Episode 198: Chris sits down with Dr. Natalie Gukasyan to discuss her work in the Johns Hopkins Center for Psychedelic & Consciousness Research. They chat about the potential of psilocybin to help with mental illness and dive into detail on the study she's conducting on psilocybin and anorexia nervosa.
Dr. Natalie Gukasyan is a psychiatrist and post-doctoral research fellow at the Johns Hopkins Center for Psychedelic and Consciousness Research in Baltimore, Maryland. After receiving her M.D. from Tulane University School of Medicine Dr. Gukasyan completed her internship and residency in psychiatry at Johns Hopkins. She is currently a co-investigator and facilitator in clinical trials investigating the safety and efficacy of psilocybin for mental health conditions including anorexia nervosa and major depressive disorder. Dr. Gukasyan is also a clinician at the Johns Hopkins Bayview Community Psychiatry Program serving patients with co-occurring mental illness and addictive disorders.
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Chris Sandel: Welcome to Episode 198 of Real Health Radio. You can find the links talked about as part of this episode at the show notes, which is www.seven-health.com/198.
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Hey everyone. Welcome back to another episode of Real Health Radio. I’m your host, Chris Sandel. This week on the show, I’m back with a guest interview, and my guest today is Dr. Natalie Gukasyan. Dr. Gukasyan is a psychiatrist and post-doctoral research fellow at the Johns Hopkins Center for Psychedelic and Consciousness Research in Baltimore, Maryland.
After receiving her M.D. from Tulane University School of Medicine, Dr. Gukasyan completed her internship and residency in psychiatry at Johns Hopkins. She is currently a co-investigator and facilitator in the clinical trials investigating the safety and efficacy of psilocybin for mental health conditions, including anorexia nervosa and major depressive disorder. Dr. Gukasyan is also a clinician at Johns Hopkins Bayview Community Psychiatry Program serving patients with co-occurring mental illness and addictive disorders.
I first became aware of Natalie at some point last year. I’ve listened to Tim Ferriss’ podcast on and off for the last 4 years or so, I’d say, and his podcast was one of the first that I really got into. I loved hearing his long form conversations with well-known celebrities and entrepreneurs. Ever since I’ve been listening to his podcast, he’s had numerous shows and guests talking about psychedelics and the research in this area. Tim’s been a real champion of this and someone who has wanted to see more of it.
Last year, he, along with a handful of others, stumped up a sizable chunk of money – I think Tim put $2 million of his own money towards this project – and the money went towards creating Johns Hopkins Center for Psychedelic and Consciousness Research, and the funds are also then for the research to be conducted over the next 3 to 5 years there looking at the use of psychedelics in treating many different conditions.
Tim released a podcast about this, which was a recording of the press conference for the Center’s open, and as part of this they went through a number of the different conditions that they were going to be doing research on and the people that would be involved as part of this research. One of the trials that they mentioned was going to be going ahead was with psilocybin and anorexia nervosa, and the person involved was Dr. Natalie Gukasyan.
If you listened to my recent podcast with Will Siu, you’ll know that this has been a topic I’ve been interested in for many years now, the area of psychedelics, so to discover that there was an active trial looking into anorexia nervosa and psilocybin was super exciting to me. So I reached out and invited Natalie on the show to chat about it.
As part of this episode, we cover Natalie’s background and how she became interested in psychedelics. This is still a taboo topic, although I think this is changing, so we chatted about what it was like to make the decision to make into this area. We then talk about psychedelics and the current research for a number of conditions – depression and addiction.
At this stage, there hasn’t been much research looking at anorexia nervosa and psychedelics, but there are reasons why it’s hypothesized that it could be useful. Natalie outlines all the reasons why they think it could be useful, looking at biological mechanisms, looking at psychological mechanisms. This is really a great overview of psychedelics in general and the many ways they work in the mind or the actions that they have within the body, but she speaks a lot directly towards anorexia and why it could be helpful in that area.
Then we chat about the current study that she is running, or was running – sidelined a little bit at the moment because of coronavirus. We talk about the intake and the screening process, the psychotherapy component of the study, the psilocybin sessions that occur as part of the study, and then the follow-up and the integration that happen after these sessions. Natalie talks about some of the early findings that they’ve seen with the people who’ve already gone through the study.
I should say that this study is ongoing, so if you’re someone who struggles with anorexia nervosa and would like to participate in the trial, you can apply. If you go to hopkinspsychedelic.org/anorexia, you can apply. I will link to that in the show notes.
We also talk about law changes that would need to take place, because at this point, psilocybin is still a Schedule I substance as part of the Controlled Substances Act, so this would need to be overturned for this to be used in practice again.
Connected to this as well, we talk about the risks of this subject, because while there’s lots of positives that we do cover, these substances aren’t a panacea, and there are risks associated with them. This is definitely true with anorexia nervosa. Natalie is cautiously optimistic, but that caution is warranted, and it’s doing studies like this that can help to understand this more.
It was really wonderful to be able to have this long form conversation with Natalie, and we got to cover a lot of information. I’m excited for the work that she’s doing, and if things pan out, as the early research is suggesting, this could be a useful tool to add to the treatment toolbox when dealing with anorexia nervosa.
That is it for this intro. Here is my conversation with Dr. Natalie Gukasyan.
Hey, Natalie. Thanks for joining me on the show today. I’m really glad to be talking to you.
Dr. Natalie Gukasyan: Thanks for having me.
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Chris Sandel: I first came across your name while listening to a Tim Ferriss podcast. He was promoting the new Johns Hopkins Psychedelic and Consciousness Research Center and talking about the different research that was going to be going on there, and your name was mentioned in connection to a research trial with psilocybin-assisted therapy, anorexia nervosa. I instantly knew that I wanted to get you on the show.
Today, I’d mostly like to chat about that research trial and the ins and outs of it as well as talking about what you’re doing at the Center and Johns Hopkins and psychedelics more generally. But as a starting place, do you want to give listeners a bit of background on yourself, like a bio of sorts? Who you are, what you do, what training you’ve done?
Dr. Natalie Gukasyan: Sure. I am a psychiatrist, and I went to undergrad at Cornell University. I studied nutrition when I was there. Eventually went to med school. Between college and med school, I actually took a detour and got involved in a lot of cardiothoracic surgery research. I thought I was going to be a CT surgeon for a very long time, but eventually I came to my senses and realizes that in all my free time, I was reading more about mental health, mental illness, and all sorts of other interesting things, like all this psychedelic research that was coming to the forefront.
I think the first time I actually came across it, I was a college student. It was around the time of 2008, back when the very first papers were coming out of the Griffiths Lab, of which I’m now a part. I was very intrigued by the findings that they were reporting, that people could have these very intense and very meaningful kinds of experiences that lead to lasting behavioral change and changes in mood, changes in worldview. At the time, though, it didn’t really seem like a viable career option to ever end up in that kind of laboratory. [laughs]
But it was always in the back of my mind, and I followed it for quite a bit of time. I was in this limbo period; I was trying to decide whether I should go to med school or pursue a more traditional research route doing a PhD in biology.
I worked at Columbia University; I was actually a research assistant at their CT surgery lab, and I did all sorts of fun stuff like fly around with their organ procurement team and got to spend a lot of time in the operating room, which I really loved. I love working with my hands, so for a minute I was convinced I was going to be a surgeon of some sort.
During med school, it was pretty late in med school, but I had my psychiatry rotation and it turns out I loved it, and I had to really reevaluate a lot of things in my life. But one of the factors that ultimately made me choose psychiatry was that, in addition to this really interesting career in which I really enjoyed working with patients, I really loved the colleagues I had in psychiatry and the things I was doing day to day, there might be this chance to end up working someday with substances like psilocybin in a clinical or research stetting.
So I went for it. After that I was trying to figure out where to do my residency, and one big factor in choosing where was where this kind of work was being done. Among those places, obviously, was Johns Hopkins, probably the premier place in the world – maybe not the universe, but certainly the world. [laughs] Luckily, that’s where I ended up.
I finished my residency last summer, so I’m fresh out. Currently I’m a post-doctoral fellow doing most of my work in the laboratory or in the research setting, and then I also do a little bit of clinical time each week. My clinical work primarily is in individuals with co-occurring mental health issues and addiction.
I’ve been at this I guess since last summer, but even before then as a resident, I spent a lot of my elective time with this group, trying to get my feet wet with what it looks like to do clinical research with substances like psilocybin.
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Chris Sandel: You talked about in 2008 or 2009, you were reading about it and that first sparked the idea of “I’d like to somehow get into doing the work with these substances.” What was it about the substances or what was it about what you were reading that was pulling you in that direction?
Dr. Natalie Gukasyan: That’s a great question. It was the first time I had seen – you hear a lot of anecdotal stories about these kinds of substances and all the very interesting, amazing, unitive experiences that people have, but it was the first time I had seen that in print, in a premier journal, in a professional journal. And people were actually able to show that not only are people saying that it’s really intense and interesting and meaningful, but it actually has long-term positive effects that we can measure.
In some of those early papers, they had not just the individuals rate their behavior and mood changes, but community raters, somebody who knew the person really well. In general, overall, it just seemed like people were making big changes.
The other interesting thing was that it’s not a drug that you take every day, you have to go fill it at the pharmacy once a month, you have to worry about side effects for months or years. It’s something that’s done just once or twice, and even though the peak effects last maybe 4 to 6 hours, the lasting effects we’re still figuring out. We’re actually thinking about maybe doing a longer term follow-up study with some of those early projects. But in some cases they certainly last longer than a year.
I hadn’t heard of anything up to that point that had those kinds of effects, so I was very intrigued by it.
Chris Sandel: I don’t know at what point you then made the decision to shift and start working at Johns Hopkins, but did this still feel like quite a taboo topic, and it was quite a difficult decision and people were saying “this isn’t great for your career”? Or had that point passed and this seemed like a really smart thing to be doing?
Dr. Natalie Gukasyan: That’s a great question. [laughs] One pivotal moment I remember was in 2010 or ’09 or something like that, and I had gone to the Horizons Conference in New York City. It was one of the earlier conferences on psychedelics that were happening. I saw, for the first time medical doctors, PhDs, up on the stage talking about their very interesting, exciting work and they were not exploding or disintegrating into thin air. [laughs] I was like, wow, these people actually have viable careers and seem to be doing really interesting work. So that was one of the first moments where it seemed like it might’ve been a possibility. It’s like, well, these folks are making it happen.
At the time, it seemed like a lot of them were later in their career, and I thought if it ever was a possibility for me, maybe it would happen after 20-30 years of doing other kinds of work and establishing myself in other ways, because for a long time that’s how it went. A lot of the “pioneers” of this latest resurgence had been doing other kinds of work before that. That’s rapidly changing, too, though. So I remember that was a pivotal time.
But it was still very much taboo, and it was not something I discussed in my interviews as a medical student. When I was interviewing for medical school, I didn’t bring it up. I don’t think I even talked about it in the residency interviews, because at the time it was still taboo. Even within the department that I work in, there’s certainly a variety of opinions on this kind of work, even right now.
So I felt like I had to tread carefully, but I also made sure to actually be honest and talk with people and my mentors about whether this was a reasonable idea to do.
The time that I actually started to get involved in this work, I was a second year resident. It was a lucky occurrence, actually. I’d tried as an intern to get involved with working with this group, but I didn’t have any time as an intern. Our schedules were so busy; we had no protected time for research. But I was working on the eating disorder unit at Johns Hopkins, rotating with Dr. Angela Guarda, who’s the director of the eating disorder program there and who’s a wonderful clinician, who I learned a lot from and I still continue to learn a lot from.
We were hanging out one evening after admitting somebody, and she mentioned offhand that Roland Griffiths was trying to get her to work on some kind of project with her, but she just didn’t have the time to get this protocol written. I was like, “That’s convenient, because I’d love to help you with that.” [laughs] That’s how I got involved, and it was very convenient because it was something I could work on in my free time, evenings and weekends.
It led to my very early involvement in this protocol. It’s actually been a work in progress for years at this point, getting the study procedures down, getting all the regulatory approvals. It’s been a while that we’ve been working on it.
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Chris Sandel: I want to go through that bit of research in a fair bit of detail. But in terms of Johns Hopkins, when did they start doing research into psychedelics again?
Dr. Natalie Gukasyan: It was around the late ’90s, early 2000s that they started doing this work. I obviously was not there at the time, but they had really carefully gotten started and were making sure everything looked kosher. So it had been a while, and a lot of those folks are still there, like Roland Griffiths, Mary Cosimano. Una McCann was one of the earlier folks involved. She’s not working directly in the lab anymore, but a lot of those people are still there.
Chris Sandel: When did the new center open?
Dr. Natalie Gukasyan: The center designation officially happened in September of 2019. That was also a really – I feel very lucky to have come onto the scene right when this center designation happened. [laughs] I feel like I was lucky in a lot of ways.
What it means basically is now, thanks to folks like Tim Ferriss and the Cohen Foundation and others, and thanks to my faculty colleagues who had worked really hard for years doing this kind of work to make a name for themselves and develop these relationships and secure this kind of funding, there’s basically now funding to cover this kind of work for the next 3 to 5 years.
One of the issues for a long time was just that; it was the money and the ability to have the time and resources to do that work, because obviously – well, a lot of the traditional funding agencies like the NIH were not at the time providing a lot of funding toward projects like these.
Chris Sandel: What other research is going on at the center? You’re doing the research with psilocybin and anorexia nervosa; what are the other bits of research being done with psilocybin?
Dr. Natalie Gukasyan: Well, at the moment there’s coronavirus, so it’s really throwing a wrench into it.
Chris Sandel: Yeah, where are you up to? Because of coronavirus, how has that affected you guys? Just everything has stopped?
Dr. Natalie Gukasyan: For the most part, almost everything at the university that is human subjects research has come to a halt unless it’s coronavirus research or like cancer drug research, things like that where if they stopped they would cause serious harm to folks. We tried to do everything we could to be able to continue doing this work, but obviously, given the state of things currently, it wasn’t feasible.
So we’re on hold in terms of recruiting new people and we can’t do any in-person assessments at the moment, but we’re all working from home. We’re still reviewing applications and things like that and doing our best to make sure we’re well-positioned when everything opens back up again.
But before all this happened, we were engaged in a number of projects. The center designation came with a 5-year plan of all the different projects we were going to be doing, and we’ve been gradually rolling those out. Anorexia, that study was one of the first to roll out. There’s also a recently launched study looking at the effects of psilocybin in people with mild cognitive impairment due to Alzheimer’s who have co-occurring mood symptoms.
We’re currently a site for a multi-site study of psilocybin for major depressive disorder through Usona, who’s our sponsor. That’s one of the two big organizations who are doing these large studies right now. So that’s a Phase II study, and eventually hopefully will be rolled into a Phase III. That’s a randomized placebo-controlled trial. I believe there are about seven sites involved, and about three of them are active at the moment, or were active before COVID came onto the scene.
But there’s a lot of other planned studies, and we’re diligently working to get those rolling. Some of the other studies that we’re trying to launch include a study for folks with PTSD. Obsessive-compulsive disorder is another thing that’s on the horizon for us. Opiate use disorder. Another project that might be coming on hopefully this year is going to be a study on people with co-occurring major depressive disorder and alcohol use disorder.
Then there’s a handful of studies that will be happening in healthy people, basically, looking at the effects of these substances on creativity, on wellbeing, personality, things like that.
In the meantime, we’re doing a lot of survey studies, which can be done on the web. That’s probably our main focus right this second because everything else is dormant.
Chris Sandel: With the survey studies, I will get the link details from you and I can put them in the show notes so if anyone wants to go and fill that out, they can.
Dr. Natalie Gukasyan: That’d be really appreciated.
00:23:25
Chris Sandel: I guess as a starting point, do you want to define psychedelics? I recently did a podcast with Will Siu where we chatted a little bit about this, but I don’t want to assume that everyone has listened to that or is aware of what the term “psychedelics” means. I just think we’re going to probably use it a lot as part of this episode, so listeners are on the same page.
Dr. Natalie Gukasyan: Sure. There are a bunch of different definitions, and even a bunch of different terms used for psychedelic substances right now, but the term that we tend to use is psychedelics, and we mean those to be drugs that are considered classic psychedelics which exert their effects primarily through a specific type of serotonin receptor, the 5-HT2A receptor.
That family of drugs includes the prodrug psilocybin, whose active form is psilocin in the body. That includes LSD, DMT, mescaline.
There’s a couple other drugs that are sometimes lumped in with psychedelics; that includes MDMA and ketamine. But those actually work by different mechanisms of action and have different abuse liability, meaning they may have a higher likelihood of creating dependency in somebody. So we do consider them, at least at the Center, certainly to be different classes of medications.
What happens when you take a psychedelic is that you have these acute changes in perception, in somatic symptoms, psychological changes, but they tend to be pretty well-circumscribed, and they differ in the duration of their actions. Psilocybin has effects that last about 4 to 6 hours. Some of the others are shorter or longer. There are different descriptions of what they’re like phenomenologically for the people who are taking them, but probably one of the bigger distinctions is the duration of action for those.
Chris Sandel: Is that part of the reason why you guys are using psilocybin, because of the length of time?
Dr. Natalie Gukasyan: That’s one of the reasons. I think the other reason is that we have so much experience with it at this point. We’ve demonstrated clearly at our center that psilocybin in particular can be given safely in a supported environment, so it’s easy – not easy, but more feasible for us to propose new studies working with this substance. We also have some on hand, so that’s convenient too.
Chris Sandel: For anyone who doesn’t know what psilocybin is, can you describe or define what it is?
Dr. Natalie Gukasyan: Psilocybin is the prodrug. When you eat psilocybin, your liver turns it into psilocin, which is the active, the actual drug. Psilocybin is found in hallucinogenic mushrooms, or magic mushrooms, as they’re called. There are many different species, at least 200 of them, that contain psilocybin in varying concentrations. So that’s the most common way that psilocybin is found out in the world.
But at our lab, we actually use a synthetic version of psilocybin that was made in a lab, which we continually test for purity and make sure that it is what we say it is and the dose is actually correct. It’s a little bit harder to gauge some of those things when you’re using a dried mushroom, which also contains other chemicals that can be mood-altering.
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Chris Sandel: With psychedelics or with psilocybin, what is the current state of knowledge around it for things like depression and addiction and, if there is anything, on anorexia nervosa that you know of?
Dr. Natalie Gukasyan: We were talking about some of the earlier studies using psilocybin. There’s also this very rich history back in the ’50s to ’60s to ’70s where it was the first wave of research of these substances, primarily with LSD. Then everything came to a screeching halt in the ’70s due to some legislation that had come out that didn’t look very favorably upon these kinds of substances.
But back when this came back online in the early 2000s, we started working with healthy people and then moved into people who had end-stage cancer and were also struggling with anxiety and mood changes related to that. From there, we saw that clearly it has some benefit for anxiety/depression, so what would happen if this was tried in other populations who didn’t have cancer, who just had straight-up major depressive disorder?
There have been a handful of studies on that so far. There’s a group out in London who published in 2016. There’s a paper where they gave 12 people a couple doses of psilocybin, basically low to moderately high doses, with treatment-resistant depression. They found that there was a 50% reduction in symptoms generally, and this was sustained at about – I believe it was 3 months.
That was very interesting, obviously, because treatment-resistant depression is no joke. In addition to suffering with it, there’s also the constant changing of medications and therapies. So the fact that there was a 50% reduction in symptoms in a lot of these folks was pretty remarkable.
We are on the tail end of another depression study. This is separate from the multi-site study, but we did a randomized weightless controlled study. I think it was about 24 people with major depressive disorder. Didn’t have to be treatment-resistant. Our group presented some of the initial findings at a conference last year, and we found that the majority, over 80%, had a clinically is response to psilocybin within a week and also at 4 months. About half of people achieved remission, so they met the depression score that said you’re not even really depressed anymore at about a month, which is pretty remarkable.
That was some of the early findings that we had, and we’re working on putting out the full initial findings from that study this year. That should be available pretty soon.
In terms of addictions, that’s a developing field. Probably the most prominent findings there include a study on smokers that was done at Hopkins by my colleagues Al Garcia and Matt Johnson. They looked at a group of people, about 15 folks, who got I believe two to three doses of psilocybin, 20-30 milligrams, in conjunction with this CBT intervention that they did. It lasted 15 weeks.
Remarkably, the majority of folks, about 80%, were abstinent from cigarette smoking at about 6 months. Clearly, even though it’s a small group, that’s pretty remarkable because a lot of the other available treatments for smoking don’t achieve anywhere near those kinds of results. And a lot of them continued to be abstinent at 12 months, about 60%.
There’s also another ongoing smoking study at the moment. They’re using a larger sample, and I believe they have a control group of some sort. It might be treatment as usual with nicotine patches.
For alcohol use disorder, there was a group at NYU who had published on that a couple years back, and they found that one or two doses of psilocybin was able to decrease the amount of heavy drinking days for people with alcohol use disorder.
Those are the main psilocybin studies that I’m aware of for addiction. It’s all very impressive, but I think the other thing to remember is that these are very small studies. There’s some issues in some of them with adequate placebo control, which is an entire – you could probably do an hour just on what that’s all about to begin with. But that’s a very thorny issue, obviously.
In a lot of this research, it’s like, placebo controlled studies are the gold standard, but how on earth do you achieve that with a substance that causes such profound subjective effects?
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Chris Sandel: In terms of anorexia nervosa, have there been studies on this before? Even if we go back to the 1950s or ’60s, had there been studies done then?
Dr. Natalie Gukasyan: There had been reports of people with anorexia nervosa receiving drugs like psilocybin. I think it was primarily LSD in most cases.
But part of the trouble back then, and part of the reason that the current resurgence and research hasn’t gotten so much attention, is that there’s a lot more rigor in what we’re doing. Back then, if you look at a lot of the research, much of it is case series or barely that. It might just be like “We saw 100 patients. Some of them were depressed, some of them had some kind of neurosis,” or some diagnosis that isn’t even used anymore today, “and in general they did fine.” And that was the research. [laughs] Obviously that’s not something we can point to in 2020 and say that this is definitely safe for consumption.
I’ve come across a couple of mentions in a handful of papers, some of them saying that this might’ve been helpful, some of them reporting on adverse events that had happened.
I remember one in particular was using extremely high doses of LSD, something like 800 micrograms, multiple times, in a teenager – somebody who’s not even 18 years old – with anorexia nervosa, and surprise, she didn’t have a very good outcome and she actually probably suffered from long-term damage from that.
So that’s the state of knowledge about anorexia nervosa we have from the earlier wave of research. In some cases it was done; it wasn’t really very well-documented. But obviously, we have started this research study because we believe that it might be useful. The reason we think it might be useful is a manifold proposition here. Part of it rests on a biological reason, part of it rests on psychological reasons – which I’m happy to talk more about too –
Chris Sandel: Definitely. Go though each of those bits.
Dr. Natalie Gukasyan: I feel like in general, there’s two stories that are told about these substances. Especially since 2000, there’s the very interesting biological aspect of this. We have all this nice imaging research. We know a thing or two about how neurotransmitters are involved. There’s still very much to be learned on that front, but we do know that psilocybin and drugs like it affect something called the default mode network.
The default mode network is a big network in the brain, of parts of the brain that are talking to each other when you’re doing nothing in particular, when you’re just twiddling your thumbs or daydreaming. It’s involved in the process of being, like “me-ness” in the brain. Thinking about yourself, thinking about other people, things like that.
We know that when somebody takes psilocybin, there’s a disruption in this network, so there’s a disruption potentially in the sense of self that can happen. We also know that there are longer term changes that can happen as a result of psychedelic use in the function of the amygdala, which is the part of the brain that’s involved in emotional responses.
Fred Barrett out of Hopkins has done some work on this. He’s shown some early results that shows that there’s decreased reactivity in this part of the brain when it’s shown emotional faces, so negatively valenced emotional faces. The amygdala doesn’t react quite as strongly.
Chris Sandel: Is this post having the substance, or are you meaning while the substance is still active within the individual?
Dr. Natalie Gukasyan: This is post having the substance. They have a baseline scan and they have some follow-up scans after that. In the follow-up scans, they don’t have as strong a reactivity. So that’s one thing that we know happens with psilocybin.
There’s also some studies about what happens in the acute state done by groups outside of ours. A lot of folks might’ve seen these very compelling images of “this is your brain normally and this is your brain on psilocybin,” where it has all these interesting connections from parts of the brain that don’t normally talk to each other that are now talking to each other. So that’s one thing that might happen; it might loosen up normal networks in the brain, temporarily at least, during acute drug effects.
The other thing we know about it is obviously that it works through this serotonin 2A receptor, and that if you block 2A receptors, for the most part you block any of these subjective psychedelic effects that can happen. The 2A receptor we know is involved in a lot of different things. We know it’s involved in some cases in depression. There’s some evidence that it might be implicated in anorexia nervosa, but the evidence for that isn’t quite as strong.
One of the hubs in the default mode network is called the angular gyrus, and it’s found to be more active in people with anorexia nervosa, and when people recover from anorexia nervosa, that corrects itself at least partially. This finding in the angular gyrus is associated with changes in interoceptive ability in people with anorexia, so when we think about sensing what’s going on in your own body or your sense of what the sensations are coming from your own body.
There’s a couple other things with the serotonin 2A receptor in anorexia. For example, there’s some overlap between OCD, and in some cases they found it with anorexia as well. There’s this genetic marker, this version of the 5-HT2A promoter region – it’s the part of the gene that is involved in actually transcribing and getting this receptor from the gene into the cell, and that is affected in both OCD and anorexia. Now we know that in some cases – in a couple small studies that have been done – has shown that psilocybin might be effective for relieving symptoms of OCD.
So those are some of the biological reasons that we think that it might fit or work with anorexia nervosa. There’s obviously, then, of the two stories – there’s the biological part, and then there’s all these very interesting subjective effects that people talk about and psychologically mediated mechanisms that people talk about.
Within psychedelic research, there’s a lot of talk about “mystical experiences,” and some folks have a hard time with that term because it doesn’t sound very scientific. [laughs] They might choose to call them peak experiences, flow experiences, things like that. But basically, it actually is a pretty well-validated construct and something that we have found a way to measure pretty reliably.
When we think about mystical experiences, probably the chief component is this aspect of unity or feeling interconnected to a lot of different things – connected to yourself, to people around you, to the universe in some cases. There’s this feeling of unity. There’s a feeling of sacredness or reverence, deeply felt positive mood. A lot of folks who have these kinds of experiences say that they actually can’t describe them with words. They’re sort of ineffable, which makes it a little bit difficult to study in some cases. [laughs]
But the interesting thing is that if you look at some of the earlier studies, they actually found that the more mystical somebody said their experience was, the better long-term effects they had. Even though it sounds a little bit out there, it’s actually something that we’ve seen over and over again and something that’s positively correlated with good outcomes in folks.
The mystical experience is one aspect of the psychological mechanism. Roland Griffiths has also coined this term “ontological shock” that can sometimes happen, meaning that the experience is so different from anything that someone has come across before that they might really reconsider their worldview or their personal view on things, or it might lead to changes in psychological flexibility. So ontological shock is another thing.
In talking with people who have been through this, there’s oftentimes a lot of stuff that comes up around insight that they might develop into some of their personal issues, their relationships, their own emotions, so that’s obviously potentially involved there.
People report this increased sense of openness, and we’ve shown that openness is a facet of personality that’s pretty well-validated; in people who have undergone psilocybin assisted treatment, they’ve actually shown that they’ve increased openness in their personality inventory months out, which is pretty remarkable and not something I’ve seen any other pharmacologic intervention accomplish before. Interestingly, the only other intervention I know of that does it is psychotherapy, and there’s obviously quite a bit of psychotherapy wrapped up in this kind of treatment. So that’s one other thing.
One interesting thing is that people can report this greater tolerance for discomfort. In the smoking study, an interesting finding was that a lot of people reported they still had a lot of the withdrawal symptoms of tobacco cessation – so they stopped, they would get sweaty, nervous, their appetite would change – but they actually were not as stressed by it as they otherwise would’ve been.
Chris Sandel: Is that in any way connected to the fact that within these mystical experiences or peak experiences, there are points at which they are very enjoyable and there are points at which they can be extremely difficult or terrifying or whatever? And if someone has had the scarier end of that spectrum and then made out the other side, it changes their perception about what they’re able to handle in real life?
Dr. Natalie Gukasyan: Yeah, that’s certainly a part of the experience for a lot of people. In some of the earlier studies here, something in the order of 20-30% of people reported a challenging experience like that. But the challenging experience was actually not really related to negative long-term outcomes, we think probably for reasons like you just said. If you go through an ordeal and you come out alive on the other end, that actually might boost your confidence and it might show or teach you that maybe you can tolerate much more than you thought you could.
But that’s also an interpretation. There’s not really any way for us to ever prove that or falsify that. But that makes sense, right?
Chris Sandel: Yeah, definitely.
00:44:35
Dr. Natalie Gukasyan: I’m a fan of this idea that there’s something about the experience that’s tied to mindfulness. Do you have much experience with mindfulness, Chris?
Chris Sandel: I have some experience with mindfulness. I’m not very good at mindfulness. [laughs] When I try and meditate, I have tried and failed repeatedly.
Dr. Natalie Gukasyan: It’s obviously a very tough thing. That’s something that we hear quite a bit from people who try to practice mindfulness. It sounds great in theory. Wow, it sounds perfect, it can solve all my problems. But actually sitting down and doing it, and also having it explained in a way that actually makes sense, given that you can’t really put it into words either, it really takes a very skilled teacher and a lot of dedication and determination to a mindfulness practice to actually achieve anything resembling what we hope somebody would achieve with a practice of mindfulness.
But some of the ways that people describe feeling after the psilocybin experience really harkens to what people say after they have a pretty well-developed mindfulness practice. There’s less chatter going on in their heads. They’re more able to separate themselves from whatever monologue is going on about this or that or some focus on the imagined future or the remembered past, which might be misremembered and not actually reflect reality – they’re more present.
I think in one sense, substances like psilocybin might be a way to give somebody that kind of experiential knowledge of what that feels like. Sometimes it might happen during the acute effects; a lot of people have the “afterglow” period in which they feel more at peace in that way. But how that works is another story, and I’m not sure there’s a very easy way to figure that out. You take psilocybin and everything gets all jumbled up, and after that there’s this calm that comes over.
And the calm can be pretty long-lasting, and I think that’s also one of the most fascinating things about this whole thing. Even though the intervention is so short, whatever happens in that 4 to 6 hours in many cases is something that the person who undergoes it can take with them for a long, long time. In the early studies, I think one of the most impressive things is that people said this is in their Top 5 most meaningful experiences in their whole life, which is really saying something. [laughs] It’s up there with like the birth of a child or the death of an immediate family member or something like that.
A lot of people have trouble hearing that. They’re like, “What kind of life have you led that this is one of your Top 5 most meaningful experiences?” But for many, that’s just what it is, and it’s really hard to describe in words what it means.
Chris Sandel: Connecting back to the mindfulness piece, while I’m terrible at meditating and trying to do mindfulness in that way, I’m very much aware of my thoughts are just a stream of consciousness; they appear in my mind. I’m not the author of my thoughts. I get mindfulness in theory a lot more than I’m getting it in practice. I’m a big fan of Sam Harris, and he’s done a lot of work around mindfulness, and I know he got his start with being interested in all this because of quite a lot of psychedelics. So I have a lot of listening I’ve done around that, but in terms of me and a mindfulness practice, that is still yet to be seen.
Dr. Natalie Gukasyan: I think there’s also a difference between sitting meditation and – the whole point of sitting meditation is to get to a place where you can take what you experience there and bring it to everything in your life. You could be mindfully eating, mindfully walking, mindfully washing the dishes, etc. It looks different for a lot of different people.
But when you sit down with somebody who’s never heard of the idea before and you tell them, “Oh yeah, that monologue running in your head is not actually you,” it’s very confusing, and very distressing in a lot of cases. [laughs] They’re like, “If it’s not me, then who am I or what am I?”
I feel like with psychedelics, what might be happening is there’s this utter destruction of that construct of this thing that you thought was you, and yet there’s still some part of you that’s left that’s observing that. Being able to be shown that in that way can be extremely powerful for folks.
On the other hand, though, many, many people come out of it and still don’t really see it that way at all, or they might’ve had a very intense somatic experience. They’ll have a lot of movement or talk about a lot of perceptual changes they had and not really relate it to a mindful state in any coherent way, but still come out and look as if they might’ve done a mindfulness-based retreat or something like that.
Chris Sandel: Let’s talk specifically about the study you’re doing. You said this has been years in the making in terms of you putting this all together. Let’s talk about what the study is going to look like. I’ve got various questions I want to ask around this, but I’ll just open it up to you; you talk about what it’s going to be.
Dr. Natalie Gukasyan: I feel like I didn’t actually get to the psychological reasons why we think this might work in anorexia, but in short –
Chris Sandel: Okay, let’s go back to that.
00:50:45
Dr. Natalie Gukasyan: In short, there’s a lot of overlap between the symptoms of anorexia nervosa and some of the other conditions that psilocybin has shown some early efficacy for. With anxiety disorders, with OCD, addiction, you can tie a lot of what people experience in anorexia to those kinds of symptoms – rumination, being very fused with what’s going on in their head, be it anxious thoughts about food, addictions or behavioral patterns that they find themselves locked in that they can’t really break free from. So that’s one possible reason it might work; maybe there’s a lot more similarity between anorexia and other sorts of mental illnesses.
There’s also a really high rate of comorbidity between anorexia and other mental health issues. It tends to be more the rule than the exception that folks with anorexia are also struggling with anxiety disorders, with depression, and then perhaps if we can help them with those other issues, then they might have an easier time handling their eating and exercise and other related things.
Then finally, there’s a little bit of anecdotal evidence – I think you asked before, what’s the evidence? There’s actually not a ton, apart from obviously those early parenthetical mentions of what happens to people with anorexia under the influence of LSD and psilocybin.
But more recently, there have been some reports of naturalistic use, so use in the community, of other psychedelics like ayahuasca for people who have issues with eating. That was a paper from Adele Lafrance, who’s up in Canada. She surveyed folks who went to these ayahuasca retreats and had a self-reported history of bulimia, anorexia, binge eating disorder, about what happened to them, if they had any benefit. Some of them did. In general, it seemed to be – she talked about the risks of doing so, and some people did experience some worsening in their symptoms, but many, or a significant part, also experienced some improvements.
That’s why we started looking into psilocybin as a potential therapeutic agent in conjunction with a nice psychotherapy package. Those are the reasons that we thought about it.
Chris Sandel: In terms of the comment you made there about ayahuasca and whether it was helpful, I know when I chatted with Will Siu, he was talking about the fact that yes, these substances are important, but they’re part of a bigger package where you then need to do the work going into, coming out of, doing integration and all of those things.
I would be interested – as part of that study, was there all of those other components? Or was it simply people going to this one retreat and that was it in terms of follow-up?
Dr. Natalie Gukasyan: Yeah, again, this was just people who had gone and done this on their own, for the most part. I imagine some of them might’ve had some kind of contact with a mental health professional or even a friend or something to talk about it, to try to integrate it, but this was not any formalized approach to integrating the experience or preparing them for the experience.
That’s one big difference about that, and also the fact that obviously the environment is really different. They’re going off to these retreat centers, and that in and of itself I imagine is kind of an ontological shock, to be halfway across the world. In some cases I guess there are people who do it locally in an underground setting, but that in and of itself might be a big difference in terms of outcomes there.
Chris Sandel: Totally. I know from working with clients with eating disorders, you put them in a novel environment and that’s a really big stress in terms of eating behaviors. So to hear that someone went to a retreat halfway around the world and their eating got worse, for me, that’s not a big surprise.
Dr. Natalie Gukasyan: Right. That’s something we’ve tried to work with a little bit in our study because a lot of our participants or people who applied for the study who we’ve screened are actually from out of town. That’s one challenge for a lot of folks who have been in the study so far. Not only are they doing this unusual approach to treatment, but they’re far from home, they’re living at a hotel for a little while.
So we’re trying to figure that part out at this point, now that we’re actually off the ground. But in the early days, we were just trying to put together what would make sense for a treatment protocol and therapy for these folks.
00:55:55
Some good background would be what the usual setup looks like in clinical studies with psilocybin that we had done prior to the anorexia study. It generally looks like about an 8-hour total preparation period. Usually it’s done over about two days, where a person hangs out with us in this treatment room, which looks kind of like a living room. It’s got couches set up and comfortable chairs and nice décor and tasteful lighting and things like that. [laughs]
We get to know them and we develop a sense of rapport and trust with them, and it actually tends to be pretty intense because usually in psychotherapy, we’re coming in and out for 40 minutes or an hour, and over the course of months, you might develop enough rapport – but this is squashing essentially 2 months of psychotherapy into a couple days. It can be very intense, and that in and of itself might probably be therapeutic.
So normally they have this 8-hour preparation period and then they have their psilocybin sessions. They’re all day long. Usually there’s between one and three separate sessions where the person comes in, we get them situated, they take the medication, and we lay them down on the couch and they have eyeshades and headphones on. The headphones are playing this preprogrammed set of music. It’s a combination of classical music, world music.
For the day, it’s pretty nondirective. We’re not really sitting there telling them, “Try this” or “Do that.” We’re mainly there as a source of support. If they have a really challenging time, if they feel like it would be helpful for them to talk about what’s going on or just to have somebody to hold their hand or put a hand on their shoulder, and to help them if they need to walk to the bathroom or something like that, make sure they don’t fall – we’re just looking out for their safety, and we’re monitoring them for any health issues that could come up like blood pressure issues are pretty common.
So they have a couple of those, and then they have usually some integration sessions around that. What that means is a follow-up session. Usually there’s one the day after their psilocybin session and then maybe a week out, and then some other follow-ups over the next month or two. We talk about what happened, get the person’s take on what it means, help them make sense of it, help them “integrate” their experience back into their daily life, because you’re not going to be on psilocybin all the time. At least in the context of the study, it’s just once or twice, maybe three times they’re going to be doing it. The important part is the work that’s put in around that, just like you said.
So that was the base for the study, or the model that had been used at the Research Center for a while. In adapting that to anorexia, some of the considerations were obviously folks with anorexia can be clinically complex. They might have a lot of different issues going on, and they might benefit from maybe a more structured approach or an approach that lasts a bit longer to make sure that relationship develops with the facilitators in a productive way, basically, meaning the person can really learn to trust them – because obviously, for a lot of folks who have anorexia, it’s not uncommon to hear that they had a contentious relationship with their treatment team. So we really try to ease into that kind of relationship with them and really make sure that we’re on the same page together.
Some of the studies we had done before used a regimented approach, like smoking, for example, used CBT as their therapeutic base. A lot of the other ones were open-ended and just like “let’s review your life story, let me tell you what’s going to happen in the psychedelic experience or on your session day.” We took a mishmash of that, and we used components of motivational interviewing to develop the therapeutic container that this is developed in.
The reason we did that is motivational interviewing, or MI for short, is based in this collaborative, compassionate approach with mutual respect and trying to take a patient’s point of view into consideration as carefully as possible, which I think is really important for people with eating disorders who might’ve had these negative experiences with treatment in the past.
Chris Sandel: Motivational interview is kind of at the core of how I work with clients. It’s had a big impact on me. So yeah, that’s something I’m a big proponent of.
Dr. Natalie Gukasyan: Yeah. That’s what we tried to do. It looks like a frankenstein-ed version where we take this MI approach to communicating, but we also do the usual stuff where we review what’s happened in their lives, what’s happened to them in treatment before, we talk about what their values are, why they’re here to begin with, how they feel about change in general, where they’re at in Prochaska and DiClemente’s Stages of Change – precontemplation, contemplation, action, preparedness, maintenance. So we talk about that and get them to think about, where have they been in that before? Have they been in recovery before? How did it feel? What were the circumstances going on at the time? We get them thinking a little bit more about that.
We do offer optional nutritional counseling. That was a big issue here. With things like depression or smoking, obviously you might just change and you might not want to smoke anymore or your depression might lift, and wow, good for you. [laughs] There’s not very much to be done after that in some cases. In many cases there is. But with anorexia nervosa, you still have to do the work, and the work can still be very challenging. Psilocybin is not going to change your eating behaviors or your exercise behaviors. Ultimately that comes down on the person.
So we do have a more behavioral focus at times, a little bit different from the other studies we’ve done, where we talk about, what are you doing? That happens a little bit after the psilocybin sessions. So they’ve had this experience, they might’ve had things shaken up a little bit; now what? What was going on before? What do you want to change? What are you going to be doing? How can we support you through that?
They have this preparation. It lasts about a month, where we meet weekly with them for a couple hours at a time. In total, it’s about the same amount of time, but it’s split over longer, so it might feel like we have more time to develop a relationship. We can see them more frequently if we want to. Our protocol allows for that.
Then they have two psilocybin sessions. The first one is a moderately high dose. It’s 20 milligrams. It’s not weight-based. that was another consideration here. Many of the other previous studies had done a weight-based dose. Obviously for folks who are underweight, that potentially could lead them to have a dose that’s low enough to not really do very much. Anecdotally, there was also some concern that people with anorexia might be less sensitive to these kinds of drugs to begin with. So we tried to do this fixed dose approach for now where they get this 20 milligram dose first, they have a couple of follow-up sessions, and then they have a second dose of 25 milligrams.
Following that, they have a month of more integration, which is actually a little bit more than is used in some of the other studies. We figured that these folks might need more help around integrating it, about behavior change and things like that. So there’s a more intense integration period or follow-up aftercare plan than for other studies that have been done before. That’s, again, where we talk more substantively about the ins and outs, the nuts and bolts of what they’re actually doing day to day. Then we follow them up for a period of about 6 months, gradually tapering the frequency with which we see them.
That’s how it stands now. We launched back around the time of the Center launch. We opened up for applications and things like that. We’ve run a handful of participants at this point. Obviously we’re stuck because of the coronavirus pandemic, but we have a little bit of information at this point. That’s where we’re at right now: looking at everything we’ve gotten and trying to understand what has worked, what hasn’t worked, now that we have this built-in breather period, to try and determine if this is really the right approach or if something needs to change.
In general, though, I think it’s a little bit too soon to really say. We’re trying to figure that out right now.
01:05:30
Chris Sandel: In terms of total numbers of participants, what was the aim when you first set up the study?
Dr. Natalie Gukasyan: We said we wanted to get 18 over the course of about 3 years. I think we’re doing pretty well with that. Now we got derailed, of course. [laughs] It’s just really unfortunate, because we had started working with a couple of people, and we were partly through the preparation period and we had to stop. Now we’re trying to figure out what to do with those folks and how to proceed there.
Chris Sandel: Are there things that would disqualify people? Things that come straight to mind where you’re like, “If this is going on, then we can’t have them as part of the study”?
Dr. Natalie Gukasyan: To be in the study, somebody has to have a current diagnosis of anorexia. They have to have had it for at least 3 years, so we’re really looking at people who clearly have been struggling with this for quite a while. They also must have had at least one go at treatment, and that means either an inpatient admission, a residential admission of a partial hospital treatment, or a certain period of outpatient treatment they have had with somebody for the purpose of treating their eating disorder.
They have to be medically stable. If they’re at a point where they would require inpatient care, residential care, they probably wouldn’t be appropriate for the study because they have to be able to be medically safe. If we’re not in the position to care for somebody in that way, then they probably wouldn’t be a good fit.
One of the other challenges for this and every other study looking at psilocybin and related compounds is the fact they have to be off of any serotonergic medication. That includes SSRIs, tricyclics, the other usual suspects for treating depression and anxiety. And we know that about half of folks who present for research who have anorexia nervosa are on those kinds of medications. If they’re on them, it’s okay, but they have to be willing and able to safely be tapered off of those medications. That can happen wit their own provider, that can happen with us, potentially. It’s a conversation. It’s not a disqualifier by any means, but it’s something that would have to happen before they received any study drug.
There’s some psychological exclusion criteria. If they have extreme bipolar disorder or schizophrenia or they have a first degree relative with any of those conditions, that’s usually a disqualifier. That comes from the history we’ve had of really carefully selecting people who would be appropriate for this kind of intervention, because theoretically there’s a risk that if somebody has a personal or family history of any of those disorders, psilocybin might precipitate mania or psychosis, which would obviously be undesirable. So we really do a careful job of screening out for people who might have those disorders.
The screening process is actually pretty intense. It takes two days. We do some medical workup as well to make sure they look okay. Again, this is a work-in-progress; at this point we’re looking back and trying to see, is this the right approach to be taking? Because there are other exclusion and inclusion criteria. We’re just trying to figure out what makes sense and whether we have the right framework for folks at the moment.
Chris Sandel: What does the percentage look like of the people who apply online and fill out the questionnaire versus how many end up as being participants because they are able to meet that criteria? Is it really difficult to find people that meet all of these things?
Dr. Natalie Gukasyan: Yeah, unfortunately that is a big challenge. Since we opened up, we’ve had somewhere around 250, maybe a little bit more, people fill out our application online. Not totally sure of the very latest numbers, but I think we might’ve reached out to somewhere between 20 and 30 of them who met initial criteria.
We scheduled a bunch of people, but the other problem is that the study is very time-intensive. For people who are from out of town, it’s not always feasible for them to participate because it requires so many study visits. They have to be able to travel with another person for some of them. We have them designate a pick-up person for their psilocybin session days that has to be there to get them at the end of the day, so that can be really financially costly. So there’s a lot of things in the way for a lot of people to be able to participate, unfortunately. Some of them are college students and they can’t really get away until the summertime, and now with coronavirus, who even knows if we’ll have a summertime or what’s going to happen with that. [laughs]
Recruitment is tough, but I think we were going at a decent pace before that. Of the people who we have screened and invited for screening, the rate of acceptance is pretty good, especially compared to some of the other studies we’ve done in populations like depression, where you have to be a certain level of depressed to be in the study. The way our criteria are right now, the way our application is, we can usually tell with pretty good certainty who might be a good fit. It doesn’t always work out, obviously, and unfortunately we do have to turn a lot of people away, but compared to – for the depression study, obviously depression is a much more common illness, so we got maybe 10 times as many applications, but a smaller percentage of those seemed to be people who might fit for the study.
Chris Sandel: From you describing everything involved, this seems so labor-intensive in terms of what has to happen for every single participant, in terms of the amount of time that they’re then seeing practitioners and they’re in the room as part of the experience, and then all the follow-up – this isn’t just a very simple “take this medication and then let us know how it all pans out for you.” There is a lot of stuff that goes into all this.
Dr. Natalie Gukasyan: Yeah, and that’s the case for pretty much every clinical research study that’s happened with psilocybin and other drugs like it. It’s very labor-intensive. You need not just one clinician, but often two in the room with somebody.
A big discussion that’s happening now is like, what is this actually going to look like if and when it gets approved for use? If it does get approved, it’ll probably get approved for depression first. So what is that going to look like? How are people going to be able to afford it? Is insurance going to say they don’t care to cover it?
In one sense it might be really cost-effective, because if you can provide somebody a chunk of psychotherapy and a couple of all-day sessions and then do much more intermittently spaced follow-ups, it might be more cost-effective than paying for a medication every month or paying for weekly psychotherapy for years and years and years. But convincing the insurance companies of that is going to be a different story.
Other groups have thought about ways that this can be a more cost-effective endeavor. There have been a couple other models people have tried out – one where somebody only has one facilitator with them, and maybe there’s multiple sessions going on at once and there’s a floating clinician who can cover for somebody if they need to leave the room to take a bathroom break or eat their lunch or something like that. But that’s going to be a big hurdle, I think. Initially when this comes out, it’s going to be unfortunately a boutique treatment that not many people are going to be able to afford.
01:13:55
Chris Sandel: Are you fairly hopeful that this is going to amount to these drugs being re-brought back into things that could be used as part of therapy? Does this in some ways feel like it will happen, we’ve just got to get the research to make it so?
Dr. Natalie Gukasyan: I’m cautiously optimistic. The early studies look great. But there have been other examples in research studies where something is brought to Phases II and III and it falls apart. I don’t think that’s out of the realm of possibility.
There are a lot of criticisms of the design of these early studies. They’re very small. On the one hand, we carefully select our participants; on the other hand, we carefully select our participants. Once this is brought into a larger pool of people, we might run into problems that we hadn’t come into before. We might find that there are some risks that we hadn’t foreseen. Hopefully we figure that out along the way in Phases II and III.
But if we get some reasonable results in Phases II and III – and I think even entities like the FDA in the United States are optimistic. We’ve now got fast track designation from the FDA for psilocybin for major depressive disorder. What that means is – my understanding is the FDA is going to work with us to try to facilitate some of the work that we’re doing and expedite some of the paperwork and things like that that the FDA has to do.
The other part of this is the legislative part. Under the Controlled Substances Act, psilocybin is still Schedule I, meaning that the government at this point in time, even though we have these nice studies, still sees psilocybin as something that has little to no benefit – really no benefit – and a lot of risk. So the other part is going to be legislative and making sure that the government reschedules the substance.
Chris Sandel: Does that feel like a big hurdle? My sense is if it gets to Stage II and Stage III and it’s all really promising and it’s for dealing with mental health issues, which is a huge crisis at the moment, that – maybe I’m just being naïve, but that feels like it should be fairly straightforward.
Dr. Natalie Gukasyan: I would hope so. [laughs] But again, I’m cautiously optimistic. I’ll believe it when I see it. There’s a number of ways that could happen. It could be an executive order, it could be through Congress. But there’s still a stigma for some people with substances like this. I can imagine that some conservative lawmakers might not be all that enthused about making psychedelics available for treatment.
But I do think times are changing very quickly. Obviously, if you look at what’s going on in the private sector, there’s already people raring to go and setting up the facilities and the infrastructure to be able to deliver this kind of treatment the next day after this is approved. So I think signs are pointing to “yes,” but I’ll believe it when I see it.
Chris Sandel: In terms of this study – coronavirus is messing with everything, but was the idea that this would be done – did you say 3 years before? Or is it just 3 years to get all the people that you need and then whatever extra time you need to actually publish and crunch the numbers, etc.?
Dr. Natalie Gukasyan: Yes, I’m hopeful by 3 years we should be able to have that done. Again, with coronavirus, who knows? We might be stalled for longer than we had imagined. But I guess we’ll just find out along the way. But hopefully in 3 years we should have this preliminary data.
The other question is, what does that mean for using a substance if and when it’s approved? Because if something gets approved, there is such a thing as off-label use for a lot of psychiatric medications, and there’s the possibility that this would be used off label. So it’s not necessarily that we’re going to have to do this pilot study and then this big Phase II and III study for people with anorexia. That would be great if we could, but this would provide some preliminary evidence of whether this is feasible, whether it’s safe, whether it’s effective at all in this population. Because that’s the other thing: it’s a nice idea, but we’re still testing the waters as to whether this makes sense and whether this actually can help people make the changes that they want to make.
Chris Sandel: You said before about the screening process has meant that for a lot of studies, it might not be a broad section of the population, so once it gets into bigger trials, there could be things that come up as part of that. As part of your screening and trying to get participants, is there a real push to “we want to have this real mix of diversity of people who are part of the study”? Or is it more like “let’s keep it as homogenous as possible so at least we know within that population group, we have an understanding of how things work”?
Dr. Natalie Gukasyan: I certainly would like for our study population to be more diverse. The counterweight to that is the fact that we’re working in a very high risk population, psychologically, medically. So we do have to exercise quite a bit of caution with who we select for this study. At least for this very early phase of it.
We’ve worked with the FDA to develop a set of rules that we’re going to follow about screening and making sure somebody’s medically well enough to undergo – certainly of all the people who have run through the Center and other studies, we’ve shown that psilocybin can pretty reliably be given safely, but because a lot of these folks have issues with low heart rate or changes in their electrolytes, they might be more prone to cardiac events or all sorts of other medical issues. We do have to be very careful on how we select people.
But we try to be diverse in terms of other co-occurring disorders. As long as they don’t have a history of bipolar or schizophrenia spectrum issues, we try not to discriminate in those terms. In that way I think we are getting at least something that resembles a representative population of people who clearly are struggling with issues with eating and over-exercise.
01:20:55
Chris Sandel: In terms of where you’re at now – I don’t know how much you can say, because it’s still in the midst, but is there anything you can comment on in terms of what the findings are or what you’ve noticed with the little participants you have had?
Dr. Natalie Gukasyan: In some ways it’s similar to what we’ve seen before, and in other ways it’s pretty different. What’s similar is that everybody’s experience is wildly different. We can’t really predict what somebody is going to experience from any information we have beforehand. There’s been quite a diversity of what people are reporting and what their session day looks like.
It is too soon to say whether we have any clear patterns. One consideration is that if you think about studies on depression, we’ve showed that psilocybin can produce a very rapid antidepressant effect that’s long-lasting and has benefits for anxiety as well, but if you take somebody who struggles with their eating and with their exercise and uses that as a coping mechanism, if they start to work on those things, understandably their anxiety and depression might go up. So that’s something we’re trying to understand how best to work with and how best to measure.
The other thing we’re trying to understand is what dose makes sense for this group. As I said, anecdotally, there’s evidence that people with anorexia nervosa are less sensitive to these medications, and we are still working on figuring out why that is. It’s not the case for everybody; we’ve certainly had people in our study so far that have a pretty classic response. But for some other people, it’s been different from what we were expecting. We’re not really sure why.
For some people it might’ve been because – if somebody’s on antidepressants for a very long time – this applies to people with depression as well, or anxiety – there might be longer lasting changes in the brain that happen. So even if you taper somebody off, there might be things that still can affect the body’s response or metabolism of this drug.
The other consideration is part of the reason people might be less sensitive is due to physiologic changes associated with starvation and being undernourished. We’re working on how to best work with that or try to understand, and looking at the folks we have run through the study so far, we’re trying to understand how the severity of their symptoms, their co-occurring issues, their recent use of other pharmacologic agents are coming together.
It would’ve been nice to be able to continue with our handful of other people we had planned to run this month. [laughs] But for now, we’re taking a look at the data and laying it all out on the table and trying to figure out if there’s anything we need to do differently.
Chris Sandel: With the people that you’ve had, or with each of the sessions, is that the first time they’ve had psilocybin? Because I know it’s obviously illegal, but a lot of people have used these things recreationally. So just getting a sense of if it’s more of the kinds of people who are putting their hands up to say “I want to do this” because they’ve had previous experiences, or not necessarily.
Dr. Natalie Gukasyan: People with anorexia in general I think have a slightly lower prevalence of ever having tried psychedelics. But we have had some applicants who have had it in the past. In general we’re looking for people who, if they have had it, haven’t had that much of it before, or might’ve taken it but didn’t really respond or took it years ago a handful of times or something like that. But for everybody we’ve run so far, they are hallucinogen naïve. They’ve never had anything like this before.
In some cases it’s kind of surprising, because somebody comes to you and they’re totally sober, they don’t even drink alcohol or smoke cigarettes, and they’re like, “Yes, I want to do psilocybin.” [laughs] It’s like a varsity level substance in a lot of ways. But they’re open to it. So I feel like I have to commend our participants for that, because they go into it with a really great mindset of being really open. We try to foster that in our preparation, like the way that you can make the most of this is to just be open to whatever the experience has to offer.
Chris Sandel: Is there anything I haven’t asked you about the study or that we haven’t chatted about that you wanted to mention?
01:26:00
Dr. Natalie Gukasyan: Usually we talk about risks of using psychedelics. We’ve talked about all the very nice-sounding benefits that have been demonstrated in some of these early studies, but usually I do try to stress the fact that these are drugs. They’re medications. They have side effects.
We are still at a place where we’re really learning what the risks are. We’ve had all these smaller studies, but we still don’t really know what’s going to happen as we extend the population in which we use these drugs. There’s certainly a possibility for serious adverse effects. While they’ve been fairly mild in the hundreds of sessions that we’ve done at the Center with other populations, we don’t really know what that’s going to look like for people with anorexia nervosa yet. There is a possibility that people could get worse. Like I said, if you’re working actively on changing your behaviors, that’s inevitably going to be anxiety-producing and very challenging. Doing it in a supported setting is probably the safest way to go about it, especially in this early stage while we’re still learning about it.
Chris Sandel: With the risk, from what you’re saying there, at least, is it more psychological as opposed to a risk of toxicity?
Dr. Natalie Gukasyan: Yeah. The risk of actual physiological toxicity is very, very low at the doses that we’re using. But people can have some somatic issues that come up. Blood pressure is a common issue that we run into constantly, so we monitor throughout the session what’s happening with somebody’s blood pressure. We tend to screen out for people with serious blood pressure issues because it’s a safety issue.
People have headache in some cases; that’s usually quite mild. If you look at studies of what happens to people who are using psychedelics out in their normal environment, something like 10% of people have reported that they might have put themselves or somebody else at physical harm as a result of using a substance. They might have been driving under the influence or caring for a child or something like that. So there’s a lot of unsafe situations that can happen.
We really stress the importance of making sure you’re in a supportive environment. People do experience significant distress, and if you’re not in a supportive environment, that can lead to challenges down the road. In many cases, people need to seek some help from a professional. We just want to stress that it sounds great, but we’re still learning about it, and there’s still a lot we don’t know. If this is ever going to make it to being available as a treatment for many people, we just have to tread carefully.
Chris Sandel: Yeah, so people don’t rush out and get psilocybin and do it on your own. It’s doing it in the right setting as part of research at this stage, because that’s really the only legal way of doing it.
Dr. Natalie Gukasyan: Yeah, there’s obviously the legal implications and things like that. Again, there have been many examples of treatments where they looked awesome in these early studies and then did not look so awesome once they made it to Phases II and III. As a clinician, people ask me about it all the time in my clinic, like, “Is this something I should do?” I say, “We just don’t have the standard of evidence that we need for me to be able to say to you ‘yeah, you should go off and do this for sure,’ because we just don’t know at this point.”
Chris Sandel: Yeah. Anything else I didn’t ask or didn’t cover yet?
Dr. Natalie Gukasyan: That’s it. I would just say we’re in limbo due to coronavirus. [laughs] But folks can still check out our website. It’s www.hopkinspsychedelic.org. We have a mailing list that goes out quarterly that people can join to get updates on our studies. We’re going to have some survey studies up soon.
I think there might already be some up there that we would love if folks could help us out with, especially if they have – usually the survey studies tend to be for people that have a history of psychedelic use. They can find out more about our anorexia study there and fill out an application. We’re still reviewing applications at the moment. So if folks are sitting around at home and are interested, that’s one thing they can do.
Chris Sandel: Perfect. I will put a link specifically to all of those things, but especially to the anorexia nervosa study and the application form as part of that.
Dr. Natalie Gukasyan: Cool.
Chris Sandel: Natalie, thank you so much for your time. I hope the coronavirus pandemic comes to an end so that you can get back to doing this research, because I’m really interested to see how this all pans out. Like you, I am cautiously optimistic about this and would like to see a time where this becomes a treatment that is on offer because it is proved to be effective.
Dr. Natalie Gukasyan: Thanks a lot for having me on. I really appreciate it, and I hope this is over and I hope that you and your listeners stay safe during this time. We’ll see what happens with our research. Hopefully we can get back on track soon.
Chris Sandel: That was my interview with Dr. Natalie Gukasyan. If you’re interested in potentially taking part in the study, please go to hopkinspsychedelic.org/anorexia, and you can fill out an application form there.
As I mentioned at the top of the show, Seven Health is currently taking on new clients. If you’re struggling with dieting, with disordered eating, with eating disorder recovery, with body image issues, or any of the topics that we cover as part of this show, then please get in contact. You can go to seven-health.com/help for more information.
Lu is doing next week’s episode, but I will be back with the one after that, and I will catch you then.
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