A 30 year journey towards Ibogaine approval: Deborah Mash, CEO of DemeRx​

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Deborah Mash: [00:00:00] The ibogaine journey seems to help patients to gain insight into what's been what's fueled the addiction. So it's almost as if they're watching a video of their life and they may relive for early childhood experiences. They may have pleasant memories. They may see scenes from things that occurred while they were using drugs or alcohol that were unpleasant memories, but they're not disturbed by them because they're watching this

[00:00:25] video. This life review. If you will, from the standpoint of a passive observer. This information that patients report seem to help them to set the resolve to make change, to bring about behavioral change, to change it up, you know, what's going to be different this time?

[00:00:47] Greg Kubin: [00:00:47] Welcome to Business Trip a podcast about psychedelic entrepreneurship. Psychedelic medicine is transforming mental, physical, and spiritual health and entrepreneurship will be key to expanding access. Business Trip explores the business models and origin stories of the most interesting companies in psychedelics.

[00:01:05] I'm your host, Greg Kubin. This week's guest is Deborah Mash. Founder and CEO of DemeRx a company developing ibogaine therapies to treat substance use disorders. Ibogaine is the naturally occurring psychoactive chemical in Iboga, a West African shrub that has traditionally been used in healing ceremonies and initiations in West Africa.

[00:01:29] Ibogaine is an incredibly powerful psychedelic. And its potential to break cycles of addiction and depression has been documented in studies as well as anecdotally in clinics throughout the world. But this past year, seeing the highest number of drug overdoses ever in America, the race is on to get ibogaine, FDA approved. Debra who founded DemeRx  has studied the compound since 1993.

[00:01:53] So you could say this has become her life's work. In today's episode, we talk about the science of ibogaine, its safety profile, navigating the mazes of the U S drug regulatory system, as well as intellectual property. And Deborah's three decade journey through Amsterdam, Miami, and the Caribbean to get ibogaine approved.

[00:02:16] And as always, don't forget to listen to the entire episode, past the credits for your sonic microdose of the day. And now to the episode.

[00:02:33] So Deborah really excited to have you on the podcast today and talk to you about DemeRx  and ibogaine and your, your story. My first question is, can you talk to us about ibogaine in terms of its history and the science behind it? 

[00:02:50]Deborah Mash: [00:02:50] Ibogaine as an indole alkaloid, isolated from the roots of Tabernanthe,  Iboga, an African shrub that grows in the regions of Gabon and Cameroon.

[00:02:59] There is over a hundred years of ethnobotany and ethno pharmacology behind this molecule. And of course in Africa, it is used as a sacred medicine by people who practice the, Bwiti  religion. Was actually marketed in France after it was developed and studied in Europe as an natural product chemistry formulation and was marketed up until the middle 1970s under the trade name.

[00:03:29] Lambarene. Lambarene was tablets of ibogaine eight milligram tablets that contained ibogaine and some other indole alkaloids from the root, but primarily  ibogaine , and this continued for a number of years, and then it fell out of clinical use. In the seventies at the time when psychedelics sort of found their way into general use in society ibogaine  too was discovered and a young heroin addict by the name of Howard Lotsof

[00:03:58] took ibogaine to experience the molecule and discovered that he was completely clean from his heroin addiction. In fact, he kicked his heroin addiction without any of the harmful pain of withdrawals. And not only did he have complete blockade of withdrawal symptoms, but he also didn't,  have a craving.

[00:04:20] So the desire to go back out and get high. Now, this was an astonishing observation, as you can imagine. So he decided to replicate the experience and this time gave the drug to six of his friends. Some of them were heroin addicts. Some of them also were freebasing cocaine. And he discovered that ibogaine had the same effect on those friends who were opiate dependent, but they too were able to kick.

[00:04:44] And the other observation was that even in the cocaine abusers, That they had reported to him that they had a diminished need to go out and get high on cocaine again. So that was really the first observation of ibogaine in clinical use. And that Seminole discovery has fueled this movement. Until today, Howard Lotsof died in 2010, but I knew him very, very well.

[00:05:12] I had met Howard and he invited me to come to Amsterdam back in 1992 to see with my own eyes. And it was interesting because at that time he was running. Participating in what was called an underground railroad of addicts, helping addicts. So these were two groups, the international coalition of addict self-help, and the Dutch addict self-help unit.

[00:05:36] So people in the United States and people in the Netherlands who were, were coordinating self-help for people who wanted to get clean from drugs and. I had been working. I had been studying the cocaine epidemic. I was on the faculty at the time at the university of Miami school of medicine. And Miami, Florida was at the front end loading of the cocaine epidemic.

[00:06:02] So I was actually studying the effects of cocaine on the brain and behavior. Miami-Dade Florida. We were really. We were really hurt by cocaine because of the trans shipment of cocaine through the Caribbean, into the shores of Miami. You can imagine that we have a lot of people that got caught up in that epidemic very early on.

[00:06:21] So I was looking for ways to break the cycle of addiction. And there was a movement at the national Institute on drug abuse at the time to try to find molecules and, you know, pharmaceutical companies, big pharma has never invested and medication development for the treatment of addiction. Why?, uh, there's a lot of, a lot of ideas about this, but, you know, treating addiction is hard.

[00:06:47] There's a stigma associated with addiction and of course, big pharma needs a big blockbuster drug because the cost of medication development for any central nervous system disorder of which addiction is an acquired disease of the brain costs money. And we're talking tens of hundred million, more than a hundred million dollars to bring a drug all the way through phase one, two, and three, and getting an NDA approved for sale of the drug.

[00:07:17] So big pharma never was really that interested. And we in my laboratory at the University of Miami began to hear about, I began and I heard about it three times. And the third time I heard about it, I had come back from a scientific meeting, the college of the problems of drug dependence, and there was a phone message for me because Howard Lotsof called me actually wanting to use some of my research to support one of his polydrug dependency patents. Lotsof had patented ibogaine for opioids,

[00:07:50] psychostimulants, nicotine, alcohol, and he was going for his fifth, patent polydrug. And I had been working on comp people who were code using cocaine and alcohol. I was getting a lot of press at the time for my research and Lotsof called me and said, I want to learn about what you're doing. And I asked him, I said, you're Howard Lotsof you work with ibogaine.

[00:08:10] I want to learn about ibogaine. And that started me on my journey. 

[00:08:15] Greg Kubin: [00:08:15] Quite an origin story. Can you talk a bit about the neuroscience and what ibogaine or I guess nor ibogaine, which is the metabolite of ibogaine is doing in the brain? 

[00:08:25] Deborah Mash: [00:08:25] When we began studying ibogaine, there was a suggestion that ibogaine was working on certain parts of the brain that were involved in the addiction loop.

[00:08:37] And the neurobiology of addiction was really just starting to come of age in the field of neuroscience and I am a neuroscientist. So I'm very interested in trying to understand what the molecular targets are for ibogaine and what the addiction circuitry is in the brain. And what chemicals are cross talking with each other. Today,

[00:08:57] I'm not really sure we understand all of the biology behind the molecule and as with other psychedelic medicines that are primarily serotonergics. We understand that there are certain respective targets, but we also know that there's probably downstream effects that may involve actual changes at the cytoplasmic level inside of the cell, as well as

[00:09:24] bringing about changes in the brain that are very important for neuroplasticity and I'm. And I'm absolutely certain thatibogaine does this. 

[00:09:34] Greg Kubin: [00:09:34] One of the most promising therapeutic aspects of psychedelics is how they promote neuroplasticity. Neuroplasticity is the ability of neural networks in the brain to form new connections in response to learning or an important experience or even trauma.

[00:09:48] This is important because neuropsychiatric diseases, including substance use disorders, depression and PTSD are often characterized by an atrophy of neurons in the prefrontal cortex, which is a part of the brain involved in decision-making and executive functioning, and may result in less control of drug seeking behavior. Psychedelic compounds like ibogaine

[00:10:08] may promote neuroplasticity to regain control of drug seeking behavior. 

[00:10:16] Deborah Mash: [00:10:16] But we do know that ibogaine and noribogaine the active metabolite of ibogaine, which my laboratory discovered for the first time and characterized has different targets. And it's really very interesting. ibogaine is an indole alkaloid.

[00:10:31] And you think about mother nature's addicting alkaloids, cocaine, opium, and nicotine, for example. There are targets in the brain receptor targets in the brain and neurotransmitter systems that are implicated. One is dopamine. The other is serotonin. Dopamine is the feel good neurotransmitter. I always like to think of it as drug, sex, rock and roll.

[00:10:52] It said, it's what makes you feel good when you get up in the morning, you get up in the morning, you jump out of bed, that's your dopamine. You're ready to get into the game. Some people don't have that feeling in the morning when they get out of bed. Some people are low on dopamine. So this may be one of the reasons

[00:11:08] why some people become dependent on drugs and alcohol and others do not. In other words, you take that first line of cocaine, that first cigarette, that first vodka martini, that first injection of heroin, and you feel normal because it's elevating your dopamine in the brain. That's why people smoke cigarettes, they get a stimulant effect.

[00:11:29] That's dopamine. So drug liking is juggling, but over time, when you start to use more and more of the substance, you develop what would be called a tolerance. That's why when you stop taking heroin or prescription opiates, you go through horrible withdrawals. You build up a tolerance. You need to take more and more of the drug

[00:11:48] to prevent you from going through withdrawal. With cocaine, the withdrawal syndrome is not the same as opioid dependency, but there is a withdrawal syndrome, nonetheless. And of course, with alcoholism, when severe alcoholics go through withdrawal, they can suffer terrible withdrawal and seizures, in fact. So this shows us that the brain has become neuro adaptive.

[00:12:10] Now ibogaine blocks opioid withdrawals because it's not only acting on serotonin, but it's also acting on what we call the NMDA receptors. And this is where ketamine acts in the brain, the same place. And it elevates the neurotransmitter glutamate. Glutamate is an excitatory neurotransmitter that regulates many different neurotransmitter systems in the brain.

[00:12:33] Ibogaine has the oneiric effects we think because of this interaction between serotonin and the NMDA blockade, that elevation in the neurotransmitter glutamate. When ibogaine, goes through the gut wall in the liver, it gets metabolized to an active metabolite, which is noribogaine. Noribogaine is very interesting molecule.

[00:12:56] And one that has really intrigued me because it acts on three distinct targets. It doesn't act on glutamate, which is why noribogaine won't have the oneiric effects. Won't have the visionary experience of the ibogaine. But what it does act on is very potent as a serotonin re-uptake inhibitor. So it's like an antidepressant.

[00:13:13] It also acts on the opioid system and it acts through Kappa opioid receptors as a partial agonist. And when it does, is it helps to reset opioid tolerance we believe. And then last but not least, there is a novel center in the brain called the habenula uses a neurotransmitter called Astro Coleen and through a nicotinic cholinergic receptors subtype, it puts the brakes on reinforcement on dopamine.

[00:13:46] So it helps to reset the brain's ability to regulate itself. And we believe that ibogaine acting on these different clusters of receptors in certain parts of the brain is why it is so effective and why it brings about this very abrupt change, where it can block opioid withdrawals and have these beneficial after effects.

[00:14:07] Greg Kubin: [00:14:07] And so that period where the brain has reset that's for a finite period of time, right? 

[00:14:14] Deborah Mash: [00:14:14] The duration of the reset, whether it's a week, a month, three months, a year, is not completely well understood. And this brings about the issue of whether ibogaine is a cure. ibogaine is not a cure. Ibogaine as an addiction interrupter, a very powerful addiction interrupter, but as you can imagine that some of the  patients that were treated with us in our St. Kitts study were people who had been abusing drugs, hard drugs for a decade.

[00:14:45] Can you imagine you take one dose of ibogaine, and you completely reset. All of the damage, the wreckage and the changes in the neurochemistry with one dose. As a scientist, that's hard to imagine, but we did see for some patients, one dose was actually able to get people out of their black hole of addiction and onto a road

[00:15:09] to recovery. Now they had to work a program. For other patients, ones that maybe have been co abused and cocaine or heroin, for example. And we have many of those as well. They might need two doses of ibogaine and some patients selected to come back to do a relapse prevention dose. I think that it's likely that individuals much like you repeat ketamine treatments,

[00:15:34] a certain series of ketamine treatments that as we learn more about the drug, that we'll be able to understand whether, depending on your level of tolerance, depending on the years of abuse and depending on your underlying psychiatric co-morbidity, you know, many people who discovered , drugs and alcohol and use them are self-medicating.

[00:15:56] They're self-medicating depression. They're self-medicating trauma

[00:16:02] Greg Kubin: [00:16:02] Renowned addiction expert Gabor Maté says the question is not why the addiction, but why the pain and the source of pain is always an invariably to be found in a person's lived experience. 

[00:16:16] Deborah Mash: [00:16:16] I think there's a lot for us to learn as we embark on our clinical trials and we start to really phenotype the patients and understand the patients that are seeking to use ibogaine for detoxification.

[00:16:29] But what we can say is that for many patients, whether it's one dose or two doses, whether they have to take it years later, we'll have a good understanding about what kind of effects ibogaine will have that are lasting. But like other psychedelic molecules, you can imagine our brain has a lot of neuroplasticity.

[00:16:50] There are changes at the synaptic level that occur. This is very important as an anti-aging tool, but you damage your brain with drugs and alcohol. How much healing can you do using a medicine like ibogaine? 

[00:17:03] Greg Kubin: [00:17:03] Ibogaine can be an anti-aging tool, you're saying? 

[00:17:07] Deborah Mash: [00:17:07] In the sense that it's turning on some of the synaptic plasticity.

[00:17:11]Greg Kubin: [00:17:11] I see.

[00:17:12] As we age,

[00:17:13] Deborah Mash: [00:17:13] you know, you hey, if you're going to abuse drugs for 10, 20 years, you're accelerating aging in your brain, make no mistake about it. Hard drugs, make bad consequences for your brain. And there are changes at the synaptic level and post synaptic level on the cellular level and the intracellular level and at the level of the DNA.

[00:17:35] So we've got to resettle all of that. As we age those protective. The turnover cellular turnover, just like with, you know, turnover in your skin, your brain ages too. So if we think that turning on these growth factors are part of the healing process as for other psychedelics. And that's why psychedelic medicines truly can be transformative to the field of neuroscience.

[00:17:58] Greg Kubin: [00:17:58] Can you describe the experience that some of your patients have shared? 

[00:18:04] Deborah Mash: [00:18:04] The oneiric experience of ibogaine for some is very profound. Patients report that when they first start to feel the drugs effect, that there is a kind of an activation of the brain, some report that they hear a high pitch sound and then the screens drop and they start to get the slide show.

[00:18:25] So it's almost as if they're watching a video of their life, and they may relive, you know, early childhood experiences. They may have pleasant memories. They may see scenes from things that occurred while they were using drugs or alcohol that were unpleasant memories, but they're not disturbed by them because they're watching this video, this life review, if you will,

[00:18:48] from the standpoint of a passive observer. This information that patients report seem to help them to set the resolve, to make change, to bring about behavioral change, to change it up. You know, what's going to be different this time. I've detoxed before. Again, and again and again, and I always go back to the drugs.

[00:19:11] I always relapsed. What's going to be different that time. Well, that the ibogaine journey seems to help patients to gain insight into what's been, you know, what's fueled the addiction. Going back kind of turning back the clock and looking back, Hey, how did I get here? You know, and what can I do now? And how can I be proactive in my life?

[00:19:33] What do I need to do so that this is not me anymore? So it, it actually even helps. We think about this. You know, we talk about pre-contemplation, contemplate of ready for change. It takes in some patients who are intractable, you know, drug users, And made them ready for change and others. It was like rewriting their own mythology. Today

[00:19:56] I'm not addicted. Today, I'm not addicted. 

[00:20:00] Greg Kubin: [00:20:00] Okay. So my last question on the science of it is the cardio toxicity is something that seems to come up when, you know, on this topic, in that for certain populations, there may be some risks to the heart. So can you talk through what percentage of the population is affected and why that's the case 

[00:20:21] Deborah Mash: [00:20:21] In our study in St.

[00:20:22] Kitts, we had no serious adverse events with our patients. Patients were screened for their general medical health. We also screen them for any cardiovascular disease that would make them disqualified from taking ibogaine. We know that hard drugs and alcohol can damage the heart. Not only does the damage, the brain, it damages the heart and damages the liver.

[00:20:48] So this patient population is at risk for drugs, which can have cardiac effects. Ibogaine, we believe has a more narrow therapeutic to toxic window. You know, if you take too much of a drug, you can have an adverse event. You need to be within a therapeutic window where, you know, the drug in the blood is safe and not going to have adverse events.

[00:21:16] People who have gotten trouble with ibogaine. And there have been,ibogaine deaths reported about 33 in the literature to date that we've reviewed. And some other case reports of what is called QT prolongation. QT prolongation is a signal in the heart that if it gets too long, if too prolonged by blocking certain channels in the heart drug blockade of certain channels called Herc channels in the heart can lead to a potential serious cardiac adverse event.

[00:21:50] DemeRx is working in our clinical trial to demonstrate those safety parameters. 

[00:21:58] Greg Kubin: [00:21:58] So along that sort of thread, you're pursuing FDA approval. You, as I understand it, I think you started DemeRx  in 2010. So you've been studying this and researching it and doing preclinical research for awhile. I believe you're approaching phase two clinical trials.

[00:22:15] So yeah. Please share with us the timeline in terms of where you've been, where you're at, where you're going and any learnings you've had along the way. 

[00:22:24] Deborah Mash: [00:22:24] I first went to the FDA with, I began in 1993 and gained their approval to commence phase one studies in the US. In 1995, I went back to the FDA with an amended protocol and they, again, granted us the green light to go forward with an external data safety monitoring committee.

[00:22:44] Unfortunately, I was unable to fund those studies, which is why we left and went XUS to St. Kitts where I started an R and D program in the Caribbean with a permission from the government of St. Kitts and patients who would sign informed consent would come into the Caribbean study with us. And we did that for a number of years.

[00:23:09] During that time, we also conducted bench research and learned more about,ibogaine and noribogaine and many several publications that came from that. Those studies submitted a lot of grant applications to the national Institute on drug abuse. We have novel composition of matter, and every time I submitted a grant, those grants were slammed down.

[00:23:32] They were deemed not competitive. Nonetheless, I was convinced it in what we had, because seeing is believing. I saw, ibogaine work with my own lives in 1992. I saw the powerful effects of this drug. So at that point I had to make a decision because I didn't want to run. I wanted to get back in the United States, get back in front of the FDA.

[00:23:52] And we thought based on our discussions with naida and our investors that perhaps noribogaine was the better molecule that the next generation molecule would be the metabolite. And we started DemeRx, to advance the metabolite and the metabolite has already gone through three phase one protocols and is phase two ready basically at this time.

[00:24:17] So we're going to be looking at some novel indications for use of noribogaine different from what we're doing with ibogaine. But when I came back into DemeRx and I had left my company for awhile, and then I came back into my company that I founded in 2017. When I came back into the company, I made a decision and I said, we're going to bring back ibogaine.

[00:24:37] We're going to have two horses in the race and two jockeys, because I want to develop ibogaine and I want to develop noribogaine, and we had target product profiles for each of them and they were different. 

[00:24:49] Greg Kubin: [00:24:49] Can you talk through the difference briefly? 

[00:24:51] Deborah Mash: [00:24:51] Ibogaine, we believe that ibogaine because it has oneiric effects and noribogaine does not is going to be the best candidate for

[00:25:02] opioid withdrawal management. That precipitating a change from being dependent on opioids, bringing about this catalyst for change, if you will. Helping patients to break their intractable cycle of addiction. That ibogaine is going to be the preferred molecule. Because not only is it very effective and don't forget.

[00:25:20] And when you take ibogaine, ibogaine is not only acting in the brain, but it's also a pro-drug is getting converted to noribogaine. So you've got ibogaine, which is washed out of the blood in 24 hours, but then you have the slow release of noribogaine in the slow wash out of nor ibogaine when we began. And I talked to my counselors and staff in St.

[00:25:43] Kitts. I said, well, we're not going to work with ibogaine anymore. And they were, no, you have to continue Dr. Mash to, to pursue ibogaine because it is a strong, you know, because it's an adjutant to psychotherapy because it helps patients to bring about behavioral change. So it's not just the neurochemistry.

[00:26:00] We, you need the generic effects of the drug. In 2017 I said, we need the oneiric effects of the drug, but wouldn't it be wonderful, if after you precipitate this change, you bring about this radical reset in the brain and you get patients treatment ready that you could have an adjunct therapy, a low dose formulation of noribogaine, that can be taken for days, weeks or months after you've completed the ibogaine detoxification.

[00:26:29] So we're looking at developing noribogaine in low dose formulations. And there's some other new intellectual property around that, which I will not discuss on this call yet.We have some interesting ideas about how to do this. And noribogaine, also could be developed in low dose formulations to help patients who want to stay abstinent.

[00:26:47] You know, we've demonstrated in animal models that nor I became will, will stop nicotine self-administration it stops alcohol drinking behavior in rodent models. Wouldn't this be wonderful? If we could help to develop a non opioid formulation that has no abuse liability, none of the risk of abuse that will also help to act on these same receptor targets that I talked about.

[00:27:13] Greg Kubin: [00:27:13] And so let's fast forward a few years from now. Let's say fingers crossed these get approved. What is the business model look like for 

[00:27:24] DemeRx? 

[00:27:25] Deborah Mash: [00:27:25] I suppose 

[00:27:26] that by that time, the business model for DemeRx will be that we will have a pharma partner that a pharmaceutical partner will emerge. Once we're able to demonstrate the stunning efficacy, if we can replicate the stunning efficacy that people report on the internet, you know, it's estimated 10,000 people or more have taken ibogaine in various settings around the world.

[00:27:47] Some of them, not the best medically sanctioned settings I might add, but they've taken it. And they report that it provides benefit. So the, the endorsement, the patient endorsement is there. Seeing is believing. The model for, ibogaine, ibogaine, should always be given in a medically safe setting.

[00:28:07] Because of the, you know, the one-off chance that you get someone who has underlying cardiac disease that wasn't disclosed and you need to be able to manage patients undergoing detoxification. And it's bringing about abrupt detoxification. Think about that. People who want to transition off of methadone, it takes a very long time to taper down here.

[00:28:31] Here we are, you take one dose of, ibogaine, you know, we had people that were swimming in the Caribbean three days later, completely detoxed, no cravings and felt wonderful. So this is kind of an amazing thing. Brexanolone is a molecule that was developed to came from the NIMH, national Institute of mental health, and made its way for the treatment of postpartum depression.

[00:28:52] Similarly, I believe that ibogaine will be used similarly to Brexanolone. In other words, you have to take it under medical monitoring. You may want to take it in a hospital or a particular setting where you have all of them. The medical safety, bells, and whistles so that it can be managed, whether it's in a, a detoxification clinic or a hospital under full medical monitor.

[00:29:14] That's howibogain, will be used. So it won't be like a siliciden treatment for noribogaine, noribogaine will be prescribed in a pill or a patch or a Depot. So your doctor will write a prescription. 

[00:29:25] Greg Kubin: [00:29:25] And it 

[00:29:25] would be at a low enough dose that it doesn't have the abuse potential? 

[00:29:28] Deborah Mash: [00:29:28] Doesn't have any safety signal.

[00:29:31] It won't have a cardiac signal. It has no abuse, potential animals will not self administer it. Nobody will abuse ibogaine, we believe. The data is there to support this, and it will be given to patients in a early recovery relapse prevention indication. 

[00:29:47] Greg Kubin: [00:29:47] Got 

[00:29:47] it. So let's talk briefly about your partnership with ATAI.

[00:29:52] Could you talk through how you've partnered with them and the way you work together? 

[00:29:56] Deborah Mash: [00:29:56] Our partnership with the ATAI Life Sciences is very much, not only at the level of funding and of course you have to have the commitment. You have to have the dollars for the research. You have to have the dollars for the clinical trials.

[00:30:09] And ATAI has decided, given us the joint venture to allow us to advance ibogaine to a proof of concept phase two protocol. So that was a significant advance for DemeRx. 

[00:30:24] Greg Kubin: [00:30:24] ATAI Life Sciences is a biopharmaceutical company that incubates and invests in companies that treat mental health disorders. DemeRx is one of 10 companies they've partnered.

[00:30:35] Quick disclosure, the Psychedelic Medicine Syndicate that Matias and I manage is an investor in ATAI. ATAI has invested over $200 million into psychedelic medicine companies, including DemeRx, 

[00:30:48] Deborah Mash: [00:30:48] But I didn't just want the funding. I can raise funding and we have raised dollars in DemeRx, what we needed was a strategic partner and ATAI and they're experts in the company are some of the best that I have ever worked with.

[00:31:09] These are incredibly talented people who are advancing on many fronts. So they have, they have the intellectual currency that we needed at DemeRx. 

[00:31:21] One other 

[00:31:21] Greg Kubin: [00:31:21] question about the, just the business, the business model. Could you talk about how you protect your IP? 

[00:31:28] Deborah Mash: [00:31:28] Intellectual properties, uh, it was not for the faint of heart and it's expensive.

[00:31:33] And of course, in order for investors to get their rate of return on investment. You need to protect the asset. So for the psychedelic molecules, many of them, those structures are known. And so you can't get composition of matter. You can get what is called novel use in some indications where you can modify the molecule in some way, or work up a fully synthetic approach to the drug.

[00:31:58] That'll be used therapeutically and that gives you new intellectual property. So there, there is a strategy. There is an intellectual property strategy that people can follow. There is a roadmap that we can follow at DemeRx. We were fortunate. We were able to get composition of matter around noribogaine.

[00:32:17] And we had an insolvate, which we had patented, which is a valuable asset. It's a different form of the molecule. So that gave us new intellectual property there. We have synthetic routes to, nor I became that we have patented. And that is an important part. So the chemistry around synthesis is important.

[00:32:38] And then of course there's methods of use. So, you know how you're. Administering the drug, what patients, et cetera, blood levels, this all goes into your method of use IP. So we have a very robust portfolio for noribogaine. Ibogaine, on the other hand, uh, is we're developing with ATAI and ATAI's guidance, so new IP around ibogaine as well.

[00:33:01] And so we're excited about that. And we also have filed patents in DemeRx for methods of use for ibogaine. But of course you have prior art as, many who work in the field of psychedelic medicines know there's a lot of prior art. So you have to get, you have to be novel. You have to be strategic. You have to be inventive.

[00:33:21] You have to make that inventive step to get that new intellectual property, but you need to get the intellectual property. And I know that there's the sort of the underground movement, people who want psychedelic medicines to be available for everyone. And don't want to have the issue of ownership and intellectual property, but you can't have one without the other.

[00:33:43] Because you have to pay for the clinical trials. We can't get through the various stages, regulatory stages, unless we have the funds to pay for the clinical trials. Unless we have the funds to manufacture GMP drug product, to give to humans for human use. This is all hugely expensive. You know, many, many

[00:34:05] hundreds of thousands of dollars upon hundreds of thousands of dollars to get you to the end game. So you've got to be able to protect the asset, and you've got to make sure that you have, you know, a rate of return for your shareholders and we're keenly the aware of this. 

[00:34:22] Greg Kubin: [00:34:22] So in terms of your experience as a entrepreneur versus a researcher, How do you think about wearing each of those hats?

[00:34:33] And have you, are you embracing the entrepreneurial side of this journey? 

[00:34:38] Deborah Mash: [00:34:38] I have always been a little bit more Maverick, even in my academic life. I started a brain bank. I have one of the largest post-mortem biorepositories of human brains in the world. And I did this with a very small startup. I took some of the tools that I learned from starting the,ibogaine clinic

[00:35:00] in St. Kitts, you can imagine I did that without NIMH funds. I raised family and friends round and set that clinic up in the Caribbean. I had people donating time. I donated all my time to that. We paid for some of our clinicians and the people who, the nurses and staff, but there was a lot of skin in the game, so to speak.

[00:35:22] And that's what it takes. If you're going to be a good entrepreneur, you've got to be you, you have to be fearless and you have to, you have to, if you believe in something, you have to just go for it. And that's what we did in St. Kitts. But that data that we, what we learned in St. Kitts, those clinical data are an important asset today in DemeRx there's no doubt that being involved as an entrepreneur, learning how to talk to investors.

[00:35:49] Learning to put together a pitch deck made me a better scientific grant writer. I did bootcamp with springboard. They launched women entrepreneurs. It's a really great organization and my company was picked and I was able to do it. They taught me how to do an elevator pitch in my, when I brought, when I learned that.

[00:36:08] And they sharpened me up for being an academic, you know, presenting the science and I had to flip it around and be able to talk about, you know, you invest X and I'm going to give you Y that made me a much better nIH grant writer, I was able to use those tools to sell my ideas. 

[00:36:26] Greg Kubin: [00:36:26] That's great. 

[00:36:27] I love that.

[00:36:27] How one domain contributes to the other and vice versa. So you've been working in and around ibogaine since 1993. What drives 

[00:36:38] you?

[00:36:39]Deborah Mash: [00:36:39] You know, my life has been very interesting and privileged because I call myself a neuroscientist and to have been able to study the human brain and to have people support my laboratory and to have research dollars, taxpayer dollars to allow me to do science,

[00:36:58] what a privilege, what a privilege. And when I, and it's really, you know, studying the human brain, the brain is, you know, the next biological frontier. So we've learned more about the human brain in the last 20 years than throughout all of human history. I never thought I would be working in the field of addiction.

[00:37:17] That was not my plan, but I like many others who have had family members addicted. I have a loved one in my family who is addicted to alcohol, and I saw that person suffer and he suffered greatly. So as luck would have it, you know, research led me to ibogaine. And that's how I learned about ibogaine was through being a researcher.

[00:37:44] And when I saw the power of the drug and I saw what it could do and how it could alleviate suffering, I couldn't let go of it. So even though it was incredibly hard and there were times when I questioned my sanity and I would have just asked myself, what's wrong with you? You know, the NIH doesn't want to fund your grants.

[00:38:04] Ibogaine is a schedule one molecule, I had a very successful laboratory. I had a great career. Why am I pursuing this? But you can't give it up because when you, you know, you get one chance in life to make a difference. And I needed to finish what I started. I started this and it was time to finish. There are too many people suffering.

[00:38:28] This is a great societal need. Addiction is a family disease. It doesn't only affect the individual. It affects the whole family. Today, opioid intoxication deaths is the number one cause of death for people under the age of 50. Look at the deaths. It's staggering. Look at the increased addiction during the pandemic.

[00:38:49] COVID-19. Society is getting sicker. It's harder. So if these drugs, if you know, I became fits in with this new transformative revolution of using psychedelic medicines to treat intractable depression, to treat trauma, MDMA, to help people to be able to live a normal life and a better life and a healthier life and a happier life and contribute more as members of society.

[00:39:19] Greg Kubin: [00:39:19] What advice would you have for other entrepreneurs and people that want to work in psychedelic medicine? 

[00:39:27] Deborah Mash: [00:39:27] Well, advice for people working in any pharmaceutical development program is buckle up, you know, Fasten your seatbelt because this is not for the faint of heart. Get ready for disappointment. Get ready for surprises.

[00:39:45] Because when you embark on this drug development highway, there's going to be a lot of detours. So you can't give up and be very smart about staging the bird. When you raise funds from investors, you use those dollars wisely don't make unnecessary mistakes because those mistakes will cost you. Not only in time, which is the enemy, but also in your ability to raise additional funds for your program.

[00:40:13] You've got to work towards those milestones. Stay the course, work the milestones. In terms of the psychedelic medicines. This is a whole new ball game. There's there, there aren't too many rodeos that, uh, you know, we've participated in. So we're, we're all very much pioneers in this regard, but my belief is that you, you must work with these molecules with purity of intention.

[00:40:40] You have to have the highest ethical standards when you embark on developing these medications for human 

[00:40:47] use. 

[00:40:48] Greg Kubin: [00:40:48] Last question. Do you think you will take it at some point in your life? 

[00:40:54] Deborah Mash: [00:40:54] I have not taken ibogaine, um, ever, and to date I have never taken ibogaine. Do I think I would take ibogaine? Well, the reason that I haven't taken ibogaine and the reason that I was quite strict about that in the St Kitts study was because I think it's very important that we have an ability to.

[00:41:17] Study it without having the experience. I believe that. Now I know that many other practitioners who are actually doing very wonderful research with other psychedelic medicines and they're doing first class studies. Many of them have used psilocybin or DMT or whatever. Um, taking MDMA. Um, for me, I wasn't addicted.

[00:41:41] And the doses of ibogaine that we had were very precious. Um, so, you know, I wasn't gonna waste a dose either on me because there was somebody else out there who, you know, that dose might save their life. So people would say, well, nobody will really know that you haven't taken ibogaine, but who would know well that's between me and God.

[00:42:02] So, uh, you know, I've sort of set my, you know, my intention to work with this, to try to maintain. Objectivity and to, to always, you know, present the facts and the information around this drug to the best of my, you know, my talents and ability, you know, if ibogaine is safe and we're able to advance and conduct a pivotal proof of concept study, this will be a huge gift for, ibogaine on the road to become available to patients, so many patients who need it.

[00:42:31] And I would never jeopardize that from help.

[00:42:40] Greg Kubin: [00:42:40] The best entrepreneurs are gritty and relentless as they navigate old mazes and institutions that stand in the way of innovation. When you think about the hoops, Deborah Mash has had to jump through to bring ibogaine therapy to market. It's kind of amazing.

[00:42:55] Getting FDA permission in the 1990s to commence phase one studies only not to find funding for those studies.

[00:43:00] So she starts a research and development program in St. Kitts with permission from the local government to study ibogaine, then unsuccessfully applies for grants from the National Institute of Drug Abuse only to come back to the United States and startsDemeRx and gets funding for her company from a partner like ATAI Life Sciences is the definition of grit.

[00:43:18] And I can't think of a better way to apply her grit than to improve the lives of those fighting addiction. 

[00:43:25] This is Business Trip, a podcast about psychedelic entrepreneurship. If you like this episode, you can help us by subscribing to the podcast and leaving a review. You can tweet at us. Or find us on the gram at businesstripfm.

[00:43:38] And if you're building a company in psychedelics are looking to get more involved in this space. Send me an email at greg@businesstrip.fm. I'm your host Greg Kubin. Business Trip is created by me and Matias Serebrinsky.  Producer and editor is Jonathan Davis. Sound design and engineering came from Zach Frank. Our theme music is by Dorian Love.

[00:44:00] And additional music credits are in the show notes. This is Business Trip. Thanks for tripping with us. We'll see you next time.

[00:44:15] Deborah Mash: [00:44:15] I grew up in the late sixties and early seventies. So I, you know, I grew up with, you know, Psychedelic drugs being used all around me. So I know about these molecules and I've studied, you know, I've, I've worked in the field of neurobiology of addiction. So I'm, I know, I know about drugs, but, um, so far so good.

[00:44:35] I've never met a man or a drug that can control me, so I don't need the ibogaine. .