February 14, 2023

Revived therapies (part 1) – Psychedelics

By Conor McKechnie and Dodi Axelson

Revived therapies (part 1) – Psychedelics

Psychedelic treatment is a therapy which is on the rise according to the increasing number of studies on the use of psylocibin, ketamine and MDMA to treat mental health disorders such as PTSD. In this episode, Conor talks to Prof. Eric Vermetten, a psychiatrist who has been working with the military in the Netherlands for the last 25 years helping Dutch armed forces and the uniformed people in the face of PTSD and psychotraumatology.

Show notes

CONOR: So, Dodi I'd like to do something a little bit different today.

DODI: Tell me.

CONOR: Well, I had a conversation with Professor Eric Vermetten, a psychiatrist who has been working with the military in the Netherlands for the last 25 years helping Dutch armed forces and the uniformed people so firefighters, paramedics, and so on. Our conversation focused on the field of psychotraumatology, which was new to me, and the interview was just absolutely fascinating. We began with what psychotraumatology is, we wandered our way through the use of new drugs and new therapies in the treatment of psychotraumatology psilocybin, psycholytics and psychedelics and the resurgence in the last few years of psychedelics as a therapeutic modality.

DODI: Oh, wow. So those are all a bunch of new words. But we often introduce new words, what is different about today?

CONOR: Well, what I'd like to do, dear listener, is to give you the whole raw conversation. So, this episode is a little bit longer than usual because I didn't really have the heart or maybe the brains to leave out any of the conversation.

DODI: So, this is your long run episode. And we all get to be flies on the wall now. So psychotraumatology is what matters today on Discovery Matters.

VERMETTEN: My name is Eric Vermetten, and I am working as a psychiatrist. I've been working as a military psychiatrist for the last 25 years in the Dutch armed forces. I was the head of research for 25 years. So, my focus pretty much in my professional life has been active-duty service members, as well as veterans that were returning from deployments such as from Afghanistan and so forth. I am also working as a professor of psychiatry at this beautiful town of Leiden, Leiden University Medical Centre, where I do research on Post Traumatic Stress Disorder, that's a disorder that's close to my heart and where my professional life has been focused.

CONOR: Is the focus of the PTSD research across all sorts of what you might call instances of PTSD or is it largely associated with people having had experiences in in conflict zones and in conflict situations?

VERMETTEN: Well, my professional life has focused on uniformed service members. So, the answer is yes, that's been my main focus. In research, we also look at civilian and psychotrauma, but probably also throughout history, uniformed service members in military have been the population that has been studied most and the knowledge that we have about PTSD pretty much comes from that population by far.

CONOR: You said two interesting things there, which I think merit definition for our listeners. First, you talked about psychotrauma. But maybe let's get the distinction between a uniformed and a non-uniformed service member, why do you make that distinction?

VERMETTEN: Okay, well, you know what? That's a very good question Conor. I think when somebody puts on the uniform because of the uniform they are exposed to potentially traumatic events. As civilians, we can also be exposed to potentially traumatic events, but then it happens to us as we go shopping, as we do our daily lives. But these guys and girls choose to wear the uniform to defend their country or in order to be policemen, or to be a nurse or a professional in a hospital setting. So, I think that distinguishes them a bit from the ones that are not wearing the uniform and are being exposed to these similar events.

CONOR: Probably, there's an element of kind of conscious choice to expose themselves to, frankly, a danger, whether it be physical or whether it be psychological. So could you talk a little bit about psycho trauma then and what we mean by that.

VERMETTEN: Psychotrauma is an event or a series of events that doesn't leave you untouched. I know that's a very ordinary definition. But they have such an impact that their lives are no longer the same. I could make it very technical, like you're going to be exposed to death or injury or serious injury of the self or others. That is the DSM classification of psychotrauma or a potential traumatic event. But in a sort of metaphorical way, it is like something that gets you under your skin. It's going to be there forever, and it's going to change the way you look at yourself and look at the world dramatically in a kind of a negative way because you wish that life was the way it was before this.

CONOR: And I assume that the results of these kinds of traumas, they manifest themselves very differently for different people. Do you sort of categorize the manifestation in any way?

VERMETTEN: We do, and this is maybe a little bit technical, but the way that these manifestations most often manifest themselves is in nightmares in disturbed sleep. Normally, we have rested sleep, and we wake up and we refresh. But people who have these memories under their skin are waking up at night, or they cannot fall asleep, because they have these nightmares that are waking them up or preventing sleep. But it also can happen during the daytime, then there are these triggers that remind them of the events that occur. That's one category. The other one is what we call avoidance, they try to block out remembrances or reminders of these events that have happened by not going to places, by not going to people, by not trusting people anymore. That's the second sort of category. And the third one is irritability, easily startled, jumpy, and those kind of things. These are the three things that can be very bothersome on top of things that people feel like 'I lost the meaning of life, and I should have died on the battlefield and I'm still alive and why bother'. It can have an existential connotation that people find very difficult to survive or to struggle with.

CONOR: There's so much that's so interesting, Eric. The sort of evolution of our understanding of this certainly through the brutality of the types of war that we fought in the last 150 years, the trauma that entailed the whole generation in the First World War, followed very rapidly by a second generation in the Second World War and an evolution of our understanding of shellshock and then becoming psychotrauma and us understanding more about it. But how would you characterize our increased understanding of this as a field that merits real epidemiological focus, if you want to call it that?

VERMETTEN: Yes, we've had a legacy of several wars. We thought that there was never going to happen again, but we have another war that's ongoing in Ukraine. So, as we speak, we see the brutality of war, we see the sexual violence of war, and we felt like no, this is never going to happen. But it is happening in front of our eyes. The things that we hear are devastating. And we will hear for the next couple of years or decades, probably from what has been going on there. And yeah, the lessons that we have learned from previous wars, hopefully will help us to get a better deal and helping the ones that are now exposed to these brutalities of the war. But still, it is devastating. It still is.

CONOR: So, what are the weaknesses and the failings in the way that we currently treat PTSD and psychotrauma?

VERMETTEN: Yeah, I liked that question a lot because in the last two decades I and others have invested very much in destigmatizing PTSD in the military and in uniform professionals. So, the problem typically is - and I'm not referring to the English only - but others is like, 'stuff it up, I'm okay, and pretend that everything is okay'. You can do that in service as it's ongoing, and 'I don't want to lose my profession as a fireman or a police officer'. Don't stuff it up, acknowledge that something's haunting you. So, we need to as professionals, and as scientists, destigmatize the disorder and tell people come early, because if you come early for treatment, the better the prognosis is. If you wait five years, and if you feel cognitive avoidance, and you drink and you drink more, and you're brutal to your wife, or your kids or so and another marriage, and another marriage, then is going to be very difficult. So, the earlier you can do something to intervene, the better the prognosis is. In some cases, it is so well that you will not lose your profession. So if you're early in the military, if you've been in Afghanistan, and you have these nightmares, and peers tell you like, 'hey, something's bothering you' go seek help, because you will be able to stay in the armed forces and you can keep your profession and you can be proud of your profession, you can continue to make a living out of that. So that's kind of a long answer. But I think that is the big lesson that we have learned come in early, and don't stigmatize.

CONOR: So, can we turn to sort of talking a little bit about what you're researching? Could you describe the new therapeutic areas that you're looking at, the use of drugs, which have previously been used in psychiatry, but maybe not in this area that have fallen out of favor and are now coming back to the forum? Are we seeing increased studies in the use of them.

VERMETTEN: Well, it’s for no reason. In Leiden, there was a colleague psychiatrist by the name of Jan Bastiaans, before we had 'PTSD', who was looking at the concentration camp syndrome, people who survived Auschwitz, or the major concentration camps and survived these camps were tormented with these memories. And what Jan Bastiaans did, there was pre-PTSD. He used psychedelics, to intervene, and to give people quote, unquote, their lives back to give them a sort of verbatim, give them the ability to explore things that they have not been able to revisit after they survived the camps. So, Jan Bastiaans did was to use LSD, and psilocybin and ketamine, and this was 50 years ago. Then, of course, there was the backlash that these psychedelics were kind of forbidden and got a lot of negative press about the use of psychedelics. But recently, psychedelics in the last 10-15 years, have shown us the potential specifically in severe cases of PTSD, it's not in the early cases if it's there for a half a year or so after your return from conflict. Now, in these really difficult complex cases, we see that these compounds that we've known for years, have great potential.

CONOR: You mentioned LSD and psilocybin and then ketamine, my limited understanding is that LSD and psilocybin or other type ketamine is slightly different. What is it that lumps them together as psychedelics in this kind of setting as a therapeutic? What are they doing that is similar to each other?

VERMETTEN: Well, you know, we all lumped them as psychedelics mind manifesting as they open the mind. So, they reveal things that are otherwise hidden. We lump them together as if they're all psychedelics, but ketamine is not really a psychedelic, and MDMA is not really a psychedelic, it's a pscholytic, it will be too detailed to go and unravel all these discrete pieces when we do call it a psychedelic and when we don't. But for the sake of now, let's call them all psychedelic, and they have mind manifesting capacities. They provide a window to the inside of the person to their soul, otherwise it is very hard to get it with ordinary psychotherapeutic processes.

CONOR: So, they allow people to explore things that perhaps are very difficult to talk about. How related to the actual biological mechanism of action is there? Are you prescribing the drug or are you prescribing the psychedelic experience? Is it that you use LSD for one type of PTSD or psilocybin for another and ketamine for another and MDMA for another? Or is it something about the common kind of opening up that's actually being prescribed?

VERMETTEN: The way you say it is proper, the opening up is what we prescribe. We use these compounds as catalysts to a psychotherapeutic process. And they may have also healing capacities. Yes, they have a potential to also do something that we call psychoblastic in the brain, they make new connections. But what we really think that matters most is that they're catalysts to the psychotherapeutic process. So, they allow the process to manifest in a way that was, I wouldn't say not be able before, but more difficult.

CONOR: It's very interesting. So, what was the trigger in the last 10 or 15 years that's really started people exploring this, because we've seen a lot of it come through in mental health research in the treatment of persistent depression, alongside talking therapies, and what we might now think of as very brutal therapies, such as electroshock therapy in the 60s and 70s. So, what has triggered the renewed interest? Is it that people are more relaxed about these types of drugs now? Or is it that there's clinical data coming through that shows that this really could be something that could fall into the mainstream treatment paradigm?

VERMETTEN: I think both. There is new data that is supportive when I was shown it about 5 or 6 years ago, it was the data with MDMA assisted psychotherapy for severe PTSD and I was shown that the people after two sessions of MDMA didn't meet criteria for PTSD anymore, I almost fell off my chair. So, like, wait a minute, when have we seen that last? In addition to a sort of a mindset that is like opening up, like, 'Hey, as I sort of lean forward, like, what is this if it's not toxic, it's not addictive?' These are things that may have been true 20 years ago, but we move beyond that. Another layer to that also, we are interested in these, let's call them altered state of consciousness. Now, I had a profound interest in hypnosis years back, and hypnosis is also an altered state of consciousness that doesn't have to do with drugs or so but exploring your inner mind. You can go very far in looking at visualization and exploring and words and meaning and narrative meanings of words. But it's fascinating to see if you then add MDMA to that process. It deepens the experience of such a level that is as fascinating. It’s not fascinating for me as a therapist, it's fascinating for the patients that feels that he or she has access to things that were deeply hidden or inaccessible.

CONOR: So, it's not just the brain and the mind that are still real mysteries, it's the fact that our own mind is a real mystery to ourselves specifically, isn't it?

VERMETTEN: Yeah, I'll give you one example that has had a profound meaning for me. Typically, you hear that when people take psilocybin it is in a way that psilocybin brings you closer to "nature". We often have these hatred feelings of being angry at the aggressor or being angry at the Germans for what they did in the Second World War, or angry at the assailant. But in the psilocybin experience, sometimes profound experiences can occur that alter a belief setting. The belief setting could sometimes be like that. We're all human and we were in a different situation back then. You did gruesome things, but we're all human. We belong to the same planet, we belong to this, I know that this can sound flaky, if I say this, but if somebody experiences it, and somebody can forgive the Nazis, for what they've done in the camps, and have a profound, like, 'hey, the Nazis were also human'. You can think yourself out of that. But you have to feel with your soul, that's the truth, that is very important for you. Then it may happen that the nightmare will stop hurting you.

CONOR: You said it sounds flaky, and of course there's still a lot of stigma associated with the disease. There's also stigma associated with the therapy here as well. There’s a challenge in that often, the description of the therapeutic process here does feel flaky. But it sounds to me like you're talking about consistent set of described experiences by many, many patients saying the same kind of thing about the experience they've had, is that correct?

VERMETTEN: Correct. That's the beauty of what we see now in science, we see that we can replicate things, we can predict, we can identify who will benefit from it, and who will probably not. So, we can stratify people who may get a good signal out of psilocybin or MDMA, or ketamine. Now, the next one is then to make it more accessible and trained therapists that can deliver this therapy in the way that it should be delivered. Because what I would say Conor is don't try this at home. Don't do it yourself, because it still is psychotherapy, it still is people that are going into a psychotherapeutic process that is catalyzed by these compounds.

CONOR: In the same way, we would never expect people to perform an appendectomy on themselves exactly the kind of thing that you need trained professional guidance. How is the field evolving, Eric? And then what's next in terms of making sure that the right kind of support exists around the patients, the therapists, and the institutions?

VERMETTEN: The working mechanism is so profoundly different because we come from an era where you would take your medication every day. You take your SSRI every day, and then you will get better. Here, you don't take medication every day, you take it maybe twice. And the therapy, an experimental session with MDMA, starts at nine and it ends at five. So, it's an eight-hour session, and you need to have these sessions a month apart. And in between these sessions, you will have weekly what we call integrative sessions, where you reflect on what has been going on in these long therapy sessions. It's a completely different working mechanism. You don't have to take MDMA later, every day. No, not at all, you take it twice, three times. And that's it. So, it's a different conceptualization of how therapy unfolds there. So, what we need to do is explore for whom this is beneficial, we need to provide training opportunities for people who like to do these therapies, we need to get regulatory agencies to prescribe the MDMA and psilocybin, then there's a whole recreational arm of using drugs, but I'm using it as a psychiatrist as a doctor. So, I brand them as medicines. I don't care so much what people do recreationally. I have nothing to say about that. But I would like to preserve these compounds as medicines. I'd like to see that centers with a good certification track record and good training would have the ability to use this, let's call it compassionate care. In the absence of formal approval at the level of the FDA, for instance, let's do compassionate care, because it works, and specific centers would then have the opportunity to deliver this care to the people who are really in need. In the military there are no drugs, but here we're talking about medicines. And I know (he's now retired) Nick Carter was a higher general in the British armed forces, and he endorsed the use of MDMA for veterans who are suffering from PTSD, and I think if the leadership then shows that there's a lean forward to exploring these drugs as medicine, I think okay, that's where we need to go. Mentioning guilt or so and let me say two words: is it very hard to tackle emotional quality, anger, rage and shame. What we typically see is when we use these compounds, that guilt is sort of melting, as if guilt is opening up. Guilt can haunt people for years. Some people have revenge and feelings of hatred. These compounds can really help to facilitate those processes. They are having a different atmosphere, having a different quality, that are not haunting people in their lives. So, to go back to your first question, if the leadership then endorses the experimental nature of these compounds, I think we can do a lot for service members who are haunted that lead terrible lives now.

CONOR: Eric, this has been absolutely fascinating. I could go on forever, ever, and ever, I find it's so interesting in terms of the progress that's being made. My last question is what's the next big step that must happen to make this move in the right direction? I mean, what are you waiting on? What's the mountain to climb, you know, today in our lifetimes, such that we leave something for the next generation to build on?

VERMETTEN: Well, it's happening already. I think there's a new generation that are forward leaning, I teach to students, and they really get it. So, they also read the book of Michael Pollan. I think they are also representative of a new generation. I'm 60, so I'm incentivized by this, this is not something that we can sort of halt or stop. So, it's going to be there, we have to regulate it. So, what I feel is we've lost it in the 60s or the 70s, we should not lose it this time, we should be careful and protective about it, teach the younger generation and hope that it will stay as a tool that can benefit many, many people.

CONOR: Superb, Eric, is there anything that you thought we should mention? Or say? Aside from don't try this at home. We're talking about therapy; we're not talking about recreational use of these compounds. Is there anything else you think we should have touched on that we didn't?

VERMETTEN: Well, we come from an era where everything was different. When I was trained as a resident in psychiatry, there was no MDMA, no psilocybin. I had to read it from the books of Jan Bastiaans from 50-60 years ago, and we have to sort of regain that momentum. We are regaining that momentum. If I look at what's now in literature, and if you just Google psychedelics, man it's brutal. So, it's maybe a hype for at least some, but there is a strong signal. So, you got me in my talking mode here and being enthusiastic about this. We talked about stigma and about it being the most difficult to treat PTSD patients. The problem that I face most is when people have existential guilt, and they commit suicide, because life is not a place where they want to be at anymore. If this compound can help them to have a perspective of life, that life is becoming meaningful again, and that they have an opportunity for reconciliation, then life is a fun place to be.

DODI: Oh, Conor, this was a delightful conversation, I see why you didn't have the heart to cut out any of the details. You know, while I was listening, I was thinking about all the current trend in Hollywood or on streaming services where humans are messing with memory as a kind of cure for PTSD. So, I think it's just fascinating to hear what a real scientist is thinking and Eric's perspective on the topic of psychotraumatology.

CONOR: I could have kept him on the phone for hours and hours, and he was so kind but this time, it's just another example of how curiosity can take us in so many different directions. But look, that's all we could squeeze into this episode. So do check the show notes for more details. Our executive producer is Andrea Kilin. This podcast is produced with the help of Bethany Grace Armitt-Brewster, she does a fabulous job. Editing mixing music by Tom Henley and the marvelous people at Banda productions. My name is not Dodi Axelson...

DODI: ...And my name is not Conor McKechnie. Make sure you rate us on Spotify or whichever platform you use. If you're listening on Spotify. We do have a poll under the episode description. It would help us if you answered that please, it makes us better see when we come back with another episode of Discovery Matters.

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