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Hey, before we get to the show, I wanted to remind you to check out our patreon@patreon.com curbsiders if you haven't signed up yet, sign up now to get ad free episodes, twice monthly, bonus episodes and a whole bunch of other cool stuff@patreon.com Curbsiders.

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The Curbsiders podcast is for entertainment, education

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and information purposes only and the topics discussed should not be used solely to

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diagnose, treat, cure or prevent any diseases or conditions. Furthermore, the views and statements expressed on this podcast are solely those of those and should not be interpreted to reflect official policy or position of any entity

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aside from Boss Cash.

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Like more hospital and affiliate outreach programs,

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if indeed there are any. In fact, there are none.

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Pretty much.

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We aren't responsible if you screw up. You should always do your own homework and let us know.

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Xena, it's so good to see you. I have to say I am absolutely loving the pineapple on your wall.

D

Thank you. That's my partner originals. You know, very exciting pineapple art.

C

Uh, so if you haven't checked us out on YouTube, it could be a great chance to see this pineapple art on Zena's wall. And on that note, welcome back to the Curbsiders Internal Medicine podcast where we use expert interviews to bring you clinical pearls and practice changing knowledge. Today we're actually going to give Matt and Paul a break and we are bringing you an episode from the Curbsiders Addiction Medicine, our miniseries on substance use disorders. So I'm Carolyn Chan and today I'm joined by my co host Dr. Zena Huxley Riker. And on ton episode we're going to discuss Kratom and other Metrogynine related products with Dr. John Tanawan. Before we get started, Xena, can you remind the audience what we do on this series?

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Of course, Carolyn. We are the Addiction Medicine podcast that uses expert interviews to demystify common addiction medicine topics, reduce stigma and inspire listeners to be fierce advocates for all individuals who use substances. And a reminder that most episodes are available for CME credit through VCU Health CE for all health professionals at curbsiders vcuhealth.org all you have to do is create an account by listening to this episode and completing CME. This can be used to count towards the new DEA 8 hour requirement on substance use disorders education.

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And this podcast is brought to you by the American College of Academic Addiction Medicine, also known as acam. ACAM offers practical and expert led education focused on curing for patients with substance use disorders in real world. Clinical settings. So be sure to check them out and learn more@acam.org acam.org on this episode

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we have a fantastic conversation with our guest, Dr. Jonathan Tonawan, who is board certified family medicine and addiction medicine physician based in Chicago. He works as an addiction medicine physician at John H. Stoker Hospital of Cook county where he works on the inpatient consult service. Dr. Tonawan also works at Moud telehealth provider QuickMD where he is able to expand access to Moud in several states. He is interested in expanding access to life saving addiction medicine care to underserved and under resourced populations. In tonight's episode, he teaches us the difference in metragynine compounds, how to manage withdrawal and use disorders from kratom and 7oh, and how to take a great history from patients who are using these products. So without further ado, let's get to it.

C

Hey John, we are so excited to have you on the show today.

B

Very excited to be here and I

C

think we really like to have our guests share a little bit about themselves so we have a chance to get to know you. So do you mind giving us a one liner to describe yourself?

B

Yeah. So I'm a 33 year old male double board certified in family medicine and addiction medicine. I'm a now adopted Chicagoan. I think I can call myself the local now. And I just love being in the city, taking runs along the lakefront and just adding to my never ending list of restaurants I need to try out.

C

Are you somebody who likes to compete and run like 5Ks or marathons or just for the enjoyment, like to jog along the lake?

B

I felt like it was a really great place for me to kind of gather my thoughts, especially during medical training. But then I kind of fell into the millennial trap of running half marathons. So I ran my first one in Houston in January and I'm starting training for my next one at the end of June for the Lifetime Chicago Half Marathon.

C

That's exciting. Congrats.

B

Thank you.

D

Awesome. I will say that I did run a half marathon recently and I can't say that it trapped me into continuing

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to run half marathons.

D

Um, I don't, I don't know that I'm gonna do it again. It was fun, but I think I'm good.

B

Still an amazing feat though. Congrats.

A

Thanks.

D

Thanks.

C

Already retiring. Xena.

D

Yeah.

C

I like how you said it was fun, but not really like, yeah, it

D

was like, it was fun till like mile 8, 9. And then I was like, all right. I don't need to keep running anymore. Like I'm good.

C

That makes sense.

D

Yeah.

C

And I think, John, you know, there are many ways people get into the field of addiction medicine. So I'm curious if you could share with us, like, what are your favor aspects of working in this field?

B

Yeah, absolutely. So I love educating people. I love teaching, kind of helping people learn about not just patients, but even fellow providers, physicians. And I think what I've grown to love about this field is I do just as much education for our patients as I do other providers. And whether it's a seasoned attending that doesn't have the time to just kind of keep track of how much the drug supply is changing or when new CPGs come out, or even just kind of helping people, you know, challenge the way they feel about taking care of someone who uses substances. I love how there's always opportunities to teach people that are both my colleagues and the people that I care for. So it's a really, it's a, it's a great part and also, you know, empowers me to keep learning, keep trying to get better at what I do. So it keeps things fun.

C

I love that. I. I think teaching people about substance use disorders and addiction, I totally agree, is really rewarding. And our field changes so rapidly. I feel like there's always like some new pearl I can give based on like local, as you said, local drug checking data or something new that I've. I've read about in the literature.

D

Yeah. I also love like sharing like things I learned from one patient with another patient and kind of like using that to spread community knowledge.

B

Especially in a field where a lot of times patients feel isolated, they feel alone. They might be scared to talk to someone about what they're going through. Being able to share like, oh, I learned this from my patient that lives on your side of town and they're experiencing something similar to you. It feels really rewarding to kind of help connect people like that.

D

Yes.

C

I don't think I'll ever be able to keep up with the lingo. So that's always fun. When I ask a patient, I'm like, can you tell me what exactly that means? Yes, like what you should know or of course you wouldn't know. And it's always fun to like see that interaction.

D

Yeah, totally.

C

So, on that note, Xena, do you want to kick us off with a case from Cash Lock Memorial?

D

Sure thing, Carolyn. All right. We have a 29 year old male who presents to clinic requesting some help. Over the last two years, he's been Using escalating amounts of Kratom, most recently in the form of 7 hydroxymitragynine or 7 oh. Now at a daily dose of at least 600mg. He has also recently started using a product called metragynine pseudoindoxyl or mp. Several times a month he visits a kava bar which he views as a safer alternative to his alcohol use. He's presenting today primarily because of cost. He can't really afford to use as much as he's been using. And he has not used any Kratom products in approximately 12 hours. On your initial exam, he's diaphoretic, anxious and has dilated pupils and he appears really uncomfortable. So to kick us off, John, can you just tell us a little bit about what Kratom is?

B

Yeah, so coming down to, I guess like the leaves of it. So Kratom is not a singular compound. It's really a leaf from a plant that's a distant cousin of the coffee tree coming from Southeast Asia. So folks in Thailand, Malaysia, Indonesia, they've been using these compounds indigenously for centuries. And kind of thinking about it on a more molecular level, Kratom isn't just one compound. Like, you know, heroin is just heroin. Kratom is actually like kind of a mix of alkaloids and they've kind of isolated the four most biologically active ones. B mitragynine, 7 hydroxy mitragynine, speciosilitine and corananthidine. And so you get this hodgepodge of bioactive alkaloids that can cause a hodgepodge of different effects.

D

And how, how do people generally consume Kratom products?

B

Yeah, so classically people would take it, take the leaves, ground them up, put them in teas, boil them down into tinctures with an emulsion. But what we're seeing now kind of in modern day use, Kratom leaves are ground into a powder. People put them into liquid, drink them as a tea or kind of put them in shakes. They can put it be put into capsules. And I have just had some patients that have progressed in their use and they're kind of dry mouthing powder at times too. There's some other formulations adjacent to Kratom that are more of the Synthetic 7 subtypes and those come in quite a few types of forms. You can buy them in blister packs where there are tablets that are scored and dosed. They sell them as gummies that you can get at smoke shops and online. I've seen some formulations where they are, I think in ice cream treats. And I've seen them as well as like tall boys. So like kind of like the same size, like a Celsius can or like a 12 ounce can of like pop or soda that kind of has a seltzer with some active mitragynine compounds in

C

it that, that's wild. And so what I'm hearing you say is that you can consume it at a bunch of ways, but I suspect that it sounds like there's so many different alkaloids that you may not even, you may be getting different combinations with different products. Is that accurate in your experience?

B

Oh, absolutely. I, you know, expert opinion. When I first see a patient that's having trouble with kratom, I really do try to kind of, you know, clarify with them. So is this Kratom or is the seven. Oh, and are you taking a powder or are you drinking like a drink from a gas station? Because it really can change expectations patients for what they're getting. And patients will tell you they're like, oh yeah, like, you know, I started with the powder, but then I developed this tolerance and now I've progressed to some of these pressed pills or these tablets and I can feel like I'm needing more and more. So I really try to figure out right away what it really is that they're taking so I can best understand how to help them.

C

That's really, that's a great pearl for taking that history. And do you feel like these products are regulated like, like what they say is on the bottle? Do you think it really is or no?

B

And patients will tell you the same thing, you know, like this guy from Cash, like Memorial is going to these, these kava bars. And you know, I have some patients that are drinking kava drinks from gas stations and they'll, you know, patients are some of our best teachers. You know, they'll tell you, I used to go to kava bars or what have you back in the day, and now I'm buying these kava shots from a gas station. And these are not one in the same. And we think that some of these drinks that report themselves to be kava might be intentionally or unintentionally adulterated with mitragynine like compounds, which then leads us into this issue with tolerance and withdrawal.

D

And can you, I know you kind of talked about the different alkaloids. Do we kind of have a sense of like, what the mechanism of actions of these different alkaloids? Like, what are they actually doing when someone's taking those different.

B

Yeah, yeah. So we know that mitragynine is like the primary one that comes out of Kratom and then the liver takes that through the sip system, can't remember which one.

C

That's okay. And nobody turns it into so many.

B

There's so many and it turns it into seven oh. It's analogous to how codeine becomes morphine in the body. And seven OH is a super active like to the mu opioid receptor. And in nature about like if you're consuming the powder, consuming the tea or what have you, about 1% of what you consume will become 7 oh. So that's, I think why we see milder effects with kratom versus like the synthetic 7OH compounds. Because if you're just taking in 7OH, you know, you don't have. You get eliminated the pro drugs. So everything there is just the active metabolite. And I think that's why we're running into these, these much higher potencies. The other, the other alkaloids I've seen like in some of like the, like just more of the pharmacological literature, there is some alpha agonism from mitragynine and 7 hydroxymetragynine. So you can get some of like those similar effects to, you know, like clonidine where it'll help with, you know, anxiety, help with your fight or flight symptoms and then a lot of mu opioid receptor activation. I did see some other studies saying that there might be some engagement as well the kappa Mu receptor or the kappa opioid receptor. So that might have some implications for mood and what have you to with. With these alkaloids.

D

So lots of stuff going on.

B

Lots of stuff going on.

C

I think thinking back to like what I hear patients, at least most recently, what I'm hearing them say is they're telling me they're using products like 7oh or metragynine. Sometimes also hear people talk about something called what they call like MGM 15, which is Dihydro 7 hydroxymitragynine. For the sake of all of our tongues, we'll just call it MGM 15 and Mitragynine pseudoendoxyl MP. Can you give us a little bit of a breakdown of like what the differences are between these products?

B

Yeah, and I think this I'll also be able to answer a question I forgot to answer last time kind of going like, so a lot of these novel compounds hitting the market, designer7oh Derivatives, if you will. I think a lot of them are born out of this patchwork of legislation that's coming out to regulate Kratom and Stepnoh a lot of states offhand. I'm licensed in Alabama, in Oklahoma, so I know in those two states kratom and 7oh have been regulated and or banned. But I think the way that the law is written is that some of them reference specifically 7 oh. So these chemists, smart folks that they are, are able to kind of look at the chemical structure of 7oH and figure out it would alter a side chain or something here and there and then release that to market where it's technically no longer a scheduled substance and can return to sale. But, you know, expert opinion in taking care of these folks that are getting this stuff, I don't really see too much of a difference in how I treat the withdrawal and the dependence on whether it's pseudo Endoxil or MP or MGM 15. They all kind of follow a very similar potency to 7 oh.

D

That's helpful to know. I feel like I haven't really been seeing as much of these other products in my patient population. Definitely a lot of 7oh and kratom, but different places, different regulations.

A

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C

So to take a moment to just sort of summarize everything. So when people are talking about Kratom, a lot of times we're thinking Kratom is a lot of substances, so a lot of alkaloids. But predominantly the things we think about from people taking more of the natural leaf product is the effects of metragynine. So this is where we're going to see that like partial mu opioid receptor agon as well as, as you said, it actually hits a couple of other receptors too. I think I've read similar things. Right. That it can impact the alpha system. I think it may even be weakly impactful on a couple of other receptors like dopamine, serotonin. That just makes it messy. And then now though, as a result we are seeing like these synthetic products that are much more potent, that act more like and are actually, you know, full opioids, full opioid agonists essentially, especially like seven. Oh. And it's making things messy.

D

Yeah, definitely changing the landscape. Where are you typically seeing that patients are getting these products?

B

Yeah, so it's a little mix of things. A really common kind of like thing I'm hearing from the patients I take care of is they go to their normal smoke shop looking for delta8thC or some of those hemp derived products. They're like regulars at these local smoke shops. And then someone will tell them like, oh, you know, like there's this new thing we have called 700H and it'll give you A boost of energy and you'll feel really great. And then from there they kind of begin to escalate their use. I know that there's been a big presence as well on the Internet. I know that sometimes when I work a shift for my telehealth company, I get Targeted ads for buying 7 oh after I work my shift. And I've seen some of these ads and you know they're on Instagram, you know they're on Facebook. And when you click through what they're offering, they market these things as energy boosters. You know, pure metragynine, you know, slow release or like no come down. So there's, it's kind of like the wild west right now on the Internet as well.

C

And when you're taking a patient history, can you walk us through what sort of information you're collecting in terms of like how often they're taking Kratom doses? Like what, what does a typical pattern or escalation of use look like?

B

Yeah, so I think what I always kind of ask, you know, what is your cumulative total daily dose? And you know, then from there I'll clarify, is that a cumulative daily dose of Kratom powder, Kratom capsules or are we talking more on the long lines of seven oh. And then normally when I get a cumulative daily dose then I ask how many times are you taking it? A lot of patients from 7 oh. Due to it's, it doesn't last very long in the body. A lot of patients oftentimes will have to dose throughout the day and sometimes waking up at night in withdrawal to dose their seven oh. So I'll also ask about frequency of dosing. I also inquire about where they purchased it from. I ask about if there's any additional substance use. I'm particularly concerned about depressants, so. And if there's any concomitant alcohol use, non prescribed opioid use, benzodiazepine use, kind of making sure we can do some counseling on that risk of respiratory depression with the mu opio receptor agonists like kratom and 7oh. And I also ask about, I also kind of try to frame like I always kind of ask a why as well. I think a lot of patients in this population specifically, you know, we talk about meeting patients where they are and a lot of patients have still pretty high levels of residual functioning, you know, DSM 5 criteria. They're still able to perform pretty well in like those sociologists personal domains. So they, I let the patient kind of frame themselves how they want to perceive what's going on. Some patients don't really like being referred to as someone with like a substance use disorder. Some people like to like frame themselves having a dependence. I try to be really careful and let patients define how they want to be defined, particularly with 7oh and kratom.

C

And when we think about like use disorder and DSM 5 criteria, like is there such thing as like a quote unquote kratom use disorder? Is that a thing? Is there a controversy around that? How should we think about these patients in terms of that spectrum? Right. Like you said, people may just be having some intermittent use, at risk use or have really some sort of compulsive use.

B

Exactly. Unfortunately there isn't one in the CPT codes yet. So I'm charting everything as like an F11 something. So it's still opioid use or opioid misuse. But you know, it's an interesting dichotomy. You know, I think taking care of a lot of patients with a bona fide opioid disorder, whether that's from non prescribed opioids or prescription opioids, it's a lot more cut and dry. But with these Kratom compounds, you know, some people are using recreationally but they're starting to feel withdrawal. So it kind of draws us back into dependence versus a use disorder, which I know has been, you know, kind of put to rest with the DSM 4 and the DSM 5. But I think there is some utility here with kratom and 7 oh yeah, I agree.

C

It's, it's like messy. I think that's the question is like will science, you know, will science do its thing as it does and refine their criteria? Right. Because they do feel and presentation like, like a little bit of a different phenotypes because as you said, depending on the product they may be hitting different receptors and it doesn't look exactly like oud. It's complicated.

D

I know you mentioned a little bit in like the kind of questions you ask folks when you're doing some history taking about like why they're using. I was curious if you could kind of go into the range of answers that you hear from folks and kind of what are some of the reasons that folks have started using these products?

B

Yeah, I think, you know, every patient is just so unique. You know, I've had patients that have had a history of fibromyalgia and they have a well meaning treating physician and they end up on opioids chronically, which isn't first line, fibromyalgia. But then their provider gets in a pickle, deprescribes them and they're having a hard time coming off of opioids. They turn to Kratom or seven oh. And then it escalates into escalating doses of kratom and 7oh. So that comes up often. A lot of patients that have chronic pain, I've seen that a lot. They've heard from friends or acquaintances. A lot of these patients are also very online. So you know, there are online support groups on Reddit or Discord and they're like, oh, I read about this online and I thought it could help me. And I've opened up this can of worms. Now I'm worse off than when I started. So that's a pretty good chunk of patients I see. And then there's a recreational crowd. You know, they were like, oh, you know, I wanted to try it, see what it felt like. And I didn't think it would just turn into something this like, I guess this, this problematic for me. I see that as well. And I think like, you know, those are, and you know, just the people that get bamboozled, that's, that's a pretty big bucket too, the bamboozled bucket. You know, I've had patients that have been in recovery for a long time from heroin or from prescription opioids and they went to a gas station, they went to a convenience store and the guy up front is telling them like, hey, we just got these in. It's a great energy booster. It comes in a little five hour energy looking bottle. So you don't think much of it and then you end up buying more and more of these and realize like, oh, dang, I think I've relapsed. And that's a pretty significant bucket too, I feel.

C

I totally agree. I see something similar with the patients I care for. I'll add one other bucket of folks I'll see is like anxiety. People will tell me it helps me relax, it helps me with my anxiety and helps me sleep with some other sometimes co occurring psychiatric disorders. Zena, what are some of the reasons you've seen for like folks in your practice describing their use?

D

Yeah, I think a lot of similar reasons that you all are mentioning. I think the only other one I would add that I didn't hear you guys mention is I think I have like a significant or a chunk of folks that feel like they maybe started for more of the like stimulant like properties and like helping them focus and like get through a work day. And then as their use escalated, it kind of no longer provided those helpful things to them anymore. But I think I definitely have like a chunk of my patients that I see like mentioning that as kind of their in which I think really that speaks to some of this, like where these products are coming from and who's marketing them to folks and like what they're marketing them for. And like, I think to your point, John, like the targeted ads say all sorts of different things and they really are targeted to like different needs of patients. And so I think there's a whole range of reasons you get for why people have started using these products for sure.

B

After I ran my half marathon in January, there was like this sports expo and I ran with a bunch of my friends from college. We all met up in Houston together and you know, free stuff. So we all got home to my, my friend's house and someone had a Kratom Saltzer on them. And I was like, where did you get this? And you know, they told me, oh, they're giving them away at the sports expo. I thought it was like a Celsius or something. And I'm like, it's not. Or not a Celsius. And then we had a, we had a lunch and learn. But you know, it's. I, my, my friend wasn't in healthcare and it was one of those things where I didn't even know what this was. So it's, it's definitely, can, definitely can be deceiving.

D

Yeah, the whole sports workout crowd is another crowd for sure.

C

And I'm curious too, John, can you tell us a little bit more about why some patients get that stimul stimulant effect and why some people get more of which is like where I think of an upper and some people get more of that downer effect.

B

Yeah, I think it really just does depend on what they're getting. I know that some of these online places will sell like, kind of like making parallels to think how people market cannabis, you know, where like, if you buy like Indica cannabis you will get this effect. If you buy Sativa cannabis, you'll get this effect. I think it might come down to some of these chemists trying to isolate specific alkaloids that might be more dopaminergic or might be more engaging of norepinephrine and then the other ones that are just really more heavily engaging the mu opioid receptor. You know, a lot what a lot of patients will tell me is at lower doses, the Kratom Feels like a stimulant. At higher doses, it becomes more of an opioid. So I want, so there might be some thresholds there to activate the mu opioid receptor while still engaging some of like those other dopaminergic norepinephrine or what have you receptors at lower doses.

C

What a messy. What a messy compound.

B

The hodgepodge.

C

True.

D

Yeah. Is there any like sense or any literature kind of talking about the rate of folks who use these products who may then go on to develop like a dependency or a use disorder?

B

Unfortunately, I have not seen any data that far. The best data I was able to find was from NIDA where they kind of were able to kind of extrapolate about 2 million people actively using kratom in the U.S. but the kratom lobby, who is very alive and active right now on a state to state basis, they were estimating more of like 11 to 16 million people using Kratom. We have some economic data. I think Kratom sales total about $2.2 billion in 2024, counting gas stations, smoke shops, online. And then the rest of the kind of goes into showing like, there's been an increase in like poison center calls regarding kratom. There's a 1200% increase over the past 10 years. And then there were 233 deaths from 2015 to 2025 related to kratom. So it's definitely becoming more and more common across different socioeconomic ends.

C

And I'm curious too. So it sounds like you can overdose on this product. What do you do to manage an overdose if somebody does on any of these substances?

B

Yeah. So there's no RCTs. Everything is coming off of case reports or expert opinion. But there have been some rat studies that show that 7 oh does cause respiratory depression. That resolves with reversal agents. So naloxone, nalmifene, there's rodent studies that show efficacy, and then there's case reports too that, you know, naloxone will work to reverse an overdose. I've seen as well that generally speaking, a lot of these overdoses associated with Kratom had other depressants at play as well, whether that's alcohol, benzodiazepines, agonist, opioids. So there's definitely a concern there for stacking. But luckily the reversal agents do seem to be helpful.

C

Well, John, you made such an excellent point and question of like, how many patients who actually use Kratom are maybe developing a use disorder. I quickly typed this into to ask a quick Search to see if we can find the answer. And it looks like in one paper that had about 2,000 folks in it, folks were meeting criteria for a substance use disorder, most likely mild or moderate. And about 25% of people who are using Kratom, definitely a significant portion. Though of course this study was an online anonymous survey, so we could be at risk of missing some key populations in terms of capturing that data accurately.

D

Thanks for finding that, Carolyn. That's super helpful. I think just bringing us back to our patient. He's presenting with some kind of typical withdrawal symptoms that we might think of for opioid withdrawal. And I'm curious, John, what your thoughts are about kind of what we should expect for withdrawal from a metrogynine derived substance. What does that kind of look like? What is the range of presentations?

B

Absolutely. I still use like the COW score or the SO scores. A lot of my patients will self rate the withdrawal score kind of their level of withdrawal. I will say that I think patients have a lot more of the somatic symptoms. So more so than like the gastrointestinal symptoms. I don't have as much as many patients like nauseous or throwing up. I hear a lot of, you know, just feeling restless, feeling achy, you know, feeling that like achiness in their bones. You know, sleep is really bad, anxiety is really bad. They're very restless. So a lot of their symptoms mimic that of like traditional opioid withdrawal. But I do notice there's a bit more of a heavier emphasis on I feel really anxious, you know, I feel really restless, I feel so foggy. So there is, I seem like there's a little bit more of like that, you know, centrally acting like, you know, neurocognitive like, like issue with withdrawal.

C

And what does the timeline typically look like? Like when do people start to present with withdrawal?

B

Yeah, I think for, for seven, oh, it's really acute. I've had patients tell me four to six hours after my last dose. I know that I'm going to start feeling bad. So it's not atypical for patients that are taking kratom derivatives of 7OH or MGM 15 or what have you to be redosing their substance maybe every four to six hours. I've seen in some more extreme cases patients that are using these substances to redose their substance every two hours at some point. And it really does become for this patient we're working with a very, very cost prohibitive problem. I have had patients tell me they're spending upwards of three to $4,000 a month on seven oh. And, you know, becomes like a really big burden for them. And that's why they kind of reach out to seek help.

D

And do you see a difference in the withdrawal presentation between, like, I know you mentioned the difference in timing of withdrawal, but like, in terms of what the withdrawal symptoms are between types of products or not as much?

B

Yeah, I think withdrawal from Kratom is a lot less severe, I would say. I've had patients tell me themselves, like, you know, I don't know, I'm having this trouble this time around. When I was using Kratom powder X amount of years ago, I was able to kind of cold turkey it, but I can't cold turkey the seven oh. And I think part of that comes from the potency between the two compounds. Kratom itself, the powder is a relatively weak opioid receptor agonist. It has less potency than morphine does, whereas 7 oh. There were some studies that came out that show that it's about 13 times more potent than morphine. And I think that could explain why we're seeing a lot more severe withdrawal and, you know, increasing use over time.

D

Yeah, I think that definitely mirrors my experience with my patients for sure. I think I, in addition to some of those like, like anxiety, restlessness symptoms, I definitely am having patients experience some, some significant, like diaphoresis and, and that kind of stuff as well in their withdrawal picture from 7oh specifically.

C

And is there a way to test for exposure to 7 oh? Like, would I find this on my typical urine drug screen?

B

I wish. Unfortunately, it's not on our typical like nine panel or ten panel urine drug screen. From my understanding, it'd be a send out and then they would have to use mass spectrometry to, you know, isolate those metabolites in the urine.

D

No urine drug screen yet. All right, so going back to our case, just gonna move us forward a little bit so you have the opportunity to ask some more questions from this patient. And they share that they started using Kratom initially to help concentrate. They were diagnosed with ADHD as a child, haven't had access to a prescriber and medication for their ADHD for the last few years. So in the beginning, the Kratom was super helpful to aid in concentration and getting work done. But our patient notes that it no longer helps with that. And ultimately he's really just using these products not to feel sick every day. So I think we talked a little bit about what the withdrawal picture looks like from these products. I'm curious if you have Thoughts about ways that we can help patients manage these withdrawal symptoms. Can we do the same things we do for other types of withdrawal? What's the deal?

B

Yes, we can. I'm a big fan of clonidine, you know, centrally acting alpha agonist, hits logos coelius of the brain, where withdrawal comes from. I've noticed it to be really, really helpful in getting my seven OH patients finally get some sleep. So that's a great adjunct for some of my patients that have, you know, some of the more GI heavy symptoms on Dansetron does the trick pretty well. And you know, I also, you know, takes this time too to you know, kind of talk with patients like, you know, for our patient now we're taking care of, he has that history of adhd. A lot of my patients do have like dual diagnosis or co occurring psychiatric disorders. And you know, it's hard at some point, it's kind of hard to dig out what substance induced versus what's organic. But you know, I try to kind of give them these comfort meds at baseline and then reassess at closer follow up to see if some of those other, you know, if the anxiety has gotten better, the agitation has gotten better before adding something on like you know, an SSRI or a mood stabilizer. You know, just really trying to make sure we can parse out what might be substance induced versus what might be organic before moving into something else.

D

And I heard you, so I heard you kind of talk about what we think of as our comfort meds for withdrawal management from opioids as being effective for these products as well. What about sort of our mainstay withdrawal management, buprenorphine and methadone? Can we use those for metragynine based withdrawal?

B

We definitely can use buprenorphine. No other CTs are out yet, but there's a bunch of great case studies with patients with a variety of presentations. I've seen case studies for patients that have used Kratom for treating cancer pain, pain after some sort of spinal injury, some mental health concerns, anxiety, depression. And a lot of these papers have people kind of getting into like a moderate level of withdrawal per the COWS or SOW scale and then doing a good old buprenorphine induction. Oh, I saw one study using rats for methadone, but I don't think I haven't seen any data for using this in, in people. I think it would make sense extrapolating what we know about how well buprenorphine works. But I think the regulatory framework around methadone in the United States might make this kind of like a gray area, you know, because is it can we really say this is an opioid use disorder when they're not. When MIT progeny is not technically an opioid? So I can see there being some gray area from a legislative or kind of like a, like a, a law perspective and whether or not this person can become a patient at an opioid treatment program with methadone.

D

Yeah, I think that's definitely an issue for kind of treatment of a use disorder long term, although I think in the hospital setting certainly methadone is an option to manage acute withdrawal for these patients.

A

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C

Could you walk us through how you would actually start buprenorphine for somebody who's coming off a metragynine product? Like, how long are you waiting? What cow scores are you getting to? What doses of buprenorphine are you starting with?

B

Absolutely. And I think it's almost, you know, it's an interesting parallel parallel because, you know, in the addiction space, we talk about inductions pre and post the era. Fentanyl and like 7 oh and kratom kind of fall in that, in that parallel as well, where kratom inductions are like pre fentanyl inductions. And then 7 oh is more along the lines of doing an induction off of fentanyl. So with Kratom, I've had patients have successful inductions in as little as 12 to 16 hours since last use. As long as they're keeping a good record of their, of their, of their SOW score. And, you know, they have a pretty good idea of, like, what withdrawal really feels like to quantify that. And their inductions go off without a hitch after at least 16 hours. And then meeting that moderate level of withdrawal for the SAO scale with seven oh, it gets a little bit more hairy. You know, volume of use comes into play, duration of use comes into play. And I normally tell folks we need to at least wait 18 to 24 hours, but closer to 24 hours to begin an induction. But even then, I have had unfortunate events of what looks like similar to precipitated withdrawal, where patients will take that initial dose of, you know, a 2 milligram or 4 milligram dose of buprenorphine and then end up feeling a little bit worse. And then at that point we just end up moving towards the macro dose and then they end up feeling a little bit better. So they would receive 16 milligrams of buprenorphine if we're in that situation, just to kind of flood the receptors with buprenorphine. But interestingly, post acute withdrawal from seven oh my. And from my experience, hangs around a little bit longer than I thought it would. Sleep is kind of. Yeah, sleep is really wonky. Anxiety is still kind of at edge for like the first week or so. But the withdrawal symptoms do get better. But I have noticed post acute withdrawal from 7oh does seem to take a while.

D

Yeah, I think I've had a similar experience with that kind of Their, like, physical withdrawal symptoms are better, but they're with the buprenorphine. But some things just kind of feeling off for a lot longer than maybe starting other initiations.

C

Totally agree. I think, I think. I think in part this is because, like, the receptors are just so messy with this compound. So sometimes I'm offering clonidine for longer, especially at night, to help with symptoms. I think there is even some data to say there may be some serotonin. Serotonergic properties, too. And if somebody's describing. I think I've intermittently had a patient described, like, brain zap, you know, like, things that sound like ssri, you know, withdrawals, like, thinking about adding something like that in and, man, I. Can you walk us through, John? How do you counsel patients through that? You know, I. I think it's really important and key to, like, normalize that. That process.

B

Yeah, I, you know, I really tell patients, like, especially the ones that get bamboozled. You know, I'm like, this is, you know, this is not what you expected. You know, this is a medication to kind of help your brain rest. Right. You know, Carolyn, you bring up a really good point where this is such a messy compound. You know, you're like, there's a lot of dysregulation there from a neurobiological standpoint. So I. I tell patients like, you know, just give yourself some grace. You know, you're. You're giving your brain a rest by getting on this medication. You know, I run into a lot of, like, some resistance sometimes when we talk about duration of. Of treatment and dose adjustments. You know, a lot of patients are loathe to go up in dose despite having withdrawal symptoms because they run into the concern that, oh, you're just replacing my 7 oh for buprenorphine. And I just kind of try to center things always from, like, a lens of, like, patient concern and patient safety, where I tell them. I'm like, you know, like, I understand where you're coming from. You weren't on anything before starting seven. Oh, now you just feel like you're stuck on this hamster of buprenorphine. But from a safety perspective, at least we know that this buprenorphine you're getting from your local pharmacy is just buprenorphine. And we can more predictably understand how that's going to work for you, and we can come with a plan together to, you know, taper you eventually. If that's what. If that's what your wish is, that's great.

C

And I'm curious what what starting dose are you using for buprenorphine for these, like, home. Home inductions?

B

Yeah, yeah. So, you know, expert opinion based off of my panel, for my patients using solely Kratom, most folks land at a daily dose of about 8 to 16 milligrams a day of buprenorphine. And, you know, depending on why a patient was using Kratom, especially if it's for, like, chronic pain or something like that, you know, they might take their dose three or four times a day just to maximize buprenorphine analgesic capabilities. But then when we run into the seven oh, folks, the dosing mirrors that of fentanyl, honestly. So most of my patients will require at least 60 milligrams a day. But I do have a fair amount of patients I take care of that are taking up to 32 milligrams a day.

D

And when you're doing those initiations, are you starting with, like, 2 milligrams? Are you having folks start with 4 or 8? Where are you kind of landing in the initiation?

B

Yeah. So once they hit that sow score, moderate severe withdrawal. I'm normally starting most people on a 4 milligram dose of sublingual, and I actually see my patients back in a week. So everyone comes back after a week. We give an initial dosage out, and after that first week, for a lot of these folks, too, it's their first time ever being on buprenorphine. So, you know, we can do some troubleshooting, you know, the squishing your mouth out, spitting it out, and not swallowing the residue, because buprenorphine is not the easiest medication to take. And, you know, then we'll do a dosage adjustment. And, you know, some people feel great on the 16, some people need that ramp up to the 24. You know, just really just trying to, you know, meet the patient where they are and making sure and get them feeling better.

C

So it sounds like it's pretty typical for you just to start 4 milligrams, like, once a day and then see them back really closely and make dose adjustments. I feel like I more frequently work in the hospital for doing addiction consults, which, like, makes it so much easier to do inductions. I feel like I will do something similar, though. I will be able to and have the opportunity to redose in the hospital because I can actually, you know, see how they're doing and ask about symptoms. So I'll do sort of a similar protocol where I'll use the COW scores. I have been very lucky and that I haven't had precipitated withdrawal yet, knock on wood in the hospital. But again, a much more easily controlled environment. And I just wait until their cow scores are greater than 8 and then get 4mg every, every 4 hours as needed until their symptoms are withdrawn. I do feel like agree with you, John. That's like, it's almost like when I used to do initiations when the supply was predominantly heroin is what it feels like. And it's simpler in some ways.

D

Messier, I would say in the outpatient setting. I've kind of had a similar experience, Caroline, of starting. I usually start folks with four and kind of instruct them to keep taking four that first day until they get to usually I'm like, you're probably going to get to 16 if they're using seven. Oh, and like kind of give that pre counseling. I also haven't had any issues with any patients having precipitated withdrawal, which has, which hoping that continues. But, and then I've had a few folks who are like, that sounds annoying. Is there a way to like do this faster? And so I've done a couple, like walked patients through, like more of a high dose initiation, like just going straight to 16 milligrams. And we've done a few of those in our hospital setting and those have gone well as well. So I definitely think there's kind of a range of options available to folks.

C

And I realize too, we keep saying the term precipitated withdrawal, but man, I don't think we've explained it. John, do you want to walk us through what that means? Yeah. In case, in case people have never listened to any of these other episodes before.

B

I'm so sorry. So I like using magnets as an analogy for this for my patients. I, I, this is part of my counseling, actually, when I tell them like, like, you know, with a 7 oh patient, telling them to wait 18 to 24 hours is agony because of how bad the withdrawals are. So what I kind of tell patients is like, hey, you know, if you think about magnets, you know, you have like the fridge magnet you buy at the rest stop and then there's the magnet that locks the door that your badge has to open. 7 oh is the refrigerator magnet and buprenorphine is the magnet that keeps the door shut. If those two magnets are going to try being attracted to something, who's going to win the buprenorphine and it's going to rip off that fridge magnet and you're going to feel horrible after that. Magnet gets ripped off and that door magnet won't even attach right away. So you're going to be feeling really crummy for, for, for quite a bit of time. So, you know, due to buprenorphine's very high affinity to the opioid receptor, it'll displace whatever opioids are sitting there or occupying the opioid receptor. And then that interchange of buprenorphine being attached and then seven oh. Or what have you coming off, you end up with the naked opioid receptor for a little bit and you're just in really, really bad withdrawal.

D

I like the magnet thing. I might have to steal that one. I always use the like dimmer switch as my example.

B

I could never get the lock and keithing right. So I just went to magnets.

C

And I'm curious too. In your practice, John, what are you seeing in terms of patients staying on it? I think that this is just a huge gap in the literature. Do patients stay on this medicine forever like they do for folks who have the more well characterized opioid use disorder? Are people just on this for a week and they're tapering? What do you sort of see clinically?

B

Yeah, so I, when I counsel patients, I extrapolate data from classic OUD where, you know, you have those really high rates of relapse if, if you leave care after, you know, less than 18 months. But I will say it does. It is very patient dependent. For patients that came to Kratom for treating chronic pain and then the buprenorphine ends up being a great pain medication for them, they're happy being on it forever and they love it because they're like, wow, like tolerance isn't a thing. And I'm like, yeah, you know, for a lot of folks it isn't. But then for the people that, you know, came to this recreationally or they were, they were in recovery from a previous opioid or stimulant use disorder, now they're on buprenorphine. I feel like there's sometimes there is more urgency for tapering and I normally ask, I counsel patients. You know, the best data we have is treatment adherence for a year and then we can try to taper together after. But I always do try to meet the patient where they are. If they're adamant on tapering or they'll start tapering themselves, I'll tell them, I understand where you're coming from. This is, you know, it can be cost prohibitive seeking care every month. You have a lot going on. I don't want you to do this alone, so I'll work with you to taper. But I also want you to know if there's something that happens along the way, we're here to support you. So I give people like, you know, I think my style right now is like, give me six months of consistent dosing and, you know, coming in on time every month. A lot of your domains are like, you know, normalizing, sleep's good, mood's good, and then we can start tapering after six months. And then that actually gets me to a year normally of treatment time. Because your tapers are hard. I tell them patients too, like, tapers are hard on your brain. So that ends up buying us about a year of treatment or more. And I think patients do like that collaborative approach. You know, I'm working with you. And patients will tell me too, like, hey, doc, let's pause this taper for this month. I have a lot going on with my family. Or hey, let's pause this paper for a while. It's the winter time and my seasonal depression doesn't feel great right now. So it's really just rolling with the resistance and kind of meeting patients where they are.

C

I like that sounds like you're just really doing a patient shared, patient centered approach, shared decision making. Because you're right. We just. We just don't have a lot of evidence specifically for Kratom, but hopefully we'll see some stuff.

B

I'm interested, though, as an aside, in using long acting injectable buprenorphine as a tapering strategy off of Kratom and seven.

D

Oh, I just did that actually very recently. My patient's doing quite well. We'll see how long it goes. But yeah, I think it's a great option for tapering in lots of settings, but also for this. For this setting. Yeah. This patient was on sublingual films, kind of got tired of it. We switched them to lai, was doing okay and kind of decided that they were done and wanted to taper off. And we're like out a couple, you know where? I think we're at like a month or two out. So he's doing well so far. We'll see.

B

Was it a one off of the LAI or did they come in for a couple?

D

It was a one off. Yeah, I've done like, for other opioid use disorder, definitely do other versions of that taper. That's maybe more doses, but this patient was kind of just ready to be done, so.

B

Awesome. Yeah, you know, my patient, my patients, my seven. Oh. Practice is primarily telehealth. So I don't have a nurse or a controlled substance refrigerator to dole this stuff out on my telehealth box. But patients are very interested in it. They'll be like, hey, I heard about this shot. And I'm like, I love the shot. So I do wonder, because I'll refer them out to local, where they're from, folks that can offer them the LAI and I feel like it's. It'd be such a great tool. So I wish the best for your patient.

D

My N of 1. I'll let you know how it goes. Yeah.

C

And for folks who aren't familiar, LAI stands for long acting injectable buprenorphine. So there are two formulations where you essentially can get the injection roughly like every four weeks with different doses. And some people can stay on it, and some people can use it as a way to taper off because if it's like slow release. So, yeah, it'll be interesting to see where the field comes and where, where the field goes sort of over the next couple of years with this. Do you, John, use anything, any, like, type of behavioral interventions as well, like counseling, stuff like that? Have found any of those to be helpful?

B

MI Motivational interviewing. It has been so helpful in helping a lot of these patients, especially in these patients that are seeking help for withdrawal and cravings. But they're still a little bit pretty contemplative about whether or not they have a problem. So, you know, just like, active listening, you know, reflecting back what they're experiencing. I get a lot of buy in. Especially when patients want to do a rapid taper. They'll be like, oh, he's like, they're like, come on. Like, I. I can't be doing this forever. You know, like, the pharmacy looks at me funny when I pick up my prescription and, you know, do some motivate, like, do some active listening, reflective listening, and be like, you know, it's really hard. I can understand, you know, feeling stigmatized by somewhere you were hoping to get health care from and how hard that might be. But on the other, on the, on the other end, you know, you're. You're doing. You're sleeping so much better, you're doing so much better at work. Again, you're saving a lot of money. So I think, you know, motivational interviewing kind of, you know, making. Having that change talk come about has been super, super helpful.

D

Yeah, definitely. Definitely lots of different stages of where folks conceptualize their use.

C

And I think, luckily for our patient, you have successfully started him on 16 milligrams of buprenorphine. And he tells you, man, he is the patient who felt bamboozled. He's like, how is it even possible that I got access to this? I had no idea what the risks were.

D

A quick update on the legal landscape. On July 1, 2026, the DEA filed its intent to temporary place 7OH and several related substances into Schedule 1 of the Controlled Substances Act. Now, intent is the keyword. This isn't law yet. There's a process before this is finalized, but barring something unexpected, we anticipate that concentrated 7OH products will soon be Schedule 1 and therefore illegal nationwide. It does not apply to traditional kratom leaf and kratom leaf products containing only trace amounts of 7 oh that occur naturally in the plant. This is evolving to end time sensitive. So for current status, Please check the DEA's website and federal Register. And keep in mind that some states already have their own kratom and seven olh laws that may be more restrictive than federal law and which may continue to evolve as this moves forward.

C

So we've covered so much today. Zena, is there anything else that we have missed that we need to cover before we go into take home points?

D

I don't think so. I think we've done a great job covering, covering this broad, expansive topic with not a lot of evidence,

C

though I think super important to generals out there, right, practicing, because you're going to see and hear about this in your practice, and it's important to be aware of what that looks like and how to treat it. So, John, can you give us maybe a couple of your take home points today for our audience?

B

I think my take home points just mirror, you know, the beauty of our specialty in addiction medicine. Meeting the patient where they are. You know, I think that all the, all the buckets of patients that we've kind of talked about that we've, you know, helped or, you know, treated coming off kratomin7 oh, there's so many different reasons why people end up getting on this stuff. So just meeting patients where they are, being a good listener, being a reflective listener, just being collaborative. You know, let them define or let them decide what language they want to describe their use. And, you know, just rolling with the resistance. You know, I tell patients, like, my first patient I treated coming off pseudo in Doxel, he's like, hey, man, have you heard about this pseudo stuff? And I'm like, no, tell me more. And then we learned together and, you know, I was able to kind of learn with him on the fly. He showed me the website he purchased his stuff from and I was able to extrapolate. I'm like, oh, this is just seven OH with a thingy added to it. So we're going to try to treat you like seven OH and hope things turn out okay. And they did. So I think you're just willing to learn alongside your patients too, because I think a lot of these patients are very online. You know, they're reading things from Reddit. You know, I had a patient ask me about this like kind of insane gabapentin taper they saw on TikTok. They're coming off 7 oh. So just, you know, being open to talking with them and seeing where they're coming from and just being collaborative.

D

Anything that you would like to plug? John Resources or yeah, I love so

B

I I love my moud job because I do a lot of rural work which is so different than working at a safety net hospital in America's third biggest city. So I would love to plug find treatment.gov because it's a great resource for finding local recovery resources for psychosocial support. A lot of the resources there are free. So for a lot of my patients that live in rural areas don't have as much going on around where they live for SUD care, findtreatment.gov is a great easy lift to kind of give your patient to see if there's something in their neck of the woods they could benefit from.

C

That's great.

D

Awesome.

C

Thanks so much for being here.

B

Happy to be here.

C

This has been another episode of our Curbsiders miniseries, the Curbsiders Addiction Medicine. Get show notes@thecurbsiders.com addiction and if you are still hungry for more, well you know what, you can join the Curbsiders Internal Medicine Patreon and get all episodes ad free twice monthly boneless episodes@patreon.com curbsiders. Of course you can also find and sign up for our listserv@thecurbsiders.com to get our weekly shownotes to your inbox.

D

We're committed to providing you with high value practice changing knowledge and to do that we need your feedback. So please subscribe, rate and review the show on Apple Podcasts or contact us at curbsiders addiction med gmail.com A reminder that this and most episodes are available for CME Credit and for all healthc care professionals through VCU health@curbsiders.vcu health.org and

C

a special thanks to ACAM, the American College of Academic Addiction Medicine. Learn more about their organization@acam.org and thank you to the entire team. The writer and producer for this incredible episode, Dr. Zena Huxley, RKER and of course Dr. Kento Sonoda, who is going to be our incredible editor and the entire Curve Ciders team. Our technical production is done by the team at Podpaste Ellsworth Proto does our social media, Jen Watto runs our Patreon and Chris the True Man Chew moderates the Discord. Stuart Brigham composed the theme music. And with all that, until next time, I'm Carolyn chan.

D

And I'm Dr. Zena Huxley Riker. Thanks for joining us today and letting us bring you some addiction medicine pearls.

C

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D

Life.

C

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