Publication Date: 10/13/22025

Duration:  23 minutes, 38 seconds

Transcript: 

NOAH CAPURSO: Today, we'll be talking about psychedelics and addiction psychiatry, what they are, how they work, and what the research actually tells us. We'll hear from Dr. Bhatt, Chief of Addiction Psychiatry at the University of New Mexico, who has been involved in some of the most closely watched psychedelic trials in recent years. Welcome to The Carlat Psychiatry Podcast. I'm Dr. Noah Capurso, the editor-in-chief of The Carlat Addiction Treatment Report, assistant medical director at Connecticut Valley Hospital, and an associate clinical professor of psychiatry at the Yale University School of Medicine. How do you define the term psychedelic, and how do they work in the brain?

SNEHAL BHATT: So, that term has undergone quite an evolution, right? I think back in the day, as a medical student, I read sort of textbooks that talk about psychotomimetic, and the idea was that these are substances that mimic psychosis. But I think they do a lot more than that, so that's not such an accurate term. On the other end of the spectrum, you hear the term entheogens, kind of “generating the God within”. That's a term you hear quite a bit, but it's not very scientific. So somewhere in between is this term hallucinogen, generating hallucinations. But to me, that's also not very accurate because from what we see in clinical trials and human experience, hallucinations may be a small part of the effect—but certainly don't capture everything. So, I think the term psychedelic makes sense, right? Kind of generating or giving rise to the hidden psyche, the hidden realities of the mind; psychedelic, sort of makes sense. There are a few things that we think about in science, I like to use the words, classic psychedelic or serotonergic psychedelic, and those are going to be compounds like, psilocybin, LSD, mescaline, DMT, the kind of things people have heard about—along with a variety of synthetic compounds that have been made in the lab over the years. One thing all these classic psychedelics have in common is that they largely bind to and activate the serotonin receptor, the 5-HT2 receptor in the brain. That's the common thing. There are differences—they do affect other receptors or their brain systems—but if I were to distill it down to one thing they do in the brain that defines classic psychedelics, it is that they bind to and activate the serotonin receptor. Now, in terms of what we see, the other things that often define a psychedelic are that the predominant effects are on things like mood, the effect, and that's something we saw in our study quite a bit. Perceptual changes, mood changes, and visual changes are the main things we see with far less of cognitive changes. We don't really see things like big changes in blood pressure or pulse, like autonomic reactivity or what's called narcosis or stupor, that you might see with methamphetamines, for example, or heroin.

NOAH CAPURSO: When most people hear the term psychedelic, they think of the classic or serotonergic psychedelics, but you indicated that there are other non-serotonergic agents that fall under the larger psychedelic umbrella. What are some of these compounds?

SNEHAL BHATT: I think the two substances relevant to this discussion: one, MDMA, which is, of course, generating a lot of attention, being investigated for treatment of post-traumatic stress disorder, and ketamine. And both of those clinically may have some effects that overlap with the psychedelics, but in the brain, what they're doing is quite different. So, ketamine is actually a dissociative anesthetic—so kind of very different mechanism of action. And MDMA has some similarities, but it's quite a bit more complex. Where we do see it affecting beyond just serotonin, other neurotransmitter systems, right? We also see it affecting kind of brain bridges, most notably the amygdala, where it's been sort of postulated that because of its neurobiological effects, MDMA can open up this window of tolerability—where people with post-traumatic stress disorder might be able to engage with some of their past traumatic experiences, not avoid them. They feel safe enough to engage with it without being overwhelmed by it. And I think that probably has to do with MDMA's fairly unique action, I would say, on the amygdala and its connectivity with kind of the learning systems, for example. Does that answer the question?

NOAH CAPURSO: And that's why it's being looked at for PTSD.

SNEHAL BHATT: To me, at least, it seems almost tailor-made for the treatment of PTSD. Right? When I think about this larger umbrella of psychedelics, MDMA perhaps holds that niche space that others do not.

NOAH CAPURSO: Now you've been closely involved in a clinical trial investigating the use of psilocybin for alcohol use disorder (Bogenschutz MP et al., JAMA Psychiatry 2022;79(10):953–962; see CATR Oct/Nov/Dec 2023 for more on this study). Tell us a little bit about the rationale behind that study.

SNEHAL BHATT: There's this treasure trove of information going back to the 1950s and ‘60s that has largely not been looked at in a lot of detail. I think it's starting to change now, but at that time, it hadn't really been looked at. So back in the ‘50s up in Saskatchewan, Canada, Osmond and Hoffer were using LSD—not in the clinical trial setting, but as a treatment for alcoholism. A number of studies actually investigated LSD primarily for the treatment of alcoholism, and many of those trials are not good quality trials, but some are. There was a meta-analysis (Krebs TS and Johansen PØ, J Psychopharmacol 2012;26(7):994–1002) done well over a decade ago, that picked out six of these studies, and they were all people with alcohol use disorder, blinded at least until the administration of the medication—the LSD or placebo. The psychosocial conditions were different, but what that meta-analysis showed is that LSD did seem to help people with alcoholism. And the number needed to treat—in other words, how many people do we have to treat to get one person to benefit from it—was a little bit lower than our current FDA-approved medications, and the effects of just a single dose of LSD administration lasted for several months—the benefits were felt for about three to six months—before they washed away. The meta-analysis is fraught with methodological issues, but when you put that together, it was enough to say we should open up this line of inquiry—see what we find in a scientific, rigorous way. And is this really worth looking at, especially when you look at the burden of alcohol use disorder on society, right? Not just in terms of like, all kinds of things—liver disease, motor vehicle accidents, and here in New Mexico, something we really focus on is this multi-generational trauma that our communities are feeling. So, when you put all that together, we can't be just satisfied with what we are now. We need to be looking at new, maybe out-of-the-box approaches, and that was enough to say, “Well, let's start looking at it,” right? And so that led to the initial pilot trial that was done here at the University of New Mexico, which was just to see if it was going to be safe and feasible. And I can talk about that if that's relevant—but I'll pause here, I guess, and check in with you.

NOAH CAPURSO: It's interesting to think about using psychedelics specifically for the treatment of addiction because psychedelics themselves can be misused, and there's concern that patients may develop addiction to the psychedelic itself. So, tell us a bit about how the potential for psychedelic misuse was considered in your trial design.

SNEHAL BHATT: Yeah, and it's a really important question. Especially for a new field—in a field that's generated so much enthusiasm—we really want to make sure that we are not causing harm. I mean, that's sort of what we base our medicine on: first, do no harm. So, it's very interesting if you look at the kind of animal studies, for example, of classic serotonergic psychedelics. They are not particularly reinforcing (Johnson MW et al., Neuropharmacology 2018;142:143–166). So, for example, if you have a rat and you expose the rat to morphine, and the rat develops an addiction to morphine, I mean, it's kind of well-known that the rat will press that lever to self-administer morphine—even at the sacrifice of things like food and water. That doesn't seem to happen in animal models with serotonergic psychedelics, and certainly in clinical trials that have been done thus far, right? What I call kind of the “psychedelic research 2.0”, which in the last couple of decades, appropriately, paid a lot of attention to this, that hasn't been seen in humans either. That is not to say—and I think this is maybe something to discuss as we go through the interview—that's not to say people do not misuse these substances. I think the potential for misuse is still there, but psychedelics aren't addictive in the way we think about other substances.

NOAH CAPURSO: How do you deal with that potential for misuse?

SNEHAL BHATT: I mean, I think the easy thing with controlled clinical trials is that—they're controlled clinical trials. So, part of the screening is that. So, for example, we certainly excluded participants who are very frequent users of psychedelics. By no means were our participants psychedelic-naive, and that was not one of the exclusion criteria, but if there were very frequent users, that was excluded. Also, I think the other big piece that we certainly utilize in our studies—and many studies are utilizing—is an extensive psychotherapy component. The preparation, the integration work, and I think empirically it's an open question, and I think we're hopefully going to get a lot more information in the years to come about, what the role of psychotherapy is, what the optimal form of psychotherapy is, right? Like, and the logistics, like how many psychotherapists, et cetera. Those are all empirically open questions, but from my bias as a psychiatrist who does a fair amount of psychotherapy, as someone who has done work in this area, done research in this area, I think from a safety standpoint, that psychotherapy work is essential, and part of the preparation, part of the integration is to bring the participant back to why we are doing this. What are your goals? What are the experiences, and what do these experiences mean that you had under the medication administration session? And I think that's a big safety piece, right? Because then we're sort of really taking away the idea that this is just fun, and how do we harness the therapeutic value, and talking about fun. At least what we found in our sessions is that for most of the participants with alcohol use disorder, these experiences were not “fun”. They were connecting with a lot of traumas, a lot of losses, often related to this long pattern of drinking. An important thing to consider is going to be, have states passed legislation or, as these substances become more widely available? How are we going to sort of—maybe— identify people who may be at risk of misusing this, and what are the safety parameters that are going to be in place? I don't have an answer to that, but that's a discussion that absolutely needs to happen.

NOAH CAPURSO: There have been questions about the accessibility of these treatments, and there have been concerns about how generalizable the findings of these studies are because of this. How can the field address these concerns regarding accessibility and generalizability?

SNEHAL BHATT: I think there are several layers to that. The first layer I think about, as a person of color, as a researcher of color, is access—around the generalizability of the findings thus far. And I think it was reported a couple of years ago that if you look at all the newer psychedelic trials, I think 85% of the participants, something like that, were white males, and I think we're losing a huge chunk of generalizability. I don't know if it was white males or just white individuals in general—you may want to fact-check me on that—maybe that goes well beyond this conversation of incarcerations related to substance use in minority communities, right? The burden that LGBTQ communities have worn. So, I think we really have to A, find ways to have first, from a research standpoint: how do we have better engagement? How do we actually engage traditionally underserved communities better, as participants and as researchers? I've had conversations a lot about, like, “Well, we need to get more indigenous people involved in research”. Like, we need to do more research. I actually think we need to back way up. I don't think that we're necessarily there where we start saying, “Here, we want to recruit you in studies.” There is a long legacy, and I can speak to this a lot, as someone who works at the University of New Mexico, where we have 23 indigenous tribes, right? And we do a lot of work with them. I think there is a long history of exploitation and distrust. So, I think we actually had to back way up and start those conversations, right? With indigenous peoples, with leaders, healers like not, “This is our idea, and we want to recruit you”, but “How can we partner with you? How can we best support you? What is it that you would like to see, and can we find ways to deal with it?” I think there are some other things, regarding kind of the cost of this. I think exploring things like group-based models of therapy, for example, can ultimately allow this scale-up to happen. So, I think more studies need to focus on, rather than one participant, two therapists—which is really going to drive up the cost—to “Are there ways, and people are starting to do this right?” Like, “Can we explore group sessions or group therapy sessions? What are the risks? What are the benefits? How do we optimize that?” I think there are just like three things to start with, and ultimately, again, more research, because if the research is there, then you can sort of make a really good argument for funders to cover some of these emerging therapeutics. I would love to see ketamine assisted therapy for PTSD be covered by New Mexico Medicaid, but until that data is there, it's going to be hard for me to make that case to make that happen.

NOAH CAPURSO: As I'm sure you're aware, there's been a tremendous amount of enthusiasm for the potential for psychedelics to be used therapeutically, and a lot of that enthusiasm has been driven by media coverage that's quite sensationalized. How do you recommend that providers discuss this topic with their patients?

SNEHAL BHATT: Stuff that's in the media is just so sensationalized. Like you read it and you think we know everything there is to know about psychedelics—and we don't. We were only scratching the surface. So, again, I think a lot of that responsibility goes back to the providers who may have that trusted relationship with their patients. And when I was thinking about that question—or conceptualizing, at least in my mind—I thought back to where medical cannabis was five years ago or seven years ago. States were starting to sort of open up pathways for medical cannabis, stores and dispensaries were opening up, it was all over the media, people were interested in it, and physicians were either unprepared—or unwilling—to talk about it, at least in a non-judgmental, engaging manner. And there were some studies, actually one that one of my medical students did that I was mentoring, where she looked at—this is like five years ago—communication patterns around medical cannabis between like clinicians, patients, and like where were they getting the information. And ultimately, what she found is that all the conversations were happening between the patient and the bud tenders at the medical dispensaries, because the physicians weren't talking about it, or the patients felt judged by the physicians. So, who did they turn to? The tend turns to the bud tenders, who were happy to give out advice. Some of it is helpful, some of it is not evidence-based. So, I think it created that communication vacuum. So, I think education is the first part. Here at UNM, we make it a point that even our medical students are getting this as part of their training, certainly our residents. And then how do you engage? We ask about it. If we don't ask about any psychedelic use or MDMAs or ketamine use, we're not going to learn about it. And then, really kind of the basic things we do are open-ended, “Well, tell me a little bit about this substance and your relationship with it. Why do you use it for better or for worse?” And just listening to our patients, and then sort of using that opportunity to provide, “Well, this is what we know, and this is what we don't know”. So, I guess learning about it is non- stigmatizing, and the third is admitting when we don't know something, which is a lot. I think those are probably the three things that I would focus on with that.

NOAH CAPURSO: There's some controversy about whether or not the subjective psychedelic experience, or what we call “the trip”, is absolutely necessary for these agents to have a positive therapeutic effect. Some say that the trip is just secondary, that it's a byproduct of whatever underlying neural process is happening that is actually responsible for the beneficial effect, but others say that the experience is essential, that it's integral to how these compounds work. What do you think about this? Do you think the subjective psychedelic experience is a necessary component?

SNEHAL BHATT: It's a really good question. I think part of it, you alluded to, we need more studies, right? I'll leave that there. Because that's probably a statement in itself. Second, there's probably some difference. If you look at that larger psychedelic umbrella, I think, as you called it initially, there's probably a difference. For example, ketamine, for acute suicidality, I mean, I think that may very well be, and likely is, a pure pharmacologic effect. Simply doing an IV administration of ketamine can help with that improvement. So, it might be substance-dependent, and perhaps it's also condition-dependent, that “What is it being used for?”, because we are certainly seeing some differences emerge between sort of psilocybin for end-of-life distress versus alcohol use disorder, for example, and it's too early for me to go into specifics. But we're seeing some differences in terms of what might be those magic factors, or those mechanisms. So, I think part of it is that it may be substance-dependent, as well as the condition we are treating, dependent. That being said, I think coming back to the psychedelics, my bias is that the subjective effects are important for the conditions for which it has been treated. So why do I say that? Because I think it's a synergy, I mean, perhaps the biological changes—which are, well, there's lots of literature on it, default mode network, synaptic plasticity, all those things—are likely creating, sort of an environment within the brain that can be harnessed, or that can be optimized using psychotherapy. There are also studies that are correlating these brain changes with subjective experiences, and ultimately, that's what patients are remembering. My patients aren't coming back saying, “My default mode network broke down, or there was entropy within my brain when you gave me psilocybin”; what they're saying is “I felt incredibly connected right to this place where generations of my family are from”, I mean, I'm using examples of actual participants with whom I work, or they're saying, “I realize the tremendous pain I caused” and part of the process was me engaging with them, talking to it, and going on this healing journey, and that's really what people are reporting. So subjectively, to me, that seems important, right? That's one of the things we do in medicine: we listen to our patients and see what's important to them and use that for further inquiry. I mean, that's medicine's done that for eons, so there's no need to change that. Second, is that certainly in our studies—and in other studies—how powerful the experience was. So, the intensity of the psychedelic experience did correlate with the change and outcomes, right? The people who had the low scores on some of these validated scales weren't benefiting the way the people who had the more intensive, and we saw that even in our pilot study. In some of the studies at Hopkins, for example, with the end-of-life distress, a kind of mystical nature has correlated with the improvement; the kind of mystical nature of the experience has correlated with that as well. And lastly, as a therapist, what am I doing right? Again, I'm not relying upon the fMRI changes, what I'm really engaging with is that subjective experience, and I think to me that's critical to help the patient—you know, support them as they bring back whatever the experiences were that happened during the medication session back into the here and the now, back into their goals, back into their relationships with the world, and with themselves.

NOAH CAPURSO: And that wraps up our conversation on psychedelics and psychiatry. As Dr. Bhatt reminds us, while the research is promising, we're still early in the process, and thoughtful evidence-based conversations with our patients are more important than ever. Thanks for joining us. Take a look at our latest issue of The Carlat Addiction Treatment Report for more up-to-date Clinical insights. Hopefully, people will check it out! Everything from Carlat Publishing is independently researched and produced. There's no funding from the pharmaceutical industry. Our newsletters and books depend entirely on reader support. There are no ads, and our authors have not received industry funding. That helps us to bring you unbiased information that you can trust. Don't forget, you can earn CME credits for listening to our podcasts. As always, thanks for listening, and have a great day.