Remodelling the Addicted Brain: Ibogaine Therapies

Remodelling the Addicted Brain: Ibogaine Therapies

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welcome everybody again to another episode of the idea me show that show the profiles the humans behind the really big ideas that are shaping our world inspiring future creators and for all those that like really great stories I'm IRA pastoring and your health aging along jeopardy ambassador along for this ride so according to the u.s. national survey on drug use and health in 2017 an estimated 20 million American adults we're battling some type of substance
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abuse drug abuse and addiction in the United States estimated it cost over 700 billion dollars annually in terms of lost workplace productivity health care expenses and crime related costs globally the numbers are further off the charts more specifically on a topic that we hear quite a lot about today in the area of opioids class of drugs that includes the illicit drug heroin but also the listed prescription painkillers oxycodone and hydrocodone coating
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fentanyl and so forth of that 20 million it's estimated around 2 million have a substance abuse disorder involving prescription pain relievers and over half a million of a substance use disorder involving heroin with tens of thousands of overdose deaths per year we're seeing an increase in infants born opiate dependent as well as a spreading of infectious diseases including HIV and hepatitis C in these populations in 2019 the most effective opiate withdrawal methods still involve substituting and
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tapering with opioid antagonists such as methadone and buprenorphine and the best outcomes are primarily seen with such treatments combined with the appropriate cyclists social interventions but most thought leaders in this space you know are pretty much on the same page that we need much better agents to impact the complex brain changes related to addiction addictions of all sorts and our pharmacotherapy attic armamentarium right now is is rather small still in this area so for today's guest i could think of no one better to come on and
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talk with us for a while about this topic take us into the future then dr. deborah mash dr. mash is the professor of neurology and like you another pharmacology the Leonard Miller School of Medicine and director the brain and down the back of University of Miami as a neuroscientist lecturer and inventor dr. mash has dedicated more than 25 years in a research career to unlocking the secrets of the human brain she's nationally recognized the leading research or neuroscience and brain disorders playing pivotal roles
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publishing 300-plus published studies investigating aging nor degeneration or psychiatric disorders she works with a team of neuroscientist pharmacologist friends of toxicologists clinical researchers to bring many basic discoveries from the bench to the patient's bedside in the early 1990s dr. mash was involved in a US fda I indeed it was truly unique for its time where she was granted this IND to permit to do Studies on an addiction stop being
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capabilities of a DEA Schedule one substance known as ibogaine and for those that may not be familiar with DEA scheduling schedule one drugs or substances are technically defined as those that at the time had no accepted medical use or a high potential of abuse including substance like heroin LSD ecstasy and so forth dr. mash and her colleagues had previously discovered through their extensive work in both the pharmacology and pharmacokinetics of ibogaine despite having rather intense visionary effects that it actually
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serves is a really interesting Pro drug that when metabolized turns into a substance known as 12 hydroxy iboga mean or nor I the game rather profound effects on binding to opiate and other to pleasure receptors in the brain nicotinic serotonin NMDA and so forth to help block the withdrawal effects very long periods of time and allowed drug addicts to properly come down off the drugs and ultimately help to remodel and a neces normalized the brain's nora chemistry in neurobiology in addition to her roles he or she
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serves as the CEO and founder of a company called Emmerich's which is a development stage biotech company that's looking to clinically develop and commercialize technologies around where ibogaine for both addiction withdrawal and other CNS indications dr. mash is a member of the Society for Neuroscience problems of drug dependence the research side and alcoholism the American Academy of Neurology the American Society for pharmacology and experimental therapeutics and the International Society of brain research a lot of stuff here so with all that dr. mash thanks so
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much for Chris Penny who thought to come on the show today thank you for inviting me it's a true pleasure having you here so you know we typically start off the show by giving our guests the floor just to talk about you your background where you grew up how you got interested in health medicine or a science and ultimately the path that that brings you in 2019 to really the epicenter of addiction therapy neuroscience nor pharmacology really when hear all about it because
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it's a fascinating journey well the journey has been a long one as we both know because you and I go back many years and have crossed paths more than one time both of our professional careers but neuroscience has always been my passion and science has been my passion since I was a child I was one of those nerdy little girls who participated in the science club the math club the rocket club and always had
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a deep love science and my passion for brain science for neuroscience really goes back to my undergraduate days but on on my on my path to where I am today neuro chemistry neuropharmacology is where I ultimately landed and my work at the University of Miami first began as a graduate student in the field of neuro pharmacology and back then I was working in the Alice Hyman field and I was
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really at the front end of that disorder and trying to understand and identify the chemical aspects of that disease and what we could do from a pharmaceutical standpoint to treat it that led me to Harvard where I I was very very privileged to complete my fellowship at Beth Israel Hospital with Professor Marcel meh Salaam in the Department of the late doctor norm Geschwind
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it was really one of the top neurology behavioral neurology groups in the world and working with dr. mess alone we advanced again more of our understanding of what is the cholinergic nervous system with that background I then was invited to come back and join the faculty at the University of Miami and I became an assistant professor in the department of neurology and I had a secondary appointment in pharmacology at the University of Miami and there I
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began and my career was off to a great start because I had funded my first NIH grants and my laboratory was was on the up when I get to Miami things change Here I am with a laboratory to study Alzheimer's disease but Miami is hit hard by the cocaine epidemic because of our close proximity to the Caribbean and the transshipment routes of cocaine from South America through the Bahamian
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corridor into Miami we got hit first cocaine exposed infants cocaine intoxication deaths the phenomenon of cocaine-related excited delirium and a colleague of mine from the CDC who I had known from my undergraduate days was in Miami came in trying to understand why they were seeing this increase in drug-related deaths to report back to the CDC and there was no understanding
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because it looked like people were dying with what they thought were recreational blood levels of cocaine on board and that leads me to my collaboration with miami-dade medical examiner's Department and that department was fantastic that was the late Joe Davis dr. Davis was a pioneer in the field of forensic medicine and the deputy medical examiner was dr. Charles wetly and dr. Charles
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wetly who was working in the area of cocaine and cocaine-related excited delirium people who would exhibit this Hulk Hogan like strength they would die in custody and so this was very controversial so they said well you know there's this woman who has a brain back dr. Deborah mash she's in the Department of Neurology somebody needs to talk to her because we need to figure out what's going on we don't have a cause of mechanism of death for most of these cases we need to work with her maybe
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it's something in the drug maybe it's a toxin in the drug and the cocaine that was coming into South Florida we thought that for a while something's going on here and it's probably the mechanism was in the brain I go over I meet with them I see a friend my old friend dr. Jim Ruttenberg from the CDC in Atlanta he had trained at Emory hmm and I knew him when I as I said as an undergraduate so this was an old friend and I listened to the story
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and I thought this is fantastic I said Jim can I get come up can I meet your boss at the CDC I want to get your data I travel up he introduces me to the boss the boss gives us permission to collaborate and I write my first grant to the National Institute on Drug Abuse I never published in the area of drug abuse I went into a room locked myself in a room came out with grant application submitted it was called CNS mechanisms and cocaine related sudden death and we were funded on a first
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submission so my life changed like overnight I was now in drug abuse research I come back in to my colleagues and I said wow we got the grant put everybody in the room and I said now we need to make sure we do the right science how are we gonna proceed and a wonderful colleague collaborator who was head of a toxicology dr. Lee Hearn said to me Debra we need to look at coca ethylene said coca would cook what and he says
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you know it's the Ethel homolog of cocaine that's warm when you drink and use cocaine in combination and I I said no I don't know that draw it on the blackboard so he sketched up the molecule on the blackboard for me and I said can you make it and he said yeah in six months we had national press we made the cover of every newspaper and I'm not exaggerating because the Society for Neuroscience gave us a press release and
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we were the Miami Vice metabolite this is action item number two and we were getting so much publicity it was really ridiculous we science magazine wrote us up as the Miami Vice metabolite again I mentioned we made the AP wire service we were just it was crazy you couldn't stop getting press and meanwhile Miami's you know South Florida's suffering from dead bodies and babies born and homes wrecked and you
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know the rest of it crime hiv/aids all of it all of it all of the scourge of drug addiction so here I am getting all this publicity we're very proud of ourselves and I'm traveling around and my the former president of the University of Miami tad foot a really remarkable human being comes to me and he said Debra I want you to lecture to the coalition of drug-free
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America you may remember and I'm your president asks you to do that you say yes sir so I go and I give a lecture and at that lecture I'm talking about coca ethylene it's the end of my lecture I mobbed by a whole group of people but a black gentleman came up to me that day and said dr. mash have you heard about this drug from Africa that can be used to wean people off with cocaine and heroin and I looked at him and I went no I've never heard of that and he's
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- really he's you know very excited about this and he wanted to explain it to me and he's explaining it to me and there's a whole crowd of people around me all trying to talk to me at the same time and there are reporters there and all this stuff and I think I was you know probably very abrupt with this man because I get I know what he was talking about he's talking about some drug that comes from Africa and it says used spiritually in Africa and the whole thing sounded just it was not what I wanted to hear on that day it was I just
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wasn't listening and I said no I'd never heard that and I said sir thank you so much for telling me about this but you I have so many people here I want to talk to me so thank you you know I appreciate it and goodbye first time I heard about ibogaine second time I heard about I began I went to the college and the problems of drug dependence and I was giving a I was invited to give a lecture on Co Kathleen so I get my lecture on Co Kathleen I'm pretty bored with Co Kathleen now okay we've been you know
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getting all this publicity media I've been lecturing on it and it's like you know I'm more on to the next what's next here we got to come up with a solution okay this is something we've described it's more lethal it's more people like the combination of coke and booze okay I get it how are we gonna deal with this what what's the solution here what are we learning I haven't really played around with my program so I didn't really know what was who was talking or what was going on at the meeting so I said I'm gonna go sit in the back of
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this room I'm gonna look at my program I'll listen to whatever is going on in this session it was I think a cocaine session and I'll relax and there was a man there by the name of Stanley Glick professor Glick from Albany who had these rats these little rats who self administer drugs and he was giving these rats this drug from Africa mm-hmm now I've heard it twice and the rats would stop taking cocaine in here and I I looked at the screen I'm watching this I
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put my program down and I went that's the same drug that that other man was talking to me about now I've heard I come back from that meeting and I had an old answering machine and I play back my answering machine and there was a call to me from a man by the name of howard lotsof and howard lotsof was calling me because he wanted to check our information on Cocoa ethylene to support a poly drug dependency patent that I then he was filing for this drug
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from Africa called ibogaine and at that point I was what is this drug how does it work what's the mechanism of action what do you know about it I need to hear about this this is you and he said yes I have four patents filed one for opioid and opioid addiction psychostimulants alcohol nicotine and now filing poly-drug I said okay what can you tell
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me and he said I will come down in Miami and I will bring my data I said please do so come down I want to hear about this he comes down to Miami with his wife Norma Alexander he brings me a box of papers kind of junky papers newspaper articles clippings anecdotal information about the drug sure I look at it it's not Dana you know anecdote is not the plural of
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data he had a lot of anecdotes but he had two things that I wanted he invited me to see it with my own eyes he invited me to go to Amsterdam where he was working with a group who were running a kind of underground railroad of addicts helping addicts called the International Coalition of addicts self-help and the Dutch addicts self-help women both of those groups together and he also had a Belgium manufacturing company that were
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experts in natural products we're manufacturing the ibogaine according to Good Manufacturing Practice something you would need if you were going to test this in a academic Medical Center sure so I I'm a pharmacologist I need an MD so I go to my colleague dr. Juan Sanchez Ramos an MD PhD in the Department of Neurology and I said one will you get on an airplane with me I'll buy the tickets
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let's go to Amsterdam let's see this I go to Amsterdam I see three men go through good treatment first of all when I got to Amsterdam I thought I had lost my mind because it was not a clinical setting there was a skytruss there who was straight out of a a Fellini movie there was this whole entourage of luck sauce
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people it was just not it was not what it was not academic it was not scientific it was not clinical it was something from a movie yeah but I'm there and there was a group of reporters there too at the time and other people it was a whole group of people and I met the young men who were going to go through the treatment and there were three young men and I will go
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to my grave with this with this experience because there was a young man Marc who had was on 100 milligrams of methadone he was taking benzodiazepines he would chip on heroin on occasion and really struggled with addiction for a very very long time and a remarkable young man just a remarkable remarkable young man really suffered another young man who was young a musician of Puerto Rican musician very talented spectacular
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also had a horrible heroin addiction and the third young man was the son of an Orthodox rabbi from New York who had struggled with cocaine addiction and had severe attention deficit disorder and was self-medicating with cocaine as a psycho stimulant all right so these three men are in three separate rooms they give them the ibogaine there's no crash carts there's no cardiac monitors there's no ID lines there's nothing but I sat at the bed and
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I stayed up all night long at the bed of these three men and I went from room to room everybody else went to sleep but I was there there were no nurses either so I helped these men I gave them water or whatever I could do you know be present for them on going through this and but I had an idea and I said to Boaz Wachtel young man and Israeli who was part of the nuts off entourage I said Boaz these young men will give me urine samples
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go get me dry ice Styrofoam container and urine cups and he did and I collected urine and I sat up with these young men and I watched these young men transform no withdrawals get up out of the bed the next day eat a full meal go shower shave clean up and sit down across the table and tell me what was going to be different in their life and tell me how good they felt and I stayed
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with them for the next few days so I got to watch their transformation and I said what is this what is this there has to be an explanation and I have to go home and I have to tell others what I just saw mm-hmm so I did I gave but the first thing was I had to get that box of urine on the plane Bogey's carry cash I went to the airport
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in Amsterdam I got my box of dry ice on them on the flight got to Miami I got it off the plane and I drove in my car to my colleague dr. Lee Hearn who worked with me on the metabolite Co Kathleen handed him the box here and I said Lee get this on the gas chromatograph mass spec show me the metabolites of ibogaine and that was the discovery of neurotic fact fascinating journey especially Ike oh I'd love to see what you said when you
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way and the dry ice would be urine in it getting on the plane but it's clear clearly a fascinating this guy a set of discoveries let's put it that way until that point now if you will take us from there I know I was you know if you spoke about obviously this long you know this wasn't something that accidently like a birdhouse them and LSD it appeared in
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the lab you have a long sort of ethno medicinal phytochemical flight of medicinal use in West Africa Gabon Cameroon Congo and so forth used for religious ceremonies very spiritual undertakings and what have you we get the substance and the metabolite back to the United States your pharmacologist psychology pharmacokinetics and so forth take us now to that point where okay
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there's an you study these amazing properties when talk a little more about that what you found in the lab but now you're going into this this gauntlet let's say of FDA and DEA where on one hand you have an amazing potential clinics have clinical trials to run in the early 1990s on the substance but it's still a Schedule one substance and DEA wants to smack you down at every particular point and from even getting in you know playing with this stuff take
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us a little bit through that journey cuz that's really another fascinating part of the progression of the story I think first of all all right so I get the you know the the great idea that one I immediately had to tell my colleagues at the National Institute on Drug Abuse because they were my boss I'm recording tonight to the NIH NIDA on an NIH funded investigator you know universities are kind of like medieval stalls you know they don't support the research they
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give you a place where you can sell your wares you have to sell your wares to the funding agencies in the end I always told my staff in my laboratory our boss I mean yes the University of Miami is my boss I have a chairman etc but really our boss is the NIH I have a duty to report back to to my boss which is the NIH so I did that and the NIH and NIDA and keep in mind I was an unknown at night at the time because I was a brand
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new investigator for that hmm you know I wasn't an established NIDA investigator here's this woman for Miami she's not you know she has a flash in the pan with Coco a scene and probably a lot of people in the end and my colleagues and peers were like who is this one right and now she wants the test ibogaine oh good that are great you know and and my personality is such that if I want to do something I will do it it's just how I
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roll you know it's my I don't know why I'm like this but definitely yes do this right so I go I go first and I also go I had a wonderful I was very very fortunate at the time too because I had a fantastic dean of research my dean of research at the University of Miami was a man by the name of dr. Bob Rubin and you could not have asked for a better research team in this man this man loved science as much as all of us he had his
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own laboratory he was brilliant he is brilliant and he just supported his faculty he wanted his faculty so when I and I had a good track record because I was getting funding so I went to dr. Rubin I explained all of this to him and I said I understand if we're gonna do a clinical trial at the University of Miami you know this is a Schedule one drug it is untested to be a new clinical trial so dr. Rubin said no it's okay we'll do it we'll go behind you Deborah so he paved the way for me with the
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University and University was excellent I went up in front of the insurance carriers we presented he gave me resources it gave me people to help me with drafting of the protocols for the FDA what resources were put in put on my on the table for me more us our group of collaborators at the medical school so that was number one if without the University behind us we one day able to do it I went up to the NIH I had been invited tonight on by dr. Charles Gretchen's cos and Frank voci who were
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heading up the medication development division at NIDA talking toga ethylene by now I'm totally burned out on Kathleen plus I've seen ibogaine do this remarkable transformation and I go in there and I give my talk and then afterwards I tell dr. Bochy and dr. Gurjit sis I said you know University of Miami's gonna file an IND fraud game I don't know this to be true but I I'm pretty much believed that when I turned
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around to leave that the two of them cracked up laughing that they laughed at me and said this woman forget about it she's never gonna get that done I'm certain I'm fairly certain that this is true in fact I should ask Frank Bochy if he was laughing that day they'd probably tell me the truth so I come back to Miami we write the IND we submit it to the FDA the FDA was
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highly collaborative the medical safety officers all of the people at the FDA were so collaborative and so wonderful to us I my experience with FDA was always good and I man Here I am I'm an anomaly I'm I don't have a big pharmaceutical company behind me I don't have a track record of clinical trials in addiction at the
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University of Miami there were a lot of negatives yes Schedule one drug heart blood soft who wasn't the most collaborative and cooperative purse with National Institute on Drug Abuse and other people it's just was the way he operated and including university of money but nonetheless we persevered and in 1993 we got approval for the first
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clinical trial in the US and that was such a huge accomplishment we couldn't believe it but it was very difficult because we went up in front of what was called the drug abuse Advisory Committee of the FDA and we had to convince our colleagues and peers and that day was a free-for-all maleeh was a free-for-all because we had an open meeting I allowed everybody to come I was so excited about this because I had you know seeing is believing and I had seen it and I I wanted to do the
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right thing and I wanted stakeholders involved and I wanted the collaboration and it wasn't my ego or the ego of our of our group down in Miami we really wanted to share and I shared I shared the discovery of the men in the metabolite immediately with NIDA immediately I gave all the data that we had because you know we needed to work with them we needed to work with NIDA if we were gonna do this somebody had to pay for the clinical trial put it that way so we go in there and the meeting
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was terrible because for a lot of reasons it was kind of a crazy meaning because howard lotsof there were demonstrations of sure is not Wars or people picketing outside the FDA was all kinds of crazy things going on the media was there was really a circus but one of the damning things was an investigator that was a night of fun and contract investigator by the name of Mark Bolivar who came in with this idea that high-dose ibogaine would cause cerebellar toxicity
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would damaged brain damaged neurons in the brain and rodents were this was shown in rats now I had done monkeys down in st. Kitts where I had been working on a grant funded by a night relay by the alcohol Institute and working with the late Frank Ervin who biological psychiatrist and also Roberta Palmer and I had been down there so I had veterinarians and we had a whole thing with monkeys down there and
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so I asked Frank to give me some monkeys which he did he gave me monkeys we dose monkeys repeatedly with ibogaine and then I brought the brains back we did full necropsies on the animals and I brought the brains back to Miami and I gave them to neuropathologists because I had the brain bank so and with wonderful neuropathologist by the name of dr. Michael Nurenberg and his collaborators in that division Michael will you help me Michael had helped me for many years on many different things and I said
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Michael will you help me you look at these monkeys and by the way he was an expert on cerebellar damage because he had been studying hepatic encephalopathy so the guy really was an expert and I said look at these brains and you tell me if there any dental currents in these monkeys because I need to tell the FDA night a week I need to report this we need to know we don't wanna hurt anybody yes so I knew it didn't do anything in monkeys this we got a net nothing dose that would be given to you in the high doses that would be given to him and
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were free of any toxicity a monkey so and humans doctor I worked in a neurology department and Juan Sanchez Ramos a phenomenal he is a phenomenal neurologist in what movement disorders we were doing posture ography very sophisticated testing of motor and cerebellar function so we had ibogaine patients patients who took high doses of ibogaine for detox and we had all this
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neurological safety hmm so we felt good about this and we presented that to the tonita and the fda and everybody you know got to see these data so I was pretty confident about that and but the meeting wasn't going well because when you raise a neurotoxic flag uh you know it's a big honor so I looked around the room I'd really had enough of it and I said I don't even know how to be honest I don't even know how I knew to do this but I said meaning closed everybody out he tried to be a sous vide
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committee lotsof in his group out University Miami in and I looked around the room and I said that regulatory attorney who's with howard lotsof he can stay in and listen everybody else have and we went into closed-door and we stayed there for hours hours and hours I think everybody was burned out including my colleagues from um and finally there was a kind of a motion made by one of the women an RN I believe an RN who may
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have been in recovery I don't remember all the details at the time but a really a compassionate clever lady who sort of made a motion and at the time I was an elected official in municipal governments I knew something about parliamentary procedure I grabbed the microphone said to the chairman of the DAC mr. chairman you have a motion on the floor let me restate the motion the motion is to allow us to go forward and I began veterans we got a second and
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that meeting gave us the open door and there's another legendary person from that meeting and his name is dr. Curtis Wright who was one of the guardians of helping us to put together a careful safe proper protocol to test ibogaine safety and pharmacokinetics and humans to start the phase one mm-hmm in 1995 I went back to the FDA there
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were a lot of things that transpired between all of this but one problem was that and howard lotsof had a death and it was a death of a young woman in the netherlands who was a healthy young woman who died from unknown causes that may may or may not been related to ibogaine and her mother showed up in my office in miami a german woman and unannounced and flew in from Germany and came to my office to meet me and said I
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want to know why my daughter died and I said I do too so with her permission we were able to get that autopsy information from the doctors who did an autopsy and we provided that information to the FDA because at that time we recognized that we should probably slow down we had to understand now we had two critical issues that we needed to sort out I wasn't worried about the cerebellar toxicity at all I
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knew that that was would not be an issue going forward but the toxicity the blood levels of I began we needed to understand more about that of course that's going to phase one is for you're gonna slowly walk up the dose and small increments you're gonna look you look at the adverse event profile you'll get the pharmacokinetics you'll you'll understand how to how to dose the drug before you start giving it to patients for detoxification how I had no
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information you know they were flying by the seat of their pants to say it gently so we figure that out we we solve that riddle we understand what happened it was an accidental overdose for that young woman represent that information to the FDA in the form of an amendment and something else happened I told her lots of I said you cannot give ibogaine in settings that are unsafe you have to be in a hospital mm-hmm it has to be
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given under full medical monitor give it under full medical monitor you'll be fine you'll never have it please don't do that anymore so I then went and got approval I got a medical doctor from Panama who had a hospital and could get a whole wing to be dedicated for this I said Howard you're gonna write and I you're gonna do it they're gonna approve Alfredo you're gonna I became by a licensed medical doctor and your patients will
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come to Miami they will get off the plane they will be evaluated by University of Miami medical doctors and psychologists they'll go to Panama they'll take ibogaine under medical monitor you'll get safety and blood levels from the patients will draw blood smile analyze them then they'll come back to Miami and we'll evaluate him and then they'll go home we'll submit that data to the update good idea we did that and so we
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collected some data from that we submitted that to the FDA and we learned more about the pharmacokinetics and the safety and something else happened a young woman who had come to Miami she had been treated with ibogaine chant two doses a small dose of emmett and the detox knows a year before she had done very well and then she relapsed a year out she wanted to go back to say could take the drug again because she felt the drug really helped her but again she had
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struggled with addiction for a very long time she's a heroin user my drug user very smart young woman very very an account very smart lovely young woman and wanted to kick the habit 100% she wanted out I don't want to be an I don't want to be addicted to heroin anymore I went out and she was convinced that ibogaine would give her that that she had done well the first time she she realized why she relapsed and she wanted to go again and this time it was gonna
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stick she come down to Miami full neurological uation of course labs clinical labs evaluation posture ography and she'd taken I became before so we knew she had no neurological deficit most town takes the drug comes back to Miami which gets to - she didn't feel good she said dr. magesh I don't feel good I think I don't know if I'm going through withdrawals or if I got the flu or what's going on so I called my colleague
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who was an internist and I said do me a favor and mid her for one day mister observe he said I don't think there's anything wrong with her she's not going through withdrawals for sure she may be she picked up a bunch she might have a little flu she might be a little dehydrated I'm I'm gonna give her fluids and we'll watch her so he did that brought her in checked her out gave her fluids she left she goes back up to New York she was in New York for about three and a half weeks and she called me up and she said doctor man I'm getting out of New York I don't want to be in this
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place anymore bad memories I've got someone who'll sponsor me in Fort Lauderdale I'm gonna move down to Fort Lauderdale and if possible can I volunteer and work for you and do some work for you and I said absolutely you come down come down to South Florida you want to work with us you know kind of be in the mix you'll get you know you'll work with your counselor you can be part of we have sort of an eye Begay and support group going in Miami I said you can be with the family in Miami absolutely come on
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day she eats sushi on a Thursday on Friday morning she doesn't feel good she has some nausea and vomiting she gets on a airplane she flies down to Miami she goes with her friend to his house continues with nausea and vomiting and the next day she gets up and she dies she was the Broward County Medical Examiner I get the phone call that she had passed away I immediately called the medical examiner's office I said this woman has taken an experimental drug I
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have a full chart on her we have all of her medical records and notes may I come down and be present at the autopsy and they knew me because remember I had been working with the medical examiners midday to Broward County so I had grant from NIDA and I was you know doing my other grants drawer so they knew me and they knew of me with the brain bank and everything else and I said also if I have your permission may I take the brain and may we at the University of Miami do the neurology on the brain because very important she's taken four
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doses of ibogaine if there's any cerebellar toxicity or toxicity in the brain we would like to know this so we can tell the FDA they said never come on down so as present at the autopsy was quite a day imagine quite a day I knew Nancy I had met with her she had done her MRI in Miami and I can remember sitting out there on the bench in front of the MRI Center and I asked we had a conversation about donating your brain I
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said you know you're pioneers you're like astronauts oh you're by boga nuts you're going up in the spaceship god forbid if anything ever happens to you you need to donate your brain mm-hmm to medical research and of course I told a lot of people to donate their brain because I'm the founder past I am the founder and past director of the university mine Brandon down the bank one of the largest collections of human brains that day everything I knew about brains was
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important to him as I brought her brain back to the University of Miami and we processed it Nancy's brain was clean there was no pathology Nancy died from causes unrelated to ibogaine we presented all of that to the FDA mm-hmm and we went back into the meeting with the FDA with the revised protocol and in 1995 the FDA gave us the full green light to go forward with an external data safety monitoring committee it was fantastic I
42:46
mean it was the best news of the day and I I was so proud of what we had done you know we was really um it was a great day I had in the room with me I invited my colleagues I had dr. bridges was sitting right next to me dr. Vaughn she was on the review panel so he was sitting at the table and when we finished that meeting dr. Sanchez Ramos was with me we were there in um people we finished the meeting I leaned over to dr. gray discus
43:16
and I said okay FDA just gave us the full green light will night have fun the study and it they had come down and visited us and we thought we might have a contract back that night it gave contracts and the medication development division and they told me to write a grant no contract so I came home and I do did what I do which is to write a grant and I submitted the grant and the
43:44
grant was not scored and that was a big surprise to me because we had so we had fantastic collaborators not only do we have our collaborators at UM that were terrific but we had UCSF we had the best pharmacokinetics Asst in the entire country number one we had Rachel Tyndale for the genotyping to work out all the
44:17
pharmacokinetics and the metabolism it was in the front-end at the University of Toronto looking at the cytochromes and characterizing cytochromes and I can remember that woman talking to me very brilliant she's one of the smartest women I've ever met in my life and she looked at the molecule and she goes Debra this is cyp2d6 she knew immediately what enzyme was involved she was right and we were going to prove it so we did that so I had all these people
44:49
collaborators let me have people from the Armed Services uniformed Armed Services Group that were going to help us with the with the neuropsychology we had counselors therapists oh my goodness we had we were dressed up for the party we had everybody on board but the thing that was so tragic here was you know when you got a grant your grant may not be perfect they never are in fact very rarely you get fun on first mission however you get scored and then you revise it right you get it you get your
45:21
feedback from the review panel in this case the fan the feedback was no darken our doorstep with this grant not for what's called nerfed not for further consideration and keep in mind that I've had funding from the NIH for over three decades I'm still collaborating on NIH grants today as I said here talking to you so it's not my first rodeo and I did have some experience with it and I served on review panels
45:52
so I understood you know I understood the process of peer review so this was a clear message that they didn't want to see this right you know I had the message loud and clear so now you know decided that they were going to do their own ibogaine IND and they put together a panel external advisors and whatnot and we participated in Miami on them I didn't really know the full extent of
46:23
this obviously because I wasn't in the in the you know in the bunker from nidus group to understand what was going on there all I knew is I we had approval to go forward mando [ __ ] but I'm a collaborator player and you know and and in my heart I wanted I wanted it to be tested I believed then as I do today that given the magnitude of the problem of addiction in our society that we in
46:55
the scientific community need to leave no stone unturned I saw this work they know it works they've seen it they have the animal data there was as you pointed out on more than a hundred years of ethnobotany ethno pharmacology around this molecule it was marketed under the trade name of lamb brain in France for many years in low doses we knew when you take a low dose of ibogaine that really you're being exposed to noir ibogaine
47:28
yes there's a huge first pass metabolism so all those people walking around with low-dose ibogaine in their blood had done the experiment with noir ID right if there had been adverse events it would have been out off the market yes all right so now we have no money and how Soph had the IP we have no IP howard lotsof hal intent the IP I couldn't do
47:59
this in the public sector with NIH funding mm-hmm there was no real foundation support except for maps the multidisciplinary Association of psychedelic studies when Rick Doblin called me the first time I hung up on he'll tell you that I I was like what Rick Doblin Maps no no don't call me I'm not no where were legitimate legitimate scientists Rick Doblin has
48:31
and he's more legitimate he has MDMA methylenedioxypyrovalerone but at the time you know I was I was you know you're right the DEA we had a DEA schedule one license we took this all very very seriously and ibogaine has no abuse liability unlike the others in the
49:03
schedule one category using ibogaine right so we tried to do everything by the book and but we have no money so it was really I I didn't know what to do and lotsof couldn't fund it he could never fund it yet he controlled the IP so where'd he go so I thought
49:35
about it and when we had the night I had the external review meeting this is 1995 now I came out of that meeting the group was not going to approve the study it was split pretty much between academia and Industry advisers and some people had said nor ibogaine would be the better molecule then I became I was in the audience I was presenting I heard the discussion people we went out of that
50:08
meaning it was clear that probably this was not going to go forward in the u.s. at least from NIDA would decide not to go forward which is what happened so night it didn't pursue their own their own clinical studies I was saying there with FDA a prick hold full greenlight no money and where do you go what do you do and there were two young men there from Goldman Sachs and I didn't have any plans for dinner because I wasn't
50:39
invited to the after party with NIDA so the goldman sachs boys came up to me and said dr. mash will you join us for dinner and I'm like yeah I'm nowhere to go let's go so I go to dinner and we start talking about the possibility of funding this thing right and my brain goes to plan B then I'd never done anything like this I couldn't walk away from this sure there were too many people suffering and I I just believed
51:09
that this maybe could be an answer for some so we started two companies one that would be a shell company to hold the intellectual property of a new idea around the nor I begin around the metabolite and I went back to my friends since in st. Kitts offshore and I went to dr. Frank Urban and I said dr. urban will you help me I had you wouldn't believe it IRA because we had so much publicity
51:40
around the ibogaine and of course media around the FDA and everything else I had a notebook of letters people who wrote to me begging for help hundreds hundreds of letters after mash if you have a clinical trial can I be a volunteer mm-hmm so we went to government of st. Kitts and this we were lucky because we had dr. Irvin a
52:10
biologic you know a by a biological scientist my mentor at Harvard a legend a visionary a cynic you know the perfect person to be the clinical director of an arm D program in the Caribbean Mandy had a great reputation he had the monkey you know he had the monkey facility there right the primate Center and he was very well respected by the government so he
52:42
got me a wonderful local doctor who had studied in the UK Kathleen Alden Ferdinand her husband who was our attorney and we had a dinner party with the prime minister who had himself a doctor dr. Denzel Douglas the head of the Ministry of Health and st. Kitts tourism many of the government officials I hosted a closed-door dinner party always keep your Visa card with you I
53:15
had to pick up that bet that dinner party and they didn't take American Express and I fed that bodyguards to so everybody we all ate and I sat next to Prime Minister and at the end of the dinner I leaned over to him and I said dr. Douglas what do you think can we go forward and he looked at me and he smiled and he said Deborah it will be done so government proved us excellent and we allowed to bring a Schedule one drug into the government pharmacy in st.
53:46
Kitts and let me just interrupt here for a minute because I think this is putting perspective from agree we are in 2019 and it's a very different let's say global pharmaceutical research environment now we have all sorts of conditional approval pathways in Japan very you know stem cell therapies and in China there's you know there's specific medical tourism zones a lot of this
54:18
stuff okay 2019 but here you are again you know I'm just trying to put this in perspective with how far ahead of the curve you were on on these things it's 1995 all this stuff is unheard of and yet you are you and essence are creating the first sort of offshore pharmaceutical research / medical tourism model which basically 25 billion years later now many drug companies are adopting the way they do things like I
54:51
think I just want to throw that out there because I it's amazing in my opinion part of the story as well just the show that you know aside from all the science you do you know your your about your politics also and you know that there's many parts of this puzzle to get things done and I just think it's really fascinating sorry for interrupting but now killing visions is created you're in st. Kitts tell us about that oh hey kids
55:20
in some ways my pride and humility of that experience most fundamental of my life the first treatments that we did in st. Kitts I can name off all six people who were there I held my breath we really had the most remarkable group of people we learned so much and
55:53
the first group of people we had there were for heroin dependent patients cocaine dependent a strong tears there were two women there were four men we didn't charge the women any money to come down there mm-hmm they were scholarships like almost 100% we had a sliding fee for service scale down there we had counselors and researchers and doctors and more doctors and
56:23
psychiatrists and and internists and you know because we knew nothing I mean this was really well we knew some things but you know now you're really going to do it now you're really going to treat patients and of course patient safety I mean I learned more cardiology than I ever wanted to learn in my life as I watched cardiac monitors it was remarkable but what I think one of the best things was dr. Irvin our clinical director who came in to me at the end of
56:56
the first round of patients and looked at me with his glasses down on his nose and he said well Debra it blocks opioid withdrawals and it did and it did and we knew that and I'd seen it before but now we showed it again and so that that remarkable experience and of course that's where the the safety where we really were able to collect open label safety and efficacy information and
57:26
provide that back to the FDA and publish on it share it with our colleagues and collaborators but you know that and we had spoken and I had the opportunity I think I spoke I met you and during that period and thinking about sourcing in the drug and and ways to get the natural product I'm again and an abundant product to go into humans how we would do that and there was
57:56
learning curve was amazing we we helped a lot of people I still get I get flowers on Mother's Day and cards and letters from people who say dr. mash thank you you gave me back my life you can't that's what it's all about and you can you can't even begin to know how that inspires me today you know I can't let this go I can't let it go especially when you have we have what we have going
58:27
on today I know what this could be for people we have to do it safely we have to do it according to what the regulatory authorities want us to do we need to get in the clinic we need to test this it needs to be done right and what we learned from st. Kitts to just kind of wrap it all up is that ibogaine is a very powerful and gentle detox not only does a block sign symptoms of withdrawal but it gets converted to the
58:58
active metabolite nor ibogaine which has a longer half-life in the blood that seems to bring about a neurochemical reset in the brain it acts on strategic targets it's a multi target approach much like what we we see the GABAergic reset with ala pregnenolone which has shown tremendous efficacy for treating a postpartum depression in women ibogaine is a similar kind of neuro chemical
59:29
reset and the nor ibogaine which stays long longer-term has much longer half-life than than ibogaine also acts on the opioid system it's a biased Kappa agonist what does that mean it's helping to to to change over intolerance in the cells themselves also elevates serotonin also acts on the part of the brain that puts the brakes on drug reward so again this fits in with modern neuroscience in
01:00:01
neuropharmacology and what we've learned from the decades of seminal research study that has come out of the National Institute on Drug Abuse so a neuro pharmacologist sitting here in the chair I love these drugs I love learning about these drugs and clinically you know after many years of st. kitts it was time to wrap it get back and get get back on shore and that's what leads us to dem wrecks and and the founding of that corporation now
01:00:33
going first to develop Noor IVA gay okay take us through all of that because you know as aside from your scientist hat aside from your clinician hat now you I know you as a extremely accomplished are charging businesswoman as well so now take us into your transition into the world of biotech 101 US side and your experience is successes hurdles and and where you're going with it because I
01:01:05
know aside because you just mentioned aside from this major problem we have nowadays billions and billions of dollars of opiate addiction and other substance abuse you also as you mentioned you're potentially sitting one a pharmacological reset opportunity for many central nervous system disorders whether that's depression or other comorbidities take us through all that because that you know you're really leading the path again into the future on this front where are you going with it tells the future so I had when I
01:01:37
decided that enough of saying kits and we needed to bring this home to Americans mm-hmm I started to put together as you said biotech startup 101 and really I was unskilled completely unskilled and all of that however I did have a meeting with Novartis and I did have discussion with Sanofi and that at that time they were working on the
01:02:10
cannabinoid receptor antagonist and remember they were developing it for obesity and they had in the back of their mind they were going to go after addiction with this molecule but unfortunately it had the little problem of a black sporting and suicidality when you antagonize the cannabinoid receptors so at the time there was a lot of disinterest in CNS pharmacology starting to emerge and blockbuster drugs were
01:02:43
being developed along vaccines viagra diabetes you know the blockbuster drugs were not in the brain right so Novartis who I met with and I met with her head of licensing I went over to Zurich right he met me came over from Basel came on the train sat with me for half a day talked to me dr. Xavier and lata state and said I'm gonna bring this back in but I want you to go in front of the FDA
01:03:15
I want you to have a pre-ind meeting so I did that I set up a pre-ind meeting with the FDA for noir ibogaine and again the FDA hears this academic investigator coming in with a new chemical entity now FDA was great and I went up in front of that committee and got their guidance what I would need to do with nor ibogaine which was basically Debra we're going to they were very clear we're gonna treat you no different than any
01:03:46
other pharmaceutical company so get the message right all right so we got that message and now I need to I need to launch and I was rescued by a group called springboard springboard launches women entrepreneurs and a woman from Africa had sent me an email who knew me and she was running a drug manufacturing unit out of Ghana and she said Debra you need to contact this group springboard so I did
01:04:17
I sent my information into springboard and springboard the way they act it's very fast they said give me you know they you send up a synopsis they look at it they ask for your business plan you got to get it there in a couple days business plan and then they said all right what a meet with you and you so I got on a plane I flew up and I was selected our company was selected as for the boot camp and they launched me and
01:04:48
then I was you know developing my elevator pitch and really learning how to do this and talk to investors and that was a great experience actually that made me a better grant writer if you can sell your ideas in one page and raise money you can write a better NIH grant and so that really helped me scientifically back in my academic game but this was remarkable and I loved it and it was at that time that I met Steve garland and I have my first investor the
01:05:19
Ross family wrote the first million dollar check and demmer X was formed and today Denver X has been reorganized and we've brought back both molecules I began in write again and we are a clinical stage drug development company I've got new management a new team around me a wonderful vice-president for clinical trials and regulatory affairs we've identified our clinical trial site
01:05:49
and the next step is to work with the health authorities in the US and elsewhere to commence three pivotal studies for ibogaine and your ibogaine running simultaneously raising money to do this and then we will move into a Phase two clinical trial and I believe that we're going to succeed I believe that we will demonstrate that the drugs can be given safely that we will understand the therapeutic blood levels
01:06:19
and then we will be able to make this available to patients and you know what we learned in st. Kitts what my counselors and therapists told me is that ibogaine is an adjuvant to psychotherapy ibogaine is very powerful because it helps patients to develop insights enter their destructive behaviors so if you think about addiction addiction is very difficult to treat we don't have a lot of medicines to treat addiction it's not a single target drug you're going to need a combination
01:06:50
and that's why I've attained or I being is so unique space because it's got the right mix of molecular targets it's hitting multiple sites in the brain you know you look at our veterans who are taking a cocktail of four or five six seven drugs treat their PTSD their addiction and their blast injury here we are but no ibogaine is a bit of a cognition enhancer we know psych data we
01:07:24
know that it diminishes cravings and desire to use we know it blocks signs of withdrawal just go on the internet and you can read all the testimonials there so we can do this we just need the help of our partners at the FDA and elsewhere in other countries so that we can test this we can demonstrate safety and we can move into pivotal efficacy studies and and provide that data for external peer review and and bring the drug products and make them available ibogaine has to be administered under
01:07:56
full medical monitor your ibogaine can be developed we believe for office based practice and we also believe that we can develop arrived again for prison use extremely exciting extremely exciting and the you know one other thing I have always admired in the story is that everything you've already spoken about is sort of this you know looking beyond here you used to describe it to me now this is not a sniper rifle this is like a shotgun effect and there's so much pharmacology and so much going on at
01:08:30
different targets but really this move beyond this single magic bullet philosophy that you know Pharma has used the last 100 years to really the development of these products that have what operators these combinatorial effects and really with the understanding that you know this is a world of systems and systems biology and the old approach might not work as some of these newer approaches and that you're championing this is just another I take my hat off to you if I had a had
01:09:00
one but you really a pie on so many different fronts and I definitely believe in everyone watching believe that you you will clearly get there and and that you have persevered so much and brought the story this far it is obviously going to get there and definitely behind you 100% I guess you know getting back to just never match now you've spoken you know a lot about influencers throughout your career and your education the people
01:09:33
that have guided you and have kept you on this path we usually ask a question on this show sort of a science fiction related question but it's not about the people that you would have wanted to meet and if I had this ability to put dr. Debra mash and my time machine over here and send you anywhere you wanted to go who are some of those folks that you know from past the eras that have inspired you that you know you would might have want to sit down have a cup of coffee with have a dinner with and it just talked to you for a little while come to my dinner party I can tell you
01:10:04
straight away okay Albert Einstein mm-hmm definitely would want him at the party I would love to have host and dinner party for her hair professor I understand I would love to have Marie Curie there mm-hmm I would just love to have there and I would enjoy having master Jesus there okay one of the greatest world historical individuals on the planet no doubt about it and I'd be
01:10:38
curious to hear what he thought of the science and I guess I mean I would from because you got to always have a good politician I think Abraham Lincoln would be great to have it detected all right so it's a sort of a diversified class but I want to cover all the bases notice I have to note two Nobel laureates man in a woman politician and a world historical leader that changed the minds
01:11:08
of hundreds of millions of people's absolutely absolutely I'd like to join it at table with you well it's really in once again we go back several years it's really been a pleasure to see you and listen to you again and hear about your passion behind this you know really thanking you for everything you do and the fact that you have stayed with this and hopefully will help we will put a lot of links up to
01:11:38
your work and and so forth we'll try to help you get the message out as wide as possible but clearly you are you're on the right path is I've always thought you are and wishing you the best and once again for everybody listening it's been dr. Debra mash professor of neurology molecular pharmacology it was in Miami and also the founder and chief executive officer or Emmerich's really doing amazing things if there's anyone that's going to break through with this massive drug addiction this opiate
01:12:09
problem this other illicit and illicit drug problem we have in the world today and as we've discussed you know this is a much wider a sort of psychological problem with the world that we're sitting in today it's it's going to be a dr. debra mash so you know once again just thank you thank you so much for staying this path and anything you want any other messages you want to wrap up with I'm giving you the floor once again thank you for joining us no I'm just very grateful thank you I refer your interest in this story and topic it's
01:12:39
been a long journey for me but I want to finish what I've started and God willing we'll get there no doubt no doubt Deborah thank you so much for thank you

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