UNLOCKING THE MIND: Can We Use Psychedelics To Heal Our BODY & MIND? | Deborah Mash

People were able to come off of 100 milligrams of methadone, chipping on heroin, some Xanax on the side, a little bit of cocaine, and completely be detoxified.

So the typical psychedelics increase serotonin by activating various growth factors that increase serotonin in the brain and the function of serotonin, the receptors and so forth. And that can help with depression and mood and many things we see with the traditional psychedelics like mushrooms or psilocybin, MDMA and so forth. What you're saying with ibogaine and iboga is that it actually affects the dopamine system, which is what we need to focus, pay attention, be alert, what we want to stimulate for pleasure. It's really the pleasure place in the brain.

Drive motivation and affect or what I like to say, drugs, sex and rock and roll.

Exactly. Why we have coffee in the morning is it increases adrenaline and dopamine, right?

Yeah, we have more neurons and neural connections in our brain than there are stars in the Milky Way galaxy. Think about that. And they turn over. They turn over. You have, you know, we're constantly building and remodeling the brain. And I'm the former director and founder of the University of Miami Brain Endowment Bank, one of the largest postmortem collections of human brains that anybody had in the world. And I went around asking people to please donate their brain for medical research. So we had, actually, I did a lot of my research was, as I mentioned in the field of Alzheimer's disease and from neurodegenerative disorders and then moved into neuropsychiatry. So I actually looked at how drugs and alcohol affect the human brain. We know that it hijacks the DNA, it turns on a lot of second messenger systems, it remodels the brain. There's actual remodeling of the brain. You're over-wiring certain circuits in the brain that are part of this intractable cycle of misuse of drugs or alcohol. That's what happens.

Here now, It's on the negative sense, these toxic compounds actually damage the brain and create disconnection, whereas these other plant compounds create reconnection.

Yes. So they help heal the brain. And that's just to me is so incredibly exciting. The other thing is that most of the classical psychedelics turn on serotonin growth factors, so what we call brain-derived growth factor, BDNF, neurotrophic factor. And ibogaine is unique in its box because it turns on dopamine growth factors, allele derived neurotrophic factor. So that makes perfectly good sense because we know that all roads, everything that people will abuse, they're abusing it to get the dopamine buzz. So if you're low dopamine and you go out and you have that first vodka martini, that cigarette, that line of cocaine, that that smoke a little heroin, chase the dragon, you're going to get this huge dopamine. So if you're low dopamine and then you take an abuse, a drug which gets you high, it gets you high because it turns on dopamine. What if ibogaine is turning on the plasticity modulator, GDNF, to help normalize dopamine in the synapse? And this is seminal research that was advanced out of the Gallo Institute by a scientist by the name of Dorit Ron. And her group did some of the original work on this.

So that's amazing. It just occurs to me that maybe, you know, that has wider applications because you take diseases like Parkinson's disease that are dopamine deficiency problems. Could this be effective in Parkinson's or are there other uses besides just addiction medicine?

Well, people have tried to bump GDNF glial derived neurotrophic factor in the brain for treatment of Parkinson's disease. It's very hard to give exogenous growth factors and get them into the brain. So the fact that these psychedelic molecules turn these things on is just crazy good. It's just wonderful science.

There's over 100,000 people who died last year up from 75,000. from opioid overdose. Often it starts with a legitimate pain prescription for pills that can be helpful but then gets out of control. There are 4 million people in America who are addicted to pain meds and heroin. A growing number are overdosing from a surge in these fentanyl spike pills that are on the open drug market out there. It's really a devastating and debilitating disease for so many people, for so many families. And it's made worse by the fact that recovery rates really for addiction using standard approaches and rehab based options don't work that well. I mean, it's a little bit, but not that great. And, I mean, drugs like methadone and suboxone can help, but we're really not very far ahead in the last, you know, 70, 80 years on addiction. Now, you've been studying this compound from a plant, from a West African tree, the bark of a shrub, I think, native to West Central Africa called Iboga. And you told a story at this conference that I went to, which sort of heralded the discovery of this as an addiction treatment medicine. Because for years it's been used in centuries, maybe it's been used as a ritual drug in rites of initiation and passage that are from a spiritual tradition. But But there was a discovery over 30 years ago in Amsterdam and then you continued on in Miami and Caribbean to actually look at this compound as being able to disrupt addiction, specifically for opioids. So can you talk about that discovery, tell us the original story and then give us an overview of this last decades of your exploration of this and then we'll get into the nitty gritty of what's going on with this research that you're doing and the importance of this drug and this compound.

Ibogaine has a very long history of ethnobotanical and ethnopharmacologic use. And in fact, it goes over a hundred years because, remember, prior to the development of novel pharmaceuticals, which really, you know, came about in the 1950s, most blockbuster drugs came from Mother Nature. So there was a real push primarily by the Europeans, but also Americans and others to look to nature for finding pharmaceutical drug candidates to be advanced for treatments of a variety of illnesses, everything from infectious diseases. And of course, the CNS division is a little bit more complicated. But ibogaine is an indole alkaloid. So what does that mean? Mother nature gives us addicting alkaloids. Addicting alkaloids are like nicotine, cocaine, opium, things that humans will take to get high come from nature. And so here's this molecule from Western Equatorial Africa that's used in low doses for stimulating behavior, a mild stimulant effect. by local people who explored, again, Mother Nature, but then in high doses found its way into ethno-Christian religious practices in Africa, and that these were by the Bwiti religion. So Iboga, like other psychedelic medicines, is a sacrament. A plant sacrament or what we call a plant teacher. so this is the interesting, you know, legend and lore that goes back over a hundred years. But the, when the pharmaceutical drug hunters were in Africa and other parts of the world, Asia, et cetera, they, they brought back ibogaine and ibogaine was really advanced in France and it made its way in low dose tablets into the French farm pharmacies. So many of the original pharmacies in France were able to make tinctures and and potions and pills in their own shop. And Ibogaine was marketed under the trade name, Lamborine, until the early 1970s. So people took it for its antidepressant effects. And what we know today is that when you take a low dose of Ibogaine, it is converted to the Ibogaine active metabolite or nor-Ibogaine. So that experiment was done actually for us for 20 years. In France, in the 60s, when people became interested in LSD and psilocybin and the so-called hallucinogens and the DEA began to clamp down on these class of drugs, there was a seminal discovery by a man named Howard Lutzoff. He died several years ago, but he is credited with this discovery. And Howard was, you know, like many other people exploring you know, molecules for consciousness, yeah, expansion. Himself was a heroin addict, and he had been abusing opioids for many years, and he took a dose of Ibogaine to experience the drug. There were groups out in California who had access to Ibogaine. It's a difficult, actually molecule to get. It's not like mushrooms, which you can, you know, you just grow and you can find them Ibogaine. is a little more complicated for one to access. But he was involved in this underground movement and he was a filmmaker, young filmmaker, etc. He takes the dose of ibogaine and discovers that he's detoxified off opiates. He completely abruptly stops taking opiates, has no cravings or desire to use the drug. go back out and get high to treat withdrawals, and he has no desire to use. So this was the original discovery.

And when was that, Deborah?

That was in the early 70s. In the early 70s, when, you know, LSD was making its way from academic universities, from Harvard and elsewhere, and became that whole movement. Ibogaine had made its way into the U.S. and diplomatic pouch and underground therapists in California were working with it and some people in New York. So he has this experience, repeats the experience with six of his friends. Some were addicted to opiates, some were abusing cocaine, hardcore cocaine abusers, using freebasing cocaine. And they too had similar experiences. With that observation, it was a number of years and Howard Lotsoff and a group around him, his entourage, forms a company called NDA International. And they start an underground railroad of addicts helping addicts. These were people, and this is what they called it, the addict self-help movement. And so people from the United States and from Amsterdam, the International Coalition of Addict Self Help and the Dutch Addict Self Help Movement started to run this underground railroad where people could go outside of Amsterdam and take ibogaine. I leave Boston. I did my fellowship at Beth Israel Hospital at Harvard and then joined the faculty at the University of Miami, right at the peak of the cocaine epidemic in South Florida. So we were Miami Vice. Cocaine was making its way through the Caribbean into Miami and we were hit front end loading of the cocaine epidemic. I had been working on Alzheimer's disease. and got pulled into this by my colleagues who were at the medical examiner's office because young people were dying from cocaine related deaths and they were dying with what we thought at the time was rather low doses of cocaine in their blood. So people didn't really know what was going on and then there were some adverse psychiatric effects. We had crack exposed infants, it was a mess, increases in crime, you know the story. I had been credited in my laboratory did work on coca ethylene, and your listeners may know what that is or not, but when you drink and use cocaine in combination, your liver trans-sterifies, and so you've got an extra drug on board. You've got coca, the ethyl homolog, or coca ethylene. We disclose this, describe it, it's more reinforcing, it takes off the edge of the cocaine, and unfortunately it's more lethal. So we disclose this, get national recognition, and in the course of getting a lot of media attention for the work, we were called the Miami Vice Metabolite, I started to hear about this drug from Africa. And it happened three times. I heard it three times. I was at a coalition for a drug free America giving a lecture about my research and a gentleman, an African American man came up to me at the podium and said, Dr. Mash, have you heard about this drug from Africa? And he's going on and on. I think I was rather short with him and abrupt because I'd never heard of it and I didn't know what he was talking about. Second time I heard about it was Stan Glick, a professor from Albany University, was working with these drug taking rats. You know, rats will self administer at high rates of responding everything that humans will abuse. So they'll drink alcohol, they'll take nicotine, cocaine, other psycho stimulants and opiates. So he gives these rats this drug from Ibogaine, they stop taking drugs. And I'm sitting in an audience listening to his presentation going, Wait a minute. That's that same molecule.

Wow.

The last thing that happened was Howard Lotsoff contacted me because our laboratory was getting so much publicity. He had several patents on Ibogaine. And he wanted to file a new patent for poly drug dependency and use our research on co-abuse of cocaine and alcohol. So he called me. And I said, who are you? What does this drug do? How does it work? What's the mechanism of action?

Yeah.

And he said, you want to come to Amsterdam and see it? And I said, yeah, I do. Here we are.

And so you went to Amsterdam and you actually witnessed addicts taking the drug and the next day being symptom free from withdrawal. Now, I'm a physician and there are physiological things that happen. It's not a psychological withdrawal. I mean, there's psychological dependence and physiological dependence. And you see with addiction to, for example, alcohol, alcoholists come in when they get off booze, they start to go on Tremors. They have all kinds of symptoms. Same thing with heroin and. Opioids and yet somehow this compound erases all of that, which kind of leads to a whole set of questions about what is it doing? How does it work? And I've even heard people share who've taken the drug that it's like a brain reset around not just addiction, but around their personality, around their mood, around their view on life. And it just seems to sort of have this really magical set of properties. It seems to go beyond just this one dose that you take to kind of deal with addiction. So how have you kind of explored this sort of sort of Pandora's box of this compound that seems unlike anything else we've ever seen? I mean, because, you know, there isn't anything in medicine that works like this. You take this thing and it's just, it's like you have to keep taking it as a normal drugs. You know, you don't take a statin once and then your cholesterol is fine forever. So how does this work? And what is the theory behind it? And what have you learned in the 30 years of researching this about this, the mechanisms of action? Because if this is true, then it seems to be such a powerful lever for addressing the opioid addiction problem, but also other kinds of addiction. We've talked about this offline about, for example, food addiction, which we know is a real phenomenon that has to do with the way the sugar affects the nucleus accumbens, the area of the brain that's responsible for pleasure and addiction. So kind of unpack the biology of this compound and what you've learned.

Yes, that's a thank you, doctor. That's a Big, obviously a big, big, big black box question. And I'm quite humble in what we've learned about this drug. But suffice it to say, I was a skeptic walking in the door. And when I saw people were able to come off of 100 milligrams of methadone, young man, 100 milligrams of methadone, chipping on heroin, doing some benzo diazepines, some Xanax on the side, a little bit of cocaine for extra recreation on top of the methadone, and completely be detoxified. Get up the next day, no withdrawals, shower and shave, come in, sit down and eat a big breakfast. Because as you know, people who are coming off opiates, they don't have an appetite. They're very sick. So all of the, you know, just complete blockade of all of the classic opioid withdrawal symptoms that are black and white. Here I was in there seeing and bleeding. And the place in Amsterdam that I visited was not a what you would expect to see in an academic medical center to say, to be polite. So it was Just people in different rooms in the wing of a hotel that had been taken over who were going through detox after given one dose. And I thought, this is, you know, wow, this is really scary here. And I had brought a medical doctor, a colleague of mine from the University of Miami, Juan Sanchez-Ramos, and I had Dr. Ramos there, but everybody went to bed. Everybody went to bed. I stayed up all night. I went from bedroom to bedroom to hotel room to hotel room with three gentlemen. Two were coming off of opioids and one was coming off, one had been abusing a lot of freebase cocaine. I went from room to room, sat by their bed, watched them, gave them water. I couldn't really do anything. There weren't any nurses or anything there, but I had an idea. I said, There's no way that you can take one dose to survive again. and have this complete reset to use the word you use, which indeed it is a reset, and all the blockaded withdrawals, and people get up and look like they've been transformed into a new person. You've got this going on here. I'm going to collect urine. So I collected urine and I asked them to sign a release for me to collect urine and I froze back urine. brought the box of urine, put it on the plane at the airport, got it on the plane, got it back to Miami, got the box, drove it over to my analytical talks group and gave it to the boys at the bench and said, find the metabolite. And that was how we discovered noribogaine because I was convinced that there had to be an active metabolite. There was no way that one dose of this drug, albeit it was a large dose, could have this protracted effects on the brain and behavior. I just, I couldn't understand it.

Yeah.

So we discovered noribogaine. And what we know today is that ibogaine goes through the liver, gets converted to this active metabolite, and the metabolite has a much longer half-life in the blood. So ibogaine is not only an active molecule, The eneric effects, the dreamlike visions of Ibogaine.

Like the hallucinogenic effects.

Yeah, the psychedelic medicine effects, if you will, are short lived. Those are very intense anywhere from about four to eight hours depending on your liver metabolism, whether you're a fast, intermediate, or slow metabolizer. And then the ibogaine is cleared from the blood. So the ibogaine is cleared from the blood in 24 hours. You've cleared the ibogaine. The noribogaine is elevated. So in the days out, you still can measure noribogaine in the blood. Half-life here is anywhere from 24 to 27 to 30 hours. So that week, you're tailing off the noribogaine. So I became very interested in noribogaine and I thought, Well, and we also knew that you could sort of dissociate the oneiric effects.

That means hallucinogenic effects.

Hallucinogenic effects of the drug. And the reason I use the oneiric is that what the patients tell us is that it's like a waking dream. So it's that lucid dream state. People wake up from a lucid dream and, you know, you're, you're in the dream, you're conscious of that you're in the dream state, but you're experiencing the dream state. So that is the experience. It's very different than what the patients tell us. It's extremely different than LSD or mushrooms or ayahuasca, for example, or MDMA, completely different. And then that, when those abrupt, when that visionary experience, hallucinations, the active waking dream state, shuts off is when the noribegane peeks in the blood. So what I think today is, and for many people that experience, the life review, the patients tell us like it was like doing a fourth step. I relived a lot of the bad things I did on drugs, how it wrecked my family, how it wrecked me, my career, et cetera. There's this insight that's that's gained from having that experience. And the therapists who were with us in the Caribbean, working with the patients said, Dr. Maahe, this is extremely important for them. This is part of the therapeutic benefit of the drug. So I think that the Ibogaine nor-Ibogaine is like a one-two punch. Ibogaine begins the brain reset. It has effects like other psychedelic medicines on neuroplasticity, and synaptic turnover and healing of the brain. So it starts the reset. It's a little bit ketamine like. Ibogaine is a little bit like ketamine. It's acting on glutamate systems in the brain similar to ketamine, but it also has a serotonergic overlay. And then the noribogaine is a very interesting molecule because it has effects on serotonin reuptake also. so mood, the mood, the anti-craving and the opioid reset is likely mediated through the action of the noribogaine. So when you look at the withdrawal, when you look at the, the stages of opioid, we'll focus on opioids, opioid withdrawal, the acute phase, depending on the opioids that you're abusing, can be, you know, 1 to 2, 36 to 48 to 72 hours of severe withdrawals.

Withdrawal, right?

The ibogaine is starting that blockade and mitigating those symptoms, but then what patients really struggle with, they can get past the acute. You know, you can take a clonidine or lopexidine, you can do a methadone taper. The lopexidine and methadone taper are what the FDA has approved for withdrawal management. There are other meds, as you well know, that are used off-label first.

Label, yeah.

Yes. So buprenorphine taper, for example, off label. But what patients then struggle with is they felt horrible. They're in a deep, dark black depression and anhedonia, a protracted depression that doesn't go away. And over days to weeks, early recovery, you know, you get stress back in your life, you're not feeling good, you can't get out of bed, you have no energy, and you're just, you were crawling out of your skin. So that contracted state is what fuels the relapse. So for us, the idea of having the eye begin, allowing people to have the journey, have this profound experience with the Ibogaine, have the reset, use that as an adjuvant to psychotherapy, use that for behavioral change, as you described. Well, use that Ibogaine initiation to be in your group, in your therapeutic setting. And then, much like MDMA is used for PTSD, you know, and you know this, people abuse drugs. Why? Because they're self-medicating. They're medicating anxiety, intractable depression, trauma, trauma, trauma. You know, all the bad boogie men that take us offline as human beings and deprive us from self-actualization and the fullness of life. And so if we can allow patients to have that experience, to regain their self-control, and to find their locus of control and feel good and feel good and then follow the ibogaine detoxification with noribogaine and a pill patch or a depot in low dose formulations. We believe we have a way.

That's amazing. So how much of the sort of reset is the process of recovery? In other words, you know, could you just give noribogaine as a pill, which may have less side effects, better tolerated, easier to administer, less complicated, less expensive, and is that good enough? Or do you think we actually need the full hallucinogenic journey to reset our relationship to reality, self, life, and so forth?

That's a fundamental question to be explored. In order to do that, we would have to, as you well know, randomize two groups of subjects and really look at relapse prevention in both groups and see where we are. When I originally was working on Ibogaine, I wanted to focus solely on the metabolite because as you describe it, it will be used as a classic pharmaceutical. It would be easier for patients and practitioners can prescribe it and we can learn about the safety and demonstrate dose and safety effects, it may be sufficient. It may be what is needed here to allow people who have been detoxed to transition. But what we know today is that if you look at depression as a model, if we take depression as a model, look at college students today. I'm always amazed with the numbers of young people that are starting our universities and coming in on antidepressants.

Yes.

And now they're staggering, right? And do we need that? Or is what people are doing, the elegant studies that are being done by Compass and others with psilocybin as a rapid-acting antidepressant, and as a therapeutic adjuvant, for people who are having difficulty with anxiety disorders or, you know, other depression, depressed mood symptoms. You know, in the old days, when I, I remember when I went to college, I probably was depressed. I think my dad died and I was definitely depressed for a while. I had reactive depression. I had anxiety, I had fear. But what did we do? We knuckled up, you know, just get over it, you know, and, you know, I used mindfulness practices and Back then it wasn't called that, but I did yoga and whatnot and I just focused down. Today, everybody wants a quick fix. And so I think that this is, I'm enthusiastic as a neuroscientist today with the development of psychedelic medicines because I do think that they bring about rapid effects. We don't know the longevity of these effects. We don't know psilocybin, is it 90 days or longer? and in some subjects it may be, some subjects maybe need one or two doses to have protracted efficacy and behavioral change.

Yeah.

With the Ibogaine, you know, breaking the intractable cycle of addiction to anything, whether it's opioids or whatever, is hard to do. People fall back into the hole, you know, it's a behavior, it's so can Would ibogaine and the oneric effects help rewire the brain? And this is Mirinich and others in, you know, who, you know, neurons that wire together, far together. Yes, thank you, doctor. And so, you know, that now I'm sitting back and, you know, kind of reopening my own view of this and thinking, you know what? Maybe these molecules are so important at a time when society is more difficult, when people are feeling more isolated, things are too fast, we don't get off the grid enough to allow our brain to heal. I talk about Orthodox, I used to give a neurobiology lecture to elderly folks and I say, you know, the thing about Orthodox Judaism is that people got off the grid.

You shut down.

Correct. You shut down for one day, spent time with family and your belief system, you're in a quiet spiritual setting. How good for the brain is that? Think how smart that is, really. We don't do it. We're constantly every minute on the internet, on our phones, It's too much. The nervous system has sensory overload. We need, maybe these molecules have a place because precisely they allow this neuroplasticity to give us a window of plasticity. This idea of psychoplastogen, the term coined by David Olson and the group at Delix Pharmaceutical who are advancing non-hallucinogenic congeners of ibogaine that could be used pharmaceutically. The idea here is can they, can others make analogs of psilocybin, ibogaine, MDMA, etc. that don't bring about the psychedelic journey experience but turn on this window of plasticity in the brain. This is really an exciting time because we're learning something very fundamental about the brain and brain has always been my that's my muse. I love studying the brain. We, neuroscientists, have learned more about the human brain in the last 20 years than throughout all of human history, but the answers can get dusty.

Yeah, it's pretty extraordinary to see the sort of intersectionality of both the sort of acute, psychedelic, kind of mystical aspects of personal insight and transformation that I've heard happen on the full dose, but then the sort of long-term sort of addiction management and antidepressant effect and maybe some other pleiotropic effects we haven't even discovered that make this sort of a long-term maintenance compound for helping maintain people free of addiction. I mean, is that how you're seeing it?

It is. That's exactly how we see it. And, you know, really, when we were Back working in St. Kitts when I left the United States, we had gotten FDA permission to test ibogaine in the 90s, 1993 and 1995, the FDA gave us the full green light to bring ibogaine forward. My issue was I couldn't fund it. I couldn't get NIH funding, even though I'd been an NIH-funded investigator my whole life. I could not get buy-in. It was too early. People were funding these types of studies. You know, and we just say no to drugs and you're going to treat, can you imagine going up in front of the Congress, the head of the National Institute on Drug Abuse going, Doctor, are you funding treating people who are addicted to hardcore drugs with a schedule one hallucinogenic drug? Yeah, right. No, Congressman, Senator, no, we're not doing that. So, I mean, I understand it, you know, I get it. But at the time, I was so depressed myself that we were the FDA was so collaborative with us. You know, FDA, everybody says, why doesn't the FDA fund your studies, Dr. Mesh? No, the FDA does not fund research. They guide research in drug development, but they do not pay for drug development. So my issue was getting the money. And we didn't have the intellectual property around and I began Howard Lutts off at it. So we, you know, this, I was the odd person out here, but When I went to St. Kitts and the University of Miami was, again, very collaborative and always very good to me as an investigator and gave me the roadmap and really allowed me to do this, to go, we didn't have people running a lot of trials. Now today with stem cells and everything, everybody's off into the Caribbean and elsewhere testing. In humans, many of my colleagues are doing that, but back when I did it, nobody was doing it. And so we really had the first, Government approved psychedelic clinic working with clinicians in St. Kitts. And that's where our safety and open label efficacy database came from. So I was able to bring those data back to my colleagues and peers. And I always had an open door policy. So I invited clinicians, more doctors, the better, who come in there and see what we were seeing, bring that message back out. But even today, people don't know about it.

Yeah, it's pretty much under the radar for most people. This whole idea of sort of traditional recovery medicine and rehab medicine and the success rate of that compared to what you're seeing as the success rates with ibogaine and even noribogaine treatment, can you kind of talk about that? Because, you know, even best treatments like AA, you know, talking about 10%, 20%, that's like, preventiNg relapses, it's pretty dismal. I mean, so how does this fit a compare to that?

It is dismal. That is the word. And of course, and families have lost retirement accounts, families to save their loved ones have mortgage, put mortgages up on their houses to pay for rehabs.

Which doesn't really work that much.

It doesn't really work that much. And it breaks my heart. I mean, I speak to families all the time calling me desperate for help. and it really breaks my heart because, you know, here we are and our work can't go fast enough. I can't tell you as I sit here today that what the number is, I will never oversell my science. You know, we don't know because you have to do this in a so-called blinded fashion. And it's going to be hard to blind eye the game against the standard of care, as you know. But what we do know is that many of our patients who detoxified with Ibogaine in the Caribbean, our counselors who were there worked on an aftercare plan. You know, what's going to be different this time? You just detoxified. But we didn't want people to think that this was a silver bullet because there is no silver bullet. There is no cure for addiction. Addiction is a chronic relapsing disorder. So what's going to be different this time? What's going to be different this time? So we sent our people back into various programs. So the outpatient, some went to inpatient, some, you know, went to meetings, you know, 90 and 90, 90 meetings in 90 days. And a lot of our people said, Dr. Mesh, I'm never going to meetings. I forget it. I've done that. We're not, I'm not doing that. I'm not going to any of those meetings. and then they would take the ibogaine and then they come back and they go, I got to go to meetings. So you would see that, you know, the cognition, what should we call it, cognition enhancement, like, man, I gotta, you know, I gotta work this thing. I've got to work it. So the clinicians, I remember Doug Talbot, who ran a large treatment, you know, he's an icon in the addiction, in the addiction field, and he called me. He called me with his therapist because we put a few people into Talbott. And he called me, he said, Patients who are treated with Ibogaine look like they're 90 days clean.

Wow.

He said, They're sitting in meetings, they're engaged, they're active, they're planning. They're planning. They're making a plan. And this was just so exciting for us because we were like, Wow. So we think that if you just, and again, the FDA is going to give us guidance on what they want to see to get the relapse indication in the label, yes? Okay, black and white on the detoxification, but the big effect is going to be exactly what you're saying, relapse prevention. Can we, is this rooted in?

I mean, you think it's going to be twice as effective, 10 times as effective? I mean, what's it look like?

I'm a gambling lady. So I would bet that the numbers are going to be really stunning, that we're going to see an effect size that's very large. And I think others believe that too. I'm not alone here on this.

You can deal with the addiction part and the biological piece, but what often drives addiction, and we've had Gabor Mate on the podcast and others, is the underlying trauma the trauma, whether they're big traumas or little traumas, whether it's abuse or neglect that happened in people's childhood that drives these behaviors when they're older. And so often, like you said earlier, people are self-medicating. And if that's true, then this really opens the door to start to heal those damaged sort of circuits in our brain. But it's not the only piece of the solution.

No, it's not.

So the therapy and the sort of post work, if you will, around the treatment of addiction after Ibogaine and or Ibogaine, what does that look like and how is that different and how do we kind of reimagine it? Because, you know, in traditional AA, there's not a lot of talk about trauma. There's not a lot of talk about these underlying reasons. It's just you're an addict. That's it. You know, give yourself to a higher power and just fix it all. But it's not really dealing with the meaning you made of what happened to you and the trauma that happened to you when you were younger that drove these addictive behaviors?

I think pharmaceutical industry has shied away from developing medications for the treatment of addiction precisely because there's so much comorbidity in this cohort. Patients find their way to drugs and alcohol maladaptive behaviors for a variety of reasons. So it's not a one one fit for anybody.

Yeah.

And, and if you look at the epidemiology, I mean, straight away, you know that women don't get addicted. We're, we're somehow protected biologically. Maybe we walk around with more dopamine because of estrogen. I think we do, actually.

I think our women don't get addicted.

Yeah, no, they're, they're less likely to get addicted. However, When women become addicts, oh my goodness, they are sicker than men. So the comorbidity, I worked with a brilliant psychiatrist who was our clinical director, Dr. Frank Herban, trained my mentor at Harvard. And Harvard psychiatrist, UCLA, McGill University, so on. When I started St. Kits, we needed to clinically phenotype our people. and I went to Frank. I had been doing research in St. Kitts with alcohol drinking monkeys down there. That's a whole nother chapter. Dr. Irvin, biological psychiatrist, skeptic, you know, he died a few years ago and I miss him so very, very much. But anyway, Dr. Irvin, you know, the first round of patients who went through St. Kitts, he came to me, his glasses went down on his nose and he looked at me and he said, well, Deborah, it blocks opioid withdrawals. And then I had, I had Dr. Irvin engaged in this. And we, so we spent a lot of time actually doing all the classic psych assessments to understand who was there. And what we learned in our cohort was that in the opioid dependent group, about 50% of them were major depressive disorder, 5.0. So I think opiates, a lot of people will find their way to opiates. Maybe, you know, start using them recreationally or, as you pointed out, legitimate pain patients who continue to take opiates. You know, somebody like me, I hate opiates. Opiates for me are dysphoric. I go in, if I have a mild, minor surgical procedure and I get prescribed opioids. I don't take them. I don't like them. They feel horrible.

I feel horrible.

I don't like them. I don't need them. Other people, you know, you can imagine the mommy who's cesarean section, the doctor gives post C-section gives an opiate and, you know, 90 days later, she's still asking for opiates. Yeah, that's our girl. You know, she's now escalated. So she's probably you know, medicating, self-medicating something else going on there. Depression, I think, is primary for opiate. For cocaine, we had a lot of comorbidity. We saw comorbidity with attention deficit disorder. You're not surprised by that. Also bipolar disorder, you're not surprised by that. And the third group was family history positive for alcohol. So, you know, cocaine and alcohol, go together. This was my research. So there's, what I'm trying to say is there's an underlying neurochemical setting that's going on in the brain and people are attracted to different classes of substances, be it alcohol, cocaine and/or nicotine or opiates, that you can kind of separate them out. And so you've got to understand what's the underlying thing. In terms of the work, the seminal work of Gabor Mate and others, you know, yeah, there's a lot of trauma. Yeah. A lot of sexual abuse and women, we saw that. And men too, men too, childhood sexual abuse, amazing, stunning, crazy, crazy. And I was away from the therapeutic group. I stayed away from that. I allowed the clinicians, I'm not one, pharmacologists, clinicians work with patients. But when I started went in on a research way and started to read charts. I, I couldn't believe what I was reading there. So that's a, that's a huge driver of maladaptive behaviors. We, we know this. We know this.

I mean, I, I think, I think for sure all the trauma plays a role. And I think so dealing with that in the post sort of treatment acute treatment with ibogaine or any other sort addiction disruptor seems really important. And so, the therapy associated with it. And, I was just talking to a guy named Jeff George who's the chairman of MAPS, the Multidisciplinary Association for Psychedelic Studies. He was talking about the goal they have of getting FDA approval for MDMA-assisted therapy. So, it's not just the drug itself, but it's combined with a whole therapeutic approach that allows you to deal with the underlying issues that caused the problem in the first place. So it seems like it's not an either or, but it's a both and.

I think that's right. And the other idea that I have in the back of my mind is, you know, when people would first go into rehab, get clean, get sober, and go into rehab, there wasn't a lot of time or energy to work on trauma The only thing you could work on was how am I going to not go out and get high?

Yeah.

So I can see a world where you can use ibogaine as an addiction interrupter and then get down to what's underneath there. What's really, what's, you know, what is the clinical phenotype? What are the underlying issues? Is it intractable depression and you're self-medicating that? Okay, well now you've just taken ibogaine, you're washing out your noribogaine and maybe your depression will start to come back and maybe over weeks to months you're gonna start to feel a wearing off effect of the ibogaine. Now would you be a good candidate perhaps for ketamine series? Maybe. How about you're a good match to psilocybin therapy? Maybe you are. So what is driving, is it a dopamine-mediated depression or is it a serotonergic-mediated depression? And here's where the biomarkers are going to come in and the clinical phenotyping to allow us to better understand, you know, what's driving the disease of addiction. What's driving the disease of addiction? Same thing with trauma. Take, you're now got detoxified people. They're not craving drugs or alcohol. Can you then have them work with the MAPS protocol to start to heal the underlying traumas and move people out of that.

State? Yeah.

So that's why I'm so excited. And the young generation, the next generation, of psychiatrists and therapists will have these tools. How wonderful is that? My father died, I will share with your listeners, my father died at 56. Alcohol used to sort. He was brilliant. He was funny, brilliant, spiritual, you know, well-read man, self-taught in many ways, but he had a horrible trauma in his life. and he experienced a major PTSD event and the loss of the life of his brother. In some ways, he blamed himself. I think he did. I was, I was a child, so I didn't really know what was going on and with my father's mental health. But he, he white-knuckled sobriety. He did everything he could to not drink. I mean, he fought it, but stress and whatnot would get him. But when he drank alcohol, it was Not a good, it was not good. And it ultimately poisoned his myocardium, his heart, and he died. He died of a broken heart, but he died, he broke his heart completely. And so I saw him suffer and he's a great motivation for me to keep working on this, yes.

So true. So I have a question I'm going to ask you, which you may not have an answer to, which is always on the top of my mind, which is how does it know? How do these plants, know what to do with our biology. In other words, how do the compounds in these plants bind to certain receptors, activate different pathways? It doesn't seem to make sense because we're humans, they're plants. What do they have to do with one another? How does it work? Did we evolve with these compounds to help regulate our biology? I talk a lot about food as medicine and I do see that these compounds are not sort of nice to have. They're kind of have to have compounds if we want to stay healthy, whether it's the anti-inflammatories in food, the antioxidants in food, the phytochemicals that help regulate all our longevity switches. And, I just finished writing a book on longevity and it's just fascinating. Look at these phytochemicals and how our bodies use these compounds from plants, not just for psychological purposes, but for maintaining all of our biological systems from mitochondria to our microbiome to our immune system to our detoxification systems. or hormonal regulation, all of this controlled in part by these plant compounds. So what's your kind of thinking about how this works? Because, you know, these compounds have been used in cultures for thousands of years. Somehow we figured it out. And, you know, humans have been using this as sort of spiritual doorways in cultures for thousands of years. And suddenly we're sort of figuring out that they have these other properties that may be medically useful. So how did that work? how does it know?

Plant teachers, right? Plant teachers. I started the discussion with you about alkaloids, that Mother Nature gives us addicting alkaloids and ibogaine is the Mother Nature's antidote to addiction, right? So it makes sense to me. They, we definitely throughout human evolution, our brains changed and our liver and our cytochromes that detoxify things that we eat evolved and adapted. There's no doubt about it. So there is this effect on the neurochemistry and signaling pathways in our brain that have evolved over the course of human evolution. There's no doubt about it. As our brain expanded and we developed language and all these things and the written word, that the food in our environment and the things we're exposed to in the environment, whether teas or tinctures or plant medicines that were known and lost, to us.

Yeah.

Had real effects and beneficial effects. So I look at this with an open mind and recognize, and I too, I'm a true believer in food is medicine. There's no doubt. I mean, there's no doubt about this. You feel better when you eat right. Hello.

And the science is there to back it up, which is quite amazing. Yeah, you know, it's sort of funny. I think about the sort of anthropocentric hubris, you know, our conceit as humans that we're separate from the natural world, that we're independent from it, that we don't really need it, that we can live in these concrete boxes in cities. And the truth is that, you know, we can eat astronaut food and be fine and live on Mars and be disconnected from the world. We are biological organisms, whether we like it or not, we're part of nature and we are intimately connected with nature in these incredible ways that are so mysterious to me. And I think Einstein said it really well. He said, I'm not interested in the spectrum of this or that element. I'm interested in the thoughts of God. The rest are details. So what are the thoughts of God? What is the mind of God? And this is sort of what we're talking about. And how does the sort of the orchestration of these molecules and our molecules all work together? together to create healing, repair, rejuvenation, end of suffering. I mean, it's just, it's kind of like an existential sort of, you know, kind of festival to think about all these things where we get to, you know, it's.

I'm going to use that. I think, you know, I, I'm, I'm a kind of an overachiever and, and lived my life full catastrophic for a lot of years and, and tried to control everything and, you know, adult child of an alcoholic, so I fit that, I kind of fit that mold. But I woke up one day and had the epiphany in my own head, which was, you know, all knowledge exists in the mind of God and you don't own this Deborah, so relax.

Exactly. Exactly.

I think this renaissance, this existential festival of knowledge that couldn't come at a more important time for us as part of the human family. and we really need to learn from, you know, from the great religions and from the ethnobotanical, you know, and plant teachers and wisdom, you know, we need to call in this wisdom.

It's really true. So I asked, I was done once in the jungle in Peru and I met this guy who was an ayahuasca guy who, you know, was administering ayahuasca. And for those who don't know, it's a It's a combination of plants, any one of which might kill you if you took it alone, but together they seem to have this beneficial effect. I said, how did you figure this out? Did a bunch of people die? He says, no, no, the plants told us. I'm like, what, you talked to the plants? He's like, yeah, the plants told us. And I'm like, it's just a realm of knowing and knowledge that we don't really accept or are familiar with in the West, but it really is what these ancient cultures have. And I, you know, I always wondered how we sort of survived all these years, 'cause there's so much nasty stuff around. If we eat, we're gonna die. so how do humans even survive? But somehow we figured it out. I, I want to sort of pivot a little bit to talk about people who might be listening and wondering about getting treatment. The, one of the challenges that I've come to understand around ibogaine, it's not like psilocybin or LSD, where there's very little lethality. These are very safe compounds, very high doses. You know, they'll be something called LD-15 in medicine, which is a lethal dose, you know, 50. That, that. seems to be not so much of an issue with these other compounds, but with Ibogaine and Iboga, it seems to be tricky and that there's a real cardiac risk in these compounds and administered in therapeutic settings like in Costa Rica or Mexico where they're used in clinics for addiction. They hook people up to an IV, they put them on an electrocardiogram, they give them oxygen, they watch them, there's medical supervision. Can you talk about this sort of aspect of it and how we navigate it? And if the, you know, how dangerous is it? And is the Norepinephrine also risky or is it just the regular Ibogaine at hallucinogenic doses?

Ibogaine has been administered to desperate people in unsafe settings and there have been deaths. And your listeners need to know this and understand this and something that I've spoken about with a very loud voice and some people get angry with me about this, but the facts are the facts. And nobody who wants to get to have a chance to break out of the pattern of maladaptive use of drugs or alcohol deserves to be given Ibogaine by someone who doesn't know what they're doing. There are unfortunately unethical individuals and it really is a buyer beware kind of situation and people buy Ibogaine on the internet. They send families will send me emails and say, Dr. Mash, I've just bought some Ibogaine on the internet and I'm like, oh hell no. No, you did not and do not give that to your child or your son or your daughter or your husband. No, no, you can't do that. You need to be under medical supervision by a qualified clinician. You need a doctor who knows what he or she is doing. period, end of story. Having said that, when we started in St. Kitts, we had no idea of any of this. Okay, we had no idea about what the benefits to risk were for Ibogaine, what the therapeutic free plasma concentration, the safe plasma concentration was in humans. And Howard Lotsoff had been getting gram quantities. of Ibogaine, which is ridiculous. I mean, that's a lot of Ibogaine. And so people look back at some of those early publications and think, well, I can take that. No, you can't. No, you cannot. You should not, and you don't. So what we did in St. Kitts, and I even think about it now, I look back on our database and our results, we treated our clinicians, our doctors there, administered Ibogaine to 277 people. Most were opiate dependent, but there were also cocaine, some were alcohol or poly drug dependent. And we did not have any deaths in same kids. But everybody was hooked up to, they were on telemetry the whole time. We prepared them to take the Ibogaine. We did full medical evaluations. Everybody had an EKG before they went in. and some people had Holter monitors or other cardiac testing to ensure that they were cardiovascularly fit to take Ibogaine because Ibogaine does have an off-target effect on the heart, just like methadone. Methadone causes what we know to be QT prolongation. So the refractory period of the heart changes and that's a dangerous thing to happen. You don't want that. Because when that refractory period changes, if there's any disease in the heart, then you have the risk of having a lethal arrhythmia.

So it's only people with pre-existing heart disease is what you're saying.

We believe that. Also, as you well know, magnesium deficiency. Many people are using drugs and alcohol. They're not nutritionally fit. So you've got to do their labs. But even when you do their labs and you measure these things, you don't know what their magnesium and calcium stores are in the heart. So you need to get people ready for IVIG. You need them to be ready and you need to have a good medical clearance and you have to have clinicians, doctors who know how to run, to manage an event in the event that you see an adverse effect of the drug.

Those are manageable if they have them.

They are manageable, doctor. They are manageable if they have them.

So you're saying in a well-supervised clinic, that's run by physicians who were knowledgeable about how to manage these events, that it's a very safe treatment.

That is that I have written that. I have published on that. I have lectured on this and I've spoken about it. And today, as we're running our clinical trial, we are currently doing that safety. Right now, that's what we're focused on, is defining the safety window. So as you said, psilocybin is extremely safe. It's hard to get in trouble with psilocybin, right? It's a huge therapeutic to toxic window, huge. For Ibogaine, it's more narrow. So we need to define it. We need to define it and we need to know. That's the concern with Ibogaine.

Yeah. So you're doing the hero's work. which is actually the drug research, the hard clinical trials, proving the safety, the efficacy, the dosing, trying to get it approved by the FDA so it can be widely adopted. But that could take years still. It's an arduous, slow process. And now there's more funding for this research. There's more interest in it. You've been doing this for decades in the dark wilderness. But now the light is coming. That's good news for everybody. And yet still, we're facing this juggernaut of addiction, not just opioid addiction, but all sorts of addiction, alcoholism, food addiction, work addiction, gambling addiction, cocaine. I mean, just all the substances, nicotine. It seems as though people hearing this might be, well, thinking, well, I don't want to wait. I know there's clinics in Mexico or Costa Rica or who knows where. should I go and should I do it? And what would you say to them? I'm sure you've been asked this question and probably as a scientist, you can't really advise that they do it, but it just seems like a desperate situation where we have a cure or a treatment, but it's not approved and yet it works.

That's an important question and you raised an important concern for people who are desperate and have loved ones ones and want to know where do I send a loved one to get Ibogaine? And I will tell you, I will share that one of my family members, I had to send for an Ibogaine treatment. And I send them to a place in Mexico with a doctor who trained with us in St. Kitts. So when I had a loved one, we didn't have a clinic anymore in St. Kitts and here was someone in my family, family member, who needed a detoxification. And I got that phone call and said, you have to detox this person in our family. And I was like, what? So I picked up the phone and I knew where to go. And I called someone and my, the doctor was wonderful and they took care of my loved one. She had a safe, by the game treatment. And she's doing very well. And she has child coming in them. very excited about all of this good stuff. It's difficult families need to ask the question. I haven't gone down and vetted all these different places. There are Ibogaine clinics popping up everywhere. Speak to your doctor, speak to the doctor who's going to be there. Make sure that you get the right cardiac tests. Speak to your clinician in the US. Tell him or her what you're thinking about doing. get the information. Read, read online. People can send me emails, they do, or they find me, they call me all the time, and I'll discuss it with you. I feel that that's a responsibility that we have. I think there are some places that are better than others. I won't endorse any of them on this call right now, but please, please, please ask the right questions and make sure that you know that what is being administered is in fact ibuprofen, because I think it takes stuff that they're not sure even what it is, and make sure that you're with a clinician. Make sure you have a doctor who spoke with you.

Well, I appreciate that, and I think people will be interested to hear that this is a treatment available and maybe it's worth exploring. I know you can't answer this because you don't have a crystal ball, but given you're so deep in the weeds on the research and the FDA approval process, what's your best guess and where we're gonna end up with a FDA approved treatment that includes norepinephrine or ibogaine?

I think about this every day. As I wake up with this thought in my mind, I go, I know you do. It's all consuming for me. A little bit gonna be the luck of the draw, right? So right now we're doing the dose escalation safety arm, and I have a assembled stellar, world-class cardiologists, electrophysiologists. So, you know, this is the big testing and it's an expensive study and we're doing it and we're going to get the answers that the regulatory agency needs to know. Once we get the answers and we've got exposure response and we know that Ibogaine can be administered safely and what we think we're seeing is a little benign transient QT prolongation. You know, methadone is a QT prolonging drug. I'll just throw that out there for the listeners. So drugs that cause QT prolongation have been approved by the FDA and other regulatory agencies. They're in use. Doctors know this and they're aware of drug interactions and whatnot. As we discussed, with that information, then we move into what is called a proof of concept study. Now, if, or I'm going to say when, we demonstrate what we've already seen in open label research and published by other groups separate from the work that I've done with my colleagues, other people who have done the same kinds of things and have publications in peer reviewed medical journals, when we demonstrate the efficacy endpoint, then we have an opportunity Working again with the FDA and other regulatory agencies to get what Compass Pharmaceutical has for psilocybin, breakthrough designation. And with that, then the question is going to be the safety database. What's going to be the size of the safety database in phase three? Is it going to be 500 people, 600 people, 1,000 people? What are the regulators going to ask us to see? and I think given the magnitude of the problem, the trillions and trillions of dollars that are being spent, the lack of other molecules that are entering the pipeline, that the regulatory agencies will absolutely Foster this research.

I think that, that, that pharmaceutical company that Purdue Pharmaceuticals, that was responsible for the a lot of the epidemic and who really had to pay billions of dollars in fines, that those billions should go to funding this kind of research.

I do too.

And actually, the tobacco companies had to pay money for funding research.

Absolutely. And I think again, I can't work fast enough personally as a person, I can't work fast enough on this. and I regret that we don't go faster, but we're doing it and we're here now. And with the support of a tie and the investors at a tie, we have the funds available to do this research, to do it the right way. This is really, as you said, this is a landmark study.

If you love that last video, you're gonna love the next one. Check it out. A society that thinks that.

People have.

To be competitive and aggressive and selfish and individualistic actually denies the very nature of human evolution and human needs.