YouSaid · the spoken record

Rick Doblin

lines on the record: 189
first: 2021-07-21
most recent: 2021-07-21
sittings or episodes: 1
sources: podcast

Every line below is reproduced as it was said and linked to the record it came from. Nothing here is summarised or generated. Directory · Search · Corrections

“I don't think it's tragic that we die. So, first off, if you believe in this collective unconscious, but we have an impact that lasts. But I think that for me at least, I've been of the view that we should be grateful for death. That death makes life precious, that if we had an infinite amount of time, I mean, I'm a bit of a procrastinator about stuff, particularly things that are really hard to do. And you just, you know, you just don't do it. And then like, where'd the day go? I was going to do this. So, if we had infinite life, we never died. Would life be precious? Would we do anything? I don't think so. So my parents gave every Jewish New Year they would make their New Year's card. And one of the quotes was fantastic. It was just, we have to make up for the brevity of life with the intensity of life.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Well, yeah, what I've discovered is that. Don't need the answers to those questions. The fact that Can feel happy that we can love, that we can have moments of happiness. That's enough. You know, figuring out these big questions, you can get lost in that. And we all can come up with our answers. What's the meaning of life? Why is there life? Why is there consciousness? I don't know that we need those answers. What we know is that social creatures that we people, other people can make us happy by certain things. We can make other people happy that one life is enough. So this other part about why is it so tragic that we die.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Try to see through that to their humanity, to what their pains and suffering, what their struggles are, to the extent that you can. And that, I think, and build long-term relationships. You never know what's going to come around 20 years from now. So you help some people try to keep these relationships going 20 years from now, something could come. And also Persistent. I think that's been the key to success. I mean, once the FDA or DEA figured out, we're not going anywhere. They're going to have to deal with us. Then we started getting some progress.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Taken a long time because you know, I feel like drugs are illegal. I always felt like the police were the predator and I'm the prey But now we're working with the police, and the police have tremendous trauma from the work that they do. We have one police officer who is now going, he's a full-time police officer. He's also a psychotherapist. And he's going through our training program to learn how to give MDMA therapy to other police officers. And I met his police chief a couple times. He got permission from his police chief to go to the second part of our training program, which is where we give MDMA to therapists who volunteer as a patient. So we have just a couple weeks ago dosed the police with MDMA. And so I think this idea of those people that are on the quote other side.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“When I started, I didn't think it would ever work. I just thought this is the only idea I have in this crazy world. This is what I want to work on. Luckily, I had support from my family that took care of my survival needs. So I could do that. But I realized that if my happiness was dependent upon accomplishments, that I might never be happy. I was able to reframe happiness in terms of effort So if I'm trying hard to get stuff. Be better, whether it's better or not, I can be happy at the end of each day. I tried. And so I think you try to separate out the goals that you have and your happiness to whether you're trying hard. The other thing I would say is that everybody has this humanity within them. So be very careful about dividing the world into us and them. And try to so one of the things that I've done that has”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“The extent that you're able to do this, and again, student debt and all this kind of stuff is a big problem there too, but really just try to Find this combination of what the world needs and what you need. The other thing to say to young people is life is a lot shorter than you think. And a 20 year plan is not really that long. So if it takes you 20 years to get in a position to do what you want to do, go for it. Have long-term plans. The other part that was so important for me to keep doing what I've been doing, basically, now it's 49 years that I've sort of been devoting my life on psychedelics since I was 18.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“And this is exactly it to young people. He said, you know, there's nothing particular that you should do, but find what makes you come alive because what the world needs is people that have come alive and are passionate. So I would say that Beware of this trap that you need vast resources that you need all this stuff. I keep thinking of the super wealthy people in first class on the Titanic. As the Titanic is sinking, you know, their money's not going to help them. The Earth is like Titanic. We're sinking, we're destroying the planet, destroying the environment. You need a certain amount of money to be comfortable, to not be at that edge of survival because once you're at that edge of survival, it's hard to think about anything else. But I'd say to young people.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Well, I would say what people often hear is that Know we're not actually here for that long a period of time. And so to the, and the world is on fire and whether humanity survives is not clear and whether how many species are we going to kill before we figure out not to do that anymore. So I would advise you to really try to Develop a combination of what do you need in terms of income for your own survival, but what does the world need in terms of Help to make the world better. And Howard Thurman, who he talked about, who ran the Good Friday experiment, the minister there, he's got a famous quote attributed to him. He says,”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“I think they're making a fundamental mistake. And I think the reason is that the more that we destigmatize this, the more that we sensitize people to this is an approach, even when people can get it on their own and do it with their friends or do it with themselves, there's going to be even more people that say, oh my God, I've got real serious issues. I would rather go to trained professionals covered by insurance. And I think it'll increase the business. Most of the for-profit companies don't see it that way. And so as a nonprofit that owns a benefit corp, we're not trying to maximize sales or profits. But I do believe that drug policy reform creates this alternative access point for people, and that will help keep the for-profits in check to some extent as well.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah. Now, the other part of this is drug policy reform. So that if we make it so that you can buy MDMA for 10 or 20 bucks on your own. And we've trained people on here's our therapeutic method. Here is our ways for peer support. Then people have an alternative from buying it from the pharma companies So, most of the for profit companies have come to this conclusion that drug policy reform is bad for their business model.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“If we create an example of something that's different, The hope is that people gravitate towards that and some of the other companies. Like even now we have Exxon and other companies, oil companies saying, oh, we're big into alternative energy and we're”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“They sell it for hundreds of dollars, but ketamine itself is one of the world's essential medicines. It's off patent. It's been around for a long time. It was the main battlefield anesthetic in Vietnam. And it's only a few bucks because it's generic. So a lot of the ketamine clinics are saying, great, thank you, Johnson. Johnson, you've helped demonstrate that ketamine is good for depression, but we're not going to buy it from you. We're going to buy it for a few bucks, and we're going to add therapy to it. Now, there's a bunch of ketamine mills, you could say, that are just prescribing the ketamine, and people are making a lot of money there. So I am worried about that. I think the best thing that we can do is create an alternative narrative, a different kind of example. We can lead by example. We can't make for-profit companies into benefit corporations unless they want to do that. We can't make them to, you know, really maximize patient outcomes.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Pharmaceutical company, but it doesn't maximize patient outcomes. What we're seeing though in these various clinics that are being set up is that a lot of people are realizing that it works better with therapy. And so the clinics are run by people that are therapists so that when they provide therapy, they're making more money. And then you need less ketamine. Also, ketamine itself, S ketamine is an isomer of ketamine that's been patented for depression.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“The other thing we've seen as an example of this is as ketamine by Johnson and Johnson for depression. And it's done by a profit maximizing company. They don't know anything about psychedelic psychotherapy or psychotherapy at all. And so they've gotten approval for eschetamine on the basis of it's just a pharmacological treatment. And it's not delivered with therapy. The results fade pretty quickly. So you need to get more ketamine. And so it's designed in a way to maximize the profits for the.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Well, I am concerned. Overall, I think the rise of the for-profit companies, we have to realize is a sign of success. That we have overcome the regulatory prohibitions. We've overcome a lot of the public attitudes that are against it. We've demonstrated some success. So the rise of the for-profit companies are a sign of the progress that we've made. On the other hand, turning things over to profit maximizing companies The big concern is that they're going to try to minimize the amount of therapy And make it so the cost is less, so insurance companies are more likely to cover it and then that they just sell the most drugs.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“So, can we get honest drug education, pure drugs, harm reduction, and knowledge about therapeutic uses? And on the one hand, and more of these thousands of psychedelic clinics, I'm hopeful. And that's our goal.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“So, can we get there? I think that we can. And I think that we need to survive the challenges that we're facing. And the hope is that by bringing psychedelics as tools forward and trying to bring the context around them. To be one of responsibility rather than just profit maximization and just get as many people to do them from all these for-profit companies, you know, can we, and then also drug policy reform and embed knowledge in the society, can we get to honest drug education? But it's the program that's used in a lot of schools now.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“One way to say this is that can we get to the point where religions are seen as like languages, where we all have this need to communicate. There's thousands of different languages. We don't say that this language is fundamentally better than this language. This language is the only right language. Everybody must speak English and Russian is bad or German is bad. Maybe we'll get to that point that religions are like that, that they're different cultural backgrounds, different symbol systems, different saints and heroes and messiahs and all this, but that Jesus is the Son of God, but so is everybody. Or, you know, the Jews are the chosen people, but so is everybody.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“So, I think that there's a very good chance, though, that psychedelics used wisely. So it's not just make psychedelics legal and everybody takes them. And as you talked about, Ted Kaczynski, it's the context that people take it in. But I think that there is a reasonable chance that enough people can sort of, you could say, clean their filters to see people More similar to them than different, not to label them as the enemy. Stan Groff, again, had this beautiful phrase about. Transparent to the transcendent. So, for our ego, can we be transparent to the transcendent? Because can the filter that we look through the world at? Be cleaned to, you could say, cleansing the doors of perception. Can it be cleaned to the point where we can see the humanity in everybody? And see that”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Okay, so I said that I think licensed legalization happens in 2035. And I think by 2050 we will have enough people hopefully spiritualized. We're also talking about, we hear so much in terms of climate change, about net zero carbon. So, our goal is net zero trauma. When do we have a world with net zero trauma? I mean, right now, you know, we have two sites in Israel. So we help a few people, but the recent war with Gaza Has traumatized millions of people on both sides. So we are a long way away from net zero trauma. But that's the hope. And that's, I think, possible. I think humanity as a whole. Like Lemmings heading over a cliff with climate change and with the nuclear proliferation and just the religious hatreds and the more the retreat to authoritarianism and fundamentalism and tribalism.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah, well, you know, Freud talked about dreams as the royal road to the unconscious. And there was a lot of, you really spent a lot of time with people. Now, right before he died in his last book, Freud wrote something, and again, this will be a rough paraphrase, but he said that in the future we may learn about the energies of the brain and there'll be ways with chemicals to influence that that will help the therapeutic process.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“And that's why we see that so many young psychiatric residents are so thrilled by psychedelics They really want to get back to treating people as individuals, not just a bunch of chemicals.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Not going to correct you. Right now, there is a crisis in psychiatry, that there are so many psychiatrists that are so fed up because they have been pharmaceuticalized. Meet people for 15 minutes, they adjust their medications. This is the way they make the most money. They've lost the art of talking to people”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“That drives them for addiction. There's Ben Sessa, Dr. Ben Sessa in England did MDMA for alcohol use disorder. And that was really great, the results he got. And it's the case that he ended up basically treating people for trauma. It's the trauma that people run, the emotional challenges that people run from into quieting that pain through drug addiction or alcoholism. So trauma is behind a lot of addiction. I think that we are going to see a revolution in psychiatry and that there will be a lot of Conditions that have Left a lot of people still suffering that psychedelic assisted therapy, different psychedelics, different approaches, but I think that we will see a lot of hope for a psychiatry and psychotherapy and that psychedelics will be a big part of changing the practice of psychiatry and psychotherapy.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“But I don't think that the results we've got are so unique to MDMA assisted therapy. I think that psilocybin assisted therapy is going to be great for people with life-threatening illnesses, cancer who are anxious about dying. looks like it's really good in the treatment of addiction. Again, these are in combination with sort of the psilocybin tobacco as cognitive behavioral therapy with psilocybin. I think that it's going to be a little bit more difficult psilocybin for depression. I don't know if it'll be quite as good. You know, there are some biological aspects sometimes to depression, but I think there'll be really good results for psilocybin for depression. I think it'll be approved. It's considered a breakthrough therapy by the FDA. IBAN is phenomenal for opiate addiction, helping people go through the withdrawal and then giving them this chance to deal with the material that they've”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah, I think that. What we've discovered, I don't think is unique to MDMA. So it's MDMA assisted psychotherapy. MDMA is ideal for PTSD. You know, maybe it won't work as well for OCD or other things. It was very strategic why we chose MDMA and why we chose PTSD.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“People keep getting better. At the two month follow-up, they're doing pretty well. But at the 12-month follow-up, they're even better. So it's durable. People have learned how to process trauma. They keep getting better. So we've not reached that point in this phase three study where everybody's got their one-year follow-up. But we have also done three and a half year follow-ups to some of the groups that were in phase two and showed that it was durable. And we're doing a long-term follow-up now to many of the people in phase two. Some of them treated 15 years ago. So that's all more for the insurance companies. So basically what we found in the paper that we just published is that it was highly efficacious, highly significant, no effect by sight, works in the hardest cases, and the safety record was great.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“No longer had PTSD, you know, more than twice as good in phase two and in phase three, we're also going to do the 12 month follow-up. That's not for the FDA. That's not for approvability. That's more for insurance companies. This is expensive. A lot of therapy time, if it fades, you know, if it's great results initially, but then it fades after six months, what's the point? And what we showed in phase two is that”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“In two of our different sites and showed no decline in cognitive functioning, so we don't think that there's any neurotoxicity happening and the doses that we use. There's no obvious functional consequences. People are getting better. The other thing that we've learned in phase two and that we still have to learn from this study. So what we showed is that is the durability of the effect. We showed that 32% of the people that got the therapy without MDMA two months after the last experimental session no longer had PTSD just with the therapy which is phenomenal because these are on average 14 years PTSD one-third had PTSD over 20 years And just with the therapy, 32% no longer had PTSD at the two months. However, those people that got MDMA was 67%.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“They're sweating or jaw clenching, or it's like temperature increase. And everybody that's been to a rave knows about or take an ecstasy. There are some side effects. But they're minor, they're transitory, and there has been this massive problem of during the 80s, the 90s, NIDA, the National Institute on Drug Abuse, was trying to say that MDMA was neurotoxic and that you take it and it's going to cause nerve terminal degeneration. It's going to be major brain damage. It's going to be significant functional consequences. Back then, they were saying that MDMA is too dangerous. It should never even be researched. Nobody should even get it once because it's poison and brain damage. Well, we no longer believe that. That was exaggerated. That was in service of the drug war. But we've done in phase two neurocognitive tests before and after.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“And that they can somehow process this. Now, it's not to say that nobody will ever commit suicide. That's our big concern in the second phase three study. As I said, it's more going to be about safety than about efficacy. We think we'll get the efficacy, but we're very concerned about, you know, safety. Because we had Problems in the first phase three study of somebody trying to kill herself twice in the placebo group, it's the background for having PTSD. So there'd have to be a disproportionate number of people in the MDMA group try to kill themselves or succeed in killing themselves than in the placebo group. The FD to say, Oh, this MDMA, it's too dangerous. We don't think that's going to happen. So those are, the other findings are that from safety is that the side effects are transitory. They're minor.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“They're part of your story, but they're not the whole story. So we discovered that the associative subtype works better. Now, none of this would be enough unless safety. So from a safety perspective, what we discovered is that there was one woman in the study that attempted to kill herself twice during the study. There was another woman that was so Worried that she might kill herself, that the therapy brought these things to the surface, that she's been pushing away, that she checked herself into a hospital in order to avoid self-harm. At the end of the study, what we learned is both of them were in the placebo group. We didn't have anybody in the MDMA group attempt to kill themselves. So, the MDMA is really helpful for giving people a sense of hope.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah. And we find that MDMA enhances memory for the trauma. That you can have these unconscious memories or memories that you cannot remember or that you've suppressed so much, but they distort your view. Your filter of the world is distorted by these fearful memories that the world can't be trusted, people can't be trusted. It's always about to happen. So we find that MDMA increases memory for the trauma, but by reducing the fear, then the memories can come to the surface. Then you can process them, let out the emotions, cry, scream, shake, whatever. And then through this MDMA effect on the amygdala and the hippocampus, it helps you store these memories into long-term storage so that they're not always about to happen. They're in the past.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“And those are considered to be the hardest to treat because the theory is that you need to be ego intact. As I said, the mystical experience is not correlated with therapeutic outcomes. And you need to be talking about what traumatized you And working through that and expressing it, letting it out, not keeping it in. So the dissociative subtype seems like it's harder for them to get back into the event because they're so dissociated. What we showed is that those people did even better on average than everybody else so that MDMA is integrative. It helps people who are so separate that they make even more rapid progress.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“That we've been able to train all these new therapists. We had about 80 therapists working at all these 15 sites. We also discovered that there's a group that's considered to be very difficult to treat, which is called the dissociative subtype. So when people are traumatized, one of the ways to psychologically survive that is you dissociate. It's like you're not there. When you do that though, it's hard to come back because when you come back, then you get all these painful memories and fearful. And so the extreme of that is called dissociative identity disorder. Kind of like schizophrenia, almost dissociative identity. So we let people in who are on the dissociative subtype.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“The FDA looks at is there a side effect? Because what that might mean is maybe you've got all your patients or most of your patients going to this one site, which is these highly experienced therapists and they're like, you know, hippies from way back and they're super experienced with psychedelics and they're getting great results, but nobody else gets good results. So we had no effect by sight, which means that's”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah. Now. When we do the within group, meaning the group that just got the MDMA plus therapy, look at their baseline and their outcomes. That's another way to look at. And that's what's going to actually happen in practice because people are going to get MDMA plus therapy. That's 2.1 effect size, two standard deviations away from the norm, as enormous effect size. The other part is that we had no effect by sight, which is very important. So we had 15 sites, two in Israel, two in Canada, 11 throughout the United States.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Well, the scale of the effect size is based on standard deviations. So an effect size of one means that your results are one standard deviation away from the norm. That's considered very large. The SSRIs, because they were like 0.3, 0.4 effect size, that's considered small effect size. Medium is starting to be around 0.6. And 0.8 and above are large effect sizes. We had what's called placebo subtraction. And what that is for us since one group had therapy and one had therapy plus MDMA, the placebo subtracted effect size. Is basically the effect of just the MDM Because you've kind of washed out the therapy. That was 0.91. So we had a large effect size, which is”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Well, if we can get one in 10,000 in the first phase three study, chances are we can get one in 20 in the second. So it's really going to be about safety for us in the second phase three study. Now, you can have a large p-value, a large significance, but you could have an effect that's not very significant. It's not clinically significant. You can have statistical significance without clinical significance. And as I said, the more people you get in the study, you can find smaller and smaller differences between two groups. Now, we showed that we had a very large effect size. So effect size is based on”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Because when you think about it, a one in 20 chance for your first phase three study, a one in 20 chance for your second phase three study, you multiply that together, it's one in 400 That's pretty good, so robust 0.001 is even better than. Two independent phase three studies, each at 0.05. What we ended up getting was 1 in 10,000, 0.0001. Outrageous You know, incredibly so that's a measure of both the difference between the two groups and the variability. And so, what it meant is that we had minimal variability that most people that got to MBA got quite a large amount of benefit from it. And most people got the placebo were more or less in the same range as well.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“And what we discovered was that the study worked better than we had even hoped. So the first thing is that you look at statistical significance. You have to get 0.05, which basically means a nickel out of $1, 1 in 20 chance that the difference between the two groups is due to some random factor rather than to your intervention. And in this case, the placebo group gets therapy, and then with inactive placebo, and then the group gets MDMA with active placebo. So you have to get 0.05. There's another measure that the FDA uses sometimes called robust, which means one in a thousand instead of one in 20, 1 in 1,000. And if you get a robust result, 0.001. And you meet some other criteria. They might agree to approve the drug on the basis of just one phase three study instead of two.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“So we did the interim analysis in March of 2020. And what we discovered to our delight was that we did not need to add any subjects. That's all we were told. We weren't told what is the results. We were just told all we were going to get is a number, zero, or you need to add X numbers of people to the study to get statistical significance. That's right around the time that COVID hit and lockdowns happened. And we ended up negotiating with FDA that we would end the study with 90 people instead of 100. It took a while for us to end up doing that. So, the paper that we just published is on the results of 90 people, I think it was 46 in the MDMA group, 44 in the placebo group.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“So, what it means is if the results aren't as good as you thought they would, you can add more people And then you'll get statistical significance. It means that your effect isn't as strong as you thought. It'll be harder to get insurance to cover it, but FDA will still approve it because FDA also believes that these are group averages. There may be some people that will later figure out respond better than others. So they'll approve it if it's statistically significant, even if it has a low effect size. The SSRIs have low effect size.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“We came to this agreement with FDA. We're going to work with chronic severe PTSD patients, including those that had attempted suicide. And we would do these two 100-person studies. And we also negotiated what's called an interim analysis. So what that means is that when the study is underway and often big, big studies, they have this kind of interim analysis where what you do is, and for us we negotiated when we had 60% or 60 people had reached the primary outcome measure and all hundred had been enrolled. Then we would take a look at the data. And if the Statistical analysis that we did was showing based on a certain effect size that we chose based on what we saw in phase two. The interim analysis is for what's called sample size reestimation.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah, yeah. And the second, but also safety as well. So one of the things we also realized when you work with a highly stigmatized drug in the midst of still the drug war and prohibition, that we need highly sympathetic subjects. And we need to make the best case we can, which means we need to work with the hardest cases so that this is really needed. And so we end up enrolling people. The first study was chronic severe PTSD and unlike many studies of PTSD, we enroll people that have previously attempted suicide. So we have multiple people that have tried to kill themselves that we felt like if we were to exclude them, what are we doing? Those are the people that need it the most.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“So once we started phase three, so then we were able to start in 2018 phase three. And the paper in Nature Medicine that just came out was the results of our first phase three study. We came to agreement with FDA that we would do two phase three studies. Each would have 100 persons in them. And what the FDA said to us is that they thought that we could prove efficacy. With smaller numbers than they wanted to see for safety. The reason they said that is that in phase two, we had a large effect size. So from a statistical point of view, the bigger of an effect that you're looking for, the fewer number of people you need to get statistical significance. You're trying to find small differences, you need large numbers of people to sort of work out the noise. So we came to agreement on two 100-person phase three studies.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“Very much so. And so we came to this agreement with FDA, though, that we would use this independent raider pool. And so We learned in phase two again that the double blind there was no solution to the double blind problem. And both the FDA and the European Medicines Agency in the end agreed that the best design was therapy with inactive placebo versus therapy with full-dose MDMA, accepting the fact that most people will be able to tell whether they got nothing or they got full dose MDMA. Most therapists will be able to tell the difference. That makes a harder test for us to show a difference between the two groups because we're giving them inactive placebo and not the anti-therapeutic effect of low-dose MDMA.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“I love it. I love it because it's always trade offs. And I acknowledge that we are all biased. And so, how do you There's something beautiful about the scientific process designed to get you to the truth.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“So we've got like 20 Raiders. And what we want to do is make it so that each raider sees each patient only once, maybe twice, but not tracking them through the study So that guys to reduce the bias in the raiders, that they don't know where this person is in the study. And so there's a fellow Bob Temple, who's like the old wise man at the FDA. He's been there since 1972. He was in charge of the Office of Science Policy, and they brought him into the final meeting of this process where we are trying to design phase three. So once FDA said, yes, you can go to phase three. That was November 29, 2016, we then negotiated for eight months on the design of phase three and all of the other information. This is fascinating.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source
“And meets the same inclusion exclusion criteria. So that's what we told. Of course, we need random assignment. The other part was when the bias double blind doesn't work as well, then the system of independent raiders is especially important. Of how you do that. So we have over a pool of raiders, over 20 of them, and we do this monthly integrator reliability tests to make sure that they evaluate so that they're given a videotape of a PTSD patient and then they're supposed to rate them according to their symptoms. And then we sort of make sure that we've got this calibrated rater pool. And it's all done by Zoom, by telemedicine, and they're randomly assigned to the next person that needs a rating.”
2021-07-21 · Lex Fridman Podcast · #202 – Rick Doblin: Psychedelics · IDENTIFIED FROM THE TRANSCRIPT · source