplate that as well?

[00:12:47] Barb Kaplan: Yeah, for sure. The other thing that’s interesting is that THC as a drug has actually been approved in the United States since 1986.

[00:12:55] David Faulkner: Whaaaat?

[00:12:56] Barb Kaplan: So, it’s a drug commonly known as Marinol, and it’s an oral preparation that was originally indicated for attenuating nausea associated with cancer chemotherapeutics. And then, it was rescheduled—what that means is that it went up on the scheduling system so that there were fewer thoughts about it being addictive and less paperwork for doctors to prescribe it—but it was rescheduled in 1992 to also add appetite stimulation for cachexia. So, actually, we have had THC legal in the United States since 1986, but it’s just a pure, synthetic THC in oil known as Marinol, and I think the challenge with it has been the bioavailability after oral dosing of THC is much lower than smoking pot. And especially if you are a regular pot smoker, you certainly know how to fine tune your pups and whatever to increase your bioavailability and/or your exposure to it. So, that has been the big argument is that the oral part of THC just isn’t as effective as somebody just going to smoke a joint.

[00:14:05] Anne Chappelle: There has been a lot in the news about vaping and vaping and vaping, and you’re studying these things in vitro, right? But you do in vivo studies, too.

[00:14:21] Barb Kaplan: We do in vivo and in vitro, yes, and we do mouse and we do a little bit of rat. We do human, and we do dog.

[00:14:28] David Faulkner: Dogs and humans: those are very interesting to me because (1) humans is relevant. (2) Dogs is a curve ball. Why dogs?

[00:14:36] Barb Kaplan: So, there’s no doubt with things like CBD that they are getting as much into veterinary medicine as they are human medicine, and I think there’s a lot of similar indications that people are trying to use these compounds in animals like humans. So again, these inflammatory diseases (osteoarthritis, rheumatoid arthritis, other immune-mediated diseases), people are trying to see whether or not they’re effective.

They’re also looking at a number of cannabinoids for pain and whether or not they could be opioid-sparing therapies so that you could reduce your opioid exposure or switch over to it or not use them at all. What we’re doing at Mississippi State, I now help to run the summer research program for veterinary students, and over the last few years, I’ve had my veterinary students test the purified compounds in vitro using dog peripheral blood mononuclear cells. So, the nice thing about the immune system is that we’re able to get immune cells just from a blood draw, and it really doesn’t matter what species it is as long as you have either IACUC or IRB approval to do that. I suppose if we had giraffes and we had an IACUC for giraffes, we could look at giraffe PBMCs. We don’t yet, so …

[00:15:47] Anne Chappelle: That inhalation deposition would be really cool in a giraffe. 

[00:15:52] Barb Kaplan: But yeah, we’ve been looking at trying to understand whether or not the dog immune cells are responding similar to what we’re seeing in the mouse and similar to what we and others have seen in human. And the other kind of cool thing about dogs is that of course, they’re outbred, so they might be a little bit more like humans rather than mice. And also, they do get some of the same diseases that we get. There’s several benefits in using the dog cells, and like I said, we can just get those cells from a blood draw. So, that’s nice, and it gives us a number of things that we can do in vitro with the dog immune cells. At this point, we are not putting CBD or THC in dogs and then looking at any kind of in vivo thing in dogs. We’re actually taking the cells out and then trying to see if they act similarly to other species that we’ve taken cells from. You know, we would hypothesize if the cannabinoids would be immune suppressive and anti-inflammatory when we use these compounds in vitro. It actually has been a little bit more challenging than that. I made the mistake several years ago of, when I designed this project, of thinking, “Oh, this will be easy.”

[00:16:57] David Faulkner: Famous last words. 

[00:16:58] Barb Kaplan: Yes. So, science karma knows when you think something should be straightforward. It hasn’t been that straightforward, and it’s actually been a little bit frustrating cuz I really thought that the dog cells would act similarly to what we’d seen in mouse and human—and they really aren’t.

So, I don’t know if it’s the breed of dogs we’re using or that we’re not seeing as drastic an effect because it’s an outbred population or what yet. But we are investigating some of those things right now. And one of the cool things that we did do early on was to verify that the CB1 and CB2 receptors were expressed in dog immune cells, which they are. So, we were able to do PCR in the blood, and then, we did some staining of the receptors in dog spleen samples. And so, we were able to find that the dogs do express both CB1 and CB2, just like we anticipated, but now we have the data to show that.

[00:17:54] Anne Chappelle: You are at Mississippi State, but you’re in the veterinary college, right?

[00:18:00] Barb Kaplan: Yes, I’m in the College of Veterinary Medicine. 

[00:18:02] Anne Chappelle: Is that unique—toxicology being in the vet area?

[00:18:07] Barb Kaplan: I don’t know that it’s unique. I think there are several departments at least in the United States where the toxicology is housed in the college or schools of veterinary medicine. So, I am not a vet myself; I’m a PhD, so my role in the college is, of course, the research. And then, I teach immunology to the first-year vet students, and then now, as I indicated earlier, I help co-direct the summer veterinary research program. So, we bring in about 15 to 20 students who have just completed their first year of vet school, and they come for the summer, and they’re matched with the mentor, and they conduct research projects. And then, there’s a big symposium that all the vet students across the country and some from abroad, they come over to the Veterinary Research Symposium and talk about their summer research. Just gives us a chance to introduce research to veterinarians and have them meet people who have established careers—if they’re a DVM and they have research in their career—to be introduced to some of those folks. 

[00:19:03] Anne Chappelle: Have you ever snagged one and gotten ’em to drop the DVM and switch to tox?

[00:19:08] Barb Kaplan: What we do have here—and I know other schools also have—are combined DVM-PhD programs. So, my first two graduate students at Mississippi State were these dual-degree students. They started their DVM and did research as their curriculum allowed, and then, once they took the NAVLE (the standardized tests) and then finished the DVM, then, they spent another three-ish years in my lab doing their dissertation.

And then, the other place where I’ve seen this work really well is especially in pathology, where people go and they get their PhD and their DVM, and then, they do a residency in pathology and become a board-certified veterinary pathologist. And I think those people are very highly sought after in industry and others. 

What I really appreciated about the two students that I had who were DVM-PhD is that they came at the project from a very different viewpoint than I did. Like, you know, I tend to get into my t cell, and they would remind me, “Dr. Kaplan, there’s an animal here.” So, it was nice to have that perspective and be reminded of the bigger picture, and they were just able to do some things that maybe I wasn’t as adept at—as far as taking blood from a mouse or whatever. Not that I can’t do that, it’s just that these are things that they maybe done clinically for a few years before they came to vet school, working with small animals and things like that. 

[00:20:30] David Faulkner: It seems like now, more than ever, it is extremely important for scientists to be communicating because it’s a battle of volume at this point—both in terms of intensity and in terms of proliferation. There’s just so much flooding the zone, as they say. One thing that I definitely see a lot of is just very flimsy Wikipedia research–based claims that show up in different products and things like that. 

[00:20:59] Barb Kaplan: And they’re everywhere, especially with cannabidiol. 

[00:21:02] David Faulkner: Oh, yeah. 

[00:21:03] Barb Kaplan: That has definitely exploded and the number of products that are available. I mean, there’s a lot we don’t know about cannabidiol. There’s a lot we don’t know about when it works, how it works, how often it works. So, we definitely have our work cut out for us in that regard. Not even just in the immune system, but I think almost everywhere for cannabidiol 

[00:21:22] David Faulkner: I mean, if the marketing materials are to be believed, it’ll do your taxes. It’ll fix your memory. 

[00:21:27] Barb Kaplan: Yes, correct. I mean, it would do my dishes and make me feel less anxious about everything. For sure, the science doesn’t support everything that’s said out there anecdotally.

[00:21:36] David Faulkner: Well and that’s frustrating, too, because there are things that we do know, and it’s just separating the truth from the marketing.

[00:21:43] Barb Kaplan: I think a frustrating thing, too, is that it takes a lot of time to effectively communicate about our science, and with all the other things that we have to do—we have to teach, we have to help run a research program, we have to get an NIH grant and train undergrads, you know, we have to write letters, we have to do all of our responsible conduct of research training and IACUCs and all that stuff—so it’s difficult to find time to also be a consistent, loud voice for effective science communication. 

[00:22:15] David Faulkner: One of the questions that I have gotten and I’ve had over the years is why study something that’s illegal? Why study an illicit drug? And obviously cannabis is a lot more complicated than that but thinking more philosophically, right? There are a lot of illegal drugs out there, and we’re seeing things like psilocybin is starting to get more investigation. MDMA is starting to get more investigation, and these things have complex histories. What would you say or how do you think about the question of why would you study a drug? Why would you study an illegal thing? Like, I went through the DARE program, 

[00:22:49] Barb Kaplan: Right, exactly. Well, I think a lot of it has to do with exposures. Regardless of whether or not these things are illegal, people are using it. People are being exposed. I think part of my responsibility as a scientist who does this is to try to understand how it works, when it works, why it works. And if it does work, is it doing what it’s supposed to do? Is it also doing something else that maybe we don’t really want it to do? And I think that this comes up with cannabis, as it does a lot of other chemicals, is that every few years there’ll be something that flashes that’s cannabinoid related that becomes a public health issue. Maybe five years ago, it was the K2/Spice issue, which people were buying these K2/Spice compounds, which were full of high levels of agonists that engaged the CB2 receptor and that was causing some toxicity. Right before COVID, we had the EVALI issue, which was a result of vaping some of the cannabinoids and came to find out, people were dying from some of this, and it was probably not necessarily due to the cannabinoid but the vehicle in which cannabinoid was placed. And so, that was causing problems. I certainly don’t think it’s not valuable to look at it just because it’s illegal because the bottom line is it’s out there. People are using it. We really need to understand, and then, if people are using it anecdotally for something, then, I think there’s value in designing a scientific experiment to see whether or not there’s science evidence to show that what they’re saying could be developed as a therapeutic. So, maybe I can contribute something to that. 

[00:24:26] Anne Chappelle: I find it interesting that in some cases, I hear people that say that they’re using these substances because they’re natural products instead of going to, “I’m gonna have an anxiety pill.” I find that attitude interesting cuz most of our pharmaceuticals are derived from plants. People say it’s safer, but is it really?

[00:24:51] Barb Kaplan: As toxicologists, we know that just because something is natural doesn’t mean it’s automatically safe. Some of the most dangerous toxicants in the world are natural. So, I think that’s another thing that we could apply effective science communication to is making sure that we are always talking about this misconception that just because something is natural, it’s good for you—because that is not always the case.

[00:25:12] David Faulkner: I think that was also really interesting to me this idea of natural versus artificial, but I think there’s something to be said, too, by the fact that cannabis as a plant has also been around in human society for many thousands of years. You could say the same thing about psilocybin mushrooms or even cocoa leaves and things like that. It seems peculiar. 

[00:25:30] Barb Kaplan: I think a major thing that’s been happening over the last 10-plus years or so, as this industry grows up around us, is that the plants are being—I don’t know if it’s genetically modified or grown under conditions to try to promote more THC in the plant. So, this is not our mother’s marijuana The percent of THC that’s in the marijuana that’s out there now, even the state legal recreational ones, is much higher than 50 years ago. So, I think we are dealing with a different dosage issue than we were 50 years ago. So even though, yes, this plant’s been around for a long time, we didn’t have whatever it is you do to make more THC and whether or not that’s actually genetic or if it’s using the light differently or whatever it is. I don’t know all the rules, but certainly, the potency of marijuana has increased over the last several years. 

[00:26:20] David Faulkner: Thinking about the trajectory, what sort of things would you like to see in the future in terms of marijuana research? Maybe the way that we deal with it as a society? 

[00:26:31] Barb Kaplan: I think there is a lot of untapped resources in the marijuana plant. I think what we’ve seen so far in the few chemicals that we have some understanding of that they’re active biologically, and they’re active biologically probably to some benefit. So, I think that we need continued research in many of these compounds. And I think that this entourage effect is also interesting and that is combining these with the terpenes and/or several of these things at once to understand that—to see if there’s something there. I think, too, as a toxicologist in this field, I am always aware of the risk to benefit. If there’s something that’s beneficial about marijuana or the compound or compound X that we haven’t studied too much yet, let’s understand it. Let’s see what effects are there. Let’s see how it works. Let’s see if there are any off-target effects and then see if it can be developed into something. And even if it can, as with almost any drug, understand the risk-to-benefit ratio. It will help you with this, but you might feel high—whatever it is. There are some people who think feeling high is an adverse effect. So, some people don’t like that feeling. And at the beginning of this, we talked about all of the roles that these endogenous cannabinoids play in our basic physiology: so, neurotransmitter release and appetite and the immune system. It’s really important to know when you’re taking these compounds in from the outside—what we call exogenously—you could really be affecting those systems. Is that something that you want to do?

[00:28:08] Anne Chappelle: So, this season of Adverse Reactions, our theme is intersections, where we see toxicology intersect with another science, and you are a toxicologist. You also are an immunologist to a certain extent, so how do you think that intersection of tox and immunology has grown. I think it’s something that we always haven’t thought of, like, “Oh, I wanna go into immunology and the toxicology of it.” Would you care to comment? 

[00:28:41] Barb Kaplan: For sure. As I indicated, my field really is toxicology, immunology, and even pharmacology, and I think that the field of immunotoxicology has grown so much in the last 20 years because I think the immune system can be involved in many of the toxic effects of compounds regardless of where they’re hitting. 

I definitely started off, I guess, more as a toxicologist and then applying that toxicology to understand how drugs and chemicals affect the immune system. For my postdoc, I went to the University of Chicago, and I got some really hardcore immunology training, which I think really helped me to think about still how toxicology affects the immune system and maybe some things that I wasn’t involved with intimately in my PhD. So, that was really good. 

And then, I think we always as toxicologists have to be thinking about doses or concentrations and same with us in immunotox. We have to know if these drugs are affecting an immune response at a certain level or not and at what point did they start affecting that level. And then, the additional veil that we have on that is do we look at the immune cells without an immune stimulant, or do we look at it with an immune stimulant? And if so, which one? And then, again, applying dose or concentration response on top of all of that. For me, I find in my work, I can’t do one without the other. So, I’m always thinking about actually all three: pharmacology, toxicology, and immunology, I’m thinking about every day in this project and in my other R15 project as well.

[00:30:21] David Faulkner: There’s the old joke: if you ask an immunologist any question, the first thing they say is, “It’s complicated.”

[00:30:28] Barb Kaplan: That is probably true.

[00:30:31] David Faulkner: So, we have a couple of questions that we ask everybody. 

[00:30:33] Anne Chappelle: What career would you have if you weren’t a scientist like this? 

[00:30:37] Barb Kaplan: This is a good question. I always think that I would’ve loved to be on Broadway—and not because I can necessarily carry a tune. I can sing oookay, but I just think that I would love engaging people, getting into kind of a world that’s not my own, pretending to be someone I’m not all the time. The challenge of having to learn the lines and also the challenge of screwing up and having to be ready and kind of turning that around.

[00:31:09] Anne Chappelle: I like that answer. 

[00:31:11] David Faulkner: I can see it. And to clarify, I wasn’t laughing at the idea. It was just so diametrically opposed to what you’re doing,

[00:31:19] Barb Kaplan: Yes, I go hide in the lab, and I don’t talk to anybody.

[00:31:22] David Faulkner: Although to be fair, honestly, like, if I weren’t doing what I’m doing, what would I like to do? I’d love to be a standup comedian.

[00:31:27] Barb Kaplan: Oh, see. Yeah, I can see it. I mean, you’ve gotta be quick on your feet, and the other thing is that I think what science teaches us is that we all have to have a thick skin and we have to take those criticisms—hopefully, mostly constructive but even when they’re not necessarily constructive, be able to take. them. And I think you do that in a lot of fields. 

[00:31:46] Anne Chappelle: Thank you for spending some time us today.

[00:31:49] Barb Kaplan: I appreciate you reaching out and having me on the show. I’m a big fan. I’ve been fangirling this whole time. I appreciate being a part of the Adverse Reactions podcast and I think it’s great you’ve reached out. So, thank you, again. I appreciate it.

[00:32:03] David Faulkner: This was so much fun. Thank you. Thank you.

[00:32:05] Adverse Reactions “Decompose” Theme Music

[00:32:12] David Faulkner: On the next episode of Adverse Reactions, “Estradiol Complicates Everything: Toxicology across the Gender Spectrum.” 

[00:32:19] Troy Roepke: So, estrogen is not the female hormone. Everybody that has gonads produces estradiol. The testes produce estradiol. Fat produces estradiol. The brain produces its own estrogen. So, even in a person with testes producing androgens, androgens will get into the brain, and it’ll be converted into estradiol. And so, some of the actions that are associated with androgens are actually estrogen acting on estrogen receptors in the brain after androgens have been converted. 

[00:32:48] Adverse Reactions “Decompose” Theme Music

[00:32:53] Anne Chappelle: Thank you, all, for joining us for this episode of Adverse Reactions, presented by the Society of Toxicology. 

[00:33:00] David Faulkner: And thank you to Dave Leve at Ma3stro Studios, 

[00:33:03] Anne Chappelle: that’s Ma3stro with a three, not an E, 

[00:33:06] David Faulkner: who created and produced all the music for Adverse Reactions, including the theme song, “Decompose.”

[00:33:12] Anne Chappelle: The viewpoints and information presented in Adverse Reactions represent those of the participating individuals. Although the Society of Toxicology holds the copyright to this production, it has, 

[00:33:23] David Faulkner: definitely,

[00:33:24] Anne Chappelle: not vetted or reviewed the information presented herein,

[00:33:29] David Faulkner: nor does presenting and distributing this podcast represent any proposal or endorsement of any position by the Society.

[00:33:35] Anne Chappelle: You can find out more information about the show at AdverseReactionsPodcast.com 

[00:33:41] David Faulkner: and more information about the Society of Toxicology on Facebook, Instagram, LinkedIn, and Twitter. 

[00:33:46] Anne Chappelle: I’m Anne Chappelle, 

[00:33:48] David Faulkner: and I’m David Faulkner. 

[00:33:49] Anne Chappelle: This podcast was approved by Anne’s mom.

[00:33:52] Adverse Reactions “Decompose” Theme Music

[00:32:48] End of Episode