Episode 252: On this episode of Real Health Radio, I'm chatting with Michael Mithoefer, MD, who has completed a number of clinical trials testing MDMA-assisted psychotherapy. We discuss what makes MDMA so useful, what the psychotherapy sessions look like and the remaining steps that are needed for MDMA to be reclassified again.
Michael Mithoefer, MD, is a psychiatrist living in Asheville, NC, with a research office in Charleston, SC. He is Senior Medical Director for Medical Affairs, Training and Supervision at MAPS Public Benefit Corporation. He and his wife, Annie Mithoefer, completed the first MAPS-sponsored Phase II clinical trial testing MDMA-assisted psychotherapy for crime-related PTSD, a subsequent study with military veterans, firefighters and police officers, and a pilot study treating couples with MDMA combined with Cognitive Behavioral Conjoint Therapy for PTSD.
He has been Medical Monitor for a series of six Phase 2 trials in the US, Canada, Switzerland and Israel, which produced data that led to breakthrough therapy designation by the FDA in 2017. He now focuses on oversight of ongoing Clinical Trials and conducting training and supervision for research therapists.
He received his MD degree from the Medical University of South Carolina (MUSC) and completed residency trainings in Internal Medicine at the University of Virginia and Psychiatry at MUSC. He has been board certified in Psychiatry, Emergency Medicine and Internal Medicine. He is a Fellow of the American Psychiatric Association and Affiliate Assistant Professor of Psychiatry and Behavioral Sciences at MUSC.
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Chris Sandel: Welcome to Episode 252 of Real Health Radio. You can find the show notes and the links talked about as part of this episode at www.seven-health.com/252.
Before we get started, I just want to mention that I’m currently taking on new clients. I specialise in helping clients to overcome eating disorders and disordered eating, chronic dieting, body dissatisfaction and poor body image, exercise compulsion and overexercising, and also helping clients to regain their periods. If you want help with any of these areas or you simply want to have a better relationship with food and body and exercise, then please get in contact. You can head over to www.seven-health.com/help, and there you can read about how I work with clients and apply for a free initial chat. The address, again, is www.seven-health.com/help, and I’ll also include that in the show notes.
Hey, everyone. Welcome back to another episode of Real Health Radio. I’m your host, Chris Sandel. I’m a nutritionist that specialises in recovery from disordered eating and eating disorders, or really just helping anyone who has a messy relationship with food and body and exercise.
Today’s show is a guest interview, and today my guest is Dr Michael Mithoefer. Michael is a psychiatrist and the senior medical director of medical affairs, training and supervision at MAPS Public Benefit Corporation. He and his wife, Annie Mithoefer, completed the first MAPS-sponsored phase 2 clinical trial testing MDMA-assisted psychotherapy for crime-related PTSD, a subsequent with military veterans, firefighters and police officers, and also a pilot study treating couples with MDMA combined with cognitive behavioural conjoint therapy for PTSD.
He has been a medical monitor for a series of six phase 2 trials in the US, Canada, Switzerland, and Israel, which produced data that led to breakthrough therapy designations by the FDA in 2017, and he now focuses on oversight of ongoing clinical trials and conducting training and supervision for research therapists. He received his MD degree from the Medical University of South Carolina and completed residency training in internal medicine at the University of Virginia and psychiatry at MUSC. He’s been board-certified in psychiatry, emergency medicine, and internal medicine. He is a fellow of the American Psychiatric Association and affiliate assistant professor of psychiatry and behavioural sciences at MUSC.
I’ve been trying to get Michael on the podcast for quite a while now. Over the last couple of years, I’ve done a number of episodes looking at research with psychedelics, and for over two decades, Michael has been at the forefront of research with MDMA-assisted therapy. Of all the psychedelics, MDMA is the one that is furthest along in its process of getting reclassified so it can be once again used legally in therapy. As Michael mentions, it could be as early as next year that this happens.
This episode is fairly specific in terms of looking at MDMA-assisted therapy, the benefits that it can offer, why it can be so useful, what the sessions look like, and then the remaining steps that are needed for MDMA to be reclassified. But we also do spend a chunk of time talking more generally about psychotherapy and some of the important elements that are crucial for it to be successful. So if you’re doing psychotherapy currently, this is a good checklist to go through to see if this is part of what is included in your process.
In the episode, I make reference to IFS, which stands for Internal Family Systems, and EMDR, which stands for eye movement desensitization and reprocessing. We don’t stop and explain what either of these are, but I did recently do a whole solo podcast on the various trauma-healing modalities, and I cover both of them in detail in that episode as well as lots of other modalities. So if you haven’t listened to that episode yet, I highly suggest you do it. It’s 249 of the podcast.
I’m really grateful for the time I had with Michael. When we spoke, he was still recovering from Covid, so he apologised before we hit record for his voice being more gravelly than usual. I don’t think it takes anything away from the conversation. At the end, I’ll be back with a couple of recommendations, but for now, let’s get on with the show. Here is my conversation with Dr Michael Mithoefer.
Hey, Michael. Thanks so much for coming on the show today. I’m excited to get this opportunity to chat with you.
Michael Mithoefer: Thank you. It’s great to be here.
Chris Sandel: For the last two decades, you’ve been doing research on MDMA-assisted therapy and trying to get MDMA to become available once again to be used in therapy.
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Today’s conversation is mostly going to be focused on all things MDMA-assisted therapy, but it would be great to just start with a bit of background on you. What were you doing prior to getting into this work?
Michael Mithoefer: Actually, I originally trained as an emergency physician and practiced emergency medicine for 10 years, and then in 1991 I went back and did a psychiatry training, psychiatry residency. Actually, in many ways my interest in this kind of approach is connected with eating disorders since one of my first rotations as a psychiatry resident was on the eating disorder and trauma unit. So I became very interested in PTSD as well as eating disorders.
At the same time I was doing my psychiatry training, I was also intermittently doing training with Stanislav Grof and Christina Grof in holotropic breath work, which is a method of shifting consciousness that really grew out of Stan Grof’s psychedelic research back when LSD was legal. So I got interested in these ideas of shifting consciousness at the same time I got interested in trauma, and as part of that, eating disorders.
Chris Sandel: Nice. What was it in 1991 that prompted that decision to go into psychiatry?
Michael Mithoefer: Well, that’s a complicated question. I’m not sure I fully understand the answer to that. [laughs] It had quite a lot to do with, after 10 years in the emergency department treating wounds and illnesses and overdoses, often I was seeing the tail end of psychological suffering, ultimately manifesting in the ER. So I was more interested in what was going on before these problems, and also a different relationship with people, getting more interested in a more collaborative relationship with patients. I was always doing things to people in the emergency room, which was sometimes very useful and satisfying, but I longed for a different kind of work. It was also my own curiosity about the nature of consciousness and my own psyche.
Chris Sandel: What is it about MDMA that really drew you to focus on it specifically?
Michael Mithoefer: Well, it was largely – the early published reports, before MDMA became illegal in 1985, there was a number of published reports of reputable psychiatrists and psychologists using MDMA as an adjunct to psychotherapy. Also, we had experienced it ourselves with a therapist back in those days. I think MDMA tends to have a quality of helping people have more self-compassion and more willingness to look honestly at their own experiences as well as other people’s experience.
We’re a long way from understanding the full mechanism, but it had to do with the fact that trauma – basically, the reason my wife, Annie, and I were interested in doing this research more than 20 years ago was not because we wanted to be researchers; it was because we were treating a lot of people with trauma, and we didn’t have adequate tools for many of them. So it was really driven by that, the clinical need.
It seemed with trauma, so much of it is about fear and not self-judgment or lack of trust. Or emotional numbing on the other hand. Those features can all get in the way of successful therapy. So it just seemed like a logical thing to explore. Here’s a drug that seems to in many cases increase trust and decrease fear and defensiveness; could that be useful in opening a window for therapeutic change to happen? That was really the rationale for it.
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Chris Sandel: Nice. What is the history of MDMA-assisted therapy? I’m aware a lot of LSD and I’ve read about that in a fair bit of detail, but I don’t know so much about MDMA and its history before it was made illegal. How much was research going on? How much information was there available from other psychiatrists that you could glean from?
Michael Mithoefer: MDMA was first synthesized by Merck Pharmaceutical in 1912 and patented in 1914. Then they never did anything with it. They were looking at it, I guess, as an intermediary compound for some drugs.
Basically, when it came into the realm of therapy was in the ’70s. Alexander ‘Sasha’ Shulgin, who was a chemist who had worked for Dow Pharmaceutical, was interested in this kind of compound, and he synthesized some and tried it and thought it was a very interesting compound and gave some to his friend, Leo Zeff, who was a therapist. Leo Zeff agreed that it could be very useful for therapy, he thought.
So he started working with people, and then Leo Zeff ended up teaching a number of other therapists, psychiatrists and psychologists and other therapists, about how he used the MDMA in conjunction with therapy. It’s been off patent for many years. It came into the realm of therapy that way. Then there were some published reports, as I said, by very reputable people. But it was fairly quiet. It wasn’t widespread.
Back then it was looked at as a tool for therapy, not a thing to take at bars or raves. But then little by little, it got into more widespread use and the DEA looked into the MDMA that was being sold in Dallas. So that’s how it ended up in Schedule I, because before 1985 it wasn’t an approved drug but it wasn’t illegal, either. So then it was put in Schedule I by the DEA, even though there were hearings, and MAPS, the Multidisciplinary Association for Psychedelic Studies – actually, Rick Doblin, who founded MAPS, was the one that put in the application for the public hearings for MDMA.
The administrative law judge concluded after testimony from a number of psychiatrists and psychologists that it should be in Schedule III, that it shouldn’t be sold in bars but it should be available for medical use. But then the DEA administrator overruled the administrator judge’s recommendation and put it in Schedule I. So then it became much more difficult to do research. Of course, the recreational use didn’t decrease.
Actually, that in a way led to the first phase of research, because a lot of countries around the world, because of the recreational use, spent a lot of money doing preclinical animal studies and other basic research on MDMA. So that actually ended up saving MAPS a lot of money when it came to doing the clinical trials as a nonprofit company.
Chris Sandel: Wow. So it suffered the same fate as LSD because of how it was being used recreationally. Kind of ruined it for the therapists.
Michael Mithoefer: Yeah, in a similar way. Nothing happened for a long time. Finally, there were a few phase 1 trials, which is the first time we gave the drug to healthy volunteers. Charlie Grob did the first one of those at UCLA, and there were a couple other of those in the US. And then we started phase 2, which is the first time you give a drug to someone with a diagnosis to test treatment effects and safety in that population. We started working on our first protocol in 2000, finally got the first study started in early 2004 for MDMA for PTSD. The research has progressed over the years from there.
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Chris Sandel: Just to back up a little bit, let’s start with the basics. What is MDMA, for listeners who are not aware of it?
Michael Mithoefer: MDMA is often referred to as a psychedelic, which means mind-manifesting, basically. That’s a fair term, I think, but it’s quite different from quasi-psychedelics like LSD or psilocybin. Other terms have been suggested: entactogen or empathogen – entactogen meaning ‘to touch within’, referring to the fact, those qualities I mentioned a little while ago; it tends to help people be more in touch with their inner experience as well as more in touch with other people’s experience, too. And in general, with less of a sense of loss of control. There aren’t hallucinations like there are, often, with classic psychedelics.
But that’s also relative, because sometimes we’ve had some people in the study say, “I don’t know why they call this ecstasy.” So it’s not just that it makes people blissed out and everything’s fine; it really does often seem to help people be more aware of what their inner process is, and that can be challenging and difficult. Processing trauma can be difficult with or without MDMA. But it seems to help people be able to face things in a way, with a sense of “This is still difficult, but I can do it without being overwhelmed.”
One of the things about this model is the drug is only administered, in most protocols, three times, a month apart, in a session.
MDMA has some of those qualities. It has some of the same biochemical effects in the brain as LSD and psilocybin. But there’s also some quite different ones. It increases serotonin and other neurotransmitters and it increases levels of some hormones like oxytocin and prolactin, for instance. It causes about a four- or five-hour experience of shifting consciousness, in which what happens is quite variable, but it tends to be helpful in supporting people talking about difficult experiences and processing trauma.
Chris Sandel: I know you’ve done some research looking at its effect on memory reconsolidation and fear. What did the research find with this?
Michael Mithoefer: You mean in terms of the mechanism?
Chris Sandel: Both the mechanism and in terms of people’s experience with it as well.
Michael Mithoefer: We have not studied the mechanisms directly. We did do before and after memory and other neuropsychological testing that showed good safety in that regard. But there are lots of theories about how it’s working, and one of the ideas is about memory reconsolidation, that if memories come up, they’re usually associated with danger and fear, but they come up in a safe setting where people can face them in a different way. Maybe they get reconsolidated with different associations to being safe. That’s one of the ideas about how it might be working. There are quite a few others.
I do want to emphasize that we’re still in clinical trials. This is not an approved drug, so a lot of this still needs to be settled.
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Chris Sandel: Are there concerns with MDMA being used in therapeutic sessions, whether that’s from toxicity or addiction potential or any other issues?
Michael Mithoefer: There are always concerns. Every drug has side effects and possible risks as well as possible benefits. There are some important medical concerns. We’ve had a good safety record, but we do very careful medical and psychological screening ahead of time. We know that MDMA increases blood pressure and pulse, kind of like moderate exercise. So it’s important that people not have some underlying medical problem that would make that dangerous. There’s some things like that in terms of medical contraindications.
In terms of psychological risks, there are psychological risks. I think a lot of them are the same risks that go with any kind of deep therapy where you’re revisiting trauma. It can stir things up. So the preparation for the experience is very important, for safety, as well as the support to help people integrate the experience afterwards.
It’s possible people with PTSD – we enrol people in our studies who’ve had suicide attempts before. Suicide is always a risk. We did not see, in our recently completed phase 3 trial, any signal that MDMA itself increased the suicide risk. That wasn’t the case. But it’s not a trivial experience to have these long sessions of processing trauma, and people need to be prepared for good support afterwards to help them not only do it safely, but make best use of the experience.
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Chris Sandel: Let’s walk through what the process looks like for someone who is part of the study. If I’m breaking it down into three different sections, you’ve got the preparation and then what happens during the session and what happens afterwards as part of integration. Starting with the preparation, what does the preparation look like?
Michael Mithoefer: Even before preparation, there’s informed consent. We have a long informed consent form so people really understand what they’re agreeing to. And then we have careful medical and psychological screening by outside physicians and psychologists. Then the preparation, we have two therapists. In many cases it’s male and female, but not necessarily.
There are three 90-minute preparation sessions where the therapists meet with the participant and begin to get to know each other, address all the questions and concerns the person might have, and prepare them for what the sessions could be like and what the approach to therapy is like, including the fact that it can stir things up. This approach, a lot of psychiatric drugs are aimed at directly suppressing symptoms; this is not that approach. This is aimed at getting at the underlying cause of the symptoms. That can be challenging, and people need to be prepared for that to decide if that’s the approach they want to take and also to know that it can be difficult at times and that doesn’t mean something has gone wrong. That’s part of the healing process.
So you have those three 90-minute sessions, and then on the day of the MDMA or placebo – in our current trials it’s inactive placebo versus MDMA –
Chris Sandel: What is the placebo that you’re using?
Michael Mithoefer: The placebo, I think it’s cellulose. We changed from lactose to cellulose. It’s just an inactive capsule that looks the same as the MDMA capsule. Nobody knows ahead of time what somebody’s going to get.
So people come to the office around 9:00 in the morning and sit and talk with the therapists and then take the capsule around 10:00. Then the three people, the two therapists and the participant, spend the day together. The participant can either sit up, leaning against pillows, or lie down on a futon or a sofa. So they have the option. And the therapists are either sitting on either side or both on the same side, depending on the arrangement.
The idea is to develop a rhythm of encouraging people to spend some time focusing on their inner experience and then alternating that with some times of talking to the therapists. There’s no schedule for that. The idea is it’s going to be different for each person, and we encourage people to be open to however their process unfolds, without having an agenda about what it should be. So the therapists and the participant are encouraged to have beginner’s mind about what’s going to happen.
Some people spend almost all the time inside, and their therapists check in every hour. Usually it’s about half and half, periods of talking versus periods of focusing inward. Often people are listening to music. It’s optional, but we have eyeshades and headphones if people are comfortable with that. So they spend the day basically encouraging people to go inside and see what comes up, and then come out and talk about it and process it as they need to.
Then at 5:30, a night attendant comes. In most of the studies, people have spent the night afterwards, although we now have some sites where they don’t have to spend the night. But either way, they’re with somebody who’s supporting. And then the therapists come back the next morning for the first integration session or follow-up session.
The purpose of those sessions is to make sure somebody’s doing okay and to also see if there are things they want to talk about in the session that happened the day before or whatever’s coming up for them. That’s pretty variable, too. Often the process does keep unfolding. We really emphasize that. It’s not just what happens during the MDMA session. Sometimes the unfolding is easy and people have further realisations and enjoy talking about it; other times, some anxiety or other difficult feelings connected to what came up in the session can come up later during that week, and we prepare people for that, and we’re there to help them process it if feelings do come up.
Then there are three 90-minute integration sessions over the several weeks after each MDMA session or placebo session, and then a month later, they have a session again. That happens three times at monthly intervals. Then there are periodic meetings with a psychologist to have the testing repeated and see how their symptom levels are doing. And then we have follow-up at two months and at one year or longer.
Chris Sandel: In terms of the fact that you have three sessions with the MDMA, how did you arrive at three?
Michael Mithoefer: We started with two, actually, and we arrived at that because we thought we needed at least two and we didn’t know if we could get permission for any. So we started with two, and in that first study, about halfway through, when we had safety data, we asked to increase to three sessions.
The reason for that was even though we actually got very good results after two sessions, there was some further improvement after three sessions. But most of it happened early on. But our thinking was, for one, if you have only two sessions, each session is either the first session or the last session, so people are either getting used to it or they’re realising it’s the last one. It’s kind of nice to have one in between that doesn’t have those connections. Also, we had the impression that maybe the three sessions, the results would be more durable.
That’s what we’re going with in our current phase 3 trials, one of which we’ve finished and the other is going on now. But we’re testing this – Rachel Yehuda at Bronx VA is doing a study now looking at two versus three sessions. Same design, same therapeutic approach as our phase 3 trials. And then there’ll be long-term follow-up to see if there is a difference between two versus three.
Chris Sandel: Is there any looking at further than three, where we think actually four could be helpful or five could be helpful? Or does it feel like the law of diminishing returns – at three you’ve maxed out?
Michael Mithoefer: Well, I think it’s going to be variable when we get into clinical use. And this should be studied more, too. We’re obviously constrained in the research. We can’t be flexible. We had some people that – well, we had one person that after one session was doing so well, he didn’t want any more sessions. He stayed in for all the measurements and continued to do well, but he felt better and he felt he didn’t need any more, and he apparently didn’t. On the other hand, there were some people who felt that some more sessions could’ve been useful.
So I think this will be sorted out if we get approval. Maybe next year, that’s a possibility. It’ll be easier to sort it out with further research and clinical experience. I think the main message still holds: it’s not about more or chronic use of MDMA. A relatively limited number of sessions or periodic sessions with long intervals in between is more the model to help people and to really integrate the experience.
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Chris Sandel: I know you’re trained in many different modalities, like Internal Family Systems and EMDR, etc. Are these then used during the MDMA-assisted therapy session?
Michael Mithoefer: In our research, it’s an interesting model; we have a manual that describes the model, and the model includes being able to address whatever’s coming up using other techniques. We don’t set out to do, for instance, Internal Family Systems work, but if people start talking about parts, then that model is very helpful.
In terms of Internal Family Systems, it was interesting; we did a sub-study – this isn’t published and it’s not a validated measure, but we made a measure to look at, after each session, whether parts came up, and if they did, who were they brought up by, the therapists or the participant. What we found was in the active doses of MDMA, which in that study was 125 to 75 – both were very effective for PTSD – in the active doses, parts came up almost 80% of the time. In the inactive dose, it was less than 30% of the time. And it was almost always brought up by the participant, not the therapists. If the therapists brought it up, the idea was they were responding to what someone was already describing.
So there does seem to be something about MDMA that facilitates awareness of the normal multiplicity of our psyche, our inner parts, and facilitates self-energy, the ability to work with them. So that’s been an observation. I think people going forward, I’m sure, are going to do studies with IFS and MDMA more directly.
As far as EMDR goes, I used to do a lot of EMDR also and found it very useful. I think where EMDR may be helpful is for the integration period. I think in the MDMA sessions, you don’t really need EMDR, but during the integration period, if things are coming up that people want to process, that could be a great way to do it. I think there are some people interested in studying that as well, about EMDR with a couple of MDMA sessions embedded in it.
Chris Sandel: Cool. The figures that you quoted with IFS – I remember reading an article that you’d written for MAPS called ‘MDMA-assisted psychotherapy: How different is it to other psychotherapy?’ This was back in 2013, I think, that it came out, so fast approaching a decade ago that you wrote this.
But you had those figures in there, and I really liked this piece because it touched on the important elements that go into any psychotherapy session and how these elements can be helpful, and then touching on how they feature in MDMA-assisted therapy. I know you listed seven of them as part of that. I know we’ve touched on some of them already, but I think it would be useful to go through them, and you can then be adding in any extra information, because I thought it was a really well-done article.
Michael Mithoefer: Oh, thank you.
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Chris Sandel: In terms of the first element, you said ‘establishing a safe and supportive therapeutic setting and a mindset conducive to healing’. I know we’ve touched on that a little bit as well as part of the preparation piece, but is there anything else you would add with this?
Michael Mithoefer: Part of that safety is really emphasizing that we’re not going to push people to go into any difficult material more than they feel ready to. The other part of the safety, of course, is very good ethical boundaries. Really, establishing a safe setting is terribly important to any therapy, but maybe even more so with these long sessions.
Chris Sandel: Am I correct, the session is like eight hours long?
Michael Mithoefer: Yeah.
Chris Sandel: That’s a long time to be in session with someone, considering often you’re doing 50 minutes or maybe longer for a session. But yeah, eight hours is a long stretch. How is it for you, being the therapist for eight hours? That sounds like a lot.
Michael Mithoefer: It does sound like a lot. And in one way it is a lot, but in another way it’s easier. You have the time. It’s really nice having a co-therapist for those long sessions. We don’t know what’ll be required going forward, but there’s a great luxury in having that much time because it makes it easier to really trust that if you encourage people to stay with what’s happening, they’re going to move through it. And if they didn’t have time to move through it, that would be a problem.
So yeah, sometimes it gets quite tiring; sometimes it gets quite emotionally intense. Good self-care for the therapist afterwards and having a way to process their own experiences afterwards is very important.
Chris Sandel: For you personally, how often are you doing them with your wife, Annie, versus with someone else?
Michael Mithoefer: I’ve done almost all the session with my wife Annie. Except for we did one study with Candice Monson and Anne Wagner, two psychologists from Toronto. Candice developed cognitive-behavioural conjoint therapy. So we did a study with Candice combining CBCT with MDMA. In that case, I worked with Candice and Anne, Annie worked with Candice and Anne. Annie and I didn’t work together. That was a lot of fun to work with really good therapists from a different background. We learned from each other. It was great.
Chris Sandel: Nice. Back to the elements, element 2, you said ‘anxiety management training and stress inoculation training’. You commented that you teach mindful breathing or just reinforce any other methods that participants have found to be effective.
Michael Mithoefer: Yeah, we talk to them about that ahead of time and practice some method for helping people calm their system. This model, we try to stay away from using medicines to decrease the anxiety directly. We want to support people to go into the anxiety or into whatever’s coming up. But it is interesting, too – the way we work with, say, anxiety or other difficult feelings depends somewhat on what part of the session it happens in.
In general, quite a few people – certainly not everybody, but quite a few people experience anxiety when the MDMA is coming on. It revs up the autonomic nervous system, so it can feel kind of like a panic attack for some people. People feel like they’re losing control because their consciousness is shifting. So early on is when we really tend to reassure people, encourage them to use their breath in that diaphragmatic breathing or mindful breathing to help them calm themselves and realise they’re going to move through this.
Later in the sessions, we actually don’t encourage people to try to relax most of the time. We usually encourage them to breathe into the experience and, as much as they’re willing to and as much as they decide to, to stay present with the difficult feelings and see what they’re going to discover and see how their inner healing wisdom is going to move them through it.
Chris Sandel: I can understand the difference between those two things, because in the second scenario you just talked about there, you’re dealing with the actual trauma and the real work that you want to deal with, whereas in the early stage it’s more just getting someone acclimatised to being in that altered state because of the MDMA.
Michael Mithoefer: Exactly. Early on, helping reassure people is part of creating safety before you encourage them to stay with it. Always emphasizing it’s a choice. We never push people. We ask them if it would be okay to stay with the anxiety or encourage them to do as much as they can, but acknowledging that we don’t know. They know better than we do.
Chris Sandel: Then the third element was exposure therapy. I think you already mentioned this, just allowing this to come up naturally at the point that it’s ready to come up.
Michael Mithoefer: Yeah. People virtually always end up doing what’s referred to as imaginal exposure, prolonged exposure therapy, revisiting the trauma. Some people go right to that, but other people have some other experience first. Maybe some affirming experience first, or something else that they process, and then they go to the ‘index trauma’. I think that’s one reason we think this inner-directive or relatively non-directive approach is useful, because it allows for each individual to have these different elements of the experience in different orders and to different degrees according to their own process.
Chris Sandel: Nice. Then #4 is cognitive restructuring.
Michael Mithoefer: We don’t set out to do cognitive-behavioural therapy, but often people notice these distortions and realise they get a new perspective about things. “Oh, I was thinking this situation is actually much more dangerous than it really is” or really noticing their thought patterns and coming to different conclusions. Certainly some of that may happen in conversation with the therapists to support them exploring that, but often it just happens spontaneously. And it’s much more powerful, I think, when people arrive at these insights themselves.
Chris Sandel: Yeah. And how much does that awareness stick? The next day when you’re doing integration and you’re chatting about that, is that awareness still there? Or is someone more struggling with “I don’t even know how I thought of it that way during that experience because that just seems so alien to me now”?
Michael Mithoefer: Maybe a little bit of each, but it’s striking how much people tend to think “That was a genuine, important experience, even if I’m feeling differently now.” It makes me think about one of the veterans – one of the things he said –
Chris Sandel: Was it the quote about him cleaning out the attic? Was that the one?
Michael Mithoefer: [laughs] No, that’s a good one too. Oh, he said, in his first session, after he’d have these quite amazing realisations about the way he kept a part of himself locked up in a cage after being in Iraq because he was afraid of it – just really helpful work – and at one point he said, “When I ask myself am I going to be able to hold on to this wisdom that I’m arriving at now, when I ask myself that question, the answer I get is I think it’s so profound, I don’t think I could ever forget it.”
It’s striking how much it tends to be a genuine experience that people don’t dismiss later. And at the same time, of course, people can – it slips away. Part of the preparation and integration is helping people remember. We all forget things, what we really know. We all lose perspective sometimes. So in the integration, we encourage people to do two paradoxical things: don’t worry about trying to hold on to the experience. They’re never going to lose that on one level. But also, have ways of reconnecting with it.
Part of the integration is encouraging people to take some time every day to check in with themselves, whether that’s through meditation or however they take some time out to see how they’re doing with their inner process. Doing that and staying connected to what they’ve realised and what they’ve experienced can be part of it, because it does make a difference, whether you have a practice to keep connected to what you’ve learned and experienced.
Chris Sandel: Could that be also – and again, I know you’re not doing this as part of the trials, but having a further MDMA session, I don’t know, a year later or two years later or whatever as a top-up of sorts?
Michael Mithoefer: That’s an interesting idea. In our long-term follow-up questionnaires, we always ask people a lot of questions later, and several people said they thought another session in six months or a year could be really useful. I think that’ll be another thing to look at and study.
Chris Sandel: The next element is transference and countertransference.
Michael Mithoefer: The transference and countertransference can be heightened by the MDMA.
Chris Sandel: For listeners who don’t know what transference and countertransference is, do you want to explain that?
Michael Mithoefer: The transference is when the patient or participant or client is having feelings about the therapists based on past experience, like their parents, for instance. Kind of projecting that onto the therapist, something from their own past experience. And the countertransference is the converse of that – the therapists are projecting things onto the person. Like if the participant reminded you of someone in your life, you want to be aware that you might be having some feelings that are about those old things.
In therapy, working with that can be very useful, because it’s a chance to deal with a relationship in real time. It can also be – I think it makes the issue of ethical boundaries all the more important. People can be more suggestible; these states can be very intense. Therapists might start feeling that they’ve got to rescue people because it’s intense. So it’s really important for the therapist to have self-awareness about this, but also, it can be a wonderful opportunity for people to have a corrective experience of say good parenting. If they suddenly can trust the therapist more, that’s a chance to have that corrective attachment experience, and it’s got to be handled with a lot of mindfulness.
Chris Sandel: The sixth element then is working with the multiplicity of the psyche, which you kind of already touched on when you were talking about the parts. Is there anything else you’d want to add here?
Michael Mithoefer: I don’t think so, no, except that I’ve found Internal Family Systems – I’ve done that training – to be very helpful in that way. And there are also other systems for inner voice dialogue and psychosynthesis. Other people have observed the same phenomenon. But it is important to not pathologize that. Some therapists may not be aware that this is a normal phenomenon and might start pathologizing it. When we realise that MDMA seems to bring up this awareness of parts more often, it’s important to be prepared for not pathologizing that.
Chris Sandel: Then the seventh element was somatic manifestations of trauma.
Michael Mithoefer: A lot of people have now read Bessel van der Kolk’s wonderful book, The Body Keeps the Score, about the importance of including the somatic elements that people are holding a lot in their body. The way that comes up in this therapy is mainly bringing attention to the body, talking to people about it in the prep sessions, asking what they’re aware in their body and then modelling that, that in the MDMA sessions, we’ll bring their attention to their body and encourage them to let their body move or express itself however it wants to.
Then sometimes people want to push and get some resistance, so we have careful agreements about doing that. And sometimes people want some nurturing touch, so we have very careful agreements about we can hold their hand if they want or put a hand on their shoulder, sometimes give them a hug. But limited body contact, and always emphasizing that they’re in control. They can always say stop. It’s important to do that with a lot of safety.
But it can make a lot of difference. Sometimes if people are trying to figure things out cognitively and feeling stuck, sometimes inviting them to go inside and focus on their body and see what they’re experiencing in their body can really help to shift things. Energy can start to move or people can realise how they’re holding tension, and a lot of release can happen. So it’s not all just about words, for sure.
00:49:27
Chris Sandel: For you, who’s obviously done psychotherapy for such a long time without MDMA and now being able to do the trials with MDMA, what are your thoughts on this? At the point at which it does become legal, how much do you think you’ll be doing MDMA-assisted therapy as the main thing that you want to be doing?
Michael Mithoefer: Well, that’ll depend. I’m 75 years old. [laughs]
Chris Sandel: But we can imagine you’re a 30-year-old if it would help you to answer this question. [laughs]
Michael Mithoefer: That’s a very interesting question. I think when people are stuck and they haven’t been responding, it can be so striking, what we’re seeing so far. It appears that if this continues to pan out with the research, there’s going to be a big demand for this and therapists are going to want to do it.
At the same time, it’s not for everybody, and I’m sure not everybody wants this approach and we’ll learn more about who it’s most suitable for. Some people responded in our clinical trials much better than others, and we don’t know how to predict that yet.
So I guess the answer, if we’re still in full-time practice, I think I might do two-thirds MDMA-assisted therapy and one-third regular therapy.
Chris Sandel: Would you have a thought of “Let’s start with regular therapy and see if that works first, and the MDMA is a backup”? Or it’s like, “Let’s start with that because I think it’s so powerful and we can save ourselves some time”? How would you think about it?
Michael Mithoefer: I think individualising it will be the important thing, but I don’t think there’s any reason so far, based on the evidence so far anyway, for relegating MDMA to a second line treatment. If some people are more interested in this approach right from the beginning – again, we’re pending finishing our clinical trial, so we don’t know for sure, but it looks like there’s no reason why it couldn’t be the first line treatment for a lot of people.
In a way, I think the division may become less stark in that I think doing an MDMA session every month, three times, is pretty fast-paced. That’s the way it’s practical for the research, it seems to work, but I think in most cases it’ll be a slower pace and people can spend more time integrating or more time in preparation.
Chris Sandel: So you’re figuring out on an individual basis, do we need just the one session, do we need the three, do we need four – based on “We did this and we’re now six weeks on, and based on this we’re now making our decision.”
Michael Mithoefer: Right. Also, we’re looking into group therapy. Chris Stauffer in Portland is going to do a group therapy study with MDMA. He’s already done some with psilocybin. So I think there’ll be lots of different combinations to combine. The beauty of this approach is there are lots of different approaches people might be taking, and they could add an occasional MDMA session to facilitate many different approaches. I think there’s going to be more and more research about that. Different ways of combining it with existing approaches.
Chris Sandel: Am I correct – it’s phase 3 at the moment that is still ongoing?
Michael Mithoefer: That’s right. The normal thing is you need two phase 3 trials to apply for a new drug application. We finished the first one and had very powerful results that were published in Nature Medicine, and that’s called the pivotal trial, which was very successful. The second is called the confirmatory trial. Same design, basically. And we’ve finished enrolment, so all 100 people are enrolled, and we expect that study to be finished perhaps this summer.
Chris Sandel: What is the makeup of the participants? Is it PTSD?
Michael Mithoefer: Yeah, it’s all people with PTSD from different causes. In the first study, less than a third were veterans. I think about 25% or something were a little over that were veterans. The rest were people with other kinds of trauma, including a lot of childhood sexual abuse and a lot of complex trauma. It wasn’t just single-incident trauma that we had in the first study, the first phase 3. Or in the second one, either.
Chris Sandel: Can you talk about the results from the first phase 3 trial?
Michael Mithoefer: Yea. The first one, we had to achieve a p value of 0.05 or less. It was our agreement with FDA. And actually, our p value was 0.0001, so it was a very, very powerful effect, MDMA with the therapy compared to all the same therapy without the MDMA. And the effect size was 0.91, so a large effect size. It was a very powerful result in the first study. We don’t know what’s going to happen with the second one, but we’ll find out before too long.
00:55:39
Chris Sandel: My work is in the area of eating disorders, which is why I’m interested in MDMA-assisted therapy along with other forms of psychedelic therapy, because they appear to be helpful with eating disorders, and you were part of a recent research publication in the Journal of Psychiatric Research called ‘MDMA-assisted therapy significantly reduces eating disorder symptoms in a randomized placebo-controlled trial of adults with severe PTSD’. Are you able to talk about that and what the results were?
Michael Mithoefer: Yeah. Interestingly, I mentioned that as a resident I was on the eating disorder service at Medical University of South Carolina in the early ’90s. Tim Brewerton was the director of that unit, and Tim is the lead author on the paper, along with Adele Lafrance and other people that are experts on eating disorders. It’s kind of come full-circle.
So this was not studying people with eating disorders, but we used the EAT-26 to measure eating disorder symptoms in our phase 3 trial. What we saw was in people with at-risk symptoms or elevated scores, they tended to get better. It’s basically pilot data to suggest that we want to do a formal eating disorder study. It hasn’t started yet, but there’s one in development.
Chris Sandel: Does that mean that the trials at this point have to be connected to PTSD? Is that a prerequisite of this stage?
Michael Mithoefer: No, not necessarily. Our confirmatory phase 3 trial, our indication that we applied for with FDA is for PTSD, so those trials have to be about PTSD. But now there’s no reason why people can’t do other trials where people don’t have to have PTSD. Of course, as you know, there’s a lot of overlap between trauma and eating disorders. But it wouldn’t have to be having a PTSD diagnosis.
00:58:07
Chris Sandel: You also completed a pilot study with treating couples with MDMA-assisted psychotherapy. What was the criteria for this, and what did the study find?
Michael Mithoefer: It was a pilot study with no control group. It was kind of a proof of principle treatment development study. We did that with Candice Monson and Anne Wagner. Back before MDMA became illegal, there were reports of it being useful with couples’ therapy, which makes sense because it can help with fear and defensiveness and help with communication, is how it appears.
We had an interest in that, but we didn’t know how we would get permission for a study to give MDMA to two people at once. But then when we started talking to Candice Monson and other people at the National PTSD Center about how to do some research, we realised that Candice had very good published data about using cognitive-behavioural conjoint therapy for working with couples to treat PTSD, where the couple was basically the patient.
Using that, combining our approach with Candice’s approach gave us a good rationale for why we needed to treat the couple together. So that’s what we did. It was only six couples, but one person had to have PTSD, and the other person had to not have PTSD in the couple. As it happened, it was all married couples, although that wasn’t a requirement. It could be any significant person.
Basically, what we did was embedded two all-day MDMA sessions using our usual approach in a course of cognitive-behavioural conjoint therapy (CBCT). So the couples would come in and do some of the modules for CBCT to learn some communication skills and that kind of thing. Then they’ve had an MDMA session with two of the therapists, either me or Annie and either Candice or Anne – somebody experienced with MDMA, somebody experienced with CBCT. They’d have a session together. We had two recliners. People had headphones that had separate volumes and eyeshades so they could both tip back and focus on their own process at times, and then they could also periodically turn and talk to each other, communicate with each other.
And then the integration period is when there were a lot – the rest of the CBCT modules occurred. Again, no control group, so we can’t prove anything, but we had very strong results in PTSD symptoms and in relationship satisfaction. And these were people who had had a lot of treatment before, so it’s very suggestive that this needs to be pursued. Actually, Anne and Candice are getting ready to do a controlled trial in Toronto with CBCT, with or without MDMA. As well as CBCT in individuals with or without MDMA. So we’ll see.
Chris Sandel: That’s great. Are there any other trials that are recruiting at the moment that you think the listeners should be aware of that they can then go and see if they qualify for?
Michael Mithoefer: I can’t think of any that are recruiting at the moment. We have a number of investigators introducing in doing investigator-initiated trials. We’ve had over 150 suggestions about that. New studies are coming online, so I think people could sign up for a free newsletter from MAPS.org. We’ll announce when new investigator-initiated trials or MAPS trials are coming online. And also www.clinicaltrials.gov. All the trials have to be registered there. I encourage people to stay tuned, because there are going to be more and more studies coming along.
Chris Sandel: Nice. I can put both of those in the show notes.
01:03:02
If everything goes to plan, when do you think MDMA-assisted therapy will be approved and open to the public, in whatever way it would be open to the public?
Michael Mithoefer: If all goes well with the current trial, then we expect approval could come in 2023. We’ll finish this study this year, and then there’s quite a process of getting all the data ready for FDA and submitting the application, and then they make a decision. We’re predicting 2023 sometime, it could well be approved, if things go well.
Chris Sandel: Will that be only for specific things in terms of PTSD or anorexia, or things that have been diagnosable? Or it will be more open than that once approval is given?
Michael Mithoefer: The indication will be for PTSD, and we don’t expect that there’ll be any limitation on off-label use. Like any other drug – we don’t know for sure what the requirements will be, but I think people will be able to start doing research much more easily into other indications and using it clinically as they’re allowed to.
Chris Sandel: How long do you think, from then, it will be before it’s more widespread or commonplace? So in the same way someone goes in for a block of EMDR or hypnotherapy, they’re going to do MDMA-assisted therapy.
Michael Mithoefer: Well, I’m not sure. We think there’s going to be a lot of demand, and we also think it’s important that this only be administered by people with proper training in the proper setting. So we think there’s going to be a REMS, a risk evaluation and mitigation strategy, that will be required by FDA. We think it’s a good idea to have a REMS. Again, we don’t know at this point for sure, but it’s likely that the REMS will be that it can only be administered in licensed clinics where people have proper training, and the drug gets shipped directly from manufacturer either to the clinic or to the participant, who then can only open it at the clinic. Something like that. So it won’t be a take-home drug.
There’ll be limitations according to how many clinics there are and how many people are trained. Right now we’ve trained a lot of therapists to work on the research, and now we’re training people to be ready for post-approval. It’s interesting that people are willing to come do the training even though the drug isn’t approved. But they realise they’re doing that at risk. A lot of people want to get prepared.
So it’ll be a matter of – one thing we are trying to pay close attention to is, how fast can we scale up the training and make the treatment available while still maintaining quality and giving people good training and making sure people are well taken care of in an ethical and skillful manner?
Chris Sandel: Are you one of the people who is doing that training? Or you’re more overseeing how that training is being run?
Michael Mithoefer: My wife and I are two of the trainers. We have three pairs of lead trainers now, and more new trainers are coming along, people who have been able to get quite a lot of experience now in the clinical trials.
Chris Sandel: Is it just MAPS that is doing the training, or people are getting training from other places as well?
Michael Mithoefer: We’re collaborating with other places too. Part of what we’re interested in is increasing the number of MAPS trainings, but also finding people that we can collaborate with. The most longstanding of those has been with California Institute of Integral Studies, CIIS. They have a programme called CPTR, Center for Psychedelic Treatment and Research. So they have a nine-month programme of monthly weekend trainings, and then Annie and I, or Bruce and Marcela from Boulder, do a week of MAPS training embedded in that. Now Bruce and Marcela are doing a similar thing with Naropa Institute in Boulder. And then there’s some other freestanding training institutes that are developing that we’re collaborating with.
I think our centralised MAPS trainings are great, but I also think we need to have a lot of regional and local centres where people can have training and ongoing supervision. So we’re hoping it’s going to develop in both of those ways.
Chris Sandel: What about the actual making of the MDMA? Are you going to be able to produce enough – and I don’t mean you, but whoever is producing it, are they going to be able to produce enough to meet up with the demand that’s expected?
Michael Mithoefer: I think so. It’s being produced by good manufacturing processes, drug manufacturers. It’s cumbersome getting it ramped up, and right now there’s a lot of MDMA instability testing to determine the shelf-life and things. But I don’t think that’s going to be a problem, ultimately.
One thing about this drug is you only take it a few times. It’s quite a different model.
Chris Sandel: Yes, definitely. Look, Michael, this has been fascinating to get to chat with you and hear about all the things connected to MDMA-assisted therapy. Is there anything I didn’t ask that you wanted to mention or to chat about?
Michael Mithoefer: Not that I can think of. Good to talk to you.
Chris Sandel: Thank you for coming on the show and for doing all the work that you’re doing. You really have been a pioneer with this stuff over the last two decades, and I must imagine that at age 75, to finally be seeing this hopefully come to fruition must feel good, for something you started in your fifties.
Michael Mithoefer: It is very gratifying, yeah. It’s gratifying and a little nerve-racking to make sure that it’s carried forward well, too. But it’s very exciting.
Chris Sandel: Yeah. Well, continue doing this work.
Michael Mithoefer: Okay. Thanks, Chris.
Chris Sandel: So that was my conversation with Dr Michael Mithoefer. It honestly feels like MDMA-assisted therapy will be something that will become legally available fairly soon. Hopefully, as Michael said, in 2023. I think that’s at least in the US; I don’t know what will happen for the rest of the world. But I was so grateful to be able to speak to him because he has so much experience with this stuff, and really has been at the forefront of the resurgence in MDMA-assisted therapy and getting this legalised again.
01:10:46
There are two recommendations I want to make for things to listen to. A couple of weekends ago, it was Glastonbury Music Festival in the UK. It’s been on hiatus for the last couple years because of the pandemic, but this was their first year back. I’ve been to the festival three or four times over the years, and each time was a truly magical experience, and I would love to go back again in the future.
Because Glastonbury has been going on for so long over here, good amounts of it is now televised on the BBC, and you can watch it on the iPlayer or you can listen to it on BBC Sounds. I constantly listen to music while I work, so I’ve listened to many of the sets as part of Glastonbury, mostly from the Electronic Music Stage, because it’s just one long, continuous mix, and there isn’t someone talking between songs and I can just be working while that’s on in the background.
One of the sets that I’ve been listening to the most is Bicep. I’ve been a huge fan of them for many years, and their live set is just incredible. Their sound is a mix of deep house and melodic techno, and they just sound huge live. They’re kind of like a newer version of The Chemical Brothers. It’s just the perfect music for me to work to. So if you are into electronic music, then I suggest checking it out. If you’re in the UK, you can find it on the iPlayer. I think it’s up there for a month. After that, or for everyone who is outside of the UK, if you Google ‘Bicep Glastonbury 2022’, it is up on SoundCloud and you can listen to it there.
The other recommendation is an album called ‘A Light for Attracting Attention’ by The Smile. I’ve been a Radiohead fan since their first album back in ’92. It’s now three decades that I’ve been into their music, and The Smile is made up of Thom Yorke and Jonny Greenwood from Radiohead, as well as the drummer, Tom Skinner, from the jazz band Sons of Kemet.
What I’ve always found interesting with Radiohead – and the same is true with this album with The Smile – is that it takes many listens to really get into. There is something about the intricacy of the music or just something in it that makes it take time to truly appreciate. We had some friends come over last weekend, and one of the guys was also into Radiohead, and we were talking about this fact that it can take so long to get into the albums. He was saying that it was through watching the TV show Peaky Blinders that he learned to really appreciate Radiohead’s album ‘In Rainbows’. When he first got it, he just didn’t get it, but after seeing it used in TV and then coming back to it, he can now appreciate the genius of it.
Interestingly, for me, ‘In Rainbows’ is one of the albums that I feel like I did fairly instantly fall in love with and still to this day is my favourite Radiohead album. So if you don’t know any of their music, it is the one I always suggest checking out first, ‘In Rainbows’.
While it is still early days with The Smile, I’m already really enjoying the album. There are days where I will put it on and listen to the whole album three or four times in a row, and it just continues to grow on me. I know that it will be one of my favourite albums of the year. It’s called ‘A Light for Attracting Attention’ and it is by The Smile.
That is it for this week’s episode. As I mentioned at the top, I’m currently taking on clients. If you want help with an eating disorder or disordered eating, chronic dieting, poor body image, exercise compulsion, or any of the topics that I cover as part of this show, then please reach out. You can head to www.seven-health.com/help, where you can find out more information.
I’ll be back next week with another episode. Take care, and I’ll catch you then.
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