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You might have thought psychedelic drugs went away with the Woodstock generation, but Veterans Affairs researchers are studying the question of whether psychedelics can be effective treatments for certain mental disorders. For details, the Federal Drive with Tom Temin turned to the Mental Health Director at the James J. Peters Medical Center in the Bronx, Dr. Rachel Yehuda.
Rachel Yehuda: It’s my pleasure. Thank you for asking me.
Tom Temin: And let’s begin with what kinds of disorders you think might be able to be helped in the first place. It sounds like not ordinary basic anxiety, or that kind of thing, but maybe more severe types of mental disorders?
Rachel Yehuda: Well, our research is going to be focused mostly on post traumatic stress disorder, which is a very big problem at the VA. But there’s a lot of evidence that suggests that psychedelic therapies might be useful for a lot of different kinds of mental health conditions. So we’re just at the beginning of this really new, exciting era. And when you have a treatment that can cut across many different mental health disorders, we call that a trans diagnostic approach, which means that the approach is in targeting one specific thing, but that it might be generally useful for a whole range of indications.
Tom Temin: All right, and before we get into how it might help, let’s define the term psychedelic, because everybody thinks of lysergic acid diethylamide, but that’s just one of a family of types of drugs?
Rachel Yehuda: Yes, you’re talking about LSD, which is perhaps the most notorious of the psychedelics. But psychedelics, in general are powerful psychoactive substances that can alter perception and alter mood. They can affect the way you think, or how you perform even cognitive tasks. They’re associated with kind of very vivid sensory experiences. Some people might call them hallucinations, but you know that you’re having a sensory experience, which is why it’s kind of different from the hallucination where you can’t trust what you’re seeing, whether it’s real or not. And the important thing to know about psychedelics is that they’re physiologically safe. They don’t really lead to dependence or addiction, although taking psychedelics, without the right kind of container or supervision might lead to psychological vulnerability. So that is where you start to see some of the potentially adverse effects of them. But they’re one of the safest physiologic drugs that we have in our toolkit.
Tom Temin: And they are therefore in other domains at this point, legal and sometimes prescribed?
Rachel Yehuda: No, they’re not legal. And that’s a very important thing to emphasize at this current time. We’re sitting here today, and these drugs have not been approved for use, certainly not federally, certainly not by the FDA, but some states are definitely establishing initiatives that might make some plant medicines legal, but the compound that we are investigating right now at the VA called MDMA, it’s not a plant medicine, per se. And it really isn’t legal anywhere that I know of in the United States right now. So when a compound isn’t legal, you can still do research on it. But you have to go through a lot of steps to make sure that everybody’s on board, the DEA, the FDA, a lot of different regulatory bodies, but it is certainly possible to do research in a compound that hasn’t yet been approved.
Tom Temin: Safe to say then that your work and the VA have gone through this groundwork to make sure that you can go ahead with these trials?
Tom Temin: Good, well, DEA you don’t want to fool around with. And therefore it will be used in these experiments with people.
Rachel Yehuda: We’ve already started. We’ve already been able to study the effects of MDMA in a handful of veterans right now. And we’re screening and getting more in the pipeline. So yes, we’re well underway with this.
Tom Temin: We’re speaking with Dr. Rachel Yehuda. She’s a mental health director at the James Peters Medical Center in the Bronx. And interesting place, the Bronx, New York City. This is where all of the work is taking place at this point is in the single location.
Rachel Yehuda: Yes, it’s a single-site study. It’s going to be a four-year study. And we’re planning to enroll between 60 and 68 combat veterans with PTSD.
Tom Temin: And what is the design of the experiment, that is to say, how does this work? You give them a dose of this and what are you measuring, what are the inputs, what are the outputs, what does it look like?
Rachel Yehuda: In most research studies, an active drug is compared against a placebo condition. And the phase two and phase three trials of MDMA-assisted psychotherapy are designed in just that way. But what we’re doing in our research is we are comparing three medicine doses of MDMA against two medicine doses of MDMA. And I should say that really it’s MDMA-assisted psychotherapy, because many people have the idea that the treatment involves just taking the psychedelic. But really there are hours and hours of psychotherapy that are associated with this treatment, including at least 12 90-minute sessions where the patient and therapists talk not under the influence of the medicine. So this is a comprehensive psychotherapy program that is assisted by being in an altered state sometimes. And so our question is, well how many of these sessions do you really need? And the MDMA-assisted psychotherapy protocol was designed by the drug sponsor MAPS [Multidisciplinary Association for Psychedelic Studies] to be three sessions. But many people report feeling better after one or two sessions, some might need more. But this is the beginning of seeing really how we can try this at home, so to speak, once MDMA-assisted psychotherapy is approved by the FDA, then it’ll be very important to try to understand how to use it in clinical practice.
Tom Temin: Right. So just to be clear, the drug is administered in conjunction or simultaneously with a talking session of 90 minutes.
Rachel Yehuda: No, no, no, there are 3 90-minute talking sessions, even before the MDMA is administered. The actual dosing session is eight hours long if you can believe it. The patient is sitting with or lying down with two therapists by their side. And it takes about eight hours for the dose of MDMA that we’re using to clear the system. Eight hours later, the patient is perfectly sober. And during the session, some patients like to talk and process their trauma. Some like to, what we call go inside, in the music with eyeshades and headphones, and people are very different about that. But the next day, after a session, there’s another 90-minute integration session. And two more to follow that, where if the patient didn’t talk very much during the session, they’ll talk a lot about what happened afterwards. And people wonder when they’re going through a session, sometimes whether they’re going to forget all the things that have happened to them. And that actually very rarely happens. A very vivid experience for people and usually they can recreate it, especially the highlights, which is really the most important.
Tom Temin: This is fascinating. And it’s nice to see that VA has done away with the 50-minute hour, you’ve got 90 minutes. It’s a bargain.
Rachel Yehuda: It’s going to be very challenging to try to implement this kind of therapy. But if there are good outcomes with it, which is our question, it’s not our assumption, it’s actually the question that we’re trying to research, then it might really be more economical to front load these kinds of intensive treatments to prevent people from having PTSD therapy for years or sometimes even decades. I mean, PTSD has proven to be a very difficult and intransigent problem. And sometimes patients come for very long periods of time. They get a little better. And of course, like every other chronic condition, there are good times and bad times, and an event can happen in the environment that can pull you back into a bad state. But you can go for long periods of time, when things are okay, then something happens, you come back, you feel like you’re at square one. So it is really a very difficult thing to treat. So if there’s an opportunity to do something very comprehensive in the beginning, kind of think about it like a surgery model, where you’re going to do something very intense, but hopefully, it’ll forestall a bigger problem. And that’s really the impetus behind these treatments. Can we do something that is really powerful and more sustained? And in whom will this work? And you know, if you enroll in one of our studies, don’t be surprised if we ask you to submit to a brain scan and blood testing for looking at molecular markers. Because we’re very interested in this question for whom is this therapy ideal? And we know off the bat, we’re not going in naively, that no treatment approach works for everyone. But I think it’s very important to try to get a better handle on who are the best candidates for this treatment. What can we reasonably expect?
Tom Temin: And do you know or do you have an inkling of what the mechanism is by which the psychedelic drug helps with PTSD? Is it sometimes shock therapy, changes the brain in some way that seems to have a lasting effect for some people or sometimes just thinking about lying on a beach in Hawaii does the same thing. What’s the mechanism here do you think?
Rachel Yehuda: Well, that’s a really interesting question. If you ask different people, they might be more forthcoming. You’re asking me so I’ll have to tell you. The honest answer for me is that we’re not really sure. A lot of the research that has been done has either been done in animal studies or in people that don’t have PTSD or don’t have other kinds of conditions. So we can’t quite know for sure what is happening. But we do know some things. We know that these drugs definitely affect the serotonin system, we know that they disrupt neural circuits in the brain, which might really give the opportunity to disrupt or reform the way that neurons talk to one another in the brain. So I know there are a lot of terms like “rewiring” and “turn on” and all that stuff. But really what we’re talking about is the ability of this drug to activate or suppress different neural circuits so that there’s an opportunity to form different kinds of connections and make different kinds of interpretations and foster different kinds of inputs and outputs in neurons. So we know that drugs promote gene expression and cellular neurogenesis. And that just means that cells can grow and dendritic plasticity, which means that inside of neurons, you can grow more branches that allow for more and better communication. But we haven’t quite put it all together. And we don’t know if these medicines are going to reverse kind of a problem that is in the brains of people already when they have a mental health condition such as PTSD, or whether the idea here is to just build a new circuit, let’s build something new here. Because we’re not going back to something that was, we might be able to do something completely new going forward. So it’s actually very exciting because the drug therapies that we have now in mental health are more predicated on this idea of fixing something, restoring, and this is rebuilding. And I really liked that from the perspective of resilience and post-traumatic growth.
Tom Temin: In the meantime, though, don’t try this at home.
Rachel Yehuda: Well, I think the idea here is that the psychotherapy and the therapeutic container are doing a lot of the work. So that really has to be emphasized. For people that will try this at home, it’s very important to understand where you might be able to have harm reduction if something does go wrong, or who you might want to turn to if you get caught in a loop. By that, people used to call it a bad trip. But for some people, what comes up during a psychedelic journey is very, very intense. And so I wouldn’t recommend it for somebody that really has a powerful mental health condition such as PTSD, because I think it can be very, very activating. And you might need somebody to talk to and that person’s not there.
Tom Temin: Got it. Dr. Rachel Yehuda is Mental Health director at the James Peters VA Medical Center in the Bronx, New York. Thanks so much for joining me.
Rachel Yehuda: Delighted to do so. Thank you so much.