Interview with Dr. Christopher McCurdy and Dr. Brian Pearson on the History and Future of Kratom Plant Science and Pharmacology

This interview is a transcript of Kratom Science Podcast #69

Dr. Christopher McCurdy

Kratom Science: I want to start off with Dr. McCurdy. You were originally with University of Mississippi. That university is known for the only federally legal cannabis farm. You started to study kratom around 2004, and I’m just wondering how you became interested in kratom?

Dr. Christopher McCurdy: It’s an interesting question because it’s a question that a lot of people don’t know the background on, so I appreciate you asking it. We were studying another plant at the time, salvia divinorum, which resulted in a new clerodane diterpene called salvinorin A, which many people know about, and it is a kappa opioid receptor agonist (McCurdy et al., 2006). We didn’t know what it was in terms of its pharmacology, but certainly based on its chemistry no one expected it to be an opioid. It was really fascinating to me coming out of an opioid chemistry training in my postdoctoral work at the University of Minnesota. 

I just thought I’ve learned so much about opioids and opioid pharmacology and chemistry that I sure would hope that I can find a way to continue this line of research, but I didn’t want to work in the chemistry area. That would compete with my postdoc advisor, who is, by the way, 90 years old and still funded and still working everyday and still kicking butt. I mean, I still look up to him and total amazement. He really focused his career on Naltrexone and making derivatives of Naltrexone, which is an opioid antagonist, and has built an entire successful career around around that one molecule, and if there’s one molecule out there that I could build a career around, I’ve seen the pathway as to how to lay this out in front of me. So I thought maybe salvinorin A would be that compound. 

Salvinorin A was known to be a hallucinogen. The plant was called Diviner’s Sage or Magic Mint. It’s a Salvia plant. We were among the first groups funded by the National Institute on Drug Abuse to study this.  Once it was realized by Brian Roth’s group that salvinorin A interacted very selectively with kappa opioid receptors (Roth et al., 2002), it became a complete mystery as to how it interacted with kappa opioid receptors because it totally breaks the mold of all the textbook requirements of a molecule and how it should interact with opioid receptors. So that intrigued me from the get go. 

It’s a neutral molecule. In other words, it can’t act like an acid or base. Many alkaloids are basic compounds and they can accept protons, and those types of interactions are very important when they are in a receptor environment. So they can form what we call salt bridges or ionic bridges. So you can imagine that it’s like a positive charge being attracted to a negative charge, and that’s how those interactions really can form. Salvinorin A was a molecule that didn’t have any ability to have a charge. It was just a very greasy molecule, not too much different from something like THC, which is not able to really participate in acid-based chemistry.

It’s a good story. We were funded by NIDA. NIDA called me and asked me to prepare a talk on naturally occurring analgesic substances and to present that at a conference sponsored by NIDA. And so I did that. And it was a really fun paper. I think it was published in Life Sciences in 2005. That paper is still one of my most highly cited papers, and that’s where, among the research I came across mitragyna speciosa (McCurdy & Scully, 2005). 

Mitragyna speciosa seemed to be relatively unexplored, untapped and there was a paper from 1972.

Macko?

Dr. Christopher McCurdy: Yeah, the Macko paper, from Smith, Kline, and French, now GlaxoSmithKline, where they were investigating mitragynine. It just blew me away the completeness of that work, and how much was there, and then they abandoned it, which seemed very odd. But I got some of the back story on it, and I don’t know if this is mythological back story or if it’s real, but it makes sense. GlaxoSmithKline – I’m sorry Smith, Kline, and French at the time – realized that that compound mitragynine really was equivalent to codeine or the emerging non-steroidal anti-inflammatory drugs like ibuprofen and naproxen at that time. But it still had some opioid activity associated with it, and they really decided there wasn’t going to be a marketplace for something that was getting flooded with non-steroidal anti-inflammatory drugs that looked to be the emerging new pain relievers. To compete with codeine is kind of like introducing a new cola to compete with Pepsi and Coca-Cola.

They kind of backed away from it and decided not to dump, at the time, probably hundreds of thousands of dollars, or millions of dollars into the development of this natural product. So it sat there. It sat dormant until some Japanese groups picked this up, a Dr. Takiyama, and Dr. Matsumoto worked on this. In Japan they did a lot of work in this area. And then again it seemed to be abandoned. 

It just seemed like a perfect time for someone to pick this up and start working with it and at the time it was totally under the radar. No one really was aware of it, no one really understood what it was doing other than traditionally it had been used as a stimulant for workers, and as a substitute for opium, and it also seemed to help people that wanted to get off of opium be able to transition off of opium.

So we just started playing around with this, trying to isolate the mitragynine compound, that major alkaloid. Everybody has gone after that alkaloid because it’s the most abundant, and generally in plant science, when you have a really abundant alkaloid produced by the plant, there’s a reason that it’s producing that alkaloid, and Brian can speak to this much more so than I can. But in general we would think that’s the pharmacologically active component of the plant, and of course it’s the most efficient thing to go after as well as produced in the highest amount and that’s why we see most all of the scientific studies have really focused on that up until recently, when we’ve been able to get enough material to to isolate the other alkaline in large quantities. 

But really that’s what brought me to it. We got a hold of three trees that I bought on the internet for $15. They came in. I had no idea if they were real. One of them died immediately. Two of them we started to propagate and you mentioned the federally-funded marijuana farm. We were able to use some of the United States Department of Agriculture agricultural research service folks that were in that Natural Products Center at the University of Mississippi. The USDA actually leases out part of that facility, and so we had some scientist there that were willing to help us try to propagate these trees. We did that fairly successfully, compared to what was discussed on the internet about how difficult it was to grow these trees. We were able to expand from those two trees up to about somewhere between sixty and seventy trees. I know you’ve talked about the the study that we’ve done before on those trees, where we isolated several alkaloids but we found them to be very low producers of mitragynine. And at the time we felt like maybe we just got the wrong thing, and we decided it was of no use, and so we sadly decided to just destroy all those trees and call it the end of the day of the project (León et al., 2009). It’s funny, it just went on pause for a number of years until we started working with Dr. Pearson. Dr. Pearson can probably take it from there on that part of the story, but the different types of trees are what we call chemotypes of trees that are present really became interesting. The age of the trees may play a role here as well, but we’re not convinced solely of that. We just believe that there exists different plants, just like we have different people. Some people have certain enzymes. Just to make a strong point: some people can eat asparagus and their urine smells funky afterwards, and some people can eat asparagus and they never have an issue. One of those individuals is lacking an enzyme to process that metabolite, and so it’s very similar to plants. They all have different personalities, if you will. 

So that’s kind of a long rambling of how we got it to this work. We dropped off for a while at Mississippi and then move to Florida. I know you’ve spoken with Lance McMahon before, and we sort of revitalized a lot of things that we were doing at that point.  I know you’ve talked with Abhishek Sharma.

I’m going to stop there and let Brian jump in because I thought it would be cool if we have the opportunity for us to do some of these things together, because the complimentary things that he brings to the table, and the science that he does is so vitally important for us to understand these plants to really gain a greater appreciation for what’s happening… the real world side if you will.

I was gonna say this is a good opportunity to talk about the alkaloids from when they start in the plant, all the way until they metabolize out of our bodies. Or at least my body. How much traditional horticultural knowledge was there about growing kratom? We hear a lot of things from growers, like you’re supposed to prune it a certain way to get the alkaloids going, etc. Was there much of any of that to go by before you started the project?

Dr. Brian Pearson

Dr. Brian Pearson: Great question, and many times when Dr. McCurdy and I are talking, we use cannabis as an example, because in many ways the industry and how people have progressed as the Cannabis industry has progressed is somewhat similar. To your question, there’s always this great literature, and there’s this internet forum for information. Some of the information can be quite good from hobbyist that have worked with this. Sometimes that information is wrong. I mean, fundamentally wrong and I question it. Looking at what was available in documented peer-reviewed science – sort of the gold standard by what we would refer to in reference in our work, there are very very very few manuscripts, peer-reviewed scientific journals talking about horticultural production and practices that were traditional. In part that may be [attributed] to the fact that Malaysia and Thailand for many years have not allowed to commercial production of kratom, and this was being cultivated Indonesia where this wasn’t well-documented, or it wasn’t much of the motivation among those growers to document it and share it perhaps with others. So the information online was a bit sparse that I was referring to –  it’s still a starting point. But some of these things, as Dr. McCurdy mentioned, the juvenility, or how we propagate, or how challenging it could be, or where the ones early on that I was concerned about along that same line was that the seed reportedly could only be germinated within 24 to 48 hours after it comes off of the tree, and that you have a very very narrow window. As a plant nerd and horticulturist, I thought oh wow, okay, how am I going to get the seed? Where am I going to find a tree close enough to do this? Later on when we were able to get our hands on seed to attempt this firsthand, we realized that, no, that’s definitely not true, because we’re germinating seed that is definitely older than 48 hours old. We have in our possession some seed that’s now going on multiple years old that we’re still able to germinate. We do keep them refrigerated. But again in busting these myths, and those myths can be fun. There’s a certain element of fun in all of this, because we’re learning things that aren’t known, aren’t documented before, and it’s rewarding. In my industry we interact with growers a lot, and parties that are interested in this knowledge. So we’re giving them information that is vital or critical, and they’re excited and enthused to hear this, especially when we’re able to tell them this with scientific certainty or statistical certainty.  

In the next breath it can also be sometimes frustrating because you’re starting from scratch in a lot of ways, genetics. Dr. McCurdy mentioned various chemotypes, and when we started running into mitragyna speciosa, the kratom tree itself, we know this is what it is, why aren’t we seeing certain alkaloids? And that has to do with the non-formal genetics that we’re getting. We’re getting what we can get from whoever picked it out of somewhere and sent it to us. It’s exciting, it’s challenging, and in many ways it’s similar to cannabis, in that cannabis has gone through that same transition. We were going from individuals cultivating it illegally, sometimes using good technique, sometimes also using very poor techniques, and we’ve seen a rapid shift in our nation and our state, which it’s coming out of individuals’ closets and moving into a more formal structure where we see and expect certain correct habits, techniques. That’s where the science of horticulture will be very helpful, to do the research to understand the science, to be able to assist people who are trying to grow trees like kratom or industrial hemp in our state. 

You’re starting to learn about what alkaloids do, how they affect people who take kratom. but alkaloids do different things in the plant. For example, nicotine in tobacco supposedly is an insecticide. Do you know anything about what the alkaloids do for the plant kratom? 

Dr. Brian Pearson: Correct. You’re absolutely on spot on that. Plants are making carbohydrates through photosynthesis and they’re electing to put this energy into forms that will be beneficial for the plant. Now in some cases, maybe some of these compounds have usefulness in human medicine, but certainly the plant is probably not involved to produce these plants for our benefit, rather its own. Again, putting significant energy and resources to develop these compounds requires a lot of energy for the plant to make them. So these questions, what is the purpose of this in nature? Is it an insecticide? Is it doing something to attract pollinators? Some kind of competitive purpose. We believe that it’s assisting these compounds produced by the plant to help it in an environment that’s damp and wet, where pathogens may be present. And so we’re working with colleagues in our institution now to further understand that. It appears it’s really to help the plant be more competitive and very humid, wet, damp environment such as Southeast Asia. 

There is a lot of talk about heavy metals that end up in a lot of the products sold in the United States. One hypothesis for that is the grinding machines might be old, and so the metals get into it that way. But there’s another idea that the metals are actually leached from the ground into the plant. Is there any truth to that, or any evidence of that?

Dr. Brian Pearson: That’s another good question. Some plants can bioaccumulate, they’re more selective of things in the soil such as heavy metals. In some cases we have ferns – a researcher here at the University of Florida at the research center I’ve worked at for many years was doing research in the use of ferns to help pull up arsenic. So they plant this fern in the ground, it would bioaccumulate arsenic, you harvest the fern, and it’s a much better way to extract the arsenic out of the soil than to try to remove the soil itself and put it in a landfill where it would essentially exist for the rest of his life. 

The question would become, and you’re correct, we have these two hypotheses, could it be from some of the processing equipment? Yes, it could definitely be metal transferred. Any kind of food equipment needs to be stainless steel to ensure that we don’t have any kind of transfers or dusts put into products that we’re going to be consuming. Equally strong, it also could be bioaccumulative of these heavy metals. To my knowledge, I have yet to see any research that is growing these plants under controlled conditions where they were purposely cultivated in soils or hydroponically where these metals were present, then to evaluate what the ability for the plant to accumulate these heavy metals in the leaves are. Some plants can do that, some do not. Oftentimes it is not in the best interest of the plant to accumulate these metals due to the toxicity standpoint to the plant itself. 

The scientific community hasn’t put forth any data that I’ve seen yet to help answer that important question. I guess to that a fact it’s sort of a long some of the lines where domestically there’s been some interest to cultivate kratom here in United States under conditions in environments where we’d have a higher level of control and knowledge of how it’s being cultivated on lands that would be prepped in the same way that other food crops will be prepared and managed in the same way and/or cultivated with pesticides or no pesticides using organic methods. That would appeal to users that are looking for a product or a food item that was made and manufactured in that production system. So I think that also is driven, without having that answer and being uncertain about how the plant is grown, who is processing it, and how it’s being shipped and handled. Due to some of that I believe that’s generated some interest among domestic consumers to investigate the potential of having a domestically-cultivated kratom products here. 

“Trees that were on the same farm in Southeast Asia, with the same environmental conditions, same soil, the same practices, and yet [the trees] had very different profiles with respect to mitragynine. “

-Dr. Brian Pearson

How hard will kratom be to standardize? You’ve found differing levels of alkaloids. Depending on the region, there’s been something that appeared in some papers stating they’ve found mitragynine at 66% in Thailand, 12% in Malaysia, there’s hardly any in the Philippines. You mentioned in an AKA presentation that that is based on very little research, and it’s not necessarily true. So with the fact that alkaloid levels are various, number one, how hard would it be to standardize? And number two, is there any truth to this regional consistency among the variants or is that just based on not enough research? 

Dr. Brian Pearson: You’re correct. In the presentation presented to the AKA, that was one of things that bothered me. We have these numbers, the 66% and 11% or 12%, and these were based off of very, very few data points, and so it was a very large extrapolation of a very small sample size. Small enough that it’s taking quite a few liberties to cast a net over an entire region or several countries to make the generalizations. 

We’ve seen some significant variability. Dr. McCurdy can speak on behalf of work that he conducted recently, that’s been recently published. Looking at trees that were on the same farm in Southeast Asia, with the same environmental conditions, same soil, the same practices, and yet had very different profiles in respect to mitragynine. 

To the question as far as standardization and moving that into a system: One of the things about the job and the clients I work with, a primary consumer of information put forward by faculty in my department are specialty crop growers. Oftentimes these are ornamental growers that are growing millions of plant units, but they have to be absolutely consistent from batch to batch and shape and color and size and weight, and that any flaw in anything that is not essentially perfect, almost manufacturer-like made, will be rejected.

Florida is the second-biggest producer of horticultural goods and specialty crop goods. So our industry in Florida is very good about getting that standardization, and that’s what interests me where the two worlds of my discipline and that of Dr. McCurdy’s come together, because when I look at natural products or herbal medicines one of the thoughts that I have and general opinions is variable concentrations from batch to batch, and potential activity that might be from pill to pill in a capsule – how do we standardize that? Step one, there’s going to be genetic variability in the plants so we have to eliminate genetic variability, which is actually relatively simple. We identify a plant that has certain characteristics we’re looking for. That could be a volume of leaf mass or a resistance to a pest or disease, and that’s where Dr. McCurdy and his team in Gainesville are so helpful because it is important to identify what alkaloids may be beneficial and those that are not, and that ultimately helps us select which plant or plants we want to move forward. 

From that point we can get them into a tissue culture facility generally, where we can mass-produce millions of plant units a year that are hundred percent genetic clones every single time, so that eliminates genetic variability.

The last component is an environmental component. So even if we have a hundred percent perfect clones of each other, then it’s a matter of understanding how the environment influences that plant again in terms of growth and yield and herbivory and alkaloid synthesis. So once we understand the environment – the light, the heat, the water or lack of water, and water stress – once we understand that we can put together a protocol that would allow for essentially very, very uniform production of plants to try to produce that variability. I think that’s achievable because we already do that with other plants for other applications, and so it’s applying that formula to this as well.

Dr. Christopher McCurdy: I if I can just jump in real quick. I think that’s a perfect explanation of how we do this for plants that are decorative and out in our yard right? But we’re shooting for precise alkaloid contents and ratios and times of the day or time of the year that those plants might have to be harvested. We still don’t know the answers to those things. It’ll take getting to that standard material and then starting to do more studies to look at ratios and alkaloid productions. 

We already see in practice something like the tobacco industry. A Marlboro cigarette pretty much tastes the same and should give you the same effect it does today as it did 30 years ago, or at least that’s the idea behind it. So it’s a blending process. Also similar to the wine and spirits industry where a bottle of Maker’s Mark bourbon tastes the same today as it did 20 years ago. A certain wine maker may blend several different barrels of wine to get to a particular taste that he or she wants his or her wine to possess that may be reminiscent of that particular label each year.

It could be a number of things that we go to. We could end up with a very genetically standardized plant material. Dr. Pearson could speak better to this, but if they’re growing out in the field, you’ve got trees that are going to be exposed more to light and heat because they’re on the south side of the field versus the north side of the field, and all kinds of variables that go into that. 

He mentioned that study we did in in Malaysia with our colleagues at the University of Science Malaysia where they went out into a plantation and picked from trees that have been existing there for years, and GPS-marked every single tree so we knew specifically which leaves came from which tree, and there was a mixture of of chemotypes within that plantation. So you had some trees that produce high levels of mitragynine and other trees that produced extremely low levels of mitragynine (Chear et al., 2021). Yet those are being sold into the marketplaces by the growers to the producers of traditional kratom tea there, and it’s all blended together. The individual themselves titrates their experience. So, you know I say some mornings I only need one cup of coffee and I’m good to go. Other mornings I’m like, man, I need three or four cups of coffee and I’d like to think that my coffee is standardized for caffeine content and everything else. But it also depends on the individual consuming it. There’s so much variability in this whole thing, getting to a standardized product it is going to be interesting, but not impossible at all. 

And just to take it one step further, if we go by United States Pharmacopeia guidelines which we’ve been talking with the USP trying to give a standardized monograph, or at least the thought of a standardized monograph for what would be a kratom USP dietary supplement sort of thing. What we would do is set limits, or set maximum amount of mitragynine that could be present to a minimum amount, and we do that with all the alkaloids, or at least all the alkaloids that would be relevant, and say that it should have at least this much, but no more than this much mitragynine. It should have probably no detectable levels of 7-hydroxymitragynine.

So from that point we could start to develop some other types of more formalized standards as well, so hopefully that answers it full circle from how it can be done in the horticulture sense, to how it could be done at the final product stage.

“You shouldn’t be taking kratom to get high. It shouldn’t be a product that’s pushed to so many doses where you get that sort of staggering euphoric effect… That’s in the traditional method where you don’t have a lot of 7-hydroxy, so that’s why we’ve been so adamant about saying that. If you take it as its pure sanctity product where there shouldn’t be 7-hydroxy present, then you shouldn’t have an issue.”

– Dr. McCurdy

As you said before, kratom really is not the function of one alkaloid. It’s kind of the entourage effect, a symphony orchestra effect. I’ve seen the presentation where you said there’s actually not 40 alkaloids in the plant, but a lot of them are produced maybe during the drying process. Especially 7-hydroxymitragynine, you’ve shown that there’s hardly any detected in the plant, but it seems to be more abundant in the dried products that Americans get. The recent study that came out about 7-hydroxymitragynine showed that if it’s metabolized from mitragynine, it seems to not have the problematic effects it has when it’s taken in the product. Would it be considered safer to take a fresh leaf product than a powdered leaf product? 

Dr. Christopher McCurdy: That’s the billion-dollar question. I don’t think I have an answer that could be really good for that question. We’ve seen and analyzed many, many dried leaf products that are in the US right now that look very similar to some of the traditional fresh leaf brewed tea products. I would like to think that some of our work, and the work of others in science, has helped to sort of point out the fact that we shouldn’t be trying to find leaf material that has a ratio of mitragynine to 7-hydroxymitragynine. We should be finding leaf material that has no detectable levels of  7-hydroxymitragynine to start with, because, yeah, we believe that when it’s ingested into the body that the amount of 7-hydroxymitragynine that’s produced from mitragynine is sort of canceled out by the other alkaloids that are present, and that the pharmacological effect is not achievable that you see when you isolate 7-hydroxy by itself. 

It’s one of those things where, if you start with a whiskey that’s 40 proof versus a full barrel-strength whiskey and you take one ounce of each, and you add another ounce on top of that, and you add another ounce on top of that, which one is going to get you feeling very tired more quickly? It’s the one with more alcohol. If we compare 7-hydroxy to the alcohol proof concentration, we want to try and keep that as low as possible so that it doesn’t impair anyone, and it doesn’t help foster abuse potential of the plant. 

You shouldn’t be taking kratom to get high. It shouldn’t be a product that’s pushed to so many doses where you get that sort of staggering euphoric effect that most people will puke before they would ever be able to absorb that much to get really high from it. That’s in the traditional method where you don’t have a lot of 7-hydroxy, so that’s why we’ve been so adamant about saying that. If you take it as its pure sanctity product where there shouldn’t be 7-hydroxy present then you shouldn’t have an issue.

And yeah, I totally feel like it’s a symphony orchestra. You take 7-hydroxy out of the mix, even the amount that would be generated as a metabolite in our bodies from mitragynine, if you take it out and you listen to it on full blast by itself, it’s comparable to other full opioid agonists like morphine, like fentanyl, and those types of things. So it’s something that we have to be very cognizant of. It’s something that the whole Kratom Community should be very cognizant of, because those are the things that are going to cause problems moving forward. So we want to make this a really beneficial product to the world, which I think we do, and the World Health Organization underscored that recently, that they don’t want to put a full investigation to this. It’s a traditional medicine in the world and the emerging science is showing promise. 

I think we’re getting hammered by some of the bad players in the history, if you will, that are trying to make a quick buck out of a product. That isn’t the right intention. The right intention here is to help people, to make the world a better place and not cause harm. I think that’s, at the end of the day, that’s what all of us and all of the responsible kratom users want to see happen. It’s going to be a few bad apples like we see in every type of industry that cause problems and raise flags for regulations. There’s so much red tape in all of our jobs because somebody screwed up and got away with something and put some other barrier in place for everybody else.

I know there was a paper on purposeful adulteration with 7-hydroxymitragynine. Is that in a lot of the extracts where that happens? And you’ve said before that if they try to oxidize it purposely, then it oxidizes some of the other alkaloids along with it, and we’re not sure what any of that does. Are you seeing a lot of that? I know you test the product samples – is there ever evidence of maybe fentanyl or somebody purposely spiking it with a stronger drug?

Dr. Christopher McCurdy: First and foremost, the paper, I think it was in 2016 on suspected adulteration of kratom products. We purchased a bunch of products and we analyzed them when we found the 7-hydroxymitragynine content to be pretty much all over the place. Some very very low-level, some very very high-level, some that we never-even-thought-possible high levels, and so the immediate thing that comes to mind is, well, somebody’s got to be adding material here. But when we looked at it a little bit closer, even after we published it, what you could see is that every time that 7-hydroxy levels went up, the mitragynine levels were much farther down. So that to us started to indicate this potential hypothesis that, well maybe mitragynine is being metabolized in the air, or by light, or by heat, or whatever it is, and we don’t know the answer to that yet. We’re certainly working on those projects, but if that’s what’s happening that could explain why you see such large levels, right? 

This product is harvested from a tree, it’s dried out in the hot sun, in some cases on the wet floor of of the jungles where it’s harvested and then it’s ground up in a grinder that could cause a lot of friction and heat in that process. They’re they’re out in the hot sun. Then they are packed into containers and shipped across the globe to the US. They’re not refrigerated or what they call reefers to make sure that a proper environment is maintained for a food product. 

So it’s no surprise that those early products that we were testing we’re all over the place, and I’m happy to say it agrees with a lot of things that are going on in independent testing labs that we’ve seen those levels of 7-hydroxy come way down in many of the dried products that are being distributed in the US. 

So then that comes to the next question: have we seen anything else there? Oh, there have been a lot of reports on the internet of ways to chemically, sort of, “home chemistry” your own kratom, and so we started trying all those out in the lab. We’re just taking everything we can find off the internet, I won’t mention specific sites or anything like that, but we reproduced those in our controlled laboratory environment. And yeah, you get increases in 7-hydroxy but it’s a non-specific oxidizing event, so you oxidize every single chemical that’s in that plant. What the result of that is, I don’t know. Most people like to take antioxidants for the benefits of health, and so the thought of taking a whole bunch of oxidized molecules into your body is really not an intelligent thing to do if you want to be on this Earth for a while. The second thing is, quite frankly, people were reporting these are non-toxic oxidizers, and that’s just false. I’m not going to go out and buy a chemical that says it’s oxidizing but it’s non-toxic. It’s non-toxic to the environment because it can be diluted out. But if you go and take a spoonful of those oxidizers along with your kratom, you might as well get yourself ready for the emergency room because it’s going to be pretty ugly. So, there’s that level.

“The whole dietary supplement industry is scary. Quite frankly, there’s regulations there, but there’s not enough people to enforce the regulations. A lot of products that are being sold – I try to speak to this as an entire industry, not just kratom – there’s stuff that’s adulterated all the time.”

– Dr. McCurdy

And then the final thing I think you asked was do we see anything like fentanyl adulterants in these? We have seen the adulteration of kratom products in the marketplace. Not from things that we’ve purchased but by emergency room physicians that have contacted us stating that they had someone admitted that swore they were only on kratom, and did not take illicit substances but their tox panels lit up for different substance uses. So we said, fine, if you can get a hold of their material that they ingested and send it to us – most of the time that wasn’t possible to get the materials. There was one material that we found that had morphine in it, and why someone would take an incredibly more expensive pharmaceutical product and put it into a plant material… To think about it this way, if you’re a new person into the market and you’re trying to establish yourself, you either put out high quality expensive well-tested products, or you put a product that’s potentially going to pack a little bit more of a punch than the other competitors, and somebody will get on it. 

And that’s yeah that’s a big reason why the whole herbal supplement industry and the whole dietary supplement industry is scary. Quite frankly, there’s regulations there but there’s not enough people to enforce the regulations. A lot of products that are being sold – I try to speak to this as an entire industry, not just kratom. There’s stuff that’s adulterated all the time. We hear about it with Viagra being present in some herbal products, and we hear about herbal products being sold that don’t even have the plant material that they say is on the package! So it’s an unfortunate scenario that someone would do that. 

We have tested two separate products from two states incredibly far from each other. One had morphine, as I said. The other one had hydrocodone present. So it’s just kind of frightening from that aspect. We have not, thankfully, seen fentanyl in anything, but it wouldn’t surprise me as fentanyl seems to be appearing in everything from marijuana to oxycodone pills and heroin, trying to increase those product “bangs” if you will. 

I still call it a wild wild west market, because it is. Until we get some real standardization in place and some real controls on what products are being sold and what kind of guarantees we’re giving to consumers buying this product… I’ve said it for years. I want to buy something that I’m signing up to take, right? If I buy a gallon of milk at the store I expect it to have all the things and the benefits that I want from the milk and not have other crap in it. 

Dr. Brian Pearson: The history of alcohol, I think, is very analogous to that. Some of our earliest laws in alcohol production that came out of England was due to adulteration of products. People were buying different types of beer, and they were getting a feeling because people were putting in compounds to try to simulate that buzz and to bypass the system because it was cheaper, and so we had standardization and regulations put in place to ensure the consumer they were purchasing what they were purchasing and then nothing toxic was added. It’s sort of similar to the United States when we came out of prohibition. If you were buying moonshine made and on top of a mountain in a still, you may not know the proof or the quality or contaminants. But certainly when a consumer now goes into a store, it has the information of who produced it, and where, and with what, and what alcohol concentration, so the consumer is guaranteed a product and the knowledge that the product is made with a certain level of safety. You see that historically in other products that may apply here to kratom and kratom products as well.

Is it just a matter of enforcement, or should there be a little bit more regulation for scientific rigor? Because in all of the dietary supplements industry, as you said, there are other products that are constantly contaminated, and they don’t face a lot of regulation. But then, when you get into developing a drug, that’s going to take a long time, lots of money. Are the GMP standards enough for kratom? Should every company have a full alkaloid panel on their product? I mean ideally, that would happen because then we can know what we’re getting.

Dr. Christopher McCurdy: Yeah, I think it would be great if you could. If that’s ever going to happen, I don’t know. But for most food products, we know exactly how much protein and fat and carbohydrate that’s in there. Questions I get all the time are what are the nutritional benefits of kratom? We’ve never really looked into it. Does that have Vitamin K? Does it have asorbic acid? Does it have certain things that would be desirable as a dietary supplement in it? Those are things that nobody’s really looked at because we’ve all been focused on the therapeutic, and making sure that we we get some science behind some of those therapeutic-type claims. But GMP is a great step forward. There’s problems with it, but it’s better than nothing. I think the problems are inherent in it, that you can be inspected and pass for GMP, and then as the inspectors leave and give you certification, when are you going to get inspected again? Are there surprise inspections? How well are those companies maintaining that quality of production every single day, and every single minute of every single day? Those are still question marks out there right now. I’m sure that there are some vendors that are top-notch, flying high above everybody, doing everything right every second of the day, and there’s others that get their certification, and maybe become a little more lax until the next recertification comes by. 

The DEA is interesting, because they’ll do surprise inspections. We have to have DEA licenses to do some of the work that we do, and they can show up any time, any day. They want to inspect your records and [make sure] you’re safe and make sure that you have adequate inventory and you’re doing the adequate level of security on the products that they’ve entrusted you to be able to possess. They can show up any day. 

Should GMP regulations be the same way? I don’t know how many people are out there that can do it.Brian and I both have worked on the industrial hemp project here in the state of Florida and the growers have to be below 0.3% THC. If they exceed that amount, they have to destroy their fields. Are there going to be enough people to go around and police that and ensure that the fields are being harvested or are adequate? It’s a big question mark for all of it. It’s never going to be a perfect system. We still have prescription drug products that get recalled because something happened, or there was a slip-up. It’s very rare at that level, but it still happens. 

“Everybody thinks that being in pharmaceutical research…the only interest that I have is going after this thing to make new pharmaceuticals and get rid of the product itself, and that’s the furthest thing, the furthest thing from the truth. What we want to do is decrease any type of harm that could be associated”

– Dr. McCurdy

I think everything we can do to provide some level of regulation helps everybody as a whole, from vendor to consumer. As we’re able to get online with product production in the United States we’ll even have greater control of that. This is why Dr. Pearson’s work is so vitally important to the future of kratom use in the United States. It’s understanding how to grow these things, how to cultivate them, how to ensure that you’re not sequestering metals, you’re not getting the wrong types of harmful chemicals near, or associated around them, even when you think they might be appropriate ways to aid the plants. If we can do it, our goal here has been to be able to understand this thing, from seed to consumer. I think Brian Pearson has a better way of describing it, but I think control over the whole industry is where it’s going to be at in getting adequate product that we really know, and we can produce with a certificate of analysis or something like that on that bottle, is the way that this needs to end up. We’re totally about trying to figure out how to make that happen, how to keep the product accessible, safe, and beneficial to everybody that needs it.

I will address the ugly elephant in the room real quick because everybody thinks that being in pharmaceutical research, and being in drug development, the only interest that I have is going after this thing to make new pharmaceuticals and get rid of the product itself, and that’s the furthest thing, the furthest thing from the truth. What we want to do is decrease any type of harm that could be associated with the benefit, so that individuals have access to something that’s natural, that’s safe, that we can trust. Can it inspire us to create pharmaceuticals? Well, heck yeah. I mean 25% of all prescription drugs are either natural products or are inspired from natural products themselves. Isolating these alkaloids, understanding the chemistry of them, understanding that specific pharmacology all being turned up on full blast is so vitally important to our understanding of how they all will come back and work in concert together within the plant as that symphony orchestra. But they also start to point us in other directions. Can we develop a whole new class in a whole new area of antidepressants, or a whole new area of anxiety medications, or a whole new area of pain medications? So there’s a lot of ways that it can be mutually beneficial down both pathways. Not to exclude one over the other, ever. That would never be anything we set out to do. 

I feel very blessed and very benefited from running into this plant the way that I did as we talked at the outset of this. It appeared it has continued to pop up in my life when I’ve tried to give up and and say we don’t have funding to do this. Suddenly, funding comes from somewhere, or interest comes from outside to help us move it forward and continue moving the work forward. I feel like I owe as much to this plant owes to the world, and so much there we just don’t understand and we haven’t tapped yet, and so much more work to do. 

The plants from that study are still growing, right?

Dr. Brian Pearson: The plants from both studies, those particular plants were unfortunately destructively harvested. But the good news is they came from known mother stock, so every one of those plants were cultivated from a mother that is still with us. We’ve amassed a collection of kratom trees and different genetics and I think that’s part of the exciting part of this future, where the synergy works out so well with Dr. McCurdy. As much as he loves to hear about the “plant nerd” side of the world, I’m just intrigued by the chemistry because that also feeds back to our work, as he was just saying so inspirationally. All these different things that this plant may be able to do in terms of improving human health. If we find there’s certain attributes, or certain compounds, alkaloids that are beneficial for specific improvements in human health, then that inspires us to target back and then to breed plants and new genetics that would target that need, so it kind of comes full circle back to us to say, okay, here’s our new goal let’s go ahead and develop plants that have the following attributes. We are blessed enough to have a brilliant young woman working on our team that came to the university several years ago who is a plant geneticist. So I think the future of this moving forward is to 1) understand the plant and understand the chemistry that it could provide us with, and then 2) what can we do to improve these plants. And this wouldn’t be GMO. You’re using plants in the same genomes. So the same thing could occur if you are breeding the plants traditionally, speeding up the process a bit by using newer molecular techniques. I’m just as excited at what the future of this plant provides to us. But those mother plants are still alive, the genetics are still with us, and it is my duty to ensure that we keep as much genetics as possible. To add to that, our team’s goal here is to try to build up a germ plasm repository so we have a large collection to draw from, to study with, and to better understand the plant. At the core, I’m a plant nerd, so I can never say no to a plant. I always take them home to my house. I collect various plants and this plant has worked its way into my heart, and so keeping them alive and making sure they’re healthy. One of my pursuits of joy and also the pursuit of my employment, so they are alive and well.  

“I think Kratom is the next medical marijuana.”

– Dr. McCurdy

Dr. Christopher McCurdy: It’s sort of like stray animals for you, I love it. I just wanted to jump on and piggy back that just a little bit, just to say about strains, and so many products being sold under different strains. You can you can buy products with different levels of mitragynine in them.  A vendor might be able to say, hey, this one is going to have a little less mitragynine than this one, and we’re going to say this one’s better for mood enhancement, or this one’s better for whatever. You can’t really tie any claim to anything anyway, it’s illegal by the FDA. But the bottom line is, I think what we’re seeing is like Dr. Pearson said, it’s just really remarkable right now. Because if we can start to understand and control the alkaloid level, production very analogous to what we’re seeing in the Cannabis industry right now, you’re going to the dispensary and you can find products with all kinds of levels of THC and CBD – I think Kratom is the next medical marijuana. I’ve said it for a while. I think what we’re going to be able to do with this genetic repository that Dr. Pearson is amassing is really understanding which chemotypes that we talked about earlier are going to be better for making you feel good, like an antidepressant type thing, or an anti-anxiety type thing, versus something that could be more for pain relief or something down the road. We will never be able to make those claims unless we have those standardized products put into place with clinical trials behind them, and then we can have those products. As long as we can demonstrate that there’s no abuse potential with those products, they would remain over-the-counter and be accessible as dietary supplements. 

There’s so much to do and there’s so much future and promise for the future with this plant. It’s just sort of giving us little clues every now and then. Keep going… I’m here for a reason for all you people. And I laugh because Dr. Pearson says no, it’s doing it completely because of its environment and that’s probably realistic, but if you get into the spiritual thoughts of it, and those types of shamanistic views of the world, they’re here for our benefit as well. I hold that very near and dear to my heart, and I really love these plants too. I generally don’t pick up just any plant and bring it home, but I have done that with a few. Particularly those that are of medicinal interest. 

Thank you guys so much for doing this, and it’s good to finally talk to you Dr/ McCurdy, and it was great talk to you Dr. Pearson.

Dr. Christopher McCurdy: Brian thank you for being persistent and getting on me. I’m really glad though at the same time that you had the opportunity to talk with some of the team members on our team before I got to come on here. They deserve so much credit for the work that we’re doing too, and I end up being the one shoved out in the front of everything all the time. I really think it’s time that this whole team gets recognition for the work that they do. I’m happy to be the cheerleader and lead it, but we’ve got incredible scientists that are working so hard to make this all happen, and pull the science from behind this plant, from the things that Dr. Pearson has learned and taught us, to the things that we’ve learned and taught him. It’s a really symbiotic relationship.

Dr. Brian Pearson: I’d like to echo that. Thank you so much Brian for the opportunity to have us talk here today. I can always talk about kratom and plants and horticulture. It’s great to know that folks out there are interested in the science that we’re doing. They’re excited about it. And they’re on board with us to try to learn about this amazing and unique plant as possible. Thank you for your time today and for helping to relay the science to a group that seems to be as enthused about it as we are.

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References

  • Babu, K. M., McCurdy, C. R., & Boyer, E. W. (2008). Opioid receptors and legal highs: Salvia divinorum and Kratom. Clinical toxicology (Philadelphia, Pa.), 46(2), 146–152. https://doi.org/10.1080/15563650701241795
  • Chear, N. J., León, F., Sharma, A., Kanumuri, S., Zwolinski, G., Abboud, K. A., Singh, D., Restrepo, L. F., Patel, A., Hiranita, T., Ramanathan, S., Hampson, A. J., McMahon, L. R., & McCurdy, C. R. (2021). Exploring the Chemistry of Alkaloids from Malaysian Mitragyna speciosa (Kratom) and the Role of Oxindoles on Human Opioid Receptors. Journal of natural products, 84(4), 1034–1043. https://doi.org/10.1021/acs.jnatprod.0c01055
  • León, F., Habib, E., Adkins, J. E., Furr, E. B., McCurdy, C. R., & Cutler, S. J. (2009). Phytochemical characterization of the leaves of Mitragyna speciosa grown in U.S.A. Natural product communications, 4(7), 907–910.
  • Lydecker, A. G., Sharma, A., McCurdy, C. R., Avery, B. A., Babu, K. M., & Boyer, E. W. (2016). Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 12(4), 341–349. https://doi.org/10.1007/s13181-016-0588-y
  • Macko, E., Weisbach, J. A., & Douglas, B. (1972). Some observations on the pharmacology of mitragynine. Archives internationales de pharmacodynamie et de therapie, 198(1), 145–161.
  • McCurdy, C. R., & Scully, S. S. (2005). Analgesic substances derived from natural products (natureceuticals). Life sciences, 78(5), 476–484. https://doi.org/10.1016/j.lfs.2005.09.006
  • McCurdy, C. R., Sufka, K. J., Smith, G. H., Warnick, J. E., & Nieto, M. J. (2006). Antinociceptive profile of salvinorin A, a structurally unique kappa opioid receptor agonist. Pharmacology, biochemistry, and behavior, 83(1), 109–113. https://doi.org/10.1016/j.pbb.2005.12.011
  • Roth, B. L., Baner, K., Westkaemper, R., Siebert, D., Rice, K. C., Steinberg, S., Ernsberger, P., & Rothman, R. B. (2002). Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences of the United States of America, 99(18), 11934–11939. https://doi.org/10.1073/pnas.182234399
  • Zhang, M., Sharma, A., León, F., Avery, B., Kjelgren, R., McCurdy, C. R., & Pearson, B. J. (2020). Effects of Nutrient Fertility on Growth and Alkaloidal Content in Mitragyna speciosa (Kratom). Frontiers in plant science, 11, 597696. https://doi.org/10.3389/fpls.2020.597696

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