6 months ago
Rick Doblin, Ph.D., is the Founder in 1986 and President of the Multidisciplinary Association for Psychedelic Studies (MAPS), a nonprofit that wholly owns its pharmaceutical arm, MAPS Public Benefit Corporation (PBC), which has completed two highly successful Phase 3 studies of MDMA-assisted therapy for PTSD. MAPS PBC stands at a crossroads between obtaining the additional resources it needs from philanthropy, ensuring public benefit is foremost, or becoming a publicly traded company. maps.org
We are now at a place where we recently announced that our second phase three study was successful and was confirmatory. Our first phase three study was incredibly successful. And to give you a sense of how successful, and we published this in Nature Medicine, the FDA looks at statistical significance. So there's efficacy and safety. So efficacy is determined by basically statistical significance. And you have to have .05, which means one in 20 chance that it's random, that it's not from what you think it was. That your intervention, your experiment said, yes, it's statistically significant. That means it's one in 20 or lower chance that you're finding is random. And you have to have two of those. And so if you have one in 20 and then you multiply them another one in 20, it's one in 400 chance that these two independent studies have produced results that are random, and then the FDA will approve it. Our first study was one in 10,000 chance that it was random. It was just incredible. Now how do you do that? How do you get such great statistical significance? You get it because you have a big difference between the two groups, and you also have not that much variability. So what it means is the people that got MDMA, pretty much of them got major benefits, and the people that got the therapy without MDMA. So I should say the people that got therapy with MDMA did great, not very much variability. It doesn't work for everybody, but we had 88% responders. We had 67% no longer had a diagnosis of PTSD. These are severe PTSD patients that had PTSD an average of 14 years, one third over 20 years. And then we had just another 21% had what's called clinically significant response. And they still have PTSD, but over time they might get better. If they could have had a forced session, they might get better. And we had a great safety record. We had nobody, actually nobody in the MDMA therapy group tried to kill themselves, tried to hurt themselves. We enroll people that have previously attempted suicide. We did have one woman try to kill herself twice during the study, but she was in the placebo group. She got therapy without MDMA. We had another woman, it was so difficult for her to confront her trauma that she checked herself into a hospital to not self-harm. She also was in the placebo group. So the results were phenomenal. And science, the journal science, one of the most important journals in the world in science, at the end of every year, they publish a list of what they think are the top 10 scientific breakthroughs of the year. And they chose our study in nature medicine as one of the world's top 10 breakthroughs of the year. It was phenomenal. And we had special appreciation for what science was willing to do, because you talked about beforehand about holes in the brain. So 20 years before, science had published this article that they never should have published. And this was by researchers at Johns Hopkins that had been funded by the Nationalists on Drug Abuse. And what they claimed is that MDMA could hurt dopamine. This was a study in primates. And they said, oh my God, MDMA can hurt dopamine. And it could cause Parkinson's. And this could be real danger. Now this was around 2002, 2003. And they had, since 1985, it had all been about MDMA supposedly hurting serotonin and causing holes in the brains from serotonin. And we had done studies in primates before with these same researchers where none of the primates died from overdoses. There didn't seem to be any problems with dopamine. But the narrative of the anti-drug people, the Nationalists on Drug Abuse about serotonin neurotoxicity was sort of diminishing. People weren't showing problems. And so what they were saying was, well, you're reducing your cognitive reserves. And so you don't show problems now, but when you get older, you're going to show problems. So the time bomb theory. Did they have evidence of this? No. And not only did they not have evidence, but a lot of older people took MDMA and they were fine. So if they had this decline of age-related decline, they were a little worried. But it does drop your dopamine levels, right? Or serotonin levels. In a short term, yes. Yeah. Yes, yes, yes, yes. It does. But it doesn't do this kind of damage to the brain in that way. They recover within a day or so. And there's mitigation techniques like with 5-HTP. We don't use those. But people do use those. Why don't you use those? Because we don't think it's necessary. So what we first proposed in 1992 is when we got permission for the first study with MDMA. And people had been using 5-HTP after MDMA. But there is a benefit to using 5-HTP. It boosts your serotonin levels quicker, correct? Yes, yes. It can be helpful. But what we do in a therapy context. So the FDA, we said, should we try administering with 5-HTP or something like that? They said, don't do that. Let's do everything under observation and see what the problems are. And if you see problems, then we should figure out how to mitigate the problems. So the key thing that we do is to say to people that when you take MDMA, it's a two-day experience. It's not a one-day experience. And the second day is for rest and for reflection. And they have no obligations, no appointments, nothing that you need to do. Just take the second day and rest. And that's where people would take 5-HTP if they wanted to. But we don't see this dip in mood anymore in the MDMA group than in the group that gets therapy without it. So people talk about Suicide Tuesdays or this depression after you've used up serotonin. But I think the rest part is part of the therapeutic process. So we have never felt the need to recommend that people do 5-HTP. I don't think it's a bad idea to do. I mean if people wanted to do it, it can be helpful. But we just feel that the rest is just as helpful and it's more therapeutic. So what... But they're not mutually exclusive. No, we could do both. Yeah, for sure. For sure. But we don't in the research. We haven't found the need. But what science had... So this idea of serotonergic neurotoxicity and holes in your brain and time bomb theories just wasn't working anymore. It wasn't persuading people. It wasn't persuading the FDA. So NIDA funded this study, Una McCann and George Riccardi, and it was in primates. And as it turned out, a bunch of the primates died of overdoses. And they published the paper in Science that said that MDMA could cause Parkinson's that could hurt dopamine. And the editor of... Science is published by the American Association for the Advancement of Science. The president of that was Alan Leshner. He used to be the head of NIDA. And he fanned the fears of MDMA and he did that in Congress and it was great because then he got more money for NIDA. Got him over a billion dollars a year. So he published a press release about this article and it said that taking MDMA was like playing Russian roulette with your brain. So it didn't seem right, this article. We knew that we'd given MDMA to primates for research and nobody died of overdoses. None of them did. We wrote a letter to the editor and we questioned it. They didn't give it the way people take it, which is orally as well. And so we kept... How'd they give it? They gave it subcutaneously. Okay. So they injected it sub-q. And so we ended up forcing them in their minds to try to replicate their results. Can I pause you for a second? How do these primates die of overdoses? They would just have heart attacks or something like that. Is that common with humans? No. So here's how this continues. So also you get more neurotoxicity in crowds for some reason when animals or people are together than when they're alone and when the temperature is higher, there's more neurotoxicity. So they tried giving more MDMA to primates with higher temperatures, more crowded in the cages and they couldn't replicate their results. But they kept defending it in public. And finally a year later, they said that... And this was super embarrassing. They had to retract the study because they were puzzled why they couldn't replicate the results. And so they took some of the tissue from one of the animals that had overdosed and died and they discovered that they had mistakenly given methamphetamine instead of MDMA. And that the bottles they said that were labeled MDMA actually had methamphetamine in them. So they got these bottles from a group called Research Triangle Institute in North Carolina. They provide all the Schedule I drugs for all the NIDA-funded researchers. So the Hopkins people blamed the people at Research Triangle Institute and said they switched the labels on the bottles. The people from Research Triangle Institute said they never do that. They always test it. They have quality control. They think that it got switched something or other at the site at Johns Hopkins. The National Institute of Drug Abuse didn't want to find out what was going on or if they did want to find out, they never made it public. So it's never clear how did this happen. But they had to retract this data and retract their papers. And it was the high watermark of neurotoxicity fears. And at the same time, Peter Jennings was doing a documentary called Ecstasy Rising. And this was the first documentary that really had a bunch of people talking about the benefits and he also talked about this problem with the methamphetamine. The other thing about methamphetamine versus MDMA is that for people that know about Adderall and other things, 10, 15 milligrams is a hefty dose. But MDMA, it's 125 milligrams, is a full dose. And so they were giving the wrong drug in MDMA quantities. And that's why they knocked off a bunch of these primates. And that's why they claimed that they saw this dopaminergic problems. And so ever since then, and that's been 20 years ago now. Do you think, do you have speculation that that was sabotage? Somebody sabotaged it somewhere. I don't think it was from research trying to let it sit. Do you think it's accidental sabotage or do you think it... I don't. I think that the researchers wouldn't have done that intentionally. But maybe somebody in the lab did it or something. But I do think that the researchers were fundamentally irresponsible to put the paper out because they should have known that there was prior primate studies where dopamine hadn't been damaged. The other thing is in the late 1980s, early 1990s, we were trying to talk about MDMA, serotonergic neurotoxicity. So I went to George Riccardi, the same researcher that did the primate study with the methamphetamine instead. And I said, I want to buy you some monkeys. You've just done studies in rats. Can you study this in monkeys, in primates? And he said he did. And again, there was no evidence of overdoses or dopamine. Also this was before brain scans came in. And so the most sophisticated way that was available at the time to look at what's going on in the brain was to do spinal taps and to take spinal fluid and look for metabolites of neurotransmitters in the brain. And I felt like I could not recommend, try to get other people to volunteer for it unless I did it myself. So I was the first one to get a spinal tap. And it was really hard. But the imagery that I did, and again, this is kind of this idea about storytelling. So the story I was telling myself as this big needle is going into my spine to try to draw out the spinal fluid was that if a woman could give birth to a child, I could at least give birth to my spinal fluid. It was like way less painful, much shorter, but I could do it. And so the imagery was I'm giving my birth to my spinal fluid to these researchers so that we can understand what's really going on with MDMA and hopefully make it into a medicine. And it didn't hurt terribly. And there was spinal headaches that you get afterwards. So a couple of days afterwards, I had headaches. But I felt like I could enroll other people. I can encourage other people to do it. So I was going to New College in Sarasota, Florida, which by the way, DeSantis is now trying to kill and has fired the president. It's the most... It's the Honors College of the State of Florida. And it is a... Why is he trying to kill it? It's just what he's doing to public education. I mean, this was the symbol of what he called the most woke school in a bunch of transgender people, a bunch of open-minded people. It started as a private school in the 60s, merged with the state when they ran out of money. So he fired the president. He stacked the board of trustees. And he's making... He wants to turn it into a conservative school. He's doing it for political purposes to try to show that he's anti-woke and that he is wanting to... What's going on in public education in Florida is really frightening. George Soros is actually interested in trying to help out at New College because George Soros actually, even though he's the boogeyman for a lot of the right wing, he funded the Central European University in Hungary after communism. And it was killed also by Orban in Hungary. So you go after public education as a way to try to control intellectual narratives. But anyway, I was at New College's school and we were experimenting with MDMA. And so I got about 35 people or so to get spinal taps, not just from New College, but from all over. And the spinal taps showed that there was no problems with dopamine. There was a little bit less serotonin metabolites, but also lower serotonin has been linked to risk-taking behavior. And so taking drugs is risk-taking behavior, particularly when they're heavily criminalized. So it was not evidence that it was serotonin neurotoxicity from MDMA, but it cleared dopamine. So these researchers should never have ignored their prior data. They were just so willing to demonize MDMA to get more grant money.