Short Wave - Psychedelic Treatment For PTSD Faces Misconduct Hurdle

Episode Date: June 3, 2024

People with post-traumatic stress disorder (PTSD) may soon have a new treatment option: MDMA, the chemical found in ecstasy. In August, the Food and Drug Administration plans to decide whether MDMA-assisted therapy for PTSD will be approved for market based on years of research. But serious allegations of research misconduct may derail the approval timeline. NPR science reporter Will Stone talks to host Emily Kwong about the clinical trials on MDMA-assisted therapy research and a recent report questioning the validity of the results. Read Will's full story here. See pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. Hey, shortwavers, Emily Kwong here with NPR science reporter Will Stone, who's been reporting on the use of psychedelics for therapy. And just a heads up, we do mention suicide and suicidal thoughts in this story. Well, welcome. Let's get into this reporting. What do you got? Hey, Emily, I'm here to talk about MDMA. That's the chemical found in ecstasy, sometimes called Molly.

Researchers have been studying MDMA as a potential. therapy for post-traumatic stress disorder, PTSD. Okay. And in August, the FDA is expected to decide whether it can be used as a treatment option outside of clinical research, meaning it would be available to many more people. This would be a big development. It would. FDA approval would be actually an enormous milestone for the movement to bring psychedelics

into the mainstream of mental health care. Wow. But recent allegations have sparked controversy over the results from one of the clinical trials, which could upset the final stretch in the drug's path to market. So today on the show, how the government is moving toward a decision about psychedelics and mental health care. And how a recent report questions the data the FDA is using to make that decision. You are listening to Shortwave, the science podcast from NPR. Okay, well, before we dive into some of the controversy, let's just talk about where we are at with psychedelics research.

How does this decision fit into all of that? So this upcoming decision by the FDA will be kind of like a test case for psychedelics. After all, there's been just an explosion of interest in these drugs and their potential for mental health. Yeah, we've been hearing about clinical studies for a while now. Researchers looking at psilocybin at LSD as treatments. That's right, Emily. And it turns out actually MDMA is further along in the regulatory process than those drugs because of decades of work involving MDMA system. therapy. Okay, what is that? Like, in MDAMA assisted therapy, do they just give people the drugs and see what happens?

Not quite. It's actually a pretty detailed protocol in which the drug is given under the supervision of two therapists. And there are several what they call dosing sessions when the person gets the drug. There are also several follow-up sessions to help people process their experiences while on the drug. Okay. So last year, results from a phase three clinical trial where published by Nature Medicine. The research was funded by the drug company Lycos Therapeutics, and it was conducted by an international consortium of scientists. Okay. And what did these clinical trials find? So in one of the trials, about 71 percent of participants who took MDMA no longer met the diagnostic criteria for PTSD when they were assessed after the treatment. Basically, that means, Emily, by clinical standards, they did not have PTSD anymore. Wow. And by comparison,

that number was 48% for the control group. So those are people who underwent the same therapy but took a placebo instead of MDMA. There needs to be more long-term data. But overall, this type of finding suggests this could be a meaningful, a potentially powerful new treatment for PTSD. Many people do not get that kind of relief from other treatments. Yeah, I mean, Will, you have been reporting on this for a few years now. Have you talked to anyone recently who's tried this treatment? I have. Some people have described it as absolutely transformational. One of them is Casey Tylek. He's a military veteran who is in the phase three trials. Casey was actually in the control group, but he did have the opportunity to do the MDMA treatment after the study. We left Iraq in 2009. We were not a small unit, and there are a lot of my friends who have killed themselves. And I really do feel this would work. It's not going to work for everybody. But I think that it's going to be one of the most effective.

of tools moving forward, and it will save lives. I know for a fact that it saved mine. Well, that's as personal as it gets when you talk about like someone's relationship to a treatment, you know? It is. And there are many examples you'll find in the media, public accounts from people who say similar things. Well, so every medical treatment comes with risks. That's important for us to talk about as a science podcast. What are some of the downsides for MDMA assisted therapy? the trials did document a variety of what are called adverse events. This ranges from nausea and anxiety to heart palpitations, but overall, the treatment was considered generally well tolerated. And in the trials, the authors do acknowledge that consistent with PTSD, there was some suicidal ideation in both groups, but there was no increase in adverse events related to suicidality in the MDMA group. All right. So that's the recap of these phase three clinical trials.

what they revealed. Earlier, you alluded, though, to some controversy, like a report questioning the trials and how that may hinder FDA approval of using MDMA as a therapy. So what are the concerns? Right. The report came from a nonprofit called the Institute for Clinical and Economic Review. This is an independent group that looks at the evidence and analyzes whether different treatments appear to be safe and effective. And they try to put numbers on on how much treatment should cost. And their work can also help health insurers, make decisions about coverage. So this institute decided to do a deep dive into the MDMA research.

They came out with a very skeptical report about the strength of the data. And just to boil it down, Emily, the conclusion was there were, quote, substantial concerns about the validity of the results of the MDMA clinical trials. Okay, concerns about the validity of the results. What were some of the accusations? Yeah, so I'll just begin by saying there's a lot here. But broadly speaking, I would say there are two veins of criticism. And the first is about the study design, the methods. For example, when you do clinical trials, it's really important to try and make sure people don't actually know if they got

the experimental treatment or a placebo. Right. Of course, that is pretty hard with psychedelics. People tend to figure out if they were taking a strong drug like MDMA or psilocybin. In the MDMA trials, most of those who got the drug could tell this was not a placebo. So like the participants could have reported feeling better because they were like, aha, I knew I had MDMA. Exactly. The report also raises concerns about the method used to assess PTSD that it may have shown improvements and symptoms related to the specific trauma that they were. focused on in the therapy, but maybe it did not capture the fact that people were actually in worse shape overall. So I would say, you know, those issues fall into one bucket of concerns outlined in the report. Okay, so those are all having kind of to do with methodology. What was

the other bucket of concerns? So the other, Emily, was much more inflammatory. The report brings up the possibility that, quote, very strong prior beliefs among therapists, investigators, and patients could have influenced the results. It points out that the therapist involved in the trials, and in some cases the patients, too, came from the psychedelic community and already had beliefs about the treatment. Here's Dr. David Rend.

He is the Institute's chief medical officer. Patients may have been pushed to report positive outcomes and pushed away from reporting negative outcomes. Huh. Okay. By patients, I'm like, who is saying all of this? So the report did not name its sources. But David says it included a small number of people, including a therapist from the trials, and some of those involved in a New York Magazine podcast about psychedelics.

That podcast was called Cover Story, and it brought to light video evidence of two therapists with a trial participant. She was under the influence of MDMA in a session and described the therapist is having inappropriate contact with her. And in the video, you can see them in the bed with her. pressed up against her, kind of spooning. I will say this was back in the phase two trials. The podcast did also feature two people who said they were in the phase three trials, the ones we've been talking about. They were administered MDMA and they said they experienced feelings of suicidality and other distress after the studies. And they felt that that wasn't really captured in the data. Here is David again from the Institute. You have a group of people who are very upset about

how these trials went. We couldn't tell, even though we talked with people where this happened, whether that represents a tiny fraction of bad events or a number of bad events large enough to have rendered the trial, just not believable. Those are some really serious allegations. Okay, so what is the response been? Like, what are the groups that are pushing this drug forward that are now under fire? So first, you have the nonprofit that pioneered this research. It's called the Multidisciplinary Association for Psychedelic Studies. It's also known as MAPS. Then you have the drug company that was incubated by MAPS, which is known as Likos Therapeutics. Lycos sponsored the clinical trials and is the company seeking FDA approval to market the drug. Right, right. Okay. So what does MAPS say?

So in a statement, a MAP said it remains fully supportive of comprehensive, high-quality research, careful analysis of safety and efficacy, and stringent regulatory oversight of any psychedelic-assisted therapy or research or delivery. They also disputed some of the most troubling allegations that came up in a petition to the FDA, which I'll get to in a bit. Okay. And what about the drug company? How did they respond? A statement from Lycos made it clear that the company stands behind the results of its clinical trials. I spoke to Willa Hall, who was a clinical psychologist in the phase three trials. She rejected the claims that bias influenced their results. I saw nothing like that. I only saw professionalism. So Willa,

and more than 70 of her colleagues have published a detailed response to the Institute's report, questioning the reliability of its sources and saying it misrepresented aspects of the trial. I think a lot of us were sort of shocked at sort of the gossipy, kind of hearsay nature of the report. We are all therapists that are invested in finding new tools to help our patients. That is true. But we also want to do it safely. Willa told me therapists meticulously detailed any adverse events. Sessions were recorded.

and to protect against bias, data from participants about their PTSD symptoms were collected online by people who did not know whether the person had taken MDMA or a placebo. I also spoke with Jennifer Mitchell at the University of California, San Francisco. She was the lead author of the published findings from the trials. I didn't feel any pressure from the sponsor to come up with anything different than what the data was providing. I didn't feel that at all and wouldn't have continued to work with them if I had felt that. Jennifer did acknowledge she doesn't know what happened every day at each trial site around the world, but she points out the FDA is closely involved in the trials and has access to all the data.

Well, okay, so this is where we're at right now. You have the FDA wing LICO's application for MDMA-assisted therapy with conflicting views on the quality of their data. So what's next? So what's next is that tomorrow a panel of advisors will discuss the data. And then there will be an opportunity for public comment for an hour and 40 minutes. Spicy? That is a lot of public comment. Uh-huh.

And one of the people I expect will speak up is Nishay Devano. She's a lecturer in the writing program at Johns Hopkins and study psychedelics. She and a group of others who've been involved in the psychedelic field over the years actually petition the FDA to hold this public meeting. And they point to the report I was talking about. And they brought up even more troubling. allegations. They say it's possible the data was manipulated that certain adverse events may have been overlooked or not reported. And to back this up, they cite an anonymous former employee of Lycos. Here's why Nushe felt like she needed to speak up. Because I think that there is a lot of potential

for MDMA, but I think that the research has to be done properly or else the rollout could harm a lot of people potentially. Okay. Well, I mean, where? I mean, where? is the rollout right now with this drug? So the FDA has actually fast-track the drug application and says it plans to make a decision by early August. Now, a spokesperson for LICO said to me, they fully support holding the public hearing. And I would just say overall, Emily, this is building up to be a pretty high profile moment for the psychedelic movement. There is a lot of money riding on this treatment and the possibility of approval. And if that is derailed, it will mean that those living with PTSD who want a new treatment, we'll have to keep waiting.

Well, we will keep an eye on how it goes. Thank you for bringing us this reporting, Willstone, from NPR Science Desk. Thank you. This episode was produced by Burley McCoy. It was edited by Amina Khan and fact-checked by Will. Josh Newell was the audio engineer. I am Emily Kwong. Thank you for listening to Shorewave from NPR.