Interview with Dr. Walter Prozialeck, Biomedical Educator and Kratom Researcher

Dr. Walter Prozialeck

Listen to this interview on Kratom Science Podcast #44

KratomScience: How do you pronounce your last name?

Dr. Walter Prozialeck: Proh-jell-eck. It’s an old Ukrainian word that means “really bad golfer”.

KS: *laughs* But I see you are a really good rugby player, it says on your Wikipedia page.

WP: Well I used to be. I’m paying the price after 22 years of that. I was diagnosed with rheumatoid arthritis when I was in my 50s. I probably had it for most of my life. I played football for six years, rugby for 22 years. So I took a bit of a beating.

KS: You’re originally from Johnstown?

WP: It was a little coal mining town near Johnstown called Dunlo. It’s a dying, rust belt, coal mining town.

KS: You have a background in osteopathy?

WP: Osteopathic medicine is the correct terminology. It started out in the late 1800s as kind of an alternative approach to medicine. Mainstream medicine, which we now call allopathic medicine – any M.D. is technically an allopathic physician – was pretty bad in the late 1800s. It was before the germ theory of infectious diseases was widely accepted. Doctors were not used to using sterile or aseptic techniques. Some of the drugs used in that era were actually pretty poisonous. Strychnine was used as a drug. Arsenic and mercury were used as drugs.

Mainstream medicine was in such a bad state that a physician named Andrew Taylor Still came up with a new approach and he called it “osteopathy”. At first, he shunned the use of drugs and surgery. He focused on the musculoskeletal aspects of medicine. Over the years, osteopathic education and practice have changed. The osteopaths won increased practice rights, which includes the ability to do surgeries and prescribe drugs. So really since the mid 1950s, there isn’t that much difference between M.D.s and D.O.s, doctors of osteopathic medicine.

I’ve been teaching pharmacology, first in Philadelphia at the osteopathic school there, and then here in Chicago. This is my 41st year of teaching. We teach the osteopathic students the same things about drugs as we teach medical students. I teach at the University of Illinois as a part-time gig. It’s the same material. Most people don’t know if their doctor is an M.D. or a D.O.

KS: Did you become interested in medicine as an outgrowth of your interest in sports?

WP: No.. As I think back I remember in 4th grade, one of my teachers was asking students “What do you want to do when you grow up?” She went around the room. I just blurted out “I want to be a scientist!” Somehow I got an interest in science at an early age. My dad was a steelworker and coal miner, and my mom was the postmaster in our little town. They pushed me on the education front. I was always a pretty good student. Never at the top of the class but never had any real trouble. They encouraged me and helped me get through college. They even helped me a bit in grad school. Even though I had a stipend, it wasn’t quite enough to live on in Philadelphia. So it was their support. And then when I did start pursuing my education I had a lot of really good role models. I had a great high school science teacher. In college, I had a couple of wonderful chemistry professors. In grad school I had a great mentor who was a psychopharmacologist Wolfgang Vogel. My postdoc mentor, Benjamin Weiss, was another psychopharmacologist. All were great role models.

KS: What made you become interested in kratom?

WP: Several lines led me to kratom. First, I got a question from one of my clinical colleagues here at Chicago College of Osteopathic Medicine. He mentioned a patient had asked him about kratom. He asked me if I knew anything about it. I really had never heard of it. So I started looking into the matter. When I saw what kratom was and saw some of the claims about its use, the fact that I was dealing with a lot of orthopedic issues and some pain issues, I naturally was interested in it. The more I read, the more interested I became. I think it was 2012 when I published my first review article on kratom. It’s been cited very highly. It was one of the first reviews on kratom published in the United States. There were several people, Chris McCurdy, me, Oliver Grundmann, who I know you’ve interviewed. It was about the same time we all got interested in this topic. It’s a topic that’s only been on the front burner in the United States for eight years or so. 

KS: And you can tell there’s getting to be more and more studies. If you go back it’s hard to find before 2012. There are a few things from the 70s and 80s.

WP: There’s actually stuff from the 1930s that almost nobody cites. I think what’s happened is we’ve become reliant on computerized literature searches. All the current journals are pretty much online, and publications are available through electronic media. What’s happened is a lot of the older research has been overlooked. It was indexed in things like the old Index Medicus which was a bound volume that scientists would search by hand. A lot of the papers that were published in the early 1900s even up into the 1950s and 60s have never really been entered into computerized databases. So a lot of those older papers just go by the wayside. Few kratom researchers have been rediscovering that old work. I just reviewed a paper where the authors had a very nice review of some of the older literature, some of which I had never seen. It was quite a good review.

KS: “Pharmacology of Kratom” from 2012 is the paper you did. We hear a lot about mitragynine and 7-hydroxymitragynine as the two main alkaloids. Can you explain what you know about some of the other alkaloids? Like speciociliatine, paynantheine, specio-…?

WP: Speciofoline? The pronunciation is the joke, especially for two guys with Pittsburgh accents.

KS: *laughs*

WP: I have focused my attention on mitragynine and 7-hydroxymitragynine. I have not done any studies on the other compounds. But there’s a lot of interest in the other compounds. There are a couple of labs who are really digging into the biochemical pharmacology of these different compounds. The big question in kratom research is “What are the roles of the multiple compounds that are present in the natural leaf?” When a person consumes the leaf, or teas made from the leaf, they’re obviously consuming a lot of compounds beside mitragynine. How these compounds interact is only something that’s beginning to be explored. They’re still identifying new compounds. The fact the National Institute of Drug Abuse is putting some money into this area now is a good development and progress is being made. It’s a very active area of research right now. Until Dr. McCurdy got the major funding, the top lab in the world was probably in Malaysia. Darshan Singh is the head of that group. They’ve been incredibly productive too.

KS: I’ve had him on the podcast too. He was trying to get me to pronounce kratom properly. “Ke-tum”.

WP: It was funny. I gave a presentation for a webinar with a group in Indonesia. I think there were five different ways people pronounced kratom.

KS: This might be related to osteopathy. Quoting from “Pharmacology of Kratom”: “A variety of chemical compounds have been isolated from kratom and shown to exhibit opioid-like activity on smooth muscle systems.” Would you explain what that means?

WP: What I mean by that is if anyone’s ever used an opioid like Vicodin, hydrocodone. One of the big side-effects is constipation. It turns out there are opioid receptors in our gut, on the smooth muscle cells of the gut, and on the neurons of the enteric nervous system, which regulates gut movement and motility. Opioids like hydrocodone, which is in Vicodin, bind to the opioid receptors, and what that does is inhibits peristaltic movement of the bowel, so the bowel slows down. That type of effect is common to all opioids. Scientists will study compounds for opioid activity by looking at their effects on intestinal smooth muscles, say from a rat. Opioids can relax some smooth muscles and contract others. Scientists can use opioid antagonists like naloxone to see if opioid receptors are involved in the response to the unknown compounds that they’re testing. So some of the compounds in kratom act on opioid receptors in the bowel and then they can cause constipation. I helped Dr. Singh with the data and writing up the results of when we looked at the subjective effects of opioids versus kratom. The kratom effects on the bowel were definitely milder than typical opioids. 

KS: In the “Update to the Pharmacology of Kratom” that you published in 2016, it says “Based on all the evidence it is clear that kratom and its mitragynine constituents are not opioids and that they should not be classified as such.” 

WP: I probably over-stated that a little bit but it’s a huge debate that is still being kicked around in the kratom community and the term that most kratom researchers have adopted is, they refer to the mitragynines as “atypical opioids”. There are some people, most notably Jack Henningfield who has been a huge supporter of kratom research and a kratom advocate. Jack has recently made the argument that we shouldn’t refer to these compounds as opioids at all because the kratom plant is not related at all to the opium poppy. The compounds are chemically a different class of compounds. They’re mainly indole or modified indole chemical structures. Their effects at opioid receptors are different. Even though they can bind to opioid receptors, the effects are different than classic opioids, and, you know, the fact that a compound binds to an opioid receptor, I’m not so sure that makes it an opioid. The best example would be naloxone which is used to treat opioid poisoning. It obviously binds to opioid receptors and displaces the drugs that the people poison themselves with, but it’s an opioid antagonist. So it’s not an opioid. 

KS: A lay person would look and and see that the FDA considers it an opioid and they might think “This is kind of like heroin or oxycontin.” From a headline, you can’t really get a detailed understanding of how it works. 

WP: There’s been some ramifications of that. The government agencies have periodically used the term opioid when referring to kratom, especially with the FDA movement to schedule the mitragynine into Schedule I substances. I think they’re looking at the science, finally. 

KS: I want to get your thoughts on the letter recently discovered from the HHS assistant health secretary to the DEA rescinding his recommendation that kratom be scheduled. This is from 2018, and the American Kratom Association, through congressman Mark Pocan from Wisconsin, ,just got their hands on it. Do you have any thoughts about that? 

WP: Yeah that was a big development and as a scientist who’s been trying to look at kratom from a scientific perspective I’ve been trying to be unbiased observer. But the fact that that letter to rescind the request to schedule kratom was pretty much not acknowledged, or was even, to a certain degree, suppressed at the level of the FDA is a bit frustrating. The fact that they were using the term “opioid” in the rationale to schedule kratom in the first place, as you mentioned before, that had some ramifications. Some of the negative ramifications of the opioid argument, which went on for the past two years even though the move to ban was rescinded, it’s had ramifications for kratom users and kratom marketers. Some of the marketers have actually played up the opioid like activity of kratom. Some vendors have marketed it as a legal high, claiming it’s like an opioid in its effects. The vast majority of user reports are that kratom’s effects are not subjectively like opioids. The euphoric effects are very attenuated with kratom and kratom compounds. They don’t have the tendency to produce euphoria or depress respiration like classic opioid. Some drug abusers see “legal opioid” and say “I’m gonna try this.” There are people trying to get high by taking kratom, and they probably pushed the dosage envelope too high and get into overdose situations. 

I have never made the argument that kratom is a totally safe drug. If it has any pharmacologic activity, which clearly does, it’s going to have side effects and toxicities and people can be poisoned with it. The key thing though is it’s clear the kratom is safer than most traditional opioids. 

“From a scientific perspective, I’ve been trying to be unbiased observer. But the fact that that letter to rescind the request to schedule kratom was not acknowledged, or was even, to a certain degree, suppressed at the level of the FDA is a bit frustrating.”

KS: Along those lines, do you know anything about how it might interact with other drugs. We’ve heard about these 44 deaths that the FDA claim. We see that in most cases there was fentanyl or other drugs involved.

WP: Some of the cases that were reported as kratom related deaths, I mean there were so many issues identified. The other drugs that the people were using is certainly a big issue. Many of the cases the people had severe depression. There was one case, it was actually a suicide, but it was after the young man had used to kratom product. It was listed as a kratom-related death even though the guy had attempted suicide several times earlier. There was one case that I’ve heard of, but I haven’t seen the report, where the guy was shot while under the influence of kratom and didn’t survive, yet it was listed as a kratom related death. That kind of stuff, as a scientist I find that kind of hard to deal with. We need to look at these cases from a cleaner forensic standpoint. Do we have the actual toxicology data on the level of mitragynine in the victim’s tissues or blood? Do we know what product the person was using? If we know what product the person was using, we could check and see if it was contaminated with other substances, because there have been reports of kratom products being adulterated. Another thing that’s missing in a lot of the overdose reports is what other drugs what was the patient taking? Do they have blood levels or tissue levels on the other drugs? What kind of doses were they using? And the fact that there are so few studies on kratom in humans – almost nothing is known about drug interactions with kratom in people. We just don’t know. The studies haven’t been done. 

KS: I want to ask you about the COVID pain case study. A guy was diagnosed with COVID, took kratom and it helped a lot with his pain and anxiety about the virus itself. This points to a bigger public health issue because COVID is actually creating thousands of chronic pain patients. Some people have pain months later. There’s a lot of mental health issues with the shutdown and everything. A lot of chronic pain patients are complaining that they’re being underprescribed their meds as a response to the opioid crisis. I’m just wondering if you want to comment on that.

WP: That case is someone that I knew about. They told me that they tried kratom. I’ve been open about my kratom research here at Midwestern, and the person who came forward is this nice young man and he told me his story. He had had previous experience using kratom for both pain from sports injuries and as just an energy booster. When he developed COVID, he had a lot of problems with a lack of energy and musculoskeletal pain and he was depressed and just couldn’t function and he decided to try kratom on his own and it seemed to help him. So I put him in contact with Dr. Corazza in London who is a clinical psychologist, I think,  who actually interviewed him over the phone and that was the basis of the case report.

The issue of pain being undertreated, that’s the consequence, as you said, of the opioid crisis. In 2015 or so, the CDC came up with new guidelines for prescribing opioids for non-cancer chronic pain. Even though they were guidelines, they weren’t absolute rules. A lot of states and clinicians and practice groups and healthcare systems have taken those guidelines and interpreted them as absolute rules, and a lot of docs were just refusing to prescribe opioids. A lot of states have restricted opioid prescribing. Some states, the initial prescription can only be a few days supply and then if the person or the physician wants to continue them on the drug, they have to be referred to a pain management specialist or pain clinic, and the problem is those clinics are few and far between, and with COVID going on it’s hard for anyone to get treated for non-COVID problems right now. A lot of pain patients, I think, are being undertreated for their pain. Which creates more demand for kratom. Now with all that said, even though access to prescription opioids has decreased in recent years, if you look at opioid overdose deaths, they’re still going up through the roof, and the only explanation is an increase in use of street opioids. The big crisis now is the fact that these fentanyl derivatives keep showing up, and they’re now, in my understanding, the number one cause of drug overdose deaths. Some of the fentanyl derivatives like carfentanil are just so powerful. It’s roulette when a patient takes a drug containing those substances. They might think they’re taking heroin, but if it’s laced with fentanyl or carfentanil they’re gonna get much more of an effect than they would have expected.

“It’s hard for anyone to get treated for non-COVID problems right now. A lot of pain patients, I think, are being under-treated for their pain. Which creates more demand for kratom.”

KS: When they’re taking prescribed drugs they know exactly what’s in it because they’re regulated. That’s an issue with kratom as well. You did a study of kratom and toxic metals. These kratom samples were purchased around Chicago. I won’t mention the company’s name, but some of these were pretty popular companies. You found a lot of nickel and lead in some of these kratom samples.

WP: Those were the two most worrisome metals. I did that in a follow-up to study – I forget it was the CDC or the FDA who did the initial study and put out a report, a consumer warning about toxic metals in kratom. I was just curious, I looked at the products that they had analyzed. I have a background in heavy metal toxicology, so it was my two careers as a metal toxicologist and someone with an interest in kratom coming together. I was just curious, so I went to several head shops in the western suburbs of Chicago and I saw what products were being sold. I had talked to kratom users about which products they use. I picked out 10 products. I bought them myself out of my own pocket, just because of the legal ramifications and funding for research is limited. So I thought that part of the study is my contribution to science. We had the two issues: the one was toxic metals and at the same time there were reports from federal agencies about their concern with kratom being linked to outbreaks of salmonella. So I collaborated with some of our microbiology faculty here and they tried to culture microbes from the kratom samples. We also assayed the kratom samples for panel with toxic metals. The final thing we did was we actually measured levels of mitragynine and 7-hydroxy. We didn’t find enough 7 hydroxymitragynine to matter. But all of the samples did contain mitragynine which means they were derived from kratom. But it was kind of troubling how dirty the products were in terms of microbial contamination and metal contamination and the microbes – we didn’t find any salmonella, which was a good thing. The microbes mostly were benign for most people, but the issue is what about immunocompromised people? Might some of the bacteria that are present be pathogenic in immunocompromised people? So that was a concern. Back to the toxic metals… The metal that I’m most concerned about is lead. The levels of lead in a few of the products, if we represented the levels as micrograms per gram of product – most people base their dose of kratom on how many grams of product they’re using – we estimated a dose of 5 to 10 grams a day which is not unreasonable for heavy kratom users. Heavy users can get up to 20 or 30 grams a day pretty easily. With levels of like 10 grams a day ingestion, for some of the products, would exceed the allowable daily intake of toxic metals, particularly lead, so there were a few of the products that I was really concerned about with lead. 

One good thing about this study: We did find a couple of products that had very low microbe burden and we didn’t find much toxic metals in two of the products. It turned out they were the most processed products. Most of the products were simply dried chopped leaf material in capsule form. The other positive note: Before I published the paper I looked at the American Kratom Association’s list of vendors and kratom dealers that have agreed to follow their recommended good manufacturing practices, and only one of the companies that makes the product that we found tested negative had signed and agreed to the American Kratom Association good manufacturing practices. All of the other products were from companies that have not agreed to those practices. So there is an uncontrolled up market out there where it’s sort of a no man’s land. Some companies are selling products that are not of really good quality and the consumer needs to be aware of what they’re buying. 

KS: The levels of lead that you found – how much kratom would somebody have to ingest – you said it was only 5 to 10 grams a day that would be toxic?

WP: Yeah, that would be it. The thing is, these metals accumulate in the body. I’m not saying someone who uses kratom occasionally is going to be poisoned with lead. I’m more concerned about the chronic users who are using some of the not-so-high quality products that contain high levels of lead. If they do this every day, they are at risk of developing chronic lead poisoning. 

KS: I asked Darshan Singh about this. There’s some people who say they were losing hair and had to take other supplements. I would not take kratom so it made me lose hair, that’s the only thing I have. Dr. Singh said that he doesn’t see that Malaysia, because they’re getting kratom right off of the tree, the stuff they make over there is fresh, and it must because of the adulterants.

WP: The whole question, and it’s something I’d love to work out but it would be a very hard study to do in a scientific manner, where do the metals come from? I don’t have an answer for that some there is one paper I’m aware of and I can’t remember the name of the author but they looked at kratom products from different parts of the world, and they tried to look at levels of metals in the kratom samples and correlate that with the metals that are common in soils from the different geographic regions of the world where the kratom samples came from. I’m not so sure about the quality of the study. I mean there were clearly differences in metal levels in different kratom products, but I’m not so sure it’s from the soil. In my paper, I did comment about possible sources and one of the confounding issues is that in the US almost all of the kratom sold here comes from Indonesia, and Indonesia is a volcanic group of islands. There’s a lot of literature about metal contamination. There’s a chance it could come from the soil, but they also it could be the way the the leaves are processed. I have never been there to observe this in person, but I’ve seen film representations of how kratom is processed. I’ve talked to people who have been there and have seen it processed at the site. And some of the equipment that’s used might not be up to modern food or drug processing standards. This ancient equipment could be leeching all sorts of metals. The fact that I found nickel with chromium in the samples, those would clearly be possibly derived from the equipment that was used to process. I tried looking at the kratom samples under the microscope. I even took a magnet to the microscope slide. I waived the magnet underneath to see if I could identify any metal particles, thinking that if it came from the equipment there might be fragments of tiny bits of metal present. I couldn’t find anything with the magnet experiment. That was one that didn’t work. But who knows where the metals come from. It would be fascinating to look at.

The microbial issue, I’ve talked to the botanist at University of Florida. I think his name is Brian Pearson, who I had a really interesting phone conversation with him right before I published the metals paper. The whole issue of how kratom grows and what are the factors that cause metals to appear in kratom? Is it absorbed from the soil. Is it from the processing of the leaves? A more basic question is what causes the mitragynine to be formed. There’s the recent paper from Florida on nutrient fertility on growth and alkaloidal content. One of the things that I thought of and  some of this came from talking with my microbiology colleagues here is, the microbiome that the plants are grown in might have an impact on what active compounds they produce. Why does tobacco produce nicotine? It’s an insecticide. Why is kratom producing mitragynine? Is it an anti-microbial? I’ve talked to some people who think it might be an anti fungal. So could it be that the plant has to be exposed to the fungus to produce the chemical defense mechanism mitragynine? There’s the issue of how variable the alkaloidal content of kratom products if they vary from one sample to another, one strain of kratom to another, might the microbial environment that those different plants were grown in, might that contribute to the difference in expression or levels of these active compounds which you probably pesticides? 

“With levels of 10 grams a day of ingestion, for some of the [kratom] products, it would exceed the allowable daily intake of toxic metals, particularly lead”

KS: The mitragynine content they say in Thailand is like 66 percent of alkaloids, and then in Malaysia it’s only 38 or something, and in the Philippines they barely found any mitragynine there…

WP: They tried growing in Florida and it’s my understanding at first they had very low levels of mitragynine and I don’t know if they’ve found an answer to how to get the plant to make more mitragynine.

KS: I’ve heard just from growers that it takes a couple years, kind of like growing grapevines for wine, it takes a couple years for the grapes to mature. That might have been because it was a four month study that they didn’t they found like such low levels

WP:  It could be a time factor, I totally agree.

KS: There is a sleep problem study that you’re on with Dr. Singh that showed fairly heavy kratom consumers had trouble sleeping and had moderate to severe pain when stopping kratom. Why does pain happen when they stop? Is it a dependency issue?

WP: My guess is –  this is a simple idea, but it seems to hold true and I I try to emphasize this when I teach pharmacology to my students. Our bodies tend to adapt to the presence of drugs and when somebody uses, say, opioids for a while, one of the things that can happen if they abruptly stop is they’ll have withdrawal symptoms, but they can also have increased pain sensitivity, and it’s not just part of the withdrawal syndrome it’s hyperalgesia where their sensitivity to pain increases. That’s one of the unwanted effects of chronic treatment with drugs. You get these rebound effects that are in the opposite direction. So it doesn’t surprise me that kratom – the people are using it probably in significant doses, and when they try to go off they have the rebound pain. Now, some of the pain might have been just kratom withdrawal, and some might be real hyperalgesia. We didn’t distinguish that in the study. 

KS: And it said “Most regular users in traditional contexts knew how to self-treat their kratom withdrawal symptoms”. That seems like sort of a cultural thing because they’ve been using it for a long time. How do they self-treat withdrawal? 

WP: I think a lot of them use benzodiazepines actually. I’d have to go back and look at the study, but drug sales – I’m not sure in Malaysia – but a lot of countries that drugs aren’t as restricted as they are in the U. S. Some countries are far more restrictive. But benzodiazepines, in my understanding, are pretty readily available. So I would suspect that’s one of the main drugs they use. 

KS: A lot of psychiatrists are recommending treatment for kratom addiction or withdrawal with buprenorphine or Suboxone. What do you think of that? 

WP: There are enough case reports that say that works, and it probably does. The problem is, and it’s one of the reasons there’s such a demand for kratom, access to things like buprenorphine and Suboxone, the product that contains buprenorphine, and other drugs like methadone, is really restricted. It’s hard for people to get them. A lot of people who use buprenorphine, it’s only a weak opioid, a partial opioid agonist, so it doesn’t produce much of a high, if you will. A lot of addicts have trouble staying on buprenorphine products. So, it works, I have no doubt. But are there other treatments? I have recently reviewed a couple of case reports with other potential treatments, I can’t divulge those because the papers haven’t been published and I haven’t even seen the final editorial decision on one of the papers, but there are possibly other approaches. If you think about the pharmacology of the mitragynines, they do affect opioid receptors to a certain degree, but that is not their only actions. They have so many other effects. A drug like buprenorphine is going to mainly target the opioid receptor mediated effects of kratom, and I don’t know that it would help with any other effects that have different underlying mechanisms. 

KS: We were looking at a study where they looked at all the receptors that the different alkaloids were binding to, including adrenergic receptors which accounts for some of the stimulant properties, I guess.

WP: It’s weird, in pharmacology. Again, I’ve been teaching this for over 40 years and students and patients like to know what what the drug does and how it does it. In pharmacology, one of the things we teach the students is mechanism of drug action. Well in psychopharmacology in particular, its becoming clear that a lot of drugs that we used to think would have a single mechanism of action probably have multiple effects. The classic ones would be the antidepressants. When I was in graduate school in the 1970s, we thought depression was caused by a deficiency of norepinephrine and serotonin and inhibiting the metabolism with MAO inhibitors would raise the level of the transmitters and that would make depression better, or giving in that in that day the only antidepressants other than MAO inhibitors were tricyclic antidepressants and they inhibit the synaptic reuptake of norepinephrine and serotonin, or serotonin and not so much norepinephrine… The bottom line is we now know that there are many other things going on for example when drugs like tricyclic antidepressants are used over time, the receptors actually adapt, the receptors for the neurotransmitters. There are changes in synaptic organization of the brain. So there’s new synapses formed. There’s actually some neuronal growth that occurs.There’s neurotrophic factors that are released. So the mechanism of action is much more complicated than it was back in 1975. It’s the same drug. In 75 we knew exactly how the drugs worked, but now that we know a lot more about the drugs we don’t know so much about how they work. So I tell the students, I list 10 biochemical actions of an antidepressant, you tell me how those effects add up to the improvement in mood of a depressed patient, and I don’t think anybody can do that. We’re just not there in the state of the knowledge. The brain is kind of a complicated organ. The point about multiple drug effects, I think it’s true with kratom. There are new antipsychotic drugs that are being introduced that have multiple mechanisms of action and they’re referred to as “dirty drugs”. It doesn’t mean they’re good or bad, it just means they have multiple effects. Our tendency is to think that multiple effects will complicate things, but we’re now finding that these multiple effects probably can add up for positive benefits in patients.

“The brain is kind of a complicated organ. The point about multiple drug effects, I think it’s true with kratom…Our tendency is to think that multiple effects will complicate things, but we’re now finding that these multiple effects probably can add up to positive benefits in patients.”

KS: Dr. Cachat calls it an entourage effect. 

WP: I like that.

KS: Is that why the the alkaloids haven’t been developed into a pharmaceutical drugs because I know like the the one paper from the seventies it was the precursor to Glaxo Smith Kline – they did a study on mitragynine and one of their conclusions was, it it looks like it has the same effect as morphine without the side effects. Why didn’t Glaxo Smith Kline develop that into a drug? Is it maybe because the plant does just fine but by itself and they can’t really compete?

WP: I think it’s probably economics. Why would anybody pay for an expensive drug in a tablet or capsule form, if they can buy a drug that does the same thing, in say an herbal product that does the exact same thing for a fraction of the price. Who would pay for something that grows on trees?

I know other people over the years have applied for patents on developing drugs based on kratom and it’s very difficult to get that type of patent approved or awarded. It can be done. I mean there are drugs that have been developed from natural products. I’m thinking of tamoxifen, the anti-cancer drug from the Pacific yew tree. So it is possible, but it’s not easy. I know some of the patent applications were denied, because the argument was you can’t patent a plant. But I know people have patented things in the past that are derived from plants, so I’m not sure of the technicalities there.

My hope for kratom is that somehow it will be regulated. With regulation there would be standards to protect the consumer so that when people buy a product they can be pretty sure that it meets federal standards, that it is what it claims to be, it’s not adulterated with other drugs, it’s not contaminated with ridiculous levels of toxic metals. That doesn’t mean it has to be completely free of metals. When we use oregano in our spaghetti sauce or marinara sauce, there are toxic metals and germs. There are microbes in herbs and spices that we use all the time. But they’re regulated. There are standards for what the microbial burden, what the mental burden have to be. They have to be within certain limits and the federal agencies have standards for most products. I think that the move to withdraw the proposal to schedule the mitragynine into Schedule I, I think it signals that the federal agencies are more willing to look at the science of kratom and make a decision, and if it’s found to be something that has useful properties, it might have some toxicities but the benefits outweigh the potential risk, and we can come up with standards to identify what an acceptable product would be, what would be acceptable dosing, and regulate. I mean, we’ve managed to regulate some pretty dangerous drugs without making them Schedule I substances. The best example is nicotine. People can buy nicotine gum, nicotine patches, and it’s a powerful drug. If we can do that with nicotine, we can do it with caffeine, why can’t we do it with kratom and the mitragynines. 

KS: And that’s the Kratom Consumer Protection Act that the American Kratom Association is trying to pass. 

WP: I’m not sure of all the states that have done this, but it’s interesting. Some of the states that have passed the protection act are states that you don’t think of as being real progressive in the area of drug use and drug abuse, but they are protecting consumers by regulating kratom. They’re not banning it, they’re regulating it which it’ll be interesting to see what standards are adapted in those particular states and see what works and what doesn’t, and maybe it can be adopted at the federal level. 

I’ve enjoyed talking with you, Brian. You’re doing a great job with the website and the podcast. I found them very informative and I’m gonna keep following what you’re doing. If I could ever help in the future, let me know.

I consider myself in this whole kratom issue, you know I’m 68 years old I’m nearing the end of what I think has been a pretty good career. Rather than just being a kratom advocate I’m trying to be an objective third party evaluator. As an educator, I think I could take that position. I do think that kratom shows so much promise. We have to move ahead with research and it could be a very important development, especially with our drug abuse crisis going on. I think we need to tell the truth. If we’re doing this research which is really exploding right now, and we find something that’s troubling, as scientists we have to talk about it. I was almost glad I found the toxic metals, because too many kratom advocates are touting it as a wonder drug. At some point we have to stand back and say, wait a minute now, is it really as good as it’s being touted, and are there any potential problems? To me the biggest problem is quality control. The consumers just don’t know what they’re getting. We need to fix that. The other thing we know almost nothing about – what about people with existing health conditions? Someone with diabetes or hypertension or obesity. Does any of this affect the response to kratom or does kratom have unusual effects in some populations? What about females versus males? Most users that in the surveys that are done are overwhelmingly male. Are there differences in responses in males and females? The drug interaction issue is huge. And all of this needs to be scientifically investigated. The fact that the feds aren’t going to immediately ban it is a good thing from a research standpoint. I think the studies can move ahead.


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