In this episode, we discuss:
- The current state of research into psychedelics for therapeutic uses
- Using MDMA to help treat post-traumatic stress disorder
- The drawbacks to increased popularity and exposure of psychedelics
- First-generation versus newer second-generation psychedelics and choosing when to use different compounds
- Dr. Gorman’s company, Fluence, and the work that they do
- Fluence website
- Add back in what the modern world has crowded out and feel and perform your best with the Adapt Naturals Core Plus Bundle. Learn more at AdaptNaturals.com
Hey, everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. I’ve been interested in the use of psychedelics and empathogens for psychotherapeutic treatment for many years. If you’ve been listening to my show for some time, I’ve had a few different guests on to talk about that from different perspectives, including Michael Mithoefer, who co-founded the [Multidisciplinary Association for Psychedelic Studies] (MAPS), [3,4-methylenedioxymethamphetamine] (MDMA) assisted psychotherapy, and [is] doing a lot of research on the application of MDMA for PTSD and other psychiatric and psychological conditions. I’ve been really excited to see how research in this field is continuing to progress, not just with MDMA, but also with psilocybin, ketamine, and other compounds that have shown promise in supporting people with depression, anxiety, PTSD, and other conditions for which conventional treatments sometimes leave a lot to be desired. The psychedelics and empathogens seem to work in a fundamentally different way, and in some cases, can lead to pretty dramatic improvements almost overnight, and these improvements are often long lasting. Ketamine is a great example of this.
For people with moderate to severe depression, I’ve seen ketamine reverse it overnight, and I’ve seen those effects last over a significant period of time. Now, none of these treatments are panaceas, and I think that’s really important to point out. Whenever there’s an exciting new development like this, there’s often a bandwagon effect, and I think sometimes the risk is that we can attribute almost miraculous powers to these new treatments. I don’t want to see that happen in the case of psychedelics and empathogens because they have so much potential when they’re used properly. And they’re not without risk. There are, I think, pitfalls, especially when they’re not used under supervision and/or when they’re used improperly. And that’s also a risk when there’s so much interest in them and they’re not easy to obtain because they’re still illegal in many cases in the [United States] and other countries. That leads to people getting them through backchannels, and sometimes people aren’t getting what they think they’re getting, and that leads to a whole bunch of different risks altogether.
I’m really excited to welcome Dr. Ingmar Gorman as my guest today. He earned his doctorate in clinical psychology at the New School for Social Research and did his clinical training at Mount Sinai Beth Israel Hospital, Columbia University, and Bellevue. Then he completed his [National Institutes of Health] postdoctoral fellowship at New York University in 2017. He served as the co-principal investigator on phase two and phase three clinical trials of MDMA-assisted psychotherapy for post-traumatic stress disorder (PTSD), and he’s also published on topics of classic psychedelics, ketamine, MDMA, and psychedelic harm reduction and integration.
He has a lot of experience in this field, and he is now the co-founder and CEO of Fluence, a psychedelic therapy training company, which is geared toward training healthcare professionals on how to use psychedelics in their practice for therapeutic purposes. I really enjoyed this conversation. If you’re interested in this topic, I think you will, too. Let’s dive in.
Chris Kresser: Dr. Ingmar Gorman, it’s a pleasure to have you on the show.
Ingmar Gorman: Pleasure to be here.
Chris Kresser: I’m curious about what got you interested in the field of psychedelics as they’re applied in a psychotherapeutic context.
Ingmar Gorman: It’s a long story, but the short version of it is that I was living in Prague in the Czech Republic. I’m half Czech and partly grew up there. It was a combination of exposure to an expatriate community that was very interested in psychedelics, as well as a long-standing history of psychedelic research in the former Czechoslovakia. As I began to do some research [and] look into some of the literature, as well as some of my own personal experiences, I realized that there really was a lot of overlooked potential to these compounds, potentially medications, that were studied in the [1940s], ‘50s, ‘60s, [and] early ‘70s, and then that research got shut down. My thinking was, “I always like an underdog story; why not contribute to more science in psychedelics and see whether there really is this overlooked potential that could be helpful to many, many people and their mental health?” That was around 2004, and at that point, after about a year, I decided to return to my undergraduate education, and I dedicated my entire career to the topic of psychedelic therapy and science and got a PhD. And here I am today.
Chris Kresser: Fantastic. I’m looking forward to diving into that in more detail. I want to share a little bit about my experience on this topic, just for full disclosure. Whenever I talk about psychedelics or empathogens in a clinical context, I like to tell people a little bit about where I’m coming from, as well. Like you, I have my own personal experience. I went to UC Berkeley as an undergrad, and, [while] not quite the same as it was in the ‘60s when my parents went there, [it’s] still definitely the type of place where people are doing this kind of exploration. I was fortunate to encounter a mentor who guided people who were interested in this on how to use psychedelics for therapeutic and even spiritual purposes. So I was very fortunate to have exposure to somebody like that at an early age and explored various psychedelics, empathogens, and plant compounds that had similar effects. I feel like those really opened a lot of doors for me and gave me insight and perspective that I wouldn’t have had otherwise. I’m sure we’ll come back to this. I like to say that they opened the doors, [but] they didn’t take me through the door[s]. I still had to do that work myself. But I’m tremendously grateful for the doors that they did open and the things that they showed me.
Over time since then, I’ve gone in and out of using psychedelics for that same purpose, always with a growth orientation, not really for recreational purposes, but just for gaining insight and perspective and clarity in ways that are more difficult to do as we inhabit our normal reality. Then as a clinician, I became really interested in their therapeutic potential for anxiety, depression, [and] PTSD. I’ve had Michael Mithoefer on the podcast, whom I’m sure you know well, and several other people who are exploring this in different ways. I’ve seen the effects firsthand of depression, anxiety, PTSD, and other mental and behavioral health conditions, and I’m aware of how lacking some of the typical treatments are and how much people suffer from these conditions. I’ve seen pretty miraculous effects in some cases with things like ketamine in people with moderate to severe depression that can be quite long lasting. And they’re not a panacea. I’m sure we’ll talk about that, as well. But I’m thrilled that people like you are out there doing this research and advancing this field forward because I think there’s so much untapped potential, and I think these treatments are so much more humane and safe than a lot of the treatments that are currently already approved and out there and in widespread use.
So [I’m] really looking forward to diving in further. [I] just wanted to give everybody a little bit more about where I’m coming from here so that they know what my background is on this topic. Let’s start with a brief summary, if that’s even possible, of the current empirical evidence and clinical trials that have examined psychedelics for psychiatric conditions like depression, etc. How would you summarize the state of the research right now?
Current Research into the Therapeutic Use of Psychedelics
Ingmar Gorman: Sure, I’m happy to do that. And thank you for sharing that background. I definitely found parallels in my own story to yours. Hopefully, we’ll return to some of the things that you had mentioned.
It’s quite a lot to summarize. I’ll say that, in the first era of modern psychedelic research, which was from perhaps the mid ‘40s to the mid ‘70s, some of the indications that were studied included alcohol use disorder [and] anxiety related to end of life. In terms of smaller studies, if you go through the literature that was published at that time, you can find dozens of different ailments or indications that were studied using primarily [lysergic acid diethylamide] (LSD) or psilocybin. MDMA, the entactogen or empathogen that you mentioned, was not really rediscovered until the mid 1970s, so you didn’t have much research there. The psychedelic renaissance, as sometimes people refer to it today, was really revitalized in the mid 2000s, began to pick up steam in [the] 2010s, and now is really moving forward with a lot of energy behind it. What you’ll notice is that some of the studies that are further along today have built upon the research that was conducted in the ‘50s, ‘60s, and ‘70s.
[For] anxiety related to end of life and alcohol use disorder, those studies were redesigned or the design[s] of those protocols were updated. You have studies today with initial results that are promising with alcohol use disorders, smoking cessation/nicotine use, [and] end-of-life anxiety, as I’d mentioned. But also depression and treatment-resistant depression. [And] some early studies looking at eating disorders, anxiety, and people living with autism spectrum disorder. I’m sure I’m leaving out some here. PTSD is where we see MDMA, or the empathogen, really being studied, and that research sponsored by MAPS, for whom Michael Mithoefer has been a major contributor, is probably the furthest along.
Maybe it’s fair to just quickly add that I’m not going to go through the whole [U.S. Food and Drug Administration] (FDA) approval process unless you would like me to. But maybe we could focus on two kinds of studies, phase two and phase three studies. Phase two studies usually [are] with 20 participants. You have compounded a drug and you have a hypothesis that it’s going to work with a particular disease. You’re looking at small samples of 20 people, and perhaps you do several of these smaller studies, and you’re looking for safety data, but also for a signal. Is there a signal here that this could potentially work for a small number of people? If you find that signal, then you scale up to what’s called a phase three study, which is where you’re looking at hundreds of people, [and] again, looking for that signal. I’ll say that with the MDMA for PTSD research, we are potentially close to the end of phase three. MAPS, just a few weeks ago, closed off recruitment for those studies, meaning that they believe they now have the number they need to submit to the FDA for review. Pretty much all [the] other studies I had mentioned are at the completion or the beginning of phase two but have not moved to phase three yet.
One last point that I’ll add here is that after phase three, once those data are collected [and] submitted to the FDA, they can do a review. If all goes well, then that compound can become a prescribable medicine. So again, MDMA for PTSD is furthest along, and if all goes well, we could, [and] I have to be very careful about how I word this [because] it’s not definite, but there’s a possibility that MDMA might become a medicine, potentially, in 2024.
Chris Kresser: That’s amazing and quite a surprise, in some ways, if you consider what you mentioned earlier [about] how the research climate was pretty hostile to these compounds not that long ago. What changed there? What are you seeing now in terms of the receptivity of [Institutional Review Boards] and the research community as a whole, the government regulators, etc.?
Ingmar Gorman: Great question. From what I’ve seen in the near past and the present and the future, one really important study was the work of Rick Strassman, who was studying [N,N-dimethyltryptamine] (DMT). In the ‘90s, [he] went through all the regulatory paperwork and hurdles [just to get the approval for] a study to look at a psychedelic in healthy humans. Many people credit him as doing all the difficult labor for a study to be just conducted. Another factor is [that] the generation of people who are in the FDA or other [similar] institutions are some of the [same] people who were more active in the 1960s and ‘70s, and now they’re in positions of authority where they may have their own perspective on the potential for these compounds. So there’s a little bit of a shift in culture there. That was maybe the ‘90s and 2000s.
When we’re talking about the present moment, there is a recognition that the medications that we have currently are not addressing the large mental health crisis. That’s not to say that current medications don’t work. They do work for some people. But I think [it’s] agreed upon that [it’s] not enough of a solution to address the scale that we’re looking at. Another element of it is also financial interest, just to be blunt. There’s a lot of potential money to be made by identifying new psychoactive compounds or psychedelic compounds that don’t even exist yet that can be patented. And also to find solutions because if you could address depression or anxiety in the United States or globally, there are so many people [who] suffer from this, as you had mentioned earlier, there is also money to be made there.
Chris Kresser: Yeah, the economic burden of depression alone worldwide is in the hundreds of billions of dollars, if not trillions of dollars. I agree, just from my outside perspective looking in, [that] it seems like the gestalt around psychedelics has changed. There’s this snowball phenomenon, where you get some studies approved, [and] that adds legitimacy. Then you get people in Silicon Valley microdosing and talking about their microdosing on podcasts, and then you get a new startup that somehow raises millions of dollars and is valued at a billion dollars that’s related to psychedelics. All of a sudden, something that was relatively fringe and verboten to talk about publicly in the past is sanctioned through all these different avenues, whether they’re governmental and regulatory, or whether it’s Silicon Valley and venture capital coming in to add their stamp of legitimacy. It does seem to me that there’s been a sea change.
Ingmar Gorman: For sure. And it’s been so rapid, it’s a little bit of a whiplash in the last three years. As I was listening to you, [there was] one thing I [wanted] to add in terms of a variable that might have contributed to this change. I think we really need to give credit to the scientists who in 2006, 2008, were doing very strict and sometimes even conservative science around psychedelics. I’m thinking particularly [about] the group from Johns Hopkins, Roland Griffiths, Matthew Johnson, and others there, as well as teams at New York University, Stephen Ross, Jeff Gus, Tony Bossis, and others who did not get too caught up in the overexuberance about these compounds and really paid a lot of attention to strict clinical research design so that when they were questioned about the legitimacy of the science, they were prepared with the data and the kind of approach so that they would be taken seriously.
Chris Kresser: It’s so important to do that, especially early on, and especially with compounds that already have a stigma surrounding them. I think that’s a great point. Let’s talk a little bit about some current theories on why psychedelics are effective. Maybe we can focus on PTSD because there’s more research on that with MDMA than anything else. What are some thoughts on what’s actually happening there in terms of the neurochemical, biological changes? And, by extension, what is MDMA doing for people with PTSD that other current treatments are not able to do?
Ingmar Gorman: This is a great question. I could talk about this for several hours.
Chris Kresser: We’re probably going to have to have you back. We’ll just do a brief summary because for this show, I just want to give people an overview of everything that’s happening in this space, and then we can have you back to drill down on specific topics.
MDMA and Post-Traumatic Stress Disorder
Ingmar Gorman: Sure, sure. First, it’s important to say that there’s more money coming in [now] to do this research, but for a large portion of time, it was really based [on] donation and fundraising. Whether it’s the donations or not, [with] clinical research at this phase, you’re going to get [the] best bang for the buck, so to speak, to evaluate whether something works or not, [rather than] how it works. So we don’t really know exactly how these treatments might work, but we have hypotheses. One way that I like to break that down [is that] it could be a passive process, where there’s just a biological effect. So if we’re talking about MDMA and PTSD, we have [the] release of serotonin, [and] there’s also oxytocin and prolactin. You have a dopamine release, as well, [and] some cortisol release. I’m not a neuroscientist, but [that’s] to say that there are many neurochemicals that are associated with the ingestion of MDMA.
How might this be helpful when it comes to PTSD? Well, one thing that we observe in brain scans is that there is a reduction in activity in the amygdala. The amygdala is a place in the brain that is processing fear. We know that in people who are living with PTSD, there’s overactivation in the amygdala. So one hypothesis might be [a] pure biological mechanism here, having some return to normal in terms of the amygdala function. But we also know that when we talk about psychedelic therapy, or MDMA therapy specifically, it’s a combination of the drug effect and the psychotherapeutic or psychological experience. So here, we could look at a combination of what’s going on biologically in the participant or patient and also the therapy that’s happening in the room. For example, oxytocin, prolactin, that’s a bonding hormone associated with a greater sense of trust. When we look at people who are living with PTSD, often, there’s also some sort of interpersonal violation that has happened there, and it’s very difficult for them to establish trust, particularly very quickly like we see in the studies where we’re talking about a three-month treatment. So there might be some facilitation of the therapeutic relationship between the therapist and this effect with oxytocin.
I could go on. We could talk about serotonin and mood; we [could] talk about dopamine and the ability to focus and learn. There’s likely [a] synergistic effect between a lot of these different neurotransmitters and healing. But there’s also another factor that may not be purely biologically mechanical in nature, like pure neurotransmission. We can also think about how the therapy is designed in MDMA-assisted psychotherapy for PTSD [and how] that might contribute to the person getting better. One of the fundamental tenants in this work, and really across different psychedelic therapies, is this notion of trusting the participants’ or patients’ intuition around their growth process. We don’t give people MDMA as the therapists say, “Okay, this is everything that you’re doing wrong in your life. And this is what you need to do better. And isn’t it terrible that you’re drinking.” No, it’s the opposite. We create an environment and a setting that allows for the participant to be their own guide. We give them the space and time to journey inward, to speak metaphorically, and begin to identify the kinds of things that will help themselves get better. I think that’s partly why these studies are so impactful because the path is not dictated by somebody externally; it’s really coming from within the person undergoing the experience.
Chris Kresser: This resonates with me because one of the things I’ve done over the years [is that] we have a health coach training program [at Kresser Institute]. And health coaching is based [on] a similar methodology and approach, where we recognize the wholeness of the client, and it embraces a positive psychology frame where each person is fundamentally whole, and it’s up to the coach to help them discover their own strategies and motivations for change. Rather than starting from the place of “You’re broken, you need to be fixed, and [I] as the outside, the clinician, the authority, the therapist, whatever, I’m going to fix you,” essentially. Which is kind of the conventional method. So I love that. And I think, from my own personal experience, that resonates as true for me. I have a theory of my own that’s not tested [and] it’s not based on mechanics that I’d love your take on.
Ingmar Gorman: I’d love to hear it.
Chris Kresser: I think that when people are dealing with severe depression, and also people with PTSD, what can happen is [that] we begin to identify as being depressed. “I’m a person [who] is depressed. Depression is my reality. This is what I experience every time I wake up, and it’s the last thing I experience before I go to bed.” And that gets enmeshed, where I no longer can experience myself in any other way than as someone who is depressed or who has PTSD. And what psychedelics do, whether it’s MDMA or psilocybin, is allow us to disidentify with that conception of ourselves and experience ourselves in a fundamentally different way, often completely free of whatever has plagued us 24/7 for months, or years, or even decades. And what that does is create hope. It allows us to conceive of the possibility that we could be free of this depression or this trauma or whatever it is that’s been so difficult for us. And that hope makes all kinds of things possible that were not possible before. I’m curious what you think of that.
Ingmar Gorman: I actually couldn’t agree more. I think that this is definitely one of the elements of what contributes to people getting better, and it can be quite astonishing. I have direct experience in these clinical trials with a participant just being astonished at the fact that they aren’t breaking down when recalling a certain memory. It’s not a blissful state, [and] it’s not an ecstatic state or a mystical state; it’s simply the experience of being able to recall certain events from the past and not be completely dissociated or completely overwhelmed by that. Even [just] a moment is such a significant event for them, considering, like you’ve said, how many decades they may [have been] living with this. I do think that it allows them to reorient to their own self-concept.
One thing that we do at Fluence when we advise different pharmaceutical companies that are looking to study psychedelics [is] we really pay attention to this element, and we bring in a fair amount of mindfulness, either to the treatment or to the training of the therapists so that they can help the participant be aware of these subtle shifts. Because sometimes [the kind of orientation a person has to their own experience] is dramatic, [and] sometimes it’s very, very subtle. I think that that’s what you’re talking about.
Chris Kresser: Right. And we will talk about Fluence and what you’re doing there, and particularly this piece around how the context has to shift, too. We’re not just talking about, “Hey, let’s switch out [selective serotonin reuptake inhibitors] (SSRIs) for psilocybin and MDMA and just write a prescription, hand them to the patient, and say ‘Good luck; we’ll see you in a few months.’” That’s obviously not how this is supposed to work. I’m curious to hear how you’re approaching that with Fluence, and we’ll come back to that, but I would like to linger on this for a little while longer if you’re willing to.
Ingmar Gorman: Absolutely.
Chris Kresser: It’s fascinating to me personally, and I think it really gets at the heart of what these medicines have to offer people. Another thing that struck me about these medicines is that [for] many people who are severely depressed, who have PTSD, [or] who have other types of conditions that are being explored or investigated in the context of psilocybin [and] MDMA, there’s a lot of guilt and blame and shame that goes along with that. “There’s something wrong with me because I’m severely depressed. There’s something wrong with me that I can’t get over this trauma. There’s something wrong with me that I constantly feel anxious.” Going back to what I said before, that leads to [an] identification and a sense of being broken. Having the experience of being able to think about a certain issue that has always in the past overwhelmed me or caused me to check out and shut down, and being able to be with myself and that experience with compassion and empathy [and] without the blame and guilt, I think what that does for people is it flips a switch where before, they thought there must be something wrong with their brain and how it works. And now, they understand, “Oh wait, yeah, there is actually something that’s not working well, but it can change.” And this is the most direct evidence you could possibly have that it can be different because you’re experiencing it as being totally different, and it didn’t take five years of a certain process or supplement or medication or therapy. It was literally like that, that it changed. Knowing that the brain can change that quickly and shift that quickly, albeit with the help of a substance or a compound, I think is tremendously liberating for people, and it gives them a lot of compassion for themselves that they may not have had before.
Thanks to renewed scientific research into compounds like MDMA, ketamine, and psilocybin, there’s an increasing case for the integration of psychedelic experiences into therapy for PTSD and other mental and behavioral health conditions. Learn more in this episode of Revolution Health Radio as Chris Kresser welcomes Dr. Ingmar Gorman to the show. #chriskresser #psychedelics #psychotherapy
Ingmar Gorman: That’s right. I’m always hesitant to stand behind just one explanation because I’ve seen so many different experiences and pathways that have led people to change and get better. I will say that, if anything, what a psychedelic can do is create a pretty dramatic shift in consciousness, meaning a dramatic shift in the way that a person experiences the world. Regardless of the content of that shift, it is a shift. So to speak to what you’re saying, it’s going from existing in the world thinking that my identity is a certain way and that the world is fixed in a certain way, and just having that temporary shift, although quite extreme and acute, [that] allows a person to say, “Maybe everything isn’t [as] set in stone as I thought.”
There’s almost a relationship to impermanence, if you will. To build onto what you’ve said though, sometimes it’s not a cure. Sometimes symptoms come back. Sometimes people struggle in new ways. For example, what I’ve seen a fair amount with PTSD and other [cases] when the mental health issue is intractable and then there’s an improvement, people have a mourning period around the periods of their life that they’ve lost, relationships, or opportunities. So it’s in contrast to some of the other existing medications. We have this phrase in the psychedelic world of healing being nonlinear, or sometimes things get worse before they get better. That’s this notion that we’re really, in these treatments, often bringing things to the surface, and perhaps getting more at the root cause of some of these issues. But that can also be a painful experience unto itself.
That’s why [you need] the therapeutic process or support. If it’s not psychotherapy, then at least having a community to help people change through this process because it’s not as simple as the things that are troubling you going away. They can often transform into other things, or there can be new challenges that arise. It’s important to see that as part of a process and not a negative side effect of a drug. That’s where the stigma can come back in, or self-incrimination. “I’ll never be healed; I’ll never get better. This is who I am.” The narrative that a person creates around their experience can, I think, have a pretty dramatic effect on them getting better.
Chris Kresser: It’s such an important point because the stories we tell have power and meaning as human beings. That’s something that’s hardwired into our DNA and has been a part of our history for millennia. That goes back to, I think, what we touched on with context. Taking one of these substances in, for example, a very sterile environment with clinicians [in] white lab coats and clipboards and stuff like that is going to be a fundamentally different experience than taking it in a context where you have a warm, supportive guide who has experience facilitating these kinds of journeys for people and can help the patient understand what they’re going through in a growth mindset, to use a psychological term.
I guess this gets at a couple of questions I wanted to ask you. We’ve really focused so far on the incredible potential and benefits of these compounds. What are some of the pitfalls that you see as these medicines gain popularity and exposure? I’m thinking of things like people taking them without that supportive context and way of understanding them, [or] people sourcing them off the black market [and] not really knowing what they’re getting, [or] people having experiences that they don’t know how to integrate because they don’t have [the] support of those tools, whether formally with a therapist who’s experienced in this world or informally through their own community.
Drawbacks to Increased Popularity and Exposure of Psychedelics
Ingmar Gorman: I think you’ve named some of the risks that can be there. From a policy perspective in the United States, I think we need to really pay attention to harm reduction, decriminalization efforts, potentially legalization, [and] not from the perspective of medicine. I think that when we’re calling something a medicine, it needs to go through the correct regulatory processes to identify safety and all the correct protocols so that people aren’t harmed in a medical context. But when it comes to people choosing to use a psychedelic outside of a medical context, I wish we had better policies to support safety. I think we can look at other countries, like the Czech Republic or Portugal, where there’s a disincentive to engage in harmful practices when it comes to the black market.
Taking a step back in terms of some of the concerns that I have, it’s quite complex. I think that right now, there’s a lot of excitement when it comes to psychedelics as medicines. And it’s not a panacea. Right now, we’re testing out what works and what doesn’t work, and we don’t really know yet. I think that because there’s a lot of media attention on the topic and there’s a lot of desperation from the public to get help, they may be willing to take greater risks around using a psychedelic for whatever they’re struggling with.
Chris Kresser: What about the difference between the purity of various substances like MDMA, that somebody might obtain [from] a random person that they heard about? That often can contain [3,4-methylenedioxyamphetamine] (MDA), which is a different compound, or various types of stimulants. Are you concerned about that with the growing attention on these compounds?
Ingmar Gorman: Sure, and there are test kits that people can purchase legally online to test what the drug that they’ve purchased [contains]. That is something that I’m concerned about. Another thing that I’m concerned about a little bit, [and] this is why I’m happy to have this conversation with you and recognize that you don’t necessarily see psychedelics as a panacea, [is that] when people read the media reports [translating] the science to the popular press, often there can be a focus on the miraculous recovery, but not so much on the story of the journey that a person had to go through from the beginning of treatment to the end of treatment. I mentioned before that it’s not just an elimination of a symptom; it really is a change process.
You talked about [how] you have to step through the door, right? [Psychedelics] open a door. I like to say that what psychedelics can do is perhaps make change easier, but it’s still up to you to make that change. One of my concerns is that there’s going to be a story that people have in their mind from what they’ve consumed in mass media, and then, if and when psychedelics become a prescribable medicine, [there’s] some degree of backlash or shock that it’s not how people had imagined [and] that the actual story is a lot more complicated. I’m concerned that [it] gets blamed on the drugs rather than on the change process.
Chris Kresser: Right. There’s an analogy here that just popped into my head [that] might be useful, which is [that] we grew up watching very romanticized ideas of love in movies. You fall in love and you ride off into the sunset, and everything is peachy and rosy from there. I think that does a disservice to people because when they get into a real relationship with a real person and start having challenges, what can often happen is [they think], “Oh, this is the wrong person for me. This is the wrong relationship. I’m just going to drop this and move on to the next one.” And that process can happen forever. I know people who are in their 50s and 60s and who are still doing that because they have this very romanticized ideal of what a loving relationship looks like and feels like. They miss the growth opportunity that those conflicts and challenges can have when you really open up to using relationship as a mirror for seeing the places where we’re stuck and we need to grow and develop on our own. I feel like there’s a similar risk there with psychedelics.
Ingmar Gorman: Absolutely. I think that’s spot on. Just to build off of that analogy, loving relationships also involve compromise. I think that is something that takes place in the psychedelic journey, as well, around what a person can change in their life, and maybe what they can’t. Acceptance. That’s also a piece of love. Compassion.
Chris Kresser: Absolutely, yeah. When we recognize that we’re not in full control over our own experience. There [are] varying degrees of control that we have in various situations, but recognizing that there are some things that influence our health, our well-being, our psychological development, [and] the way we inhabit ourselves that really had nothing to do with us, that were outside of our own volition, that happened when we were at a very early stage in our lives, even surrounding the birth process. We know there’s a lot of research showing that things that happen during the birth process can have lifelong effects, psychologically. I think the compassion comes from being able to see that and experience that and accept that this is just part of my makeup in the same way that I have brown hair and blue eyes and this is my body type. I find this is a razor’s edge between, on one hand, accepting that we’re not in full control of our experience, but on the other hand, always maintaining that ability to respond in an appropriate way. And I think psychedelics offer a lot of potential there.
Ingmar Gorman: Yeah, I agree. I share the same sentiment that we are inheritors to things that we are not in control of, but we do have the opportunity to respond to it in a way that can be better for ourselves, for our community, [and] the people around us.
Chris Kresser: I want to ask one more question [about] the general world of psychedelics, and [then] I want to move on to talk about Fluence and what you’re up to because, as you may know, I’ve trained clinicians and healthcare practitioners for six years now, and then more recently, we had a health coach training program. So this is obviously a big area of interest to me, and we have a lot of practitioners in the audience [who] I’m sure will be interested to hear about what you do.
We’ve talked mostly about MDMA, [and] a little bit about psilocybin. Ketamine is another substance that’s seeing a lot of use, particularly for depression. I’m curious if there are any newer substances, or older substances that are being rehabilitated, that might be less familiar to people [but] that you feel like are on the next wave of exploration and might be something that people see used in 10 years, five years, whatever it is.
First- and Second-Generation Psychedelics and When to Use Different Compounds
Ingmar Gorman: I think maybe one way to split that up is sometimes people use the [terms] first-generation and second-generation psychedelics. The first-generation [psychedelics] are more of the naturally occurring ones. Although MDMA is not naturally occurring, [it] would probably go into that box. Some of the lesser known ones [are], for example, [5-methoxy-N,N-dimethyltryptamine] (5-MeO-DMT), [which] is a compound that Fluence is working [on] with a company called Beckley Psytech. They will be launching phase two studies to treat treatment-resistant depression, as well as some other indications. So that’s one that’s being revitalized, if you will. There are also other organizations that are looking at that compound.
Chris Kresser: And very interesting and different. Very fast [acting], comes on quickly, lasts for a much shorter time and ends more quickly, and doesn’t have as much of an extended effect [as] psilocybin and MDMA, and especially LSD, which has a much longer time frame associated with it.
Ingmar Gorman: Right, the acute duration of the drug effect is very short, particularly compared to LSD. [That] has important implications for how the treatment is disseminated and how it’s accessed. One of the largest costs associated with psychedelic therapy is the time of the therapist. So if you have a therapist, [or] two therapists, present for an eight-hour psychotherapy session with psilocybin, that has a different cost than, say, 5-MeO-DMT, which might be 45 minutes or two hours. So there’s an upside to that. The question is, does it work as well? And we don’t know yet.
Another [is] cactus, [like] peyote or mescaline. [Those are] being studied or will be studied soon. There are a number of other compounds, but I can’t really speak to the exact ones because I’m either under [non-disclosure agreements] or I don’t know what they are. But those are the second-generation psychedelics. That’s where companies are looking to either alter an existing molecule or create a new molecule to see whether the benefits can be maintained [while] maybe shortening the duration of the effect, or having a different kind of effect that could be helpful for treatment. The big attention though is really toward the accessibility question. Can we increase the safety of these compounds? Can we make it something that fits into a shorter period of time so that it can be affordable? Then there’s also pushback on that topic. Some people might say, “Well, you need six hours. That’s part of the process.” All these are really, really exciting, empirical questions. That’s what my PhD mentor would always say, “That’s an empirical question.” Meaning we can do the study and see what happens.
Chris Kresser: People sometimes don’t have an appreciation for the very trial and error nature of science. That it is part of the scientific process to come up with that. That’s fundamentally what science is. You make a guess and you check it out, in layperson’s terms.
I have my own experience and thoughts about which psychedelic or substance I might consider, depending on what I’m currently exploring or interested in, or what kind of effect that I feel like I’m looking for, [or] what’s going on in my life, etc. From a therapeutic perspective, [what] do you think about the three most common ones that you’re working with—MDMA, psilocybin, and ketamine? When somebody comes to you, or is part of a study or something like that, when are you going to think about one of those versus the other? Where do you see each one having the greatest application and benefit?
Ingmar Gorman: Great question. Somebody once told me, and I agree, that MDMA is really a great drug for PTSD because of what it does, in terms of the biological effects and the creation of safety. The person who rediscovered MDMA, Sasha Shulgin, used to refer to it as an easily controllable state of consciousness. You mentioned control earlier, which is a really important theme when it comes to these experiences. We know that in your ordinary state of consciousness, [if you] try to control your experience, you’re not going to have a good time. It’s very hard to control your experience.
Chris Kresser: Don’t think about an elephant, right?
Ingmar Gorman: Right. Now add a psychedelic or a compound that changes your state of consciousness. When you try to control your experience, the anxiety or tension that’s created there can get amplified. What’s nice about MDMA is that when you have somebody who’s gone through something very traumatic, the state that MDMA induces is one where a person’s state of mind can more easily adapt to what is happening in the present moment. It kind of facilitates [an] acceptance of what’s happening and a sense of safety. We don’t see that really in, say, psilocybin. So although there are studies to be done on psilocybin for PTSD, one differentiator [between] psilocybin and MDMA is something referred to as the mystical experience. We have quantifiable data from empirical studies that demonstrate that there’s a greater likelihood of having a mystical experience with psilocybin than with MDMA.
I’m somewhat critical of this construct, but let’s just go with it for a while—that there’s something about having a mystical experience that is helpful for people. The concept of self-transcendence, or unity with all things. Perhaps that slightly more spiritual emphasis or experience with psilocybin [is] potentially more helpful when it comes to, say, addictive disorders, where there is often such a loss of meaning in life or such disconnection in people’s lives, that this sort of mystical, transcendent experience of connection is reparative for somebody.
When it comes to ketamine, I’m not a medical doctor, but I should say that in terms of physiological safety, I believe you would rank it as being [safer] than psilocybin [or] MDMA. MDMA is an amphetamine. It’s a stimulant, [so] there [are] some risks associated with that. I’m not sure [about] psilocybin versus ketamine in terms of which one is more physiologically safe. But we know that ketamine is used in emergency rooms. It does not have a lot of medications that interact with it. It’s given to children because it doesn’t suppress breathing during certain surgeries and procedures. So ketamine is one where I would think it can be useful, depending on the health of the person. It’s [safer]. We have really solid evidence that it’s really, really helpful for people who are acutely and intensely suicidal. It seems pretty clear that if that’s something that somebody’s really struggling with, that the depression is that intense, [then] ketamine would be a good choice.
Chris Kresser: Yeah, I’ve seen near miraculous responses in people with suicidal ideation [and] severe depression, having a single ketamine treatment and feeling almost completely normal the next day. I don’t know of any other treatment for depression and suicidal ideation that has that potential. So it’s a pretty exciting application.
Going back to the differences between these three substances, there [are] obviously the biochemical, mechanistic differences that we don’t even fully understand. But I appreciate the distinctions you were making [between] MDMA and something like psilocybin. We didn’t mention LSD and mescaline. The biggest difference, from my perspective, is the alteration of perspective or consciousness. With MDMA, it’s a lot more about compassion, empathy, being able to put myself in someone else’s shoes and fully inhabit that experience. [To] see things from that perspective and drop a lot of the defenses [and] habitual ways that we interact with one another and just settle into our heart and really be in that place of unconditional love and undefended love.
That’s an incredibly precious thing to be able to experience and offer, and that can change us in fundamental ways. But there aren’t typically visuals associated with MDMA, [like] a hallucination or even shifts in perception. Whereas with these other substances [like] psilocybin, mushrooms, LSD, mescaline, DMT, to varying degrees, depending on the dose and depending on how they affect someone, there can be profound changes in our experience of physical reality around us. Going back to something you said earlier, it creates a sense of not only impermanence, but also that our perception of the world around us is limited by our sense organs. That what we see every day is not the only thing that’s there. And that opens up a whole range of possibilit[ies] and questions and inquiry and wonder and awe at what it is to be human and live in this incredible world, and how little of reality we can actually perceive.
Ingmar Gorman: Yeah, I’d love to riff on that a little bit. Aldous Huxley had this hypothesis of the brain or mind as being a filter. We know this from very basic perception, that we filter out information. Because if we were really to perceive everything that was coming at us at once, not just externally, but also internally, we wouldn’t be able to exist. It would be overwhelming. [We] wouldn’t be able to navigate the world. Aldous Huxley’s hypothesis was that perhaps what psychedelics do is inhibit the amount of filtration. In other words, [they] open up the aperture, if you will, of experience, or open up the valve so that more water is flowing through the faucet so that there’s more that’s accessible. And that’s not just a biological limitation. I would say, and others have said before me, that this is also culturally bound. What we value as important, we may be more likely to be aware of than those things that we culturally value less. There’s a phenomenon with people who smoke called attentional bias, where they’re more likely to, say, notice cigarette butts on the ground. Or if you’re using alcohol, then perhaps you’re more likely to notice the liquor store on the corner. [That’s] just an example of how different people notice different things. And when a person has this temporary experience of being on a psychedelic, they can reorient or re-relate to not just the things that they put into a different value hierarchy, but also become aware of aspects of their experience or past that they previously neglected but can now be aware of. I find that [it] may be a place where people can access some insight into themselves and how they might want to be different moving forward after the experience.
Chris Kresser: Yeah, the self concept is not cemented in. It’s labile, and we actually can recreate it every moment with choices that we make, and we can make different choices that will lead to a different way of experiencing ourselves. I love that.
The Work of Fluence Training
Chris Kresser: That’s maybe a good way to shift gears here. I want to hear a little bit more about Fluence and what you’re doing. We’ve been talking about various aspects of why it’s so important to train clinicians and people who are going to be using these substances in a therapeutic context with individuals because it’s not the same as just learning about the effects of a pharmaceutical drug, writing a prescription, and sending someone to a pharmacy. It’s a fundamentally different context and interaction. So tell us a little bit about what you’re doing with Fluence to address that.
Ingmar Gorman: Fluence is essentially a training or psychedelic education company. We focus on primarily training licensed mental health professionals, but a majority of our content and classes can be taken by anybody. Fluence was born out of an observation that people are having psychedelic experiences all the time. Roughly 10 percent of the U.S. population has had a psychedelic experience at some point in their life.
Chris Kresser: Wow, I didn’t realize the number was that high.
Ingmar Gorman: Yeah, and [that’s] from a paper published in 2012, based [on] data from 2010. So it’s possible that the lifetime prevalence might be even higher. But at least 10 percent is a safe guess. Yet how many clinicians are aware of psychedelics and what those experiences entail? In fact, I would say, [and] I think this is changing, but probably still today, not only are they not informed about psychedelics, [but] they’re [also] misinformed about them, due [in part] to the drug war or just them being an oddball drug. If you go through mental health training and you choose to specialize in substance use treatment or addiction, you’re very unlikely to encounter the topic of psychedelics because they don’t have the typical pattern of habitual use. They tend to usually not be problematic, although they can be. A mental health professional is not going to have any clue about them unless they’ve been interested in them themselves. So we created Fluence to address that problem.
We wanted people in the world who have psychedelic experiences, if they turn to a therapist, to have some sense of confidence or a pathway to be able to work with somebody who’s going to understand their wish to have a psychedelic experience or anxiety that might be coming from a past psychedelic experience, or somebody who might be just wanting to continue to reap the benefits of psychedelics. So we created this training program. When that was up and running, we had another observation, which is that there are all these emerging psychedelic pharmaceutical companies. This is around 2019 [or] 2020, and they have expertise in how to take a drug through the FDA process and potentially turn it into a medicine. They have pharma expertise, they have expertise in a molecule, but they know nothing about psychotherapy because historically, it is the Food and Drug Administration. It is not the Psychotherapy Administration.
What we are doing is working with these drug companies to create a psychotherapy manual to make sure good psychotherapy is part of the treatment process for these molecules. Those are the two sides of our business. One is training clinicians in the community, and the other one is working with what we call enterprise clients or drug companies that are looking to take their drug through this process and eventually go to market.
Chris Kresser: Are you at all concerned? Part of my original training was as an herbalist, and I have an appreciation for the complexity of plant compounds. And as far as we’ve come in our own capacity for molecular analysis and looking at individual constituent compounds and what impacts they have, I don’t think we’re even close to understanding the synergy of how compounds interrelate within a whole plant. There’s a real bias in the botanical medicine community to use whole plants for that reason. The more allopathic concept is to take out an active ingredient and then amplify that, and that’s not without risk. We can cause problems.
I’m wondering if you have any similar concerns as the pharmaceutical industry starts to get interested in this field, that [the] same kind of phenomenon is going to happen. There’ll be a few studies published on a plant medicine, a certain compound will be identified as potentially one of the main psychoactive compounds, and then all of a sudden, there’ll be a drug with that compound, but it won’t have the same impact that the full plant medicine had.
Ingmar Gorman: Yeah. There’s a lot to say here. It’s important to remind your listeners that when we talk about the research process and the FDA, we’re talking about single molecules. So we’re not using fungi; we’re using psilocybin, the synthetic psilocybin. But there are companies out there [that] are looking to more closely examine all the different compounds that are in the mushroom to see if there’s some synergistic effect between what’s in them. This also poses a challenge for, say, ayahuasca, which is a combination of different plants and will likely not be approved.
Chris Kresser: It’s very difficult to study that. I understand the need to isolate variables in a research study; I get that. And I don’t know that there’s an easy solution to this quandary. I think it’s just something we’re going to have to work with over a long period of time.
Ingmar Gorman: Well, it’s interesting. This poses another series of challenges, but we could look at Oregon, [which] recently legalized psilocybin therapy. It’s not yet accessible, [and] all the regulatory pieces are being put into place. The goal is 2023 for there to be legalized psilocybin therapy. And there’ll be full fungi use. So it’s not to say that this won’t necessarily be accessible. But again, be careful. It’s not gone through the federal regulatory process. I think what you were also alluding to is something like opium becoming amplified to heroin and fentanyl, or the coca leaf [and] cocaine. It’s an interesting question whether we will see these molecules being taken from plants and then modified in such a way to increase the potency [and] the intensity. I somehow feel like that’s [not] going to be such a risk because the desired effect or the way that these compounds work isn’t through intensifying the experience of it or the potency.
Chris Kresser: Yeah, it’s not always “more is better.” There’s a dose. And of course, pharmaceutical companies are familiar with that concept. There’s often a U-shaped curve in terms of the efficacy of these substances. So that makes sense. Just speaking from personal experience, a certain type of mushroom has a slightly different impact and feeling and experience for me than when I take a different type of mushroom. And I imagine that’s lost when you’re taking synthetic psilocybin. Not that that is any kind of deal breaker or a reason not to pursue this, but it’s just worth noting and pointing out.
All right, this could go on, and I would definitely love to have you back because I’m really fascinated, as you can probably gather, [by] this topic, and [I] love talking about it. So thank you so much for joining me on this show, Ingmar. Where can people find out more about Fluence and the work you’re doing?
Ingmar Gorman: The best place to learn about Fluence is at FluenceTraining.com. We also have a Contact page there, if you want to reach out and ask me questions. I’d be delighted to hear from you.
Chris Kresser: Great. Thanks, everybody, for listening. [I] hope you enjoyed the show. Keep sending your questions in to ChrisKresser.com/podcastquestion. We’ll see you next time.
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