The Future of Psychedelics in Healthcare

Transcript for Season 3, Episode 4: The Future of Psychedelics in Healthcare

Dr. Matthew Johnson: Pretty much unheard of to say, “Oh, you're gonna have one administration of a medication. And it's in your system for, you know, several hours, it's outta your system in a day. But six months later, a year later, we're gonna probe and we're gonna see it's still affecting your behavior in a positive way.” I've heard it numerous times that—  including from patients who have been in therapy for years or even decades — and say, “This is like years of therapy, you know, in an afternoon.”

Judith Warner: Welcome to The World as You'll Know It, I'm your host, Judith Warner.

This season, we're focusing on the brain. Specifically, we're looking at some of the most recent and astonishing advancements in brain science. Discoveries that have completely altered our understanding of how the brain works, what it's capable of, and how it can be changed.

Today, a bit paradoxically, we’re looking at substances that have been in use for millennia:  psychedelics. Their ability to transform — sometimes radically — the way people see the world is mythic. And about 70 years ago, psychedelics were heralded as a possible answer to many of society’s most entrenched problems, being studied as potential treatments for issues like depression and alcoholism.

And then, all that stopped. The sixties happened. The language around psychedelics became all about fear. Funding went away, and research came to a halt.   

But, today they’re back. With a fair bit of hype, and a lot of renewed hope, based on some really solid science.  

Joining us to talk about what this means is Dr. Matthew Johnson, a professor of psychiatry and behavioral sciences at Johns Hopkins University. As a member of the Hopkins Center for Psychedelic & Consciousness Research, he’s been on the frontlines of psychedelic research for almost twenty years and has pioneered using psilocybin — magic mushrooms — to treat addiction. 

Welcome Matt, thank you so much for joining us.

Dr. Matthew Johnson: You're welcome, Judy. My pleasure. 

Judith Warner: So it seems like we’re on the cusp, or even in the midst of, a whole new era of psychedelic research. And there’s a lot to cover: history and science and regulation. But first, I’d love to know what drew you to this field.

Dr. Matthew Johnson: I really just fell in love with this broader area of psychopharmacology, how drugs affect the brain, the mind behavior. I mean, whether it's caffeine, you know, alcohol, illicit drugs, you know, therapeutic drugs, or, you know, so-called, you know, drugs of addiction or of abuse. It's all, it was all just very fascinating. And I discovered that academic world did some rat research with cocaine when I was in college. But I came across this history doing some, you know, a paper on, the use of psychedelics therapeutically back in the sixties and, and really figured out that, oh, wow, this, the rug was pulled out, not because we sort of concluded there was no future, but more because it kind of got out of the lab and there was this political reaction to it. And, you know, gosh, I'm ultimately interested in drugs and behavior. And I just don't know of another drug class where you have examples of people saying that they did this drug one time, sometimes like 30, 40, 50 years ago. And they say it changed their life for the better.

Judith Warner: Exactly what are these substances with these magical powers? How, how do you define them?

Dr. Matthew Johnson: “Psychedelics” is a very general term. And I think that the most meaningful definition is a drug that has strong effects in altering someone's perception of reality, including their perception of themselves. Now, once we delve into like how that is happening in the brain, you have one class called the classic psychedelics, and that includes LSD and psilocybin mushrooms and DMT, which is in ayahuasca and mescaline, which is in peyote. Those all work by mimicking serotonin at a particular type of serotonin receptors. And then you have other drugs like MDMA that's not a classic psychedelic, but it's still called a psychedelic in that more general sense. And it, it kind of floods the system with, with natural serotonin.

Judith Warner:  So you mentioned a bit earlier the use of psychedelics back in the early 60s. When the rug was pulled out from lots of research being done. What were those studies looking at? What drugs were being tested?

Dr. Matthew Johnson: It was primarily LSD. The compound that was second most prevalent was mescaline. So interestingly not psilocybin, which is the main classic psychedelic under clinical investigation today. But the two leading therapeutic areas of research were treating cancer patients, and these were terminal cancer patients who had substantial anxiety. Um, you can call it existential distress, uh, about their, their coming death. Not — so not trying to treat the cancer itself, you know, prevent the tumors from coming back and this type of thing, but helping the person essentially to come to peace with the fact that they're gonna die, and to alleviate a lot of that suffering that can come at those times. The other, um, was the use of, of the psychedelics to treat alcoholism. It would appear that the results just from the, the few randomized studies, I mean, it looked as good as anything we have today in terms of a medication.

Judith Warner: And so, then fast forward to today. You said that psilocybin is now the main drug being studied. Is it picking up where those other drugs left off, in, in terms of what it’s being used to treat? 

Dr. Matthew Johnson: The most rigorous evidence to date, if we're talking about psilocybin, is in the treatment of, of, you know, cancer patients with end-of-life distress. So showing large improvements in, in depression and anxiety symptoms. And so, the reason I say it's the most rigorous body of evidence is that there's been three, um, independent randomized clinical trials, including one that I, and, and colleagues ran, at Hopkins. And they just showed, from a single high-dose session, very large reductions in both depression and anxiety symptoms that looked virtually untouched six months later. And that's the, I would say the paradigm-shifting aspect of this, in other words, what's really different. What's the new thing about this treatment? We think about mental health, psychiatric meds. It's, you know, you take a pill every day and it reduces symptoms and you keep taking it and hopefully you keep getting relief. Um, it's pretty much unheard of to say, oh, you're gonna have one administration of a medication. And it's in your system for, you know, several hours, it's outta your system in a day. But six months later, a year later, we're gonna probe and we're gonna see it's that experience or having had that drug. It's still affecting your behavior in a positive way.

Judith Warner: What is, what’s the uniqueness that makes that incredible, uh, effect happen? 

Dr. Matthew Johnson: This is still actively being debated and researched, but I think the answer is that psychedelics work by allowing an experience to unfold, and people learn from that experience. And so that makes it more like a psychotherapy. Or, I would say more broadly, a life experience. Someone could say, “Oh, there was that the first time I fell in love” or “When I became a parent” or “The first time I visited another culture and really felt, you know, felt what it was like to be in the minority.” Just some, some things in your life you can point to. And there was a shift there. This is more in that category. And, this is still in the area of emerging research, but it may be and appears to be that the brain is more plastic. It's more able to absorb new information to be more flexible and, and potentially make long-term changes in the days following that experience. So you might have kind of a double whammy, this kind of perfect opportunity for alternative perspective taking to, to have this broader view of the world outside of your normal constraints, narrowed perspectives, and then combined with this neuroplasticity, this kind of, this increased ability of the brain to learn something from the experience and make it a permanent change.

Judith Warner: It's like psychotherapy on steroids.

Dr. Matthew Johnson: When it works well. And it doesn't always work well and no treatment always works. I've heard it, numerous times that, including from patients who have been in therapy for years or even decades and say, “This is like years of therapy, you know, in an afternoon.” Now that is overstating a little bit, because all these folks have had all the preparation, you know, you know, four to eight hours and previous meetings developing a rapport. But nonetheless. Still, a pretty discreet short term intervention that people say is like doing years of therapy.

Judith Warner: Can you walk us through what it looks like in your lab, let's say, when somebody is in a study and is coming in for treatment, just with the preparation, the guides, all of that?

Dr. Matthew Johnson: The first phase is really important. It's the screening. And so someone might spend, uh, you know, typically, um, two half days in the lab, filling out questionnaires, going through a physical, taking their blood and looking at their liver enzymes and all that stuff, but also taking structured psychiatric screening. And you're really probing for something: Is there some sort of, um, propensity for disorders like schizophrenia? When someone passes all of those, uh, medical psychiatric screenings, and if they participate in the study, then there's the preparation phase. So this is, depending on the study, anywhere from four to eight hours of preparation for my work. Where we're treating people to, to quit smoking with psilocybin, it includes both specific preparation for the psilocybin sessions, as well as preparation for quitting smoking, sort of this talk therapy that's a little more standard for anyone uh, who's quitting smoking. 

The most important aspect of that is really the rapport building. It's not telling them one thing or another about the psilocybin experiences they might have, but, it's getting used to the human beings. And it's typically two. And we often call them guides, the people who will be there in that therapeutic role. When you're in the room, when, when you're on psilocybin, they'll be there. If you have some anxiety, that's gonna be the person to hold your hand, and, and reassure you that you're being kept safe. Um, so that relationship is key.

Judith Warner: Are they psychologists?

Dr. Matthew Johnson: It varies. They could be a, a psychologist. They could be a social worker I think as these things become considered as treatments by the FDA, then we're gonna get more of the territory where it's gonna be, there's gonna be some type of regulation in terms of what type of degree the person has to have, what type of licensure the person has to have.

Judith Warner: So then what happens, let's say, the day of? The day of treatment? 

Dr. Matthew Johnson: For the smoking research, that's also the first session is the day where they're gonna be quitting smoking. So that's a double whammy in terms of being a big day, right? But for any psilocybin session, it's a, it's a big day. 

So on that day, they come in early in the morning, do some minimal questionnaires, check in to see how the person's doing, check their blood pressure, but then pretty much get to it. They swallow a, a pill. The session room that they've, they've been exposed to before, the preparation sessions, at least some of them have happened in this room. So that's not new. And it will take anywhere from uh, 15 minutes to 45 minutes for it to kick in, typically. During that time, we can engage in some discussion. There's some art books they can look through. And music is playing during this entire time and during this whole experience. And once the person starts to feel an effect, that's when we invite them to lay down on the couch rather than sitting up. And then we put eye shades on them, have them listen to headphones, through which this, you know, already selected, you know, course of music is playing. And then they're really encouraged to have an inward experience. Don't worry about us. Don't worry about the room. Just focus on your inner experience and try not to overanalyze it.

Judith Warner: How long does it generally last? The trip? 

Dr. Matthew Johnson: Five to six hours.

Judith Warner: And, and then what happens?

Dr. Matthew Johnson: They come down and that's a gradual process and they're sort of feeling pretty much back to normal. About six hours later, they often feel exhausted. So not normal per se, but they're no longer experiencing the psilocybin effects. They're experiencing the aftermath, the exhaustion, if anything. And the potential contemplation of this very, very different experience. And so what we do is we send them home with a loved one. Traditionally, we invite the person into the room for 10 minutes to kind of sit down — the, the family member or the loved one, the friend taking them home to kind of have a gentle, you know, handoff, uh, and sort of let that person see, you know, the environment the person was in for the day.

Judith Warner: And then when do they start to digest it with you? And what does that look like? Sound like?

Dr. Matthew Johnson: There's a, uh, typically a meeting the very next day, um, called an “integration meeting.” And that just is a discussion of the experience. The biggest technique is just what could be called “supportive therapy.” It's like, you know, reflective listening, taking the person seriously, but you know, the, it's not like the guide or the therapist has any, this sort of like dream interpretation, you know, kind of these mystical answers. “Oh, well you had an experience where you had a vision of an eagle, that symbolizes this or that.” You know, it's like nothing like that. It's just processing, helping the person sort through, come to their own meaning from it.

Judith Warner: How many people, you know, have you studied and what's the percentage rate of success that you've had?

Dr. Matthew Johnson: So for helping people quit smoking at this point across the studies, uh, and the laboratory research, over 100, uh, now. And then in other studies across mini studies, gosh, it's, uh, hundreds. I mean, I think, well over 500, you know, folks, uh, through Hopkins over the years and the various studies. Our small pilot study had a very high success rate of 80 percent smoke- free. And that's biologically confirmed. We confirmed that by looking at their breath samples and their urine samples that can tell us if they've been smoking. Um, but 80 percent, at six months, and that held up to 67 percent a, a year later. So a year after the target quit date. So those are very high success rates. Six months later, even you, you typically only get success rates in the twenties or thirties for the best medications. 

Judith Warner: You've described the effect on the brain as like shaking a snow globe. What do these drugs do to the brain that allows something so major to happen so fast?

Dr. Matthew Johnson: Yeah. And this is an area that's really complex and we could speak about different levels. We know that, that a drug like psilocybin hits a certain type of serotonin receptor, a brain receptor that normally receives serotonin the way a lock would receive a key. But instead of serotonin fitting into that receptor, now psilocybin is kind of mimicking, uh, serotonin fitting into that keyhole, but then it's affecting the brain and the cell, the neuron and the brain in a very different way. Obviously serotonin itself, which is floating through our heads right now, is not psychedelic. So it affects the system in a different way. It seems like there is an overall increase in the connectivity across the brain. What that means is, areas of the brain that don't normally jive with each other, now they're moving and grooving with each other. There's a correlation between their activity instead of it just being kind of independent.

Judith Warner: You talked about plasticity, you know, that plasticity is playing a role here. Is the plasticity greater with psilocybin treatment or other psychedelic treatment? And why is that exactly? 

Dr. Matthew Johnson: So we know in rats that different forms of the neuroplasticity unfold and what that means is it can mean branching of, of neurons, brain cells. Growing of branches, like just like a tree would grow branches. And those are the things that could potentially, um, form connections with other neurons. 

We also know that synaptogenesis happens and that refers over that those forming of new connections with those various branches. Some evidence suggesting perhaps neurogenesis, which is actually the birth of new neurons. There's many forms of neuroplasticity. And so it does seem clear that at least in some of these forms of neuroplasticity, that these psychedelics have powerful effects. We do not know, whether those are unfolding in people. It's a very good bet, I think, that they are. And we don't know whether that is underlying and responsible for some of the therapeutic effects. So that's at the horizon.

Judith Warner: Your colleague Roland Griffiths, who has been a big deal in psychedelics research for a really long time, in 2020 wrote something really striking. And he said, “Recent popular press books, websites, podcasts, and media reports have uncritically promoted presumed benefits of psychedelics. Patient demand is growing as is the interest in the general population with the possibility that expectations are outpacing the current data on what outcomes can be confidently foreseen.” I mean that is two years ago and things are changing really fast, but do you agree with that? I mean, are we in some ways getting ahead of ourselves with our expectations or, getting ahead of ourselves in terms of the science? 

Dr. Matthew Johnson: That's uh, yes, there's a lot of hype around psychedelics and we should follow the FDA pathway in terms of really evaluating its regulation as a medicine. The, the definitive phase three studies haven't been done. That said, uh, this is a really complex area. But Roland's also, and we disagree about these things. I mean, he said a number of times he thinks psychedelics can save humanity. And I just, I just, to me, that's one of the examples of what went wrong in the sixties. That, you know, that, that generation, they really dropped the ball. Um. A lot of people are doing important work to save humanity and psychedelics hopefully can play a role in mental healthcare. But I think this kind of over-bloated expectation about transforming the future of humanity, or, that's where we start to get into really troubled territory.

Judith Warner: And so getting the FDA on board with evaluating these drugs, which it now is, seems like a pretty critical piece of the puzzle in terms of tamping down that hype. So where are we with that? What drugs is the FDA looking at now and, and which ones might be approved the soonest? 

Dr. Matthew Johnson: Yeah, so the most advanced research is being done with MDMA for treating PTSD. So one out of two FDA studies have been conducted and that work looks really promising in terms of showing the two things that the FDA need to approve safety and efficacy. Does it work? And is it not gonna, you know, harm people? I would imagine that could be approved in two years. Psilocybin for treating depression is, uh, just a little bit behind that, I think. So maybe three, four years away from psilocybin being approved for depression. The huge caveat is, of course, you know, depends on the results of that phase three work.

Judith Warner: I know these aren't your studies, but the depression studies, and the MDMA studies for PTSD. Do you know what the success rate generally has been, and how do they compare to standard treatments? 

Dr. Matthew Johnson: All of these treatments have shown pretty large effects. There's some variability across studies, but with the large majority of people, whether they're talking PTSD or depression, you know, six months later, very large portions are seeing substantial reductions in, in their symptoms. So the majority in, in, in various studies showing that they don't even meet the criteria for having a disorder anymore. And then others, you know, having substantial reduction. So they're fairly large effects, in terms of the treatment of these disorders.

Judith Warner: So, let's say someone is listening right now and they suffer from depression, or PTSD. And they hear this and think, “Okay, wow, I'm just gonna go out and take a whole lot of mushrooms.” Do you worry about that? 

Dr. Matthew Johnson: I'm not encouraging people, based on the research, to do it on their own. For one reason, because we've done these things under really specific conditions. You know, we're screening out people that might have some increased risk factor. We are monitoring people. Um, we're preparing them. And so all that is likely to be very different. I've done surveys of thousands of people at this point that have taken these drugs that say they just took it for fun and they stopped smoking or stopped drinking or stopped doing cocaine, this type of thing. That, it really appears to happen too. But it certainly seems like one’s chances of success, we have no idea how to gauge it. They’re certainly lower without that professional help. And the, on the other side in terms of risk. Yeah, there are very real risks.

Judith Warner: Can you talk about those?

Dr. Matthew Johnson: Yeah. So it depends on what compound we're talking about. With MDMA, it's more likely for there to be a, a straight-up medical risk. So a cardiovascular problem, it has stimulant properties. It is also possible for people to have heart problems. We weed out for psilocybin. So we exclude people that have severe heart disease, the type of person that, they could have a heart attack, shoveling snow and going up flights of stairs. But MDMA is even more of a concern. So, those are all things you can screen for and you can test in a very rigorous way. But then also on the psychiatric side, it appears over the decades of observation that people with either active psychotic disorders like schizophrenia or a predisposition for having those disorders, it appears that those people can be destabilized with a psychedelic experience. And I think of it the same way that their disease state can be triggered or exacerbated by any number of intense, potentially traumatic, life events.

Judith Warner: How common is it for people in the studies to have a bad trip?

Dr. Matthew Johnson: Oh yeah. So it happens on about a, a third of the sessions. So in the research, we call them “challenging experiences” because, the really bad thing that can happen when someone's, when this happens on their own, is not that they're feeling anxiety. It’s that they run across the street, cuz they, they're freaking out and they get hit by a car. That's an example. It's rare, but it has happened. People, you know, are highly intoxicated and they do something and they get hurt or they get arrested because they just go out and make a fool of themselves in public. And this type of thing. Now, someone could have, you know, one of the most kind of fearful experiences of their life, but in the context of having been prepared for that, having a trusted person there to hold their hand and to reassure them that they're not being left alone, we haven't seen any long-term evidence of harms that have come from it. Some people say they wouldn't wanna do it again. Um, but we've never seen any, anybody that claims that they've been long-term harmed from it. A lot of people say that they actually valued, even though we do our best to minimize them, they actually value those difficult experiences they vary. But sometimes it has to do with, you know, looking at yourself in a difficult way, um, you know, facing your demons, this type of thing. Or just kind of, going through this existential fear and persevering, having some faith that it's gonna be okay. And getting through the other side, you know, running that gauntlet seems to make someone feel like they've gone through something. A rite of passage.

Judith Warner: You know, in a sense it seems like, the train is out of the station already. When it comes to commercialization, the road to either legalization or just decriminalization. So, what do you picture, you know, as a kind of ideal future pathway for all of this to come out well and minimizing harm, what do you think needs to happen?

Dr. Matthew Johnson: I think we need to continue the federal funding of research. We are in the, in the age where there's, uh, a lot of, uh, investment now, in terms of companies looking towards FDA approval. I think overall it's a good, that's a good thing, but we do need that basis of federally funded research that, you know, really across science often forms the basis. And it's the area where you're more likely to have more kind of rigorous work to address safety factors, kind of at a more, fundamental level and learn something about these drugs and how to appropriately shepherd them into the future. We also, need more public information. Yes, this is promising, but yes, there are risks, you know? And so informing the public. I do think that there's more of a, a role for you know, local state and the federal government in terms of, really not from kind of a, a “scared straight,” uh, sort of, uh, kind of extremist position. But realistically, you know, kinda let people know, “Yeah, you've probably heard about these things. Maybe you're interested and there is some research and here's where the state of the evidence and here's what we know about the risks of these in the human animal.” 

Judith Warner: What do you think of microdosing? That seems to have come into uh, fashion? I feel like I hear and read about people doing it all the time.

Dr. Matthew Johnson: There's no evidence to date that it's actually having the therapeutic effects that are claimed. It's possible, but, if, if it is working, in other words, causing, you know, these therapeutic effects. And there's various claims, you know, from antidepressant effects to PTSD treatment, to, improving focus, this type of thing.You know, if, if there is an effect there, it's a much different model than the psychedelic therapy I've been describing with high doses. 

Judith Warner: Well, we’re undoubtedly going to be hearing a lot more about that. But I'm eager to know what's next for you. And what are you most excited about on the horizon, in your own research, or in other people's research, in what you see coming down the pike? 

Dr. Matthew Johnson: I guess in the big picture I'm looking forward to figuring out and, as a field, us all figuring out what are the common elements linking together, these different disorders. One of the big picture, amazing things with the psychedelic work is that they seem to be working for really distinct disorders. And so I think the backdrop of that is, psychedelics as a tool to help teach us the nature of these disorders. Maybe there's more in common between addiction and depression than we normally, um, acknowledged, um, because we're seeing this transdiagnostic efficacy. In other words, it's working for these apparently separate disorders. So the more we learn about the long-term effects of it in the brain, the closer we're gonna get to actually understanding more about the nature of these disorders, period.

Judith Warner: That's such an interesting way to think about psychedelic research, and, really, all research into disorders like depression and addiction. These diseases that are just so hard to treat in the brain. And I guess it also perfectly sums up what we need in the future.  

I can’t wait to learn what you find. This has been wonderful. Thank you so much for joining us. 

Dr. Matthew Johnson: You're welcome. It's been my pleasure. I've enjoyed the conversation.

Credits:

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