One Dose That Heals Addiction, PTSD, and Brain Injury? The Science of Ibogaine

Dr. Mark Hyman
What you said blew my mind, which is that there's this compound out there that can abruptly interrupt withdrawal from addiction, that can help treat PTSD, depression, traumatic brain injury better than anything else we have out there on the market, in orders of magnitude more.

Dr. Mark Hyman
Doctor. Nolan Williams. Is a triple board certified neuropsychiatrist. And founder of Stanford's Brain Stimulation Lab. He's redefining how we treat depression, PTSD, and addiction.

Using brain stimulation, psychedelics, and neuroscience instead of meds.

Nolan Williams
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.

Dr. Mark Hyman
I think this is like a really paradigm shifting moment where work like yours have have really sort of pushed the envelope and say, hey, wait a minute. Like, we're thinking about mental illness all wrong. We're talking about like one dose, one day having effect to reverse your brain age by year and a half and a That's pretty remarkable. Is it dangerous for these people? Alright.

Nolan, great to have you on the podcast. Thanks for being here.

Nolan Williams
Yeah. Thanks for having me.

Dr. Mark Hyman
You know, I followed your work. I first heard you talk about three or four years ago. What you said blew my mind, which is that there's this compound out there that can abruptly interrupt withdrawal from addiction, that can help treat PTSD, depression, traumatic brain injury better than anything else we have out there on the market in orders of magnitude more. And I became very interested in following this conversation about this incredible compound called ibogaine that we're gonna learn more about today. And it comes from a bark of a tree in Gabon in West Africa.

It's used in ritual ceremony there for different kinds of ritual transitions through life. It's got a fascinating history. I maybe would love to start by by helping us understand, you know, what what is it exactly? And when was it first sort of discovered to be useful in mental health, which is really the focus of your work at Stanford and a lot of the published trials you've done and the exciting work to actually scale this up and make it more affordable and accessible and usable to many, many people who suffer. Because, you know, the truth is one in four people have had sexual abuse, which is crazy.

Yeah. Trauma is a real thing, whether it's micro traumas because your parents neglected you or big traumas, Gammer Matte talks about big t, little t trauma. They can register in your nervous system and have lifelong effects on your mental health, on your functioning, on your perceptual worldview, and all that influences your ability to be happy and function in the world and have a filled life. And, you know, psychiatric medicine is just very antiquated. It's it's very crude.

It's it's tremendous side effects of the drugs we use. Many of them don't work very well. And we're kind of in this unfortunate situation where mental health crisis is bigger than ever. We have fewer things that really work, and this seems to hold the promise of something really quite different.

Nolan Williams
Yeah. Thanks for for the intro there. Yeah. It's, you know, it's an interesting compound. It's been around for a long time.

It's an African root bark psychedelic, as you suggested, from Gabon in Central West Africa, kind of neighboring areas. And the group of people that use it is are called the Buiti, and Buiti just means that you've you've taken iboga and and ritual ceremony. Right? And so folks have been doing this for quite a long time, and they've been doing it because it has a it produces this kind of what people would call a transformative psychological experience. So people will go into this.

They'll have kind of a a massive change in consciousness over the course of, you know, twenty four to thirty six hours. And during that time, they'll have a psychological experience of reevaluating earlier life emotionally salient memories. And and for maybe all of us, for a lot of us, those are, you know, trauma at various scales. You know? And people will take a look at those earlier life kind of emotionally salient events.

They'll do it from a a position, kind of a third party position of seeing it from neutrality. So unlike MDMA where people will take that and they'll need to while taking that kind of be led into a memory, and then they have this kind of positive emotion about it. IBM seem you know, from the subjective sense people will report, seems to produce kind of a neutrality, and it kind of automatically puts people in that space. So the the you're not you're not being you're not being Guided or led. Guided or there's no therapist.

The drug just automatically puts your brain into this mode, it seems, and then people have what they call this life review or a slideshow where they're looking at these emotionally salient memories over time. And when they do that, they're able to see they're able to see the, you know, the memories from a different lens. And, you know, it looks like they reconsolidate the memories, and then they're able to, with that reconsolidation, really be able to kind of tolerate them or see them in a different way or accept them. And that that's pretty powerful. To your point, you know, psychiatric medicine has has created tools that look a lot like, you know, medieval or fifteenth century whatever keys.

Right? Like, we've thought about the brain like a a single tooth key that you put the key into the lock and you turn it, and the key unlocks the door. But the the brain is probably much more like a modern day key with a lot of different pins and a lot of different interactions. So when you put the key into the lock, it really needs to interact with a lot of different systems. The problem with, in my view, with with kind of current psychopharmacology in the way that we see it is that we still think that it's a single neurotransmitter, single receptor problem.

Serotonin's low. So take serotonin reptake inhibitors like Prozac or your dopamine's low, so take basically speed, otherwise known as Adderall or Ritalin. If you look at the pharmacology of Ibogaine, it's very broad acting. Right? So it actually interacts with a with a lot of I mean, essentially, all of the neurotransmitter systems in in a unique way.

And it's probably you know, if this were to, you know, ultimately be as therapeutic as the initial signals are and we're able to see in big multisite trials the sort of data that we're seeing now in in our studies and studies coming out of that are gonna be completed soon out of Texas, then it tells us something about the way we're thinking about pharmacology and that this kind of idea of a dirty drug or a a kind of a multi receptor drug system is probably correct. And this idea of a single neurotransmitter system, low serotonin or whatever, where we're simplifying things down is probably oversimplified, you know, and then those tools are too coarse. You know,

Dr. Mark Hyman
in medicine, we call the the sort of multiple effect phenomenon pleiotropic effects, which means they work on many many different pathways and systems. You know, I wanna get into sort of more of the applications of it and what you what you found, but the mechanism of action is really interesting because we're sort of still deciphering that, but it works on both the structure and the function of the brain. So it doesn't just change it in the moment. It seems to have lasting changes, which is why and I think we're still trying to figure out, you know, why why if you take it once if you're a heroin addict that your addiction cravings go away and your withdrawal symptoms don't happen, which is something you is a physiological response. It's not like they're psychologically suppressing the withdrawal symptom, they just don't have them.

Yeah. And that's really fascinating. And I think, you know, for PTSD, you've got the NMDA receptors which are the sort of excitatory receptors that get calmed down, which get over excited with trauma. It does affect somehow the the serotonin system. It affects brain factors like BDNF which is otherwise known as brain derived neurotrophic factor that helps stimulate brain growth and connectivity, neurogenesis, neuroplasticity, more brain cells, more connections between brain cells.

So they do all these really interesting things that repair the brain, heal the brain. Even in traumatic brain injury, which is where you get banged on the head from something where you're in a war zone and you get some kind of traumatic brain injury. It seems to work on that too. So it seems to have all these varying effects. And they also sort of inhibit what we call the default mode network, which is what a lot of other psychedelics do.

It's sort the ego and the self protection part of your brain, which is, you know, makes us feel separate and disconnected. And when that is suppressed, whether you meditate for forty years or you take psilocybin or LSD, MDMA, or Ibogaine, that quiets down quickly and your your sense of disconnection and separateness is suspended for a moment and it allows you to sort of see how you're actually part of a greater greater whole. And that and so I I kinda would love you to unpack some of the the mechanisms and how they work in these different disease states because it's like seems like a one size fits all. You know, you got PTSD. You got depression.

You got anxiety. You got trauma. You got brain injury. Can you kinda unpack those for us and talk about, you know, how they affect across these various pathways in the brain?

Nolan Williams
Yeah. That's a great question. So the other mechanism that that we've thought a lot about that's unique to Ibogaine is glial derived neurotrophic factor. Right? So glial derived neurotrophic factor is a neurotrophic factor that that's involved with dopamine neuron kind of health.

Right? And so it upregulates dopamine neuron health. And so there was a study, you know, twenty years ago or something where they took mice and they mice or rats, and they train them to self administer, meaning that they basically you know, it's a mouse, you know, rat model of addiction, you know, where they're drinking alcohol out of a out of a a tube. And if you take a mouse and you do that little rat bartender there and then Something like that. Yeah.

Yeah. They they they they pull up to the bar. They'll they'll drink and until eventually they die. Right? And if you take a mouse like that and you give them iodine, you can actually reverse it.

They'll stop self administering alcohol, which is cool. If you take a mouse and you inject glial derived neurotrophic factor into the ventral tegmental area, which is the dopamine producing area that's involved with more of the reward system, you can also produce the same effect. They will stop self administering. Inject just Ibogaine just into that area, you can recapitulate the effect. Right?

And people have also shown that you can produce this effect by directly stimulating into those areas. Right? And so it's probably that at least the anti addiction mechanism of Ibogaine is that it's restoring dopamine function within that that ventral tegmental area in a way that resets the reward system. Then the the next piece of data that we have, we published in Nature Mental Health, I don't know, a week ago or something, which is a really interesting study where people with that in our trial that received ibogaine, had, had EEG, like, brainwave tests before, after, and one month after they received Ibogaine. And what we saw is this kind of general slowing of all of the the kind of different power spectra of the of the EEG.

Right? So people had a general kind of physiologic slowing of their brain after, and the slowing actually was correlated with the the strength of the trip, like the amount that they had a psychological effect Yeah. But also, interestingly, the reduction in PTSD symptoms and the improvement in cognition. And so, you know, that's it's a it's a first step study. You know?

The it was pretty good, I think, in the sense we got in nature mental mental health. But, you know, we need to do some more work on this. So I'm not claiming that this is definitive, but it's likely that if you you have an EEG, you may be able to tune the dose to the physiology of the brain instead of getting a subjective readout. You you just you you increase the dose, and then that may also allow for you to tune the PTSD effects, which is really cool. Right?

So you're kind of, you know, flipping

Dr. Mark Hyman
people need more, some need less, and you can tell by the EEG who needs what, and they can upward

Nolan Williams
That would be the promise. Right? That would be you know, if if it plays out, that would be and and we do this already in medicine, as you know. We use BIS monitors and anesthesia to to kinda measure the level of anesthesia. Or if somebody is, you know, being fully anesthetized with, like, propofol, you can actually you can actually burst suppress them.

And you you're, you know, you're using an EEG to help you dose a drug. You know? So that's not a new concept in in in neurology. It's just a new concept within kinda psychiatry. Right?

Dr. Mark Hyman
Right.

Nolan Williams
And so being able to figure that out, I think, is useful.

Dr. Mark Hyman
Well, that that that's the old joke is neurologists pay no attention to the mind and psychiatrists pay no attention to the brain. And here you are, you know, looking at psychiatry through the lens of the brain, not just the mind. Yeah. You know, Freud kinda took us down the path of mind only psychiatry and talk therapy and psychoanalysis. And it's sort of striking because, you know, you hear, oh, well, yeah, I heard psychoanalysis say, well, you could come to psychoanalysis five days a week for the next twenty years, and then you'll maybe see some improvement.

Here you're like, well, you can go, you know, to Mexico and do one Ibogaine journey, and, like, that takes care of, like, twenty years of psychotherapy. I mean, it's kinda crazy.

Nolan Williams
Yeah. I mean, you know, there's a lot of work to do to to kind of totally prove that. I mean, that's what that's certainly what people will say. That's what Claudio Naranjo said, I think, in in, you know, the Argentinian psychiatrist many many decades ago about ibogaine. It's just one of these things where we're gonna have to do Do the work.

You know, do the good work to figure it out. But I think that the problem and the kinda common theme of what we've been working on, the problem in psychiatry that's kind of out there right now is this problem of things taking too long to your point. You know? People can have an entire, you know, tragic life problem over the course of the time it would take, you know, for many of our treatments to work. I mean, psychotherapy psychoanalysis for ten years is one.

Just normal oral antidepressants. You know? I mean, we've seen, you know, people start out an oral antidepressant and lose their job by the time it it starts to have an effect. Right? And and so you end up being in this situation where we're not really matching the speed of the illness and the speed of the disability from the illness with the speed of the treatment.

Dr. Mark Hyman
It's kind of an exciting moment in psychiatry because we're we were in a very reductionist phenomenologically driven framework for psychiatry where psychiatric illnesses were described by their symptoms, not by their causes or their mechanisms. And what's really exciting to me in psychiatry, because I I've been thinking about this for decades, I wrote a book almost 20 ago called the Ultramind Solution, which details how the brain is influenced by everything happening in your body and and you can actually use those physiological levers to change psychiatric symptoms. So if we need to treat inflammation or mitochondrial function or the microbiome or, you know, with psychedelics, you're altering some kind of structure function of your brain that you can kind of change things that seem fairly fixed and permanent in somebody that we and we ascribe all kinds of meaning, and we have all these stigmas against these things. And, you know, if someone's limping because their meniscus is torn in their knee, we don't go, oh, you're you're you're a fuck up. You know?

Like but when when someone has a mental illness, there's a stigma of, oh, there's something wrong with you. Like, it's it's kinda you're crazy. It's your fault. But actually, there's literally physiological and structural things happening within the brain that make it not work, just like if your knee doesn't work or you're limping because you've got a meniscus tear. But now we're able to start to image those things, to see those changes in patterns, and to to actually treat the the structure and function of the brain through a a multipronged approach.

Most psychiatric illnesses are inflammatory problems in the brain. So if you have inflammation in your knee, it hurts. But if your brain doesn't hurt, it just creates all these crazy psychiatric symptoms. I think this is, like, a really paradigm shifting moment where work like yours have have really sort of pushed the envelope and say, yeah, hey, wait a minute. Like, we're thinking about mental illness all wrong, and looking at the wrong end of the stick.

And to me, that's exciting because so many people are suffering, but it's not happening fast enough. You're involved in the whole field, but I I think there is and there is funding now going into research. And I think in Texas, there's $50,000,000 allocated for research effort on iBeGain, which is like I was sort of shocked to see. And your work is kinda taking it to a new level. And the other thing that I think, you know, we're we're in now is this both metabolic nutritional psychiatry revolution and this psychedelic psychiatry revolution.

They're two, I think, synergistic. I'd like to see them all work together more. The question, you know, in psychedelics is there's a lot of them out there, and people I think maybe are confused. There's MDMA, there's psilocybin, there's LSD, there's ketamine, you know, and now there's ibogaine. And probably people are less familiar with ibogaine, but it seems to be significantly different in its effects than many of these other psychedelics, which have a lot of benefits.

So how is it how is it different from other psychedelics mechanistically and and even experientially for people?

Nolan Williams
To your point, there's a there's a wide range of psychedelics to you know, right now, there's not really an approval for any classic psychedelics. You know, there's no and that you know, there is some interest at the level of the current administration in in the health and human services secretary and all of that as far as kinda getting that done. But as as of now, you know, there's not there's not an approval. And so there's, you know, there's a lot of trials around MDMA for PTSD, psilocybin primarily for depression. People are trying LSD for generalized anxiety disorder, other things.

And Ibogaine is probably the the latest person to the party or, you know, whatever to the party in the sense that the But

Dr. Mark Hyman
it's plant to the party.

Nolan Williams
Yeah. The latest the the last plant to the party. The the the reason for that is because ibogaine has the most complexity to it and and the most inherent risk to it. And so the problem with ibogaine as an inherent risk problem is that it has this cardiac risk. Right?

So it actually will prolong the QT interval. For people that don't know, it's a kind of a part of the physiology of the heart. Lots of drugs do that. Antipsychotics do that. Right?

Geodon, for in particular, does that at at a great degree, so it's not a unique you know, within psychiatry, lots of drugs that do that. Within medicine, as you know, there's lots of drugs that do that. But, you know, it it prolongs the QT quite a bit for a very short period of time, And there have been there have been a couple of deaths, you know, because people are getting administered Ibogaine in unmonitored or minimally monitored settings. And so the problem with doing Ibogaine research is that, you know, it's it's been a problem of how do you do a study with a drug that you don't have any human data on because everybody's scared to do the study because of of the kind of case reports of risk. So we started, you know, the work that we did actually studying people that were already going to Mexico to to take Ibogaine.

Right? So they were already headed down there. They were already kind of consented to go down there. And then our job was, you know, simply to kind of do an observational study around that phenomenon that was already happening. And and that allowed us to get some data and enough public visibility to then be able to justify what's going on now, which is to try to get an IND to do this in The United States and all that stuff.

And so, you know, people have a varying degree.

Dr. Mark Hyman
IND is just for people listening as investigational new drug application. So how do we go to the FDA and ask for permission to study something? You need an application for

Nolan Williams
that. You need an application and and there's a chicken and egg problem of of, like, how do you take such a complicated drug and get an IND? And so there's a lot of that that goes on, and so people have had a hard time doing this. And you could say, well, you know, there's this is a drug with with risk. You know, should we be doing this or not?

The reality is is that, you know, there are drugs that are more risky from a heart standpoint that are already approved by the FDA than Ibogaine. And so Tecosyn is a cardiac drug. And if you ask the electrophysiologists, know, you cardiac electrophysiologists, and and you show them the Ibogaine data, they say, well, this is a risk, but Tikosyn is just as much of a risk, and we've gotten approval for Tikosyn. And so what ends up happening, which is really interesting, is I think what has happened with Ibogaine is because of the stigmatization of mental illness and the issue of how to think about it, people end up being in a scenario where they're looking at this and they're saying, is this problem that you have worth the risk? And Tikosyn's used for, like, atrial fibrillation and for for Yeah.

For for other kinds of arrhythmias. Yeah. And so people say, well, this has a one in one hundred risk of of a torsades event, but, like, if we don't do it, then somebody's gonna die from a stroke from A fib, so we can justify this risk with that risk.

Dr. Mark Hyman
Yeah.

Nolan Williams
Right? And the and and we know in in opiate use disorder that there's gonna there's a huge overdose risk in a person that's untreated. And so we're the problem at a fundamental level is we're saying, well, by not allowing you to study Ibogaine, you're saying, well, this risk isn't actually real or it's personality or whatever it is, whatever kind of justification that we come up with. And that justification allows us to say, no, actually, we're not gonna study this. Right.

Dr. Mark Hyman
Instead of understanding how many years of quality of life are lost, which is a real metric, quality of years

Nolan Williams
Yeah. Absolutely. Or or or real death risk.

Dr. Mark Hyman
You know? Risk from overdose. Yeah. It is a bit bit of a double standard because it's I think it's part of the bias in stigmatization of mental illness. It's not a real thing, you know, your your heart arrhythmia is a real thing, but but your depression is not a real thing, and your PTSD not a real thing.

But, yeah, it's it's amazing. And and so they work not just differently in terms of the effect on this risk, which is why it's different, but it has profoundly different effects on the brain that are are very different than many other psychedelic. I mean, if the fur the first story I heard about it was, you know, maybe fifty years ago, there was some drug addict who was in Amsterdam and Yep. Somebody said, hey, try these cool pills, man. And he did.

And the next day his addiction was gone. His cravings were gone. So that was sort of the beginning of the understanding it's affecting addiction medicine. But but it's just got all these broader effects. So it's it's different than than and seems to be longer lasting and more powerful in terms of resetting the brain, and then then sort of like almost a neurochemical reset than than many of these other compounds, which work but don't have these persistent lasting effects as much.

Nolan Williams
Yeah. So Howard Latsoff was the first so so just in the history of all this, you know, we know that we were using this for at least three hundred years, you know, prob you know, most likely much longer than that. The French started discovered this in the Western world in about 1900. It was on the French French formulary from 1930 to 1966, and it was actually a lower dose called labyrinth and was, like, a daily microdose, essentially. And so we there's thirty six years Oh,

Dr. Mark Hyman
wow.

Nolan Williams
For attention problems and depression and things like that. Wow. And so for thirty six years, it was used by the French and then placed on the French version of the Controlled Substances Act in '66. And and it, you know, and it was put on The US 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 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.

Dr. Mark Hyman
It's not a party drug.

Nolan Williams
It's not a party drug. So it it it stops self administration, and, you you know, it has this this profound, you know, 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 US Controlled Substance Act, schedule one substance, which is where it stayed, you know, since then and really prevented folks from using it. And so Howard Lhotsov had the story that you're describing, had this resolution of his addiction and spent his entire life trying to get this, you know, kind of out of the off the controlled substances list and as a therapeutic.

And it's a very complicated timeline for folks to to kinda get through. And 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 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 the idea that we make plants illegal and then make them inaccessible for science is like it's a in three hundred years, we're gonna look at that and think that's just the craziest thing, I think.

Dr. Mark Hyman
Yeah. And we we have to study these things. And, you know, if if if the initial data that you've done and others have done, actually bear bear out to be true, it's it's revolutionary in psychiatry. And I hope so. I mean, I think it could really, you know, impact this incredible degree of trauma and PTSD and depression, anxiety, traumatic brain injury.

That's even fun fascinating to me, the brain injury stuff. But the 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 and, you know, it just it's almost seems too good to be true how this works. But it does it does have to be administered in a way that's safe because it it 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 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 card.

If someone comes in with cardiac arrest, you give them all these drugs, you give epinephrine, you give them this drug, you give them that drug, And then finally, like, if every other drug fails and they're still in this terrible arrhythmia, you give them IV magnesium. That's right. That's right. That's That's right. I'm like, why don't we start out with that, you know?

That's right. You know, I've given a lot of IV magnesium in my life. It's very safe. We use it all the time in medicine for preeclampsia or hypertension pregnancy, for preterm labor.

Nolan Williams
Yep.

Dr. Mark Hyman
And doctors don't somehow think of it as a, you know, as a 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, it brings it to also caffeine, alcohol, a lot of things that we do actually cause us to deplete magnesium. 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 if it's done in a controlled way.

And that that's mitigated all those potential risk if you've never had a case in the magnesium administered patients that you've used. I begin with. Right?

Nolan Williams
I mean, I, you know, I I personally don't administer it. I just talk to talk to folks in in places that do, and what they what they tell me is that, for instance, one clinic wasn't really using it until a couple of years ago, you know, and they'd had a, you know, a bad outcome, and then they, you know, started using it. They hadn't had any cases since then. And the and the rationale is, you know, as you as you point out that magnesium is actually the treatment in the American Heart Association guidelines treatment for for torsades, the fatal arrhythmia that's the result of 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 wanna even call it that, is that you're bathing the heart in in this kind of stabilizing agent so that when the Ibogaine interacts with the 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. And that's the idea because the drug, you know, 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 to stabilize the heart, you can prevent this from happening.

Dr. Mark Hyman
Right now, you know, there there's it seems to me we're just sort of at this beginning of the sort of a phase of research which is gonna 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 gonna 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?

Nolan Williams
Bunch of different answers for that. But, you know, the kinda short answer is, yes. I I I can't foresee a time when ibogaine isn't gonna be a monitored drug. Now Ibogaine at the current doses that people use, the kind of what we call flood doses. Now the the deal is 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 the the 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 you need to have this experience? Or can you just have an agent that just changes brain plasticity and that's it? So that's a TBD sort of question. But that may be a way to do it. There are other alk you know, Ibogaine alkali 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 be and there's some, you know, very early kind of anecdotal data around this that people with with Parkinson's and that sort of thing taking micro doses actually show improvements. And so it's one of these things where the the Texas effort's gonna be important to really hashing out what what this is.

Dr. Mark Hyman
You know, the these effects of dopamine and other things are are powerful. The ability for us to sort of navigate different mental illnesses with these drugs is is fascinating to me because we never really had these the drugs that are or compounds that are so diverse in their effects and affect so many different conditions and have such a a magnitude effect greater than what we have. So may maybe you could spend a minute sort of talking about your more recent study in magnesium and Ibogaine and 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 the sort of physiological change that you saw with looking at functional MRIs and EEGs and other other assessment techniques. Because we'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.

Nolan Williams
So ibogaine is is a a compound that 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, we 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 the you can take a brain MRI and you can have AI guess a brain age. You can scan them the second time, it'll be very close to the first one.

You scan them a third time, it's gonna 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, know, you're a you're 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.

Dr. Mark Hyman
You're talking about me specifically? Yeah. Yeah. I'm 65. I hope it's younger than that.

That's what I'm saying.

Nolan Williams
Right? So let let's say let's say we scan your brain and maybe maybe your brain is 55 Yeah. And that's what AI and and so it's not very good at predicting what the chronological age is because that 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. And if you scan them three times, you're gonna 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.

Dr. Mark Hyman
Wow. And compound if you keep doing it?

Nolan Williams
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. But 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.

Dr. 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.

Nolan Williams
Yeah. And it and it may actually make sense

Dr. Mark Hyman
We're talking about,

Dr. Mark Hyman
like, one dose, one day having an effect to reverse your brain age by year and a half at a month. That's pretty remarkable.

Nolan Williams
Yeah. I mean, it's it's a, you know, it's an open question in the sense that, you know, you need to, you know, we need to do the work, but what you don't see is much of a change right after. And so what 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 gonna be able to change the brain in five days or whatever. It's gonna take some time. The the one of the

Dr. Mark Hyman
things that I I heard is that the there's a metabolite of ibogaine called noribogaine Yep. That lasts longer. And I I'm wondering if that explains some of the the tale of these effects of the addiction and inhibition, withdrawal inhibition, and maybe some of these other deeper neurological effects. And and that and I don't know

Nolan Williams
if that noriabagin has the same cardiac risks or if anybody's looking at studying that. So noriabagin does have a similar cardiac profile. Ibogaine is metabolized into noribogaine normally through two d six. And so you see people with getting ibogaine, and they they metabolize to noribogaine in in roughly twelve hour eight to twelve hours or something like that. And 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 give out noreibogaine as a treatment? And that's an open question, you know, and that work needs to be done. The the issue I think with noreibogaine, if you think about PTSD is that the ibogaine seems to be the thing that produces the earlier life re remembering stuff, not the noreibogaine part. Interesting. So the life review, watching a movie

Dr. Mark Hyman
of your life, seeing what happened, remetabolizing it in a way that allows you to be at peace with it and kinda move on from that Yeah. Doesn't happen with the norebugine. It happens with the With the

Nolan Williams
that that's 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 wanna have the you know, if the goal is to have the experience drive some of the therapeutic effect, then it probably requires the IBN. 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 of the PTSD improvement. So if you take that out Yeah.

You may be taking out at least Some

Dr. Mark Hyman
of the benefit.

Nolan Williams
Some of the at least the PTSD benefit.

Dr. Mark Hyman
I have this theory, and I I wanted to know if you've ever thought of this, which is when you look at the global population and you look at, you know, the obesity epidemic, it's it's staggering. There's over two and a half billion people overweight in the world. Obesity is exploding across the planet. And in America where, you know, seventy five percent of us are overweight, forty two percent are obese. The Yale food addiction scale is a way of measuring food addiction.

And Kelly Brown and others developed it. And fourteen percent of the global population is addicted to food. Including fourteen percent of kids. Yeah. You know, that's about the same as alcohol.

Alcohol addiction is about fourteen percent. And I wonder if if, you know, everybody's talking about Ozempic and and jumpy ones, but could this be like a unlock for people with with food addiction who are addicted to sugar, who are struggling, who 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, you know, how does somebody eat a, you know, a whole sheet cake? I couldn't never do that, but people do. And I think that, you know, is an application. It seems to be a multibillion dollar application.

Nolan Williams
So our data, we we also collected alcohol use. And what we found was and we're gonna publish this soon that people's alcohol use really precipitously dropped almost close to to zero. And so just to you know, almost everybody just really dramatic improvements in alcohol and and maintained it. And so and we've 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, no. 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 wanna drink coffee anymore. They really didn't and so so I always think that so placebo is expectancy. Right?

And the degree of the ex expectation that you have about how a drug is gonna 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 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. Pretty amazing.

It looks like it was driven primarily by by expectancy. And so if the person's being told in medicine, I'm gonna do this thing, and when I do this thing, this that thing that I'm gonna do is gonna drive this outcome, then the person has this expectation of that outcome. And and that's hard. Right? Like, somebody's going down there and they think this is a TBI treatment or whatever it is, then it's hard to 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. Yeah. Or now everybody stopped drinking alcohol. And if you ask them their pre treatment kind of pretest probability of any of that was gonna happen, they'd tell you no.

Like, they they'd say, I I didn't know that was gonna happen. Yeah. They all just came back fascinated with this thing that happened that they didn't have any expectancy for.

Dr. Mark Hyman
Yeah.

Nolan Williams
You know, we don't know for sure, but the signal is certainly there. The this this appears to be, you know, if if you kinda read the the 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 opioid use disorder because those are the kinds of folks that are, in many ways, desperate enough to to have taken ibogaine in the last several decades.

Dr. 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 as my guess, right, with ibogaine?

Nolan Williams
Yeah. I mean, the yeah. Nobody that I know of. Yeah.

Dr. Mark Hyman
I think it could be an interesting offshoot study. Like, does it does their food behavior change? Does their cravings for sugar change? Does their you know, like because I think it's like that that I mean, you're talking about opioid addiction killing seventy thousand people a year, but the food addiction part, you know, kills a lot lot more. You know, chronic disease related food is, you know, killing million plus people a year Hundred percent.

In America.

Nolan Williams
So it's like

Dr. Mark Hyman
to be I think it'd be an interesting little kind of side hustle to kinda look at that in in your data and see what happens if people change their diets or they change their weight loss. Like, there's other things you can look at. So encourage you to check that out because I have this theory. But if if it because if it works, it's a it's a big unlock, you know, and it probably a lot a lot better than taking Ozempic. So I wanna I wanna 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.

And with with Ibogaine and some of other psychedelic therapies, we're talking about, you know, eighty to ninety percent 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?

Nolan Williams
Yeah. I mean, the so the degree of the effects that we observed were were quite striking. The, you know, the data is limited, you know, 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 gonna be helpful.

In this hypothetical future scenario where, you know, you're right and this is this these are the degrees in which people change compared to conventional treatments, it's a 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 you're talking about a two to three point difference on a 60 scale, and the inner rater reliability on that scale is two points.

Dr. Mark Hyman
Yeah. So, basically, it's like nothing.

Nolan Williams
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 than in the placebo group. I'm not arguing that, but, like, it's the yeah. The the observer, you know, differences are that level. So it's very hard to discern if if you've got totally skilled raters and they have that problem how effective these drugs really can be.

Dr. Mark Hyman
So those are not, but then the Ibogaine is far more.

Nolan Williams
Yeah. I mean, we're seeing, you know, in some cases, a 20 or 30 change on a 60 scale where that scale as a generality people don't really score above mid thirties on. On the on the Montgomery Asperger depression rating scale, that scale doesn't have a if you're you're above thirty, thirty five, 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, you know, 20 change in a lot of people on that scale.

Dr. Mark Hyman
The the the use case for this drug is is across, like, a whole bunch of different issues that that seem not necessarily related, like, what does brain injury have to do with PTSD, have to do with depression? And how do you think that the the we sort of so you 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?

Nolan Williams
It's an open question, you know. I think we've gotta 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. You know? 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? And so those two epilepsy syndromes in kids are really devastating. Sometimes kids have two to 300 seizures a day. You have to put them on potassium bromide, which is like what we give dogs for epilepsy. Yeah.

You know? And and you end up being in a situation where, you know, kids still seizing. And so the 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.

Dr. Mark Hyman
Wow.

Nolan Williams
Right? And so they were administering On their own. On their moving to at the time, moving to Denver. This was, you know, Sanjay Gupta did, like, a special on this fifteen or twenty years ago. So all these families that with Lennox Gastaut 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.

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 kid's potassium bromide and all this stuff, and then you give them high dose CBD and they wake up, you know, for the first time. And so what c 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. Yep. And I think that's what's gonna happen with with these ibig these iboga alkaloids. Right?

Is that we have to

Dr. Mark Hyman
The only thing is just the whole plant is 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 port parts, and then it doesn't necessarily have the benefit of the whole plant.

Nolan Williams
That is the open question. So there's a there's gonna be an experiment on this, you know. Colorado is gonna is basically gonna 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's gonna die and you give them this thing and their and and their probability of dying goes way down, we should probably be doing that. And I think that's the like, so if 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 gonna do it no matter what I think. And so it's one of these things where that's gonna happen, and then there's gonna be a kind of a more pure Western medicine pharma play that's gonna happen for several. And and then there's this kind of organic chemistry thing where they're changing the molecule thing too that's maybe that's not even psychoactive. And I think we're we'll we'll get in totality the answer over the next ten years.

Dr. Mark Hyman
Yeah.

Nolan Williams
And and the reality is 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, it's we're not in a situation where none of them work, but that's possible too. But at least we we, you know, we gave it a a a college try for sure. But it's the beauty is I think that's all happening, and we're gonna be able to really actually sort it out, and fingers crossed.

Dr. Mark Hyman
Yeah. Pretty amazing. Yeah. This 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 the NDMA stuff is interesting because, you know, that's undergoing a phase c trials and other 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, I b g, not needing the psychotherapy component. Do people need follow-up, support, treatment integration? Is it is it have to be done in a psychiatric context where there's more continuity of care? It's just like go in and take it, close your eyes, wake up twelve hours later, and that's it.

Nolan Williams
So there there is a there's a pre post therapy requirement. There's a within dosing therapy non requirement, it appears. Right? Although, 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 you've you've studied is if you if you give somebody MDMA, they have a a positively valenced experience. Yeah. Right? Have this they feel good, and they feel good about, you know, the the people around them. And they feel good about the memories they've had.

And so if they look at traumatic memories, they're gonna see those memories from kind of a an alternative perspective because they're seeing the world through a lens. And and I think that's very useful as a tool. I think it's also very tricky as a tool. There's a analysis of the, you know, events that happened in Israel with the with the rave. Yeah.

Right? And in that situation, there was a certain percentage of those people who are actually on MDMA. I don't know if you know about it. Yeah. 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 The mosque came in and

Dr. Mark Hyman
terrorized Nobel festival in Israel on October 7, and the people who took the MDMA were less traumatized after than the ones who didn't.

Nolan Williams
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 gonna happen or tell them what that 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 kinda get through. And 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 Yeah. For themselves mentally. Yeah. That they need help with, generally.

And they yeah. Basically, all need help with. Yeah.

Dr. Mark Hyman
I'm fascinated because, you know, the there's effects on disease states or, you know, things that are problematic for people, like PTSD, traumatic brain injury, depression, etcetera. But then there's the brain enhancement component. And I I know a number of people have gone down there into Mexico and didn't have these problems, but use 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 as a sort of an enhancement drug?

In other words, that it it doesn't just treat disease, that it may actually improve your overall cognitive function, memory, mood, neuroplasticity, and neurogenesis, and things that that, you know, we all would like to have better brains. Right?

Nolan Williams
Yeah. So what we observed in the veterans was that they had a improvement in 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 gonna see that too. But, you know, at least you can see in a 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.

There'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, you know, it's gotta be studied.

Dr. Mark Hyman
Yeah. It would be interesting as it just it's more of like a longevity enhancement drug. And we we don't really think much about those things in medicine at all. We 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. Right?

Probiotics, for example, is something that can optimize health as opposed to an antibiotic. Yeah. 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? Yeah.

And this seems like it has that kind of potential.

Nolan Williams
What really need to understand, I think, is why were the Bouilleti taking this for hundreds of years? You know? And why did the French think this was helpful for thirty six? 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 you have a even in the thirties to '66, you know, which is kind of a different era, obviously, to have a drug on the formulary for thirty six years that that would you know, wasn't doing anything for the French. It seems unlikely. It's possible.

But unlikely that that that would have stuck around and been sold for thirty six years. And so my suspicion is is that there were some disease treatment effects, but maybe maybe these effects too. Who knows?

Dr. Mark Hyman
Yeah. I wonder if there's any people around who took it back then who who are in their nineties probably now from from what the effect on them. I I I think this is such an exciting moment, in psychiatry and medicine. And I think, you know, a lot of people are 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 there's really this is like a whole revolution. And I I wonder if you've if you've thought about, you know, combining the things that you're doing with other kind of metabolic psychiatry stuff that your colleagues doing at Stanford around nutritional psychiatry and metabolic psychiatry and and combining both modalities as a way of even improving health outcomes and mental health outcomes.

Nolan Williams
A 100%. Yeah. I mean, I think we I've taken the stance that if you look at, like, MI care, people having a heart attack, what do we do now? We we throw an aspirin. We throw a statin.

We we, you know, we we we do a heart cath. We do all these things in summation that all independently were shown in isolation to benefit. Right.

Dr. Mark Hyman
We we pay a cocktail therapy as opposed to a single therapy.

Nolan Williams
Right? The challenge, right, right now is to we're in cardiology nineteen fifties. Right? So we're having to we maybe have a pacemaker or we have, you know, 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 and do the trials in each one of the tools. Now, for my kids or, you know, whatever the the, you know, the folks that are gonna end up or my students or your students, the 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 gonna be the way we deal with things in the future as we say, okay. Well, we're gonna, you know and you're doing a lot of this already. We're gonna measure all of these things. We're gonna modify your diet, your metabolic, know, all of that good stuff. We're gonna do brain based things.

I think the interesting question ultimately is if we're in such a diseased 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? But 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, 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, one 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. Oh, yeah. I mean, it's huge. I mean but I I don't think that the dietary change alone or nutritional metabolic changes alone can can do the kinds of

Dr. Mark Hyman
things that these these psychedelic compounds do. Yeah. And what's fascinating is we've sort of and this always fascinates me. I don't know if you have theory about this, but how how is it that all these plants have compounds that interact with our biology in these profound ways that change us. And 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. Oh. It's ayahuasca and, you know, should be both Indians in South America or peyote in North America

Nolan Williams
or whatever. If you look at the thinking that the 17 hundreds physicians had about vitamin c containing fruits, like citrus fruit, and the way they thought about it as it relates to scurvy, you kinda 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 this was considered a South American or an African exotic plant.

And so most of the physicians that they actually rejected citrus fruit as a treatment for scurvy. And so, as you know, the story of anti fruiters. Right? There were lots of people in the British Royal Society that said that the that the limes and lemons may actually be making scurvy worse. And I think that's the situation that that we've 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 the man 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 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 that's the way we've been looking looking at plant based psychedelics for a long time, and hopefully that changes.

Dr. Mark Hyman
Pretty amazing. And this and and and the the sort of I keep kind of doubling down on the magnitude of size of the effect, and I wanna sort of double down on it because I think you when you look at the 30 special ops, you know, special forces veterans who had brain injury, you know, you've had really large effect sizes, you know, like the disability ratings dropped dramatically from moderate disability to, like, no disability. You had PTSD dropped by eighty eight percent, depression dropped by eighty seven percent, anxiety by eighty one percent, improved cognition. Seems like too good to be true. Right?

Nolan Williams
When my postdoc showed me the data, didn't believe them, and I told them to go back and reanalyze it. Yeah. You know? And so we, you know, we that's why I I don't I don't make claims about it, you know, because I I think that we have to at least be replicated by another group in order to justify. So we need to be replicated by another group in order to justify it.

Now I'm hearing from my colleagues in in out of Texas that they are seeing very similar effects. Right? And so I want them to formally see that Yeah. If that's what it is, and publish that. And then and then we can say it wasn't, you know, our site or whatever, that 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, but it would be unusual to have that level of an effect for for this sort of level of expectancy.

Dr. Mark Hyman
I mean, they didn't expect that big of a change, so they would you're less likely to see it. Yeah. The veterans had have you followed them ongoingly, and they still have the lasting effects.

Nolan Williams
So we have day data out to a year. It isn't published yet. It's kind of in review now, And that looks really good. Most people hold it.

Dr. Mark Hyman
And you're 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?

Nolan Williams
If you think about psychiatry and epochs, you know, the first one being talk therapy, and and we learned something important there that spoken word can have effects on, you know, mental states and effect you know, and and and now more recently, suggesting that it's having effect on the brain itself. And that's that was useful. Psychiatry two point o, this idea that pharmacology can have an effect at the level of synapse, and that was also very useful. Right? I got a lot of people would say schizophrenia out of asylums and that sort of thing.

You like Thorazine? Yeah. Like Thorazine. Yeah.

Dr. Mark Hyman
Yeah. Chemical straight jackets, we call them.

Nolan Williams
And then psychiatry three point o, this idea that you can actually look at the psychiatry one point o and two point o 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.

Dr. Mark Hyman
Yeah. Electric shock therapy.

Nolan Williams
Yeah. Can you use insights from before and make things much safer and better and much more tolerated with patients? And that's really that's really been, I think, the emphasis for our work. And so when we look at IBM, we're looking at it from the lens of the circuit. When we're looking at, let's 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 need 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.

Dr. Mark Hyman
Amazing. Well, we're 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'm like, this is just nuts. And I don't mean that as a pun.

I just mean the way we treated people, the the amount of suffering that's going on, the the 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, wow.

You know, can I try it? What do I do? What if I wanna 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, Ambeo and also Mexico. There's there's a few places out there. What do you say to people who wanna go sort of explore this? Who

Nolan Williams
Yeah. I mean, the good news is is that we, you know, it looks like there's actually gonna be some US trials soon, you know. And so being able to do this from inside of The US is is kind of the ultimate goal. You know, folks go to these places and, you know, these other countries, but the the ultimate goal is is is really to see that that folks can do this safely in The US. And so I think, you know, five, ten years ago, I would 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 the hope is is if everything goes to 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 Let's see what happens. And see what happens.

And so it is is coming soon. You know? We'll have to see what happens with the FDA. But but, yeah, I think that's that's an exciting moment for folks in, you know, being able to to have access to to an experimental therapeutic like this.

Dr. Mark Hyman
And and if people wanna go down and try this in Mexico, do you advise against it? Do you say it's your own risk? Could you

Nolan Williams
It's definitely people's own risk. I mean, I look. It's it's one of these things where we still don't know that much about this. Like, in our in our Stanford study, we're really clear with people that they had to have already signed up to have anything to do with

Dr. Mark Hyman
Couldn't encourage them to do it. Yeah.

Nolan Williams
Yeah. We couldn't encourage them to 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.

Dr. Mark Hyman
I wanna 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 Mhmm. Which is personality disorders. Yeah. Borderline personality, narcissistic personality, schizoaffective. 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 iBGain experience has any impact on these more embedded, like, deep seated traumas that are harder to undo?

Nolan Williams
It's a great question. I mean, the, you know, the Hopkins group demonstrated this profound personality change that they observed out to a year, I think, early on with their trials of psilocybin. And so there's definitely data that there's personality change, you know, in and around psilocybin use. It's an open question. And the 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 they're religious or not.

And so, actually, people that I think it was, like, sixteen percent of people were not religious prior to to taking Ibogaine, and and there's a increased kind of sense of of a higher A higher power. Or 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.

Dr. Mark Hyman
Is it dangerous for these people to do anything?

Nolan Williams
It's certainly dangerous for people with with a psychotic history, you know. I think people with bipolar disorder, that's gonna be dangerous. Maybe somebody with severe borderline, maybe, you know, it just depends. It depends on a kinda individual basis. The problem at a fundamental level is we just haven't studied this enough to really know.

Dr. Mark Hyman
We don't have enough data sets to know what's going on with these people. 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?

Nolan Williams
We have to do we have a lot of work to do to kinda 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. That's a psychiatric.

Purely psychiatric or dementia. One out of two. One out of two.

Dr. Mark Hyman
That's a lot. Half of the population of the world is gonna have some mental illness at some point in their life.

Nolan Williams
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.

Dr. Mark Hyman
Definitely not through therapy.

Nolan Williams
Definitely not through therapy. You'd have to have half the world become I mean, maybe with AI, you know, all of us are trying to figure out.

Dr. Mark Hyman
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 gonna do a podcast about soon, that that also is is another unlock, I think, in terms of mental health. 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, then you could have a easier time doing doing that other hard work. What studies are on the horizon for you that you're you're looking at doing?

Nolan Williams
We're looking forward to seeing what happens with 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, you know, what's gonna happen with the FDA. And 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.

Dr. Mark Hyman
When you say biology, you mean biomarkers, blood tests, or and what what would be the thing you're looking at in addition to functional MRIs and the EEGs, which are brain imaging and brain electrical studies?

Nolan Williams
We hope to do, you know, some of that, at least the EEG side of things. But, yeah, it's a it's a great question, maybe something interesting to talk about later, but, you know, around is there blood, you know, any kind of blood based biomarkers that would be of interest to because we'll have IVs in everybody, you know.

Dr. Mark Hyman
Fascinating work. Incredible what you're doing. It's you're definitely going out a limb in a psychiatric world. I think, you know, you're brave and, you know, but you're at Stanford and respected institution and they seem to be in support of you doing this work, which is amazing.

Nolan Williams
Yeah.

Dr. Mark Hyman
And, it it you know, we need a Hail Mary in psychiatry because, we are in a bad state as a world. We're all divided and disconnected and isolated and struggling with various forms of just anxiety of living in the twenty first century to more serious mental illness. And the unlock that you and your colleagues are trying to get with this work in the whole psychedelic field is just amazing. So thanks for

Nolan Williams
doing what you do. Yeah. Thanks for having me. Yeah. Good to see you.

Dr. Mark Hyman
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