Forty Years at the PTSD Frontier

Journal of Clinical Psychiatry

https://www.psychiatrist.com/jcp/

Dr. Barbara O. Rothbaum — LinkedIn

https://www.linkedin.com/in/barbara-rothbaum-9339546 

Emory Healthcare Veterans Program

https://www.emoryhealthcare.org/lp/veterans-ptsd

The intensive outpatient program for post-9/11 veterans discussed throughout this episode.

Wounded Warrior Project — Warrior Care Network

https://www.woundedwarriorproject.org/programs/warrior-care-network

Funds the four IOP programs, including Emory’s, discussed in the episode. No cost to veterans.

Dr. Barbara O. Rothbaum is a tenured professor in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine, where she holds the Paul A. Janssen Chair in Neuropsychopharmacology. She serves as director of the Trauma and Anxiety Recovery Program, director of the Emory Healthcare Veterans Program — a nationally recognized intensive outpatient program for post-9/11 veterans — and, as of 2025, science director of the Emory Center for Psychedelics and Spirituality. She holds fellowship designations from ACNP, the National Academy of Inventors, AAAS, and APA.

Ben Everett, PhD, is the creator and host of The JCP Podcast, a series that brings together leading voices in psychiatry to explore the latest research and its clinical implications. Everett earned his PhD in Biochemistry with an emphasis in Neuroscience from the University of Tennessee Health Science Center. Over a two-decade career spanning academia, publishing, and the pharmaceutical industry, he has helped launch more than a dozen new treatments across psychiatry, neurology, and cardiometabolic medicine. His current work focuses on translating complex scientific advances into accessible, evidence-based insights that inform clinical practice and foster meaningful dialogue among mental health professionals.

This transcript has been auto-generated and may contain errors. Please refer to the original recording for full accuracy.

00:00 – Introduction and Guest Biography

Dr. Ben Everett: Hello, and welcome to the JCP podcast, where we explore the science and stories shaping mental health care today. your host, Ben Everett, Senior Scientific Director with Physicians Postgraduate Press, publisher of the Journal of Clinical Psychiatry. On this podcast, we speak with clinicians, researchers, and thought leaders advancing the field of psychiatry with a focus on not just what’s new, but what’s meaningful for our listeners in their clinical practice. On today’s episode, we speak with clinician, researcher, and thought leader who has spent nearly four decades advancing the field of PTSD. My guest today is Dr. Barbara Rothbaum, a tenured professor in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine, where she holds the Paul A. Janssen Chair in Neuropsychopharmacology. She serves as the director of the Trauma and Anxiety Recovery Program, director of the Emory Healthcare Veterans Program, which is a nationally recognized intensive outpatient program for post-9/11 veterans, which is supported by the Wounded Warrior Project, and as of 2025, science director of the Emory Center for Psychedelics and Spirituality. She also serves on the editorial board of the Journal of Clinical Psychiatry. Dr. Rothbaum received her PhD in clinical psychology from the University of Georgia training in behavioral therapy at Middlesex Hospital Medical School in London. She served on the DSM-IV PTSD subcommittee, was a member of the Institute of Medicine’s Committee on the assessment of ongoing efforts in the treatment of PTSD, and has briefed the DoD, VA, and congressional subcommittees on its findings. She is past president of the International Society of Trauma Stress Studies and holds fellowship designations from ACNP, the National Academy of Inventors, AAAS, APA. Her career is defined by three interlocking contributions, developing and disseminating trauma-focused CBT, including decades of work with prolonged exposure therapy and VA cooperative trials, inventing virtual reality exposure therapy, co-founding Virtually Better, Incorporated, 1996, and co-developing the Brave Mind system, now deployed at more than 50 VA health systems. she has conducted translational research on pharmacological augmentation of exposure therapy and psychedelic-assisted psychopharmacology, including over a decade of active MDMA research. She’s currently co-investigator on a $5.2 million DoD grant examining MDMA’s impact on fear extinction and its combination with prolonged exposure. She is a licensed MDMA-assisted therapist. honors include International Society of Trauma Stress Studies, or ISTSS, Lifetime Achievement Award, the Robert S. Laufer Award for Outstanding Scientific Achievement, the APA Division 56 Award for Outstanding Contributions to the Practice of Trauma Psychology, among others. She has authored more than 400 scientific papers and multiple books on PTSD treatment. that, Dr. Rothbaum, welcome to the podcast.

Dr. Barbara O. Rothbaum: Thank you, Ben. I think we’re done, right?

Dr. Ben Everett: Well, you certainly have an extensive career, and when we worked together a little bit when I was working at Lykos. So just a disclaimer, I did spend a couple years at Lykos working on MDMA-assisted therapy as well. It’s where we originally met. Look, thanks for your time this afternoon.

03:30 – Career Origins: Starting with Edna Foa

Dr. Ben Everett: We’re gonna get right into it, but we like to start every episode with a couple of icebreaker questions just so people can kind of get to know you and, you know, what guided your career and the way it went. Let’s start at the beginning. Since you received your PhD, you’ve been studying PTSD treatments for about 40 years. What drew you to trauma in the first place? Was there a patient or a moment early on that crystallized that this was gonna be your life’s work?

Dr. Barbara O. Rothbaum: I wish I could tell you something that inspiring. It was my first job. My first job was with Dr. Edna Foa, who had, I think, one of the first grants studying actual PTSD at that point. Because as PTSD became a diagnosis in nineteen eighty. And I remember telling her on the phone, “I’ve never treated PTSD before.” And she said back, “That’s okay. Neither have we.” And we started it together.

Dr. Ben Everett: That’s interesting. All right, so you trained in behavior therapy in London before joining Emory. did that early grounding in behavioral science shape the way you approach problems, both in the clinic and in research?

Dr. Barbara O. Rothbaum: I tend to think very pragmatically about what patients are experiencing, what kinds of problems they’re having, and what they need to learn to be able to function better. And so I think even before I was a cognitive behavior therapist, I was probably a cognitive behavior therapist at heart. And even before I was an exposure therapist, I was probably an exposure therapist at heart. So it, it fit.

05:30 – A Career at the Intersection of Therapy, Technology, and Pharmacology

Dr. Ben Everett: That’s nice. It’s one of those things you were doing it before maybe we had names for it. It was just kind of organic for you. That’s good. you’ve really been at the intersection of psychotherapy, pharmacology, and technology in a way that is a little unusual. You know, typically I feel like we see researchers really just go deep into one area. Was this kind of breadth and width intentional, or did it just happen organically? “Hey, we’ve got new technology, we’ve got new, new pharmacology,” and it just kind of all went together? or was it just circumstantial?

Dr. Barbara O. Rothbaum: I think a number of times across my life and my career, I’ve been in exactly the right place at exactly the right time. So as I mentioned, my first job out of graduate school, my first faculty position was with Edna Foa, working on what I think was the first grant on PTSD and what would later become prolonged exposure therapy. It’s funny ’cause at the time, and for a few years, we knew everything in the world, all the work going on PTSD. So it was at the beginning– not the beginning of PTSD, ’cause have had PTSD as long as humans have been humans, but the beginning of when it was recognized as a disorder and treated as a specific disorder. then for the virtual reality exposure therapy, I’d moved to Atlanta, to Emory, a computer scientist from Georgia Tech called me up and said there was an Emory Georgia Tech seed funding grant, and he needed an exposure therapist. he made fun of me because that was in nineteen ninety-three. And I asked him to send me his CV ’cause I wanted to make sure he was legitimate ’cause I said, “You wanna do what?” And that was first time that anybody’s ever used virtual reality to treat a psychological or psychiatric disorder, and that paper was published in nineteen ninety-five. And then all along, been looking at ways to either treat PTSD or improve cognitive behavior therapy was able… For example, I think I was a PI on the early Pfizer studies that– where sertraline later on got the FDA indication for PTSD and started different studies of combining different medications, especially with exposure therapy, but with cognitive behavior therapy and doing some clinical trials just with the medications. So it’s like Malcolm Gladwell says, right? Being in the right place at the right time and having the right skills to take advantage of it too, all right.

08:00 – First-Line Psychotherapies: PE, CPT, and EMDR

Dr. Ben Everett: So, you know, we’ve talked about psychotherapy, so I think this is a great segue to really our first segment. So we know VA, DOD, APA, ISTSS, among others, they all converge on therapy as really the first line of treatment before pharmacology. And then specifically, there’s really three different areas of therapy that now are recommended.

Dr. Ben Everett: So there’s prolonged exposure, which you’re really an expert in. Cognitive processing therapy and EMDR is the strongest first-line recommendations. So that convergence has really been stable for some time now. So for our listeners who might be a little less familiar, can you briefly walk us through the rationale for very specific trauma-based or trauma-focused exposure-based therapy? What’s the mechanism that you’re really trying to get to for these patients?

Dr. Barbara O. Rothbaum: Absolutely. To start with, most of the PTSD symptoms are part of the normal response to trauma. If somebody holds a knife to your throat and says, “Don’t scream or I’ll cut you,” you’re gonna have problems sleeping. You’re gonna be scared to go outside by yourself. You’re gonna be upset when you think about it.

Dr. Barbara O. Rothbaum: That’s normal What we think happens with some people is that they don’t emotionally process it. I make a lot of analogies to the grief process. I think there’s no way to the other side of the pain except through it. for various reasons, people avoid it, and they don’t process it, and then it haunts them.

Dr. Barbara O. Rothbaum: And then the haunting comes out in the PTSD symptoms, especially like the re-experiencing symptoms. It really feels like people are haunted by what happened to them. So we think that especially for cognitive behavior therapy, CBT, for PTSD, that what we’re doing is helping people to approach the trauma memory and reminders, but in a therapeutic manner so that something changes. So don’t just approach it and run away scared. Nothing has changed. So for prolonged exposure, what we do is we ask people to go back in their mind’s eye to the time of the traumatic event and recount it out loud repeatedly during a session. And usually we record that now, usually on their phones, and ask them to practice that for homework. And again, what we’re trying to do is help them emotionally process. The opposite of avoiding. You don’t learn anything from avoiding, you learn from approaching. And what I’ve seen in PTSD is that we believe our stories what happened more so than what actually happened. And so if you are avoiding thinking about what happened, then you can’t possibly change your interpretation of it. So for example, a number of our veterans their traumatic story might go something like driving back to base, hidden IED, Jones died, and it was my fault because I was driving. And then if you can’t go there, then you can’t possibly think about it differently. Whereas then in exposure therapy, we’re helping people approach this memory, approach reminders. Once their distress about it comes down, they can look at it differently and come to a different understanding. For example, it sucks that Jones died, but I did everything I could. The insurgent planted the IED so that no one would see it. There were eight eyes on the road. I actually did everything I could for Jones after it happened, so it’s terrible that he died, but it wasn’t my fault.

Dr. Barbara O. Rothbaum: And that’s a way different way to carry this memory forward. And I think in general, for all of the cognitive behavior therapies for PTSD, we’re trying to help people approach the memory and think about it differently, have a different relationship to the trauma memory and reminders that it doesn’t interfere with their current everyday life. So in PE, it’s through imaginal exposure and what we call in vivo exposure, and that just means in real life. we will help people approach situations that they’ve been avoiding that are realistically safe and stay in them long enough to learn in their bodies and their brains the situation doesn’t pose the level of threat that it feels like to have that new learning. In cognitive processing therapy, or CPT, it’s a cognitive therapy, so it’s more focused on the thoughts especially maladaptive thoughts in certain areas, so safety, trust what CPT therapists call stuck points, and helps modify cognitive errors. In EMDR, eye movement desensitization and reprocessing, you ask the person to get a picture of the worst moment in their mind’s eye, to focus on words that go with that picture.

Dr. Barbara O. Rothbaum: Not necessarily words that were uttered, but words that have endured “I’m gonna die,” something like that. Focus on the feelings they get in their body when they think of that and see that, and then while they’re doing all of that, to follow therapist’s fingers moving back and forth in front of them. And all three of these are what we call empirically based treatments, empirically supported treatments for PTSD, and they’re all pretty short. all can be delivered in about nine to 12 sessions.

13:30 – Comparing the Therapies: Evidence and Patient Fit

Dr. Ben Everett: So that’s really good. And I know especially in the VA, there have been issues, you know, you’ve got a lot of veterans coming back from from the wars and a shortage of therapists. so it’s good that this can be delivered in a short period of time. when we look at, these different methodologies that you just went through, is there any real clear evidence that, hey, one is better, or is it like trying to fit the therapy for the patient?

Dr. Ben Everett: Or is it really just they kinda work the same and it’s, you know, maybe one VA has a little bit more expertise in EMDR and this VA is a little bit better in PE, but they all work about the same? Kinda where’s the evidence on that now?

Dr. Barbara O. Rothbaum: I want to give kudos to the VA because more than a few years ago, they started rolling out and training therapists in empirically supported treatments. So at almost any VA, you should be able to have options. There have been several head-to-head studies in, in a recent study by Paula Schnurr, I think it was published in twenty-two, PE did a little bit better than CPT, but they were both very effective I did a study years ago comparing PE to EMDR, and they were both effective immediately post-treatment. At follow-up, the EMDR folks lost a little bit of gains. The PE folks gained a little bit more, so then at follow-up, PE was a little bit more effective. partly it depends on what the patient will do. So I like to have options. I like to have choices for PTSD patients and explain the treatments and see what they’re willing to do.

Dr. Barbara O. Rothbaum: ‘Cause the biggest problems with PTSD treatment is, one, people don’t get it, and they don’t get it for lots of reasons. Their PTSD isn’t identified as PTSD. Access to people like me who know how to treat PTSD and avoidance that we talked about earlier. dropout from PTSD treatment is a huge problem across all treatments, and it can get as high as about fifty percent in general clinics.

15:30 – The Emory Healthcare Veterans Program and the IOP Model

Dr. Barbara O. Rothbaum: So getting the patient to agree to a therapy that makes sense to them and that ideally they’ll commit to finishing. I to talk for a second about the Emory Healthcare Veterans Program we have a new model. We have an intensive outpatient program, an IOP, and it’s– we’re offering mass therapy.

Dr. Barbara O. Rothbaum: So we’re able to bring post-nine eleven veterans from all around the country. We fly them into Atlanta, put them up at the hotel across the street from our clinic, feed them, and give them more therapy in two weeks than most people get in an entire year. And we have different tracks. So for example, people on the PTSD track receive daily PE therapy, we have a better than a ninety percent retention rate. So I really think that this IOP format is the secret sauce to treating PTSD because it helps combat avoidance. They only need to make the decision once to come to treatment. They come to Atlanta, and we’re gonna kinda drag them through until they’re really on board, and they stay with it. What’s also interesting is that we start a new cohort of veterans every Monday. So in a two-week program, at any given point, some folks are gonna be in their first week, and some folks will be in their second week. And it’s amazing what a difference a week makes when you’re talking about a therapy this compressed, this intense every day. And so the second-week patients can help encourage the first-week patients, and the first-week patients see how well the second-week patients are doing, and, and that helps keep them in and doing what they need to do.

Dr. Ben Everett: It’s amazing. I know when I was you know, in this space and, and reading about these different programs and talking to the people doing these programs, yeah, the IOP model really seems to, to, to have accelerated the ability for patients to go into remission and, and to remain in remission. And while I know you’re very proud of your program, y’all are doing really good, good work, there’s four or five of these programs across the country.

Dr. Ben Everett: I know Chicago has one, there’s one in Boston, and there’s one in Southern California, I believe. Maybe that’s four. I might be missing one. just for veterans, the– these, these IOPs are available. You know, you can find one close to you. And through the support of the Wounded Warrior Foundation, it’s– it– all expenses are paid, correct? Like, the, the veterans, it– Yeah, nothing out of pocket.

Dr. Barbara O. Rothbaum: yeah, the four of us are part of the Warrior Care Network that supported, it was stood up by the Wounded Warrior Project. And yes, we will all try to help, and help is available all… There’s at n- no expense. It’s no cost to the warrior, to the veteran, or their family.

Dr. Ben Everett: Yeah. And that’s really what’s so important for this. So access to evidence-based, you know, comprehensive treatment in a quick period of time and at no cost to the veteran. So that’s amazing. I know one other thing that I found really interesting about the program is there’s so many comorbidities that go with PTSD, depression.

Dr. Ben Everett: You know, almost all these patients have very high rates of depression. so, you know, if it’s recommended that maybe some rTMS would be beneficial for this patient, they can get the TMS while they’re in their intensive outpatient. So it’s really comprehensive across not just looking at the trauma, but other comorbidities that might be there as well.

Dr. Barbara O. Rothbaum: Yeah. About half of the folks with PTSD also have comorbid major depression. And what we found in general is when you treat the PTSD effectively, the depression decreases, especially if the depression’s secondary to the PTSD. In the Emory Healthcare Veterans Program, we have different tracks. So we have the PTSD track if PTSD is primary, and we have what we call the general track if PTSD isn’t primary.

Dr. Barbara O. Rothbaum: And so then we’ll treat whatever they’re presenting with depression, anxiety. We also have sub-tracts. we have a TBI track if they’re presenting with significant traumatic brain injury symptoms. We have a SUD track if they’ve got problems with substance use or misuse, and we treat everything simultaneously. we’ve had– I think we’ve treated over sixteen hundred folks at this point. We just celebrated our ten-year anniversary late last year. So we can pretty much tell by the end of the first week if someone is on the trajectory to get the full response or not. if they’re not, then that’s where we can augment their therapy with something like the rTMS and maybe in the future, maybe with psychedelics if it looks like that might be helpful.

21:00 – Recognizing PTSD in Primary Care

Dr. Ben Everett: Just amazing what you’re doing for these patients. And yeah, just to level set for our listeners that maybe don’t treat a lot of PTSD, even though you’re probably seeing the patients kind of whether you know it or not, is I believe it was about a fully a third of our men and women who served abroad in these theaters will qualify for a diagnosis of PTSD. They may not know it, and this– y- you didn’t have to see combat to have PTSD. There’s a number of other things that can, you know,  be involved military sexual trauma. you know, I remember talking to people who, were in like logistics and the insight, like planning the missions and just looking at the video and whatnot, and even for them, they can have PTSD.

Dr. Ben Everett: So just wanna put that out there to make people know, there’s a lot of different ways that you can, you know, end up with a diagnosis of PTSD.

Dr. Barbara O. Rothbaum: Ben, I want to capitalize on that for a minute because a lot of times when I talk, for example, to primary care doctors I will tell them that they see more patients with PTSD than I do even though I specialize in it. And they said, “No, we don’t.” And I said, “Yes, you do. You’re just not recognizing it.”

Dr. Barbara O. Rothbaum: Because they don’t walk in and say, “I’m the victim of childhood sexual abuse. I have PTSD.” Very often they present with a comorbidity. They’ll present with anxiety or problems sleeping or maybe substance use or misuse. Patients with PTSD are often the frequent flyers in primary care practices. They have a lot of physical complaints. So I always assess for a trauma history, and it will sometimes change my picture of the patient sitting in front of me.

Dr. Ben Everett: It’s so important in terms of just raising awareness and, and educating those primary care colleagues. So we’ve talked about a couple of different things. I know written exposure therapy has also been shown to have lower rates of– or been associated with lower rates of dropouts in, in some of these clinical trials. Anything you want to say about written exposure therapy?

Dr. Barbara O. Rothbaum: Yeah, again I’m all for options. I want patients to have options. Most of the studies on WET, written exposure therapy, that I’m aware of are different designs. They’re called non-inferiority designs, and so that’s different than a head-to-head comparison. It’s a little bit different, but again, I want folks to have options.

23:30 – Pharmacotherapy: The Limits of SSRIs

Dr. Ben Everett: Yeah. Options are so important. So speaking of options or lack of options, maybe we ought to transition over to pharmacotherapy. So you mentioned sertraline earlier. Sertraline and paroxetine are the only two drugs on the market that have an actual indication for PTSD, and they were approved over twenty-five years ago. So it’s not been really any progress in the field in that area, but there has been some, some efforts to, to, to get some new drugs approved. And I, I think we’ll get there eventually for some of these things. But, yeah, let’s kind of talk about the, the state of, of where we are with research, kind of what’s happened and, you know, why maybe the, the current drugs aren’t working as well as, as we might like them to.

Dr. Ben Everett: I know that the SSRIs the effect sizes are pretty small, so that’s just one thing. Just seem to not work that well. There may be some gender-based differences or some sex-assigned at birth differences. and then some patients, you know, do have some side effects with them, and they just won’t stay on them if they’re having some, you know, sexual side effects or other things like that. so with just the two on-the-market drugs right now, on-label drugs, you know, how do you see them being used in the clinic? And, you know, do you see them being misused or underutilized or anything like that?

Dr. Barbara O. Rothbaum: I don’t think that anybody thinks that SSRIs are really the treatment for PTSD. I personally will think of them like weak coffee for PTSD. You know that maybe you can get a little bit of effect maybe on mood, maybe on, on thinking and being able to dismiss some thoughts. But since they’re not really the treatment for PTSD, then people are often treated with polypharmacy.

Dr. Barbara O. Rothbaum: Most of our folks come to us on several medications because, again, it’s not really the good treatment. If someone comes to us treatment-naive, which is hardly ever the case anymore, but if they do, then everything else being equal, we’re gonna recommend starting with one of the cognitive behavior therapies first.

Dr. Barbara O. Rothbaum: And if you’re coming to us, it’s probably gonna be PE that we’re gonna try first because PE does have more evidence than any other intervention for PTSD, including these two FDA-approved medications. It’s recommended by every single PTSD treatment guideline. if they’re treatment-naive, we’re gonna start with the psychotherapy first because that works in a lot of people, and very often the treatment gains are maintained even after therapy. What we saw in the early sertraline studies is that even for folks who got better, they needed to be maintained on the medication, or they would lose those gains. have been several combination studies of generally SSRIs and exposure therapy. Overall, the combination therapy is no more effective than the psychotherapy alone, than the exposure therapy alone. And the combination therapy, combination of pharmacotherapy and psychotherapy, are not recommended in any of the treatment guidelines. So it’s easier for more patients to get prescribed a medication than to get an evidence-based psychotherapy. But if it’s available, we recommend the psychotherapy first.

Dr. Ben Everett: Well, the guidelines are very clear that psychotherapy should be first, but it’s that access piece and really where patients may start in their journey if they’re seeing a primary care physician because, you know, “I’m just having trouble sleeping,” or, “I’m just really anxious.” If they don’t think to probe as to what’s the root cause of that, you know, they go, “Okay, well, a little anxiety, we’ll give you some sertraline or some paroxetine, or, you know, we’ll give you some trazodone.  You’ll sleep a little bit better.” But that’s not getting to the root cause of the you know, anxiety, trauma, sleep disorder, whatever it is.

27:30 – Recent Drug Development Setbacks: MDMA and Brexpiprazole

Dr. Ben Everett: All right. So let’s turn now to the two most recent misses, and without doing full postmortems, you know, I think both drug development programs had some issues, and they were called out in the FDA advisory committee meetings that they had for these.

Dr. Ben Everett: So the first was looking at MDMA-assisted therapy, and then the second was brexpiprazole, so the atypical antipsychotic brexpiprazole added to sertraline versus sertraline alone. Both did not do well at their advisory committee meetings. Very lopsided no votes, and in both cases, the FDA subsequently gave the sponsors what we call complete response letters, essentially saying– detailing what they would have to do if they want to move forward. And in both cases, I believe they were just told, “You’re gonna need to do a new phase three, you know, program to address these causes.” So kind of what do you think about the state of drug development in PTSD right now? You know and not getting into any politics of, oh, I think the FDA this or the drug sponsors this.

Dr. Ben Everett: Let’s just look at this kind of, know, from a thirty thousand foot view maybe. You know, why has it been so difficult to get some new drugs approved for PTSD?

Dr. Barbara O. Rothbaum: I think there are a number of reasons, and I also think it’s terrible that we haven’t had a new drug approved for PTSD in twenty-five years. that’s not because we don’t understand PTSD or we don’t think that there would be effective medications. It’s for various other reasons. So PTSD is hard to treat. And again, not getting political, but drug companies are companies and they’re businesses and they’re meant to make money. And if they are worried that their medication is not gonna be effective for PTSD and not gonna make money, then they’re not even gonna start. So I am so appreciative when anybody is looking at PTSD and trying to develop and test medications for PTSD because we need them desperately. I think that the FDA is not as familiar with PTSD. Like we said, there hasn’t been anything approved in twenty-five years, so it’s not like they have a lot of experience. with MDMA I really actually do think it was fairly political when you said on one of the committee meetings, they’re like, “I can’t believe with the size of this effect I’m gonna say no.” Because the data was actually very strong, and I think it was political that some of the criticisms that they got and held to a different standard. So for example, the functional unblinding. In cancer treatment, people know when they’re on the active treatment or not. Antipsychotics, people know when they’re on the active treatment.

Dr. Barbara O. Rothbaum: Functional unblinding is not something new. But it got a lot of attention. The psychotherapy aspect, I think then, the FDA says we don’t regulate psychotherapy, but then they kinda did by saying it wasn’t an evidence-based psychotherapy. I look at the data in the second phase three trial, I think seventy percent, if I’m remembering correctly, of the patients no longer met PTSD criteria at the end of the trial.

Dr. Barbara O. Rothbaum: That’s better than in any of our other PTSD studies. So yeah so I really, felt that there was a there and I think a lot of other people did. Like you said I think that it probably will be eventually approved. It’s just gonna take longer and more work. And this might be a place to talk about some that we’ve been doing.

31:00 – Translational MDMA Research and Combining with Prolonged Exposure

Dr. Barbara O. Rothbaum: So as you mentioned, we’ve been doing translational research with MDMA for about a decade. We started with an animal model, a rodent model, and we found that MDMA facilitated the extinction of fear. And that was very cool. We also found in that study that SSRIs blocked that effect. So that sucks because so many of our patients are on SSRIs, but it’s important to know.

Dr. Barbara O. Rothbaum: So if a patient’s gonna receive MDMA, they do need to be discontinued off of their SSRIs. Then we followed it up with a healthy human study we did pretty much the same design that we did with the animal study. So what was fear conditioning and then the next day before fear extinction training, that’s where they were randomly assigned to receive MDMA or placebo and then fear extinction training and then brought them back for extinction recall testing.

Dr. Barbara O. Rothbaum: We found that the MDMA was associated with more extinction retention responders. What does that mean? It means their bodies remembered they didn’t need to be scared anymore. obvious implications for PTSD treatment, but we knew all of this was leading up to doing it with PTSD patients. So we have been combining MDMA with the mass two week prolonged exposure therapy that we talked about earlier, where we’ve been doing it in an open clinical trial, so take it all with a grain of salt. was mainly as a proof of concept. A lot of the folks in the psychedelic wor- world said, “You can’t do that. Patients can’t do prolonged exposure on MDMA.” And then a lot of people said, “You shouldn’t do that. Don’t make people do prolonged exposure on MDMA.” we’ve so far seen an eighty-one percent decrease in PTSD symptoms on the CAPS-5-R.

Dr. Barbara O. Rothbaum: That’s the clinician administered PTSD scale revised It’s an open clinical trial. Take that with a grain of salt. What I do feel absolutely confident in saying is they can be combined on dosing day, and they are so synergistic. We t- we talked about our regular psychiatric medications. Think about them.

Dr. Barbara O. Rothbaum: They’re all meant to suppress symptoms. Think about antipsychotics, antidepressants, antianxiety, whereas the psychedelics help people process experiences and emotions. it feels very synergistic, the MDMA and the exposure therapy, especially on dosing day, but the whole treatment, it’s really all about approaching everything that arises and helping people to emotionally process it. it has been so much easier even than I thought it would be for people on dosing day on MDMA to engage in exposure therapy. That’s part of why psychedelic therapists have been using MDMA for decades because it is easy to work with the patient on it, it really has been beautiful. And I’ve been doing this work, as you pointed out, for a long time, and I have not used the word beautiful as much as I have in the past year to describe PTSD treatment.

Dr. Ben Everett: It’s really amazing. I know like I gave my disclaimer. I, I worked on these programs at, at Lykos, so I am a little biased. But yeah, I mean, but I think when the science guides you, I think it’s a little maybe okay to be biased. And, and, and y- when we look at what MDMA does compared to some of the classical, you know, psychedelics, it’s not just a flood of serotonin.

Dr. Ben Everett: It’s, it’s really working across the– all three mono- monoaminergics. also, you know, it– you get changes in neural steroids. You’ve got the oxytocin release. So it really helps the patient y- lean into the, the therapeutic alliance with their therapist. And we also see a, a decrease in blood flow to the amygdala, and that’s really where, you know, from a structural standpoint, that’s where we think a lot of the, the fear extinction and the, the pushback that a lot of patients have to it.

Dr. Ben Everett: And so when we look at patients that drop out from these psychotherapies because it’s too hard or whatever, you know, the MDMA really allows the patient to get through that, you know, feeling of the pushback or whatever. I’m not putting this very eloquently as you have.

Dr. Ben Everett: But I think MDMA really will eventually be approved. I know there’s some other companies that are working on it now. But I love the work that you’re doing. And I wouldn’t say to take it with a grain of salt. I think so long as it’s properly, you know, disclosed, hey, it’s, it’s open label.

Dr. Ben Everett: You know, there’s not a comparator at this point in time. But you’ve got to start with an evidence base to, to then move this into, you know, a more rigorous you know, controlled trial. and the functional unblinding thing. Yeah, that was something people kept on bringing up. And it’s like you said, that is not unique to, to psychedelics.

Dr. Ben Everett: It’s not even unique to psychiatry. You see it in all different areas of medicine. Just the informed consent process where you tell a patient, “Hey, you know, most patients that take this, they’re gonna get indigestion.” Well, if you tell patients they’re probably gonna get indigestion, you’re gonna see an increase in indigestion, dyspepsia, even in the placebo group.

Dr. Ben Everett: So a lot of it is sort of power of suggestion. It’s the right way to do it, obviously, with the informed consent. But, yeah, it’s interesting. I’ve talked way more than I normally talk.

Dr. Barbara O. Rothbaum: what’s also cool, what I like about our design, so we’re only giving one dose of MDMA, and then we’re giving the PE every day for two weeks. So with MDMA and I think all of the psychedelics, people think of them as neuroplastogens. They induce neuroplasticity. So we think that we’re really capitalizing on that giving the PE that works on learning every day after one dose. It’s also really cool ’cause we see a lot of self-compassion with the MDMA and, that’s the opposite of what we see with PTSD. We see so much self-blame and guilt. And so it’s really beautiful when people can open up and be a little bit more compassionate with themselves.

37:30 – Lessons from Australia’s MDMA Approval

Dr. Ben Everett: Yeah. All right, so we know that Australia did approve MDMA-assisted therapy a couple of years ago in 2023. They looked at it very differently than from how the FDA did. You know, any pros or cons or things that you think we can learn from, from the way Australia looked at the data and the way that they, you know, moved it through to approval?

Dr. Barbara O. Rothbaum: Yeah, I think we’ve got a big lesson. So Australia, a-as far as what I’ve seen and seen in the media, there have not been problems with safety. Where the big problem is access. What I heard is that the wait list are like two thousand people. And so we really need to get ahead of this to figure out when they are approved, because I think that they will be approved.

Dr. Barbara O. Rothbaum: I think folks are expecting– who knows? Folks were expecting the MDMA to be approved in twenty twenty-four, but people are expecting psilocybin to be approved for treatment-resistant depression probably by the end of this year. I think what we need to learn from Australia is we need to be prepared to deliver these therapies in a safe and effective environment because the access is an issue there.

39:00 – The Broader Psychedelic Landscape: Psilocybin, Ketamine, and Others

Dr. Ben Everett: Yeah. Yeah, for sure. all right, so beyond MDMA, you just mentioned psilocybin. I know that LSD is also being looked at, not necessarily for PTSD, but for anxiety and other things. Of the psychedelics that are being, and we can lump them all in, even though, okay, technically, you know, we could say MDMA, I think is an entactogen, not a classical psychedelic.

Dr. Ben Everett: We could say ketamine is a dissociative, but these things all get lumped in together. Where do you, you know, think i-i- is there better evidence for one versus the other? Again, I mentioned, I think MDMA is kind of especially unique for treating trauma, but, you know, I think more options are better. So, you know, what else do you know about like ketamine, LSD, psilocybin, anything else for PTSD at this point in time? Any trials underway?

Dr. Barbara O. Rothbaum: Yeah. As you said, I think the strongest evidence is for MDMA-assisted therapy with the two phase three trials. Psilocybin had an open clinical trial for PTSD that was effective, and I think that they are planning– they’re doing a multi-site trial as now. We are about to see our first patient. We’re continuing the MDMA PE work and about to do a small RCT comparing for PTSD, psilocybin plus support, so the regular psilocybin model versus psilocybin plus the two weeks of PE to see if it boosts the response or the durability of the response. So I think that, there’s a little bit of data out there that looks like psilocybin could be effective for PTSD as well. Ketamine, a number of people have looked at it in PTSD. What worries me a little bit about it is in most of the studies, people– there are a lot of variabilities in the dose and the administration, whether it’s combined with psychotherapy or not. So it’s hard to draw firm conclusions, and it looks like the response decreases in most people after about two weeks. So we’re about to do a study combining low-dose sublingual ketamine combined with the two-week prolonged exposure to see again, if it boosts response and then if the– thinking of them synergistically, does the ketamine boost the prolonged exposure response, and does the prolonged exposure then maintain the ketamine response?

Dr. Ben Everett: Yeah, that would be interesting.

Dr. Barbara O. Rothbaum: Yeah, I’m not aware of any data of LSD for PTSD. I think I saw one did on GAD, generalized anxiety.

Dr. Ben Everett: It’s GAD, and that’s the path that Yeah, I can’t even remember which, which company that is that’s, that’s doing that one.

Dr. Barbara O. Rothbaum: So I think methylone, right? Didn’t they get the FDA, what is it? Not

Dr. Ben Everett: Yeah, they’ve got the breakthrough therapy designation. Thank you.

Dr. Barbara O. Rothbaum: They’ll be looking at that for PTSD. Some people are talking about Ibogaine, obviously. I’m not an expert in Ibogaine the little bit of data I’m aware of looks like it’s stronger for substance use disorder and maybe opioid use disorder. But it– with those, I– there’s also probably a lot of PTSD and TBI.

Dr. Ben Everett: Yeah. and that’s kind of how I think about the psychedelics is at least right now the, the primary evidence seems to be kind of in one area. Like ibogaine is really more substance use MDMA is trauma, psilocybin is really depression, LSD is sort of anxiety. It doesn’t mean that they won’t all end up getting indications, you know, at some point in the future, but you kind of go with where the evidence base is to begin with.

Dr. Barbara O. Rothbaum: Then it’s easier to use. This has been the hardest research I’ve ever done. It’s taken years just to get all of the compliance and approvals in place. So even if they’re approved for something and they’re not Schedule 1, that’ll make it easier.

43:00 – Virtual Reality Exposure Therapy and the Brave Mind System

Dr. Ben Everett: All right. Well, look, let’s transition into virtual reality, artificial intelligence. So you, you know, as we mentioned, you really invented this modality earlier worked with a, a gentleman over at Georgia Tech, it sounds like. so tell us where, you know, where you are with this right now.

Dr. Ben Everett: Tell us about your Brave Mind program.

Dr. Barbara O. Rothbaum: Yeah. First let me start with the, a little of the history of VR. So our very first study was with the fear of heights, and what we found in that study is by the end of the study, without us even asking people to, seven out of 10 of the people exposed themselves to real-life height situations. So that’s what’s important. It doesn’t matter if somebody can expose themselves to a virtual elevator if they can’t get on a real elevator, but it does transfer. And then the next studies, actually my favorite VR apps are for the fear of flying, the virtual airplanes, because of the feasibility. For years, I’ve been treating folks with the fear of flying, and so many therapists will not because it’s a pain. If I have to drive to the airport, if I have to arrange to be able to go on an airplane, if I have to fly with a patient, it’s hours. Insurance isn’t gonna cover it, so it’s very expensive. And with the virtual airplane, I can exactly control the stimulus. If my patient’s not ready for turbulence, I can guarantee there won’t be turbulence.

Dr. Barbara O. Rothbaum: When they are ready for turbulence, I can guarantee there will be turbulence. We can take off and land as many times as we need to without leaving my office and all within the one-hour therapy session. So it really– it’s not– it works just as well as using a regular airplane. It’s just the feasibility is so much easier. So we went from using the VR and then treating PTSD, and then my worlds came together, w- the first one was w- we created a virtual Vietnam, thinking, okay if people were still in the system, they probably had treatment-resistant PTSD, it did seem to work. And then worked on a virtual Iraq and Afghanistan that now has evolved into Brave Mind, and it’s basically PE in VR. So as I said, in PE, we ask people to close their eyes and go back in their mind’s eye and picture the traumatic event.

Dr. Barbara O. Rothbaum: In VRE, virtual reality exposure therapy, their eyes are open, and the therapist is matching what the patient is describing in their imaginal exposure. So if they’re saying, “I’m driving back to base on a desert highway, hit an IED right front, everything fills with smoke,” the therapist can create that.

Dr. Barbara O. Rothbaum: And so we’re doing imaginal exposure to their most traumatic memories from Iraq or Afghanistan, but now immersed in this VR. And let me back up. They’re wearing what’s called a head-mounted display. That’s basically like a strappy helmet, got two television screens in front of each eye. It’s got earphones, and it’s got a position tracker. So just as my view changes when I move my head in reality, so it does in the virtual reality. For many of our environments, we have people sitting on a raised platform That has a base shaker, a woofer, a speaker underneath it, so they can feel the vibration. So for example, you can feel the vibrations of the Humvee, or if you’re in the virtual airplane, you can feel the turbulence of the landing gear coming up, and it just adds to the sensation.

Dr. Barbara O. Rothbaum: So it’s a potent stimulus. People are seeing it, they’re hearing it, they’re smelling it. For some environments we have smell, so we can introduce the smells. and with PTSD, they’re remembering it, in their mind’s eye. So it’s a very potent stimulus.

Dr. Ben Everett: Yeah, I’ve seen some of the demos. It’s really pretty– it is absolutely amazing what is going on, and it’s very effective, and I think that’s really– what matters at the end of the day, is how effective it is for patients. And one of the things I was struck with when I was doing this work was military sexual trauma and just you know, it’s been a big problem for the military.

Dr. Ben Everett: They’re doing a better job of looking at it and trying to uncover it now. But the people that are impacted by MST have very, very high rates of PTSD and very severe and extreme PTSD. So now you’ve extended this system to military sexual trauma as well, and that required building an entirely new environment. What was that like?

Dr. Barbara O. Rothbaum: So Dr. Skip Rizzo at University of Southern California and his team built the Brave Mind and the n-new one for MST. We worked on it together. So what you wanna do in the virtual reality, it’s expensive to build it, so you want to try to create an environment that you can use flexibly and individually for patients. We don’t need to recreate everything because when we’re doing, for PTSD, we’re doing imaginal exposure, so they’re seeing it in their mind’s eye. I actually think it’s better not to show it in the virtual reality if it’s not gonna match exactly. I think it’s better to have them imagine it and just being placed in this environment. for example, when we started with the virtual Iraq and Afghanistan, I asked for no blood. If you see an injury, unless it’s a medic, so we have them for medics, but if you see an injury, it’s probably not gonna match what the patient actually saw. And so then when there’s a mismatch, it takes them out of it. And all of us have a reaction to blood and injury, so we don’t want to just evoke something that’s a natural threat. also in the MST scenarios, I asked for no perpetrator. Again, if somebody is coming at you, that is a natural threat, and we should all have a response to that. That’s not what we’re treating in PTSD.

Dr. Barbara O. Rothbaum: PTSD is the memory of something happening, not an actual threat. So again, in their mind’s eye, we’re asking them to picture the perpetrator, to picture what was happening, and in the VR, we’re just placing them in that environment.

49:30 – Resilience, Hope, and the Future of PTSD Treatment

Dr. Ben Everett: Well, That’s great. I think I could talk to you for at least another half hour, another hour. I had some more stuff planned, but I know we’re at the end of our time together today. So maybe if I can just ask you one last kind of thought question and, you know, what gives you the most hope right now? You’ve come so– well, we, but through a lot of the work that you and your collaborators have done, we’ve come a long way in 40 years. So what gives you the most hope right now?

Dr. Barbara O. Rothbaum: I’ve become a real believer in the resilience of the human spirit. I will be with a patient, and I will feel a- almost like I’m holding their broken heart in my hand, the pain in the room is so palpable. I’ll think to myself, “How can anybody get over this?” And then they do. So I really am a believer in the resilience of the human spirit.

Dr. Barbara O. Rothbaum: I wanna get the message of hope out there that treatment works. A lot of folks with PTSD say, “Why should I go through treatment? My life is ruined because of what happened to me. You can’t change that.” What’s going on now is probably PTSD or depression or something else that we can treat, so really a message of hope.

Dr. Ben Everett: That’s great. Dr. Rothbaum, I want to thank you for coming on today. It’s been a pleasure hanging out again. Really thank you for your time joining us today, sharing your 40 years’ worth of hard-won perspective on this very difficult to treat consequential problem in psychiatry of post-traumatic stress disorder. It’s really been an illuminating conversation. I think our listeners are really gonna learn a lot from this episode. so with that, thank you very much for coming on.

Dr. Barbara O. Rothbaum: My pleasure. Thank you.

Dr. Ben Everett: This has been the JCP podcast. Insightful, evidence-based, human-centered.