Addiction Medicine Made Easy | Fighting back against addiction
Addiction is killing us. Over 100,000 Americans died of drug overdose in the last year, and over 100,000 Americans died from alcohol use in the last year. We need to include addiction medicine as a part of everyone's practice! We take topics in addiction medicine and break them down into digestible nuggets and clinical pearls that you can use at the bedside. We are trying to create an army of health care providers all over the world who want to fight back against addiction - and we hope you will join us.*This podcast was previously the Addiction in Emergency Medicine and Acute Care podcast*
Addiction Medicine Made Easy | Fighting back against addiction
The Science on Kratom: Kratom Journal Club (Bonus with CME)
* Link to get CME at the bottom of the show notes *
Ever wondered if a plant could be both a herbal remedy and a controversial subject in addiction medicine? Join us as we uncover the multifaceted nature of Kratom with Dr. Sonia Del Tredici and Dr. John Keenan from the Addiction Medicine Journal Club podcast for a journal club style episode on Kratom. Together, we explore Kratom's historical uses for pain relief and fatigue management and its growing popularity as an aid in opioid withdrawal. This episode promises to give you a thorough understanding of its pharmacological effects, including interactions with opioid receptors and anti-inflammatory benefits.
Our conversation shifts to the intriguing trends in Kratom usage across the United States. We dissect three recent studies on Kratom, highlighting Kratom's allure as a perceived safer option for managing anxiety, depression, and pain. Despite its benefits, we don't shy away from discussing its potential for addiction and the demographic reach of its users. This episode challenges listeners to consider whether the overlap between Kratom users and those with other substance use disorders is surprising or expected, urging healthcare providers to adopt open-ended dialogues to address patient needs effectively.
In a deep dive into Kratom Use Disorder, our discussion includes a fascinating case series study examining the use of buprenorphine for treatment. We highlight the study's findings on withdrawal management and Kratom metabolite reduction, exploring the effectiveness of buprenorphine in stabilizing patients. With a significant portion of patients remaining in follow-up care, we ponder the subjective effects of using Kratom alongside buprenorphine. Tune in to grasp the complexities of Kratom use and the importance of education and ongoing research, as we prepare for an upcoming interview with an industry professional to continue this enlightening series.
Our episode reviews three studies on Kratom to facilitate our discussion. Here are those studies:
Smith KE, Dunn KE, Rogers JM, Grundmann O, McCurdy CR, Garcia-Romeu A, Schriefer D, Swogger MT, Epstein DH. Kratom use as more than a "self-treatment". Am J Drug Alcohol Abuse. 2022 Nov 2;48(6):684-694.
Hill K, Grundmann O, Smith KE, Stanciu CN. Prevalence of Kratom Use Disorder Among Kratom Consumers. J Addict Med. 2024 May-Jun 01;18(3):306-312.
Broyan, V. R., Brar, J. K., Allgaier, Student, T., & Allgaier, J. T. (2022). Long-term buprenorphine treatment for kratom use disorder: A case series. Substance Abuse, 43(1), 763–766.
To contact Dr. Grover: ammadeeasy@fastmail.com
Follow this link to get CME for this episode:
https://micaresed.org/courses/podcast-addiction-medicine-journal-club/
Hello, my friends. Welcome to the Addiction Medicine Made Easy podcast, where we take topics in addiction medicine and break them down into digestible nuggets and clinical pearls that you can use at the bedside. Dr Casey Grover here as your host once again.
Speaker 2:All right. Thank you so much for joining me today on this bonus episode, and I like to always give gratitude as we start. So first thank you to the Montage Health Foundation for their support of this podcast, and I also want to share some gratitude that I have a new partner organization, the nonprofit Central Coast Overdose Prevention. With that, we'll move on to discuss today's episode. This is a bonus episode.
Speaker 2:I've been working with my friends Drs Sonia Deltrenici and John Keenan from the Addiction Medicine Journal Club podcast. We did a joint episode on Kratom recently and this current episode is the follow-up to that first episode. We wanted to get started on the topic of Kratom by discussing what we've learned by talking to our patients and then follow it up with a review of some scientific articles on Kratom, and this follow-up episode is where we discuss the scientific articles. Now, if you are an avid listener of the Addiction Medicine Journal Club podcast, first of all I love your taste in podcasts. They do an awesome job and they're one of my favorites. But second, you will already have heard this episode, as John and Sonia released it on their podcast earlier this month. I've really enjoyed collaborating with them and we are hoping to do more joint episodes in the future.
Speaker 1:So with that here we go a deep dive into the literature on Kratom.
Speaker 3:Welcome everybody. This is Dr Sonia Deltredici and I am joined by our two other addiction doctors, dr John Keenan and Dr Casey Grover. Say hi guys.
Speaker 4:How's it going? Good evening.
Speaker 3:This is another joint episode between the Addiction Medicine Journal Club and the Addiction Medicine Made Easy podcast. If you listened to our first joint episode on kratom, you've heard us with some informal chit-chat about our personal experiences treating patients with kratom use disorder and what we had learned, just kind of getting our first glimpse of this substance and what it is doing to and doing for our patients. So tonight we are back again to discuss some of the literature about kratom use disorder and kratom use in general, and so we're going to have a journal club tonight, a little different from our typical journal club format. Those of you who listen to the Addiction Medicine Journal Club podcast. We're going to discuss three articles briefly, in less detail than we normally do, but we wanted to get through all three so that our listeners could really have a sense of what's out there about Kratom. So with that said, casey, you want to take it away?
Speaker 2:Yeah. So once again, so excited to be podcasting with you guys. This has been super fun and I've really enjoyed it, so I think we're hopefully going to do some more topics in the future. So, just to level set, kratom refers to a tree-like herb that grows naturally in the southeastern Asia-Pacific region, and the scientific name is Mitragyna speciosa. It has both stimulant and opioid-like properties, and there are multiple traditional medical uses for kratom, including pain relief and to stave off fatigue. It has also been used recreationally for euphoric effects and more recently, it has been used to manage opioid dependence and withdrawal.
Speaker 2:Kratom affects multiple receptors in the body. In the body, it's an agonist at the mu and kappa opioid receptors, and there's also some evidence that it inhibits the cyclooxygenase 2 enzyme to produce an anti-inflammatory effect. So and I forgot one thing it also does have alpha 2 agonist effects. So, the way I think of it, it's a combination of opioids, stimulants, clonidine and ibuprofen, and I actually came up with a brand name. If we want to brand this thing, I think it would be methoxycloniprofen. What do you think? Right? Because it's got methamphetamine, oxycodone, clonidine and ibuprofen.
Speaker 3:Okay, I was funny. You guys don't have to laugh, I like it. We need a trade name.
Speaker 2:A trade name. I know we were just talking about swag and this might have more marketability than the t-shirts, so with that we'll go into the first article. So I get to present the first one, and I'm going to be presenting a paper that looks at why do people use Kratom and John and Sonja. If I present differently than you normally do, please feel free to add any details that I missed over. It's a very data-dense paper. I think that's why you guys gave it to me.
Speaker 3:I just have to interrupt because I will say that John and I both got articles that were very short and were kind of like almost like research letters just a few tables, and then the article that Casey chose is like 25 pages long.
Speaker 2:Oh Jesus, we're sorry, it was very dense. The tables were enormous, so I'll do my best to keep it high level.
Speaker 4:Lots of data.
Speaker 2:Yeah, lots of data. The paper is entitled Freedom as More Than a Self-Treatment. Kirsten Smith is the first author and it was published in the American Journal of Drug and Alcohol Abuse in 2022. And I always like the introduction to the paper because they kind of give you some backstory.
Speaker 2:So the authors note that in the United States, kratom use has been expanding and some of the reasons that people cite when they say why they use Kratom is basically the self-treatment of various symptoms and conditions chronic pain, fatigue, anxiety and depression, for example. And some people also use it to self-manage their addictions or others just want to have more energy and a better mood. And the authors note that the data that we have on why people use Kratom is very limited, because they're just looking at the reasons why people state they use, without kind of putting it in the greater context of the person's health and experience and said another way. Previous studies have really stopped at why do you use, whereas these authors wanted to dig deeper and that's a great segue into the methods of the paper.
Speaker 2:The study was done in the spring of 2021 as a part of a bigger study on substance use in general, and the authors contacted people who use Kratom by recruiting them through a platform for research crowdsourcing and I had not heard of this before called Amazon Mechanical Turk. I hadn't heard of that, and people were included if they were over 18, lived in the United States and had used Kratom at least once. They got a final sample size of 129 people and just in case anyone wants to participate in an experiment like this in the future, the participants were paid $7.25. I thought that was kind of a low amount to pay people for a research study.
Speaker 3:Yeah, I think, though, on Mechanical Turk that's kind of high, because a lot of what you do there pays like $0.05 or $1. I think we did some paper I forget what, john, that was done on Mechanical Turk as well. So 7.25 is pretty good for that.
Speaker 4:Inflation.
Speaker 2:Yeah, and to the author's point of wanting to dig deeper, they looked at a lot of aspects of the Kratom use. Where did people buy it? Why did they buy it? What did they think about it? Were they open about the use of Kratom? And then, how did their use of kratom affect their experiences in the healthcare system? And so it's a very simple methodology. It's basically just a survey and it was relatively detailed. Yeah, it's a pretty straightforward paper, so we'll go on to the results, and there are a lot of results, so I'll try to keep it high level and avoid it getting too numbery, if that's even a word. So first let's look at who was in the study. No-transcript.
Speaker 2:Interestingly, most people started using it. About three quarters started using it after 2015,. And most people bought it from multiple sources. The vast majority bought Kratom at smoke shops or vape shops. About a quarter bought it from gas stations. I always find it interesting when we sell potentially, you know, coordination-impairing substances at gas stations, like beer and kratom, but that is what it is. And then 30% went to like an herbal shop to buy their kratom.
Speaker 2:Next, the authors looked at why do people use kratom, and I thought the authors were super clever here. The number one reason for use endorsed by about 70% of the respondents was, and I quote, just to feel less crappy in general and improve my quality of life. That's pretty honest, right, and that was the number one reason why people used Kratom. I thought that was a very insightful question. The next most common reason to use Kratom was the treatment of anxiety and, just below that, low energy. About half of respondents said that's why they used it. Just below that was pain relief. About half of the users said they used it to relieve pain, and then on down the list, depression, boosting energy, treating social anxiety and treating depression and chronic pain. And about a third actually chose to use it because they thought it was safer than other substances. That goes back to your podcast episode Kreative at least it's not fentanyl, right it's safer than other substances. A pretty low percentage about 15%. They used to treat opioid addiction and a little more 18% said they used to treat alcohol addiction and a little more 18% said they used it to treat alcohol addiction, which I thought was interesting, and a very small amount less than 10% used it to self-treat stimulant addiction. So I thought it was interesting that there were multiple different addictions that people tried to treat with kratom. I was only aware of people using it for opioids.
Speaker 2:The next thing the authors looked at was what do people mix with Kratom if they're using Kratom. In other words, how much do we see comorbid substance use with Kratom? And they did a really extensive list. If you look at table three, there were like 25 different substances, from alcohol all the way down to testosterone. 100% of Kratom users also used alcohol. I'm not quite sure where to file that, whether that's accessibility. There's some sort of mix between them. 95% used tobacco and 93% used cannabis. So a lot of people are mixing Kratom with legal substances. About 80% used prescription opioids and just kind of across the board there's a high rate at which people mix Kratom and other substances that we would consider potentially addictive. I won't go through the whole list because it's just too long, but table three of the article is great.
Speaker 2:The next question the authors looked at was well, how often do people actually use Kratom? It turned out that two-thirds had used Kratom in the last year and half had used in the last month. So it wasn't really a sample of a lot of regular users, but it seems like there was a significant percentage of I've used in the past, or intermittent users. The next item that they looked at was how do people conceptualize Kratom. This was very interesting. Two thirdsthirds thought it should be legal and two-thirds also thought it is therapeutic. So that goes back to some of the kind of more societal issues around it that we discussed in the last episode. Only about a quarter thought it was addictive, which is surprising, maybe because they're only using it intermittently. And then only 14% described it as an opioid which I think we thoroughly investigated in the last podcast and only 5% thought it should be illegal. So the vast majority of people had a pretty positive perception of it.
Speaker 2:The next thing they looked at was openness about Credo. About half of people who used it said that they were open about their Kratom use, but they didn't really specify. Is that like friends, family, your bus driver, your pastor? They just said you were open about it. And then lastly I thought this was really interesting how did people using Kratom experience healthcare?
Speaker 2:About a third of patients who used Kratom said they felt stigmatized for using it when they went to an ER or urgent care and I kind of expected that and go addiction medicine. Only 8% of patients who use Kratom felt stigmatized when they were seeing an addiction provider. So addiction medicine was what's much better about not having people feel stigmatized. So addiction medicine was what's much better about not having people feel stigmatized. About half of the people in this study said that they struggled getting their needs met by the US healthcare system, which is what pushed them to Kratom, and the biggest unmet need was pain. Mental health symptoms were pretty close behind. So that was a whirlwind tour through the data, john and Sonja, any call-outs that you want to make or any points that you thought I missed?
Speaker 3:Well, it's nothing that you missed, but I just thought it was kind of cool because the paper I'm going to present about what is Kratom Use Disorder shares two of the authors with this paper and if you look at the questions they ask, there's definitely some overlap in the surveys, because mine is a survey paper also, but the numbers are very different, and so I always think about who's in the study. And these are people and correct me if I'm wrong I don't not sure I understand. Are these people who are currently using Kratom or just people who have used Kratom in the past?
Speaker 2:It's a single use, once, at any point in your life.
Speaker 3:Right, okay, so that's the difference, because my paper is going to be people who are currently actively using Kratom, so the numbers end up being a little different. So these are people who've used it at least once, which it doesn't necessarily lead to bias. But I think with any of these survey studies, who's going to use Kratom? You know, it's one of these products that, like some groups, everybody knows about it and other groups nobody knows about it. You know, like I asked a bunch of people, I know, like my friends and I was trying to find a botanist who could talk to me about kratom. No one had even heard of it, you know. And then here it is for sale at, like all these tobacco huts, so I'm sure people who frequent tobacco huts have heard of it. So it's's like it's not a random sample of the population, people who have you know, who know about and use Kratom. So I just think that's not a good or bad about the study, but it just I always think about who's the underlying population in one of these surveys.
Speaker 4:Yeah, yeah, I think it was really good the way you kind of pulled out those call outs from all those tables. There's a lot of data. I think you know kind of key takeaways I took away from that you kind of highlighted. I thought it was very interesting, kind of the comorbid kind of other substance use kind of all kind of legal or kind of within our kind of legal constraints. Also, kind of the high association with kind of patients seeking pain relief, kind of reflection of our really kind of lack of options in that domain. Still, and the fact that they were like felt that like they were kind of failed. So they were like it's almost like they were reaching here in kind of the this kind of confines of our current operational system, trying to get some outcome that they weren't receiving. So interesting points.
Speaker 2:Yeah, I'm going to move on to the discussion section, so the authors had a really long discussion. Once again, I think that's why you guys gave me this paper, so I'm going to make just a couple of key points that I pulled out of the discussion section authors made. That I liked was they feel like Kreative, when they asked people. Kreative is a pragmatic way to deal with the unpleasant feelings that get in the way of normal life, whether it's anxiety, depression, pain, low energy. People are just practical, trying to feel better. I think that's a lot of what we deal with in addiction medicine in general. They also noted that Kreative was perceived as safer than other substances, which brought people to it because they felt like it was less likely to be either addictive or cause an overdose or cause harm, and, maybe because it's sold as a supplement, that it is poorly labeled. So that's a whole separate issue and, as I mentioned, the poor labeling, the potential for addiction or dependence is really underappreciated, particularly when you go into the store and there's really just no mention of it at all.
Speaker 2:The authors also dug into how kratom compares to other substances, in other words, how much do people like kratom versus other substances, and what they found is that 50% of respondents rated, compared to other substances, kratom as one of their most favorite substances to use. So I thought that was interesting. So they really kind of tried to tease out like, do you like cannabis, do you like alcohol? Kratom was often in people's top number of substances, and so I think there certainly is an amount of euphoria that we need to consider as well, just because people rate it so highly compared to other substances.
Speaker 2:And then the authors describe their limitations, and the main one they call out is that they did not ask patients if they use kratom to manage kratom withdrawal as opposed to opioid withdrawal. So that would have been a nice piece to find out if people are self-identifying, that they are dependent on kratom and have to use to stay well. And then they wrap up the article with a moving forward section. They basically kind of put it all together and say you know, given the complex reasons why people use Kratom, healthcare providers should really focus on asking open-ended questions why do you use? What unmet medical needs do you have? And then also be willing to address those unmedical needs, whether it's pain, insomnia, anxiety, whatever. And then also healthcare providers need to get informed so they can educate patients on Kratom. So thus we're doing the podcast.
Speaker 3:Oh, that's a whirlwind. Yeah, it was fun, I learned a lot. So can I ask you guys a question? That is sort of related to your article, casey, and I was going to talk about it with my article, but I feel like it fits in right here, which is why people use Kratom, and this generated a lot of discussion in our live journal club we did with our colleagues last week. There's a huge overlap between people who use Kratom In my article they're using Kratom currently and people who have other substance use disorders, and I wonder what you thought of that. Do you think that that's? Does that surprise you? Does that not surprise you?
Speaker 2:Yeah, I'll take a stab at this. So you know, people always ask me is there such thing as a gateway drug? And my answer is always people who use substances. If you hang out with them, they're going to be using substances and they may offer you one and you may be inclined to take one, and then, when you're using a substance, it inhibits your executive function. You may make a decision that you wouldn't otherwise make. Like sure I'll smoke some cannabis after three beers. So I've never been in a smoke shop in my life, right, and we know that there's very high rates of tobacco use and people use other drug paraphernalia, like bongs that are sold in smoke shops. So I feel like people that are already in that world are going to be exposed to it, whereas I never had a reason to walk into a smoke shop. So I feel like it's more that they're sold where they are, as opposed to that people are gravitating to it for another reason.
Speaker 2:I think the other thing we have to consider and I haven't done this and I'm afraid to, but if you go on kind of the message boards online, there used to be a message board called Opiophile. I don't know if it's still around, but it was a message board where people would just talk about their opiates how do you get the doctor to give you Dilaudid, et cetera. So there's probably a lot of kind of in the darker corners of the internet, a lot of discussion about this. Uh, that kind of perpetuates use. And again, if you're asking for help with opiates or pain or whatever, and someone says, have you tried this? Have you tried this? What about kratom? I think that's probably again, it's that kind of a company you keep that that leads people to this and again, that bias being towards the company, you keep being people with substance use disorders and who use substances right, that's an interesting thought.
Speaker 3:yeah, those forums are not so dark if you spend any time on Reddit. I have not gone to r slash Kratom, but I thought it's pretty good. Yeah, we were just thinking about it. We also wondered about you know, people who do have a history of substance use disorder if there's a sort of continuing desire to alter your consciousness and a continuing seeking, like you said at the beginning of your article, people who just want to feel different, want something to take to cope with discomfort mental and physical of daily life. And I feel like that's a characteristic of people with substance use disorder, and I don't know if they had that characteristic before they developed substance use disorder or it's because of the substance use disorder they've lost their capacity to tolerate discomfort. But to me, that sort of drew, that fact drew me in that maybe that's why there's that overlap too, that that's a group of people seeking something to help with discomfort.
Speaker 2:Yeah, the other addiction doctor in the practice, the lovely Dr Reb Close, who happens to be my spouse. The way she describes it is feel something, take something.
Speaker 3:Well, right, and that maybe would drive people to look towards Kratom for help with anything. All right, are we ready for the second article? Let's do it, all right. So this article is about the diagnosis of kratom use disorder, which of course, is not in the DSM-5, but maybe someday will be. So it's called the Prevalence of Kratom Use Disorder Among Kratom Consumers and it shares several authors with the other paper and it was published in Addiction Medicine in 2024. Addiction Medicine in 2024.
Speaker 3:So you know, as Casey said earlier, the kratom alkaloids act on a whole bunch of receptors in the brain the adrenergic, noradrenergic, serotonergic, opioid receptors. So they have clinical effects similar to both stimulants and opioids and many consumers report significant benefits. But as use increases in our population and the general data says anywhere between about 1% to 6% of our population is currently using Kratom there's a certain subset of patients who find that their use has become uncontrollable and they develop what we would view as a substance use disorder. So the question asked in this article is could uncontrollable Kratom use meet the DSM-4 or DSM-5 criteria for substance use disorder and what is the prevalence of kratom use disorder as defined by these DSM criteria among current kratom consumers? So is it the same as opioid use disorder or is there something different about it? So the clinical question here this was a survey study 2,061 people and they completed an online anonymous survey. They were recruited specifically from online communities that dealt with Kratom, both pro and anti Kratom communities. They tried to get both sides but, of course, if you're currently using Kratom, you probably are a little more on the pro side than the anti side, on the pro side than the anti side. In terms of inclusion, you just had to be an adult over 18 and currently consuming kratom. People in the study were about 52% male. The mean age was 47, mostly Americans, mostly in the American South. You were only excluded if you didn't complete the survey correctly and the outcome was kratom consumption patterns, adverse effects, comorbidities and then the components of the DSM criteria for substance use disorder. Did you meet them? And this was done recently, in you know, february to May of 2023. So this is newish data within you know, about two years old.
Speaker 3:I thought it was a really good study. So basically, just a survey of anonymous online. They did a good job with the data. Some strengths is that they recruited from a variety of online communities. They tried to get people who are not just all super pro-Kratom and only had good experiences. It's a unique data set, and what I mean by that is this is an emerging issue with very little data, so this is a really unique paper, and they did use these previously validated criteria for substance use disorder, ie the criteria from the DSM, to define Kratom use disorder.
Speaker 3:There were some serious limitations, though. First off, it's an anonymous survey. There is no objective data. There's no guarantee of truthfulness of any of the answers. There's also serious selection bias. So I think most people who would be recruited to this study might have a favorable attitude towards Kratom. You know you're participating in some kind of online Kratom-related group. You're taking Kratom currently. You're engaged with the product.
Speaker 3:A lot of people who had adverse effects would maybe no longer be using because they experienced adverse effects.
Speaker 3:And then the other limitation, and you guys let me know what you think you can meet the DSM criteria for substance use disorder with just tolerance and withdrawal, and the only exception being is if you're under a prescriber's supervision, like with prescribed opioids or many prescribed medications, where you get tolerance and withdrawal over time.
Speaker 3:But if it's a substance that's not prescribed, just tolerance and withdrawal itself is enough to meet criteria for substance use disorder. But patients may not perceive tolerance and withdrawal as a problem. You know, think of yourself and your own caffeine consumption. Like I, have tolerance and withdrawal to caffeine. I don't really view that as a problem or a disorder. It's just tolerance and withdrawal and most people are pretty comfortable with that as a you know, pharmacologic effect, without feeling like it's a problem. So many of the people with creative use disorder are actually not experiencing harm, even though experiencing harm is the true hallmark of a substance use disorder. So to me that's a limitation of trying to define a substance use disorder with this compound that for most consumers seems relatively safe. So before we talk about the results, any thoughts on this paper overall or how they structured it.
Speaker 2:Yeah, I think the one point I would make about your point about tolerance and withdrawal, the reason that's excluded for under the care of a provider is because you're getting it regularly for a medical need, right? So in order to develop tolerance and withdrawal, you have to take a substance regularly, meaning these are people that are not able to self-regulate their kratom use enough to not develop tolerance and withdrawal. Same thing for you and caffeine. You can't regulate your caffeine intake well enough to avoid the dependence of withdrawal. So I think the reason it's in there is it just represents the level of use spontaneously, which represents that these are relatively heavy users. So I think that would qualify as a mild disorder. If you use it enough that you get sick when you stop, you probably need to cut down, Maybe or maybe not. You're caffeine excluded, of course.
Speaker 3:Of course don't touch the coffee, but a lot of these criteria for substance use disorder are sort of self-referential and, to me, are a little bit circular. So we'll talk about who met what criteria and then we can see if we really think they're experiencing harm. So results I'm going to skip over what I was going to talk about, which was first, which is people's reasons for using Kratom is relatively similar to the study that Casey presented mostly to self-treat pain in this group, chronic pain management, just to feel less crappy. Like you said, that was another one of the same authors, same question about 51% it's safe, gives you energy, treats anxiety, depression, social anxiety, sleepiness. About 26% of people were using it as a substitute for opioids, which I thought was interesting in this survey, you know, and so that was interesting, but mostly the same reasons you have presented in your paper, casey. Very few people were doing it just for fun, so for recreation or fun was only 14%. Most people were treating.
Speaker 3:A specific negative thing that they wanted to go away, though, are whether or not the respondents are experiencing the DSM-5 symptoms of kratom use disorder, so they divided the data up into looking at the full sample and then those with kratom use disorder and without kratom use disorder. The majority of the symptoms have to do with tolerance, withdrawal and uncontrolled use. But other than that, very few people experience the actual adverse effects from the kratom itself. The most common symptom of harm was about 5% of respondents said they continued to use it despite causing physical or psychological problems. But you know, if you look at the full sample, about 31% of people experienced tolerance, 21% experienced withdrawal, so one in five. You know chronic users do have withdrawal, which isn't terrible, but 16% experienced cravings, 14% experience increased use and to me these are kind of circular, like cravings. I know they're not the same as withdrawal, but like the cravings go with withdrawal. The increased use goes with the tolerance. About 9% experienced inability to cut down, again going with withdrawal and cravings. So I feel those are all kind of circular.
Speaker 3:And then you get to what I said, like the continuing to use despite it causing medical problems, and that's about 5% of consumers. A small percentage of people continued to use despite social problems. About 3% of people spent a lot of time trying to obtain use and recover from use. About 1.7% said it contributed to failure to fulfill their obligations. So those more harmful ones, 5% and down. So if you look at the people who actually met criteria for kratom use disorder, again, the majority were tolerance 81%. Withdrawal 68%. Cravings 57%, increased use 53%. So just all of this stuff with the escalating use If you get to harm, that was about the highest was about 20% of people continued to use despite it causing medical problems in the people who actually had Kratom use disorder. You know, and if you look at the actual prevalence of the Kratom use disorder, of the people who had the Kratom use disorder, about 66% was mild, 20% was moderate and only 13.9% was severe. So what do you guys think of that result in terms of who has what with Kratom use disorder?
Speaker 4:You know what I kind of thought about after we presented this at the Live Journal Club. I had my clinic afterwards and honestly, if you were to sub out Kratom with buprenorphine, literally almost this entire paper would describe any day in my clinic. You know we talk about kind of like opioid use disorder treatment kind of what are we targeting? We're targeting those like you know the criteria for diagnosis, like do they have kind of familial issues? They have issues with kind of legal problems? Do they have issues kind of with functionality?
Speaker 4:But you know this article for like why they use Kratom. That's actually kind of the exact same reasons where the majority of my patients come to me for buprenorphine. You know they basically they want to feel better, they feel kind of run down, cruddy, they lack energy. You know they don't kind of self-report to me that they feel that they're at risk of not having a job or that they want to repair necessarily all of them kind of a relationship in their life. And then, even when you look at kind of what we're calling kratom use disorder symptoms like tolerance, withdrawal, cravings those are all very common with overlap with patients that I kind of see in the clinic. It's kind of interesting how it kind of the analogy between the two. It's very similar.
Speaker 3:Well, and I think it can be similar because they're both legal. You know it doesn't destroy your life or throw your life into chaos. So most of the really bad effects of drugs not most, but many have to do with it being illegal. And if it's legal and the supply is relatively safe although Kratom is unlabeled and unregulated, so who knows how safe it is you don't have as many of those other health problems related to it. But yeah, you're right, it's kind of like a low-level opioid.
Speaker 2:Yeah, I think my take-home was that if tolerance and withdrawal are the main issues, the package should say so, meaning that this goes back to a need for better labeling, that this goes back to a need for better labeling, and when I met with some of the folks in the creative industry, that was something that I felt like they said they wanted to be a part of.
Speaker 2:Granted, there's and I joke, probably a bad joke given the politics in America right now but there's the creative right and the creative left. The creative right is that creative is evil and the creative left is creative for all, and so I feel like, depending where you are on that spectrum, from what I heard from the folks in the creative industry, it shapes what you think should be on the label, which is probably why there hasn't been better labeling yet, because people can't necessarily agree what should be on it. But I think what I took away is, again, if tolerance and withdrawal are the main issues, then that's something that I need my patients to know about that. Hey, if you use it regularly like oxycodone, it's going to be something that you're going to be dealing with. Withdrawal if you want to stop it.
Speaker 3:Well, right, and if you're counseling your patients, you could tell them. About 24% of habitual consumers will develop creative abuse disorder. You know most of it again is tolerance, withdrawal cravings, using more than you meant to, but still one in four of habitual users are struggling with too much use probably. So I think I will also counsel people to look out for this escalating use. You know there are if you're in the Kratom. You know for people who use Kratom regularly there is some promotion of taking holidays, not taking it every day. Watching out for escal who use Kratom regularly. There is some promotion of taking holidays, not taking it every day. Watching out for escalating use, that kind of thing to avoid that tolerance.
Speaker 3:But if people do develop Kratom use disorder, only about 14% was it severe, which is about 3.5% of the total habitual users, but still a fairly large number of people in our country, given how common Kratom use is. So that's my takeaway. I was really glad I read this paper because it the total habitual users, but still a fairly large number of people in our country, given how common Kratom use is. So that's my takeaway. I was really glad I read this paper because it, you know, there's a lot of like what is this stuff and how bad is it for you really? So I would say the risk of Kratom use disorder is very high. You know one in four habitual consumers and people should definitely be aware of it. And the problem is, once you put that on the label, it's like well, wait, we're selling something that one in four people will develop a use disorder for you know. So once you put it on the label, you're acknowledging that we have a problem.
Speaker 4:It's surprising how high the rate of kind of the severe criteria is. To me, that's kind of much higher than I was expecting. I don't know if you felt the way I was expecting. I don't know if you felt the way I'd be honest with you. I ask my patients about this now I have a couple people, but I'm not hearing it nonstop. Like many other substances. I'm surprised, though, that it affected a subgroup that much at that percentage.
Speaker 3:Yeah, I don't know if I had any expectation at all To me. I just don't know, because I also feel like this is a subset of the population predisposed to have a positive effect. So actually I think the true number is probably higher than in this study All right you ready for our? Last article, john, you're going to close it out with treatment of creative use disorder.
Speaker 4:Yeah, and actually after Casey presented, I actually feel kind of bad now because this was actually like a pretty sweet article for me to review.
Speaker 3:It was really easy to understand.
Speaker 4:It was like four pages read very like easy. I actually kind of read it. I was like that was like a nice, a little article to read while I was like laying on the couch and Casey's over there on the heavy bag, so I feel a little bad. So this is a long-term buprenorphine treatment for creative use disorder. It's a case series from the Substance Abuse Journal from February 2022. You know a little bit of background, just kind of kind of a bridge after we already talked about this introduction, but we talked about kind of this kind of multi-mechanism of action and certainly a lot of kind of the concern regarding kratom use and kratom use disorder. Possibility is related to kind of the effects of kratom on the mu opioid receptor. It seems kind of a little bit less likely off of the cyclooxygenase or the amphetamine-like stimulant effect. So therefore, because of that, it seems like the mu opioid receptor is probably a great target for treatment and so that's why there's a thought that can we use at least buprenorphine to treat this. Anecdotally, prior to the start of this kind of case series, they talked about that there has been kind of case reports kind of previously published about buprenorphine being used successfully. So in this clinic they basically wanted to do a follow-up seeing. You know, is this something that they can use on a more large scale than one or two cases? They did a case series. The clinical question is pretty straightforward and very relevant it's can buprenorphine, here with the combination formulation, be being effective treatment for patients with creative use disorder? It's a case series study, so 28 adult patients and they actually self-identified that their primary substance use disorder was creative use disorder. So it's a self-identified substance use disorder by the patients at 28 clinics and it was basically evaluating the effect of treatment with buprenorphine on both retention but also kind of what dose was required for capture and kind of how patients felt in terms of comfort level as they progressed through treatment at these clinics. The patients were all adults. They were age 18 and above. It was 28 patients.
Speaker 4:Most of these were recruited from the Pacific Northwest kind of Alaska, washington, montana, north Dakota region, with the vast majority being from Washington state. They basically had this archived data from their clinic. I really love the fact that the authors that did this. This was basically just their clinic's data on them using this, so there was no real industry funding bias. They just wanted to report a larger amount of results of how they were treating this in their clinic. The big variables that they analyzed were past duration of kratom use. They did average daily dose of kratom. They did buprenorphine induction stabilization doses and they did urine drug testing results at week 0, 4, 6, 8, 10, and 12 consistently. There was other ones in between, but those are the ones they analyzed versus each other. They did look at other things like duration of treatment and cleric clinic treatment status, but the big ones were kind of the UDT results, kind of dosage and kind of retention to care.
Speaker 4:Not unlike probably what the majority of us do in clinical practice, this treatment involved a home induction.
Speaker 4:The home induction instructed patients with Kratom use disorder to not use Kratom or any kind of opioids, benzodiazepines, alcohol or sedatives within 24 hours and then do a home induction.
Speaker 4:It was, you know, relatively what you would expect, kind of a daily home induction. The only difference here was they did a once daily dose and I think kind of many of us kind of gravitate towards the split dosing anecdotally and if the patients still were having kind of withdrawal symptoms, weren't comfortable, they would follow them up one to three days after that initiation home induction and then anyone that was kind of comfortable. They saw them a week later, so relatively close follow-up a week and then one to four days if they were kind of struggling. The statistical analysis was pretty basic. It's kind of just basically descriptive statistics of those variables of interest. The only kind of one fancy statistics they did was a quick Pearson's correlation coefficient and they basically were looking at kind of how much kratom use people were doing at baseline and did that correlate whatsoever to their stabilizing dose for buprenorphine. Any thoughts on what they did here or what they were looking at?
Speaker 3:No, but it's just real nice to see someone publish a paper that's just from their clinic and their patients, you know, because I think we're all doing interesting stuff, but it's big enough like 28 patients. It's not a single patient or two patients or three patients.
Speaker 4:You know, I think it's big enough to draw some good conclusions about. Yeah, god love them. The authors report a conflict of interest of that. They received a salary from their job at this clinic. That was a conflict of interest. I was like how wholesome is that right? So is the trial valid? It's a case series, so you have to take that with what that is. This is a non-industry fronted case series from a clinic, a bunch of people in the field that treat this kind of giving us their results for a relatively large case series of patients. They were treating Relatively narrow age group, 24 to 53.
Speaker 4:So not kind of generalizable to your adolescence or kind of your kind of geriatric patients with substance use disorder. And these patients also self-identify creative as their primary substance use disorder. I think we've talked about this many times, sonia, you and me. I always find interesting, like when you kind of look at like factually, a patient writes down like what issues they've had with what substances over their life and which one they identify as their primary substance use disorder, and I don't always find that the two correlate. To be quite honest, I feel like sometimes people identify as having this disorder but really another one is the one that's kind of driving the chaos and legal complications. So I mean it's important but that may not have been their primary disorder, especially as we've talked about with a lot of our other kind of data about Kratom, that most of these patients have other substance use disorders or transitioning from another substance use disorder. So I would probably argue not to play devil's advocate that probably whatever they transition to or from might actually be their true substance use disorder. I don't know.
Speaker 3:Right, the kratom is like a way station between opioid use disorder and say buprenorphine or something. Yeah.
Speaker 4:So you know it wasn't blinded. There was no random selection here. This is basically patients that came to this clinic and they were just trying to treat these people no FDA approved options currently so they were kind of doing the best they can, were just trying to treat these people. They have no FDA approved options currently, so they were kind of doing the best they can to kind of work with these people, kind of what I think all of us do every day. The only thing I wish we had from the case here is I wish we had some kind of comorbid conditions, like I would love to see like which ones were dual diagnosis. It would be nice to know a little bit how they got there. Like are they treating pain? Anecdotally?
Speaker 4:I find that kind of chronic pain and substance use disorder treatments a little different than people that are seeking it more for kind of a euphoric state of mind or chasing something, just kind of. How you kind of approach them is a little different. But overall it's a really kind of robust study for something that we don't really have a great answer for. So the results, like we talked about, total 28 patients age 24 to 53. The average age was 36, kind of very relevant Clinic locations. Northeast US, most Washington State, that was 12 to 28. The creative use of baseline kind of ranged quite substantially anywhere from 0.6 grams to greater than 850 grams per day. So very kind of large dosing variations here between what these patients were on. And it's funny that you know duration was anywhere from a month to 25 years. So kind of interestingly that you know patients progressed to creative use disorder that quickly. I thought kind of even having people on the one month side and then 25 years is really long.
Speaker 3:I kind of almost wonder where they were even getting it 25 years ago well, right, like, like, it certainly wasn't being sold, as it is now 25 years ago. I guess if you're, you know malaysian and you're maybe you're using it, you know from somewhere else where there's a well, there's a way, I guess.
Speaker 4:Yeah, so some information about kind of induction and stabilizing dosage. So four to eight milligrams was typically the starting dose and that was the overwhelming majority. So 16 of 28 patients fell within that starting dose. It's 57%, so just a little over half on our typical four to eight Stabilizing dose. The majority stabilized on 12 to 16 milligrams, so that was 19 out of 28. So it's about 70% of patients stabilized on that dose and the range was 4 milligrams up to 20 milligrams, so relatively kind of narrow range, pretty representative of what I think we kind of most of us use this medication for opioid use disorder. For, In terms of initial induction, 15 of the 28 patients so the overwhelming majority reported improvement of withdrawal symptoms and cravings after induction by that second appointment.
Speaker 4:So the induction dose was pretty successful at kind of improving where they started from. Even though there was a large improvement, stabilization took two to three weeks for the majority of these patients. So people kind of felt their best after kind of two to three weeks engaged in care in the clinic. Interestingly, the one statistic they did the Pearson correlation coefficient. There was actually no association whatsoever between kind of baseline, kratom use and the buprenorphine treatment target dose.
Speaker 4:So it's kind of interesting. There was no kind of change there, Something we care about every time we talk about these kind of treatments with buprenorphine. There was zero cases of precipitated withdrawal with this medication. That is great to know and that's I mean, that's a whole like another topic we've talked about a bunch of times like what is the true incidence of this phenomenon, but it's good to know here. I guess, because you're going from a partial to a partial, it probably is pretty safe to start treatment. I wonder if they even looked at kind of like a more in real time induction on any of these patients in the future since then.
Speaker 3:Well, it's also just a low, you know, compared to some of the stuff we do, it's a relatively low dose. So you know it's, it's not. It's just not as potent. And you know, I don't know about the poor person in this study who was taking 850 grams a day of Kratom. That's like almost a kilogram of Kratom. That's so much, but a lot of people probably pretty small dose. So you would hope they wouldn't have precipitated withdrawal. One would hope 850 grams a day.
Speaker 4:Greater than.
Speaker 3:Greater than.
Speaker 4:I mean so? I mean self-reported again, right. So I mean, sometimes maybe this is a Superman story, but that's what they were reporting, they were doing. Yeah it's a lot.
Speaker 3:Patient follow-up.
Speaker 4:I actually thought this was really kind of great 71.4% of the patients actually engage in continued follow-up throughout this case series. So that would kind of compared to what we do in a lot of addiction medicine. It was 71% follow-up, that's pretty darn good. So 20 of 28 kind of stayed in treatment and the eight that were lost to follow-up, one moved out of town, one tapered off and just self-discharged. So basically that was kind of a successful transition off. And then only six were truly lost to follow-up. So kind of even less than that truly were like kind of like. This isn't for me, I'm out.
Speaker 4:A duration of treatment and care ranged from five to 22 months, with an average of 11 months. So pretty good again for addiction medicine. When you look at the neuro drug testing results of interest, just shy of 70% of patients had negative results for opioids throughout treatment. So that's pretty good. And then when you look at kind of results for the dributabolites, for the kratom at week four, 68% of participants had negative metabolite testing. At week eight and twelve it was 82%. So even kind of as the treatment went on.
Speaker 4:There still was some kind of intermittent use for a subset of the patients, but kind of as the treatment went on. There still was some kind of intermittent use for a subset of the patients, but kind of relatively very quickly there was kind of capture of this and kind of it started to kind of disappear out of the urine drug testing results. Nine out of 28, so that's 32 percent of the patients about a third of them actually were either restarted or intermittently used Kratom throughout the duration of the follow-up. So you know it worked really well. But a third were still kind of dabbling back and forth for one reason or another. They don't really say why. The majority of those were basically reporting occasional use sporadically throughout, not kind of continuous use.
Speaker 3:I'd be interested to know, you know, how people, when they are taking buprenorphine and they do use a full opioid love oxycodone. They really don't feel much effect. I kind of would love to ask these people what did the kratom feel like when you're on the buprenorphine? Do you get just like only the stimulant effect or you know, or what's it feel like? We'll have to if anybody has any patients.
Speaker 2:You can ask them.
Speaker 4:Yeah, I actually have one on. I want to ask because I know they're still dabbling. I want to ask them. I think next Tuesday That'd be a good question.
Speaker 4:Yeah, so kind of I'll go to that, I'll take away from this, but kind of summarize kind of the key points here. Kind of basically low induction doses were very effective here in the majority of patients. You know four to eight milligrams stabilizing doses, 12 to 16 milligrams in most of these participants or recipients of treatment, which is very similar to what we do for the majority of our buprenorphine patients. Very effective at alleviating withdrawal. You know stabilization can take up to a couple of weeks, two to three weeks, so kind of don't dismay if you're not getting the results you want immediately. I think very similar to our patient with opioid use disorder.
Speaker 4:Opioid or buprenorphine stabilization dose does not necessarily correlate to kind of duration or amount of past use. So kind of a big discrepancy between kind of what dose you have to use to kind of keep someone in treatment, what dose treats withdrawal and what dose actually treats cravings, which you know it seems to be a theme in addiction medicine. Most patients 70 plus percent continued treatment with this. So they were satisfied and continued follow-up and it was very quick Within the first month almost 70 percent of your patients were no longer testing positive for this substance and it kind of was effective up to 82% at 12 weeks. So overall kind of a very interesting case series. That kind of gives credence to, I think, a practice a lot of us are already doing, kind of using buprenorphine off label for treatment of patients with this. I'm not sure what you guys think about those results.
Speaker 2:Love them. It matches my clinical practice. Bupe works great and I let people self-titrate where they feel most comfortable in terms of cravings and withdrawal. And yeah, I'll be starting one of my creative patients on buprenorphine, hopefully next week.
Speaker 3:Awesome. Hope it goes well for her or him.
Speaker 4:Yeah, this article made me feel better about myself, because I feel like sometimes there's so much of medicine that doesn't fit in the box. Right, you have these little boxes like this conditions here, this conditions here, but people don't exist in reality inside the boxes, and so you have to kind of like use what you know it kind of tailored to a person, and so I've kind of been doing this, at least for the two patients I have treated, and it's nice to know that I'm not doing a bad thing and that this actually probably is effective right Validates a practice I'm already doing.
Speaker 2:Yeah, that's great. Oh, but I think it's. You know, and I was talking to one of my patients about this today you know how do we define sobriety, right? You know, one of my patients was like you know, hey, doc, I'm sober, I'm only on cannabis. It's like well, no, there's some discussion there. I think if someone's using Kratom and you get them on bupe and they don't withdraw, they do use Kratom and they're working and they're a family member, like great. So I don't necessarily know if I felt like I was outside the norm using buprenorphine for Kratom, but thank you for reassuring me that I am inside the norm them, but thank you for reassuring me that I am inside the norm.
Speaker 4:You're in California. Do they call that California sober in California too, or is that just a East Coast thing? Yeah.
Speaker 2:No, I've mentioned it to some of my patients, like hey, they call this California sober, but we do not use that term.
Speaker 4:Yeah, I was about to say. I wonder how they feel about it in California.
Speaker 2:It's okay. Well, I was one of the few Californians playing lacrosse in the 90s and 2000s.
Speaker 3:Cause it's much more of a East Coast sport.
Speaker 2:So so I'd I'd go to lacrosse like tournaments and camps, and the East Coast players would say, let's do the California stretch where you land your back in the sun I was like hey, we don't do that.
Speaker 3:Oh my gosh. Well, look, guys, this has been an awesome discussion of three interesting articles about Kratom. I'm looking forward to much more research and I'm interested to hear what our audience's experience have been treating Kratom use disorder. With that said, I will let you guys all sign off. I think, casey, you've got somewhere to be, john and I have to be just in bed because it's kind of late and that's all I got.
Speaker 2:So much fun, wonderful. Thank you so much. Good night, and that is the end of this episode. Kratom is such a fascinating topic. I'll be doing an interview with someone who works in the Kratom industry soon and that episode will be coming out in December. We have so much to learn on this topic. Please consider sharing this podcast with a friend or colleague. We have so much work to do to improve education about addiction and with that, thanks for listening and thanks for what you do. And don't forget treating addiction saves lives, thank you.