The Origin Story of MDMA Research: Annie and Michael Mithoefer

Annie Mithoefer 10:02

They’re they get better. But it takes 2 or 3 years. Yeah. Yeah.

Dr. Sandy Newes 10:08

That you mean the breathwork?

Annie Mithoefer 10:10

Yeah. Doing the breathwork continuously as a practice. So all.

Michael Mithoefer 10:14

You know, I view all these as just tools for shifting consciousness. One Psilocybin’s one and and breathwork is one, so. Yeah. So we decided. Okay, well, we’re very well aware we had experienced MDMA with a therapist ourselves since the 60s. And we knew about the papers. The case reports George Greer and Rick Talbot and others had written about using MDMA in therapy, but they hadn’t done research, you know, before it was illegal. So we were like, this is not okay. People are coming with suffering saying, what can I do? Right. When what we have to offer doesn’t work. They’re saying, what can I do? And we’re thinking, you could do this, but we can’t offer that. You know, maybe this would help. There’s reason to believe. You know, it’s a matter of. We didn’t know, but we knew that we needed research because there were very promising case reports for reputable people. That’s a signal that you need to really pursue it vigorously with controlled research. But no one had done that.

Dr. Sandy Newes 11:18

Well, and all the research that came before, before it was all shut down. Granted, it wasn’t an MDMA at that point because the molecule hadn’t made it right into into being able to kind of even be utilized that way. I don’t even know exactly when it was synthesized, but you know, that other types of research was really promising and it was just squashed, right?

Annie Mithoefer 11:37

Yeah.

Michael Mithoefer 11:37

Stan Grof had a paper in Journal of the American Medical Association about LSD for alcoholism. Yes.

Annie Mithoefer 11:43

But all. All of the practitioners that were using MDMA before it got shut down. I mean, there were lots of them between.

Michael Mithoefer 11:53

Probably a couple thousand between. Yeah. 85 or so and.

Annie Mithoefer 11:58

Well, it was shut down in 85. I mean.

Michael Mithoefer 12:00

Yeah, I mean between the late 70s and, and 80, 84 was emergency scheduling.

Annie Mithoefer 12:05

Yeah. Right.

Michael Mithoefer 12:05

So.

Dr. Sandy Newes 12:06

Well, and the number of just anecdotal reports, really, frankly, myself being one of them, where you’re just like, oh, my God, my life is totally different from this moment forward. Like, I see things dramatically different. And whether that be in, you know, patients or people in the quote unquote, normal population or, you know, people who have trauma histories who are still functioning in the normal population. And, I mean, there’s just so many of those reports. Yes.

Annie Mithoefer 12:33

Yeah.

Michael Mithoefer 12:34

Yeah. That’s I mean, if you talk about the placebo effect and stuff later, we can get into that more. But that’s one of the striking things is like, people don’t just take a pill and say, I feel better now. They have a coherent, complex, very intricate and interesting process psychological process. They can describe about what that entails. So it’s pretty hard to just write that off for me anyway.

Annie Mithoefer 13:01

Yeah. So then you look for Rick.

Michael Mithoefer 13:02

So then we thought, okay, we’ve got to do some research on this. How can we do it? We were members of MAPS, but we never met Rick because we found out about MAPS from Rick’s old girlfriend, Kylie Taylor, who was one of the breathwork teachers. And so we were members.

Dr. Sandy Newes 13:18

Funny how these things, just like, you know, these like seemingly random occurrences that lead us into dramatically different directions, it’s great.

Michael Mithoefer 13:26

So we thought, well, we were wondering how we could do the research. And then actually, I heard something on NPR about Deborah Mash’s ibogaine work in Saint Kitts, and I ended up going down there to see what she was doing. Interesting. So I got the idea. Okay, we’ll have to go to an offshore nation. I wonder which is the best one to go to. Maybe I should ask Rick Dalton. He would probably know.

Annie Mithoefer 13:52

Yeah, right.

Michael Mithoefer 13:53

So I called Rick, and he lived in Charlotte.

Annie Mithoefer 13:55

No, no, no, we saw Rick at the. I called him, and he was. Oh, okay. That’s right okay, I forgot. And then I kind of I dropped. Of course you did. You got.

Dr. Sandy Newes 14:04

His number. I probably called friend or his ex-girlfriend.

Annie Mithoefer 14:08

I think you very.

Dr. Sandy Newes 14:08

Literally how.

Annie Mithoefer 14:09

This happened.

Michael Mithoefer 14:10

I think it was probably in the MAPS bulletin.

Annie Mithoefer 14:12

You probably called, like the day you got back from Saint Kitts. Anyway, it wasn’t.

Michael Mithoefer 14:16

Home. I never got around to calling him back. And then a couple of months later, we get this pamphlet about Ralph Metzner’s first annual Ayahuasca Conference in San Francisco. And I said to Annie, let’s go to that. We’re interested in ayahuasca anyway, and maybe we’ll get some leads on how to do psychedelic therapy, right? So we went to the meeting. We walk in the room. It was all in one room. It was a small Conference. There were some very cool people there, and I saw Rick Doblin across the room and I recognized him.

Annie Mithoefer 14:45

Is that him? Yes.

Michael Mithoefer 14:49

I recognize him from the MAPS bulletin. Right. So I went over and introduced myself, and I said, can you advise me on which offshore nation I should go to to do psychedelic research? And he said, you’re a psychiatrist. I said, yeah. You want to do psychedelic research? He said, you can do it here. You’re the person I’ve been waiting for. Exactly. I was the person he’d been waiting for. He was a person we’d been waiting for. He said, you can do it here and we’ll help you. Yeah.

Dr. Sandy Newes 15:16

Oh, wow. And you’re like, seriously?

Annie Mithoefer 15:18

Yeah. But okay.

Michael Mithoefer 15:20

It just seemed totally natural. Okay, cool. Great.

Dr. Sandy Newes 15:22

And you were all in Charleston and the Charleston Medical Center.

Annie Mithoefer 15:25

Well, no, we had a private office.

Dr. Sandy Newes 15:28

Yeah.

Annie Mithoefer 15:28

Okay.

Michael Mithoefer 15:29

Yeah, we had a private practice. I was on the clinical faculty at the medical school, but we didn’t work there. Yeah. So Rick said, what do you want to study? And I said, MDMA, LSD, psilocybin and ayahuasca mainly.

Dr. Sandy Newes 15:44

We’ll leave DMT.

Annie Mithoefer 15:45

For the others, he said. Yeah.

Michael Mithoefer 15:46

Me too, but we got to start somewhere, right? So we had about a 20 minute conversation, and we agreed the best way to start was MDMA for PTSD. That’s what made the most sense. And that was and.

Annie Mithoefer 15:59

That’s what we were doing. And we were doing PTSD anyway.

Dr. Sandy Newes 16:01

We were doing in your office. That’s what you were doing with the breathwork.

Michael Mithoefer 16:04

Rick was most interested in MDMA, so it was a really good fit. So Rick said, why don’t you go home and write a draft protocol and we’ll start working on it? That was in January of 2000, I think.

Annie Mithoefer 16:15

Awesome.

Michael Mithoefer 16:16

A year later, and yeah, in October of 2001, we submitted our FDA application. So it took a little over about a year and a half. We had a lot of input from many experts about the protocol, because we didn’t know about research at that time.

Dr. Sandy Newes 16:32

Yeah. So I imagine you all must have also just hit it off on a personal level, too. I mean, to commit.

Annie Mithoefer 16:37

To its. 20 Plus. They’re a match made in heaven. Working together, they both have the same kind of energy.

Michael Mithoefer 16:43

And although Rick’s got more of it, but he’s younger.

Annie Mithoefer 16:46

And and they’re both they need somebody to ground them, which I do. And that’s where Rick’s Rick’s wife Lyn grants him so well.

Michael Mithoefer 16:55

Rick has always said we have a similar risk tolerance.

Annie Mithoefer 16:58

So there you go.

Michael Mithoefer 16:59

That we work together pretty well. And, you know, we’re really, really good friends now. And it’s.

Dr. Sandy Newes 17:05

So I would love to hear what you have to offer about that. Your role. Like you know, how you show up.

Annie Mithoefer 17:09

Well, yeah. You know, I love working with the patients. And really, I think Michael and I both love this, but we love processing things with people. And getting into, like, you know, what is the cause of this? Or, you know, really processing deep processing.

So I loved working that way with people. So, you know, if I knew now what, how long it had taken and how much work it was, I don’t know that I would have done it. You realize.

Dr. Sandy Newes 17:45

That you were, like, signing on for a lifetime mission because it really.

Annie Mithoefer 17:48

Has. It really has been. Yeah, but it’s all been worth it for the patients, you know, because the people we saw, you know, we could get we could help people get better. But when we got to work with people with MDMA, yeah, it was a lot different seeing people really heal quickly. Yeah.

Dr. Sandy Newes 18:12

So you saw some things in breathwork. You saw that there was utility in combining that with a therapeutic approach for PTSD and then enter MDMA. And you saw all that come together. Yeah. In a different.

Annie Mithoefer 18:24

Way. Right. And we had to learn how to be researchers. Right. Because there was MAPS really wasn’t.

We were the team. There were people from MAPS.

Michael Mithoefer 18:33

There were five of us at that time. Me, Andy, Rick, Ilsa and Valerie. Maybe. Yeah.

Annie Mithoefer 18:39

And so.

Dr. Sandy Newes 18:40

Five of you. And now it’s.

Annie Mithoefer 18:41

Just like I had to do all the learn how to do the charting and everything. So it was all new there. There was an element of, like, in the beginning, you know, we got a lot of scrutiny in Charleston and that, you know, I still have a little bit of PTSD about that, just like bringing something into Charleston and the critics and what people were saying, you know, there were newspaper articles and things. So what are.

Dr. Sandy Newes 19:12

Approximately what time frame?

Annie Mithoefer 19:13

That was when we were first getting approval.

Dr. Sandy Newes 19:15

So that would have been 2001.

Annie Mithoefer 19:18

Yeah. 2001. And, you know, but then we got through that, you know, we got through that. But what did they say?

Dr. Sandy Newes 19:25

Like. And how was that for you? I mean, were you like picking up newspapers and being like, oh my God. Yeah.

Annie Mithoefer 19:29

Yeah. They, they had a newspaper article that we didn’t talk to the person that was writing the the article ahead of time, he said. Doctor Mithoefer is giving MDMA to his patients.

Michael Mithoefer 19:43

Front page MDMA is is an illegal drug, yet Doctor Mithoefer gives it to his patients every day.

Dr. Sandy Newes 19:50

Every day you’re like, oh no. And you know.

Annie Mithoefer 19:53

We had patients who are like, you know, 70 years old that would come to the office with their Bible. And, you know, regular patients. And they’re like, my friends just said that you were doing this, you know. Yeah. So, you know, there was a lot of a lot of that kind of attitude. I mean, what would you do?

Dr. Sandy Newes 20:12

Would you just be like, actually, that’s just false, or did you try to call a lawyer or.

Michael Mithoefer 20:16

Like usually they said, but but it must be okay because you know. Yeah, they’re a good guy. I, we.

Annie Mithoefer 20:22

Got called a lawyer and got that retracted. Yeah. Of course, there were.

Michael Mithoefer 20:25

Some ways in which I figured we must be on the right track because we’re causing a lot of consternation. But. But yeah, that was a mistake. We’ve learned a lot about the media hopefully since then, but that was a Charleston reporter. I kept refusing to talk to him because we just wanted we don’t want a lot of publicity. We want to get the data. Leave us alone. But yeah, that wasn’t working. But the first article. Oh, sorry.

Dr. Sandy Newes 20:46

Just a moment of, like, what you just said. Like our patients, like, knew. You know, they knew we were a good guy. They liked us. That really speaks a lot about you as clinicians, right? That here’s your patients. Like getting all of this. Like, first of all that they’re like, sure breathwork and what we’re combining that and then you get they get all this and they’re still like oh okay, well we trust you. You must have done an extraordinary job of developing trust, which is such a big part of this work. Yeah. Like so I just want to recognize that.

Annie Mithoefer 21:15

Thank you. Well thank you, Sandy.

Michael Mithoefer 21:16

One of my favorite experiences at the local hardware store, which, you know, we’ve been going to for about 35 or 40 years by that really great hardware store. And the after the paper, the paper, the thing came out. Then we got the lawyer and they put a retraction in. So I walk into the hardware store and the owner says, geez, doc, I saw they published a retraction, but that was lame. The article was on the front page.

They put the retraction on the back on Friday. So even the hardware store guy was supporting it.

Dr. Sandy Newes 21:48

So, see, I mean, people are like, go you. So you had already like, earned people’s trust. Yeah. You know, developed support. And you know, I just appreciate that and recognize that that just being a critical part of the process.

Annie Mithoefer 22:01

Well, thanks. Yeah.

Michael Mithoefer 22:02

Yeah. Being reasonable helps, you know. Right. Yeah.

Dr. Sandy Newes 22:07

Yeah. So you’re in Charleston. All this stuff like you are a team. You’re writing this trial or you’re submitting for the first trial. And it was just a team of five.

It was like the two of you and Rick and two other people. Yeah.

Michael Mithoefer 22:22

At the site, it was just us.

Annie Mithoefer 22:24

Yeah. Yeah. Well, we had a psychologist in town that we worked with.

Michael Mithoefer 22:29

They did the testing.

Annie Mithoefer 22:29

They did all the testing. We did? Yeah.

Michael Mithoefer 22:31

We called people with the appointments, we did the screening, we did all the paperwork. We cooked the food, we did wash the sheets.

Annie Mithoefer 22:38

We picked them up at the airport.

Michael Mithoefer 22:41

There was nobody else to do anything.

Annie Mithoefer 22:43

Big thing. Yeah. And I think, you know, doing breathwork for years. That’s what taught us, like when you’re taking care of people in those states, you really when you’re doing therapy with people, you’re taking care of them. So it was like something we’d learned from breathwork.

Dr. Sandy Newes 23:02

Well, and I think that’s just one of the things that’s important for people to know. Like, there really is a fundamental difference between a 6 or 8 hour session and a one hour session. The level of like care and right, you know, kind of the the importance to be present with the person, with the client in that it’s just different.

Annie Mithoefer 23:21

It is different.

Dr. Sandy Newes 23:22

Sessions are different. And I know that’s been one of the criticisms that leverage, like, what are you all doing? And we’ll get to that. But just, you know, like that level of care being primary. But yeah, which is really, you know, a part of Ben, part of psychotherapy from the beginning. I mean, that’s unconditional positive regard. Like, you know, humanistic psychology, people say like, oh, that’s not a that’s not a thing. Well, it is a thing. It’s been a part of therapeutic process forever. Yeah. And any sort of human relations, the caring piece, the showing up piece, the being able to be present.

Michael Mithoefer 23:55

And the innate capacity to heal. Yeah. Hippocrates said the physician treats, nature heals. I mean, it’s not new, right? No one’s ever claimed physicians are healing people, right? We’re just creating favorable conditions, right.

Dr. Sandy Newes 24:09

Creating the optimal conditions for healing and then moving that forward using established methods and interventions and techniques that have been looked at in a variety of different domains. That seems when you put it that way, it seems to make perfect sense. Yeah.

Michael Mithoefer 24:23

So yeah, it seems very dramatically new because their psychedelic medicines evolved. But. Yeah, as you say, it’s.

Annie Mithoefer 24:31

Well and the.

Michael Mithoefer 24:32

Rogers was talking about this. Many, many people have talked about this.

Dr. Sandy Newes 24:36

Great, great. You know, man’s search for meaning Viktor Frankl. Right. You know.

I mean, I’ve seen the opposite, but really, you know, like people accessing their own inner wisdom and their own inner healing is not a new concept. Yeah. No.

Annie Mithoefer 24:52

So it’s an old. Yeah. Very old concept. Yeah.

Dr. Sandy Newes 24:56

Yeah. So okay, so at this point we’re up to the early 2000. You’re submitting, you’re running the trials, you’re learning research methodology. You know, I was trained as a psychotherapy outcome research methodology, you know, in methodology to apply to outdoor based therapeutic programming, which doesn’t sound like it is the same, but it it is actually like a very similar and parallel.

Annie Mithoefer 25:18

Yeah.

Dr. Sandy Newes 25:18

Like, you know, longer sessions and different types of things. And the reason I’m bringing that up is just the recognition of the difficult, like how incredibly difficult it is to write up and develop and fund and run in a way that is actually scientifically valid. Clinical trials like that’s a monumental undertaking. And I don’t think people realize, like, you don’t just like, you know, do some therapy and, you know, write some notes. Not good.

Annie Mithoefer 25:45

Especially when you’re doing it for the FDA. Right? Exactly. Yeah. So which is.

Dr. Sandy Newes 25:51

An interesting question. So when did the FDA enter into this discussion with you all? Because I don’t know. Again, that’s another thing I don’t think people realize is that the FDA, my understanding and, you know, based on our conversations too, that the FDA has really been a partner at every step of this along the way. Right, right. So it’s not.

Annie Mithoefer 26:08

Like they had to get the protocol approved by the FDA. Yeah. And we had to get approval from the IRB. Yeah. Which also took a long time. And we don’t have time to go into that. And the DEA, which also took a long time, which we don’t have time to go into. But there were a lot of obstacles, a lot of obstacles.

Michael Mithoefer 26:29

But yeah, the FDA, we submitted our first application October 1st, 2001. Yeah, about 28 days later, they emailed and said, we want a phone call. Rick and I had a phone call with them and we discussed different things like, well, maybe you should only treat people that have taken MDMA. No, we don’t think that’s a good idea. Okay. You need to do the blood pressure every 15 minutes. We don’t think we do. Yes you do. Okay. You know. Yeah. We did some horse trading and worked out any concerns. And it was approved. They said, okay, write it down, fax it to us. You’re ready to go. Took another two and a half years for the DEA and the IRB and they said but yeah, so but yeah, we’ve been talking we’ve been exchanging documents and having both online and in person meetings with FDA since November of 2001. We’ve had a lot of them. Right. And they’ve been, you know, partners may not be quite the right word, but we’ve been moving forward with them every step of the way. They review things we get, we make agreements, they tell us what we can do next. They know that. That’s one reason I’m still somewhat hopeful they may approve, despite the Adcom, the advisory committee, because the advisory committee did not understand our research well at all. FDA understands it intimately, and they’ve got all the raw data. They analyze it themselves. They don’t care what our analysis is. They just they make their own conclusions.

Annie Mithoefer 27:58

They analyze it themselves.

Dr. Sandy Newes 27:59

I did not know that. Oh, interesting.

Michael Mithoefer 28:01

They don’t care what you’ve published or anything. Just give us the raw data. And then they’ve been to the sites and spent weeks inspecting the original raw data records to make sure everything matches so they know.

Annie Mithoefer 28:14

So much back up to the the studies just because there there were some criticisms about the safety, this and that. The vital signs. Like Michael said, we had to do vital signs every 15 minutes, sometimes every five minutes, depending on what blood pressure was happening, what pulse. In the first study we had an ER doctor and an ER nurse in the front room of the office for every person, for every for every session. I mean, not every not integration sessions, they never had to do anything. We never had to call them for anything.

Dr. Sandy Newes 28:50

So let me, let me put a little context to what you’re saying. Okay. So just recently there was just a consensus statement of experts. You know, you all are obviously like the experts, but I would imagine you couldn’t be on such a thing because of bias and things like that. But where they they named basically, they said there’s urgency. There’s this is why they need to look at it. And then we can talk about some of the methodology. There’s urgency. We’ve got 13 million people suffering in the US with PTSD. We’ve got 17 veterans a day that are committing suicide. This is timely. This is urgent. This is efficacy. Like we’ve got multiple rounds of studies that are showing consistent results at fairly unprecedented levels. And then there’s the safety, which is what you’re talking about. And what I’m hearing you saying is that there was safety from the very beginning, like the safety data has been gathered. The FDA is aware of it.

Annie Mithoefer 29:40

Yeah. And then we got to a point in phase three where they only had to take the blood pressure at the beginning, at the beginning of the supplemental dose. And at the end of the day, unless something was going on for someone. So it took us years.

Michael Mithoefer 29:57

We got seven, six studies to walk it back from every 15 minutes and, and two physicians and two nurses to not needing that stuff. But we didn’t just decide that. We very methodically went through one day after each time we discuss it with the FDA and they’d say, okay, we agree you can do the blood pressure less often. You’ve got a track record, it’s not necessary. So we very intentionally and carefully figured out what level of medical support was needed. And we started with a very, very conservative level. So it wasn’t just a Cavalier not needing to measure.

Dr. Sandy Newes 30:33

So like every hour. Well, how often did you have to check the blood pressure?

Michael Mithoefer 30:36

Every 15 minutes for four hours? For four hours, then every 30 minutes for for the rest of the time, right. Except if it got above certain levels which were not all that high.

Annie Mithoefer 30:47

160 over 110.

Michael Mithoefer 30:49

So it was. Very conservative.

Dr. Sandy Newes 30:52

Right. Well, I can validate having just seen videos, having just gone through the training like, you know, there would be this like dance, right, where somebody would just be like gently putting on the blood pressure cuff and there’s a clock over there. Sometimes it would ding and then they’d go get it. And you know that in and of itself, like, how do you work that into the therapeutic process without that being invasive.

Annie Mithoefer 31:13

Right. We wouldn’t mind it.

Michael Mithoefer 31:14

Yeah, we were concerned about that. But actually, if if people had any reaction, it was more like, I’m sorry, you have to go to so much trouble to do this. This seems like a hassle. No.

Annie Mithoefer 31:27

No. They would also be like, I’m glad you’re keeping me safe. Totally. Yeah. Oh, yeah. Yeah. That’s something. Somebody watching? What’s going on? Yeah. Yeah.

Dr. Sandy Newes 31:36

No, I mean, that feels good. Like, you know, I do ketamine assisted psychotherapy, and the patients love, you know? Yeah. We’re like being medically cared for. That helps people drop in. Yeah. So what I’m hearing you saying is, in the beginning, it was like, literally every 15 minutes for the first four hours, this would obviously be tracked. You would have had data tracking methods. Those would have gone to the FDA. The FDA is looking at it independently. Right. And so over time.

Michael Mithoefer 32:00

We had tapes from the blood pressure machine so we could prove it. And the FDA received all that information.

Annie Mithoefer 32:06

Yeah. Yeah.

Dr. Sandy Newes 32:07

Yeah. So I imagine and I want to revisit these three points, but I imagine, you know, like for me kind of watching that having like very literally just gone through this training, it was like, oof. And like I said in the beginning, I thought about you all immediately, and I thought about Marcel and Bruce, who I’d just spent time with. And just like, I mean, obviously there’s like, there’s going to be a part that wants to kind of like talk about the methodology and we’ll get there. But like, what was that like for you on a personal level, having like devoted so much like mission, it’s a mission. It’s a 20 year mission, right? Yeah. You know, it’s not just work I’m hearing. It’s life. It’s relationships, it’s community. It’s learning, it’s commitment. And and then to just be like, oh.

Annie Mithoefer 32:51

Well, I started out being really proud. Yeah. Of MAPS of Lagos, of Beara and then and, and I then I started listening to the public. Well, and then I realized that Barra didn’t get time to answer the questions and I was starting to, wow, that’s too bad. And then started listening to the public comments.

And yeah, it it made me sad. Yeah, it made me sad that it. Yeah there were, there were some people that were harmed. And the thing I think that wasn’t named was clinical research can be harmful for people. Oh yeah. So putting people through like our phase two studies, people could cross over. In the beginning, we didn’t have approval for people to cross over for the first five patients. Because means what crossover means that they can get MDMA after they go through the placebo. Okay. Okay.

Dr. Sandy Newes 33:55

Which, by the way, you know, for anybody who’s not familiar like that is state of the art psychotherapy outcome research methodology. You don’t have a waitlist control. You have a placebo group that gets exactly the equivalent treatment. And then you’ve got the experimental group and then the opportunity later. If the placebo group wants to get the experimental treatment, that is like the highest level that I was taught.

Annie Mithoefer 34:20

And the placebo group is the therapy only group because they were getting therapy during that time. Yeah. So in the beginning, we could not let the first five patients cross over and get MDMA because the FDA said we don’t have enough evidence that that should happen. So after the first five and think about those first five people, they’re going through this study, you know, they are they come in and it’s their last chance. They think, yeah, I’m on the it’s the end of the line for me.

Dr. Sandy Newes 34:56

Can you say more.

Annie Mithoefer 34:56

Like just yeah I. Mean there was one man, one man that said the only thing that was keeping him alive were his two cats. And when they died, he was going to commit suicide, you know, and he year old cat, and they were old cats, and he was in that first group and he had tremendous PTSD. But he also had really, really bad depression. Yeah. And so we had to wait till we got all five, and then we got approval for those to cross over. Well, then from then on in phase two, people could cross over. They could go through the placebo part, and then they could immediately cross over if they wanted to. Or they could wait a month and cross over. Okay. And do the study all over again with interesting MDMA in phase three. We didn’t. The FDA wouldn’t let us do that. They said we want to have everybody go through. So the first phase three study there were 90 participants because of Covid. There were only 90. Yeah. But all 90 people had to go through before those people could cross over. And so like if you’re number one, you know it’s going to be three years is a while.

Dr. Sandy Newes 36:11

I mean, it was a long time, right? Yeah.

Annie Mithoefer 36:13

Yeah. Yeah. And people people were suicidal. I mean, when they realized, you know. I didn’t get it. Yeah. You know, they they’d heard. And that’s the other thing. They’d heard so much about the people that had been helped by it. So, you know that. So getting harmed and and then some people that took things out of context said things about our therapy approach. Yeah, it saddened me. I think that’s anger, but mostly sad for the patients, for the participants that went through our study because they wanted to get help, but also they knew this might help other people with PTSD. So that’s something.

Dr. Sandy Newes 36:58

You mentioned just in conversation, that that what you saw was people just really wanting participants, like feeling really good about the fact that they were participating in something that had the potential to be helpful for others.

Michael Mithoefer 37:10

Yeah, and so many of the veterans told us, well, I feel kind of guilty that when I talk to other veterans because I’ve had this opportunity and they’re still suffering, but at least they’re saying, well, they’re glad to know there’s something out there. There might be a possibility for them in the future. So they were not only the people that were in the study. There were many, many people tracking this because they really were hoping for themselves. So the number of people that were sad about it or disappointed was pretty large. So I was sad and I was angry, and also in a peculiar way, it felt very familiar because this is how it was all the time for the first ten years. Sure, here we misunderstood what we were doing. They accused us of this, that and the other thing. It feels more like that’s what it was always like. And then, you know, once we began to get good data, suddenly everything was, you know, sweetness and light, and the media was talking about it as a serious possibility for treatment. That’s true. And now we’re kind of falling back. And I think, Sandy, I think you put your finger on part of it when you discuss this was a very good design for psychedelic psychotherapy research. But there’s massive confusion because this is drug development research, according to the FDA. The FDA knows a great deal about drug development research and almost nothing about psychotherapy research. Right.

Dr. Sandy Newes 38:38

Well, and I think that’s to me, that’s the crux of the matter. And, you know, when when I went through the training, you know, we to me, I was at a trauma training. I was not at an MDMA training. I was at a, you know, medication assisted psychotherapy training. Right. And I think that’s, you know, that that’s a fundamental difference like that people don’t really understand. You know, I work with ketamine and ketamine and ketamine assisted psychotherapy are completely different, like the medicine is a tool, but the therapy is really the overlay. And so it seems like what people don’t really get is that the FDA is just generally doesn’t have protocols in place, you know, to do psychotherapy outcome research with drugs. And so, you know, seemed to me like the review panel was coming from the drug side. Yeah. 

And that makes sense. You know, like that’s what they do. But there are different methodological considerations. Yeah.

Michael Mithoefer 39:35

Well, and the FDA does understand now I think after these 20 plus years that therapy is important here. I think they understand that they even I even made a video for them from the sessions to watch. They’ve seen the therapy. Yeah. But they don’t it’s not their bailiwick. They’re not going to regulate that. And they don’t you know, they don’t have in-depth capacity in that way. But they do understand it. But I think the adcom did not understand it. Yeah. And I think part of that is this difference. It’s never happened before. A real psychotherapy drug combination going through FDA. It just hasn’t happened.

Annie Mithoefer 40:15

There hasn’t been a path for that either. There isn’t a path for that.

Michael Mithoefer 40:19

It’s confusing to people. I mean, the adcom, I’m sure there are. There are good people doing their job as best they can.

Dr. Sandy Newes 40:25

I mean, it’s their job to rule out all. I mean, that’s the scientific method, right? Rule out all alternative hypothesis for the data. And that’s what they were doing. Like, you know, it’s just that it seemed like there were other considerations that they weren’t taking into account.

Annie Mithoefer 40:39

Yeah, yeah, yeah.

Michael Mithoefer 40:41

Some serious ones. And I think, frankly, I think one reason this, you know, initially this was threatening to people because it was these dangerous drugs they thought people got over that they saw it’s going to be serious treatment. But now I think it’s actually threatening to the way people have been practicing medicine and psychology. Oh for sure. So I think that’s part of it. There’s a lot of confusion because, you know, when you start talking about we don’t know how to heal people. We need we want to support them in their own innate capacity to heal. That’s just 180 degrees from the way most people are trained. We’re the experts. We know how to. We have this form of therapy. This is the protocol. This is how you do it. And or we have this medicine and we’re giving people a medicine and we’ll see what the medicine does. It’s just an entirely different model. If we really pay attention to what people are reporting from these sessions. They’re describing a whole different approach to human healing that’s so much deeper and richer than the mental health system or is doing for the most part. There are notable exceptions. Yeah. And.

Annie Mithoefer 42:09

Well, and the way psychiatry has, has been for the last, what, 20 years? Yeah. Yeah. It I mean, it’s been concentrating on getting rid of symptoms with medicines and not looking at the underlying cause.

Dr. Sandy Newes 42:27

Well, and I think one of the things I think is so interesting, like, you know, the VA has bought into prolonged exposure because that’s what they have the best data on. And, you know, the neurobiological approaches to working with trauma, people with somatic people would say, well, they’re just putting them into dissociation. That’s a separate conversation. But, you know, what I’ve wondered about is, like you’re saying like they’re like, oh, you know, it’s it’s going against what they’ve been doing, but really it’s not. To me, it’s like a both and it’s just like an evolution of the field. Like there are some elements, what I saw in videos and what I understand when you know, when the events emerge. There are some elements that have some parallels to exposure therapy. Sure, this is done in a different way. It’s not like, okay, we’re going to talk about doing it, and now we’re doing suds. And you know, where are you right now? And, you know, kind of moving and pushing in that direction. It’s that inner wisdom allowing that to naturally emerge when it does and then working with it.

Annie Mithoefer 43:21

Correct. Yeah. Good point.

Dr. Sandy Newes 43:22

I mean, is that so to me it’s like what about the both and, you know, perspective on the scientific method. Like to me this is an evolution of the science.

Annie Mithoefer 43:32

Oh I agree.

Dr. Sandy Newes 43:32

You know like it’s it’s actually building on what has come before in the therapeutic model that you all developed.

Michael Mithoefer 43:39

Yeah. And I think that. Yeah. And actually I wrote a paper for the math bullet in 2013 about this. Seems strange, but look at all the things that are elements of other therapies that come up spontaneously in the MDMA sessions. Imaginal exposure does happen. Yeah. Cognitive to recognizing and correcting cognitive distortions does happen. Transference does happen. You know, psychodynamic things do happen. Somatic things do happen. People become aware of parts. All these elements of these other therapies tend to manifest spontaneously. So the difference is not that I mean, they’re all tapping into the same thing. Like you say, the difference is the role of the therapist. I think, yeah, that people get uncomfortable because it’s much less prescriptive about what they need to do.

Dr. Sandy Newes 44:31

And yet again, from my psychotherapy outcome research training, like Manualized protocols, are protocols that have a manual that guides it. It’s not scripted, right?

Annie Mithoefer 44:45

You know, you don’t have to do it. Exactly. I mean, you do it, but you don’t have to do it exactly how it says, because.

Dr. Sandy Newes 44:52

That’s not realistic. Like that’s not real work. Right? Like what I was taught is if really, you know, the therapeutic relationship is the primary determinant of outcome. And that’s been found over and over and over again like that. That is the primary determinant of outcome. Then you have to put the relationship first and then draw from the techniques and the skills and relational fashion, which is what it seems like you all have done repeatedly.

Michael Mithoefer 45:16

And that confuses the hell out of people if they’re thinking of it as a drug development process, you know? Yeah, yeah.

Outro 45:30

Thanks for listening to Living Medicine. Be sure to check out part two of this interview in a subsequent episode. Thanks for listening to Living Medicine. We’ll see you again next time. Be sure to click subscribe to get future episodes.