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[00:00:00.320 --> 00:00:02.000] Coming up on this episode of the Dr.
[00:00:02.000 --> 00:00:15.920] Hyman Show, what you said blew my mind, which is that there's this compound out there that can abruptly interrupt a withdrawal from addiction that can help treat PTSD, depression, traumatic brain injury better than anything else we have out there on the market.
[00:00:15.920 --> 00:00:17.520] And orders of magnitude more.
[00:00:17.520 --> 00:00:17.840] Dr.
[00:00:17.840 --> 00:00:23.840] Nolan Williams is a triple board-certified neuropsychiatrist and founder of Stanford's Brain Stimulation Lab.
[00:00:23.840 --> 00:00:31.600] He's redefining how we treat depression, PTSD, and addiction using brain stimulation, psychedelics, and neuroscience instead of meds.
[00:00:31.600 --> 00:00:40.400] 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.
[00:00:40.400 --> 00:00:48.400] I think this is like a really paradigm-shifting moment where work like yours have really started to push the envelope and say, hey, wait a minute, like we're thinking about mental illness all wrong.
[00:00:48.400 --> 00:00:51.280] We're talking about like one dose, one day, having one dose.
[00:00:51.280 --> 00:00:54.080] It's a effect to reverse your brain age by a year and a half out of a month.
[00:00:54.080 --> 00:00:55.200] That's pretty remarkable.
[00:00:55.200 --> 00:00:56.800] Is it dangerous for these people to do?
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[00:02:50.360 --> 00:02:52.520] All right, Nolan, great to have you on the podcast.
[00:02:52.520 --> 00:02:53.240] Thanks for being here.
[00:02:53.240 --> 00:02:54.040] Yeah, thanks for having me.
[00:02:54.360 --> 00:02:55.640] You know, I followed your work.
[00:02:55.640 --> 00:03:17.960] 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 a withdrawal from addiction, that can help treat PTSD, depression, traumatic brain injury better than anything else we have out there on the market, and orders of magnitude more.
[00:03:18.280 --> 00:03:26.680] And I became very interested in following this conversation about this incredible compound called ibogaine that we're going to learn more about today.
[00:03:26.680 --> 00:03:33.080] And it comes from a bark of a tree in Gabon, in West Africa.
[00:03:33.080 --> 00:03:38.440] It's used in ritual ceremony there for different kinds of ritual transitions through life.
[00:03:38.440 --> 00:03:40.840] It's got a fascinating history.
[00:03:41.000 --> 00:03:46.960] I maybe would love to start by helping us understand, you know, what is it exactly?
[00:03:46.960 --> 00:04:03.920] 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 public 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.
[00:04:03.920 --> 00:04:08.640] Because, you know, the truth is, one in four people have had sexual abuse, which is crazy.
[00:04:08.800 --> 00:04:13.840] Trauma is a real thing, whether it's micro-traumas because your parents neglected you, or big traumas.
[00:04:14.080 --> 00:04:17.280] Gabbar Mati talks about big tea, little tea trauma.
[00:04:17.280 --> 00:04:28.400] 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 fulfilled life.
[00:04:28.400 --> 00:04:31.760] And, you know, psychiatric medicine is just very antiquated.
[00:04:32.000 --> 00:04:33.200] It's very crude.
[00:04:33.520 --> 00:04:37.760] It's tremendous side effects of the drugs we use.
[00:04:38.000 --> 00:04:40.640] Many of them don't work very well.
[00:04:40.640 --> 00:04:46.400] And we're kind of in this unfortunate situation where mental health crisis is bigger than ever.
[00:04:46.400 --> 00:04:49.040] We have fewer things that really work.
[00:04:49.040 --> 00:04:52.640] And this seems to hold the promise of something really quite different.
[00:04:52.640 --> 00:04:54.960] Yeah, thanks for the intro there.
[00:04:54.960 --> 00:04:58.000] Yeah, it's an interesting compound.
[00:04:58.000 --> 00:04:59.360] It's been around for a long time.
[00:04:59.360 --> 00:05:07.840] It's an African root bark psychedelic, as you suggested, from Gabon and Central West Africa, so kind of neighboring areas.
[00:05:07.840 --> 00:05:12.800] And the group of people that use it are called the Buiti.
[00:05:12.800 --> 00:05:18.080] And Buiti just means that you've taken Iboga and rituals ceremony, right?
[00:05:18.080 --> 00:05:23.680] And so folks have been doing this for quite a long time.
[00:05:24.000 --> 00:05:32.680] And they've been doing it because it has a, it produces this kind of what people would call a transformative psychological experience.
[00:05:32.840 --> 00:05:42.280] So people will go into this, they'll have kind of a massive change in consciousness over the course of, you know, 24 to 36 hours.
[00:05:42.280 --> 00:05:51.320] And during that time, they'll have a psychological experience of reevaluating earlier life emotionally salient memories.
[00:05:51.320 --> 00:05:58.520] And for maybe all of us, for a lot of us, those are trauma at various scales, you know.
[00:05:59.480 --> 00:06:11.800] And people will take a look at those earlier life kind of emotionally salient events, but they'll do it from a position, kind of a third-party position of seeing it from neutrality.
[00:06:11.800 --> 00:06:23.080] 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.
[00:06:23.080 --> 00:06:33.720] IBM seems, 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.
[00:06:33.720 --> 00:06:40.280] So you're not being guided, or there's no therapist.
[00:06:40.280 --> 00:06:44.200] The drug just automatically puts your brain into this mode, it seems.
[00:06:44.200 --> 00:06:51.240] And then people have what they call this life review or slideshow where they're looking at these emotionally salient memories over time.
[00:06:51.240 --> 00:06:58.520] And when they do that, they're able to see, they're able to see the, you know, the memories from a different lens.
[00:06:58.520 --> 00:07:10.680] 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.
[00:07:10.680 --> 00:07:12.760] And that's pretty powerful.
[00:07:12.760 --> 00:07:22.160] To your point, you know, psychiatric medicine has created tools that look a lot like you know medieval or 15th century whatever keys, right?
[00:07:22.160 --> 00:07:30.240] Like we've thought about the brain like a single-tooth key that you put the key into the lock and you turn it and the key unlocks the door.
[00:07:30.240 --> 00:07:37.840] But the brain is probably much more like a modern-day key with a lot of different pins and a lot of different interactions.
[00:07:37.840 --> 00:07:43.920] So when you put the key into the lock, it really needs to interact with a lot of different systems.
[00:07:43.920 --> 00:07:57.360] The problem with, in my view, with kind of current psychopharmacology and the way that we see it is that we still think that it's a single neurotransmitter or single receptor problem.
[00:07:57.360 --> 00:08:07.040] Serotonin's low, so take serotonin reptake inhibitors like Prozac or your dopamine's low, so take basically speed, otherwise known as Adderall or Riddle.
[00:08:07.280 --> 00:08:11.520] If you look at the pharmacology of Ibogaine, it's very broad acting, right?
[00:08:11.520 --> 00:08:19.600] So it actually interacts with a lot of, I mean, essentially all the neurotransmitter systems in a unique way.
[00:08:19.600 --> 00:08:50.400] 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 multi-site trials the sort of data that we're seeing now in our studies and studies coming out of that are going to 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 kind of a multi-receptor drug system is probably correct.
[00:08:50.400 --> 00:08:58.080] And this idea of a single neurotransmitter system, low serotonin or whatever, where we're simplifying things down is probably oversimplified.
[00:08:58.080 --> 00:09:00.000] You know, and those tools are too coarse.
[00:09:00.520 --> 00:09:10.040] You know, in medicine, we call these sort of multiple effect phenomenon pleiotropic effects, which means they work on many, many different pathways and systems.
[00:09:10.040 --> 00:09:24.680] You know, I want to get into sort of more of the applications of it and 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.
[00:09:24.680 --> 00:09:26.440] So it doesn't just change it in the moment.
[00:09:26.440 --> 00:09:41.640] It seems to have lasting changes, which is why, and I think we're still trying to figure out, you know, 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.
[00:09:41.640 --> 00:09:45.400] It's not like they're psychologically suppressing the withdrawal symptoms.
[00:09:45.400 --> 00:09:46.600] They just don't have them.
[00:09:47.000 --> 00:09:48.120] And that's really fascinating.
[00:09:48.120 --> 00:09:59.080] 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 overexcited with trauma.
[00:09:59.080 --> 00:10:02.040] It does affect somehow the serotonin system.
[00:10:02.040 --> 00:10:07.160] It affects brain factors like PDNF, which is otherwise known as brain-derived neurotrophic factor.
[00:10:07.160 --> 00:10:14.760] It helps stimulate brain growth and connectivity, neurogenesis, neuroplasticity, more brain cells, more connections between brain cells.
[00:10:14.760 --> 00:10:19.320] So they do all these really interesting things that repair the brain, to heal the brain.
[00:10:19.320 --> 00:10:28.360] 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.
[00:10:28.360 --> 00:10:30.920] So it seems to have all these varying effects.
[00:10:30.920 --> 00:10:36.120] And they also sort of inhibit what we call the default mode network, which is what a lot of other psychedelics do.
[00:10:36.120 --> 00:10:42.360] It's sort of the ego and the self-protection part of your brain, which is, you know, makes us feel separate and disconnected.
[00:10:42.360 --> 00:11:00.000] And when that is suppressed, whether you meditate for 40 years or you take psilocybin or LSD, MDMA, or Ibogaine, that quiets down quickly and 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 whole.
[00:11:00.000 --> 00:11:09.120] And that and so I kind of would love you to unpack some of the mechanisms and how they work in these different disease states because it's like seems like a one-size-fits-all.
[00:11:09.120 --> 00:11:13.360] You know, you got PTSD, you got depression, you got anxiety, you got trauma, you got brain injury.
[00:11:13.360 --> 00:11:20.640] Can you kind of unpack those for us and talk about how they affect across these various pathways in the brain?
[00:11:20.640 --> 00:11:21.920] Yeah, that's a great question.
[00:11:22.560 --> 00:11:30.960] So the other mechanism that we've thought a lot about that's unique to ibogaine is glial-derived neurotrophic factor, right?
[00:11:30.960 --> 00:11:40.720] So glial-derived neurotrophic factor is a neurotrophic factor that's involved with dopamine neuron kind of health, right?
[00:11:40.720 --> 00:11:43.840] And so it upregulates dopamine neuron health.
[00:11:43.840 --> 00:12:02.960] And so there was a study, you know, 20 years ago or something where they took mice and mice or rats and they trained 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 tube.
[00:12:02.960 --> 00:12:06.000] And if you take a mouse and you do that.
[00:12:06.080 --> 00:12:07.440] Oh, little rat bartender there?
[00:12:07.840 --> 00:12:08.400] Something like that.
[00:12:08.400 --> 00:12:10.880] Yeah, they pull up to the bar.
[00:12:10.880 --> 00:12:13.920] They'll drink until eventually they die, right?
[00:12:14.400 --> 00:12:22.400] And if you take a mouse like that and you give them ibogaine, you can actually reverse it.
[00:12:22.400 --> 00:12:25.840] They'll stop self-administering alcohol, which is cool.
[00:12:25.840 --> 00:12:41.000] 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.
[00:12:41.000 --> 00:12:43.480] They will stop self-administering.
[00:12:43.640 --> 00:12:50.120] Inject just ibogaine just into that area, you can recapitulate the effect, right?
[00:12:50.120 --> 00:12:57.160] And people have also shown that you can produce this effect by directly stimulating into those areas, right?
[00:12:57.160 --> 00:13:15.720] And so it's probably that at least the anti-addiction mechanism of ibogaine is that it's restoring dopamine function within that ventral tegmental area in a way that resets the reward system.
[00:13:16.360 --> 00:13:38.200] 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 in our trial that received ibogaine had EEG brainwave tests before, after, and one month after they received ibogaine.
[00:13:38.200 --> 00:13:47.960] And what we saw is this kind of general slowing of all of the kind of different power spectra of the EEG, right?
[00:13:47.960 --> 00:13:54.520] So people had a general kind of physiologic slowing of their brain after.
[00:13:54.520 --> 00:14:11.320] And the slowing actually was correlated with the strength of the trip, like the amount that they had a psychological effect, but also interestingly, the reduction in PTSD symptoms and the improvement in cognition.
[00:14:11.320 --> 00:14:15.200] And so, you know, that's, it's a first-step study.
[00:14:14.840 --> 00:14:20.080] You know, it was pretty good, I think, in the sense we got into nature mental health.
[00:14:20.400 --> 00:14:22.640] But, you know, we need to do some more work on this.
[00:14:22.640 --> 00:14:39.280] So I'm not claiming that this is definitive, but it's likely that if you have an EEG, you may be able to tune the dose to the physiology of the brain instead of getting a subjective readout.
[00:14:39.440 --> 00:14:48.160] 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?
[00:14:48.160 --> 00:14:49.680] So you're kind of, you know, fully.
[00:14:49.840 --> 00:14:54.560] Some people need more, some people need less, and you can tell by the EEG who needs what, and then can upper.
[00:14:55.360 --> 00:14:56.800] That would be the promise, right?
[00:14:56.800 --> 00:15:02.400] That would be, you know, if it plays out, that would be, and we do this already in medicine, as you know.
[00:15:02.400 --> 00:15:08.800] We use biz monitors and anesthesia to kind of measure the level of anesthesia.
[00:15:08.800 --> 00:15:17.760] Or if somebody is, you know, being fully anesthetized with like propofol, you can actually birth suppress them.
[00:15:17.760 --> 00:15:22.160] And you're using an EEG to help you dose a drug.
[00:15:22.160 --> 00:15:25.600] You know, so that's not a new concept in neurology.
[00:15:25.600 --> 00:15:28.560] It's just a new concept within kind of psychiatry, right?
[00:15:28.960 --> 00:15:32.000] And so being able to figure that out, I think, is useful.
[00:15:32.000 --> 00:15:39.040] Well, that's the old joke: neurologists pay no attention to the mind, and psychiatrists pay no attention to the brain.
[00:15:39.040 --> 00:15:44.400] And here you are, you know, looking at psychiatry through the lens of the brain, not just the mind.
[00:15:44.880 --> 00:15:51.760] Freud kind of took us down the path of mind-only psychiatry and talk therapy and psychoanalysis.
[00:15:52.080 --> 00:16:03.080] And it's sort of striking because, you know, you hear, oh, well, yeah, I've heard psychoanalysis say, well, you could come to psychoanalysis five days a week for the next 20 years and then you'll maybe see some improvement.
[00:16:03.720 --> 00:16:12.520] And here you're like, well, you can go to Mexico and do one Ibogaine journey and like that takes care of like 20 years of psychotherapy.
[00:16:12.520 --> 00:16:14.600] I mean, it's kind of crazy.
[00:16:14.600 --> 00:16:20.760] Yeah, I mean, you know, there's a lot of work to do to kind of totally prove that.
[00:16:20.760 --> 00:16:23.000] I mean, that's what, that's certainly what people will say.
[00:16:23.000 --> 00:16:32.360] That's what Claudio Naranjo said, I think, in, you know, the Argentinian psychiatrist many, many decades ago about Ibogaine.
[00:16:32.360 --> 00:16:38.760] It's just one of these things where we're going to have to do the work, you know, do the good work to figure it out.
[00:16:38.760 --> 00:16:54.280] But I think that the problem and the kind of 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.
[00:16:54.280 --> 00:17:05.480] You know, people can have an entire tragic life problem over the course of the time it would take, you know, for many of our treatments to work.
[00:17:05.480 --> 00:17:09.160] I mean, psychoanalysis for 10 years is one.
[00:17:09.160 --> 00:17:11.960] Just normal oral antidepressants, you know?
[00:17:11.960 --> 00:17:19.640] I mean, we've seen people start out an oral antidepressant and lose their job by the time it starts to have any effect, right?
[00:17:19.640 --> 00:17:30.360] 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.
[00:17:30.360 --> 00:17:45.000] It's kind of an exciting moment in psychiatry because 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.
[00:17:45.840 --> 00:17:58.720] And what's really exciting to me in psychiatry, because I've been thinking about this for decades, I wrote a book almost 20 years ago called The Ultra Mind Solution, which details how the brain is influenced by everything happening in your body.
[00:17:59.280 --> 00:18:04.640] And you can actually use those physiological levers to change psychiatric symptoms.
[00:18:04.640 --> 00:18:24.400] So if we 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 ascribe all kinds of meaning and we have all these stigmas against these things.
[00:18:24.400 --> 00:18:31.520] And, you know, if someone's limping because their meniscus is torn in their knee, we don't go, oh, you're a fuck-up.
[00:18:32.800 --> 00:18:37.520] But when someone has a mental illness, there's a stigma of, oh, there's something wrong with you.
[00:18:37.520 --> 00:18:40.160] Like, it's kind of, you're crazy.
[00:18:40.160 --> 00:18:41.040] It's your fault.
[00:18:41.040 --> 00:18:47.600] But actually, there's literally physiological and structural things happening within the brain that make it not work.
[00:18:47.600 --> 00:18:51.200] Just like if your knee doesn't work or you're limping because you've got a meniscus tear.
[00:18:51.200 --> 00:19:03.280] But now we're able to start to image those things, to see those changes in patterns, and to actually treat the structure and function of the brain through a multi-pronged approach.
[00:19:03.280 --> 00:19:06.480] Most psychiatric illnesses are inflammatory problems in the brain.
[00:19:06.480 --> 00:19:08.240] So if you have inflammation in your knee, it hurts.
[00:19:08.240 --> 00:19:13.520] But if your brain doesn't hurt, it just creates all these crazy psychiatric symptoms.
[00:19:13.600 --> 00:19:24.640] I think this is like a really paradigm shifting moment where work like yours have really started to pushed the envelope and say, hey, wait a minute, like we're thinking about mental illness all wrong and looking at the wrong end of the stick.
[00:19:24.640 --> 00:19:28.880] And to me, that's exciting because so many people are suffering, but it's not happening fast enough.
[00:19:28.880 --> 00:19:30.120] You're involved in the whole field.
[00:19:29.840 --> 00:19:33.000] But I think there is, and there is funding now going into research.
[00:19:33.080 --> 00:19:38.600] And I think in Texas, there's $50 million allocated for a research effort on Ibogaine, which is like I was sort of shocked to see.
[00:19:38.600 --> 00:19:40.840] And your work has kind of taken it to a new level.
[00:19:40.840 --> 00:19:49.320] And the thing that I think we're in now is this both metabolic nutritional psychiatry revolution and this psychedelic psychiatry revolution.
[00:19:49.400 --> 00:19:51.080] They're too, I think, synergistic.
[00:19:51.080 --> 00:19:53.240] I'd like to see them work together more.
[00:19:57.080 --> 00:20:01.400] When it comes to your health, knowledge is power because most of us are flying blind.
[00:20:01.400 --> 00:20:04.520] We're getting basic labs once a year and hoping everything's fine.
[00:20:04.520 --> 00:20:09.800] That's why I help build function health to give you access to the same testing I use for myself and for my patients.
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[00:21:58.560 --> 00:22:03.280] The question with psychedelics is there's a lot of them out there, and people I think maybe are confused.
[00:22:03.280 --> 00:22:20.800] 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.
[00:22:20.800 --> 00:22:27.600] So, how is it different from other psychedelics mechanistically and even experientially for people?
[00:22:27.600 --> 00:22:30.480] To your point, there's a wide range of psychedelics.
[00:22:31.680 --> 00:22:36.640] Right now, there's not really an approval for any classic psychedelics.
[00:22:36.640 --> 00:22:47.440] You know, there's no, and that, you know, there is some interest at the level of the current administration and the Health and Human Services Secretary and all of that as far as kind of getting that done.
[00:22:47.440 --> 00:22:52.000] But as of now, you know, there's not an approval.
[00:22:52.000 --> 00:23:00.600] And so there's, you know, there's a lot of trials around MDMA for PTSD, psilocybin primarily for depression.
[00:22:59.680 --> 00:23:04.440] People are trying LSD for generalized anxiety disorder, other things.
[00:23:05.080 --> 00:23:17.880] And ibogaine is probably the latest person to the party or whatever to the party in the sense that the plant to the party.
[00:23:17.880 --> 00:23:20.440] Yeah, the last plant to the party.
[00:23:21.400 --> 00:23:29.560] The reason for that is because ibogaine has the most complexity to it and the most inherent risk to it.
[00:23:29.560 --> 00:23:36.360] And so the problem with ibogaine as an inherent risk problem is that it has this cardiac risk, right?
[00:23:36.360 --> 00:23:40.280] So it actually will prolong the QT interval.
[00:23:40.280 --> 00:23:45.320] For people that don't know, it's a kind of a part of the physiology of the heart.
[00:23:45.320 --> 00:23:47.000] Lots of drugs do that.
[00:23:47.720 --> 00:23:49.880] Antipsychotics do that, right?
[00:23:50.200 --> 00:23:54.360] Geodon in particular does that at a great degree.
[00:23:54.360 --> 00:23:58.920] So it's not a unique, you know, within psychiatry, lots of drugs that do that.
[00:23:58.920 --> 00:24:02.280] Within medicine, as you know, there's lots of drugs that do that.
[00:24:02.280 --> 00:24:07.960] But, you know, it prolongs the QT quite a bit for a very short period of time.
[00:24:07.960 --> 00:24:18.760] And there have been a couple of deaths because people were getting administered Ibogaine in unmonitored or minimally monitored settings.
[00:24:18.760 --> 00:24:38.520] And so the problem with doing ibogaine research is that 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 the kind of case reports of risk.
[00:24:38.520 --> 00:24:46.640] So, we started, you know, the work that we did actually studying people that were already going to Mexico to take ibogaine, right?
[00:24:44.840 --> 00:24:51.040] So, they were already headed down there, they were already kind of consented to go down there.
[00:24:51.280 --> 00:25:00.960] And then, our job was, you know, simply to kind of do an observational study around that phenomenon that was already happening.
[00:25:00.960 --> 00:25:13.200] 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.
[00:25:13.200 --> 00:25:15.600] And so, you know, people have a varying degree.
[00:25:15.840 --> 00:25:19.120] IND is just for people listening as investigational new drug applications.
[00:25:19.120 --> 00:25:22.960] So, how do we go to the FDA and ask for permission to study something?
[00:25:22.960 --> 00:25:25.840] You need an application for that.
[00:25:25.840 --> 00:25:32.720] You need an application, and there's a chicken and egg problem of like, how do you take such a complicated drug and get an IND?
[00:25:32.720 --> 00:25:35.200] And so, there's a lot of that that goes on.
[00:25:35.200 --> 00:25:37.680] And so, people have had a hard time doing this.
[00:25:37.680 --> 00:25:41.280] And you could say, well, you know, this is a drug with risk.
[00:25:41.280 --> 00:25:43.440] You know, should we be doing this or not?
[00:25:43.440 --> 00:25:53.200] 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.
[00:25:53.200 --> 00:25:56.160] And so, Tecosin is a cardiac drug.
[00:25:56.160 --> 00:26:06.720] And if you ask the electrophysiologists, you know, cardiac electrophysiologists, and you show them the ibogaine data, they say, well, this is a risk, but Tecosin is just as much of a risk.
[00:26:06.720 --> 00:26:08.400] And we've gotten approval for Tekosin.
[00:26:08.720 --> 00:26:19.880] 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.
[00:26:19.880 --> 00:26:27.360] 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?
[00:26:27.360 --> 00:26:32.920] And Tecosin's used for like atrial fibrillation and for other kinds of arrhythmias.
[00:26:33.480 --> 00:26:43.000] And so people say, Well, this has a one in 100 risk of a torsad's event, but like if we don't do it, then somebody's going to die from a stroke from AFib.
[00:26:43.160 --> 00:26:47.320] So we can justify this risk with that risk, right?
[00:26:47.320 --> 00:26:55.000] And we know in opiate use disorder that there's a huge overdose risk in a person that's untreated.
[00:26:55.000 --> 00:27:11.080] And so 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.
[00:27:11.080 --> 00:27:16.040] And that justification allows us to say, no, actually, we're not going to study this.
[00:27:16.120 --> 00:27:21.720] Instead of understanding how many years of quality of life are lost, which is a real metric, quality of years.
[00:27:22.200 --> 00:27:22.920] Yeah, absolutely.
[00:27:22.920 --> 00:27:24.120] Or real death risk.
[00:27:24.600 --> 00:27:25.560] Death risk from overdose.
[00:27:25.560 --> 00:27:31.560] Yeah, it is a bit of a double standard because I think it's part of the bias in stigmatization of mental illness.
[00:27:31.560 --> 00:27:33.080] It's not a real thing.
[00:27:33.080 --> 00:27:39.400] You know, your heart arrhythmia is a real thing, but your depression is not a real thing, or your speed is not a real thing.
[00:27:40.040 --> 00:27:41.480] But yeah, it's amazing.
[00:27:41.480 --> 00:27:55.160] 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 very different than many other psychedelic.
[00:27:55.400 --> 00:28:05.320] I mean, the first story I heard about it was, you know, maybe 50 years ago, there was some drug addict who was in Amsterdam, and somebody said, Hey, try these cool pills, man.
[00:28:05.640 --> 00:28:07.160] And he did.
[00:28:07.480 --> 00:28:10.040] And the next day, his addiction was gone.
[00:28:10.040 --> 00:28:10.920] His cravings were gone.
[00:28:11.080 --> 00:28:14.560] So that was sort of the beginning of the understanding of effect in addiction medicine.
[00:28:14.440 --> 00:28:16.960] But it's just got all these broader effects.
[00:28:17.200 --> 00:28:33.680] So it's different than seems to be longer-lasting and more powerful in terms of resetting the brain and the sort of like almost a neurochemical reset than many of these other compounds, which work but don't have these persistent-lasting effects as much.
[00:28:33.680 --> 00:28:47.600] Yeah, so Howard Lotsov was the first, so just in the history of all this, you know, we know that Buiti were using this for at least 300 years, you know, probably, you know, most likely much longer than that.
[00:28:47.920 --> 00:28:54.480] The French started, discovered this in the Western world in about 1900.
[00:28:54.480 --> 00:29:00.880] It was on the French formulary from 1930 to 1966.
[00:29:00.880 --> 00:29:10.160] And it was actually a lower doses called labyrinth and was like a daily micro dose, essentially.
[00:29:10.160 --> 00:29:14.960] And so there's 36 years for attention problems and depression and things like that.
[00:29:14.960 --> 00:29:15.520] Wow.
[00:29:15.520 --> 00:29:21.600] And so for 36 years, it was used by the French and then placed on the French version of the Controlled Substances Act in 66.
[00:29:22.400 --> 00:29:24.640] And it was put on the U.S.
[00:29:24.640 --> 00:29:33.440] Controlled Substances Act, even though it doesn't really meet criteria for a controlled substance, for the description of a controlled substance.
[00:29:33.440 --> 00:29:37.200] It is neither, people don't self-administer it.
[00:29:38.000 --> 00:29:40.800] There's no animal data to suggest that there's a self-administration.
[00:29:40.800 --> 00:29:45.520] In fact, it reverses self-administration of other addictive compounds.
[00:29:45.520 --> 00:29:46.480] It's not a party drug.
[00:29:46.720 --> 00:29:47.760] It's not a party drug.
[00:29:47.760 --> 00:29:59.440] So it stops self-administration and it has this profound kind of psychological effect that doesn't really, it's not really reinforcing, right?
[00:29:59.440 --> 00:30:06.040] And so it doesn't really meet controlled substances description, but it was lumped in to the U.S.
[00:30:06.120 --> 00:30:14.680] Controlled Substance Act, Schedule I Substance, which is where it stayed since then and really prevented folks from using it.
[00:30:14.680 --> 00:30:30.200] And so Howard Lotsov 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.
[00:30:30.200 --> 00:30:35.240] And it's a very complicated timeline for folks to kind of get through.
[00:30:35.240 --> 00:30:48.520] And I think we're getting a signal now that finally we may be able to see that happen in our lifetimes that it could be that we could actually study this thing and make a real decision of whether or not it's useful.
[00:30:48.520 --> 00:30:58.760] 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.
[00:30:58.760 --> 00:31:03.160] That's an important study to do anyways from a public health standpoint, right?
[00:31:03.160 --> 00:31:16.280] Like the idea that we make plants illegal and then make them inaccessible for science is like it's a in 300 years, we're going to look at that and think that's just the craziest thing, I think.
[00:31:16.280 --> 00:31:18.120] Yeah, I mean, we have to study these things.
[00:31:18.120 --> 00:31:30.200] 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.
[00:31:30.200 --> 00:31:41.960] And I mean, I think it could really impact this incredible degree of trauma and PTSD and depression, anxiety, traumatic brain injury.
[00:31:41.960 --> 00:31:44.360] That's even fascinating to me, the brain injury stuff.
[00:31:44.320 --> 00:31:55.360] But the pathways that it works on are a lot of different pathways that reduce inflammation, oxidative stress, that increase neural protection, resilience of your cells.
[00:31:56.240 --> 00:32:01.440] And, you know, it just almost seems too good to be true how this works.
[00:32:01.440 --> 00:32:11.680] But it does have to be administered in a way that's safe because this risk of cardiac arrhythmias is high, and then you have to monitor that.
[00:32:11.920 --> 00:32:20.320] But with the magnesium therapy, which is what we use, it's funny to me that, you know, I used to work in the emergency room, and we had this thing called the crash card.
[00:32:20.320 --> 00:32:26.240] If someone comes in with cardiac arrest, you give them all these drugs, you give them epinephrine, you give them this drug, you give them that drug.
[00:32:26.240 --> 00:32:32.080] And then finally, like if every other drug fails and they're still in this terrible arrhythmia, you give them IV magnesium.
[00:32:32.080 --> 00:32:32.480] That's right.
[00:32:32.480 --> 00:32:33.040] That's right.
[00:32:33.040 --> 00:32:34.560] That's like the last draw.
[00:32:34.560 --> 00:32:36.320] I'm like, why don't we start out with that?
[00:32:36.720 --> 00:32:37.200] That's right.
[00:32:37.200 --> 00:32:39.440] You know, I've given a lot of IV magnesium in my life.
[00:32:39.440 --> 00:32:40.320] It's very safe.
[00:32:40.320 --> 00:32:45.600] We use it all the time in medicine for preeclampsia or hypertension in pregnancy for preterm labor.
[00:32:46.000 --> 00:32:53.280] Doctors don't somehow think of it as a compound that we should be using except in these extreme situations.
[00:32:53.280 --> 00:32:58.160] But it's actually one of the most important minerals and many of us are low in it or insufficient in it.
[00:32:58.160 --> 00:33:00.400] And I think stress causes it to be low.
[00:33:01.120 --> 00:33:08.000] Also caffeine, alcohol, a lot of things that we do actually cause us to deplete magnesium.
[00:33:08.000 --> 00:33:13.120] A lot of people are on anti-hypertensive drugs that cause you to lose magnesium, diuretics.
[00:33:13.120 --> 00:33:20.000] So you basically, you know, can mitigate a lot of these effects by tanking people up on magnesium if it's done in a controlled way.
[00:33:20.000 --> 00:33:23.280] And that's mitigated all those potential risks.
[00:33:23.280 --> 00:33:29.040] If you've never had a case in the magnesium administrative patients that you've used ibogaine with, right?
[00:33:29.040 --> 00:33:34.760] I mean, I, you know, I personally don't administer it.
[00:33:34.920 --> 00:33:55.000] 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, you know, and they'd had a, you know, a bad outcome, and then they, you know, started using it, and they hadn't had any cases since then.
[00:33:55.000 --> 00:34:10.440] And 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.
[00:34:10.440 --> 00:34:13.720] If you give magnesium, you can get some people out of torsades.
[00:34:13.720 --> 00:34:44.520] 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.
[00:34:44.520 --> 00:34:51.160] And that's the idea because the drug comes and goes, and then nobody has a risk of like post-treatment arrhythmia.
[00:34:51.160 --> 00:34:53.960] It's only during the kind of the peak levels of the drug.
[00:34:53.960 --> 00:34:59.160] And so if you can give magnesium to stabilize the heart, you can prevent this from happening.
[00:34:59.480 --> 00:35:17.520] Right now, 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.
[00:35:17.680 --> 00:35:24.960] But the question is: you know, do you still think people are going to need to be in a moderate setting with IB magnesium in order to actually safely take it?
[00:35:24.960 --> 00:35:28.560] Because it sounds like it's not something you can just sort of like prescribe people, right?
[00:35:28.560 --> 00:35:30.480] A bunch of different answers for that.
[00:35:30.480 --> 00:35:38.240] 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.
[00:35:38.240 --> 00:35:44.720] Now, Ibogaine at the current doses that people use, the kind of what we call flood doses.
[00:35:44.720 --> 00:35:55.760] 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.
[00:35:55.760 --> 00:36:02.960] If they're successful in doing that, then you're in a situation where one of these ibogaine analogs may be the solution.
[00:36:03.040 --> 00:36:05.280] Maybe you could take that at home or whatever.
[00:36:05.600 --> 00:36:08.160] And a lot of them aren't particularly psychedelic, right?
[00:36:08.160 --> 00:36:11.760] And so there's this, as you know, a big open question of do you need to have the trip?
[00:36:11.760 --> 00:36:13.600] Do you need to have this experience?
[00:36:13.600 --> 00:36:17.360] Or can you just have an agent that just changes brain plasticity and that's it?
[00:36:17.360 --> 00:36:20.480] And so that's a TBD sort of question.
[00:36:21.120 --> 00:36:23.120] But that may be a way to do it.
[00:36:23.120 --> 00:36:31.200] There are other iboga alkaloids that have more or less cardiotoxicity.
[00:36:31.520 --> 00:36:33.280] So that's a question.
[00:36:33.280 --> 00:36:38.320] And then we haven't really studied the dose ranges of ibogaine well at all.
[00:36:38.720 --> 00:36:50.960] And so it may be, 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.
[00:36:50.960 --> 00:36:59.000] And so it's one of these things where the Texas effort is going to be important to really hashing out what this is.
[00:36:58.640 --> 00:37:02.840] You know, these effects of dopamine and other things are powerful.
[00:37:03.160 --> 00:37:23.000] 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 that are 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.
[00:37:23.000 --> 00:37:50.120] So maybe you could spend a minute talking about your more recent study on 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 sort of physiological change that you saw with looking at functional MRIs and EEGs and other assessment techniques.
[00:37:50.120 --> 00:37:55.400] Because you're now looking at what's happening in the brain in ways that we couldn't really do before and that nobody's really looked at.
[00:37:55.400 --> 00:38:05.480] So ibogaine is a compound that, like I said, produces that physiologic kind of EEG-based change that we just published on.
[00:38:05.480 --> 00:38:09.480] We have more data that's kind of in review now.
[00:38:09.800 --> 00:38:22.360] Where we actually took, we took the MRI brain scans and fed them into an analysis pipeline around AI guessing the brain age.
[00:38:22.360 --> 00:38:28.920] So as Mark, you probably already know, you can take a brain MRI and you can have AI guess a brain age.
[00:38:28.920 --> 00:38:32.760] You can scan them the second time and it'll be very close to the first one.
[00:38:32.760 --> 00:38:35.080] You scan them a third time, it's gonna be very close.
[00:38:35.080 --> 00:38:45.840] 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?
[00:38:45.840 --> 00:38:52.240] And so, you know, you're you're you're a young guy in the sense you look very young, right?
[00:38:52.560 --> 00:39:01.600] And I would suspect your brain looks very young, and I would suspect that it's younger than your chronological age.
[00:39:01.680 --> 00:39:03.040] You're talking about me specifically?
[00:39:03.040 --> 00:39:04.640] Yeah, yeah, I'm 65.
[00:39:04.640 --> 00:39:05.840] I hope it's younger than that.
[00:39:05.920 --> 00:39:06.800] That's what I'm saying, right?
[00:39:06.800 --> 00:39:12.880] So, let's say we scan your brain, and maybe your brain is 55, and that's what AI.
[00:39:12.880 --> 00:39:27.200] 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?
[00:39:27.200 --> 00:39:39.520] And so, 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.
[00:39:39.520 --> 00:39:42.400] And if you scan them three times, you're gonna see that it's 75.
[00:39:42.400 --> 00:39:51.680] And what this is showing is as a group average, people have about a year and a half younger-looking brain at one month.
[00:39:51.680 --> 00:39:52.000] Wow.
[00:39:52.240 --> 00:39:54.000] And compound if you keep doing it?
[00:39:54.000 --> 00:39:55.680] This is what everybody keeps asking me.
[00:39:55.680 --> 00:40:00.960] I have no idea about that question, but it's a good question, right?
[00:40:02.720 --> 00:40:07.360] Can you lock the brain into an age if you just keep re-exposing it?
[00:40:07.360 --> 00:40:11.520] You know, it's a much further along the road question, but it's an intriguing one.
[00:40:11.520 --> 00:40:21.520] 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.
[00:40:21.520 --> 00:40:30.000] 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.
[00:40:30.520 --> 00:40:38.200] 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.
[00:40:38.200 --> 00:40:40.200] Yeah, and it may actually make sense.
[00:40:40.280 --> 00:40:46.440] We're talking about like one dose, one day, having an effect to reverse your brain age by a year and a half and a month.
[00:40:46.440 --> 00:40:47.880] That's pretty remarkable.
[00:40:47.880 --> 00:40:58.200] 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.
[00:40:58.200 --> 00:41:04.520] And so, what whereas you do see that with PTSD and depression and everything else, you see it really quickly.
[00:41:04.520 --> 00:41:09.960] But with traumatic brain injury disability and with the brain age, it takes the month.
[00:41:09.960 --> 00:41:10.840] And it makes sense.
[00:41:10.840 --> 00:41:18.040] Like, if these are more hard neurological issues, you're not going to be able to change the brain in five days or whatever.
[00:41:18.040 --> 00:41:19.480] It's going to take some time.
[00:41:19.800 --> 00:41:29.240] One of the things that I heard is that there's a metabolite of ibogaine called noribogaine that lasts longer.
[00:41:29.240 --> 00:41:40.280] And I'm wondering if that explains some of the tail of these effects of the addiction and inhibition, withdrawal inhibition, and maybe some of these other deeper neurological effects.
[00:41:41.720 --> 00:41:46.440] And I don't know if that noribogaine has the same cardiac risks or if anybody's looking at studying that.
[00:41:46.440 --> 00:41:49.160] So the noribogaine does have a similar cardiac profile.
[00:41:49.160 --> 00:41:53.880] Ibogaine is metabolized into noribigain normally through 2D6.
[00:41:53.880 --> 00:42:05.240] And so you see people with getting ibogaine and they metabolize to noribogaine in roughly 12 hours, 8 to 12 hours, or something like that.
[00:42:05.240 --> 00:42:14.360] 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 noribogaine as a treatment?
[00:42:14.360 --> 00:42:17.120] And that's an open question, you know, and that work needs to be done.
[00:42:18.000 --> 00:42:31.120] 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.
[00:42:31.680 --> 00:42:32.320] Interesting.
[00:42:32.320 --> 00:42:45.120] 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.
[00:42:45.120 --> 00:42:53.200] It happens with the based off of the subjective effects and the timeline of the drug, that's what it looks like, right?
[00:42:53.200 --> 00:43:05.600] 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.
[00:43:05.600 --> 00:43:16.240] 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.
[00:43:16.240 --> 00:43:23.280] So if you take that out, you may be taking out at least some of the, at least the PTSD benefit.
[00:43:23.280 --> 00:43:34.560] 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.
[00:43:34.560 --> 00:43:37.520] There's over 2.5 billion people overweight in the world.
[00:43:37.840 --> 00:43:40.480] Obesity is exploding across the planet.
[00:43:40.480 --> 00:43:45.760] And in America, we're 75% of us are overweight, 42% are obese.
[00:43:45.760 --> 00:43:49.120] The Yale Food Addiction Scale is a way of measuring food addiction.
[00:43:49.440 --> 00:43:51.360] And Kelly Brunnell and others developed it.
[00:43:51.360 --> 00:43:57.440] And 14% of the global population is addicted to food, including 14% of kids.
[00:43:58.200 --> 00:44:00.040] And that's about the same as alcohol.
[00:43:59.520 --> 00:44:02.120] Alcohol addiction is about 14%.
[00:44:03.080 --> 00:44:21.080] And I wonder if, you know, everybody's talking about Ozempic and GLP 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?
[00:44:21.080 --> 00:44:27.400] I think there's, you know, when you look at genetics, there's genetics involved in people who tend to move towards more addiction.
[00:44:27.400 --> 00:44:30.360] They don't benefit as much from this dopamine simulation.
[00:44:30.360 --> 00:44:32.120] They need more to feel the same pleasure.
[00:44:32.120 --> 00:44:35.320] And so, you know, how does someone eat a whole sheet cake?
[00:44:35.320 --> 00:44:37.720] I couldn't ever do that, but people do.
[00:44:38.040 --> 00:44:44.920] And I think that, you know, as an application, it seems to be a multi-billion dollar application.
[00:44:44.920 --> 00:44:47.800] So our data, we also collected alcohol use.
[00:44:48.200 --> 00:44:58.760] 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.
[00:44:58.760 --> 00:45:07.800] And so just almost everybody, just really dramatic improvements in alcohol and maintained it.
[00:45:07.800 --> 00:45:11.880] And so, and we also have some biology around that that we're looking at.
[00:45:11.880 --> 00:45:17.080] And so, you know, all those guys, if you asked them, are you going down there to stop drinking?
[00:45:17.080 --> 00:45:21.320] They would have told you, no, I'm trying to deal with my like TBI or whatever.
[00:45:21.720 --> 00:45:27.480] And then, you know, nearly everybody came back and reported they really didn't want to drink coffee anymore.
[00:45:27.480 --> 00:45:28.440] They really didn't.
[00:45:28.760 --> 00:45:34.760] And so I always think that, so placebo is expectancy, right?
[00:45:34.760 --> 00:45:41.880] And the degree of the expectation that you have about how a drug is going to work drives a lot of the effect.
[00:45:41.880 --> 00:45:53.840] 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.
[00:45:53.840 --> 00:46:02.320] And the total knee patients and the kind of the fake surgery incision folks had no difference in outcome.
[00:46:03.280 --> 00:46:07.840] It looks like it was driven primarily by expectancy.
[00:46:07.840 --> 00:46:20.960] And so, if the person's being told in medicine, I'm going to do this thing, and when I do this thing, that thing that I'm going to do is drive this outcome, then the person has this expectation of that outcome.
[00:46:20.960 --> 00:46:22.240] And that's hard, right?
[00:46:22.240 --> 00:46:33.280] 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 related to that, not placebo.
[00:46:33.280 --> 00:46:43.840] 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.
[00:46:44.480 --> 00:46:46.880] Or now everybody stopped drinking alcohol.
[00:46:46.880 --> 00:46:53.520] 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.
[00:46:53.520 --> 00:46:55.760] Like, they'd say, I didn't know that was going to happen.
[00:46:56.080 --> 00:47:01.760] They all just came back fascinated with this thing that happened that they didn't have any expectancy for.
[00:47:02.160 --> 00:47:30.000] 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 re-org, 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.
[00:47:30.280 --> 00:47:36.120] So, there's all kinds of effects that we're just sort of learning about, and I think with obesity, nobody's probably looking at that as my guess, right?
[00:47:36.120 --> 00:47:37.240] With Ibogaine?
[00:47:37.240 --> 00:47:39.960] Yeah, I mean, yeah, nobody that I know of, yeah.
[00:47:39.960 --> 00:47:41.880] I think it could be an interesting offshoot study.
[00:47:41.880 --> 00:47:43.800] Like, does their food behavior change?
[00:47:43.800 --> 00:47:46.760] Does their cravings for sugar change?
[00:47:48.360 --> 00:47:57.240] Because I think it's like that, that, I mean, you're talking about opioid addiction killing 70,000 people a year, but the food addiction part kills a lot, lot more.
[00:47:57.240 --> 00:48:03.400] You know, chronic disease-related food is killing a million-plus people a year in America.
[00:48:03.400 --> 00:48:13.000] So, to me, I think it'd be an interesting little kind of side hustle to kind of look at that and your data and see what happens if people change their diets, do they change their weight loss?
[00:48:13.000 --> 00:48:15.000] Like, there's other things you can look at.
[00:48:15.000 --> 00:48:17.960] So, I encourage you to check that out because I have this theory.
[00:48:17.960 --> 00:48:24.040] But if it, because if it works, it's a big unlock, you know, and it's probably a lot better than taking Ozempic.
[00:48:24.040 --> 00:48:39.640] 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.
[00:48:39.640 --> 00:48:48.760] And with Ibogaine and some of the other psychedelic therapies, we're talking about 80 to 90% reductions in symptoms and things that you just don't see.
[00:48:48.760 --> 00:48:53.960] So, can you talk about the magnitude of the effects and how it's different than traditional psychiatric treatments?
[00:48:53.960 --> 00:48:58.200] Yeah, I mean, so the degree of the effects that we observed were quite striking.
[00:48:58.200 --> 00:49:04.520] The you know, the data is limited, you know, so that needs to get replicated.
[00:49:04.520 --> 00:49:10.680] And I've heard, you know, that there's another group out of Texas that they're seeing very similar effects to us.
[00:49:10.680 --> 00:49:14.920] And so, if that holds, and that's really the case, then, you know, that's going to be helpful.
[00:49:16.000 --> 00:49:25.600] In this hypothetical future scenario where, you know, you're right, and this is these are the degrees in which people change compared to conventional treatments.
[00:49:25.920 --> 00:49:26.880] It's a huge difference.
[00:49:26.880 --> 00:49:47.360] 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, and the inter-rater reliability on that scale is two points.
[00:49:47.360 --> 00:49:49.200] Yeah, so basically, it's like nothing.
[00:49:49.200 --> 00:49:55.280] So the noise between raiders is the same amount of change as the change observed.
[00:49:55.280 --> 00:50:00.960] Now, on average, they're seeing the change greater in the active group than in the placebo group.
[00:50:00.960 --> 00:50:10.000] I'm not arguing that, but like it's the, yeah, the observer, you know, differences are that level.
[00:50:10.000 --> 00:50:19.520] So it's very hard to discern if you've got totally skilled raiders and they have that problem, how effective these drugs really can be.
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[00:52:31.800 --> 00:52:35.080] So, those are not, but then the ibogaine is far more.
[00:52:35.080 --> 00:52:47.920] 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, as a generality, people don't really score above mid-30s on.
[00:52:48.480 --> 00:52:56.960] 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.
[00:52:56.960 --> 00:52:59.120] You know, you need to go to the hospital or something like that.
[00:52:59.120 --> 00:53:04.480] And so we're seeing a 20-point change in a lot of people on that scale.
[00:53:04.800 --> 00:53:12.080] The use case for this drug is across a whole bunch of different issues that seem not necessarily related.
[00:53:12.080 --> 00:53:16.240] Like, what does brain injury have to do with PTSD, have to do with depression?
[00:53:16.240 --> 00:53:26.880] And how do you think that we sort of start to apply these compounds to these conditions in a more systematic way where deliberately working on different pathways that these drugs work on?
[00:53:26.880 --> 00:53:28.480] It's an open question, you know.
[00:53:28.480 --> 00:53:37.200] I think we've got to spend the time to understand what the different alkaloids do and then use those.
[00:53:37.520 --> 00:53:47.360] It's kind of like where GW Pharmaceuticals was as it relates to cannabinoids, you know, and so there's an approval.
[00:53:47.360 --> 00:53:58.160] 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.
[00:53:58.160 --> 00:54:01.120] So Lenox Gasto and Gervais syndrome, right?
[00:54:01.120 --> 00:54:06.240] And so those two epilepsy syndromes in kids are really devastating.
[00:54:06.240 --> 00:54:09.840] Sometimes kids have two to three hundred seizures a day.
[00:54:09.840 --> 00:54:16.080] You have to put them on potassium bromide, which is like what we give dogs for epilepsy, you know.
[00:54:17.040 --> 00:54:23.040] And you end up being in a situation where, you know, kids still seizing.
[00:54:23.040 --> 00:54:36.600] 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.
[00:54:37.320 --> 00:54:37.640] Right.
[00:54:37.640 --> 00:54:43.240] And so they were administering on their moving to at the time, moving to Denver.
[00:54:43.240 --> 00:54:48.040] This was, you know, Sanjay Gupta did like a special on this 15 or 20 years ago.
[00:54:48.040 --> 00:54:58.120] So all these families that Linux Gasto kids moving to Denver and then figuring out on their own, buying cannabis and then extracting it, extracting CBD.
[00:54:58.120 --> 00:55:05.240] So they called it Charlotte's Web, which is this pure CBD cannabis, and they extract that out.
[00:55:05.560 --> 00:55:16.120] 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.
[00:55:16.120 --> 00:55:19.240] Maybe it's a little anxiolytic, but it doesn't make people high.
[00:55:19.240 --> 00:55:24.200] You know, the kids were actually waking up and they were less encephalopathic when they would take it.
[00:55:24.920 --> 00:55:36.120] And, you know, you give this to a kid and they come out of an epilepsy fit, you know, and so all these families were seeing this kids, potassium bromide and all this stuff.
[00:55:36.120 --> 00:55:42.200] And then you give them high-dose CBD and they wake up, you know, for the first time.
[00:55:42.200 --> 00:55:47.160] And so what GW did is they said, okay, we're going to make a pure CBD drug.
[00:55:47.240 --> 00:55:48.040] We're going to get that through.
[00:55:48.040 --> 00:55:58.920] And then we're going to 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.
[00:55:59.400 --> 00:56:04.360] And I think that's what's going to happen with these iboga alkaloids, right?
[00:56:04.360 --> 00:56:05.160] Is that we have to.
[00:56:05.480 --> 00:56:16.240] You don't think it's just the whole plant, it's 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.
[00:56:16.240 --> 00:56:17.520] That is the open question.
[00:56:14.840 --> 00:56:20.080] So, there's going to be an experiment on this.
[00:56:20.400 --> 00:56:33.760] You know, Colorado is going to is basically gonna allow for whole plant-derived iboga alkaloids to be used for people, you know, out inside of Colorado.
[00:56:33.760 --> 00:56:37.280] And so, the question ends up being: is that the road?
[00:56:37.280 --> 00:56:39.360] Is it isolating ibogaine?
[00:56:39.360 --> 00:56:40.960] Is it isolating other alkaloids?
[00:56:40.960 --> 00:56:42.000] I'm a pragmatist.
[00:56:42.000 --> 00:56:54.000] Like, I don't have like a philosophical view on this other than, you know, if somebody's going to die and you give them this thing and their probability of dying goes way down, we should probably be doing that.
[00:56:54.000 --> 00:57:00.080] And I think that's like, so if that's what happens in Colorado, then that'd be good.
[00:57:00.080 --> 00:57:09.040] I mean, I have some open concerns about it because of the cardiac risk, and I'm pretty public about that, but they're going to do it no matter what I think.
[00:57:09.040 --> 00:57:17.920] 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.
[00:57:18.080 --> 00:57:23.200] And then there's this kind of organic chemistry thing where they're changing the molecule thing too.
[00:57:23.200 --> 00:57:25.120] That's maybe that's not even psychoactive.
[00:57:25.120 --> 00:57:29.760] And I think we'll get in totality the answer over the next 10 years.
[00:57:29.760 --> 00:57:30.160] Yeah.
[00:57:30.160 --> 00:57:34.640] And the reality is, is that if it all works, that's amazing.
[00:57:34.640 --> 00:57:37.360] If one of them works, we know a lot more about how the brain works.
[00:57:37.360 --> 00:57:41.440] I mean, hopefully, we're not in a situation where none of them work, but that's possible too.
[00:57:41.760 --> 00:57:45.360] But at least we gave it a college try for sure.
[00:57:45.360 --> 00:57:50.800] But the beauty is, I think that's all happening, and we're going to be able to really actually sort it out.
[00:57:50.800 --> 00:57:52.000] And fingers crossed.
[00:57:52.000 --> 00:57:52.880] Yeah, pretty amazing.
[00:57:52.880 --> 00:57:58.640] Yeah, this is sort of an interesting moment where we have these new compounds we never had before where we're looking at them.
[00:57:58.640 --> 00:58:11.480] But the NDMA 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.
[00:58:12.360 --> 00:58:20.120] But what you're talking about, IB gain, not needing the psychotherapy component, do people need follow-up support, treatment, integration?
[00:58:20.440 --> 00:58:24.120] Does it have to be done in a psychiatric context where there's more continuity of care?
[00:58:24.200 --> 00:58:28.920] It's just like go in and take it, close your eyes, wake up 12 hours later, and that's it.
[00:58:28.920 --> 00:58:33.640] So there's a pre-post therapy requirement.
[00:58:33.640 --> 00:58:41.320] There's a within dosing therapy non-requirement, it appears, right?
[00:58:41.320 --> 00:58:44.840] Although, like, nobody's really, you know, could be very helpful.
[00:58:44.840 --> 00:58:45.560] We don't know.
[00:58:45.560 --> 00:58:56.760] But what happens with MDMA, as you know, is, you know, I think you've studied, is if you give somebody MDMA, they have a positively balanced experience.
[00:58:56.760 --> 00:58:57.400] Yeah.
[00:58:57.400 --> 00:58:57.720] Right?
[00:58:57.720 --> 00:59:03.800] They have this, they feel good and they feel good about, you know, the people around them.
[00:59:03.800 --> 00:59:05.560] And they feel good about the memories they've had.
[00:59:05.560 --> 00:59:14.760] 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.
[00:59:14.760 --> 00:59:17.000] And I think that's very useful as a tool.
[00:59:17.000 --> 00:59:18.920] I think it's also very tricky as a tool.
[00:59:18.920 --> 00:59:25.880] There's an analysis of the events that happened in Israel with the rave, right?
[00:59:25.880 --> 00:59:30.760] And in that situation, there was a certain percentage of those people who are actually on MDMA.
[00:59:30.760 --> 00:59:31.800] I don't know if you know about this.
[00:59:32.120 --> 00:59:43.680] 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.
[00:59:43.760 --> 00:59:53.520] The boss came in and terrorized the festival in Israel on October 7th, and the people who took the MDMA were less traumatized after than the ones who didn't.
[00:59:53.520 --> 00:59:54.080] Correct.
[00:59:54.080 --> 00:59:54.640] Yeah.
[00:59:54.640 --> 01:00:00.000] And so, you know, what it's a terrible story, obviously.
[01:00:00.000 --> 01:00:05.760] What's interesting about that data is that it tells you something about it being protective, right?
[01:00:05.760 --> 01:00:22.320] 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 valenced place.
[01:00:22.320 --> 01:00:28.080] But, you know, it's probably true that you need to, you know, have a guide to guide people with that drug.
[01:00:28.080 --> 01:00:38.160] 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.
[01:00:38.480 --> 01:00:47.120] 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?
[01:00:47.120 --> 01:00:55.120] They have to unpack all of the earlier life, you know, in many cases, traumatic memories that they have to kind of get through.
[01:00:55.120 --> 01:00:59.600] And in that situation, it's driven by the drug.
[01:00:59.600 --> 01:01:03.040] It's not driven by a therapist telling them, hey, go look at this memory.
[01:01:03.040 --> 01:01:04.960] It's like the drug is doing that.
[01:01:04.960 --> 01:01:10.000] But then the person has to come out of it and really actually sort it out for themselves mentally.
[01:01:10.480 --> 01:01:12.000] That they need help with, generally.
[01:01:12.000 --> 01:01:14.080] Then they, yeah, basically all need help with.
[01:01:14.480 --> 01:01:25.280] I'm fascinated because, you know, there's effects on disease states or, you know, things that are problematic for people, like PTSD, traumatic brain injury, depression, et cetera.
[01:01:25.280 --> 01:01:27.760] But then there's the brain enhancement component.
[01:01:27.760 --> 01:01:38.920] And I've known a number of people who've 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.
[01:01:38.920 --> 01:01:44.200] And you mentioned briefly about the reversal of the brain age as sort of a hint at that.
[01:01:44.200 --> 01:01:49.560] Can you talk more about how it might be used as a sort of an enhancement drug?
[01:01:49.560 --> 01:02:01.720] 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, you know, we all would like to have better brains, right?
[01:02:01.720 --> 01:02:10.920] Yeah, so what we observed in the veterans was that they had an improvement in statistically significant improvement in some aspects of cognition, particularly around frontal control.
[01:02:10.920 --> 01:02:18.120] 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.
[01:02:18.440 --> 01:02:23.400] But, you know, at least you can see in a diseased population an improvement there.
[01:02:23.400 --> 01:02:30.120] Whereas like with a lot of the oral antidepressants and whatnot, you're not really seeing an improvement in cognition.
[01:02:30.120 --> 01:02:37.480] There's not really a good drug in psychiatry that's approved for depression that improves cognition.
[01:02:37.480 --> 01:02:42.600] And so at least we're getting signals of it with ibogaine, but it's, you know, it's got to be studied.
[01:02:42.600 --> 01:02:48.440] Yeah, it would be interesting as

Prompt 2: Key Takeaways

Now please extract the key takeaways from the transcript content I provided.

Extract the most important key takeaways from this part of the conversation. Use a single sentence statement (the key takeaway) rather than milquetoast descriptions like "the hosts discuss...". 

Limit the key takeaways to a maximum of 3. The key takeaways should be insightful and knowledge-additive. 

IMPORTANT: Return ONLY valid JSON, no explanations or markdown. Ensure:
- All strings are properly quoted and escaped
- No trailing commas
- All braces and brackets are balanced
Format: {"key_takeaways": ["takeaway 1", "takeaway 2"]}

Prompt 3: Segments

Now identify 2-4 distinct topical segments from this part of the conversation.

For each segment, identify:
- Descriptive title (3-6 words)  
- START timestamp when this topic begins (HH:MM:SS format)
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Most important Key takeaway from that segment. Key takeaway must be specific and knowledge-additive.
- Brief summary of the discussion

IMPORTANT: The timestamp should mark when the topic/segment STARTS, not a range. Look for topic transitions and conversation shifts.

Return ONLY valid JSON. Ensure all strings are properly quoted, no trailing commas:
{
  "segments": [
    {
      "segment_title": "Topic Discussion", 
      "timestamp": "01:15:30",
      "key_takeaway": "main point from this segment",
      "segment_summary": "brief description of what was discussed"
    }
  ]
}

Timestamp format: HH:MM:SS (e.g., 00:05:30, 01:22:45) marking the START of each segment.

Prompt 4: Media Mentions

Now scan the transcript content I provided for ACTUAL mentions of specific media titles:

Find explicit mentions of:
- Books (with specific titles)
- Movies (with specific titles)  
- TV Shows (with specific titles)
- Music/Songs (with specific titles)

DO NOT include:
- Websites, URLs, or web services
- Other podcasts or podcast names

IMPORTANT: 
- Only include items explicitly mentioned by name. Do not invent titles.
- Valid categories are: "Book", "Movie", "TV Show", "Music"
- Include the exact phrase where each item was mentioned
- Find the nearest proximate timestamp where it appears in the conversation
- THE TIMESTAMP OF THE MEDIA MENTION IS IMPORTANT - DO NOT INVENT TIMESTAMPS AND DO NOT MISATTRIBUTE TIMESTAMPS
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Timestamps are given as ranges, e.g. 01:13:42.520 --> 01:13:46.720. Use the EARLIER of the 2 timestamps in the range.

Return ONLY valid JSON. Ensure all strings are properly quoted and escaped, no trailing commas:
{
  "media_mentions": [
    {
      "title": "Exact Title as Mentioned",
      "category": "Book",
      "author_artist": "N/A",
      "context": "Brief context of why it was mentioned",
      "context_phrase": "The exact sentence or phrase where it was mentioned",
      "timestamp": "estimated time like 01:15:30"
    }
  ]
}

If no media is mentioned, return: {"media_mentions": []}

Prompt 5: Context Setup

You are an expert data extractor tasked with analyzing a podcast transcript. 
I will provide you with part 2 of 2 from a podcast transcript. 
I will then ask you to extract different types of information from this content in subsequent messages. Please confirm you have received and understood the transcript content.

Transcript section:
lly all need help with.
[01:01:14.480 --> 01:01:25.280] I'm fascinated because, you know, there's effects on disease states or, you know, things that are problematic for people, like PTSD, traumatic brain injury, depression, et cetera.
[01:01:25.280 --> 01:01:27.760] But then there's the brain enhancement component.
[01:01:27.760 --> 01:01:38.920] And I've known a number of people who've 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.
[01:01:38.920 --> 01:01:44.200] And you mentioned briefly about the reversal of the brain age as sort of a hint at that.
[01:01:44.200 --> 01:01:49.560] Can you talk more about how it might be used as a sort of an enhancement drug?
[01:01:49.560 --> 01:02:01.720] 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, you know, we all would like to have better brains, right?
[01:02:01.720 --> 01:02:10.920] Yeah, so what we observed in the veterans was that they had an improvement in statistically significant improvement in some aspects of cognition, particularly around frontal control.
[01:02:10.920 --> 01:02:18.120] 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.
[01:02:18.440 --> 01:02:23.400] But, you know, at least you can see in a diseased population an improvement there.
[01:02:23.400 --> 01:02:30.120] Whereas like with a lot of the oral antidepressants and whatnot, you're not really seeing an improvement in cognition.
[01:02:30.120 --> 01:02:37.480] There's not really a good drug in psychiatry that's approved for depression that improves cognition.
[01:02:37.480 --> 01:02:42.600] And so at least we're getting signals of it with ibogaine, but it's, you know, it's got to be studied.
[01:02:42.600 --> 01:02:48.440] Yeah, it would be interesting as just as more of like a longevity enhancement drug.
[01:02:48.440 --> 01:02:51.720] And we don't really think much about those things in medicine at all.
[01:02:51.720 --> 01:03:00.200] 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.
[01:03:00.520 --> 01:03:05.640] Probiotics, for example, is something that can optimize health as opposed to an antibiotic.
[01:03:05.880 --> 01:03:09.720] And in functional medicine, that's a lot what we think about: what are the ways to enhance function?
[01:03:09.720 --> 01:03:13.320] What are the pro-drugs as opposed to anti-drugs, right?
[01:03:13.880 --> 01:03:16.640] And it seems like it has that kind of potential.
[01:03:17.200 --> 01:03:25.440] What we really need to understand, I think, is why were the Buiti taking this for hundreds of years, you know, and why do the French think this was helpful for 36?
[01:03:25.600 --> 01:03:26.080] Yeah.
[01:03:26.080 --> 01:03:31.360] You know, and I think that could give us a signal about what it could do for that, right?
[01:03:31.360 --> 01:03:55.360] Because it seems to me that you have a even in the 30s to 66, you know, 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.
[01:03:55.360 --> 01:04:01.920] And so my suspicion is that there were some disease treatment effects, but maybe these effects too.
[01:04:01.920 --> 01:04:02.240] Who knows?
[01:04:02.400 --> 01:04:10.640] Yeah, I wonder if there's any people around us who took it back then who are in their 90s probably now from what the effect on them.
[01:04:11.200 --> 01:04:14.720] I think this is such an exciting moment in psychiatry and medicine.
[01:04:14.720 --> 01:04:19.440] And I think a lot of people are stuck in mental health issues.
[01:04:19.440 --> 01:04:21.680] And we live in an increasingly stressful society.
[01:04:21.680 --> 01:04:24.800] And there's just such a limited set of tools for people.
[01:04:24.800 --> 01:04:30.800] 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.
[01:04:30.800 --> 01:04:52.560] And I wonder if you've thought about combining the things that you're doing with other kind of metabolic psychiatry stuff that your colleagues are 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.
[01:04:52.880 --> 01:04:53.600] 100%.
[01:04:53.600 --> 01:04:53.920] Yeah.
[01:04:53.920 --> 01:05:02.920] I mean, I think we, I've taken the stance that if you look at like MICARA, like people having a heart attack, what do we do now?
[01:05:03.160 --> 01:05:14.760] We throw an aspirin, we throw statin, we do a heart cath, we do all these things in summation that all independently were shown in isolation to benefit.
[01:05:14.760 --> 01:05:18.360] Right, we hit a cocktail therapy as opposed to a single therapy, right?
[01:05:18.360 --> 01:05:25.000] The challenge right now is to, we're in cardiology 1950s, right?
[01:05:25.160 --> 01:05:42.360] 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 and make more tools and improve those tools and do the trials in each one of the tools.
[01:05:42.360 --> 01:06:00.520] Now, 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.
[01:06:00.520 --> 01:06:01.720] I think absolutely.
[01:06:01.720 --> 01:06:08.760] You know, I think that's going to be the way we deal with things in the future: we say, okay, well, we're going to, you know, and you're doing a lot of this already.
[01:06:08.760 --> 01:06:10.600] We're going to measure all of these things.
[01:06:10.600 --> 01:06:15.000] We're going to modify your diet, your metabolics, you know, all of that good stuff.
[01:06:15.000 --> 01:06:16.680] We're going to do brain-based things.
[01:06:16.680 --> 01:06:33.800] 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 of that stuff, and people end up being way over here.
[01:06:33.800 --> 01:06:37.000] Do you need multiple therapies to get you back on track?
[01:06:37.000 --> 01:06:44.440] 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.
[01:06:44.480 --> 01:06:58.880] To me, that's one of the big questions that yourself and others are trying to tackle, which is 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?
[01:06:58.880 --> 01:07:01.840] And it's an important question and one we have to ask.
[01:07:01.840 --> 01:07:08.000] You know, we have increasing rates, we don't know why, and so maybe it is because of diet.
[01:07:08.000 --> 01:07:09.440] Oh, yeah, I mean, it's huge.
[01:07:09.440 --> 01:07:22.320] I mean, but I don't think that the dietary change alone or nutritional metabolic changes alone can do the kinds of things that these psychedelic compounds do.
[01:07:22.880 --> 01:07:27.840] And what's fascinating is we've sort of this always fascinates me.
[01:07:27.840 --> 01:07:37.840] 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?
[01:07:37.840 --> 01:07:40.640] And I wonder if somehow we co-evolve with these plants.
[01:07:40.640 --> 01:07:46.480] And if you look across all indigenous societies, they all have some sort of psychedelic something that they play with.
[01:07:46.720 --> 01:07:53.360] It's ayahuasca and Indians in South America or peyote in North America or whatever.
[01:07:53.360 --> 01:08:10.560] If 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.
[01:08:10.880 --> 01:08:18.240] Many of them thought these were, you know, there weren't that many limes and lemons in Europe at the time, right?
[01:08:18.480 --> 01:08:24.240] This was considered a South American or an African exotic plant.
[01:08:24.560 --> 01:08:31.960] And so most of the physicians of the day actually rejected citrus fruit as a treatment for scurvy.
[01:08:32.040 --> 01:08:35.000] And so, as you know, the story of anti-fruiters, right?
[01:08:35.000 --> 01:08:42.680] There were lots of people in the British Royal Society that said that the limes and lemons may actually be making scurvy worse.
[01:08:42.680 --> 01:08:59.080] And 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.
[01:08:59.080 --> 01:09:15.320] 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.
[01:09:15.320 --> 01:09:24.520] Plant, not so sure about that, you know, and I think that's that's the way we've been looking at plant-based psychedelics for a long time, and hopefully that changes.
[01:09:24.520 --> 01:09:25.080] Pretty amazing.
[01:09:25.080 --> 01:09:46.200] And this, and the, the sort of, I keep kind of doubling down on the magnitude of the size of the effect, and I want to sort of double down on that 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 modern disability to like no disability.
[01:09:46.200 --> 01:09:53.640] You had PTSD drop by 88%, depression dropped by 87%, anxiety by 81%, improved cognition.
[01:09:53.720 --> 01:09:55.800] Seems like too good to be true, right?
[01:09:55.800 --> 01:10:00.520] When my postdoc showed me the data, I didn't believe him, and I told him to go back and reanalyze it.
[01:10:00.520 --> 01:10:00.840] Yeah.
[01:10:00.840 --> 01:10:12.920] 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.
[01:10:12.920 --> 01:10:15.680] So we need to be replicated by another group in order to justify it.
[01:10:15.760 --> 01:10:22.000] Now I'm hearing from my colleagues out of Texas that they are seeing very similar effects, right?
[01:10:22.000 --> 01:10:28.240] And so I want them to formally see that, if that's what it is, and publish that.
[01:10:28.240 --> 01:10:36.080] And then we can say it wasn't, you know, our site or whatever, that at least in an open label way, this is what this looks like.
[01:10:36.080 --> 01:10:38.720] And then the next step is to do the big trials.
[01:10:38.720 --> 01:10:46.240] But it would be unusual to have that level of an effect for this sort of level of expectancy.
[01:10:46.240 --> 01:10:50.640] I mean, they didn't expect that big of a change, so they would less likely to see it.
[01:10:50.640 --> 01:10:51.040] Yeah.
[01:10:51.040 --> 01:10:53.440] The veterans had, have you followed them ongoingly?
[01:10:53.440 --> 01:10:55.200] Are they still have the lasting effects?
[01:10:55.200 --> 01:10:56.800] So we have data out to year.
[01:10:56.800 --> 01:10:58.000] It isn't published yet.
[01:10:58.000 --> 01:11:00.160] It's kind of in review now, actually.
[01:11:00.160 --> 01:11:01.680] And that looks really good.
[01:11:02.000 --> 01:11:03.120] Most people hold it.
[01:11:03.120 --> 01:11:09.600] And you're talking now more about this idea of circuit-based psychiatry, which helps explain some of the things you're seeing.
[01:11:09.600 --> 01:11:13.760] Can you kind of unpack what that is and how it differs from our current view of psychiatry?
[01:11:13.760 --> 01:11:33.280] If you think about psychiatry and epochs, you know, the first one being talk therapy, and we learned something important there that spoken word can have effects on, you know, mental states and effect, you know, and now more recently, data suggesting that it's having an effect on the brain itself.
[01:11:33.280 --> 01:11:35.440] And that was useful.
[01:11:35.440 --> 01:11:43.440] Psychiatry 2.0, this idea that pharmacology can have an effect at the level of the synapse.
[01:11:43.440 --> 01:11:44.960] And that was also very useful, right?
[01:11:44.960 --> 01:11:49.840] That got a lot of people with, say, schizophrenia out of asylums and that sort of thing.
[01:11:50.080 --> 01:11:50.960] They like thorazine.
[01:11:51.360 --> 01:11:52.240] Yeah, like thorazine, yeah.
[01:11:52.560 --> 01:11:54.640] The chemical straitjackets, we call them.
[01:11:54.640 --> 01:12:11.480] 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?
[01:12:11.480 --> 01:12:13.640] Because at the end of the day, lots of...
[01:12:13.880 --> 01:12:18.360] the psychiatric treatments that we have are suboptimal for patients' desires, right?
[01:12:18.360 --> 01:12:19.880] ECT is a great example of that.
[01:12:20.360 --> 01:12:21.400] Electric shock therapy.
[01:12:21.960 --> 01:12:28.600] Can you use insights from before and make things much safer and better and much more tolerated with patients?
[01:12:28.600 --> 01:12:32.920] And that's really been, I think, the emphasis for our work.
[01:12:32.920 --> 01:12:36.840] And so when we look at IBM, we're looking at it from the lens of the circuit.
[01:12:36.840 --> 01:12:43.080] When we're looking at, I'd say, stimulation of the brain, we're looking at it from the lens of the circuit.
[01:12:43.080 --> 01:12:58.920] 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.
[01:12:58.920 --> 01:12:59.560] Amazing.
[01:12:59.560 --> 01:13:09.960] 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.
[01:13:10.200 --> 01:13:12.440] I was like, I spent a month there.
[01:13:12.440 --> 01:13:14.520] I was like, this is just nuts.
[01:13:14.520 --> 01:13:16.200] And I don't mean that as a pun.
[01:13:16.200 --> 01:13:23.560] I just mean the way we treated people, the amount of suffering that's going on, the lack of really good treatments.
[01:13:23.560 --> 01:13:24.920] It feels really hopeful.
[01:13:24.920 --> 01:13:26.440] It feels like a hopeful moment.
[01:13:26.440 --> 01:13:29.720] But it doesn't feel like we're going fast enough to me.
[01:13:29.720 --> 01:13:33.400] It feels like we're still in this sort of glacial pace of change.
[01:13:33.400 --> 01:13:35.560] And science proceeds that way, unfortunately.
[01:13:35.560 --> 01:13:38.760] But I think many people listening go, wow, you know, can I try it?
[01:13:38.760 --> 01:13:39.480] What do I do?
[01:13:39.480 --> 01:13:40.680] What if I want to go do it?
[01:13:40.680 --> 01:13:41.960] I have this addiction issue.
[01:13:41.960 --> 01:13:43.000] I've got PTSD.
[01:13:43.000 --> 01:13:43.920] I've got trauma.
[01:13:43.640 --> 01:13:49.760] There's a few places people go, like in Mexico, beyond, or Ambio, and also in Mexico.
[01:13:43.880 --> 01:13:51.280] There's a few places out there.
[01:13:51.600 --> 01:13:53.760] What do you say to people who want to go sort of explore this?
[01:13:54.240 --> 01:14:00.080] Yeah, I mean, the good news is that we, you know, it looks like there's actually going to be some U.S.
[01:14:00.080 --> 01:14:05.280] trials soon, you know, and so being able to do this from inside of the U.S.
[01:14:05.280 --> 01:14:07.600] is kind of the ultimate goal.
[01:14:07.600 --> 01:14:20.160] You know, folks go to these places and these other countries, but the ultimate goal is really to see that folks can do this safely in the U.S.
[01:14:20.400 --> 01:14:29.680] And so I think 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.
[01:14:29.680 --> 01:14:46.080] And the hope 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?
[01:14:46.080 --> 01:14:48.640] And so that's and see what happens.
[01:14:48.640 --> 01:14:51.840] And so it is coming soon.
[01:14:51.840 --> 01:14:54.320] You know, we'll have to see what happens with the FDA.
[01:14:54.320 --> 01:15:04.800] But yeah, I think that's an exciting moment for folks and being able to have access to an experimental therapeutic like this.
[01:15:04.800 --> 01:15:08.400] And if people want to go down and try this in Mexico, do you advise against it?
[01:15:08.400 --> 01:15:10.320] Do you say at your own risk?
[01:15:11.120 --> 01:15:12.480] It's definitely a people's own risk.
[01:15:12.480 --> 01:15:17.760] I mean, look, it's one of these things where we still don't know that much about this.
[01:15:17.760 --> 01:15:25.920] 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.
[01:15:26.480 --> 01:15:28.000] Couldn't encourage them to do it, yeah.
[01:15:28.000 --> 01:15:30.840] Yeah, we couldn't encourage them to do it.
[01:15:29.280 --> 01:15:35.080] We didn't really participate in any of the processes for them to do it.
[01:15:35.400 --> 01:15:39.640] We simply just studied people that were already going down there.
[01:15:39.640 --> 01:15:52.520] 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.
[01:15:52.520 --> 01:15:52.920] Yeah.
[01:15:52.920 --> 01:15:55.720] Borderline personality, narcissistic personality, that gets so effective.
[01:15:55.720 --> 01:16:01.160] There's all these personality disorders, which are more like fixed personality traits that are hard to change.
[01:16:01.160 --> 01:16:17.480] 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.
[01:16:17.480 --> 01:16:18.280] It's a great question.
[01:16:18.280 --> 01:16:30.920] I mean, the Hopkins group demonstrated this profound personality change that they observed out to a year, I think, early on with their trials of psilocybin.
[01:16:30.920 --> 01:16:38.760] And so there's definitely data that there's personality change, you know, in and around psilocybin use.
[01:16:38.760 --> 01:16:40.200] It's an open question.
[01:16:40.200 --> 01:16:51.880] 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.
[01:16:51.880 --> 01:17:00.680] And so actually people that I think it was like 16% of people were not religious prior to taking Ibogaine.
[01:17:00.680 --> 01:17:11.160] And there's an increased kind of sense of a higher power or whatever after like almost, you know, two-thirds of people.
[01:17:11.160 --> 01:17:17.120] And so, this question of how do people see the world that they live in is really interesting.
[01:17:17.120 --> 01:17:23.680] But yeah, you know, nobody's done a personality inventory study with Ibogaine, so it's still an open question.
[01:17:23.680 --> 01:17:25.680] Is it dangerous for these people to do anything?
[01:17:25.680 --> 01:17:31.280] It's certainly dangerous for people with a psychotic history, you know.
[01:17:31.280 --> 01:17:34.960] I think people with bipolar disorder, that's going to be dangerous.
[01:17:34.960 --> 01:17:38.400] Maybe somebody with severe borderline, maybe, you know, it just depends.
[01:17:38.880 --> 01:17:41.120] It depends on a kind of individual basis.
[01:17:41.120 --> 01:17:44.720] The problem at a fundamental level is we just haven't studied this enough to really know.
[01:17:44.720 --> 01:17:47.520] We don't have enough data sets to know what's going on with these people.
[01:17:47.520 --> 01:17:48.400] Yeah, interesting.
[01:17:48.400 --> 01:17:57.600] 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?
[01:17:57.600 --> 01:18:03.840] 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.
[01:18:03.840 --> 01:18:20.960] 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 the profound suffering that's out there.
[01:18:20.960 --> 01:18:29.920] 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.
[01:18:29.920 --> 01:18:30.800] That's a psychiatric.
[01:18:31.040 --> 01:18:32.880] Purely psychiatric or dementia.
[01:18:32.880 --> 01:18:33.680] One out of two.
[01:18:33.680 --> 01:18:34.400] One out of two.
[01:18:34.400 --> 01:18:35.600] That's a lot.
[01:18:35.600 --> 01:18:40.640] Half of the population of the world is going to have some mental illness at some point in their life.
[01:18:40.640 --> 01:18:42.000] It's a scaling problem.
[01:18:42.000 --> 01:18:42.640] Think about it.
[01:18:42.640 --> 01:18:47.600] I mean, at the end of the day, we would never be able to actually effectively deal with that.
[01:18:47.600 --> 01:18:49.120] Definitely not through therapy.
[01:18:49.120 --> 01:18:50.160] Definitely not through therapy.
[01:18:50.160 --> 01:18:51.680] You'd have to have half the world become therapy.
[01:18:51.760 --> 01:18:54.400] I mean, maybe with AI, you know, all of us are trying to figure out.
[01:18:54.640 --> 01:18:54.960] That's right.
[01:18:54.960 --> 01:18:57.040] AI therapists are pretty damn good.
[01:18:57.040 --> 01:18:59.360] This psychedelic revolution to me is very promising.
[01:18:59.360 --> 01:19:08.760] 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.
[01:19:08.760 --> 01:19:17.480] It's harder for people to do that because it requires a lot of lifestyle change, whereas this is just a sort of a brain reset that then seems like it would facilitate behavioral lifestyle change.
[01:19:17.480 --> 01:19:22.920] It's almost like this could set the stage and then you could have an easier time doing that other hard work.
[01:19:22.920 --> 01:19:26.040] What studies are on the horizon for you that you're looking at doing?
[01:19:26.040 --> 01:19:37.080] We're looking forward to seeing what happens, this Texas effort, and hopefully there's some funding for Texas-based universities to do this and to do these treatments.
[01:19:37.080 --> 01:19:41.960] But yeah, it's an open question about what's going to happen with the FDA.
[01:19:41.960 --> 01:19:47.960] And I think if the FDA comes through and lets us do the studies, there'll be a normal healthy control study.
[01:19:47.960 --> 01:19:53.880] We're hoping to add some biology to that and then subsequently, hopefully, some traumatic brain injury studies.
[01:19:53.880 --> 01:19:55.880] When you say biology, do you mean biomarkers, blood tests?
[01:19:56.120 --> 01:20:03.240] And 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?
[01:20:03.240 --> 01:20:06.680] We hope to do some of that, at least the EEG side of things.
[01:20:06.680 --> 01:20:16.840] 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, you know.
[01:20:16.840 --> 01:20:17.880] Fascinating work.
[01:20:18.120 --> 01:20:19.400] Incredible what you're doing.
[01:20:19.720 --> 01:20:24.200] You're definitely going out of limb in the psychiatric world.
[01:20:24.200 --> 01:20:33.080] I think you're brave, but you're at Stanford and a respected institution and they seem to be in support of you doing this work, which is amazing.
[01:20:33.400 --> 01:20:40.280] And we need a Hail Mary in psychiatry because we are in a bad state as a world.
[01:20:40.840 --> 01:21:00.320] We're all divided and disconnected and isolated and struggling with various forms of just the 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.
[01:21:00.320 --> 01:21:01.120] It's just amazing.
[01:21:01.120 --> 01:21:02.800] So thanks for doing what you do.
[01:21:02.800 --> 01:21:03.760] Yeah, thanks for having me.
[01:21:04.320 --> 01:21:10.720] When it comes to supplements, you only want the best for your body, the kind with the highest quality, cleanest, and most potent ingredients you can get.
[01:21:10.720 --> 01:21:18.720] That's exactly what you'll find at my supplement store where I've hand-selected each and every product to meet the most rigorous standards for safety, purity, and effectiveness.
[01:21:18.720 --> 01:21:23.120] These are the only supplements I recommend to my patients, and they're also what I use myself.
[01:21:23.120 --> 01:21:37.760] Whether you want to optimize longevity or reduce your disease risk, or you're looking to improve your sleep, blood, sugar, metabolism, gut health, you name it, drhyman.com has the world's best selection of top quality premium supplements, all backed by science and expertly vetted by me, Dr.
[01:21:37.760 --> 01:21:38.800] Mark Hyman.
[01:21:38.800 --> 01:21:43.760] So check out drhyman.com because when it comes to your health, nothing less than the very best will do.
[01:21:43.760 --> 01:21:47.520] That's drhyman.com, d-r-h-y-m-a-n.com.
[01:21:48.240 --> 01:21:52.400] If you love this podcast, please share it with someone else you think would also enjoy it.
[01:21:52.400 --> 01:21:55.440] You can find me on all social media channels at drmarkhyman.
[01:21:55.440 --> 01:21:56.000] Please reach out.
[01:21:56.000 --> 01:21:58.000] I'd love to hear your comments and questions.
[01:21:58.000 --> 01:22:00.320] Don't forget to rate, review, and subscribe to the Dr.
[01:22:00.320 --> 01:22:02.480] Hyman Show wherever you get your podcasts.
[01:22:02.480 --> 01:22:04.720] And don't forget to check out my YouTube channel at Dr.
[01:22:04.720 --> 01:22:07.920] MarkHyman for video versions of this podcast and more.
[01:22:07.920 --> 01:22:09.840] Thank you so much again for tuning in.
[01:22:09.840 --> 01:22:11.200] We'll see you next time on the Dr.
[01:22:11.200 --> 01:22:12.160] Hyman Show.
[01:22:12.160 --> 01:22:19.200] 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.
[01:22:19.200 --> 01:22:22.080] This podcast represents my opinions and my guests' opinions.
[01:22:22.080 --> 01:22:25.920] Neither myself nor the podcast endorses the views or statements of my guests.
[01:22:25.920 --> 01:22:32.760] This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional.
[01:22:33.000 --> 01:22:39.160] This podcast is provided with the understanding that it does not constitute medical or other professional advice or services.
[01:22:39.160 --> 01:22:43.560] If you're looking for help in your journey, please seek out a qualified medical practitioner.
[01:22:43.560 --> 01:22:51.960] And if you're looking for a functional medicine practitioner, visit my clinic, theultrawellnesscenter at ultrawellnesscenter.com, and request to become a patient.
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[01:23:04.600 --> 01:23:09.000] So I'd like to express gratitude to sponsors that made today's podcast possible.
[01:23:09.000 --> 01:23:10.760] Thanks so much again for listening.

Prompt 6: Key Takeaways

Now please extract the key takeaways from the transcript content I provided.

Extract the most important key takeaways from this part of the conversation. Use a single sentence statement (the key takeaway) rather than milquetoast descriptions like "the hosts discuss...". 

Limit the key takeaways to a maximum of 3. The key takeaways should be insightful and knowledge-additive. 

IMPORTANT: Return ONLY valid JSON, no explanations or markdown. Ensure:
- All strings are properly quoted and escaped
- No trailing commas
- All braces and brackets are balanced
Format: {"key_takeaways": ["takeaway 1", "takeaway 2"]}

Prompt 7: Segments

Now identify 2-4 distinct topical segments from this part of the conversation.

For each segment, identify:
- Descriptive title (3-6 words)  
- START timestamp when this topic begins (HH:MM:SS format)
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Most important Key takeaway from that segment. Key takeaway must be specific and knowledge-additive.
- Brief summary of the discussion

IMPORTANT: The timestamp should mark when the topic/segment STARTS, not a range. Look for topic transitions and conversation shifts.

Return ONLY valid JSON. Ensure all strings are properly quoted, no trailing commas:
{
  "segments": [
    {
      "segment_title": "Topic Discussion", 
      "timestamp": "01:15:30",
      "key_takeaway": "main point from this segment",
      "segment_summary": "brief description of what was discussed"
    }
  ]
}

Timestamp format: HH:MM:SS (e.g., 00:05:30, 01:22:45) marking the START of each segment.

Prompt 8: Media Mentions

Now scan the transcript content I provided for ACTUAL mentions of specific media titles:

Find explicit mentions of:
- Books (with specific titles)
- Movies (with specific titles)  
- TV Shows (with specific titles)
- Music/Songs (with specific titles)

DO NOT include:
- Websites, URLs, or web services
- Other podcasts or podcast names

IMPORTANT: 
- Only include items explicitly mentioned by name. Do not invent titles.
- Valid categories are: "Book", "Movie", "TV Show", "Music"
- Include the exact phrase where each item was mentioned
- Find the nearest proximate timestamp where it appears in the conversation
- THE TIMESTAMP OF THE MEDIA MENTION IS IMPORTANT - DO NOT INVENT TIMESTAMPS AND DO NOT MISATTRIBUTE TIMESTAMPS
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Timestamps are given as ranges, e.g. 01:13:42.520 --> 01:13:46.720. Use the EARLIER of the 2 timestamps in the range.

Return ONLY valid JSON. Ensure all strings are properly quoted and escaped, no trailing commas:
{
  "media_mentions": [
    {
      "title": "Exact Title as Mentioned",
      "category": "Book",
      "author_artist": "N/A",
      "context": "Brief context of why it was mentioned",
      "context_phrase": "The exact sentence or phrase where it was mentioned",
      "timestamp": "estimated time like 01:15:30"
    }
  ]
}

If no media is mentioned, return: {"media_mentions": []}

Full Transcript

[00:00:00.320 --> 00:00:02.000] Coming up on this episode of the Dr.
[00:00:02.000 --> 00:00:15.920] Hyman Show, what you said blew my mind, which is that there's this compound out there that can abruptly interrupt a withdrawal from addiction that can help treat PTSD, depression, traumatic brain injury better than anything else we have out there on the market.
[00:00:15.920 --> 00:00:17.520] And orders of magnitude more.
[00:00:17.520 --> 00:00:17.840] Dr.
[00:00:17.840 --> 00:00:23.840] Nolan Williams is a triple board-certified neuropsychiatrist and founder of Stanford's Brain Stimulation Lab.
[00:00:23.840 --> 00:00:31.600] He's redefining how we treat depression, PTSD, and addiction using brain stimulation, psychedelics, and neuroscience instead of meds.
[00:00:31.600 --> 00:00:40.400] 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.
[00:00:40.400 --> 00:00:48.400] I think this is like a really paradigm-shifting moment where work like yours have really started to push the envelope and say, hey, wait a minute, like we're thinking about mental illness all wrong.
[00:00:48.400 --> 00:00:51.280] We're talking about like one dose, one day, having one dose.
[00:00:51.280 --> 00:00:54.080] It's a effect to reverse your brain age by a year and a half out of a month.
[00:00:54.080 --> 00:00:55.200] That's pretty remarkable.
[00:00:55.200 --> 00:00:56.800] Is it dangerous for these people to do?
[00:01:02.000 --> 00:01:05.360] When I'm working with my patients, the gut is ground zero for health.
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[00:01:30.000 --> 00:01:35.200] What's especially exciting is that DSO1 is clinically proven to promote short-chain fatty acid production.
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[00:02:50.360 --> 00:02:52.520] All right, Nolan, great to have you on the podcast.
[00:02:52.520 --> 00:02:53.240] Thanks for being here.
[00:02:53.240 --> 00:02:54.040] Yeah, thanks for having me.
[00:02:54.360 --> 00:02:55.640] You know, I followed your work.
[00:02:55.640 --> 00:03:17.960] 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 a withdrawal from addiction, that can help treat PTSD, depression, traumatic brain injury better than anything else we have out there on the market, and orders of magnitude more.
[00:03:18.280 --> 00:03:26.680] And I became very interested in following this conversation about this incredible compound called ibogaine that we're going to learn more about today.
[00:03:26.680 --> 00:03:33.080] And it comes from a bark of a tree in Gabon, in West Africa.
[00:03:33.080 --> 00:03:38.440] It's used in ritual ceremony there for different kinds of ritual transitions through life.
[00:03:38.440 --> 00:03:40.840] It's got a fascinating history.
[00:03:41.000 --> 00:03:46.960] I maybe would love to start by helping us understand, you know, what is it exactly?
[00:03:46.960 --> 00:04:03.920] 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 public 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.
[00:04:03.920 --> 00:04:08.640] Because, you know, the truth is, one in four people have had sexual abuse, which is crazy.
[00:04:08.800 --> 00:04:13.840] Trauma is a real thing, whether it's micro-traumas because your parents neglected you, or big traumas.
[00:04:14.080 --> 00:04:17.280] Gabbar Mati talks about big tea, little tea trauma.
[00:04:17.280 --> 00:04:28.400] 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 fulfilled life.
[00:04:28.400 --> 00:04:31.760] And, you know, psychiatric medicine is just very antiquated.
[00:04:32.000 --> 00:04:33.200] It's very crude.
[00:04:33.520 --> 00:04:37.760] It's tremendous side effects of the drugs we use.
[00:04:38.000 --> 00:04:40.640] Many of them don't work very well.
[00:04:40.640 --> 00:04:46.400] And we're kind of in this unfortunate situation where mental health crisis is bigger than ever.
[00:04:46.400 --> 00:04:49.040] We have fewer things that really work.
[00:04:49.040 --> 00:04:52.640] And this seems to hold the promise of something really quite different.
[00:04:52.640 --> 00:04:54.960] Yeah, thanks for the intro there.
[00:04:54.960 --> 00:04:58.000] Yeah, it's an interesting compound.
[00:04:58.000 --> 00:04:59.360] It's been around for a long time.
[00:04:59.360 --> 00:05:07.840] It's an African root bark psychedelic, as you suggested, from Gabon and Central West Africa, so kind of neighboring areas.
[00:05:07.840 --> 00:05:12.800] And the group of people that use it are called the Buiti.
[00:05:12.800 --> 00:05:18.080] And Buiti just means that you've taken Iboga and rituals ceremony, right?
[00:05:18.080 --> 00:05:23.680] And so folks have been doing this for quite a long time.
[00:05:24.000 --> 00:05:32.680] And they've been doing it because it has a, it produces this kind of what people would call a transformative psychological experience.
[00:05:32.840 --> 00:05:42.280] So people will go into this, they'll have kind of a massive change in consciousness over the course of, you know, 24 to 36 hours.
[00:05:42.280 --> 00:05:51.320] And during that time, they'll have a psychological experience of reevaluating earlier life emotionally salient memories.
[00:05:51.320 --> 00:05:58.520] And for maybe all of us, for a lot of us, those are trauma at various scales, you know.
[00:05:59.480 --> 00:06:11.800] And people will take a look at those earlier life kind of emotionally salient events, but they'll do it from a position, kind of a third-party position of seeing it from neutrality.
[00:06:11.800 --> 00:06:23.080] 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.
[00:06:23.080 --> 00:06:33.720] IBM seems, 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.
[00:06:33.720 --> 00:06:40.280] So you're not being guided, or there's no therapist.
[00:06:40.280 --> 00:06:44.200] The drug just automatically puts your brain into this mode, it seems.
[00:06:44.200 --> 00:06:51.240] And then people have what they call this life review or slideshow where they're looking at these emotionally salient memories over time.
[00:06:51.240 --> 00:06:58.520] And when they do that, they're able to see, they're able to see the, you know, the memories from a different lens.
[00:06:58.520 --> 00:07:10.680] 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.
[00:07:10.680 --> 00:07:12.760] And that's pretty powerful.
[00:07:12.760 --> 00:07:22.160] To your point, you know, psychiatric medicine has created tools that look a lot like you know medieval or 15th century whatever keys, right?
[00:07:22.160 --> 00:07:30.240] Like we've thought about the brain like a single-tooth key that you put the key into the lock and you turn it and the key unlocks the door.
[00:07:30.240 --> 00:07:37.840] But the brain is probably much more like a modern-day key with a lot of different pins and a lot of different interactions.
[00:07:37.840 --> 00:07:43.920] So when you put the key into the lock, it really needs to interact with a lot of different systems.
[00:07:43.920 --> 00:07:57.360] The problem with, in my view, with kind of current psychopharmacology and the way that we see it is that we still think that it's a single neurotransmitter or single receptor problem.
[00:07:57.360 --> 00:08:07.040] Serotonin's low, so take serotonin reptake inhibitors like Prozac or your dopamine's low, so take basically speed, otherwise known as Adderall or Riddle.
[00:08:07.280 --> 00:08:11.520] If you look at the pharmacology of Ibogaine, it's very broad acting, right?
[00:08:11.520 --> 00:08:19.600] So it actually interacts with a lot of, I mean, essentially all the neurotransmitter systems in a unique way.
[00:08:19.600 --> 00:08:50.400] 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 multi-site trials the sort of data that we're seeing now in our studies and studies coming out of that are going to 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 kind of a multi-receptor drug system is probably correct.
[00:08:50.400 --> 00:08:58.080] And this idea of a single neurotransmitter system, low serotonin or whatever, where we're simplifying things down is probably oversimplified.
[00:08:58.080 --> 00:09:00.000] You know, and those tools are too coarse.
[00:09:00.520 --> 00:09:10.040] You know, in medicine, we call these sort of multiple effect phenomenon pleiotropic effects, which means they work on many, many different pathways and systems.
[00:09:10.040 --> 00:09:24.680] You know, I want to get into sort of more of the applications of it and 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.
[00:09:24.680 --> 00:09:26.440] So it doesn't just change it in the moment.
[00:09:26.440 --> 00:09:41.640] It seems to have lasting changes, which is why, and I think we're still trying to figure out, you know, 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.
[00:09:41.640 --> 00:09:45.400] It's not like they're psychologically suppressing the withdrawal symptoms.
[00:09:45.400 --> 00:09:46.600] They just don't have them.
[00:09:47.000 --> 00:09:48.120] And that's really fascinating.
[00:09:48.120 --> 00:09:59.080] 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 overexcited with trauma.
[00:09:59.080 --> 00:10:02.040] It does affect somehow the serotonin system.
[00:10:02.040 --> 00:10:07.160] It affects brain factors like PDNF, which is otherwise known as brain-derived neurotrophic factor.
[00:10:07.160 --> 00:10:14.760] It helps stimulate brain growth and connectivity, neurogenesis, neuroplasticity, more brain cells, more connections between brain cells.
[00:10:14.760 --> 00:10:19.320] So they do all these really interesting things that repair the brain, to heal the brain.
[00:10:19.320 --> 00:10:28.360] 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.
[00:10:28.360 --> 00:10:30.920] So it seems to have all these varying effects.
[00:10:30.920 --> 00:10:36.120] And they also sort of inhibit what we call the default mode network, which is what a lot of other psychedelics do.
[00:10:36.120 --> 00:10:42.360] It's sort of the ego and the self-protection part of your brain, which is, you know, makes us feel separate and disconnected.
[00:10:42.360 --> 00:11:00.000] And when that is suppressed, whether you meditate for 40 years or you take psilocybin or LSD, MDMA, or Ibogaine, that quiets down quickly and 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 whole.
[00:11:00.000 --> 00:11:09.120] And that and so I kind of would love you to unpack some of the mechanisms and how they work in these different disease states because it's like seems like a one-size-fits-all.
[00:11:09.120 --> 00:11:13.360] You know, you got PTSD, you got depression, you got anxiety, you got trauma, you got brain injury.
[00:11:13.360 --> 00:11:20.640] Can you kind of unpack those for us and talk about how they affect across these various pathways in the brain?
[00:11:20.640 --> 00:11:21.920] Yeah, that's a great question.
[00:11:22.560 --> 00:11:30.960] So the other mechanism that we've thought a lot about that's unique to ibogaine is glial-derived neurotrophic factor, right?
[00:11:30.960 --> 00:11:40.720] So glial-derived neurotrophic factor is a neurotrophic factor that's involved with dopamine neuron kind of health, right?
[00:11:40.720 --> 00:11:43.840] And so it upregulates dopamine neuron health.
[00:11:43.840 --> 00:12:02.960] And so there was a study, you know, 20 years ago or something where they took mice and mice or rats and they trained 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 tube.
[00:12:02.960 --> 00:12:06.000] And if you take a mouse and you do that.
[00:12:06.080 --> 00:12:07.440] Oh, little rat bartender there?
[00:12:07.840 --> 00:12:08.400] Something like that.
[00:12:08.400 --> 00:12:10.880] Yeah, they pull up to the bar.
[00:12:10.880 --> 00:12:13.920] They'll drink until eventually they die, right?
[00:12:14.400 --> 00:12:22.400] And if you take a mouse like that and you give them ibogaine, you can actually reverse it.
[00:12:22.400 --> 00:12:25.840] They'll stop self-administering alcohol, which is cool.
[00:12:25.840 --> 00:12:41.000] 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.
[00:12:41.000 --> 00:12:43.480] They will stop self-administering.
[00:12:43.640 --> 00:12:50.120] Inject just ibogaine just into that area, you can recapitulate the effect, right?
[00:12:50.120 --> 00:12:57.160] And people have also shown that you can produce this effect by directly stimulating into those areas, right?
[00:12:57.160 --> 00:13:15.720] And so it's probably that at least the anti-addiction mechanism of ibogaine is that it's restoring dopamine function within that ventral tegmental area in a way that resets the reward system.
[00:13:16.360 --> 00:13:38.200] 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 in our trial that received ibogaine had EEG brainwave tests before, after, and one month after they received ibogaine.
[00:13:38.200 --> 00:13:47.960] And what we saw is this kind of general slowing of all of the kind of different power spectra of the EEG, right?
[00:13:47.960 --> 00:13:54.520] So people had a general kind of physiologic slowing of their brain after.
[00:13:54.520 --> 00:14:11.320] And the slowing actually was correlated with the strength of the trip, like the amount that they had a psychological effect, but also interestingly, the reduction in PTSD symptoms and the improvement in cognition.
[00:14:11.320 --> 00:14:15.200] And so, you know, that's, it's a first-step study.
[00:14:14.840 --> 00:14:20.080] You know, it was pretty good, I think, in the sense we got into nature mental health.
[00:14:20.400 --> 00:14:22.640] But, you know, we need to do some more work on this.
[00:14:22.640 --> 00:14:39.280] So I'm not claiming that this is definitive, but it's likely that if you have an EEG, you may be able to tune the dose to the physiology of the brain instead of getting a subjective readout.
[00:14:39.440 --> 00:14:48.160] 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?
[00:14:48.160 --> 00:14:49.680] So you're kind of, you know, fully.
[00:14:49.840 --> 00:14:54.560] Some people need more, some people need less, and you can tell by the EEG who needs what, and then can upper.
[00:14:55.360 --> 00:14:56.800] That would be the promise, right?
[00:14:56.800 --> 00:15:02.400] That would be, you know, if it plays out, that would be, and we do this already in medicine, as you know.
[00:15:02.400 --> 00:15:08.800] We use biz monitors and anesthesia to kind of measure the level of anesthesia.
[00:15:08.800 --> 00:15:17.760] Or if somebody is, you know, being fully anesthetized with like propofol, you can actually birth suppress them.
[00:15:17.760 --> 00:15:22.160] And you're using an EEG to help you dose a drug.
[00:15:22.160 --> 00:15:25.600] You know, so that's not a new concept in neurology.
[00:15:25.600 --> 00:15:28.560] It's just a new concept within kind of psychiatry, right?
[00:15:28.960 --> 00:15:32.000] And so being able to figure that out, I think, is useful.
[00:15:32.000 --> 00:15:39.040] Well, that's the old joke: neurologists pay no attention to the mind, and psychiatrists pay no attention to the brain.
[00:15:39.040 --> 00:15:44.400] And here you are, you know, looking at psychiatry through the lens of the brain, not just the mind.
[00:15:44.880 --> 00:15:51.760] Freud kind of took us down the path of mind-only psychiatry and talk therapy and psychoanalysis.
[00:15:52.080 --> 00:16:03.080] And it's sort of striking because, you know, you hear, oh, well, yeah, I've heard psychoanalysis say, well, you could come to psychoanalysis five days a week for the next 20 years and then you'll maybe see some improvement.
[00:16:03.720 --> 00:16:12.520] And here you're like, well, you can go to Mexico and do one Ibogaine journey and like that takes care of like 20 years of psychotherapy.
[00:16:12.520 --> 00:16:14.600] I mean, it's kind of crazy.
[00:16:14.600 --> 00:16:20.760] Yeah, I mean, you know, there's a lot of work to do to kind of totally prove that.
[00:16:20.760 --> 00:16:23.000] I mean, that's what, that's certainly what people will say.
[00:16:23.000 --> 00:16:32.360] That's what Claudio Naranjo said, I think, in, you know, the Argentinian psychiatrist many, many decades ago about Ibogaine.
[00:16:32.360 --> 00:16:38.760] It's just one of these things where we're going to have to do the work, you know, do the good work to figure it out.
[00:16:38.760 --> 00:16:54.280] But I think that the problem and the kind of 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.
[00:16:54.280 --> 00:17:05.480] You know, people can have an entire tragic life problem over the course of the time it would take, you know, for many of our treatments to work.
[00:17:05.480 --> 00:17:09.160] I mean, psychoanalysis for 10 years is one.
[00:17:09.160 --> 00:17:11.960] Just normal oral antidepressants, you know?
[00:17:11.960 --> 00:17:19.640] I mean, we've seen people start out an oral antidepressant and lose their job by the time it starts to have any effect, right?
[00:17:19.640 --> 00:17:30.360] 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.
[00:17:30.360 --> 00:17:45.000] It's kind of an exciting moment in psychiatry because 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.
[00:17:45.840 --> 00:17:58.720] And what's really exciting to me in psychiatry, because I've been thinking about this for decades, I wrote a book almost 20 years ago called The Ultra Mind Solution, which details how the brain is influenced by everything happening in your body.
[00:17:59.280 --> 00:18:04.640] And you can actually use those physiological levers to change psychiatric symptoms.
[00:18:04.640 --> 00:18:24.400] So if we 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 ascribe all kinds of meaning and we have all these stigmas against these things.
[00:18:24.400 --> 00:18:31.520] And, you know, if someone's limping because their meniscus is torn in their knee, we don't go, oh, you're a fuck-up.
[00:18:32.800 --> 00:18:37.520] But when someone has a mental illness, there's a stigma of, oh, there's something wrong with you.
[00:18:37.520 --> 00:18:40.160] Like, it's kind of, you're crazy.
[00:18:40.160 --> 00:18:41.040] It's your fault.
[00:18:41.040 --> 00:18:47.600] But actually, there's literally physiological and structural things happening within the brain that make it not work.
[00:18:47.600 --> 00:18:51.200] Just like if your knee doesn't work or you're limping because you've got a meniscus tear.
[00:18:51.200 --> 00:19:03.280] But now we're able to start to image those things, to see those changes in patterns, and to actually treat the structure and function of the brain through a multi-pronged approach.
[00:19:03.280 --> 00:19:06.480] Most psychiatric illnesses are inflammatory problems in the brain.
[00:19:06.480 --> 00:19:08.240] So if you have inflammation in your knee, it hurts.
[00:19:08.240 --> 00:19:13.520] But if your brain doesn't hurt, it just creates all these crazy psychiatric symptoms.
[00:19:13.600 --> 00:19:24.640] I think this is like a really paradigm shifting moment where work like yours have really started to pushed the envelope and say, hey, wait a minute, like we're thinking about mental illness all wrong and looking at the wrong end of the stick.
[00:19:24.640 --> 00:19:28.880] And to me, that's exciting because so many people are suffering, but it's not happening fast enough.
[00:19:28.880 --> 00:19:30.120] You're involved in the whole field.
[00:19:29.840 --> 00:19:33.000] But I think there is, and there is funding now going into research.
[00:19:33.080 --> 00:19:38.600] And I think in Texas, there's $50 million allocated for a research effort on Ibogaine, which is like I was sort of shocked to see.
[00:19:38.600 --> 00:19:40.840] And your work has kind of taken it to a new level.
[00:19:40.840 --> 00:19:49.320] And the thing that I think we're in now is this both metabolic nutritional psychiatry revolution and this psychedelic psychiatry revolution.
[00:19:49.400 --> 00:19:51.080] They're too, I think, synergistic.
[00:19:51.080 --> 00:19:53.240] I'd like to see them work together more.
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[00:21:58.560 --> 00:22:03.280] The question with psychedelics is there's a lot of them out there, and people I think maybe are confused.
[00:22:03.280 --> 00:22:20.800] 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.
[00:22:20.800 --> 00:22:27.600] So, how is it different from other psychedelics mechanistically and even experientially for people?
[00:22:27.600 --> 00:22:30.480] To your point, there's a wide range of psychedelics.
[00:22:31.680 --> 00:22:36.640] Right now, there's not really an approval for any classic psychedelics.
[00:22:36.640 --> 00:22:47.440] You know, there's no, and that, you know, there is some interest at the level of the current administration and the Health and Human Services Secretary and all of that as far as kind of getting that done.
[00:22:47.440 --> 00:22:52.000] But as of now, you know, there's not an approval.
[00:22:52.000 --> 00:23:00.600] And so there's, you know, there's a lot of trials around MDMA for PTSD, psilocybin primarily for depression.
[00:22:59.680 --> 00:23:04.440] People are trying LSD for generalized anxiety disorder, other things.
[00:23:05.080 --> 00:23:17.880] And ibogaine is probably the latest person to the party or whatever to the party in the sense that the plant to the party.
[00:23:17.880 --> 00:23:20.440] Yeah, the last plant to the party.
[00:23:21.400 --> 00:23:29.560] The reason for that is because ibogaine has the most complexity to it and the most inherent risk to it.
[00:23:29.560 --> 00:23:36.360] And so the problem with ibogaine as an inherent risk problem is that it has this cardiac risk, right?
[00:23:36.360 --> 00:23:40.280] So it actually will prolong the QT interval.
[00:23:40.280 --> 00:23:45.320] For people that don't know, it's a kind of a part of the physiology of the heart.
[00:23:45.320 --> 00:23:47.000] Lots of drugs do that.
[00:23:47.720 --> 00:23:49.880] Antipsychotics do that, right?
[00:23:50.200 --> 00:23:54.360] Geodon in particular does that at a great degree.
[00:23:54.360 --> 00:23:58.920] So it's not a unique, you know, within psychiatry, lots of drugs that do that.
[00:23:58.920 --> 00:24:02.280] Within medicine, as you know, there's lots of drugs that do that.
[00:24:02.280 --> 00:24:07.960] But, you know, it prolongs the QT quite a bit for a very short period of time.
[00:24:07.960 --> 00:24:18.760] And there have been a couple of deaths because people were getting administered Ibogaine in unmonitored or minimally monitored settings.
[00:24:18.760 --> 00:24:38.520] And so the problem with doing ibogaine research is that 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 the kind of case reports of risk.
[00:24:38.520 --> 00:24:46.640] So, we started, you know, the work that we did actually studying people that were already going to Mexico to take ibogaine, right?
[00:24:44.840 --> 00:24:51.040] So, they were already headed down there, they were already kind of consented to go down there.
[00:24:51.280 --> 00:25:00.960] And then, our job was, you know, simply to kind of do an observational study around that phenomenon that was already happening.
[00:25:00.960 --> 00:25:13.200] 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.
[00:25:13.200 --> 00:25:15.600] And so, you know, people have a varying degree.
[00:25:15.840 --> 00:25:19.120] IND is just for people listening as investigational new drug applications.
[00:25:19.120 --> 00:25:22.960] So, how do we go to the FDA and ask for permission to study something?
[00:25:22.960 --> 00:25:25.840] You need an application for that.
[00:25:25.840 --> 00:25:32.720] You need an application, and there's a chicken and egg problem of like, how do you take such a complicated drug and get an IND?
[00:25:32.720 --> 00:25:35.200] And so, there's a lot of that that goes on.
[00:25:35.200 --> 00:25:37.680] And so, people have had a hard time doing this.
[00:25:37.680 --> 00:25:41.280] And you could say, well, you know, this is a drug with risk.
[00:25:41.280 --> 00:25:43.440] You know, should we be doing this or not?
[00:25:43.440 --> 00:25:53.200] 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.
[00:25:53.200 --> 00:25:56.160] And so, Tecosin is a cardiac drug.
[00:25:56.160 --> 00:26:06.720] And if you ask the electrophysiologists, you know, cardiac electrophysiologists, and you show them the ibogaine data, they say, well, this is a risk, but Tecosin is just as much of a risk.
[00:26:06.720 --> 00:26:08.400] And we've gotten approval for Tekosin.
[00:26:08.720 --> 00:26:19.880] 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.
[00:26:19.880 --> 00:26:27.360] 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?
[00:26:27.360 --> 00:26:32.920] And Tecosin's used for like atrial fibrillation and for other kinds of arrhythmias.
[00:26:33.480 --> 00:26:43.000] And so people say, Well, this has a one in 100 risk of a torsad's event, but like if we don't do it, then somebody's going to die from a stroke from AFib.
[00:26:43.160 --> 00:26:47.320] So we can justify this risk with that risk, right?
[00:26:47.320 --> 00:26:55.000] And we know in opiate use disorder that there's a huge overdose risk in a person that's untreated.
[00:26:55.000 --> 00:27:11.080] And so 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.
[00:27:11.080 --> 00:27:16.040] And that justification allows us to say, no, actually, we're not going to study this.
[00:27:16.120 --> 00:27:21.720] Instead of understanding how many years of quality of life are lost, which is a real metric, quality of years.
[00:27:22.200 --> 00:27:22.920] Yeah, absolutely.
[00:27:22.920 --> 00:27:24.120] Or real death risk.
[00:27:24.600 --> 00:27:25.560] Death risk from overdose.
[00:27:25.560 --> 00:27:31.560] Yeah, it is a bit of a double standard because I think it's part of the bias in stigmatization of mental illness.
[00:27:31.560 --> 00:27:33.080] It's not a real thing.
[00:27:33.080 --> 00:27:39.400] You know, your heart arrhythmia is a real thing, but your depression is not a real thing, or your speed is not a real thing.
[00:27:40.040 --> 00:27:41.480] But yeah, it's amazing.
[00:27:41.480 --> 00:27:55.160] 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 very different than many other psychedelic.
[00:27:55.400 --> 00:28:05.320] I mean, the first story I heard about it was, you know, maybe 50 years ago, there was some drug addict who was in Amsterdam, and somebody said, Hey, try these cool pills, man.
[00:28:05.640 --> 00:28:07.160] And he did.
[00:28:07.480 --> 00:28:10.040] And the next day, his addiction was gone.
[00:28:10.040 --> 00:28:10.920] His cravings were gone.
[00:28:11.080 --> 00:28:14.560] So that was sort of the beginning of the understanding of effect in addiction medicine.
[00:28:14.440 --> 00:28:16.960] But it's just got all these broader effects.
[00:28:17.200 --> 00:28:33.680] So it's different than seems to be longer-lasting and more powerful in terms of resetting the brain and the sort of like almost a neurochemical reset than many of these other compounds, which work but don't have these persistent-lasting effects as much.
[00:28:33.680 --> 00:28:47.600] Yeah, so Howard Lotsov was the first, so just in the history of all this, you know, we know that Buiti were using this for at least 300 years, you know, probably, you know, most likely much longer than that.
[00:28:47.920 --> 00:28:54.480] The French started, discovered this in the Western world in about 1900.
[00:28:54.480 --> 00:29:00.880] It was on the French formulary from 1930 to 1966.
[00:29:00.880 --> 00:29:10.160] And it was actually a lower doses called labyrinth and was like a daily micro dose, essentially.
[00:29:10.160 --> 00:29:14.960] And so there's 36 years for attention problems and depression and things like that.
[00:29:14.960 --> 00:29:15.520] Wow.
[00:29:15.520 --> 00:29:21.600] And so for 36 years, it was used by the French and then placed on the French version of the Controlled Substances Act in 66.
[00:29:22.400 --> 00:29:24.640] And it was put on the U.S.
[00:29:24.640 --> 00:29:33.440] Controlled Substances Act, even though it doesn't really meet criteria for a controlled substance, for the description of a controlled substance.
[00:29:33.440 --> 00:29:37.200] It is neither, people don't self-administer it.
[00:29:38.000 --> 00:29:40.800] There's no animal data to suggest that there's a self-administration.
[00:29:40.800 --> 00:29:45.520] In fact, it reverses self-administration of other addictive compounds.
[00:29:45.520 --> 00:29:46.480] It's not a party drug.
[00:29:46.720 --> 00:29:47.760] It's not a party drug.
[00:29:47.760 --> 00:29:59.440] So it stops self-administration and it has this profound kind of psychological effect that doesn't really, it's not really reinforcing, right?
[00:29:59.440 --> 00:30:06.040] And so it doesn't really meet controlled substances description, but it was lumped in to the U.S.
[00:30:06.120 --> 00:30:14.680] Controlled Substance Act, Schedule I Substance, which is where it stayed since then and really prevented folks from using it.
[00:30:14.680 --> 00:30:30.200] And so Howard Lotsov 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.
[00:30:30.200 --> 00:30:35.240] And it's a very complicated timeline for folks to kind of get through.
[00:30:35.240 --> 00:30:48.520] And I think we're getting a signal now that finally we may be able to see that happen in our lifetimes that it could be that we could actually study this thing and make a real decision of whether or not it's useful.
[00:30:48.520 --> 00:30:58.760] 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.
[00:30:58.760 --> 00:31:03.160] That's an important study to do anyways from a public health standpoint, right?
[00:31:03.160 --> 00:31:16.280] Like the idea that we make plants illegal and then make them inaccessible for science is like it's a in 300 years, we're going to look at that and think that's just the craziest thing, I think.
[00:31:16.280 --> 00:31:18.120] Yeah, I mean, we have to study these things.
[00:31:18.120 --> 00:31:30.200] 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.
[00:31:30.200 --> 00:31:41.960] And I mean, I think it could really impact this incredible degree of trauma and PTSD and depression, anxiety, traumatic brain injury.
[00:31:41.960 --> 00:31:44.360] That's even fascinating to me, the brain injury stuff.
[00:31:44.320 --> 00:31:55.360] But the pathways that it works on are a lot of different pathways that reduce inflammation, oxidative stress, that increase neural protection, resilience of your cells.
[00:31:56.240 --> 00:32:01.440] And, you know, it just almost seems too good to be true how this works.
[00:32:01.440 --> 00:32:11.680] But it does have to be administered in a way that's safe because this risk of cardiac arrhythmias is high, and then you have to monitor that.
[00:32:11.920 --> 00:32:20.320] But with the magnesium therapy, which is what we use, it's funny to me that, you know, I used to work in the emergency room, and we had this thing called the crash card.
[00:32:20.320 --> 00:32:26.240] If someone comes in with cardiac arrest, you give them all these drugs, you give them epinephrine, you give them this drug, you give them that drug.
[00:32:26.240 --> 00:32:32.080] And then finally, like if every other drug fails and they're still in this terrible arrhythmia, you give them IV magnesium.
[00:32:32.080 --> 00:32:32.480] That's right.
[00:32:32.480 --> 00:32:33.040] That's right.
[00:32:33.040 --> 00:32:34.560] That's like the last draw.
[00:32:34.560 --> 00:32:36.320] I'm like, why don't we start out with that?
[00:32:36.720 --> 00:32:37.200] That's right.
[00:32:37.200 --> 00:32:39.440] You know, I've given a lot of IV magnesium in my life.
[00:32:39.440 --> 00:32:40.320] It's very safe.
[00:32:40.320 --> 00:32:45.600] We use it all the time in medicine for preeclampsia or hypertension in pregnancy for preterm labor.
[00:32:46.000 --> 00:32:53.280] Doctors don't somehow think of it as a compound that we should be using except in these extreme situations.
[00:32:53.280 --> 00:32:58.160] But it's actually one of the most important minerals and many of us are low in it or insufficient in it.
[00:32:58.160 --> 00:33:00.400] And I think stress causes it to be low.
[00:33:01.120 --> 00:33:08.000] Also caffeine, alcohol, a lot of things that we do actually cause us to deplete magnesium.
[00:33:08.000 --> 00:33:13.120] A lot of people are on anti-hypertensive drugs that cause you to lose magnesium, diuretics.
[00:33:13.120 --> 00:33:20.000] So you basically, you know, can mitigate a lot of these effects by tanking people up on magnesium if it's done in a controlled way.
[00:33:20.000 --> 00:33:23.280] And that's mitigated all those potential risks.
[00:33:23.280 --> 00:33:29.040] If you've never had a case in the magnesium administrative patients that you've used ibogaine with, right?
[00:33:29.040 --> 00:33:34.760] I mean, I, you know, I personally don't administer it.
[00:33:34.920 --> 00:33:55.000] 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, you know, and they'd had a, you know, a bad outcome, and then they, you know, started using it, and they hadn't had any cases since then.
[00:33:55.000 --> 00:34:10.440] And 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.
[00:34:10.440 --> 00:34:13.720] If you give magnesium, you can get some people out of torsades.
[00:34:13.720 --> 00:34:44.520] 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.
[00:34:44.520 --> 00:34:51.160] And that's the idea because the drug comes and goes, and then nobody has a risk of like post-treatment arrhythmia.
[00:34:51.160 --> 00:34:53.960] It's only during the kind of the peak levels of the drug.
[00:34:53.960 --> 00:34:59.160] And so if you can give magnesium to stabilize the heart, you can prevent this from happening.
[00:34:59.480 --> 00:35:17.520] Right now, 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.
[00:35:17.680 --> 00:35:24.960] But the question is: you know, do you still think people are going to need to be in a moderate setting with IB magnesium in order to actually safely take it?
[00:35:24.960 --> 00:35:28.560] Because it sounds like it's not something you can just sort of like prescribe people, right?
[00:35:28.560 --> 00:35:30.480] A bunch of different answers for that.
[00:35:30.480 --> 00:35:38.240] 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.
[00:35:38.240 --> 00:35:44.720] Now, Ibogaine at the current doses that people use, the kind of what we call flood doses.
[00:35:44.720 --> 00:35:55.760] 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.
[00:35:55.760 --> 00:36:02.960] If they're successful in doing that, then you're in a situation where one of these ibogaine analogs may be the solution.
[00:36:03.040 --> 00:36:05.280] Maybe you could take that at home or whatever.
[00:36:05.600 --> 00:36:08.160] And a lot of them aren't particularly psychedelic, right?
[00:36:08.160 --> 00:36:11.760] And so there's this, as you know, a big open question of do you need to have the trip?
[00:36:11.760 --> 00:36:13.600] Do you need to have this experience?
[00:36:13.600 --> 00:36:17.360] Or can you just have an agent that just changes brain plasticity and that's it?
[00:36:17.360 --> 00:36:20.480] And so that's a TBD sort of question.
[00:36:21.120 --> 00:36:23.120] But that may be a way to do it.
[00:36:23.120 --> 00:36:31.200] There are other iboga alkaloids that have more or less cardiotoxicity.
[00:36:31.520 --> 00:36:33.280] So that's a question.
[00:36:33.280 --> 00:36:38.320] And then we haven't really studied the dose ranges of ibogaine well at all.
[00:36:38.720 --> 00:36:50.960] And so it may be, 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.
[00:36:50.960 --> 00:36:59.000] And so it's one of these things where the Texas effort is going to be important to really hashing out what this is.
[00:36:58.640 --> 00:37:02.840] You know, these effects of dopamine and other things are powerful.
[00:37:03.160 --> 00:37:23.000] 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 that are 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.
[00:37:23.000 --> 00:37:50.120] So maybe you could spend a minute talking about your more recent study on 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 sort of physiological change that you saw with looking at functional MRIs and EEGs and other assessment techniques.
[00:37:50.120 --> 00:37:55.400] Because you're now looking at what's happening in the brain in ways that we couldn't really do before and that nobody's really looked at.
[00:37:55.400 --> 00:38:05.480] So ibogaine is a compound that, like I said, produces that physiologic kind of EEG-based change that we just published on.
[00:38:05.480 --> 00:38:09.480] We have more data that's kind of in review now.
[00:38:09.800 --> 00:38:22.360] Where we actually took, we took the MRI brain scans and fed them into an analysis pipeline around AI guessing the brain age.
[00:38:22.360 --> 00:38:28.920] So as Mark, you probably already know, you can take a brain MRI and you can have AI guess a brain age.
[00:38:28.920 --> 00:38:32.760] You can scan them the second time and it'll be very close to the first one.
[00:38:32.760 --> 00:38:35.080] You scan them a third time, it's gonna be very close.
[00:38:35.080 --> 00:38:45.840] 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?
[00:38:45.840 --> 00:38:52.240] And so, you know, you're you're you're a young guy in the sense you look very young, right?
[00:38:52.560 --> 00:39:01.600] And I would suspect your brain looks very young, and I would suspect that it's younger than your chronological age.
[00:39:01.680 --> 00:39:03.040] You're talking about me specifically?
[00:39:03.040 --> 00:39:04.640] Yeah, yeah, I'm 65.
[00:39:04.640 --> 00:39:05.840] I hope it's younger than that.
[00:39:05.920 --> 00:39:06.800] That's what I'm saying, right?
[00:39:06.800 --> 00:39:12.880] So, let's say we scan your brain, and maybe your brain is 55, and that's what AI.
[00:39:12.880 --> 00:39:27.200] 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?
[00:39:27.200 --> 00:39:39.520] And so, 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.
[00:39:39.520 --> 00:39:42.400] And if you scan them three times, you're gonna see that it's 75.
[00:39:42.400 --> 00:39:51.680] And what this is showing is as a group average, people have about a year and a half younger-looking brain at one month.
[00:39:51.680 --> 00:39:52.000] Wow.
[00:39:52.240 --> 00:39:54.000] And compound if you keep doing it?
[00:39:54.000 --> 00:39:55.680] This is what everybody keeps asking me.
[00:39:55.680 --> 00:40:00.960] I have no idea about that question, but it's a good question, right?
[00:40:02.720 --> 00:40:07.360] Can you lock the brain into an age if you just keep re-exposing it?
[00:40:07.360 --> 00:40:11.520] You know, it's a much further along the road question, but it's an intriguing one.
[00:40:11.520 --> 00:40:21.520] 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.
[00:40:21.520 --> 00:40:30.000] 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.
[00:40:30.520 --> 00:40:38.200] 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.
[00:40:38.200 --> 00:40:40.200] Yeah, and it may actually make sense.
[00:40:40.280 --> 00:40:46.440] We're talking about like one dose, one day, having an effect to reverse your brain age by a year and a half and a month.
[00:40:46.440 --> 00:40:47.880] That's pretty remarkable.
[00:40:47.880 --> 00:40:58.200] 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.
[00:40:58.200 --> 00:41:04.520] And so, what whereas you do see that with PTSD and depression and everything else, you see it really quickly.
[00:41:04.520 --> 00:41:09.960] But with traumatic brain injury disability and with the brain age, it takes the month.
[00:41:09.960 --> 00:41:10.840] And it makes sense.
[00:41:10.840 --> 00:41:18.040] Like, if these are more hard neurological issues, you're not going to be able to change the brain in five days or whatever.
[00:41:18.040 --> 00:41:19.480] It's going to take some time.
[00:41:19.800 --> 00:41:29.240] One of the things that I heard is that there's a metabolite of ibogaine called noribogaine that lasts longer.
[00:41:29.240 --> 00:41:40.280] And I'm wondering if that explains some of the tail of these effects of the addiction and inhibition, withdrawal inhibition, and maybe some of these other deeper neurological effects.
[00:41:41.720 --> 00:41:46.440] And I don't know if that noribogaine has the same cardiac risks or if anybody's looking at studying that.
[00:41:46.440 --> 00:41:49.160] So the noribogaine does have a similar cardiac profile.
[00:41:49.160 --> 00:41:53.880] Ibogaine is metabolized into noribigain normally through 2D6.
[00:41:53.880 --> 00:42:05.240] And so you see people with getting ibogaine and they metabolize to noribogaine in roughly 12 hours, 8 to 12 hours, or something like that.
[00:42:05.240 --> 00:42:14.360] 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 noribogaine as a treatment?
[00:42:14.360 --> 00:42:17.120] And that's an open question, you know, and that work needs to be done.
[00:42:18.000 --> 00:42:31.120] 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.
[00:42:31.680 --> 00:42:32.320] Interesting.
[00:42:32.320 --> 00:42:45.120] 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.
[00:42:45.120 --> 00:42:53.200] It happens with the based off of the subjective effects and the timeline of the drug, that's what it looks like, right?
[00:42:53.200 --> 00:43:05.600] 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.
[00:43:05.600 --> 00:43:16.240] 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.
[00:43:16.240 --> 00:43:23.280] So if you take that out, you may be taking out at least some of the, at least the PTSD benefit.
[00:43:23.280 --> 00:43:34.560] 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.
[00:43:34.560 --> 00:43:37.520] There's over 2.5 billion people overweight in the world.
[00:43:37.840 --> 00:43:40.480] Obesity is exploding across the planet.
[00:43:40.480 --> 00:43:45.760] And in America, we're 75% of us are overweight, 42% are obese.
[00:43:45.760 --> 00:43:49.120] The Yale Food Addiction Scale is a way of measuring food addiction.
[00:43:49.440 --> 00:43:51.360] And Kelly Brunnell and others developed it.
[00:43:51.360 --> 00:43:57.440] And 14% of the global population is addicted to food, including 14% of kids.
[00:43:58.200 --> 00:44:00.040] And that's about the same as alcohol.
[00:43:59.520 --> 00:44:02.120] Alcohol addiction is about 14%.
[00:44:03.080 --> 00:44:21.080] And I wonder if, you know, everybody's talking about Ozempic and GLP 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?
[00:44:21.080 --> 00:44:27.400] I think there's, you know, when you look at genetics, there's genetics involved in people who tend to move towards more addiction.
[00:44:27.400 --> 00:44:30.360] They don't benefit as much from this dopamine simulation.
[00:44:30.360 --> 00:44:32.120] They need more to feel the same pleasure.
[00:44:32.120 --> 00:44:35.320] And so, you know, how does someone eat a whole sheet cake?
[00:44:35.320 --> 00:44:37.720] I couldn't ever do that, but people do.
[00:44:38.040 --> 00:44:44.920] And I think that, you know, as an application, it seems to be a multi-billion dollar application.
[00:44:44.920 --> 00:44:47.800] So our data, we also collected alcohol use.
[00:44:48.200 --> 00:44:58.760] 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.
[00:44:58.760 --> 00:45:07.800] And so just almost everybody, just really dramatic improvements in alcohol and maintained it.
[00:45:07.800 --> 00:45:11.880] And so, and we also have some biology around that that we're looking at.
[00:45:11.880 --> 00:45:17.080] And so, you know, all those guys, if you asked them, are you going down there to stop drinking?
[00:45:17.080 --> 00:45:21.320] They would have told you, no, I'm trying to deal with my like TBI or whatever.
[00:45:21.720 --> 00:45:27.480] And then, you know, nearly everybody came back and reported they really didn't want to drink coffee anymore.
[00:45:27.480 --> 00:45:28.440] They really didn't.
[00:45:28.760 --> 00:45:34.760] And so I always think that, so placebo is expectancy, right?
[00:45:34.760 --> 00:45:41.880] And the degree of the expectation that you have about how a drug is going to work drives a lot of the effect.
[00:45:41.880 --> 00:45:53.840] 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.
[00:45:53.840 --> 00:46:02.320] And the total knee patients and the kind of the fake surgery incision folks had no difference in outcome.
[00:46:03.280 --> 00:46:07.840] It looks like it was driven primarily by expectancy.
[00:46:07.840 --> 00:46:20.960] And so, if the person's being told in medicine, I'm going to do this thing, and when I do this thing, that thing that I'm going to do is drive this outcome, then the person has this expectation of that outcome.
[00:46:20.960 --> 00:46:22.240] And that's hard, right?
[00:46:22.240 --> 00:46:33.280] 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 related to that, not placebo.
[00:46:33.280 --> 00:46:43.840] 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.
[00:46:44.480 --> 00:46:46.880] Or now everybody stopped drinking alcohol.
[00:46:46.880 --> 00:46:53.520] 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.
[00:46:53.520 --> 00:46:55.760] Like, they'd say, I didn't know that was going to happen.
[00:46:56.080 --> 00:47:01.760] They all just came back fascinated with this thing that happened that they didn't have any expectancy for.
[00:47:02.160 --> 00:47:30.000] 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 re-org, 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.
[00:47:30.280 --> 00:47:36.120] So, there's all kinds of effects that we're just sort of learning about, and I think with obesity, nobody's probably looking at that as my guess, right?
[00:47:36.120 --> 00:47:37.240] With Ibogaine?
[00:47:37.240 --> 00:47:39.960] Yeah, I mean, yeah, nobody that I know of, yeah.
[00:47:39.960 --> 00:47:41.880] I think it could be an interesting offshoot study.
[00:47:41.880 --> 00:47:43.800] Like, does their food behavior change?
[00:47:43.800 --> 00:47:46.760] Does their cravings for sugar change?
[00:47:48.360 --> 00:47:57.240] Because I think it's like that, that, I mean, you're talking about opioid addiction killing 70,000 people a year, but the food addiction part kills a lot, lot more.
[00:47:57.240 --> 00:48:03.400] You know, chronic disease-related food is killing a million-plus people a year in America.
[00:48:03.400 --> 00:48:13.000] So, to me, I think it'd be an interesting little kind of side hustle to kind of look at that and your data and see what happens if people change their diets, do they change their weight loss?
[00:48:13.000 --> 00:48:15.000] Like, there's other things you can look at.
[00:48:15.000 --> 00:48:17.960] So, I encourage you to check that out because I have this theory.
[00:48:17.960 --> 00:48:24.040] But if it, because if it works, it's a big unlock, you know, and it's probably a lot better than taking Ozempic.
[00:48:24.040 --> 00:48:39.640] 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.
[00:48:39.640 --> 00:48:48.760] And with Ibogaine and some of the other psychedelic therapies, we're talking about 80 to 90% reductions in symptoms and things that you just don't see.
[00:48:48.760 --> 00:48:53.960] So, can you talk about the magnitude of the effects and how it's different than traditional psychiatric treatments?
[00:48:53.960 --> 00:48:58.200] Yeah, I mean, so the degree of the effects that we observed were quite striking.
[00:48:58.200 --> 00:49:04.520] The you know, the data is limited, you know, so that needs to get replicated.
[00:49:04.520 --> 00:49:10.680] And I've heard, you know, that there's another group out of Texas that they're seeing very similar effects to us.
[00:49:10.680 --> 00:49:14.920] And so, if that holds, and that's really the case, then, you know, that's going to be helpful.
[00:49:16.000 --> 00:49:25.600] In this hypothetical future scenario where, you know, you're right, and this is these are the degrees in which people change compared to conventional treatments.
[00:49:25.920 --> 00:49:26.880] It's a huge difference.
[00:49:26.880 --> 00:49:47.360] 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, and the inter-rater reliability on that scale is two points.
[00:49:47.360 --> 00:49:49.200] Yeah, so basically, it's like nothing.
[00:49:49.200 --> 00:49:55.280] So the noise between raiders is the same amount of change as the change observed.
[00:49:55.280 --> 00:50:00.960] Now, on average, they're seeing the change greater in the active group than in the placebo group.
[00:50:00.960 --> 00:50:10.000] I'm not arguing that, but like it's the, yeah, the observer, you know, differences are that level.
[00:50:10.000 --> 00:50:19.520] So it's very hard to discern if you've got totally skilled raiders and they have that problem, how effective these drugs really can be.
[00:50:21.440 --> 00:50:24.160] You wouldn't drink dirty water, so why breathe unfiltered air?
[00:50:24.160 --> 00:50:31.600] Indoor air can carry a wide range of invisible particles, like mold, allergens, VOCs, smoke, and even airborne bacteria and viruses.
[00:50:31.600 --> 00:50:34.320] And most of us are breathing it in all day without realizing it.
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[00:52:31.800 --> 00:52:35.080] So, those are not, but then the ibogaine is far more.
[00:52:35.080 --> 00:52:47.920] 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, as a generality, people don't really score above mid-30s on.
[00:52:48.480 --> 00:52:56.960] 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.
[00:52:56.960 --> 00:52:59.120] You know, you need to go to the hospital or something like that.
[00:52:59.120 --> 00:53:04.480] And so we're seeing a 20-point change in a lot of people on that scale.
[00:53:04.800 --> 00:53:12.080] The use case for this drug is across a whole bunch of different issues that seem not necessarily related.
[00:53:12.080 --> 00:53:16.240] Like, what does brain injury have to do with PTSD, have to do with depression?
[00:53:16.240 --> 00:53:26.880] And how do you think that we sort of start to apply these compounds to these conditions in a more systematic way where deliberately working on different pathways that these drugs work on?
[00:53:26.880 --> 00:53:28.480] It's an open question, you know.
[00:53:28.480 --> 00:53:37.200] I think we've got to spend the time to understand what the different alkaloids do and then use those.
[00:53:37.520 --> 00:53:47.360] It's kind of like where GW Pharmaceuticals was as it relates to cannabinoids, you know, and so there's an approval.
[00:53:47.360 --> 00:53:58.160] 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.
[00:53:58.160 --> 00:54:01.120] So Lenox Gasto and Gervais syndrome, right?
[00:54:01.120 --> 00:54:06.240] And so those two epilepsy syndromes in kids are really devastating.
[00:54:06.240 --> 00:54:09.840] Sometimes kids have two to three hundred seizures a day.
[00:54:09.840 --> 00:54:16.080] You have to put them on potassium bromide, which is like what we give dogs for epilepsy, you know.
[00:54:17.040 --> 00:54:23.040] And you end up being in a situation where, you know, kids still seizing.
[00:54:23.040 --> 00:54:36.600] 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.
[00:54:37.320 --> 00:54:37.640] Right.
[00:54:37.640 --> 00:54:43.240] And so they were administering on their moving to at the time, moving to Denver.
[00:54:43.240 --> 00:54:48.040] This was, you know, Sanjay Gupta did like a special on this 15 or 20 years ago.
[00:54:48.040 --> 00:54:58.120] So all these families that Linux Gasto kids moving to Denver and then figuring out on their own, buying cannabis and then extracting it, extracting CBD.
[00:54:58.120 --> 00:55:05.240] So they called it Charlotte's Web, which is this pure CBD cannabis, and they extract that out.
[00:55:05.560 --> 00:55:16.120] 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.
[00:55:16.120 --> 00:55:19.240] Maybe it's a little anxiolytic, but it doesn't make people high.
[00:55:19.240 --> 00:55:24.200] You know, the kids were actually waking up and they were less encephalopathic when they would take it.
[00:55:24.920 --> 00:55:36.120] And, you know, you give this to a kid and they come out of an epilepsy fit, you know, and so all these families were seeing this kids, potassium bromide and all this stuff.
[00:55:36.120 --> 00:55:42.200] And then you give them high-dose CBD and they wake up, you know, for the first time.
[00:55:42.200 --> 00:55:47.160] And so what GW did is they said, okay, we're going to make a pure CBD drug.
[00:55:47.240 --> 00:55:48.040] We're going to get that through.
[00:55:48.040 --> 00:55:58.920] And then we're going to 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.
[00:55:59.400 --> 00:56:04.360] And I think that's what's going to happen with these iboga alkaloids, right?
[00:56:04.360 --> 00:56:05.160] Is that we have to.
[00:56:05.480 --> 00:56:16.240] You don't think it's just the whole plant, it's 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.
[00:56:16.240 --> 00:56:17.520] That is the open question.
[00:56:14.840 --> 00:56:20.080] So, there's going to be an experiment on this.
[00:56:20.400 --> 00:56:33.760] You know, Colorado is going to is basically gonna allow for whole plant-derived iboga alkaloids to be used for people, you know, out inside of Colorado.
[00:56:33.760 --> 00:56:37.280] And so, the question ends up being: is that the road?
[00:56:37.280 --> 00:56:39.360] Is it isolating ibogaine?
[00:56:39.360 --> 00:56:40.960] Is it isolating other alkaloids?
[00:56:40.960 --> 00:56:42.000] I'm a pragmatist.
[00:56:42.000 --> 00:56:54.000] Like, I don't have like a philosophical view on this other than, you know, if somebody's going to die and you give them this thing and their probability of dying goes way down, we should probably be doing that.
[00:56:54.000 --> 00:57:00.080] And I think that's like, so if that's what happens in Colorado, then that'd be good.
[00:57:00.080 --> 00:57:09.040] I mean, I have some open concerns about it because of the cardiac risk, and I'm pretty public about that, but they're going to do it no matter what I think.
[00:57:09.040 --> 00:57:17.920] 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.
[00:57:18.080 --> 00:57:23.200] And then there's this kind of organic chemistry thing where they're changing the molecule thing too.
[00:57:23.200 --> 00:57:25.120] That's maybe that's not even psychoactive.
[00:57:25.120 --> 00:57:29.760] And I think we'll get in totality the answer over the next 10 years.
[00:57:29.760 --> 00:57:30.160] Yeah.
[00:57:30.160 --> 00:57:34.640] And the reality is, is that if it all works, that's amazing.
[00:57:34.640 --> 00:57:37.360] If one of them works, we know a lot more about how the brain works.
[00:57:37.360 --> 00:57:41.440] I mean, hopefully, we're not in a situation where none of them work, but that's possible too.
[00:57:41.760 --> 00:57:45.360] But at least we gave it a college try for sure.
[00:57:45.360 --> 00:57:50.800] But the beauty is, I think that's all happening, and we're going to be able to really actually sort it out.
[00:57:50.800 --> 00:57:52.000] And fingers crossed.
[00:57:52.000 --> 00:57:52.880] Yeah, pretty amazing.
[00:57:52.880 --> 00:57:58.640] Yeah, this is sort of an interesting moment where we have these new compounds we never had before where we're looking at them.
[00:57:58.640 --> 00:58:11.480] But the NDMA 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.
[00:58:12.360 --> 00:58:20.120] But what you're talking about, IB gain, not needing the psychotherapy component, do people need follow-up support, treatment, integration?
[00:58:20.440 --> 00:58:24.120] Does it have to be done in a psychiatric context where there's more continuity of care?
[00:58:24.200 --> 00:58:28.920] It's just like go in and take it, close your eyes, wake up 12 hours later, and that's it.
[00:58:28.920 --> 00:58:33.640] So there's a pre-post therapy requirement.
[00:58:33.640 --> 00:58:41.320] There's a within dosing therapy non-requirement, it appears, right?
[00:58:41.320 --> 00:58:44.840] Although, like, nobody's really, you know, could be very helpful.
[00:58:44.840 --> 00:58:45.560] We don't know.
[00:58:45.560 --> 00:58:56.760] But what happens with MDMA, as you know, is, you know, I think you've studied, is if you give somebody MDMA, they have a positively balanced experience.
[00:58:56.760 --> 00:58:57.400] Yeah.
[00:58:57.400 --> 00:58:57.720] Right?
[00:58:57.720 --> 00:59:03.800] They have this, they feel good and they feel good about, you know, the people around them.
[00:59:03.800 --> 00:59:05.560] And they feel good about the memories they've had.
[00:59:05.560 --> 00:59:14.760] 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.
[00:59:14.760 --> 00:59:17.000] And I think that's very useful as a tool.
[00:59:17.000 --> 00:59:18.920] I think it's also very tricky as a tool.
[00:59:18.920 --> 00:59:25.880] There's an analysis of the events that happened in Israel with the rave, right?
[00:59:25.880 --> 00:59:30.760] And in that situation, there was a certain percentage of those people who are actually on MDMA.
[00:59:30.760 --> 00:59:31.800] I don't know if you know about this.
[00:59:32.120 --> 00:59:43.680] 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.
[00:59:43.760 --> 00:59:53.520] The boss came in and terrorized the festival in Israel on October 7th, and the people who took the MDMA were less traumatized after than the ones who didn't.
[00:59:53.520 --> 00:59:54.080] Correct.
[00:59:54.080 --> 00:59:54.640] Yeah.
[00:59:54.640 --> 01:00:00.000] And so, you know, what it's a terrible story, obviously.
[01:00:00.000 --> 01:00:05.760] What's interesting about that data is that it tells you something about it being protective, right?
[01:00:05.760 --> 01:00:22.320] 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 valenced place.
[01:00:22.320 --> 01:00:28.080] But, you know, it's probably true that you need to, you know, have a guide to guide people with that drug.
[01:00:28.080 --> 01:00:38.160] 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.
[01:00:38.480 --> 01:00:47.120] 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?
[01:00:47.120 --> 01:00:55.120] They have to unpack all of the earlier life, you know, in many cases, traumatic memories that they have to kind of get through.
[01:00:55.120 --> 01:00:59.600] And in that situation, it's driven by the drug.
[01:00:59.600 --> 01:01:03.040] It's not driven by a therapist telling them, hey, go look at this memory.
[01:01:03.040 --> 01:01:04.960] It's like the drug is doing that.
[01:01:04.960 --> 01:01:10.000] But then the person has to come out of it and really actually sort it out for themselves mentally.
[01:01:10.480 --> 01:01:12.000] That they need help with, generally.
[01:01:12.000 --> 01:01:14.080] Then they, yeah, basically all need help with.
[01:01:14.480 --> 01:01:25.280] I'm fascinated because, you know, there's effects on disease states or, you know, things that are problematic for people, like PTSD, traumatic brain injury, depression, et cetera.
[01:01:25.280 --> 01:01:27.760] But then there's the brain enhancement component.
[01:01:27.760 --> 01:01:38.920] And I've known a number of people who've 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.
[01:01:38.920 --> 01:01:44.200] And you mentioned briefly about the reversal of the brain age as sort of a hint at that.
[01:01:44.200 --> 01:01:49.560] Can you talk more about how it might be used as a sort of an enhancement drug?
[01:01:49.560 --> 01:02:01.720] 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, you know, we all would like to have better brains, right?
[01:02:01.720 --> 01:02:10.920] Yeah, so what we observed in the veterans was that they had an improvement in statistically significant improvement in some aspects of cognition, particularly around frontal control.
[01:02:10.920 --> 01:02:18.120] 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.
[01:02:18.440 --> 01:02:23.400] But, you know, at least you can see in a diseased population an improvement there.
[01:02:23.400 --> 01:02:30.120] Whereas like with a lot of the oral antidepressants and whatnot, you're not really seeing an improvement in cognition.
[01:02:30.120 --> 01:02:37.480] There's not really a good drug in psychiatry that's approved for depression that improves cognition.
[01:02:37.480 --> 01:02:42.600] And so at least we're getting signals of it with ibogaine, but it's, you know, it's got to be studied.
[01:02:42.600 --> 01:02:48.440] Yeah, it would be interesting as just as more of like a longevity enhancement drug.
[01:02:48.440 --> 01:02:51.720] And we don't really think much about those things in medicine at all.
[01:02:51.720 --> 01:03:00.200] 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.
[01:03:00.520 --> 01:03:05.640] Probiotics, for example, is something that can optimize health as opposed to an antibiotic.
[01:03:05.880 --> 01:03:09.720] And in functional medicine, that's a lot what we think about: what are the ways to enhance function?
[01:03:09.720 --> 01:03:13.320] What are the pro-drugs as opposed to anti-drugs, right?
[01:03:13.880 --> 01:03:16.640] And it seems like it has that kind of potential.
[01:03:17.200 --> 01:03:25.440] What we really need to understand, I think, is why were the Buiti taking this for hundreds of years, you know, and why do the French think this was helpful for 36?
[01:03:25.600 --> 01:03:26.080] Yeah.
[01:03:26.080 --> 01:03:31.360] You know, and I think that could give us a signal about what it could do for that, right?
[01:03:31.360 --> 01:03:55.360] Because it seems to me that you have a even in the 30s to 66, you know, 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.
[01:03:55.360 --> 01:04:01.920] And so my suspicion is that there were some disease treatment effects, but maybe these effects too.
[01:04:01.920 --> 01:04:02.240] Who knows?
[01:04:02.400 --> 01:04:10.640] Yeah, I wonder if there's any people around us who took it back then who are in their 90s probably now from what the effect on them.
[01:04:11.200 --> 01:04:14.720] I think this is such an exciting moment in psychiatry and medicine.
[01:04:14.720 --> 01:04:19.440] And I think a lot of people are stuck in mental health issues.
[01:04:19.440 --> 01:04:21.680] And we live in an increasingly stressful society.
[01:04:21.680 --> 01:04:24.800] And there's just such a limited set of tools for people.
[01:04:24.800 --> 01:04:30.800] 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.
[01:04:30.800 --> 01:04:52.560] And I wonder if you've thought about combining the things that you're doing with other kind of metabolic psychiatry stuff that your colleagues are 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.
[01:04:52.880 --> 01:04:53.600] 100%.
[01:04:53.600 --> 01:04:53.920] Yeah.
[01:04:53.920 --> 01:05:02.920] I mean, I think we, I've taken the stance that if you look at like MICARA, like people having a heart attack, what do we do now?
[01:05:03.160 --> 01:05:14.760] We throw an aspirin, we throw statin, we do a heart cath, we do all these things in summation that all independently were shown in isolation to benefit.
[01:05:14.760 --> 01:05:18.360] Right, we hit a cocktail therapy as opposed to a single therapy, right?
[01:05:18.360 --> 01:05:25.000] The challenge right now is to, we're in cardiology 1950s, right?
[01:05:25.160 --> 01:05:42.360] 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 and make more tools and improve those tools and do the trials in each one of the tools.
[01:05:42.360 --> 01:06:00.520] Now, 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.
[01:06:00.520 --> 01:06:01.720] I think absolutely.
[01:06:01.720 --> 01:06:08.760] You know, I think that's going to be the way we deal with things in the future: we say, okay, well, we're going to, you know, and you're doing a lot of this already.
[01:06:08.760 --> 01:06:10.600] We're going to measure all of these things.
[01:06:10.600 --> 01:06:15.000] We're going to modify your diet, your metabolics, you know, all of that good stuff.
[01:06:15.000 --> 01:06:16.680] We're going to do brain-based things.
[01:06:16.680 --> 01:06:33.800] 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 of that stuff, and people end up being way over here.
[01:06:33.800 --> 01:06:37.000] Do you need multiple therapies to get you back on track?
[01:06:37.000 --> 01:06:44.440] 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.
[01:06:44.480 --> 01:06:58.880] To me, that's one of the big questions that yourself and others are trying to tackle, which is 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?
[01:06:58.880 --> 01:07:01.840] And it's an important question and one we have to ask.
[01:07:01.840 --> 01:07:08.000] You know, we have increasing rates, we don't know why, and so maybe it is because of diet.
[01:07:08.000 --> 01:07:09.440] Oh, yeah, I mean, it's huge.
[01:07:09.440 --> 01:07:22.320] I mean, but I don't think that the dietary change alone or nutritional metabolic changes alone can do the kinds of things that these psychedelic compounds do.
[01:07:22.880 --> 01:07:27.840] And what's fascinating is we've sort of this always fascinates me.
[01:07:27.840 --> 01:07:37.840] 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?
[01:07:37.840 --> 01:07:40.640] And I wonder if somehow we co-evolve with these plants.
[01:07:40.640 --> 01:07:46.480] And if you look across all indigenous societies, they all have some sort of psychedelic something that they play with.
[01:07:46.720 --> 01:07:53.360] It's ayahuasca and Indians in South America or peyote in North America or whatever.
[01:07:53.360 --> 01:08:10.560] If 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.
[01:08:10.880 --> 01:08:18.240] Many of them thought these were, you know, there weren't that many limes and lemons in Europe at the time, right?
[01:08:18.480 --> 01:08:24.240] This was considered a South American or an African exotic plant.
[01:08:24.560 --> 01:08:31.960] And so most of the physicians of the day actually rejected citrus fruit as a treatment for scurvy.
[01:08:32.040 --> 01:08:35.000] And so, as you know, the story of anti-fruiters, right?
[01:08:35.000 --> 01:08:42.680] There were lots of people in the British Royal Society that said that the limes and lemons may actually be making scurvy worse.
[01:08:42.680 --> 01:08:59.080] And 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.
[01:08:59.080 --> 01:09:15.320] 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.
[01:09:15.320 --> 01:09:24.520] Plant, not so sure about that, you know, and I think that's that's the way we've been looking at plant-based psychedelics for a long time, and hopefully that changes.
[01:09:24.520 --> 01:09:25.080] Pretty amazing.
[01:09:25.080 --> 01:09:46.200] And this, and the, the sort of, I keep kind of doubling down on the magnitude of the size of the effect, and I want to sort of double down on that 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 modern disability to like no disability.
[01:09:46.200 --> 01:09:53.640] You had PTSD drop by 88%, depression dropped by 87%, anxiety by 81%, improved cognition.
[01:09:53.720 --> 01:09:55.800] Seems like too good to be true, right?
[01:09:55.800 --> 01:10:00.520] When my postdoc showed me the data, I didn't believe him, and I told him to go back and reanalyze it.
[01:10:00.520 --> 01:10:00.840] Yeah.
[01:10:00.840 --> 01:10:12.920] 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.
[01:10:12.920 --> 01:10:15.680] So we need to be replicated by another group in order to justify it.
[01:10:15.760 --> 01:10:22.000] Now I'm hearing from my colleagues out of Texas that they are seeing very similar effects, right?
[01:10:22.000 --> 01:10:28.240] And so I want them to formally see that, if that's what it is, and publish that.
[01:10:28.240 --> 01:10:36.080] And then we can say it wasn't, you know, our site or whatever, that at least in an open label way, this is what this looks like.
[01:10:36.080 --> 01:10:38.720] And then the next step is to do the big trials.
[01:10:38.720 --> 01:10:46.240] But it would be unusual to have that level of an effect for this sort of level of expectancy.
[01:10:46.240 --> 01:10:50.640] I mean, they didn't expect that big of a change, so they would less likely to see it.
[01:10:50.640 --> 01:10:51.040] Yeah.
[01:10:51.040 --> 01:10:53.440] The veterans had, have you followed them ongoingly?
[01:10:53.440 --> 01:10:55.200] Are they still have the lasting effects?
[01:10:55.200 --> 01:10:56.800] So we have data out to year.
[01:10:56.800 --> 01:10:58.000] It isn't published yet.
[01:10:58.000 --> 01:11:00.160] It's kind of in review now, actually.
[01:11:00.160 --> 01:11:01.680] And that looks really good.
[01:11:02.000 --> 01:11:03.120] Most people hold it.
[01:11:03.120 --> 01:11:09.600] And you're talking now more about this idea of circuit-based psychiatry, which helps explain some of the things you're seeing.
[01:11:09.600 --> 01:11:13.760] Can you kind of unpack what that is and how it differs from our current view of psychiatry?
[01:11:13.760 --> 01:11:33.280] If you think about psychiatry and epochs, you know, the first one being talk therapy, and we learned something important there that spoken word can have effects on, you know, mental states and effect, you know, and now more recently, data suggesting that it's having an effect on the brain itself.
[01:11:33.280 --> 01:11:35.440] And that was useful.
[01:11:35.440 --> 01:11:43.440] Psychiatry 2.0, this idea that pharmacology can have an effect at the level of the synapse.
[01:11:43.440 --> 01:11:44.960] And that was also very useful, right?
[01:11:44.960 --> 01:11:49.840] That got a lot of people with, say, schizophrenia out of asylums and that sort of thing.
[01:11:50.080 --> 01:11:50.960] They like thorazine.
[01:11:51.360 --> 01:11:52.240] Yeah, like thorazine, yeah.
[01:11:52.560 --> 01:11:54.640] The chemical straitjackets, we call them.
[01:11:54.640 --> 01:12:11.480] 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?
[01:12:11.480 --> 01:12:13.640] Because at the end of the day, lots of...
[01:12:13.880 --> 01:12:18.360] the psychiatric treatments that we have are suboptimal for patients' desires, right?
[01:12:18.360 --> 01:12:19.880] ECT is a great example of that.
[01:12:20.360 --> 01:12:21.400] Electric shock therapy.
[01:12:21.960 --> 01:12:28.600] Can you use insights from before and make things much safer and better and much more tolerated with patients?
[01:12:28.600 --> 01:12:32.920] And that's really been, I think, the emphasis for our work.
[01:12:32.920 --> 01:12:36.840] And so when we look at IBM, we're looking at it from the lens of the circuit.
[01:12:36.840 --> 01:12:43.080] When we're looking at, I'd say, stimulation of the brain, we're looking at it from the lens of the circuit.
[01:12:43.080 --> 01:12:58.920] 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.
[01:12:58.920 --> 01:12:59.560] Amazing.
[01:12:59.560 --> 01:13:09.960] 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.
[01:13:10.200 --> 01:13:12.440] I was like, I spent a month there.
[01:13:12.440 --> 01:13:14.520] I was like, this is just nuts.
[01:13:14.520 --> 01:13:16.200] And I don't mean that as a pun.
[01:13:16.200 --> 01:13:23.560] I just mean the way we treated people, the amount of suffering that's going on, the lack of really good treatments.
[01:13:23.560 --> 01:13:24.920] It feels really hopeful.
[01:13:24.920 --> 01:13:26.440] It feels like a hopeful moment.
[01:13:26.440 --> 01:13:29.720] But it doesn't feel like we're going fast enough to me.
[01:13:29.720 --> 01:13:33.400] It feels like we're still in this sort of glacial pace of change.
[01:13:33.400 --> 01:13:35.560] And science proceeds that way, unfortunately.
[01:13:35.560 --> 01:13:38.760] But I think many people listening go, wow, you know, can I try it?
[01:13:38.760 --> 01:13:39.480] What do I do?
[01:13:39.480 --> 01:13:40.680] What if I want to go do it?
[01:13:40.680 --> 01:13:41.960] I have this addiction issue.
[01:13:41.960 --> 01:13:43.000] I've got PTSD.
[01:13:43.000 --> 01:13:43.920] I've got trauma.
[01:13:43.640 --> 01:13:49.760] There's a few places people go, like in Mexico, beyond, or Ambio, and also in Mexico.
[01:13:43.880 --> 01:13:51.280] There's a few places out there.
[01:13:51.600 --> 01:13:53.760] What do you say to people who want to go sort of explore this?
[01:13:54.240 --> 01:14:00.080] Yeah, I mean, the good news is that we, you know, it looks like there's actually going to be some U.S.
[01:14:00.080 --> 01:14:05.280] trials soon, you know, and so being able to do this from inside of the U.S.
[01:14:05.280 --> 01:14:07.600] is kind of the ultimate goal.
[01:14:07.600 --> 01:14:20.160] You know, folks go to these places and these other countries, but the ultimate goal is really to see that folks can do this safely in the U.S.
[01:14:20.400 --> 01:14:29.680] And so I think 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.
[01:14:29.680 --> 01:14:46.080] And the hope 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?
[01:14:46.080 --> 01:14:48.640] And so that's and see what happens.
[01:14:48.640 --> 01:14:51.840] And so it is coming soon.
[01:14:51.840 --> 01:14:54.320] You know, we'll have to see what happens with the FDA.
[01:14:54.320 --> 01:15:04.800] But yeah, I think that's an exciting moment for folks and being able to have access to an experimental therapeutic like this.
[01:15:04.800 --> 01:15:08.400] And if people want to go down and try this in Mexico, do you advise against it?
[01:15:08.400 --> 01:15:10.320] Do you say at your own risk?
[01:15:11.120 --> 01:15:12.480] It's definitely a people's own risk.
[01:15:12.480 --> 01:15:17.760] I mean, look, it's one of these things where we still don't know that much about this.
[01:15:17.760 --> 01:15:25.920] 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.
[01:15:26.480 --> 01:15:28.000] Couldn't encourage them to do it, yeah.
[01:15:28.000 --> 01:15:30.840] Yeah, we couldn't encourage them to do it.
[01:15:29.280 --> 01:15:35.080] We didn't really participate in any of the processes for them to do it.
[01:15:35.400 --> 01:15:39.640] We simply just studied people that were already going down there.
[01:15:39.640 --> 01:15:52.520] 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.
[01:15:52.520 --> 01:15:52.920] Yeah.
[01:15:52.920 --> 01:15:55.720] Borderline personality, narcissistic personality, that gets so effective.
[01:15:55.720 --> 01:16:01.160] There's all these personality disorders, which are more like fixed personality traits that are hard to change.
[01:16:01.160 --> 01:16:17.480] 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.
[01:16:17.480 --> 01:16:18.280] It's a great question.
[01:16:18.280 --> 01:16:30.920] I mean, the Hopkins group demonstrated this profound personality change that they observed out to a year, I think, early on with their trials of psilocybin.
[01:16:30.920 --> 01:16:38.760] And so there's definitely data that there's personality change, you know, in and around psilocybin use.
[01:16:38.760 --> 01:16:40.200] It's an open question.
[01:16:40.200 --> 01:16:51.880] 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.
[01:16:51.880 --> 01:17:00.680] And so actually people that I think it was like 16% of people were not religious prior to taking Ibogaine.
[01:17:00.680 --> 01:17:11.160] And there's an increased kind of sense of a higher power or whatever after like almost, you know, two-thirds of people.
[01:17:11.160 --> 01:17:17.120] And so, this question of how do people see the world that they live in is really interesting.
[01:17:17.120 --> 01:17:23.680] But yeah, you know, nobody's done a personality inventory study with Ibogaine, so it's still an open question.
[01:17:23.680 --> 01:17:25.680] Is it dangerous for these people to do anything?
[01:17:25.680 --> 01:17:31.280] It's certainly dangerous for people with a psychotic history, you know.
[01:17:31.280 --> 01:17:34.960] I think people with bipolar disorder, that's going to be dangerous.
[01:17:34.960 --> 01:17:38.400] Maybe somebody with severe borderline, maybe, you know, it just depends.
[01:17:38.880 --> 01:17:41.120] It depends on a kind of individual basis.
[01:17:41.120 --> 01:17:44.720] The problem at a fundamental level is we just haven't studied this enough to really know.
[01:17:44.720 --> 01:17:47.520] We don't have enough data sets to know what's going on with these people.
[01:17:47.520 --> 01:17:48.400] Yeah, interesting.
[01:17:48.400 --> 01:17:57.600] 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?
[01:17:57.600 --> 01:18:03.840] 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.
[01:18:03.840 --> 01:18:20.960] 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 the profound suffering that's out there.
[01:18:20.960 --> 01:18:29.920] 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.
[01:18:29.920 --> 01:18:30.800] That's a psychiatric.
[01:18:31.040 --> 01:18:32.880] Purely psychiatric or dementia.
[01:18:32.880 --> 01:18:33.680] One out of two.
[01:18:33.680 --> 01:18:34.400] One out of two.
[01:18:34.400 --> 01:18:35.600] That's a lot.
[01:18:35.600 --> 01:18:40.640] Half of the population of the world is going to have some mental illness at some point in their life.
[01:18:40.640 --> 01:18:42.000] It's a scaling problem.
[01:18:42.000 --> 01:18:42.640] Think about it.
[01:18:42.640 --> 01:18:47.600] I mean, at the end of the day, we would never be able to actually effectively deal with that.
[01:18:47.600 --> 01:18:49.120] Definitely not through therapy.
[01:18:49.120 --> 01:18:50.160] Definitely not through therapy.
[01:18:50.160 --> 01:18:51.680] You'd have to have half the world become therapy.
[01:18:51.760 --> 01:18:54.400] I mean, maybe with AI, you know, all of us are trying to figure out.
[01:18:54.640 --> 01:18:54.960] That's right.
[01:18:54.960 --> 01:18:57.040] AI therapists are pretty damn good.
[01:18:57.040 --> 01:18:59.360] This psychedelic revolution to me is very promising.
[01:18:59.360 --> 01:19:08.760] 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.
[01:19:08.760 --> 01:19:17.480] It's harder for people to do that because it requires a lot of lifestyle change, whereas this is just a sort of a brain reset that then seems like it would facilitate behavioral lifestyle change.
[01:19:17.480 --> 01:19:22.920] It's almost like this could set the stage and then you could have an easier time doing that other hard work.
[01:19:22.920 --> 01:19:26.040] What studies are on the horizon for you that you're looking at doing?
[01:19:26.040 --> 01:19:37.080] We're looking forward to seeing what happens, this Texas effort, and hopefully there's some funding for Texas-based universities to do this and to do these treatments.
[01:19:37.080 --> 01:19:41.960] But yeah, it's an open question about what's going to happen with the FDA.
[01:19:41.960 --> 01:19:47.960] And I think if the FDA comes through and lets us do the studies, there'll be a normal healthy control study.
[01:19:47.960 --> 01:19:53.880] We're hoping to add some biology to that and then subsequently, hopefully, some traumatic brain injury studies.
[01:19:53.880 --> 01:19:55.880] When you say biology, do you mean biomarkers, blood tests?
[01:19:56.120 --> 01:20:03.240] And 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?
[01:20:03.240 --> 01:20:06.680] We hope to do some of that, at least the EEG side of things.
[01:20:06.680 --> 01:20:16.840] 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, you know.
[01:20:16.840 --> 01:20:17.880] Fascinating work.
[01:20:18.120 --> 01:20:19.400] Incredible what you're doing.
[01:20:19.720 --> 01:20:24.200] You're definitely going out of limb in the psychiatric world.
[01:20:24.200 --> 01:20:33.080] I think you're brave, but you're at Stanford and a respected institution and they seem to be in support of you doing this work, which is amazing.
[01:20:33.400 --> 01:20:40.280] And we need a Hail Mary in psychiatry because we are in a bad state as a world.
[01:20:40.840 --> 01:21:00.320] We're all divided and disconnected and isolated and struggling with various forms of just the 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.
[01:21:00.320 --> 01:21:01.120] It's just amazing.
[01:21:01.120 --> 01:21:02.800] So thanks for doing what you do.
[01:21:02.800 --> 01:21:03.760] Yeah, thanks for having me.
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