FDA has been taking a look at psychedelics as a potential treatment for psychiatric and substance abuse disorders, recently publishing a final guidance for drug sponsors conducting clinical trials of psychedelics, including psilocybin, LSD, and MDMA.
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“This is of interest to psycho-oncologists that have been looking into this question for at least two decades around cancer-related anxiety, depression, and PTSD,” said Sara Willa Ernst, a reporter with The Cancer Letter. “Could psilocybin specifically be a treatment to help cancer patients and cancer survivors deal with psychological distress that comes from a cancer diagnosis?”
However, regulatory challenges emerge when FDA is tasked with evaluating a treatment that may (or may not) rely on both a drug and a psychotherapy component to improve outcomes. In this episode of The Cancer Letter Podcast, Sara and Paul Goldberg, editor and publisher of The Cancer Letter, discuss the tricky regulatory landscape facing psycho-oncologists.
“FDA does not regulate psychotherapy,” Sara said. “I think a lot of the sources, the clinical trialists I talked to said, admittedly, ‘This is kind of a weird space for FDA to approve or not approve.’”
But psycho-oncology experts with experience administering psychedelic therapy are almost uniformly convinced that the psychotherapy component is critical to the treatment’s efficacy. Most of Sara’s sources ended up “echoing the same thing—that the psychotherapy component is very crucial,” she said.
While FDA is staying in its lane and remaining agnostic to a question for which there is not yet satisfying data, Sara said her sources are concerned about what that might mean for the development of the field.
“FDA has opened the door—at least in the final guidance—to applications that kind of de-emphasize the psychotherapy aspect. So, that might be a whole lot cheaper for a pharmaceutical company that is trying to bring a drug to market to go in that direction as opposed to the real hefty lift of a factorial design trial [to demonstrate the role of psychotherapy],” Sara said.
“A lot of methodologists are having a lot of fun deciphering this,” Paul said. “How do you go forward with this? Could be very interesting.”
This episode is sponsored by the University of Kentucky Markey Cancer Center. Learn more at ukhealthcare.com/markey.
Stories mentioned in this podcast include:
- The Directors: Two leaders in data science have a warp speed vision for AI, with cancer clinical trials leading the way Knudsen and Thoelke
- FDA final guidance on psychedelics opens the door to psycho-oncology research
- OMB proposal to sideline peer review sparks widespread opposition
- Cancer progress is not reaching everyone. Native Nations must be part of the solution.
- The future of oncology: Early-career scientists need mentorship and a new academic model
This episode was transcribed using transcription services. It has been reviewed by our editorial staff, but the transcript may be imperfect.
The following is a transcript of this week’s In the Headlines, a weekly series on The Cancer Letter Podcast:
Jacquelyn Cobb: This week on The Cancer Letter Podcast…
Sara Willa Ernst: The FDA is looking at psychedelics as a potential treatment for anxiety and depression as well as substance abuse disorders. And this is of interest to psycho-oncologists that have been looking into this question for at least two decades around cancer-related anxiety, depression, and PTSD. Could psilocybin specifically be a treatment to help cancer patients and cancer survivors deal with psychological distress that comes from a cancer diagnosis?
Paul Goldberg: You’re listening to The Cancer Letter Podcast. The Cancer Letter is a weekly independent magazine covering oncology since 1973. I’m your host, Paul Goldberg, editor and publisher of The Cancer Letter.
Jacquelyn Cobb: And I’m your host, Jacquelyn Cobb, associate editor of The Cancer Letter. We’ll be bringing you the latest stories, groundbreaking research, and critical conversations shaping oncology.
Paul Goldberg: So let’s get going.
Sara Willa Ernst: Hey, Paul.
Paul Goldberg: Hi, Sara. How are you?
Sara Willa Ernst: I’m doing good. How are you?
Paul Goldberg: Great. Great. Now that the Canadian fires, the smog has passed, I think we’re both breathing a little easier, literally.
Sara Willa Ernst: Definitely. People might hear the little raspiness in my voice. It kind of got me for a few days kind of coughing up a lung, but I think we’re on the up and up.
Paul Goldberg: Well, I was thinking I could go biking, or I could just smoke some cigarettes. I’m almost a never-smoker, but maybe this is the time to start.
Sara Willa Ernst: Which one’s more tempting?
Paul Goldberg: Biking. But if it’s equivalent, you know.
Sara Willa Ernst: Well, I have this great image in my head of you just zooming down on a mountain bike with two cigarettes in both hands. Not the right place to be talking about this.
Paul Goldberg: No.
Sara Willa Ernst: But yeah, this is another episode of The Cancer Letter Podcast with Sara Willa Ernst and Paul Goldberg. And Jacquelyn is out today, but I think we are going to man the ship good. Why don’t we go through this week’s issue?
Paul Goldberg: Yeah. Let’s jump in.
Sara Willa Ernst: Yeah. So on the cover of last week’s issue, we had the directors. This was an amazing conversation that Paul had with Karen Knudsen, who is the CEO of the Parker Institute for Cancer Immunotherapy, and also Kent Thoelke, who’s the founder and CEO of Paradigm Health. And they were talking about artificial intelligence and what that’s going to mean for specifically clinical trial infrastructure. So if you want to listen more to that conversation, we got an entire podcast out that’s ready for y’all.
But other than that, the second story was a story that I wrote, a B story about an FDA guidance on psychedelics. And so this is kind of some follow-up coverage from a previous cover story a few weeks ago about psychedelics and how federal policy is changing around something that has really been kind of locked up and criminalized and ignored by the federal government for decades. Other than that, we had a story about what’s happening at OMB and some of the changes that they’re trying to make when it comes to research infrastructure.
Claire wrote that story, and it’s a big compilation of nearly 500,000 comments that the federal government received in response to some of the changes that they’re proposing. And so, if you want to read what ASCO has said, what AACR has said, what the National Breast Cancer Coalition has said, AACI, it’s all there, and it’ll give you a sense of really what people are thinking in response to the proposal.
We had one sponsored article, and we also had a guest editorial. The guest editorial was called Cancer Progress Is Not Reaching Everyone. Native Nations Must Be Part of the Solution. And the sponsored content, that article was The Future of Oncology: Early-Career Scientists Need Mentorship and a New Academic Model. So it is a chock-full issue, but I think we’re really going to just dive into the story that I wrote and Paul helped edit. And that one was about psychedelics specifically.
Paul Goldberg: All right, let’s do psychedelics.
Sara Willa Ernst: The FDA is looking at psychedelics as a potential treatment for anxiety and depression as well as substance abuse disorders. And this is of interest to psycho-oncologists that have been looking into this question for at least two decades around cancer-related anxiety, depression, and PTSD. Could psilocybin specifically be a treatment to help cancer patients and cancer survivors deal with just the kind of psychological distress that comes from a cancer diagnosis?
And so the final guidance came out and apparently was pretty similar to the draft guidance. And there were some thoughts by my sources and the people that I reached out to. I think the big thing was this question around the psychotherapy component that goes with psilocybin or other types of psychedelics. Usually it’s not just the drug, but there is this preparation session that you’ll have with a therapist and also an integration session to help you.
Paul Goldberg: Can I get in? Yeah. It’s kind of an interesting question of when you’re really dealing with drug approval, how do you work in issues such as talking therapy? I mean, when… do you require it? How do you require it? On what basis do you require it? How does it fall under the rubric of practice of medicine? How did that work out in the story?
Sara Willa Ernst: Yeah. I mean, FDA does not regulate psychotherapy. And I think a lot of the sources, the clinical trialists I talked to said, admittedly, this is kind of a weird space for FDA to approve or not approve. FDA responded to it in a way that I think generated some concern by the mostly academic sources that I talked to. They see that psychotherapy is a very crucial component. And if they were to hypothesize why this therapy… they’ve seen signs that this therapy works, it’s because it’s of this pairing of psilocybin plus psychotherapy.
Paul Goldberg: Actually, this would be a good spot to read some of the comments you got. What did your sources say?
Sara Willa Ernst: This is one of my favorite quotes in the story. It’s by Stacy Fischer, who works at the University of Colorado Cancer Center. And she said, “If you asked me to hypothesize mechanistically about how psilocybin works to improve psychological distress associated with a serious cancer diagnosis, I would say it’s the combination. The therapy works well because of a period of neuroplasticity, openness, and cognitive flexibility related to the psilocybin.” So she very much sees it as an important combination to maintain.
Paul Goldberg: Interesting. Interesting. Any other quotes? Anything else on the story?
Sara Willa Ernst: Yeah. I mean, Stacy Fischer wasn’t the only one trying to protect the psychotherapy component. Folks at UCSF, the Translational Psychedelic Research Program, they had sent some comments during the 2023 draft guidance. Also, Johns Hopkins University and the Ohio State University all kind of echoing the same thing that the psychotherapy component is very crucial, but FDA is a little bit more skeptical around it.
Paul Goldberg: Well, it’s their job, right. And they do regulate drugs, and psychotherapy is not a drug. I mean, psychiatric drugs are used, and they are used sometimes with talk therapy. So I just wonder how that works in psychiatry because they do. The agency does approve psychiatric drugs. So how does that work statistically?
Sara Willa Ernst: I think in a lot of ways this is untrekked territory, and there’s not a lot of drugs that the protocols in these clinical trials are specifically with the psychotherapy component. Usually, it’s just that one isolated variable of the drug.
Paul Goldberg: Mm-hmm. How soon do you think they’re going to approve or have an approval decision on the first of those drugs? I think one of them are… two of them are on the National Priority Voucher Program, which is a short track.
Sara Willa Ernst: Yeah. So this is kind of part of an entire policy change from the Trump administration. They had submitted a… They had issued an executive order a few months ago, which is what the cover story that I wrote and the cover story that you edited was about. And they had issued three National Priority Vouchers, two for psilocybin for major depressive disorder and also treatment-resistant depression, and then one for a drug called methylone for post-traumatic stress disorder.
In terms of the timeline of the approvals, I’m not sure, but the fact that they had been issued National Priority Vouchers, I think, is a sign of interest. And specifically, in the executive order, they used the word accelerate. So it seems like speed is something that the Trump administration is concerned with.
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Paul Goldberg: Well, you know what we probably ought to do, and this is kind of probably where we start… should’ve started the conversation, is a recap of the history of what’s been happening because this is not your standard bringing your drug to FDA situation. This is more of a question of Manosphere, Joe Rogan doing a lengthy podcast about psychedelic drugs, which by itself doesn’t really matter much because most… both you and I missed it.
And I suspect a lot of people who read… listen to this podcast missed it as well. But what happened next is Trump was brought into this by Rogan, right. And he says, “Well, what do you want me to do? Approve a drug?” Which is kind of an amazing thing to say. And then there’s this discussion. But the reason these drugs were never really submitted to FDA and the reason there hasn’t been a whole lot of research is because of the Nixon War on Drugs. Correct me if I’m wrong.
Sara Willa Ernst: Yeah, exactly.
Paul Goldberg: 50 years of policy being upended, maybe appropriately. Who are we to say? We’re just dog-faced journalists.
Sara Willa Ernst: Yeah. I mean, it’s very out of character how this federal policy change made. This is kind of the top of the cover story that I wrote, but to set a scene, Joe Rogan sent a text to President Trump and told him about the treatment potential of Ibogaine when it comes to alcoholism.
And this came after an hour, two-hour-long interview that Joe Rogan did with former Texas Governor Rick Perry, who’s become a total advocate for Ibogaine. And so essentially, yeah, a guy with a podcast does an interview, and then has friends in high places and texts the president, and president says, “Do you want an FDA approval?” And so that was all mentioned at the press conference in the Oval Office and gives some context just about how federal policy is made in 2026.
Paul Goldberg: So let’s back up a little more. So basically you have a podcast, then you have a text message, then you have a National Priority Voucher by FDA.
Sara Willa Ernst: Exactly.
Paul Goldberg: And then now you have an FDA guidance for drug approvals for how to prepare the drug approval applications, the NDAs. So that’s where we are, and we’ll be on it for quite a bit longer. But anything we missed? Anything you wanted to add to this?
Sara Willa Ernst: I think in the FDA final guidance that just came out, the story that we just wrote, FDA expresses this hesitation or skepticism around the importance of the psychotherapy component with psilocybin or a different psychedelic drug. And essentially they’re saying, “We want really strong evidence to show that the psychotherapy component is efficacious.”
And what they ended up suggesting in the final guidance is something called factorial design. Factorial design, basically there’s four arms, placebo and intensive therapy, placebo and minimal/no therapy, active drug and intensive therapy. And the last one is active drug and minimal or no therapy. And talking to the clinical trialist, they’re very supportive of this.
They feel like it’ll answer a lot of questions that have gone unanswered. Is there a difference between two hours of therapy versus four hours of therapy? How intense and how often does the therapy really need to occur in order to really kind of refine the protocols? The downside of that is that factorial design is usually expensive.
Paul Goldberg: Yeah. Yeah. Is there money enough in these drugs that somebody might want to do this kind of trial? By the way, how many patients do you think we’re talking about here?
Sara Willa Ernst: For cancer patients or just in general?
Paul Goldberg: Well, actually, yeah, indications are not uniform. This is really… A lot of methodologists are having a lot of fun deciphering this. How do you go forward with this? Could be very interesting.
Sara Willa Ernst: Yeah. I think it’s unclear at this moment whether a factorial design trial will happen because of the resources that are required. And especially because FDA has opened the door to… at least in the final guidance, to applications that kind of de-emphasize the psychotherapy aspect. So that might be a whole lot cheaper for a pharmaceutical company that is trying to bring a drug to market to go in that direction as opposed to the real hefty lift of a factorial design trial.
Paul Goldberg: It might be very interesting to see how this is discussed. Maybe a story can be done with… by calling our friends who are… who design trials and asking them what their thinking is about this, because it’s not something that’s intuitive. It could be a very interesting story about how to combine what we know about this with what FDA does to approve drugs. So kind of what to expect might be a very interesting story, do you think?
Sara Willa Ernst: You’re assigning me a story right now.
Paul Goldberg: Well, I’m not assigning it. I’m thinking about a story, thinking through it, and it would be good to have your thoughts on this. I think it would be a really worthwhile exercise to look at how to design those trials that are in the guidance, in the final guidance. And this is the final guidance, so you should take it seriously. Yeah?
Sara Willa Ernst: Yeah. Yeah, it’s the final guidance. I would be very interested in that. And it sounds like we have more follow-up reporting to do.
Paul Goldberg: Yeah. Well, it’s an ongoing story, and it’s one of those things where The Cancer Letter has always done the same thing, which is we go back, go back, go back as how many million times we need to just follow up, and we’re done when we say we’re done. So in this case, it’s a story people will be seeing a lot of.
And personally, as an editor, I would love to see a story about how to interpret that guidance. How not… How clinical trials methodology experts look at this. How somebody like maybe Don Berry looks at it at… I’m just throwing out one name, but there are others. How they kind of look at this and say, “Hey, we can do this trial.” Or, “Hey, no, they’re hallucinating.” Appropriate joke-
Sara Willa Ernst: Ha ha ha.
Paul Goldberg: … here. Ha ha ha. Is FDA [inaudible 00:18:04] hallucinating?” And they’ve said a good thing that it is, if it is.
Sara Willa Ernst: Yeah. I mean, it sounds like I have more reporting to do ahead of me.
Paul Goldberg: Oh my God. You’ll have a blast. Some of the coolest people in the world design clinical trials.
Sara Willa Ernst: Yeah. There’s definitely an art and a science to it.
Paul Goldberg: Well, let’s stay with the science.
Sara Willa Ernst: The science. Yeah.
Paul Goldberg: So anyway, so what else did we have that was fun to do? Let’s talk about the OMB guidance. Half a million responses, comments to this OMB document, OMB proposal. That’s quite amazing, isn’t it?
Sara Willa Ernst: Yeah. I mean, it’s pretty unbelievable. And it was in a pretty short period of time, right?
Paul Goldberg: Oh, yeah.
Sara Willa Ernst: It’s just flooded in.
Paul Goldberg: Well, it wasn’t spontaneous. It was supposed to.
Sara Willa Ernst: Did anything kind of jump out to you in terms of the comments in the story?
Paul Goldberg: No. Well, the comments are terrific, all of them. The next… The part… And the fact that they arrived as they arrived is really terrific. And I just thought assigning the story that it would be important for people to be able to find commentaries… comments by various organizations. So we put together a list, and it’s kind of like having an index to a telephone book. It would save some time. But to me, this is probably one of the most important changes to be proposed in how clinical trials are conducted.
Because really it goes back to World War II when the US government first became interested in supporting science. And that’s really the beginning of it all. Vannevar Bush was… came up with this idea of the reliance on peer review. So if we do not rely on peer review, gosh, what do we rely on? Political review? Political review, hierarchies? Well, we do have scientific hierarchies, but I think a decision was made that having those scientific hierarchies, which can be busted up pretty well, is better than having political hierarchies.
That’s kind of the story. And I don’t think we’re done with that either, because what’s the administration going to do with this now? They have 500,000 comments. The clock is ticking. October 1st is when they would like to get this enacted. Of course, it’s going to be challenged in courts. Of course, it’s going to be challenged in Congress. Interesting part would be how the party aligns… align on this.
So far it’s Dems against some… vast majority Republicans for, but that too can change. So Susan Collins has been against it, which is kind of… which is hugely important. And the question is, does she survive the midterms? So the whole thing is going to be another one of those sagas that we cover and cover and cover. Or I should say Odyssey that we cover and cover and cover. Or the [inaudible 00:21:57] that we cover and cover. But in any case, it’s something we’ll cover and cover and cover.
Sara Willa Ernst: Yeah. I mean, it’s hugely important to our readers. I mean, that’s clear, in just… I’m sure many, many of them had contributed to the comments themselves. I see the OMB story being a story that is going to continue on and on for months to come. And we will be on top of all of that.
Paul Goldberg: Yeah.
Sara Willa Ernst: Yeah. And also, I wanted to dive in a little bit into the sponsor article that’s titled The Future of Oncology: Early-Career Scientists Need Mentorship and a New Academic Model. This was written by Marcel van den Brink. He’s with City of Hope. And I thought it was a pretty interesting article. Does anything kind of pop out to you specifically, Paul, when you’re reading it?
Paul Goldberg: Yeah. Yeah. It’s really a story about how do you protect our biggest resource and most important resource, and really the hope for the future, which is young investigators, early career investigators. How do you keep them working? And one of the issues is, of course, one-on-one mentorship.
That’s huge because think of all the things in our careers, and we’re not scientists, that matter the most. It’s the one-on-one mentorship by somebody who is more senior in your career. Once that’s lost, there’s no way back. That’s not Marcel speaking. It’s me. But the other bit that’s interesting is that the system, the new… the existing academic model protected… excuse me, encouraged solar researchers or…
Sara Willa Ernst: Solar, he calls it the solo investigator model in the story.
Paul Goldberg: Yeah, the lone wolves out there. Maybe that’s the wrong image, but you can’t… Yeah. So it encouraged that. And what’s happening now is a more collaborative world where research is done more collaboratively. And maybe there is a way to recognize this in the way young researchers, early-career investigators, are being encouraged to stay in there to keep it going because the world does change.
Sara Willa Ernst: He talks about in the article just where the incentives and where the rewards are set up in the solo investigator model. If you are a young investigator to be first author or last author on a paper is the goal. It’s where you’re trying to go.
And trying to acquire or to be awarded an individual grant, those are where the rewards and the incentives are set up and encourages people to do more individual solo work. And so I think the author is kind of questioning how do we build a system that it rewards people for collaborative work instead of solo work.
Paul Goldberg: Yeah, there is a reason to, there is a time. This is a good time to re-engineer, to think in those kind of very broad terms and the fundamentals. So I found that piece very interesting.
Sara Willa Ernst: Yeah. Yeah. And you kind of mentioned this. Some of the ideas are a little universal. They definitely apply in scientific research, but they apply to journalism for us as well. As a younger journalist, wanting to have that type of mentorship and wanting to work collaboratively and soaking everything up is exactly what I crave. So-
Paul Goldberg: Mm-hmm.
Sara Willa Ernst: … I relate a lot.
Paul Goldberg: Yeah. Yeah. No, this is definitely an interesting piece that resonates in the newsrooms, which, of course, that’s not Marcel’s intent. Anyway, well, great. Thank you so much. This is a great time to be a journalist, isn’t it, Sara?
Sara Willa Ernst: Yeah. And I think that’s how we end every podcast is us just saying thank you for letting us do the work that we do.
Paul Goldberg: Well, thank you. And thanks for listening.
Jacquelyn Cobb: Thank you for joining us on The Cancer Letter Podcast, where we explore the stories shaping the future of oncology. For more in-depth reporting and analysis, visit us at cancerletter.com. With over 200 site license subscriptions, you may already have access through your workplace. If you found this episode valuable, don’t forget to subscribe, rate, and share. Together, we’ll keep the conversation going.
Paul Goldberg: Until next time, stay informed, stay engaged, and thank you for listening.
