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Introduction

Ben Lewis

Benjamin Lewis, MD, Associate Professor (Clinical), practices inpatient adult psychiatry at the University of Utah Huntsman Mental Health Institute where his clinical interests involve the diagnosis and treatment of major psychiatric disorders. He has additional interests in medical ethics, the philosophy of psychiatry, and the emerging science and clinical applications of psychedelic medicine.

Resources:

University of Utah Psychedelic Science Initiative (U-PSI)

TEDTalkxSalt Lake City with Ben Lewis:

Could psychedelics help patients in therapy?

Transcript:

This podcast discusses trauma related to illness, including suicide. If you’re having suicidal thoughts, you can dial or text the Suicide and Crisis Lifeline at nine, eight eight.  That’s 9-8-8.

David Pace 0:00

Hi, my name is David Pace and this is Pace Yourself, a podcast from the University of Utah College of Science on Wellness. Today, my guest is Dr. Ben Lewis, an associate professor of psychiatry in the Department of Psychiatry at the Huntsman Mental Health Institute here at the U. Dr. Lewis’s research focuses on psychedelic-assisted therapies and his clinical work focuses on adult inpatient psychiatry, as well as ketamine-assisted psychotherapy. He’s currently the clinical director of the Huntsman Mental Health Institute Ketamine Assisted Psychotherapy Clinic in Park City, Utah. Welcome, Ben. It’s so good to have you here. Great. 

Ben Lewis 1:51

Great to be here. Yeah, Thanks. Thanks for having me, David. 

David Pace 1:54

Yeah. So, as I mentioned in an email to you yesterday, my first introduction to psychedelic-assisted psychotherapy was in the prime video movie or series, legal drama on CBS titled “The Good Fight” with lead actress Christine Baranski. She plays an attorney who is having major anxiety over the run up to and the result of the 2016 presidential election. And I’m sure there are a lot of misconceptions about psychedelic-assisted therapies. And I’m sure Christine Baranski perhaps didn’t help that, but maybe she did. I don’t know. Can you give us a brief background on its history? Bring us up to date? 

Ben Lewis 2:36

Sure. Happy to. I’m not familiar with that show, so I’m not certain how psychedelic-assisted therapies were presented there. And I think you’re right. There’s a lot of media attention currently on this topic, and that is a mixed bag. Some of that is accurate, some of that is not-so-accurate. And also a time where there’s a lot of hype and perhaps some overpromising on this set of therapies as well. And so I do think it’s a nuanced, middle ground message in terms of kind of the state of the science and in many ways, nothing new. Psychedelics have been around for millennia and have been used in different ways by different indigenous groups for spiritual and ceremonial purposes, often in group settings. And there had been a really robust period of clinical research in the 1950s and through the 1960s in psychiatry, looking at psilocybin and mescaline and LSD, specifically for mental health purposes. And a lot of those studies were very promising for a range of conditions, studied for alcohol and substance use disorders, studied for depression, studied for existential distress associated with end-of-life for terminal illness at that period of time. And yeah, a lot of very promising results and all of that really came to an end in the early 1970s when these compounds were all rescheduled, put on schedule one during the Nixon administration, and effectively that shut down any clinical research for the next 40 years or so, 40 to 50 years. And really more recently in the last decade, and then more more significantly in the last five years, there has been a real resurgence in interest in clinical trials looking at a range of different classic psychedelics, including psilocybin and LSD. 

David Pace 4:49

So you’ve got two clinical trials going on right now. Is that correct? 

Ben Lewis 4:54

Well, let’s see. We have a number of them. Actually, we have we have. ..

David Pace 5:02

Well, let me tell you the first two that I think you’re doing based upon my research. One is, I think what you were just talking about, although it says that it’s in combination with mindfulness=based stress reduction to address burnout and depression in frontline health care providers. Is that clinical trial over? 

Ben Lewis 5:25

That’s correct. Yeah. We have finished that trial. We’re currently writing up the results. We ran that trial over a couple of years. And you’re right, that was a study looking at the combination of group psilocybin-assisted therapy and mindfulness based stress reduction – MBSR, which is annualized eight week mindfulness training program, and that’s run through our Resiliency Center. So we used those resources and enrolled physicians and nurses who were dealing with depression and burnout related to the COVID 19 pandemic. And yeah, really, really fun and challenging and interesting study. We randomized participants to either just receiving the mindfulness training. So people either did an eight-week mindfulness training protocol or they did that same program with a high-dose group psilocybin session and asking the question, are there differences between the groups in terms of, you know, severity of depressive symptoms, severity of burnout? We looked at a range of outcomes related to just mindfulness. Like, is this a helpful thing as far as mindfulness training? So yeah, we finished that study.

We did another group trial with psilocybin for patients dealing with depression associated with cancer. That was our first psilocybin trial here at the U. We finished that a few years ago. We’re running a few other studies, actually. We’re running a trial for treatment-resistant depression with psilocybin, and we’re running a study for postpartum depression. Also not using psilocybin, but using a sort of novel, short-acting psychedelic called 4-HO-DiPT. And then we have a couple studies with ketamine, assisted psychotherapy going on right now. 

Ketamine vs psyilocybin 

David Pace 7:24

So ketamine is, I understand, is FDA-approved in certain settings, but not necessarily for some of the stuff that you’re doing clinical trials in? 

Ben Lewis 7:36

Yeah, that’s correct. Ketamine is used clinically. Currently, it has an FDA approval in its Spravato®  formulation, which is a nasal spray, and that’s approved for treatment resistant depression. Ketamine is used in as an I.V. infusion, also for depression. This style of working with ketamine that I’ve been doing clinically in that we’re doing research with is ketamine, assisted psychotherapy. So a little bit of a different framework for using that medicine. And in also to be clear, ketamine is distinct from other classic psychedelics. It’s distinct pharmacologically. The risk profile with ketamine is pretty different than, say, psilocybin. Classic psychedelics, like psilocybin, are still on schedule one, so we can’t use them clinically. Really, we’re using them only for research purposes and you have to go through hurdles with the FDA and the DEA, whereas ketamine is clinically available. And so in certain respects, easier to to study, currently. 

David Pace 8:43

So I’m interested in this interface or how mindfulness might inform the use of these psychedelics, because I think a lot of us are familiar with mindfulness. 

David Pace 9:00

Is that is that designed to process the experience? Because we’re really talking about having an experience or what? Yeah, people used to call a trip, maybe they still do, right? And so is the mindfulness really to like in a guided way to try to process the experience, whatever that might have been for the individual. Is that the intent? 

Ben Lewis 9:23

Yeah, it’s a great question and I think there’s different angles for thinking about that. I think there are experiential elements of overlap between states that people can access through mindfulness meditation, in psychedelics. Certain kinds of non-dual experiences are overlapping with those practices. There’s also, to your point, questions about how to adequately prepare somebody for an experience with something like psilocybin where they maybe have some tools for navigating what can be a challenging or difficult or very unusual experience.

And then on the flip side, there are questions about how do we integrate or sustain those kinds of benefits that might happen. Right? And I think in a complementary way, there are questions: Are those kinds of experiences with the psychedelic? Are they helpful in sustaining or growing or developing a mindfulness practice? So many of those questions, we don’t really have great answers to right now. This is not super well studied, but most of those questions really inform the motivations for a study like this. 

David Pace 10:45

What are the group-based interventions that you’re talking about? 

Ben Lewis 10:49

So one real challenge with, say, the majority of psychedelic-assisted therapies in clinical trials is that they’re typically individual format, so they involve two therapists per participant. And it’s a long session, right? It’s an eight-hour dosing day typically with psilocybin. So a long, long day. And it’s bookended by preparatory sessions and then integration sessions on the flip side. So it’s very resource-intensive, and so like to move a single participant through that protocol that might be 20 hours times two, so 40 therapist hours. And there are just really significant questions how might we scale this or make this accessible for the ability to treat more people down the road? So there are research questions, there is a safe and feasible to do, and then there are there are questions just in terms of scalability when this rolls out is a form of clinical treatment.  

Ben Lewis 11:58

So the group models we’ve done and this has been novel in terms of the research we’ve done here has involved the full-group format. So we’ll have a group of say, five participants and we’ll do group preparation where, you know, people are engaging in a group format, kind of moving into the dosing-day session. And then we have a full group dosing session where everybody’s in the same room. We have music played over a speaker system to do that and then group integration, and that has not been done in the modern era. So we’ve done two trials with that model so far, and they’ve been small studies, but they’ve been feasible, they’ve been safe, they have seemed in certain ways to suggest some unique efficacy of that group environment for people with this kind of experience. 

David Pace 12:55

So it sounds to me like you’re talking that this is not like a one on one talk therapy thing, but there’s a kind of a social element to this kind of therapy that might inform or aid what results you’re maybe gunning for. 

Ben Lewis 13:14

Yeah, exactly. I think part of, for instance, depression and burnout can be a real sense of isolation, a real sense of disconnection. And so it has felt like that group format makes a lot of sense in a lot of ways as far as targeting those kinds of conditions. And insofar as that group format dosing session, it’s not especially interactive. It’s a pretty internal experience. People are wearing eyeshades. It’s, you know, there’s not a lot of interaction per se on that day apart from before and after the dosing sessions. 

David Pace 13:58

So it’s not like a group therapy scenario where you’re sharing stories. 

Ben Lewis 14:03

Not during the active drug effects, but certainly before during preparatory sessions and then subsequent integration sessions. Yeah, it really does have a group therapy feel to it. 

David Pace 14:17

So the brain chemical that we’re working with, at least in ketamine, is called glutamate. 

Ben Lewis 14:25

Yeah. 

classic psychedelics

David Pace 14:25

And is that different than what you’re using with the other psychedelics? 

Ben Lewis 14:29

Yeah. Good question. And ketamine is distinct. It works differently in the brain. It works on the glutamatergic system by targeting NMDA receptors. And that’s very different than something like psilocybin, which is considered a classic psychedelic, and classic psychedelics really refer to psilocybin, LSD, DMT, mescaline. So like a family of different compounds that all act on the serotonin 2A receptor, so a different receptor subtype, different certainly duration of effect with those compounds, different experiential effects, presumably different clinical effects, and some overlapping elements too. So there are overlapping elements in the kinds of therapeutic approaches that we might use. They’re overlapping effects for what people might experience on those different compounds with some distinctions. 

David Pace 15:31

And they’ve got to be extremely unique to each individual. Isn’t that part of the difficulty in measuring and assessing the value of these psychedelics? 

Ben Lewis 15:43

Yeah, exactly. Those experiences are really different for everybody. They tend to have a quality of ineffability, so people can’t really describe or characterize or put into words what that experience was like or meant to them. And are quite varied, unpredictable. And there are many questions as to what is the relationship between the experience itself and therapeutic outcomes. We don’t know the answer to a lot of those questions. Most studies to date have shown that certain kinds of experiences that people have — the higher the magnitude on those experiences — the more significant and sustained the therapeutic effects. And that’s been studied primarily in terms of this concept of mystical experience. And there’s a range of questionnaires that get used to, you know, imperfectly characterize what people might have experienced. And most of the studies to date have have really shown that the higher the magnitude of mystical experience that people experience during the session, which is really characterized by a sense of connection, a sense of ineffability, a sense of sacredness, a sense of deep personal meaning, those experiences seem to predict therapeutic response, which is like an interesting and like very unusual thing in psychiatry. 

spiritual enhancement

David Pace 17:24

So, yeah, you walked into your typical psychotherapist office and, maybe I’m speculating here, but I’ve had some therapy myself, and you start talking about spiritual matters, spiritual enhancement, which is what these drugs can can do, along with a whole list of other maladies that it can address. Although spirituality, I guess, is not a malady, but a condition, I guess is the better word. And you can’t get very far with a lot of psychotherapists if you start talking about religion or spirituality, in my experience. And so this is kind of like you were hinting at just now, it’s like, we’re not in Kansas anymore. That’s right. In some way. Is that must be kind of exhilarating. 

Ben Lewis 18:21

Yeah, well, exhilarating, scary, uncertain, right. Like, and it brings in all of these elements that science has historically been somewhat antithetical to. Right. And for new, really good, deep reasons, though, I would say, I mean, I don’t think there’s anything about spirituality that is not open to scientific study, and I don’t think it necessarily has to be woo-woo in ways that preclude thinking carefully about it and studying it and taking it seriously as an avenue, an important vein of human flourishing and well-being. 

Ben Lewis 19:06

There’s a there’s a philosopher, Thomas Metzinger, who wrote this great essay called “Spirituality and Intellectual Honesty,” which I always come back to, and this essay really argues that spirituality and science share this common underlying value of intellectual honesty, a sort of radical kind of honesty. And I sort of like that framing for spirituality. But yeah, I don’t think it’s very easy in the field of psychedelic science to strip out elements of spiritual experience for people. That’s an important part of what people experience, and it seems to be important as far as what happens for them therapeutically. 

David Pace 19:56

Yeah, well, I think it’s an opportunity to bridge a divide that maybe doesn’t really need to be there. Actually, there’s a lot of literature, I won’t say a lot of literature, but some literature now around the “spirituality of science.” And of course everybody just kind of around here, kind of ducks, ducks and covers when they hear that, you know, especially when you’re in an environment here where religion is very the civilizing force of the state. Right. In many ways, politics and otherwise. But yeah, I think it’s an opportunity, and I’m glad that you suggested human wellness because of course that’s what this podcast is about. So we’ve approached this, just as a little back story to this podcast, we’ve approached this with eight dimensions of wellness that the National Institutes of Health, have established, one of those of which is spirituality. So it’s kind of nice to see. And of course, the irony of all of that is that they’re all related, right? And so it’s kind of superficial in a way to break it out into components. And we found that out very quickly ast year, didn’t we Ross because every time we tried to talk about social wellness, we very quickly started talking about physical wellness, mental health. In a way we went. So maybe we should have all been taking a trip. I don’t know. Maybe that would have helped. 

Ben Lewis 21:27

I could see a utility in sort of dividing different categories because there are ways in which we might neglect certain aspects that, when framed in a certain way, maybe become a little bit more salient, right? 

David Pace 21:40

Well, and the notion of holistic health, you know, and wellness is huge right now, somewhat of a buzz term. But I think it’s worth unpacking really a lot because there are these segmented, siloed disciplines that we’ve had traditionally. And the modernist experiment, if you will, since the Enlightenment, we’ve kind of broken those up into silos, which is a danger. So again, it must be a bit exhilarating for you to kind of see these connections coming together and seeing opportunities to explore them. 

from Maine to Iowa Medical School

Ben Lewis 22:25

Absolutely. I mean, I went into psychiatry in the first place because it seemed to offer this broader way of thinking about humans and approaching various ways in which people suffer or struggle, and this for me has been a really wonderful way of kind of connecting with that original motivation for me.

David Pace 22:51

Tell us a little bit about your background. Where are you from and where did you go to school and and what was your journey into psychiatry? Did you decide you wanted to be a medical doctor to begin with, or did you decide that you wanted to be a psychiatrist right out of the gate? 

Ben Lewis 23:05

Yeah, I had a little bit of a yeah, and not a not a very direct path, I guess. I grew up in Maine mostly and went to undergrad in Cambridge at Harvard University and studied English and philosophy. So medicine was not really on my radar at that point in time, although my father was a physician. So it was it was on my radar to some extent. I met my now wife during undergrad and we subsequently moved to Iowa City when she got into medical school. And it seemed to me, Jeez, that doesn’t look so bad. It seems to be fine what you’re doing there. I think I could probably do that as well. And so I took pre-med classes and, and then eventually went to medical school at the University of Iowa with much less ease than my partner. 

David Pace 24:00

Well you were a Humanities guy. 

Ben Lewis 24:02

Humanities guy.

David Pace 24:03

The dangers of humanities.

Ben Lewis 24:05

You know, prior to that, I had been first volunteering and then working in a research lab at the University of Iowa that was at that time run by Antonio Damasio, and they were doing a whole range of really cool projects around emotion and consciousness and autobiographical memory. And I really liked that. I really liked the way we were engaging with study participants. I really liked thinking about the brain. I liked kind of all of the philosophy of mind stuff that went into that. So I was thinking, you know, in relation to medical school, something about the brain: neurology, psychiatry, and then just really liked psychiatry a lot more in school.

We finished. My wife did a public health degree, so we finished at the same time and then couples-matched here for residency back in 2008. So and then have been here since then a little, little while.

David Pace 25:08

Yeah. So let’s talk really quickly before we pivot to maybe what most of our listeners want to know. Like, am I a candidate for this? I’m interested in the conditions that it looks like PTSD is one of them. I wanted you to expand on those kind of hard core conditions that people are suffering from, that this therapy or therapies could could help. 

Ben Lewis 25:55

That answer is a little different depending on which compound you’re talking about. And so, for instance, starting with ketamine, really the bulk of the evidence for ketamine is in treatment-resistant depression and treatment-resistant anxiety disorders. And so that’s mainly what we treat in our clinic right now, looking at psychedelics like psilocybin or LSD. Again, these are still predominantly in sort of research phases and have been studied for depression, including treatment-resistant depression; have been studied for substance and alcohol use disorders; have been studied for anxiety. They have been studied for end of life, existential distress or anxiety and depressive symptoms surrounding fears around death and dying. You mentioned PTSD and that’s really referencing MDMA. So, again, a somewhat distinct chemical, not a classic psychedelic. 

David Pace 26:59

Tell me again what MDMA is. 

Ben Lewis 27:00

MDMA, the street name or the street drug name for MDMA is ecstasy or Adam. And, you know, has had a history in the club drug scene. And MDMA has been studied extensively at this point for PTSD, post-traumatic stress disorder. And there have been two completed phase three trials for MDMA, assisted psychotherapy, for PTSD. And in fact, that compound was just reviewed by the FDA this past summer, this past July. And the FDA said, no. The FDA did not approve MDMA assisted therapy based on two phase three trials that had been sponsored by Mapp/Lycos now, which was a big deal and a disappointment and in many ways spurred a lot of discussion, a lot of strong feelings there. Certainly problems with the approach to certain elements of the approach to those trials. So the FDA and the preceding advisory committee meeting, they put their fingers on some very legitimate concerns and issues and came down pretty hard against approving that medicine, requesting that that company completes another phase three trial, really digging into some safety data prior to approving that medicine. So that was a was a pretty big deal for the field as a whole. And certainly pushes back the timeline of that style of treatment being available for people clinically. 

David Pace 28:49

Yeah. I was reading in the “Lancet” regional health journal out of Europe, but I guess it was just almost exactly a year ago when it came out. But they were talking about the, first of all, the need for new therapies in this way. They were talking about how many people suffer from mental illness in Europe. And I’m sure that it’s just as bad here. I’m trying to find that statistic readily. But they also were talking about how complex the treatment protocol is of these sorts of attempted therapies, and definitely that there needs to be more trials and so forth. They’re being obviously cautious, which is why I suppose we have these trials and these institutions that try to keep us on track. But I guess I was just struck by what a problem mental illness is. And I don’t know, maybe you could talk briefly about that and the kind of the broad picture of mental illness as we move forward through this technological age, which I think is being linked to some of the isolation that people are feeling and the despair and the confusion, maybe.

Yeah. Can you speak briefly about that broad picture of mental illness in the United States, maybe in particular? 

Ben Lewis 30:31

Sure yeah, I think you’re totally right. You know, there are certain things we can do in mental health fields and in psychiatry, and there is just an ocean that we’re not really able to effectively do a whole lot about. And for me, that has just taken an increasing toll as a psychiatrist over my career, where I’ve practiced predominantly inpatient, adult psychiatry. PTSD, for instance, our current treatments are inadequate, and there’s really no other way to to say that a huge fraction of people are not helped by the medicines that are available. A huge fraction of people are not able to really complete or adhere to the evidence-based psychotherapies for PTSD, and the impact of that condition over time — which is a chronic condition — hose impacts are just huge and growing. And to your point regarding the milieu we find ourselves in now, where we have sort of increasing sense of existential crisis; we have an increasing sense of disconnection in large part levied by our technological devices and the way we were living in modern society; many features of mental illness appear to be getting worse.

And so a huge motivation for me with this field is this hope surrounding a style of treatment and a way of engaging that, yeah, holds promise of being effective in a sustained way for people. And for sure, many, many questions still to be answered and still pretty early on and in understanding that. But I think enormous promise is there, especially for very difficult to treat conditions. 

David Pace 32:31

Yeah the single dose psilocybin is that what it’s called has been incredibly promising at least in the studies that they have done. Maybe not as big of the study as they need, but it’s apparently, according to The Lancet, it’s just striking at how those single dose experiences can shift, get people out of their “stuckness.” 

Ben Lewis 32:56

Yeah. Yeah. And I think it’s a different model than taking a medicine every day forever. Right. It’s a discrete number of sessions: one or several.  And again, like a lot of of questions still, there have been studies looking at, for instance, treatment-resistant depression. And there are still a number of questions in terms of how long are those benefits sustained and that differs for different patients. Right? But yeah, no, I think you’re totally right. There’s been a lot of like early, very, very promising results with this style of treatment. 

David Pace 33:36

So I found the statistics that I was referencing earlier from the Lancet article, almost 1 billion people, they estimate, have mental health conditions globally. And in the European Union alone, mental health problems affect more than one in six people and the economic cost exceeds 4% of the gross domestic product. So we’re talking about a major crisis or opportunity to rethink something. 

Ben Lewis 34:05

Exactly. 

David Pace 34:08

So there’s PTSD, there’s depression, there’s alcohol use disorders, addictions, social anxiety, like the kind that Christine Baranski was having in her show. And I think it’s very telling that we’re talking about this just weeks before the election, again, I’m sure a lot of that has happening. And again, enhancement of spirituality being another condition that this can deeply affect.

Is this for me?

So here’s a couple of questions for you. I think we’re kind of wrapping up here. If someone were to ask, am I a candidate for this kind of therapy, what would you first ask them? 

Ben Lewis 34:50

Yeah, I think as far as enrolling in a clinical trial, a lot of those parameters are very, very narrow. That’s a very limiting aspect right now for people who are interested in accessing this kind of treatment. It’s also a really interesting time and that there are legalization measures afoot in states where this is now clinically available: Oregon and Colorado. So there are a range of pathways and, you know, they’re not all aligned with similar thinking necessarily or similar models.

But engaging in clinical trials with classic psychedelics is hard. I mean, they’re very limited and they’re hard to get into and very specific and pretty narrow and also very intensive for participants. So that’s a real challenge. There’s many more people that are really interested in these kinds of treatments than we have availability for in trials or like in clinical avenues. And then it gets interesting as well because there’s a whole host of underground avenues that people people access this to. And those are heterogeneous in terms of what that looks like and in terms of safety.

So it’s tricky. It’s tricky to navigate in this, tricky to advise people on this topic.

Looking at ketamine, yeah, that that is much more accessible. So ketamine is available clinically. People are receiving ketamine infusions and ketamine treatments. Ketamine assisted psychotherapy is clinically available for certain conditions. So that’s much more of like a available clinical avenue for people right now. 

David Pace 36:44

So it really it’s it’s very individual, and it’s very just depends on the diagnosis of the psychiatrist which. I assume you have to have a prescription to get into these trials and to get some help. 

Ben Lewis 37:00

So yeah, to enroll in a trial. Basically, people just need to go through a screening process So  people can contact our study coordinator team to to be if they think they’re eligible for a trial on, say, postpartum depression or treatment resistant depression can either reach out to me. We have information for our study coordinator contact and that would put somebody on a list of people to be screened and that would include like reviewing medical records, sort of consulting with their outpatient providers, reviewing medications, reviewing other health conditions that might be like an exclusion criteria, making sure they’re not on any like conflicting medications. 

David Pace 37:51

So yeah, a lot of questions to answer. It’s very interesting to have this available to us in our backyard in a way.

So we are observing here at the University of Utah Mental Illness Awareness Week this week. So we want to thank Dr. Ben Lewis, professor of psychiatry here in the Department of Psychiatry at the Huntsman Mental Health Institute for joining us today. And we will put some of these resources in our transcript with some links that maybe you can share with us. 

Ben Lewis 38:35

Sounds great. 

David Pace 38:36

Yeah. So thank you again, Ben. Anything else you want to say before we sign off? 

Ben Lewis 38:40

Yeah. Thank you, David. Yeah, Pleasure talking with you. Thanks for the opportunity. 

David Pace 38:43

Thank you.