Dr. Peter Silverstone on the Science of Psychedelic Therapy

Introduction (00:01)

Boni Wagner Stafford (00:41)

Welcome to the podcast, Peter. We are joined by Wall Street Journal bestselling author, Dr. Peter Silverstone, who in April of 2022 published the book, The Promise of Psychedelics: Science-Based Hope for Better Mental Health. I had to pause for a moment on the subtitle. But Peter, welcome.

Peter Silverstone (01:02)

Thank you.

Boni Wagner Stafford (01:03)

We’re very excited. You’re the very first Wall Street Journal bestselling author that we’ve talked to on the podcast. Let me dig in a little bit. That was a goal of yours from the very beginning when we first started working together in 2021. Tell me about what that meant for you.

Peter Silverstone (01:20)

Well, I think that when you write books – and I’ve written other books before – when you write books, it’s nice to think that what you write is actually interesting to people. And probably the only way you can actually measure that is to say, are people interested in putting their own money towards that, digging in their own pocket, and they feel that it’s valuable? And this is a real, for me, a sign that the topic is of interest to people. And so I think for me, it was very gratifying and humbling, in all honesty, that so many people found the book useful and ended up buying it. And that’s lovely. 

And so it was an aspiration at the beginning: goal, aspiration, something I wanted to achieve. Because I thought, well, at least I know that there’s interest in this and that the time spent on this is not wasted and is worthwhile. And in fact, I was completely blown away by how many people have ended up buying this book. I don’t know what the stats are now, but it’s a significant number. And I think that just talks to the interest and the need in this space.

Boni Wagner Stafford (02:23)

Yes, I would agree with that. And I don’t have updated numbers for you either, but I do know that after the first, I think it was 10 or 14 days, that ebook’s alone moved: There were 5,000 copies of the ebook sold. And that is a significant achievement in a short period of time and speaks to an accomplishment on a number of levels. 

But so let’s dig in. And you’re right, it is topical. There’s a lot of conversation now about psychedelics, in many areas. And just for the listeners: You’re not talking about psychedelics being great for all things and all people at any time. Your position is, based on the fact that you’re a psychiatrist and a researcher and a scientist, your view is that their use has a specific application. Can you just tell us a little bit about that?

Peter Silverstone (03:26)

So you’re exactly right. I think these are powerful compounds. They impact everybody’s brains, not always in the same way, but often in a similar way. And the question is, can they be used to help people who have significant mental health problems or mental health disorders? And that’s, for me, the interest and the reason for the title: the promise of psychedelics. There is real potential. There is real hope. There is real optimism. But that does not mean that, “Off you go; go and grab some mushrooms,” or whatever it is you use, “and everything will be fine.” 

And I think there are two parts to this that I wanted to really bring out in the book. The first was that the range of psychedelics is huge; they have different actions. And we’re at the testing stage. We’re not at, “Yes, they’ve been proven.” There’s a lot of suggestive evidence, but the reason for the science-based words in the second part is I wanted the literature to reflect the reality. You know, that it is, we’re at the testing stage. So that’s the first part. The second part is that these compounds by themselves are not going to be as effective as if you combine them with the right psychotherapy. It’s called psychedelic assisted psychotherapy. It’s the two together. And the second part is, do we have programs to focus on the types of psychotherapy, the types of therapy specifically that are going to benefit or work with psychedelics? And if we use latest evidence, are there some particular approaches we can do?

So the book really has several components. The first is to say this is the reality of the conditions. These are the things where there’s potential help if you look at major depression or post-traumatic stress disorder or addictions, possibly some other areas as well. So these are the areas we can look at. Here’s the range of the various psychedelics – and there’s lots of them, but what are the most interesting ones? What are the safest ones? And where are we? And then what are the therapies or particular type of therapy that we can use to really make this work for most patients? 

And so that’s the book summed up. A lot of new ideas, a lot of new thinking, bringing people up to date with where the evidence is – which I think there’s a lot of misinformation, there’s a lot of hope, but it’s not simply, “Go off, take a psychedelic and you’ll be cured.” I truly wish that was the case. It’s not. And so I think that is the last part, which is my personal view, is that these drugs are very powerful and there are some potential risks. So should they be freely available for everybody to take whenever they want? No, I don’t think that’s the case right now. Might that change over time? Possibly. But that’s not what I’m advocating for. I’m not advocating for, “Go and take whatever you want and everything will be fine.” I think that’s simply not the case.

Boni Wagner Stafford (06:11)

Yeah. I’m going to go into the therapy end of it in just a moment, but I just want to dig into what you’ve done with the presentation of the psychedelics in The Promise of Psychedelics. Because I think it’s an interesting take, which is that you’ve not only described what the psychedelics are, given a little bit of history, a little bit of their science background, you talk about how they work, what the risks are and what the potential benefits are, but you’ve ranked them. Tell me about that.

Peter Silverstone (06:43)

Well, that was, as I was writing the book, there was some feedback from many people, which helped clarify how I can best express the differences between them. Because there’s a lot of psychedelics. If you go on Wikipedia, there’s over 850 listed, and the probable number is probably close to a thousand. So you have a huge range of compounds. Some are similar; some are very different. And so you can say, well, “What about this, or what about this, or what about this?”

And what I wanted to do is say, “What are the ones that are going to be most likely to have clinical usefulness?” And then ending up with basically three groups: those that could be potentially useful, which are termed “wannabes”. There is some evidence – a bit early, but we’ll see where the evidence takes us. 

Then the next group, which is “contenders”. “I could have been a contender,” is that line from a movie. And I do use a lot of, I was going to say pop culture references, but they’re pop culture for my generation. So they’re not always ...

Boni Wagner Stafford (07:50)

Oh, it was pop culture at the time.

Peter Silverstone (07:53)

Pop culture at the time. You’re right. But not the most current pop culture. Anyway, “I could have been a contender” was a line from a well-known movie. And the group of that is not yet ready for prime time, but maybe. And then what are the best? 

And it ended up that in my view there were three psychedelics which I felt would be most likely to be useful and the soonest that people will be able to get them. And those three were psilocybin, which was number one; ketamine, which is currently legal, is number two – and we can discuss whether or not it’s a psychedelic; that’s a separate conversation; and number three is MDMA or commonly the street drug known as ecstasy. Those are the three top and those were then listed as gold, silver and bronze medal winners, just because it seemed to work in the description. But they’re all interesting. They’re all different. And if I’m going to put money on where we will be, it’ll be those three, I think, over the next few years. 

There are a couple of others that are coming along, and other people have other drugs in development, but we’ll see where they go and what actually ends up happening with the others. For those three, I would expect that in the next few years, those will be available for doctors to prescribe in certain and limited circumstances. Or drugs similar to those.

Boni Wagner Stafford (09:11)

Right. So you’ve talked a couple of times about the therapy component and the fact that based on your research and your academic and practical experience as a psychiatrist and a scientist, that it’s not the psychedelics in and of themselves that offer the promise, but it is when they are paired with appropriate therapy. And tell me about that appropriate therapy. Does it currently exist?

Peter Silverstone (09:46)

So let me start back with why the therapy is needed. I’ll use an example. And just to be very clear, I have never taken psychedelics. It’s not in my interest in taking them. I see these as useful treatments; not as something that I want to use recreationally. I know others have different approaches. So when I’m describing experience, these are not my personal experiences. But if you look at the experiences described repeatedly with LSD – kind of a classic psychedelic that we think about – people have experiences called trips that last many hours. And during those, a very wide range of experiences can occur. And those can be feeling out-of-body experiences. Those can feel oneness with nature. You can see and hear things that are very different. 

And probably the reason that people have such a varied set of experiences is that LSD will make changes in opening connections. But it opens lots of connections and the actual path you follow can vary enormously. So you can go down one of a huge number of paths that will be personal to you. And there’ll be some similarities to what other people have, but potentially something quite different. So how do you try and say, “Well, I want you to not go down infinite paths.”? It’s like going into a forest and saying, “Okay, I’m, you know – there’s 50 or a hundred different paths. Which one should I follow? Well, I want to follow this path because at the end of this path, it gets me to where I want to go. I’m going to make this up and say it’s a well. I’m trying to find my way to a well like a maze.” How do you do that? 

Well, that’s why you need the appropriate psychotherapy. It guides you down the right path, supports you while you’re going down there, and helps reinforce what you’ve gained from going down that path so that the experience can translate into some longer-term outcomes.

And I think that’s why these two need to be given together. The therapy by itself can of course have utility in some patients. Some patients, we know, benefit enormously from therapy. Cognitive behavioural therapy is the common one. But for psychedelic assisted psychotherapy, for more severe mental health problems which have not responded, I think you’re going to need the combination always. I don’t ever see the situation where you’ll say, “Oh, just take this pill.”

Now ketamine, which I talked about as the silver medal winner, is sometimes given by itself. But I think the evidence is pretty clear that if you want better impact – longer lasting impact – combining it with appropriate psychotherapy works. So I think the evidence is there. 

The next question, which is, what is there in the psychotherapy? And the answer is there’s gaps. I mean, there’s massive, massive gaps. Because there’s been very little research in this area because psychedelics have had such an issue and because psychedelics really haven’t been legalized in the way that have allowed therapists to develop, there’s a gap. So what I do in the book, and what I really believe in, is that we need therapists that take advantage of our latest understanding. What areas of the brain are we trying to target? What specific components of therapy may target them? And then how do we leverage that and other tools via feedback tools, all kinds of other information, to personalize a program so that for you as an individual, this is the best therapy to go with: a personalized psychedelic, whichever one turns out to be most useful for your symptoms. 

So I think that we’re starting down that path and experience over the next two to three years, as we start to test and develop therapies, will be there. And what I’ve done in the book is talk about what I consider to be the most appropriate therapy approach. I called it almond therapy. And that’s because I’m targeting an area of the brain called the amygdale and the amygdala is just Latin for “almond”. So it’s almond therapy. Very much designed to go alongside psychedelics. And that’s where we are. 

And the last wrinkle to this is I’m a scientist, so here it is designed, here is why I think it is going to work, but until I’ve done the studies – until we’ve shown that it has an independent effect; that it actually does what we think it’ll do – it’s not proven. So we’re at the stage of starting to prove that the therapy itself does everything we expect. And as we do that, we test the psychedelics as well.

Boni Wagner Stafford (14:15)

Yeah. So you’ve got the hypothesis and you’re setting out now to prove or disprove your hypothesis. But based on previous evidence, scientific experience, as well as therapeutic experience, this is what you think is going to work, hence the hypothesis. That’s great. So the therapy that you do describe – almond therapy – in the book is connected, and the book is connected to, you know …  You’re staking your entrepreneurial – what do you call it? You’re staking your entrepreneurial bets, I guess, on this. You’ve started a company and the book is very much part of delivering the message and helping to educate people, I guess, about the potential. So tell me about the connection to your company, Zylorion Health.

Peter Silverstone (15:06)

So I think from my perspective, most, if not all companies, but most companies focus … Most biotechnology companies – and I’ve been in that space as well before – focus on the compound: Here we have this drug; this drug will do X. I don’t think that there has been another company that has from the get-go said, “We are going to develop new compounds,” which is what Zylorion has done, “but also pair that with new evidence-based therapies.” I think a lot are starting to do that, but we were one of the first. 

And the third leg of the stool, as it were, is to say, “Well, how can we collect the data electronically? What data can we collect? How can we use the latest tools – whether that’s virtual reality, biofeedback, heart rate variability, and so on – to actually improve outcomes?” And that, using artificial intelligence and machine learning, allows us, for an individual, to very accurately make sure that both the therapy and the compound are really highly personalized and targeted for their needs. So I think the reason I started the company is because I think the evidence is very clear. Governments aren’t going to do this, and a profit motive is a very important driver. And of course, I always say, “I want to do well, but I want to do well by doing good.”

And the reason for starting the company instead of just publishing the information is that I know publishing the information doesn’t get things done. Whereas here we have an opportunity with a company to really drive forward the new approaches that I hypothesize will work: have to prove them, have to go through all the formal regulatory steps, have to show that it works in the conditions, have to do very rigorous clinical studies. But the lights at the end of the tunnel for that, or gold at the end of the rainbow – depending which analogy you want to use – is that we may end up with treatments that are really, really effective, can be personalized and get better because the more people that use them, the more information we have, the better will become the AI engine – the insight engine – to allow us to personalize more. 

So that really links. Both the research and the business are all focused on the same thing, which is, better clinical outcomes for patients. Because fundamentally, every day I see patients – and my practice involves seeing mostly new patients – every day I see patients, I see some – sometimes many – who haven’t responded to existing treatments. That’s why they’ve come to me. And to have these additional tools or approaches is something I would love to have access to. Not that I’m saying they’ll work with everybody, because they won’t, but if they help 20 percent or 40 percent or 60 percent, that will be a huge transformation. Because people get stuck for years and years in these terrible, terrible mental health conditions. So there is promise; there is hope. I genuinely believe there’s hope. And the reason I think I can best achieve those goals is through commercialization. So that’s why I took that particular route.

Boni Wagner Stafford (18:16)

Right. So a couple of different ways I want to go here. There’s a statistic that you bring in, right off the top of the book, about the percentage of people with significant mental health issues that are not helped with current forms of treatment. Can you just give me that number? It’s kind of startling.

Peter Silverstone (18:36)

Yeah, so these are estimates, but if you look at the number of people with mental health problems globally, that is staggering. When you add them all together and you add in COVID and everything else, we’re probably looking at the entire population of the planet, possibly one billion people have various forms of mental health issues. Of the people who have them, some will resolve spontaneously, which is great. Some will have chronic conditions: conditions that last three months, six months, nine months. And of those, a large percentage will not respond. Is it a third? Is it more? It depends on the condition and the type. But for depression, for treatment-resistant depression – that is, people who don’t respond – that’s generally accepted: That’s about a third of all patients with chronic depression do not respond to standard treatments. So we need new help. 

If you look at post-traumatic stress disorder, numbers are probably worse. We have no medication, none, which seems to work for post-traumatic stress disorder right now. And the only compound that seems to be most exciting to this time is actually a psychedelic: MDMA. 

So I think the need and the opportunity are really there. The number, as I say, is often quoted as one third, but it does vary between conditions. Sometimes it’s higher; sometimes it’s lower. But it’s a lot of people: A lot of people with huge needs for which there’s no treatment.

Boni Wagner Stafford (20:06)

Yeah. Okay. To back to Zylorion again. Tell me about the team and what you guys are focusing on. What’s happening right now?

Peter Silverstone (20:20)

I’m very lucky that other people have also felt the desire to really work in this space. And we’ve got, I think, one of the best teams in the business and lots of varied and relevant experience, both in terms of the actual team and our advisory board and our actual board. So I think we’re really well placed to be able to look at these areas. 

And as I said, there’s three areas. There’s the compound itself and developing compounds and testing compounds. Then there’s the therapy component. And then last but not least is the digital component: the electronic AI component. And so being able to work with a team where we can cover all bases really well, I think is very gratifying and very exciting. And also a lot of fun, which are not words one often uses and associates with business. But it’s great and I’m really excited with what we’re doing, you know.

Hesitation or proviso is that like all clinical research, money is always required. These are very expensive programs. And so part of my job as the CEO is also to help let other people know what we’re doing and make people aware because investment is key to allow us to actually achieve what we want. Going through a regulatory path is a very expensive process for any drug and we need to do it properly. So, you know, pros and cons, but I am excited about the team we have. I really believe in my colleagues, a superb group of people. And I’m very excited and lucky that they’ve chosen to join me in this journey.

Boni Wagner Stafford (22:01)

So what would you say your number one challenge is with where you’re at with Zylorion? I mean, it’s a gargantuan undertaking from all those, the three scientific areas, that you’ve undertaken and then making sure that you’ve got the underpinnings of support so that you can get the work done over the long haul. But tell me what would you say is the biggest challenging area for you right now?

Peter Silverstone (22:34)

Well, one, obviously, I said is money. You’ve got to have the funding to allow you to move forward. So that, without funding: In any area of endeavour, you know, time and money are always the issues one is scrabbling with. So I’m going to put that aside because, you know, you need to get things done as soon as possible and that costs money. And so that’s probably the biggest issue. 

But beyond that, there are a lot of other linked issues. First of all, we’re dealing with substances which have quite a lot of stigma to the past or people don’t understand them. There’s regulatory issues involved around these: What can you do? What can’t you do? There’s a lot of misunderstanding of these. You know, if I was to take another area, cancer drugs, oncology drugs, you’re not going to have the same issues around, well, is this useful? Will it get – will it become problematic? Will people become addicted? And so on. So there’s a lot of areas you have to cover. 

The second is the technical challenges of doing studies in the mental health space, which are not always obvious. You can certainly say – I’ll now use depression as an example: Here we have someone who has severe depression and we’re going to treat them with a drug. How someone does will in part depend upon their expectation. If they come into the study and they think, “Oh, I’m taking a wonder drug; I’m going to be fantastic,” they do well. That’s an expectation effect. But if they don’t do well, they can get much more disappointed: “Oh, I had all my hopes pinned on this and it’s obviously hopeless and not working on me.” And so the mental health response to being in a study is much bigger than other areas. 

And often this is shown in what we call the placebo effect. If you take people with an illness such as depression and you give a group an active drug, or what you think is an active drug, and some you give a dummy drug, like a sugar pill, the people who have the dummy drug – the sugar pill or the placebo – will have changes. Most people in a month will have a headache of some kind. They just will. And if you’re recording your daily number of headaches, some people who have the sugar pill will record a headache. And then we say, “Well, I’ve got a headache. I’m taking this pill. I think this pill caused the headache,” that’s an attribution bias. 

The problem is if people start coming, we talk to them, we ask how they’re doing, how are things this week, we take an interest in them, that will help their mental health. Which is good, but it means that even if they’re on a sugar pill, their mental health improves. And so that placebo response – that response to nonspecific interventions – can make it very, very hard to show the difference between that and what else the pill and the therapy does. So there’s a technical issue that’s quite hard for mental health studies. It’s the reason a lot of companies have actually … A lot of the large pharmaceutical companies have actually stopped doing work in this area because of the technical problems. There are some other linked issues about doing mental health studies that can be very difficult. 

Another issue that is really hard about this space is the fact that the symptoms are across many conditions. If you have high blood pressure, I can measure your high blood pressure and you have it or you don’t. Well, if I have a low mood, does that mean I’m depressed? Well, you can have a low mood in post-traumatic stress disorder. You can have a low mood when you’re anxious. You can have a low mood with chronic pain. And so the symptoms are across many different areas. And we have a real problem in psychiatry in that we use symptoms to define the illness. “Okay, you have a low mood and your sleep is bad and you have poor concentration. So I’m going to say you have depression.” But there are many, many different types of symptoms and syndromes where you see the same things over and over. So it can be really very hard to say, “Okay, this is pure depression,” or, “This is pure anxiety,” or, “This is something else.” 

And then when you’re looking at psychedelics, it’s very likely that they work across diagnoses: transdiagnostic. They might work for PTSD and anxiety and depression, for example. 

So we have another order of another layer of problem when we’re doing studies, which is, what are we actually studying and how do we know when we succeed? There are no markers. It’s not like you can take your blood pressure or measure some blood tests and say, “Okay, well, this has changed. So we’re successful.” And so that and the subjective nature of it: a bit like pain, you know. “How much pain do you have?” Well, I can tell you what pain I’m experiencing, but I can’t measure pain objectively. Same with mood or anxiety. So there are a lot of complexities about doing studies in this way, which makes it more expensive and more time consuming and higher risk. Coming back to time and money. So that was a very long answer to, I think, the problems that we have. But this space is a complex one. 

And yet I talk about the promise. The promise is real. So we have to overcome these issues. We have to. We have to figure out how to do studies in a way that are acceptable to us and in a way that is acceptable to regulatory authorities, because the need, the desire and the opportunity are so great.

Boni Wagner Stafford (28:00)

Yeah, very interesting. Well, I’m a big fan of the book and the issues that you’ve raised. Of course, I know the book very well, being the publisher of the book, but The Promise of Psychedelics: Science-Based Hope for Better Mental Health, a Wall Street Journal bestseller by Dr. Peter Silverstone. And a very revealing and interesting conversation. Dr. Silverstone, thank you so much for joining us. And I will be placing the relevant links. So if you want to find out more about Dr. Silverstone, about Zylorion Health or about the book, you’ll be able to find that in the show notes. So thanks very much for joining us.

Peter Silverstone (28:42)

Thank you for having me on and good luck with your podcast series.

Boni Wagner Stafford (28:55)

Thank you. 

(Outro.)