Herbs and Pharmaceuticals—How to Navigate Herb–Drug Interactions with Dr. Marisa Marciano

Welcome to the Virtual Herbalism Conference. I'm your host, Lindsey Feldpausch. In this session, we are joined by Dr. Marisa Marciano. Dr. Marisa is a naturopathic physician, a clinical herbalist, and a leading voice in the integrative herbal medicine field. Dr. Marisa is also the creator of the Naturopathic Herbalist, an extensive online resource for practitioners and students. She's the co-author of the book Evidence Informed Botanical Medicine: Herbs, Nutrition, Hormones, and Medications. She also leads the direct to practitioner tincture company Herbal Energetics.

In this conversation, Herbs and Pharmaceuticals: How to Navigate Herb-Drug Interactions, we'll explore the complex and often misunderstood potential of herb-drug interactions. We'll talk about how herbs and pharmaceuticals can work together safely and where caution is needed. With her deep clinical experience and evidence-informed approach, Dr. Marisa helps us move beyond fear-based thinking towards a nuanced, practical understanding of how to navigate the terrain of herbs and pharmaceuticals.

Dr. Marisa, thank you so much for being here with us today.

Lindsey, thanks for having me. I'm so thrilled to be a part of this.

It's wonderful. It's such a joy to have you. I have already shared, but I feel like I grew up on your website as an herbalist.

Which I love to hear and makes me feel a little bit old, but that's okay. It's okay. It's still an honor. I don't think we're that much far apart in age, but you're doing big things and you've shared your knowledge with the world in a beautiful way. We're grateful not only for your work on the internet, but here as well to have you today. So thank you for being here.

I'd love to start off with you providing an overview of herb-drug interactions, which sounds like a big question. Yes. I really want to hear from you the level of concern that you hold in regards to herb-drug interactions and any advice you have to share with the audience in regards.

Yeah, thanks. I thought this was a great topic to bring to light because I get asked about it so much, particularly from clinicians and herbal clinicians that are starting out. It's scary. It's like we take very seriously as a naturopathic doctor and as part of our medical oath is to first do no harm. And so when we feel fearful about what we're doing in a clinical setting and that we might actually, you know, there might be some harm posed to a patient, I get that it brings up a lot. And when I was thinking about preparing for what we were going to chat about I thought about that fear, which comes up as a clinician, period, when you're starting out. For patients who are maybe brand new to herbs in this a setting, a clinical setting, there also can be some fear about definitely combining herbs and drugs, also just taking herbs and like, What's this herb going to do to me? How will it make me feel? It's like we're overcoming lots of fears when we're starting. But when I think about what are the top ones for clinicians, especially starting out, herb-drug interactions is huge potentially, however minimal the risk of making somebody feel bad is really scary. And you can do that just by giving a herb on its own, or you can do it when you start looking at these more complicated interactions between herbs and drugs.

So the big piece that I find freeing when we talk about herbs and drugs is that remembering that herb-drug interactions are not and do not always need to be bad, because that's the first thing we think about, is that a herb-drug interaction is a negative thing that we need to be really scared of. And that is not necessarily true. Many times we can actually work with herb-drug interactions and have them be beneficial for our patients. We can actually help to reduce potentially the dose of the medication that somebody is taking or reduce the side effects that they might be experiencing from that medication. I think we always tend to ask, Oh, how will the herb impact the drug? Also at the same time, we need to ask, How is this drug going to impact the herb that I'm going to prescribe to this person? We tend to lift the drug up on a pedestal and say, We can't touch what's going on here with our herbs. But I think we need to step back and actually think like, hey, maybe actually we can lift the herb up in this situation to be the major therapeutic goal of what we're doing and how can maybe the drug perhaps support that, or how can we improve the efficacy of our herb while maintaining the safety overall? So those are some big things that I thought about right off the bat.

Yeah, that positive effect. And I think I was going to say, I was going to say about that. But yeah, the fear component is something we all need to work through, and we need to trust where we're at in the moment, too, as clinicians, where we're starting out. I think having a little bit of healthy fear can be good. It actually is a sign that you are doing your diligence as a clinician, if you care about these types of things. I think about it as a new mom where I've got two littles, and you worry about all of these things. And talking to more experienced moms, they all often say the fact that you're thinking about this shows how much you care about making sure that your child is able to grow healthy and strong. So yeah, I think about it in that way, too, that it's good to have a little bit of these fears, but we need to just step back and appreciate the herbs in these situations as being not necessarily a bad thing all of the time. So yeah, that's my big overview about it. But then we can get into more details here, of course we will.

But I think that we can also look at these herb junk interactions perhaps a little too generally. If we make these really big generalizations about them all being bad or that we take a whole class of drugs and we say we can't take that herb with any antidepressant, without recognizing that there are many different classes of antidepressants, that that herb might have been studied in various scenarios and showing a benefit with some antidepressants, that we do these big blanket statements about herb-drug interactions. We do this with herbs in pregnancy and herbs in lactation and a lot of the safety concerns. The internet is notoriously bad for finding interactions with literally some huge safety concern with any herb because of these speculative or theoretical risks based on often pretty poor understandings of the herbs that are what they do. And as herbalists, I mean, it would be, wouldn't it be wonderful? We're starting to see we have some great resources out there, but research into safety on herbs being done by herbalists who actually understand how the herbs are working in the body, that is almost never the case when we look at much of the research that's done, and we can maybe get into how do you evaluate some of that research, too. But it's an incredibly narrow view that people are taking of the action, and it's often, as I say, very speculative. So we need to establish that level of risk with each individual case, each individual person. We can't make these sweeping generalizations. We need to look at the exact herb, at the exact dose with the exact medication that we're talking about in the individual that's sitting in front of us. And then we establish the level of risk. Then we decide what we're comfortable with within our scope and what the patient is comfortable with once fully informed of the potential risks that we've done our due diligence to explore.

I appreciate that positive spin, Dr. Marisa. I would like to dive into a little bit of terminology. This can be overwhelming in regards to our drug interactions, and in many ways, even just pharmaceutical medication names alone. But can you please discuss and define pharmacokinetics and pharmacodynamics for our audience, and how these tie into herb-drug interactions?

Definitely, yes. Both are super relevant and important terms and also scary, brings it back to school memorizing the definition of whatever. Then when you're not a pharmacist, and I'm not a pharmacist, so anyway, a lot of the terms when we start trying to understand herb-drug interactions can seem a little bit overwhelming. The drug names, the mechanisms, all of it. It's like, Ah! Okay, let's try to break down those two as simply as we can.

Pharmacokinetics is the investigation into what the body is doing to the herb or the drug. In the research and the science that's done around pharmacology, we're talking about these are processes like metabolism. How is the liver metabolizing the herb? How is the liver breaking down the drug, excreting the drug? Mobilizing it, moving it around the body, those types of things, distributing it around the body. These are relevant when we think about, very often what comes up with herb-drug interactions is drugs will be labeled as inducers or inhibitors of various enzyme pathways. And if a drug shares that enzyme pathway, then there's a theoretical or speculative interaction there between the herb and the drug. I just want to say that these enzymes, well, there's many, and they can get discombobulated trying to memorize all of the different P450 enzyme system, CYP enzymes. But yeah, just know that you'll often see this come up as the CYP450 enzyme system, which is a collection of many different enzymes. I think an important thing when we talk about herb-drug interactions, too, to highlight is that those enzymes, which are so responsible for, again, metabolizing, distributing all of these, breaking down, excreting, all of these actions, are different in every single person. You have a different set of enzymes than I do, than the thousands of other people listening, potentially today. Our genetics will dictate which enzymes we make, how many of them we make, how well they're functioning, our nutritional status. It's endless, all of the different things. So it is not person to person. But in a lab setting, we can look, we can basically isolate these enzymes and see what happens and see what constituents of the herb or ingredients of the drug are responsible. What are they doing to these enzymes? And so often we can see the enzymes being induced, and so that might increase the clearance of the drug or the herb from the body. So basically, you're metabolizing it faster, so you might get a dip in the effectiveness, or they might inhibit that metabolic pathway. And so you might actually end up with greater levels of the drug or the herb within your body over time. So you're impacting what the body is doing with the herb or the drug. And so this can be really relevant to potentially toxicity levels, creating more toxicity of a drug or increasing the potential toxicity of a herb or decreasing the effectiveness of a drug or herb. So that's a big part when we talk about interaction. So that's pharmacokinetics.

Pharmacodynamics, I think, is perhaps a little bit more clinically relevant, or I think about it as what shows up in your face in clinic a little bit more. It's looking at what the herb or drug does to the body and is very much like additive or agonistic or antagonistic overall effects. So I think about combining a sedative herb with a sedative medication. That's going to be a pharmacodynamic effect where both have the same action and you're going to get potentially very sleepy. And that would be a case where you wouldn't want to drive your car or you wouldn't want to be having to be acutely present. That's an example of the mechanisms of action of the herbs and the drugs, and how do they interact with each other and what is the overall effect that is produced within the body. So, yeah, both are really important, the pharmacodynamics and the pharmacokinetics. Hopefully, that helps. So, yeah, I think about one is like, what's the body doing to the herb or the drug? And then the dynamic effect is what is the herb or drug doing to the body? In the body? Or what's the body doing to it? And then, what is it doing to the body? We have to look at both and weigh what's going to be happening in both of those situations when we talk about potential harms.

I think that's a really important foundational setting for us to move forward with this conversation, Dr. Marisa. I appreciate that. I want to hear, when we're looking at the impacts that herb-drug interactions can have, either on the body or on the potentiation of, say, the activity of either, what are our biggest drug classes that we're concerned about impacting, and what are our red flags here? I love the idea of red flags, just keeping that always in your mind. What needs to be on my radar?

So any drug that has what's called a narrow therapeutic window, meaning that they have this small margin between an effective dose and a toxic dose. This means that any variation in the blood concentration of those drugs can lead to a less effective medication, you're not getting the intended effects, or the potential for toxicity. So you can very easily, like everyone out there can just use the internet, what are drugs with a narrow therapeutic window? And look those up. The ones are going to be—and this is whenever I think about herb-drug interactions, I'm trying to think about in establishing the level of risk, it's like, what is the worst case scenario? What could be the really awful thing that could happen? Often, these are going to be drugs like blood thinners. If you mess with the dose of a blood thinner, that can be a really bad thing. You can cause a real harm in a person if they are not able to clot effectively. So that's a red flag that's going to jump up in my head. Drugs that are involved in mood stabilization, things like lithium. I'm not talking about SSRIs, but like lithium or anticonvulsants that are helping people to reduce the risk of seizures, antiretroviral medications that are helping control HIV. Those are serious things that we want to be extra, extra careful with. So yeah, I think it's different than if you're talking about... And the intensity, and we'll talk maybe a little bit about this, too, but the mechanisms of actions of some of our herbs, we know there are some that can have this effect against general classes of medications. But I think about anything that is having a known targeted effect on the nervous system that can cause serious imbalances within the nervous system or within the circulatory system, specifically with coagulation. Those are the big ones that I think about. The immune system, we can play with a little bit there, but yeah, HIV is definitely one I wouldn't want to mess with. I would say actually another one potentially is blood glucose management. So patients that might have... You need to keep their blood sugars in a really tight window, type 1 diabetics and type 2 to a certain degree. But yeah, you know that they're going to feel pretty awful if they get their drugs outside of that therapeutic window. Those are a few of the ones that jump to mind. But yeah, it's a big, big list. But actually, not that big a list. I mean, the drugs themselves is a big list, but the classes of the ones that are really serious to me is not that big.

I think it's super helpful for us to have the list, right? Because if we can reference the list, then we can say, Okay, we just don't mess with those. I do want to ask you is folks who have had organ transplants within the medication utilized for reducing rejection, impacting the immune system, would you add that?

I would be careful there. Yeah, definitely. With immune stimulant herbs and immunosuppressives, I would avoid in that case. Yeah, most likely.

Thank you. Okay, so that, again, super helpful. Let's move into, you already mentioned mechanicalistically, we're going to talk about some specific herb-drug interaction pathways that we see most often being implicated for problematic behavior. Can you speak to me... The problem herbs. Which herbs are our usual suspects for this and these pathways?

Sure. I want to talk about St. John's wort first because I think it's really interesting. I'll just give a shout out to Dr. Kerry Bone, who did a wonderful webinar. I'm sure people can try to access it, but it was on herb-drug interactions. It was a few years ago where he did such a wonderful, very thorough review of the research around St. John's wort and the risk with SSRIs, which gets shouted from the rooftops. Everybody is so fearful of this combination. And so I really appreciated his deep dive there. And I'll just pull out some of the things that I found useful to remember and that highlight some of the important considerations when we talk about herb-drug interactions.

So the first thing is that we took St. John's wort, and this was actually in the early 2000s, like late 1990s, early 2000s. It was when all these case reports came out about this potential risk of St. John's wort, and combining it with SSRI and the potential for what's called serotonin syndrome, which essentially is the idea was that St. John's Wort was like nature's Prozac, acts the same way as antidepressants or SSRIs due to block the reuptake of serotonin, so the body has more serotonin acting at a receptor sites. These SSRIs are doing the same thing. Putting them together caused these case reports of serotonin syndrome, and people would experience really bad stomach upset, agitation, restlessness, irritability, and it can be quite serious if not treated, potentially life-threatening. But this was happening. And then that was the end of it. It was like, well, the herb works this way, the drug works this way. They jumped to these really large conclusions. The reality is St. John's wort is so much more than that. Thinking about it in that way, like a drug, is to me quite problematic in herbal medicine. It's something that the conventional system will do very readily, is just try to figure the one mechanism action that the herb has, which because that's what drugs do, but we know that that's not how herbs work. And in fact, it's debatable the impact that St. John's wort has upon serotonin reuptake in our body. It appears to work in different ways, actually, to improve depression, primarily through BDNF, or brain-derived neurotropic factor, and increasing that, and decreasing inflammation, and working on other neurotransmitter pathways. It is not just about serotonin whatsoever. There's also a constituent in St. John's wort hyperforin that is interestingly responsible for increasing the clearance of SSRI medications. In fact, combining St. John's wort with these medications, if you think back to the pharmacokinetic effects that we talked about, it in fact, clears it faster. So you're actually potentially getting a decreased effect of the serotonergic activity of that medication. So that's overlooked, which is great. But the pharmacodynamic effect where it's like, that's where the theoretical interaction there was. It's like, okay, they're both acting on serotonin, so therefore that's what's responsible. I think it's also worth noting in these studies, so the hyperforin content, the short time period—I'm always curious about why haven't we seen this repeated since the early 2000? In 25 years, there's been almost silence, or at least no clear indication of this being a recurring issue. So that's interesting to me as well about St. John's wort. There have also been studies showing St. John's wort having a benefit when used alongside some antidepressants. Depends on the class of the antidepressant. And there are some antidepressants, not SSRIs, but this different class, that we know for sure they shouldn't be combined, that it's been well-established and legitimate good research that there might be a negative interaction there. So all that to say that can you use St. John's wort alongside SSRIs in clinical practice? Yes, I do. I do it in a way that is individualized, that is often we're looking at weaning off the medication while we wean up. So dosing is very important. Dosing is very important when it comes to herb-drug interactions. The amount of the herb that you're taking—licorice is another problematic one, right? All of the concerns that we can see often around the toxicity concerns and the herb-drug interactions are quite high doses. People taking quite high doses of licorice, specifically high doses of glycyrrhizin over time. Can you use licorice in small amounts in some people on certain medications safely? Absolutely, you can. It's not black and white, which is frustrating. We just want an answer when we're looking for these things. We want a resource that tells us do it or don't. That is, unfortunately, when we talk about herb-drug interactions, not ever, or very rarely going to be the case, that it is a clear yes or no. You have to use your clinical judgment. And your clinical judgment at the beginning is... You might need to reach out and ask people, and don't go to the internet. Ask herbalists. Talk to people that have been using these herbs in these settings and get answers that way about what you feel comfortable doing because the level of risk just changes the patient also. I've had patients, for example, with SSRIs who, when I first started practice, I had this whole weaning schedule set up and we were going to be super careful, and then they would come in the next time and be like, Yeah, I just stopped it on my own. I'm like, What? She's like, Yeah, I just stopped it, and I just stopped taking the herb. I was horrified at the moment. I thought, Oh, no. I knew that you were supposed to wean off that, and we're supposed to do this slowly. Each patient is just going to, with their comfort level and your comfort level, you have to meet them in the middle, too.

I did also want to just highlight that with St. John's wort, specifically, when we're talking about the mechanism of action and how this might impact herb-drug interactions, that the idea that St. John's wort opposes the reuptake of neurotransmitters, like serotonin, and I'm going to access nature's Prozac has not been established in any in vivo studies. It's been something that has been observed in vitro. I think that's really important when we learn to evaluate the research around herb-drug interactions is knowing what's been shown in a test tube and what's been shown in a person. And if I don't have evidence that that is a large risk in a person, then I'm far less concerned, too. So the mechanism—and that's very often we'll see when we start researching herb-drug interactions—that the mechanism of action of concern has been studied in vitro, or maybe in a rodent and it was injected. It's like, well, how do we... There's different forms and different doses all need to be evaluated when we look at what the risk is of mechanism of action with herbs and drugs.

I love that you brought up the injection into rodents, which is a very real way in which researchers come to conclusions about herbs and single concentrated constituents, right?

Totally. Yeah. They can just say that it's contraindicated based on this, yeah, a high-dose injection of glycyrrhizin. It's like, well, we would never consume, we couldn't possibly even consume that amount orally as humans. It's not really reasonable. I think we see this in calamus with asarone. We see in sassafras with safrole. Then these constituents are labeled carcinogenic after high concentrated doses are injected into rodents and in turn cause tumors. It's fascinating, and I'm so glad that you brought that up because I think it's very important that we do look at the research and the source of that information. Also, as you've mentioned, the dosage. I think dosage is important, as you have I've already expressed. I wonder, Dr. Marisa, is the form of the herb and also the administration and the timing of the administration. I would love to hear you speak towards.

Sure. Yes. So yes, to all of those things. And whenever I'm investigating herb-drug interactions, I'm always interested in the research, what form was used. Most often, it's a standardized extract. So there's a specific constituent that the herb has been standardized to, and it might be quite high, it might not be, but very rarely is it a tea or a tincture. Sometimes it will be alcohol extracts, methanol extracts. But that's very relevant because that's going to make... I know as a herbalist what constituents are going to be extracted in each form of medicine, and I can approximate how much what I'm using is going to reflect what was done in the study. If I'm using a herb that I know is not going to... I'm using a tea, and I know that that tea is not going to extract the constituent very well into water, then the risk is even lower for me. It helps me establish the level of risk. So form is very important. Injection, as we talked about. I'm not injecting any herbs. So that's, again, helps me assess. Timing and dosage is hugely important. Very often, again, these animal studies are using dosages that might not reflect what could be even consumed in a human. But I will care a little bit more if there is a clinical study with a good number of individuals included in it that show adverse effects at a specific dose of some herbs. That's really relevant to me. I'll reflect on what those dosages are for sure, because often I think about herbs like ashwagandha. We have a lot of that research about... Some herbs we have this huge breadth of clinical research to draw from, and others we just don't. And then timing. So this is something I generally do in my practice, is I generally say to take herbs and drugs at least an hour away from each other, an hour or two, just to help decrease the potential for there being an interaction. It gives the body time to just deal with each thing. And then I've seen some writings and herbalists talk about four hours, taking a little bit more time there. But an hour or two away from drugs if you want to, I think, be... A little bit of conscientious there is good. And then I did just want to also bring up, so timing, because something that comes up a lot is with anticoagulants and potential blood thin effects of some herbs is around surgery. I do like to stop herbs with the potential for blood thinning effects before surgery, about a week, 5-7 days before surgery. That's just a timing thing that comes to mind, too, that I thought I would mention. But then after that, we get right back on. Timing, I think it's possible that there can be herb-drug interactions occurring outside of that, even if you wait longer than 4 hours. The body, every drug, there's long acting or slow release drugs and medications that... I also think a lot about gut flora. So one thing we haven't mentioned is that many herbs and drugs, the enzymes and the ability to activate many herbs and drugs takes place in the gut. And depending on gut health, that timing can vary for people, too. Or maybe the activity is very much related to the health of the gut. If patients have been on antibiotics recently, that's a timing thing, too. If that's happened recently, it's going to make a huge impact on the effectiveness of the herb or the drug. You might need to do some work for a little bit of time doing gut healing often before we expect the herbs to be able to act as effectively as they can. Timing is... I think we always need to be thinking about, throughout the course of a day, basically, the potential for a risk to occur.

Okay, Dr. Marisa, you have set the stage and built this beautiful foundation for us to feel more comfortable in this herb-drug interaction realm. For folks out there who are listening, can you share with them how you feel they should go about checking for interaction potential? And if there's any databases that you consider reliable that you could share with the audience?

Absolutely. Absolutely. So I have my own little process, but I wanted to share—and I get no kickbacks. There's no skin in the game for me of this, but there's a new resource that I've just come to light. I'm not sure, Lindsey, if you've heard of Efficasafe. I don't know if you're familiar with that one. So it's E-F-F-I-C-A-S-A-F-E, Efficasafe. And it's a herbalist who created this database, and it is very impressive. So I've been using that lately. I encourage you can do a free seven-day trial. I encourage people to check it out. What I love about it, and what I'm looking for in any resource is that it can lead me back to the original research. If there is a risk, I want to know that whoever's telling me that that risk exists can take me back to where that risk came. I want to see the original study. I want to know if it was in vitro, if it was in a person, if it was a case report, if it was in an animal. I want to be able to find that information easily. So I like that Efficasafe does that. That is something that most websites do not. And then I also really like the American Herbal Products Association Safety Handbook. It's a beast, but it also does a great job at looking at the levels of evidence, again, in vitro, in animals, in humans, telling me exactly what's there. It's updated fairly regularly. And then I like... So I'll give a shout out to one of my herbal teachers, who's Dr. Eric Yarnell, and he has a website called Bot Med Rocks. Anyway, there's a lot of wonderful databases and articles on there. It's not a quick reference, but you can find good information that you're looking for. And he's written some wonderful articles on things like deep dives into what's the risk between ginkgo and anticoagulants? What's the risk of licorice and hypertension? He's done some really great work there. So I highly recommend people checking him out and also just exploring. Unfortunately, there's not going to be one place you can go. You're going to have to do a little bit of looking around. There's going to be some weird random herb, and it's not going to be in this book, and it's not going to be in this book. You're going to have to do some digging, usually. And then I'll go to the... Well, I have a book as well, too. So I have a quick reference guide. Thank you, Lindsey. I have... So in the new edition, we have a whole herb-drug interactions appendix. So it's very just quick. It's like a quick that I can look to for many major things that pop out there, and all the monographs have it included as well. And then go to good old Pubmed and Google Scholar, and I'll try to just see what comes up just from, again, trying to look at the levels of evidence there, any clinical studies that I can find. I'm hopping around between a few different places, but always trying to get as specific about exactly what the drug is with the herb, as opposed to just generalizations, remembering as I navigate that I want to know, what can I find specific to this person, this case, rather than just, are antidepressants safe with St. John's wort? That's too broad a question. You have to narrow it down when you're doing your research there.

These are some really great references, Dr. Marisa. For the audience, I had held up her book, which is absolutely one of my go-to's, and this is the quick reference version. It is so handy to have when you are working with clients to reach for and to really be able to take a glimpse into specific herb-drug interactions. I know you have already spoken towards SSRIs, but psychotropic medications are very common these days, and not just SSRIs. We have SNRIs, we have MAO inhibitors, we have benzodiazepines. Can you speak towards these herb-drug interaction considerations a little more deeply and how you work with patients who are on these medications, wishing to support them with herbs?

Again, it depends. I really am focused in the visit on if the patient... I'm never pushing a herb on a patient. If the drug is working for them, we're looking at a level of severity here. Some people are really committed. They really don't want to be on the medication. They really want an alternative. They really want to come off. I'm going to approach that differently than somebody who is happy with how the medication is treating them, and they're not getting any side effects. And so I just want to preface that, that it's not always about, how do I get the herb in here? It's just meeting the person with where they're at and explaining potential risks. A lot of this has to do with... We really have to be ensuring informed consent that the patients understand that I've done my due diligence and I've explored all of the potential risks that could occur here from either a pharmacokinetic standpoint or a pharmacodynamic standpoint. And so with the psychotropics, I'll say it's possible that this herb might work on this certain pathway in or it's possible that there are... I might not know definitively because unfortunately, 90% of the time, it's, like I say, not black and white. It will be gray. And so we'll say, these are the things that we might be looking for in terms of if there was an adverse effect, if maybe this is going to impact the effectiveness of your medication, we want to be monitoring these things and being aware of these things. Then it's a lot of monitoring. I don't think I brought up that sufficiently at this point, but monitoring and understanding that we don't know everything and having those conversations with patients is really important to me. I will try to highlight as much as I can if there's been positive research about the combinations of certain SNRIs and medications, or if we know nothing at all, which is sometimes the case, too. It's like, I wish that I could tell you, but we actually don't have any information on this. So that's a level of risk that you may or may not feel comfortable with. So all that to say, we need so much more research in this area. The ones that I'm most concerned about are classes like the MAOI's, which are like monoamine oxidase inhibitors. We know that there are certain herb-drugs. Even coffee can... I think we forget that simple daily things like coffee or if you have grapefruit juice in the morning. Lots of things have the potential to cause pretty serious interactions combined with those drugs, with that drug class. So it's such a big, broad topic. We need to just get as specific as we can with the person, the herb, the drug, establish the risk to the best of our ability. In general, though, I would say things like benzodiazepines in combination with sedating herbs, again, it's not as if they can't be used together, but to know that there's potential additive effects there. So I think about kava or herbs that work on GABA, those might make you sleepy, and that might be your desired effect if you're taking it before bed, but definitely not before you are getting in your... To drive to work in the morning. So there it's... Yeah, maybe I'm answering as clearly as I could, Lindsey, but it's kind of broad, or it's the opposite. It's actually much more tailored individually to the person rather than being able to, I think, make huge generalizations there, too.

I think that's important to hear as well and really even the combination of benzodiazepines with sedentary herbs and knowing that there is a risk there for great potentiation. Then you need to decide how likely is that to happen in this person. Have you informed the person that that's likely to happen? What's the level of risk between that being a serious issue? Or is it actually maybe beneficial in that case? There's so many questions that just we need to ask ourselves in those scenarios rather than it just being, again, black and white.

I think that there are a lot of times where folks who are on psychotropic medications that are getting the support that they need from the medications, but then are looking towards herbs and it's like, oh, so many contraindications are found for particularly our nervine herbs. Then in my practice, I would go towards the more nutritive, gentle...

Exactly. I would agree that if there's not strong rationale for kava, then don't give kava, or whatever it might be. I think that's actually great advice for people who are starting out is, you can't go wrong with nettle, ever. Or chamomile. Obviously, you'll find things telling you that there's a risk with these gentle herbs, too. But I think we know as herbalists, the herbs that have been tried and for thousands of years and are very gentle acting and that are those ones we can really lean on. There are always in clinical practice, the anomalies, the paradoxical effects. These occur with or without the drugs. We just have to, as herbalists, do our best to know the herbs well, to know what they do, and to be able to understand as best as we can when the herb may be involved in this. Back to St. John's wort, I think, interestingly, a lot of the case reports that came out about serotonin syndrome, they blamed St. John's wort, but also they were also taking a medication that causes serotonin syndrome. We can, I think, hopefully tease through some of that mess with our knowledge, our herbal knowledge, as best we can.

We have such a focus, too, on the potential for herb-drug interactions, and we should because we want to support people's wellness and not do harm, right? But drug/drug interactions are huge. I feel like that is an area of study that is under-researched as well from my perspective.

Absolutely. It's shocking. You see the number of drugs that people are on and then throw in their nutritional supplements. There's very little sense for the most part of what is actually occurring, what is doing what in those cases. Then the herbs get demonized, unfortunately, as soon as they get added in.

I think this is a good segue into my question for you, Dr. Marisa, about red flags that you see when you want your patients to stop an herb immediately and how we can train ourselves to spot those in our own clinical practices or within ourselves.

I think one of the fastest ways to notice in your body or for a patient to notice if a herb is not fitting is a little bit of increased heart rate. You might feel it in your chest. You could teach them to take their pulse. But yeah, a little bit of anxiousness and heart palpitations are always something that the body is just reacting in a bit of a fight or flight to the situation. So that's often a time that I'll say, just stop. Any sort of anaphylactic allergic responses. Drugs can be responsible for that. Sometimes can herbs can too. Very rarely life-threatening, but that's often still something that I want to discontinue. Then, when I think about common herb-drug interactions and things that I would be monitoring, I think about the things that I'm able to monitor through bloodwork, perhaps, or maybe not super relevant to this chat, but signs and symptoms that people might be expressing be related to hypoglycemia, low blood sugar, so feeling just confused, maybe a little bit cold, but sweaty, shaky, dizziness, headache. Those are the types of things. Or again, serotonin syndrome, potentially what that might look like is agitation. Again, maybe some gut, heart rate, some gut upset. Like, diarrhea, any obvious response to the body just trying to get rid of something. Those are some of the key things that your fluish feelings would be a sign to stop. Those would be some of the key ones.

You mentioned increased heart rate, palpitations. I would love for you to speak towards cardiovascular medications and use of herbs alongside those because I feel like this is another area that we see commonly experience for herb-drug interactions.

Yeah, for sure. Well, I think the big one is hawthorn, right? Everyone wants to know, is hawthorn safe with all of these different antihypertensives? Without me, again, doing a big blanket statement, you find out what drug exactly the person is on, do your due diligence, look to see if there's a known interaction there with hawthorn. I think there is a real risk of additive hypotensive effects, not necessarily with hawthorn, sometimes with hawthorn, but I think about herbs like motherwort sometimes or other stronger hypotensives. Rauvolfia is another that I'm—mistletoe, maybe—I'm being really cautious with those types of herbs when people are already on antihypertensive medications. So medications that are aiming to decrease their blood pressure. You don't want to put somebody into a... I think that's most commonly the concern is about lowering the blood pressure too much rather than raising the blood pressure too much. So yeah, hypotensives, potential additive effect there. However, I think it's a wonderful example. And hawthorn has that more amphoteric effect on the heart, in the cardiovascular system. Again, it's not a drug. It's not just a straight hypotensive. It is helping with improving the regularity of heartbeats, with the potential inflammation within the whole of the circulatory system. It's going to have so many benefits for people with hypertension. I absolutely combine it with people on these medications, monitoring blood pressure. So again, monitoring, coming back to monitoring what the potential adverse effect might be, and adjusting the dose. Very often, we can help decrease the dose of various antihypertensive medications once some herbs are included that are going to have the multiple beneficial effects on the circulatory system, the cardiovascular system, rather than just lowering the blood pressure, which these drugs actually aren't... Anyway, they can do a decent job of, but often you're combining one, two, three different cardiovascular medications together to keep blood pressure down. You can absolutely help. Think about diuretics. People are taking hydrochlorothiazide as a diuretic, and it's like, well, you could also just drink... There's various teas that can be really helpful there. And to get them off of that or to... Yeah, you can do some playing there. I speak to that as a naturopathic physician. Again, this is like, different people are going to have different levels of comfort here. I'm just speaking from where I stand. But if you're going to the internet, you're going to find that hawthorn is contraindicated and unsafe in these cases. I don't believe it to be. It can absolutely be used effectively in the right setting with the right knowledge and skill set. Just keeping that in mind, it can be very helpful, actually, in those cases.

This is one of those positive herb-drug interactions. As a physician, you do have licensure to work to reduce people's medications through the implementation of herbal protocols, which is absolutely a beautiful thing. I would love to segue into you sharing a case or two, positive or maybe potentially problematic, where herb-drug interactions have altered a medication or an herb's effect, and what you saw in those cases.

Sure. One that I also wanted to just speak to is licorice, because licorice comes up with a lot of interactions. I think the main concern there being There's the potential for, with high dose licorice long term, taking it over two weeks, it's different for every person, but some pretty high daily gram doses, you have the potential for potassium loss. So your body can hold on to sodium and excrete potassium and various electrolyte imbalances—well, that being one, and others can occur. And you can create what's called pseudo hyperaldosteronism, which essentially is a fake form of hypertension, but it can increase blood pressure, and everyone has this concern around blood pressure and licorice. I have seen this, and I want to just speak to people who have... I guess it's not exactly herb-drug interaction, but in this one case, it didn't have to do with blood pressure, but it was blood sugar that I had a patient who was a type 1 diabetic, and so he controlled his blood sugars really, really closely. So this was an interesting case because he was monitoring his blood sugars multiple times throughout the day, so we could really see what was happening in combination with the licorice. So he had a peptic ulcer, and I had prescribed DGL, which is a deglycyrrhizinated form of licorice. So I thought, okay, it doesn't have the glycyrrhizin in it, which I know is most responsible for those effects on hypertension. This was early in my practice, but I didn't think about potential effects on blood sugar for him. And so this was like my oopsy. The poor guy, he took just the DGL. It really helped his ulcer, but he said, Holy moly, what it did to my blood sugar is it just like, spiked it through the roof. And I was like, Oh my gosh, I'm so sorry. I didn't think about that. I was in my head about the hypertension piece for him. And so I thought I was being on the safe side by taking the glycyrrhizin out. So anyhow, he was fine, but it was just an example of, oh, wow, that was a clear, direct. Those blood sugars spiked. I should mention, he was on a long-acting insulin as well. There was this antagonistic effect of those where I thought it would have lowered his blood sugar, but it didn't. So it was a surprising one. I guess I share that case to say there's surprises sometimes and the importance of monitoring in those cases and having the patient closely monitoring themselves and you knowing what to do next is important there too.

And then there was another. I had a patient who was a very active woman who was also... She consumed a lot of caffeine, a lot of coffee, and she was also taking an ADHD medication. She was diagnosed with ADHD, so it was dexedrine. At the time, she was looking for support for her... She was training for a marathon, so I was like, oh, some adaptogens would be good here. And so I prescribed, I made her an adaptogenic formula that she could take before her runs. Anyway, we figured it out through going through each of the herbs eventually that was included in it. But I

included some Eleutherococcus, some Siberian ginseng there—and that was the one that just... It made her feel incredibly anxious and just over stimulated in combination with the dexedrine. And I had some other adaptogens in there that were, I thought, going to help balance it out. But for her, we tried individually each herb in office to see what the feeling was that she was having. And we knew that it was just that additive effect of those stimulants together. We were decreasing her caffeine, and we were trying to reduce her dose of the dexedrine. But anyhow, it was a little bit of a playing with dosages there and taking out the Eleutherococcus and finding adaptogens that were a better fit for her because that one was just a little bit too stimulating for her.

So, yeah, those are just two cases I can think of where I learned from those situations in different ways to be just monitoring is, I guess, the takeaway there of whenever we're using herbs and drugs, what might happen and what can we do to switch it up once we see a result that maybe we don't want.

I would love for you, final question, to provide some wrap it up in a bow advice for folks who are either herbalists or practitioners out there who want to build confidence in regards to herb-drug interactions. Just remember that your approach needs to be patient-centered. I think that's really important, respecting what the wishes of the patient are in these situations really rather than getting in your head about what needs to be done. Working with patients that are already taking medications is about this constant conversation that you're having about their comfort level and where they're at and where they want to go. So that individual determination of whether you're going to be doing this or not is the first step before you just jump to, is it safe if I give this? And then ensure that you've done your due diligence for sure and practice within your scope. If you're not comfortable, then refer out. That's always a really important piece. And remember that there are not going to be black and white answers. And the reality is you do need to lean on your clinical judgment. There may not be an answer, or reach out to other herbalists, hopefully in your network. Ask questions. I get questions still from students that are in practice now, and I'm always happy to help with helping them figure it out. Even myself, I might not know the answer off the top of my head. It's very rare that we do. We have to investigate each case as a stand-alone. And so I like working through those. I think people can be very, very open to helping in those situations. So remember that, too, that it's just really your responsibility to inform of any risks. Do you do diligence. Do your research. Flow through those resources that we talked about and then monitor the patient appropriately and refer out if it's outside of your scope. Those would be the main takeaways that I would have and just bringing it back to letting go of fear, but also always being that person that they can count on to acknowledge, whether they are experiencing something that doesn't feel right in their body, that you're there to support them through what that looks like. And if it feels risky, then don't go there. Listening to your patient and to yourself and your intuition in those situations, I think, is quite important, too.

Some very solid advice, Dr. Marisa. Could you please you share with our listeners how they can learn more from you and the work that you do out in the world?

Yeah. I am currently living in a small community, coastal community in British Columbia. Two years ago, we came here, left our clinic practice in Vancouver. Now, my main thing that I do is tincture making. I currently have a company called Herbal Energetics, and we do practitioner-to-practitioner compounding and manufacturing of herbal tinctures, all organic, wildcrafted or locally sourced. That's my main thing that I'm doing right now. I'm kind of stepped away from clinical practice for the time being. So you can find me there at HerbalEnergetics. Ca. I also have the website, the NaturopathicHerbalist. Com, which I haven't put a lot of work into lately, but I do I have dreams of things that I would like to build out there. And if people wanted to check that out, I hope they do. It's a hopefully useful resource for people to just have available, lots of just free herbal content, amazing herbal content, much like the Herbal Academy has. But I organized in a way that I think when you're starting out with herbal medicine can be helpful. So please do check that out. If I'm building things to come from an education standpoint, that's where they'll be. Then you can find me at Dr.Marciano. Com if you just want to learn about my practice approach and a little bit of what I do. I dabble in lots of different areas in the herbal world, and I'm just always happy to be a resource for people anywhere along their path, so feel free to reach out.

Thank you so much, Dr. Marisa. We will make sure to get all of those links in the chat so folks can find you. I am so grateful for your time and teachings today and for your website over my entire herbal journey. Thank you. That was really, really fun. Hope everyone enjoys the conference.