One Dose That Heals Addiction, PTSD, and Brain Injury? Dr. Nolan Williams on The Science of Ibogaine

25:37And, you know, and it was put on the U.S. Controlled Substances Act, even though it doesn't really meet criteria for the, for a controlled substance, for the description of a controlled substance. It is neither, people don't self-administer it. There's no, there's no animal data to suggest that there's a self-administration. In fact, it reverses self-administration of other addictive compounds. It's not a party drug.

26:02Dr. Mark Hyman:It's not a party drug. So it stops self-administration, and it has this profound kind of psychological effect that doesn't really, it's not really reinforcing, right? And so it doesn't really meet controlled substances description, but it was lumped in to the U.S. Controlled Substance Act, Schedule I substance, which is where it stayed since then and really prevented folks from using it. And so Howard Lotsoff had the story that you're describing, had this resolution of his addiction and spent his entire life trying to get this kind of out of the off the controlled substances list and as a therapeutic.

26:45And it's a very complicated timeline for folks to kind of get through. And I think we're getting a signal now that finally we may be able to see that happen in our lifetimes that, you know, it could be that we could actually study this thing and make a real decision of whether or not it's useful. And even if it doesn't work, like, let's say all of this is just a bunch of psychological effects and it doesn't really do any of the things that people think it does and all that stuff. That's an important study to do anyways from a public health standpoint, right? Like the idea that we make plants illegal and then make them inaccessible for science is like, in 300 years, we're going to look at that and think that's just the craziest thing, I think.

27:32Dr. Mark Hyman:And we have to study these things. And, you know, if the initial data that you've done and others have done actually bear out to be true, it's revolutionary in psychiatry. I hope so. I mean, I think it could really impact this incredible degree of trauma and PTSD and depression, anxiety, traumatic brain injury. That's even fascinating to me, the brain injury stuff. But the pathways that it works on are a lot of different pathways that reduce inflammation, oxidative stress, that increase neuroprotection, resilience of your cells. And, you know, it almost seems too good to be true. know how this works but it does have to be administered in a way that's safe because it is risk of cardiac arrhythmias is high and then you have to monitor that but but with the magnesium therapy which is you know what we use it's funny to me that that you know I used to work in the emergency room and we had this thing called the crash cart if someone comes in with cardiac arrest you give them all these drugs you give epinephrine you give them this drug you give that drug and then finally like if every other drug fails and they're still in this terrible arrhythmia you give them ivy magnesium that's right that's like the last straw like why don't we start out with that you know that's right you know i've given a lot of ivy magnesium in my life it's very safe we use it all the time in medicine for pre-eclampsia hypertension pregnancy for pre-term labor and doctors don't somehow think of it as a you know uh as a compound that we should be using except in these extreme situations but it's actually one of the most important minerals and many of us are low in it or insufficient in it and I think stress causes it to be low, also caffeine, alcohol, a lot of things that we do actually cause us to complete magnesium.

29:23Dr. Mark Hyman:A lot of people are on antihypertensive drugs that cause you to lose magnesium, diuretics. So you basically you know can mitigate a lot of these effects by taking people up on magnesium and if it's done in a controlled way. That's mitigated all those potential risks who've never had a case in the magnesium-administry patients that you've used Ibogaine with, right? I mean, I personally don't administer it. I just talk to folks in places that do, and what they tell me is that, for instance, one clinic wasn't really using it until a couple of years ago, and they'd had a bad outcome, and then they started using it, and they hadn't had any cases since then.

30:10And the rationale is, you know, as you point out, that magnesium is actually the treatment in the American Heart Association guidelines treatment for torsades, the fatal arrhythmia that's the result of Ibogaine. If you give magnesium, you can get some people out of torsades. And so the view here is if you're prophylactically administering magnesium before you give Ibogaine, then maybe what you're doing, and this is such a low risk drug, if you want to even call it that, is that you're bathing the heart in this kind of stabilizing agent so that when the Ibogaine interacts with the potassium channels that are involved in the HERG potassium channels are involved in this arrhythmia, that they won't throw the heart into the rhythm.

31:00And that's the idea because the drug comes and goes and then nobody has a risk of like post-treatment arrhythmia. It's only during the kind of the peak levels of the drug. And so if you can give magnesium and stabilize the heart, you can prevent this from happening.

31:14Dr. Mark Hyman:Right now, you know, there's, it seems to me, we're just sort of at this beginning of this sort of a phase of research, which is going to help us unpack the underlying benefits, the mechanisms, safety, and that'll lead to a path to potentially approval as a pill that you can take. But the question is, you know, do you still think people are going to need to be in a moderate setting with IV magnesium in order to actually safely take it? Because it sounds like it's not something you can just sort of like prescribe people, right? A bunch of different answers for that. But, you know, the kind of short answer is, yes, I can't foresee a time when Ibogaine isn't going to be a monitored drug.

31:53Now, Ibogaine at the current doses that people use, the kind of what we call flood doses. Now, the deal is that there's a bunch of companies that are trying to modify the ibogaine molecule to make it not have the cardiac effects. If they're successful in doing that, then you're in a situation where one of these ibogaine analogs may be the solution. Maybe you could take that at home or whatever. And a lot of them aren't particularly psychedelic, right? And so there's this, as you know, big open question of, do you need to have the trip? Do can you just have an agent that just changes brain plasticity and that's it?

32:33So that's a TBD sort of question. But that may be a way to do it. There are other, you know, ibogaine alkaloids, I'm sorry, iboga alkaloids that have, you know, more or less cardiotoxicity. So that's a question. And then we haven't really studied the dose ranges of ibogaine well at all, you know, and so it may And there's some very early kind of anecdotal data around this that people with Parkinson's and that sort of thing taking micro doses actually show improvements. And so it's one of these things where the Texas effort is going to be important to really hashing out what this is.

33:14Dr. Mark Hyman:You know, these effects of dopamine and other things are powerful. The ability for us to sort of navigate different mental illnesses with these drugs is fascinating to me because we've never really had these drugs or compounds that are so diverse in their effects and affect so many different conditions and have such a magnitude effect greater than what we have. So maybe you could spend a minute talking about your more recent study on magnesium and ibogaine in the veterans and what you found in terms of the orders of magnitude improvement compared to conventional therapies around depression, TBI, brain injury, PTSD, and what you found in terms of the connectivity in the brain, what you found in terms of the sort of physiological changes that you saw with looking at functional MRIs and EEGs and other assessment techniques.

34:05Dr. Mark Hyman:Because you're now looking at what's happening in the brain in ways that we couldn't really do before and that nobody really looked at. So Ibogaine is a compound that, like I said, produces that physiologic kind of EEG-based change that we just published on. We have more data that's kind of in review now where we actually took the MRI brain scans and fed them into an analysis pipeline around AI guessing the brain age. So as Mark, you probably already know, you can take a brain MRI and you can have AI guess a brain age. You can scan them the second time and it'll be very close to the first one.

34:48You scan them a third time, it's going to be very close. So three different scans fed into the algorithm, guesses within a very close range of each other, but not necessarily of your chronological age. Right. And so, you know, you're a young guy in the sense you look very young. right? And I would suspect your brain looks very young. And I would suspect that it's younger than your chronological age. You're talking about me specifically? Yeah.

35:19Dr. Mark Hyman:Yeah, I'm 65. I hope it's younger than that. That's what I'm saying, right? So let's say we scan your brain and maybe your brain is 55. And that's what AI. And so it's not very good at predicting what the chronological age is because that has much more to do with your lifestyle choices, but it's very good at being consistent about what that brain age is and mapping it onto other folks' brain age, right? And so, and, and, and, you know, as an alternative, right, there are some people at your age that are already developing Alzheimer's or, you know, MCI or whatever it is, and their brain age is 75.

35:55And if you scan them three times, you're going to see that it's 75. And what this, what this is showing is as a group average, people have about a year and a half younger looking brain at one month. Wow. Does it compound if you keep doing it? This is what everybody keeps asking me. I have no idea about that question, but it's a, it's a good question, right? Is, is can you, can you lock the brain into an age if you just keep re-exposing it? You know, it's a much further along the road question, but it's an intriguing one. Like I didn't, you know, my postdoc who's kind of obsessed with brain age did, you know, ran all these analyses and came to me and said, Hey, you know, we're seeing this and we're seeing it de-age the brain.

36:37But what we don't see is any real, I mean, there's a little bit of change right after, but it takes a month before you really start to see the brain age change.

36:46Dr. Mark Hyman:I wonder if it's like affecting epigenetic expression or gene expression in some way, because it seems like that's a pretty profound effect. Yeah, and it actually makes sense. We're talking about like one dose, one day, having an effect to reverse your brain age by a year and a half at a month. That's pretty remarkable. Yeah, I mean, it's an open question in the sense that we need to do the work, but what you don't see is much of a change right after. And so whereas you do see that with PTSD and depression and everything else, you see it really quickly. but with traumatic brain injury disability and with the brain age it takes the month and it makes sense like if these are more hard neurological issues you're not going to be able to change the brain in five days or whatever it's going to take some time.

37:35One of the things that I heard is that

37:38Dr. Mark Hyman:there's a metabolite of ibogaine called noribogaine that lasts longer and I'm wondering if that explain some of the tail of these effects of the addiction and inhibition, withdrawal inhibition, and maybe some of these other deeper neurological effects. And I don't know if that neuroibogaine has the same cardiac risks or if anybody's looking at studying that. So the neuroibogaine does have a similar cardiac profile. Ibogaine is metabolized into neuroibogaine normally through 2D6. And so you see people with getting Ibogaine and they metabolize to nor Ibogaine in roughly 12 hours, 8 to 12 hours or something like that.

38:20And so, you know, there's lots of folks, Deborah Mash is the biggest proponent, but lots of folks saying, well, why don't we give nor Ibogaine as a treatment? And that's an open question, you know, and that work needs to be done. The issue, I think, with noribogaine, if you think about PTSD, is that the ibogaine seems to be the thing that produces the earlier life re-remembering stuff, not the noribogaine part. Interesting.

38:48Dr. Mark Hyman:So the life review, watching a movie over life, seeing what happened, re-metabolizing it in a way that allows you to be at peace with it and kind of move on from that, doesn't happen with the noribogaine. It happens with the... Yeah, that's based off of the subjective effects and the timeline of the drug. That's what it looks like, right? And so if you want to have the, you know, if the goal is to have the experience drive some of the therapeutic effect, then it probably requires the Ibogaine. And what we found with the EEG stuff that I published a week ago is the degree of that subjective effect is correlated with the degree of the PTSD improvement.

39:31So if you take that out, you may be taking out at least some of the benefit, some of the at least the PTSD benefit.

39:38Dr. Mark Hyman:I have this theory and I wanted to know if you've ever thought of this, which is when you look at the global population and you look at the obesity epidemic, it's staggering. There's over 2.5 billion people overweight in the world. Obesity is exploding across the planet. And in America, we're, you know, 75 % of us are overweight, 42 % are obese. The Yale food addiction scale is a way of measuring food addiction. And Kelly Brownell and others developed it. And 14 % of the global population is addicted to food, including 14 % of kids. Yeah. You know, that's about the same as alcohol. Alcohol addiction is about 14%.

40:18Dr. Mark Hyman:And I wonder if, you know, everybody's talking about Ozempic and jumpy ones, but could this be like an unlock for people with food addiction who are addicted to sugar, who are struggling, who may have underlying dopamine receptor issues? I think there's, you know, when you look at genetics, there's genetics involved in people who tend to move towards more addiction. They don't benefit as much from this dopamine simulation. They need more to feel the same pleasure. And so how does somebody eat a whole sheet cake? I couldn't ever do that, but people do. And I think that is an application. It seems to be a multi-billion dollar application.

41:00So our data, we also collected alcohol use. And what we found was, and we're going to publish this soon, that people's alcohol use really precipitously dropped almost close to zero. And so just almost everybody just really dramatic improvements in alcohol and maintained it. And so and we also have some biology around that that we're looking at. And so, you know, all those guys, if you ask them, are you going down there to stop drinking? They would have told, you know, I'm trying to deal with my like TBI or whatever. And then, you know, nearly everybody came back and reported they really didn't want to drink coffee anymore.

41:43or they really didn't. And so I always think that, so placebo is expectancy, right? And the degree of the expectation that you have about how a drug is going to work drives a lot of the effect. So like, I don't know, you probably have seen this New England Journal of Medicine total knee replacement study where they did a total, they either did an incision and did nothing or did a total knee and the total knee patients in the, in the kind of the fake surgery incision folks had no difference in outcomes. It looks like it was driven primarily by, by expectancy. And so if the person's being told in medicine, I'm going to do this thing.

42:27And when I do this thing, this, that thing that I'm going to do is going to drive this outcome. Then the person has this expectation of that outcome. And that's hard, right? Like that's somebody's going down there and they think this is a TBI treatment or whatever it is, then it's hard to feel good about the data, you know, related to that, not placebo. But what I like to see is when you have off target effects, like we intended to look at TBI disability in this study, but now everybody stopped drinking coffee or now everybody stopped drinking alcohol. And if you ask them their pre-treatment kind of pre-test probability of any of that was going to happen, they'd tell you no.

43:09Like they'd say, I didn't know that was going to happen. They all just came back fascinated with this thing that happened that they didn't have any expectancy for. You know, we don't know for sure, but the signal is certainly there that this appears to be, you know, if you kind of read the limited data that we have, this appears to be kind of a global dopamine reward system reorg, and that we've just seen it work in opiate use disorder, because those are the kinds of folks that are, in many ways, desperate enough to have taken Ibogaine in the last several decades.

43:46Dr. Mark Hyman:So there's all kinds of effects we're just sort of learning about. And I think with obesity, nobody's probably looking at that, is my guess, right? With Ibogaine? Yeah, I mean, yeah, nobody that I know of, yeah. I think it could be an interesting offshoot study. Like, does their food behavior change? Does their cravings for sugar change? Does their cravings for... Because I think it's like... I mean, you're talking about opioid addiction killing 70 ,000 people a year, but the food addiction part kills a lot, lot more. Chronic disease-related food is killing a million-plus people a year in America.

44:19Dr. Mark Hyman:So to me, I think it would be an interesting little kind of side hustle to kind of look at that in your data and see what happens if people change their diets and they change their weight loss. Like there's other things you can look at. So I encourage you to check that out because I have this theory. But if it, because if it works, it's a big unlock, you know, and it's probably a lot better than taking Ozempic. So I want to sort of help people understand that this is not just like an incremental therapy because, you know, as we sort of started out talking about, a lot of the psychiatric treatments we have don't really work well or have marginal benefits or have a lot of side effects.

44:55Dr. Mark Hyman:And with Ibogaine and some of these other psychedelic therapies, we're talking about 80 % to 90 % reductions in symptoms and things that you just don't see. So can you talk about the magnitude of the effects and how it's different than traditional psychiatric treatments? Yeah, I mean, so the degree of the effects that we observed were quite striking.

45:17The data is limited, so that needs to get replicated. And I've heard, you know, that there's another group out of Texas that they're seeing very similar effects to us. And so if that holds and that's really the case, then, you know, that's going to be helpful. In this hypothetical future scenario where, you know, you're right and these are the degrees in which people change compared to conventional treatments, it's a huge difference. I mean, if you look at oral antidepressant differences between active and placebo for some of the pivotal trials that led to approval for something like Prozac, you're talking about a two to three point difference on a 60 point scale.

45:56And the inter-rater reliability on that scale is two points. Yeah. So basically it's like nothing. So the noise between raters is the same amount of change as the change observed. Now, on average, they're seeing the change greater in the active group than in the placebo group. I'm not arguing that, but, like, it's the, yeah, the observer, you know, differences are that level. So it's very hard to discern if you've got totally skilled raters and they have that problem, how effective these drugs really can be.

46:42Dr. Mark Hyman:So those are not, but then the Ibogaine is far more. Yeah, I mean, we're seeing, you know, in some cases a 20 or 30 point change on a 60 point scale where that scale is a generality. People don't really score above mid 30s on the Montgomery Asperg depression rating scale. That scale doesn't have a if you're above 30, 35, you're in really bad shape. You know, you need to go to the hospital or something like that. And so we're seeing a 20-point change in a lot of people on that scale. The use case for this drug is across a whole bunch of different issues that seem not necessarily related, like what does brain injury have to do with PTSD, have to do with depression?

47:27Dr. Mark Hyman:And how do you think that we can start to apply these compounds to these conditions in a more systematic way where deliberately working on different pathways that these drugs work on? It's an open question. I think we've got to spend the time to understand what the different alkaloids do and then use those. It's kind of like where GW Pharmaceuticals was as it relates to cannabinoids. And so there's an approval. I don't know if it's like a full approval or an orphan approval, but there's an approval for CBD, cannabidiol, for pediatric epilepsy syndrome, so Lennox-Gastaut and Dravet syndrome, right?

48:12And so those two epilepsy syndromes in kids are really devastating. Sometimes kids have 200 to 300 seizures a day. You have to put them on potassium bromide, which is like what we give dogs for epilepsy, you know. and you end up being in a situation where, you know, kids still seizing. And so the kind of interesting story there, which is another story like the veteran story, where there are all these families that figured out that if they could give their kid lots of CBD, the kid would stop seizing. Right. And so they were administering. On their own. On their, moving to, at the time, moving to Denver.

48:54This was, you know, Sanjay Gupta did like a special on this 15 or 20 years ago. So all these families with Lennox Guesto kids moving to Denver and then figuring out on their own, buying cannabis and then extracting it, extracting CBD. So they called it Charlotte's Web, which is this pure CBD cannabis, and they extract that out. and so GW Pharmaceuticals says well let's you know let's in the UK farm you know and this is like not doesn't make people like CBD doesn't really make people high maybe it's a little anxiolytic but it doesn't make people high you know the kids were actually waking up and they were less encephalopathic when they would take it yeah and you know you give this to a kid and they they come out of an epilepsy fit you know and so all these families were seeing this kids potassium bromide and all this stuff and then you give them uh high dose cbd and they wake up you know for the first time and so what gw did is they said okay we're gonna make a pure cbd drug we're gonna get that through and they're gonna make a whole host of other cannabinoid drugs to try to really discern to your point what's driving what with variable actions on different neurotransmitter systems and all of that yeah and i think that's what's going to happen with with these iboga alkaloids, right?

50:15Is that we have to...

50:16Dr. Mark Hyman:You don't think it's just the whole plant and you need to take the whole thing as opposed to breaking it down, which is what we do in medicine and break things down in their component parts and then it doesn't necessarily have the benefit of the whole plant. That is the open question. So there's going to be an experiment on this. Colorado is basically going to allow for whole plant derived iboga alkaloids to be used for people, you know, out inside of Colorado. And so the question ends up being, is that the road? Is it isolating ibogaine? Is it isolating other alkaloids? I'm a pragmatist. Like I don't have a, I don't have like a philosophical view on this other than, you know, if somebody is going to die and you give them this thing and their probability of dying goes way down, we should probably be doing that.

51:05And I think that's like, so if that's what happens in Colorado, then that'd be good. I mean, I have some open concerns about it because of the cardiac, you know, risk. And I'm pretty public about that. But they're not, they're going to do it no matter what I think. And so it's one of these things where that's going to happen. And then there's going to be a kind of a more pure Western medicine pharma play that's going to happen, or several. And then there's this kind of organic chemistry thing where they're changing the molecule thing, too. Maybe that's not even psychoactive. And I think we'll get in totality the answer over the next 10 years.

51:41And the reality is that if it all works, that's amazing. If one of them works, we know a lot more about how the brain works. I mean, hopefully we're not in a situation where none of them work, but that's possible, too. But at least we gave it a college try for sure. But the beauty is I think that's all happening and we're going to be able to really actually sort it out. And fingers crossed.

52:03Dr. Mark Hyman:Yeah, pretty amazing. This is sort of an interesting moment where we have these new compounds we never had before where we're looking at them. But the MDMA stuff is interesting because that's undergoing phase three trials and other sort of data that's looking at the effectiveness of this. But it's usually combined with psychotherapy. Yep. but what you're talking about ibogaine not needing the psychotherapy component do people need follow up support treatment integration is it have to be done in a psychiatric context where there's more continuity of care it's just like going and take it close your eyes wake up 12 hours later and that's it so there there is a there's a pre-post therapy requirement there's a within dosing therapy non-requirement, it appears, right?

52:52Although like nobody's really, you know, could be very helpful. We don't know. But what happens with MDMA is, you know, is, you know, I think you've studied is if you, if you give somebody MDMA, they have a positively valenced experience. Yeah. Right. They have this, they feel good and they feel good about, you know, the people around them and they feel good about the memories they've had. And so if they look at traumatic memories, they're going to see those memories from kind of an alternative perspective because they're seeing the world through a lens. And I think that's very useful as a tool.

53:28I think it's also very tricky as a tool. There's an analysis of the events that happened in Israel with the rave, right? And in that situation, there was a certain percentage of those people that were actually on MDMA. I don't know if you know, but they actually saw a statistically significantly lower PTSD onset in individuals that were on MDMA compared to people that weren't for that experience, for that kind of traumatic experience.

53:55Dr. Mark Hyman:Hamas came in and terrorized the festival in Israel on October 7th. And people who took the MDMA were less traumatized after than the ones who didn't. Correct. Yeah. And so, you know, what it's terrible story, obviously, what's interesting about that data is that it tells you something about it being protective, right? And those folks, you know, I'm sure it was clearly still traumatizing to them. But for some reason, it didn't lock them into, you know, as many people into a permanently traumatized state because they were seeing things from a positively valence place. but you know it's probably true that you need to you know have a guide to guide people with that drug with ibogaine what's really interesting about it is you can prepare people you tell them what's going to happen or tell them what you think could happen or a variety of things that could happen and then they take it and they have this long experience and then they come out of it and they have to unpack all of the stuff that they saw right they have to unpack all of the earlier life, you know, in many cases, traumatic memories that they have to kind of get through.

55:06And in that situation, it's driven by the drug. It's not driven by a therapist telling him, hey, go look at this memory. It's like the drug is doing that. But then the person has to come out of it and really actually sort it out for themselves mentally. Yeah. And that they need help with generally.

55:23Dr. Mark Hyman:And they, yeah, basically all need help with. Yeah. I'm fascinated because, Because there's effects on disease states or things that are problematic for people like PTSD, traumatic brain injury, depression, etc. But then there's the brain enhancement component. And I know a number of people have gone down there into Mexico and didn't have these problems, but used it as a way to sort of create neurocognitive and neuropsychiatric enhancement. And you mentioned briefly about the reversal of the brain age as sort of a hint at that. Can you talk more about how it might be used as a sort of an enhancement drug?

56:00Dr. Mark Hyman:In other words, that it doesn't just treat disease, that it may actually improve your overall cognitive function, memory, mood, neuroplasticity, neurogenesis, and things that we all would like to have better brains, right? Yeah, so what we observed in the veterans was that they had a statistically significant improvement in some aspects of cognition, particularly around frontal control. You know, it's an open question as to whether or not in a non-TBI, non-PTSD individual, you're going to see that too. But, you know, at least you can see in a diseased population an improvement there. Whereas like with a lot of the oral antidepressants and whatnot, you're not really seeing an improvement in cognition.

56:41There's not really a good drug in psychiatry that's approved for depression that improves cognition. And so at least we're getting signals of it with ibogaine, but it's got to be studied.

56:53Dr. Mark Hyman:Yeah, it would be interesting as more of like a longevity enhancement drug. And we don't really think much about those things in medicine at all. We think about things that suppress or inhibit or block some pathway rather than things that optimize, enhance, and improve the functioning of human physiology. Probiotics are an example of something that can optimize health as opposed to an antibiotic. and in functional medicine that's a lot we think about is one of the ways to enhance function one of the pro drugs as opposed to anti-drugs right and and it seems like it has that kind of potential what we really need to understand i think is why were the boiti taking this for hundreds of years you know and why did the french think this was helpful for 36 yeah you know and i think that could give us a signal about what it what it could do for that right because it seems to me that that even in the 30s to 66, which is kind of a different era, obviously, to have a drug on the formulary for 36 years that wasn't doing anything for the French, it seems unlikely, it's possible, but unlikely that that would have stuck around and been sold for 36 years.

58:06And so my suspicion is that there were some disease treatment effects, but maybe these effects too, who knows?

58:13Dr. Mark Hyman:Yeah, I wonder if there's any people around who took it back then, who are in their 90s probably now, from what the effect on them. I think this is such an exciting moment in psychiatry and medicine. And I think a lot of people are stuck in mental health issues. And we live in an increasingly stressful society. And there's just such a limited set of tools for people. Therapy can help a little bit. And some of the medication can help a little bit. But this is like a whole revolution. And I wonder if you've thought about combining the things that you're doing with other kind of metabolic psychiatry stuff that your colleague's doing at Stanford around nutritional psychiatry and metabolic psychiatry and combining both modalities as a way of even improving health outcomes and mental health outcomes.

59:04Dr. Mark Hyman:A hundred percent. Yeah. I mean, I think we, I've taken the stance that if you look at like, am I, Carol, like people having a heart attack, what do we do now? We throw an aspirin, we throw statin, we, you know, we, we, we do a heart cath. We do all of these things in summation that all independently were shown in isolation to benefit. Right. We pay a cocktail therapy as opposed to a single therapy, right? The challenge right now is to, we're in cardiology 1950s, right? So we're having to, we maybe have a pacemaker, we have a couple of drugs or whatever it is, and we need to now figure out what to do with all the limited tool set to make more tools and improve those tools and do the trials in each one of the tools.

59:53Now, or my kids or, you know, whatever the folks that are going to end up or my students or your students, the folks that end up combining all of these therapeutics together because there have been trials to show synergy. I think absolutely. You know, I think that's going to be the way we deal with things in the future as we say, OK, well, we're going to, you know, and you're doing a lot of this already. We're going to measure all of these things. we're going to modify your diet your metabolic you know all of that good stuff we're going to do brain-based things I think the interesting question ultimately is if we're in such a disease society that we end up being so far off of like the normal range metabolically stress all that stuff and people end up being way over here do you need multiple therapies to get you back on track.

1:00:48But then if we just had the right dietary interventions to begin with, that maybe we don't need to do all this other stuff. To me, that's one of the big questions that, you know, yourself and others are trying to tackle, which is, you know, a lot of folks now in government is this question of, if we can just have kids eat healthy, is there a world where we have less mental illness? And it's an important question and one that we have to, We have to ask, you know, we have increasing rates, we don't know why. And so maybe it is because of diet.

1:01:19Dr. Mark Hyman:Oh, yeah, I mean, it's huge. I mean, but I don't think that the dietary changes alone or nutritional metabolic changes alone can do the kinds of things that these psychedelic compounds do. And what's fascinating is we've sort of... It always fascinates me, I don't know if you have a theory about this, but how is it that all these plants have compounds that interact with our biology in these profound ways that change us? And I wonder if somehow we co-evolve with these plants. And if you look across all indigenous societies, they all have some sort of psychedelic something that they play with. It's ayahuasca and, you know, should be Indians in South America or peyote in North America or whatever.

1:02:04If you look at the thinking that the 1700s physicians had about vitamin C containing fruits like citrus fruit and the way they thought about it as it relates to scurvy, you kind of understand where we're at today. Many of them thought these were, you know, there weren't that many limes and lemons in Europe at the time. Right. This was considered a South American or an African exotic plant. And so most of the physicians today actually rejected citrus fruit as a treatment for scurvy. And so, as you know, the story of anti-fruitors, right? There were lots of people in the British Royal Society that said that the limes and lemons may actually be making scurvy worse.

1:02:53And I think that's the situation that we maybe find ourselves in now or used to find ourselves in where somehow we've conflated the solution with the problem in this very weird way and that we blame a plant because man didn't make it. And I think it actually has a greater philosophical problem with the way that we have, you know, that we see the world in our hubris, that for some reason we have this view that SSRI, that's totally fine because man made that and we understand it. Plant, not so sure about that, you know. And I think that's the way we've been looking at plant-based psychedelics for a long time and hopefully that changes.

1:03:35Dr. Mark Hyman:Pretty amazing. And I keep kind of doubling down on the magnitude of the size of the effect, and I want to sort of double down on it because I think when you look at the 30 special ops, you know, special forces veterans who had brain injury, you know, you found really large effect sizes, you know, like the disability ratings dropped dramatically from moderate disability to like no disability, had PTSD drop by 88%, depression drop by 87%, anxiety by 81%, improved cognition. and it seems like too good to be true, right? When my postdoc showed me the data, I didn't believe them, and I told them to go back and reanalyze it.

1:04:11Yeah. You know, and so we, you know, we, that's why I don't make claims about it, you know, because I think that we have to at least be replicated by another group in order to justify it. So we need to be replicated by another group in order to justify it. Now I'm hearing from my colleagues out of Texas that they are seeing very similar effects, right? And so I want them to formally see that, if that's what it is, and publish that. And then we can say it wasn't our site or whatever, that at least in an open label way, this is what this looks like. And then the next step is to do the big trials.

1:04:49But it would be unusual to have that level of an effect for this sort of level of expectancy.

1:04:57Dr. Mark Hyman:They didn't expect that big of a change, so you were less likely to see it. Yeah. The veterans, have you followed them ongoingly? Do they still have the lasting effects? So we have data out to a year. It isn't published yet. It's kind of in review now, actually. And that looks really good. Most people hold it. And you're talking now more about this idea of circuit-based psychiatry, which helps explain some of the things you're seeing. Can you kind of unpack what that is and how it differs from our current view of psychiatry? If you think about psychiatry and epochs, you know, the first one being talk therapy.

1:05:30and we learned something important there that spoken word can have effects on mental states and now more recently data suggesting that it's having an effect on the brain itself. And that was useful. Psychiatry 2.0, this idea that pharmacology can have an effect at the level of synapse, and that was also very useful, right? That got a lot of people would say schizophrenia any out of asylums and that sort of thing. Like Thorazine. Yeah, like Thorazine, yeah.

1:06:03Dr. Mark Hyman:Chemical straitjackets, we call them. And then psychiatry 3.0, this idea that you can actually look at the psychiatry 1.0 and 2.0 innovations from the frame of the circuit and improve upon them, right? Because at the end of the day, lots of the psychiatric treatments that we have are suboptimal for patients' desires, right? ECT is a great example of that. Electric shock therapy, yeah. Can you use insights from before and make things much safer and better and much more tolerated with patients? And that's really been, I think, the emphasis for our work. And so when we look at IBAN, we're looking at it from the lens of the circuit.

1:06:47When we're looking at, I'd say, stimulation of the brain, we're looking at it from the lens of the circuit. And that's helpful because, you know, the whole brain doesn't necessarily need to be exposed to things really, at least in depression, it looks like from our OCD data, that you can get big effects from just isolating one brain circuit and modifying it.

1:07:10Dr. Mark Hyman:Amazing. Well, we're in a kind of revolutionary time in psychiatry, which is exciting to me because I remember first working in a psych hospital in residency. I was like, I spent a month there. I was like, this is just nuts. And I don't mean that as a pun. I just mean the way we treated people, the amount of suffering that's going on, the lack of really good treatments. It feels really hopeful. It feels like a hopeful moment. But it doesn't feel like we're going fast enough to me. It feels like we're still in this sort of glacial pace of change. And science proceeds that way, unfortunately. But I think many people listening are going, wow, can I try it?

1:07:50Dr. Mark Hyman:What do I do? What if I want to go do it? I have this addiction issue. I've got PTSD. I've got trauma. There's a few places people go, like in Mexico, beyond, or Ambio and also Mexico. There's a few places out there. What do you say to people who want to go sort of explore this? Yeah, I mean, the good news is that we, you know, it looks like there's actually going to be some U.S. trials soon, you know. And so being able to do this from inside of the U.S. is kind of the ultimate goal. You know, folks go to these places and, you know, these other countries. But the ultimate goal is really to see that folks can do this safely in the U.S.

1:08:31And so I think, you know, five, ten years ago, I wouldn't be able to say anything right now with you asking me this. But now, at least, we have the ability. And the hope is, is if everything goes through the FDA, there'll be a normal healthy control study. that the FDA will have that IND, that new investigational new drug application through, and you'd be able to actually give people Ibogaine that are normal, healthy controls, right? And so that's... And see what happens. And see what happens. And so it is coming soon, you know, we'll have to see what happens with the FDA. But yeah, I think that's an exciting moment for folks and, you know, being able to have access to an experimental therapeutic like this.

1:09:16Dr. Mark Hyman:And if people want to go down and try this in Mexico, do you advise against it? You say it's your own risk? It's definitely people's own risk. I mean, look, it's one of these things where we still don't know that much about this. Like in our Stanford study, we were really clear with people that they had to have already signed up to have anything to do with. Couldn't encourage them to do it. Yeah. Yeah, we couldn't encourage them to do it. we didn't really participate in any of the processes for them to do it. We simply just studied people that were already going down there. I want to ask you a question about a particular flavor of mental illness that is incredibly difficult to treat, that is really generally from a lot of trauma, which is personality disorders.

1:10:04Dr. Mark Hyman:Borderline personality, narcissistic personality, it's so effective. There's all these personality disorders, which are more like fixed personality traits that are hard to change. And I'm curious if this kind of life review, the sort of narrative unfolding of your life like a movie during an Ibogaine experience has any impact on these more embedded, like deep-seated traumas that are harder to undo. It's a great question. I mean, the Hopkins group demonstrated this profound personality change that they observed out to a year, I think, early on with their trials with psilocybin. And so there's definitely data that there's personality change, you know, in and around psilocybin use.

1:10:50It's an open question. And the other thing that's interesting, which is data that isn't published yet, but was collected was around folks that will say they're, you know, they're religious or not. And so actually people that I think it was like 16 % of people were not religious prior to taking Ibogaine. And there's an increased kind of sense of a higher power or whatever after like almost, you know, two thirds of people. And so this question of how do people see the world that they live in is really interesting. But yeah, you know, nobody's done a personality inventory study with Ibogaine, so it's still open question.

1:11:34Is it dangerous for these people to do anything? It's certainly dangerous for people with a psychotic history, you know. I think people with bipolar disorder, that's going to be dangerous. Maybe somebody with severe borderline, maybe, you know, it just depends. It depends on a kind of individual basis. The problem at a fundamental level is we just haven't studied this enough to really know. You don't have data sets to know what's going on with these people.

1:11:58Dr. Mark Hyman:Yeah, interesting. So where do you see in closing, where do you see this in five to ten years in terms of psychiatry, psychedelic therapy in general, and Ibogaine specifically? We have to do, we have a lot of work to do to kind of get this to the next step, a lot of studies to do. But, you know, if somehow this is able to get all the way to the finish line, I think that, you know, society will be in a much better place from a mental health standpoint, if all the data continues to look like it does, just because of, you know, the profound suffering that's out there. I mean, there was a WHO statistic that really struck me, which is one out of two people will have a DSM diagnosis at some point in their lifetime.

1:12:41That's a psychiatric. Purely psychiatric or dementia. One out of two. One out of two.

1:12:45Dr. Mark Hyman:That's a lot. Half of the population of the world is going to have some mental illness at some point in their life. It's a scaling problem. Think about it. I mean, at the end of the day, we would never be able to actually effectively deal with that. Definitely not through therapy. Definitely not through therapy. You'd have to have half the world become therapy. I mean, maybe with AI, you know, all of us are trying to figure out. That's right. AI therapists are pretty damn good. This psychedelic revolution to me is very promising. And then combined with the metabolic psychiatry revolution, which we're going to do a podcast about soon, that also is another unlock, I think, in terms of mental health.

1:13:20Dr. Mark Hyman:It's harder for people to do that because it requires a lot of lifestyle change whereas this is a sort of a brain reset that then seems like it would facilitate behavioral lifestyle change it's almost like this could set the stage and then you can have an easier time doing doing that other hard work what studies are on the horizon for you that you're you're looking at doing we're looking forward to seeing what happens the this texas effort and and hopefully there's you know some funding for texas-based universities to do this you know and to do do the the you know these treatments but Yeah, it's an open question about what's going to happen with the FDA.

1:13:53And I think if the FDA comes through and lets us do the studies, there'll be a normal healthy control study. We're hoping to add some biology to that. And then subsequently, hopefully, some traumatic brain injury studies.

1:14:05Dr. Mark Hyman:When you say biology, you mean biomarkers, blood tests? What would be the things you're looking at in addition to the functional MRIs and the EEGs, which are brain imaging and brain electrical studies? We hope to do some of that, at least the EEG side of things. But yeah, it's a great question, maybe something interesting to talk about later, but around is there any kind of blood-based biomarkers that would be of interest to... because we'll have IVs in everybody. Fascinating work. Incredible what you're doing. You're definitely going on a limb in the psychiatric world. I think you're brave, but you're at Stanford in a respected institution, and they seem to be in support of you doing this work, which is amazing.

1:14:43Dr. Mark Hyman:and uh you know we need to hail mary in psychiatry because uh we are in a bad state as a world um we're all divided and disconnected and isolated and struggling with various forms of just anxiety of living in the 21st century to more serious mental illness and the unlock that you and your colleagues are trying to get with this work and the whole psychedelic field is just amazing so So thanks for doing what you do. Yeah, thanks for having me. Yeah, good to see you. If you love this podcast, please share it with someone else you think would also enjoy it. You can find me on all social media channels at Dr.

1:15:22Dr. Mark Hyman:Mark Hyman. Please reach out. I'd love to hear your comments and questions. Don't forget to rate, review, and subscribe to The Dr. Hyman Show wherever you get your podcasts. And don't forget to check out my YouTube channel at Dr. Mark Hyman for video versions of this podcast and more. Thank you so much again for tuning in. We'll see you next time on The Dr. Hyman Show. This podcast is separate from my clinical practice at the Ultra Wellness Center, my work at Cleveland Clinic, and Function Health, where I am Chief Medical Officer. This podcast represents my opinions and my guests' opinions. Neither myself nor the podcast endorses the views or statements of my guests.

1:15:53Dr. Mark Hyman:This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided with the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, please seek out a qualified medical practitioner. And if you're looking for a functional medicine practitioner, visit my clinic, the Ultra Wellness Center at ultrawellnesscenter.com and request to become a patient. It's important to have someone in your corner who is a trained, licensed healthcare practitioner and can help you make changes, especially when it comes to your health.

1:16:27Dr. Mark Hyman:This podcast is free as part of my mission to bring practical ways of improving health to the public. So I'd like to express gratitude to sponsors that made today's podcast possible. Thanks so much again for listening.