Boris Heifets:
What if you could take the drug out of the trip? In other words, recreate a psychedelic-like experience without reference to a psychedelic drug itself?
Elizabeth Koch:
Hi, I'm Elizabeth Koch. We all live inside our own personal, private Perception Box, built by our genes and the physical, social, and cultural environment in which we were born and raised. In this podcast, we explore how although the walls of this mental box are always present, they can expand in states like awe, wonder, and curiosity, or contract in response to anxiety, fear, and anger.
I'd like to introduce our esteemed hosts, two incredible and distinguished minds. Dr. Heather Berlin, Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City, and Dr. Christof Koch, Chief Scientist for the Tiny Blue Dot Foundation and the current Meritorious Investigator and former President of the Allen Institute for Brain Science. Welcome to the Science of Perception Box.
Heather Berlin:
Hi, everybody. Welcome to Science of Perception Box. I'm your co-host, Dr. Heather Berlin.
Chistof Koch:
And I'm your co-host, Dr. Christof Koch.
Heather Berlin:
So every week we feature an aspect of the science of Perception Box, highlighting the latest research together with our expert guests. This week we're exploring the powerful research around psychedelics and dream states in the practice of anesthesiology with a researcher and doctor who has been as fascinated about consciousness as we are.
Dr. Boris Heifets is a board-certified anesthesiologist who specializes in providing anesthesia for neurological surgery. He's practiced at Stanford since 2010. In addition to treating patients, Dr. Heifets also directs clinical research and basic neuroscience. His research group studies how new rapid-acting psychiatric therapies like ketamine, MDMA, and psilocybin produce lasting changes in nervous system function, behavior, and therapeutic outcomes. But first, we want to share our own connection to psychedelics. So Christof, how have psychedelics helped you expand your Perception Box?
Chistof Koch:
They made me lose a sense of self. They made me lose my sense of body, of an external world, but there was still consciousness. And they made me lose my fear of death.
Heather Berlin:
Well, that's pretty profound.
Chistof Koch:
Yeah.
Heather Berlin:
So do you think you're a more relaxed person now?
Chistof Koch:
Yes, certainly.
Heather Berlin:
You seem very relaxed. Well, Boris, thanks for joining us.
Boris Heifets:
Thanks for having me.
Heather Berlin:
So how did you become interested in psychedelics as an anesthesiologist?
Boris Heifets:
So I became interested in psychedelics well before I became an anesthesiologist.
Heather Berlin:
Ah, I see.
Boris Heifets:
The question is, how did I become interested in anesthesiology as a psychedelics-
Heather Berlin:
Explorer.
Boris Heifets:
Explorer.
Chistof Koch:
You mean a psychonaut.
Boris Heifets:
Well, I've done some research on the topic before becoming a doctor. When I was towards the end of my PhD training, so I did an MD and a PhD at Einstein in New York, I had this question of, well, how am I going to apply this? What we're doing is we're looking at synaptic responses in brain tissue, we're looking at the inner workings of how circuits function in the brain. And I didn't want to lose that, and I wanted to pick a specialty that would allow me the most access to that kind of thinking and that kind of environment, not to mention this background interest in psychedelics.
I think when I started medical school, my mom told me, "Drop it. You can't have a career studying psychedelics. It's hippie science." This was in 2000, probably good advice. But when it came time to pick a specialty, I was thinking about psychiatry and neurology, neurosurgery, and anesthesiology. And the closest I could get to applied neuroscience was actually anesthesiology. You give a drug and you see its effect on the brain, the body, on consciousness itself. And that, to me, it never gets old.
Chistof Koch:
How do you know their consciousness is gone as compared to they're unable to talk and they're unable to signal that they're still there? How do you know they're not present?
Boris Heifets:
So we have a lot of interviews with patients after surgery that can attest to that. What's remarkable about anesthesia is that it's not like sleep. And when you close your eyes as you are anesthetized for surgery, when you open them, many patients will feel that no time has passed. Which is very different from when you wake up, you kind of have an intuitive sense of how long you may have slept. So that's already one difference just at the level of what the patient experiences.
One of the earliest concerns for anesthesia, as we were developing anesthetic techniques to keep people immobile and pain-free and amnestic during surgery, is there's something called the Brice Questionnaire. What's the last thing you remember before going to sleep? What's the first thing you remember when you wake up? And did you have any dreams during anesthesia? Do you recall anything? And that's basically how we set standards for what depth of anesthesia we use.
Chistof Koch:
How often does it happen that, I guess, depending on the type of anesthesia and the duration, that people do recall something that does relate in some way to something that did happen in the OR?
Boris Heifets:
So it's around one in a 1,000, so awareness under general anesthesia, even with EEG monitors. So we're monitoring brain function, we're getting a sense of the depth, but we're clearly not getting the whole picture because every once in a while a patient will recall something.
Now, I want to put a qualifier on that before nobody ever has surgery again after listening to this podcast. I've seen one case like this, and in an elderly woman, not who I would've expected. Though the thing she said was, "Everything was so far away, everyone was touching me really softly." But she was recalling conversations in the OR. So there's a deep disconnection, but she was able to maintain some sort of input from the real world. So again, that's one in 1,000.
Chistof Koch:
And no pain, right? Because pain is controlled separately.
Boris Heifets:
She didn't complain of pain, she didn't complain... It was a little bit distressing to her because she knew what happened. But she wasn't paralyzed. The thing that I was most worried about is did you feel trapped? And thank God she didn't. And that's, again, advances in anesthesia have allowed us to do surgery without paralysis even, in some cases. So again, that's maybe a topic for another time, but it's a rare complication that we do worry about. And again, that was the early concern of anesthesiologists, is that we want to make sure that consciousness is gone, right? Deep disconnection, disconnected unconsciousness that's reversible at the end of surgery.
Now, in the last 20 years, anesthesia has gotten a lot safer. We've started innovating things like nerve blocks, for example. So now we have a little bit more room to think about how much do I want to sedate this patient? What kind of experience do I want to provide? And that's where things start to get a little bit interesting.
Heather Berlin:
So before we get into the research, can you tell us a little bit about how psychedelics work in the brain and how they can be used as a therapeutic intervention?
Boris Heifets:
Sure. So this is a very hot topic right now. And when we talk about psychedelics, what are we talking about? There's the classic psychedelics: LSD, psilocybin-
Heather Berlin:
The classics.
Boris Heifets:
The classics, the greatest hits. And then there are other drugs that are, I would say, psychedelic adjacent. That a lot of people will identify psychedelic-like properties in these drugs. Drugs like MDMA, which is nearing approval, potentially, for PTSD. Ketamine.
Chistof Koch:
Assisted therapy.
Boris Heifets:
Yes, MDMA assisted therapy, which we're going to return to that point, I hope. And these drugs are not... They don't have the same perceptual effect, but they clearly are acutely psychoactive in a profound way that is very memorable and unmistakable.
And what ties all of these together and what has led to this explosion of research and excitement is that when you provide a space for people to have a powerful psychoactive drug in a safe setting, and just let their mind wander, things come out. If you have PTSD, if you have painful memories, if there are things that you haven't been able to resolve in your life, what people talk about is getting a new perspective.
Whether it be like, "What is going on in my body? Where is this pain coming from?" Or, "Who is this person who's always depressed and pessimistic?" This perspective shift is something that people across these drug classes will talk about. And to me, that's what defines this broad class. They're acutely psychoactive, powerfully so. Their effects are rapid. That perspective shift or however you want to call it, it's rapid.
Chistof Koch:
Change in the Perception Box.
Boris Heifets:
You can put it that way as well. And finally, the effects are durable. This is very different from modern mental healthcare. You don't take these drugs every day. Long after the ketamine or the MDMA or the psilocybin has cleared your bloodstream, you are still feeling those positive effects. This is a sea change in how therapy is delivered. And I want to emphasize again, it is far more complex than just giving someone a drug, putting them in a room while they happen to have their experience.
Heather Berlin:
So it's the synergistic effect between the actual, physical effects of the drug in the brains and this psychological effect or impact.
Boris Heifets:
Well, I would challenge that. I think that's actually one of the biggest debates right now. And it has implications; is it the drug or the trip that's responsible for these therapeutic benefits and the-
Heather Berlin:
Right. Because you get the same benefits without-
Chistof Koch:
Assuming that conceptually, A and B, empirically, experimentally, you can separate those two.
Boris Heifets:
That's exactly it. Right. That's why there's the debate, is right now all we're looking at is correlation.
Chistof Koch:
And so tell us more about this debate.
Boris Heifets:
It boils down to this, is you can think of... The complexity of psychotherapy, you can simplify into three basic stages. There's preparation, which involves setting expectations, building rapport. There's the drug experience itself, a possibly eight hour extravaganza sometimes.
Chistof Koch:
24 hours [inaudible 00:11:37].
Boris Heifets:
Or 48. It depends. The dose is everything. And then there's the integration. Making sense of what happens and trying to incorporate those changes into your life.
Chistof Koch:
Which can take weeks, right?
Boris Heifets:
And in trials, that's how long it takes, is that you have weeks of after-therapy. So the inclination, based on decades of experience in pharma is, well, it's got to be that little crystalline entity in the middle of all of this that's driving these effects. But in reality, as you pointed out, you cannot possibly attribute to one factor the therapeutic change, unless you can independently manipulate them. And this is where the science comes in. I'm going to put in a brief plug for why any of this matters. There are people who believe, not without cause, that it's enough that it works. Why get so bent out of shape about how it works? It's just enough that it does work.
And I would answer to that, is one thing that anesthesia has brought me in contact with is some of the most advanced medicine on Earth. And when I see... One of the most magical moments in residency, and I don't mean to gross you out, but watching a transplanted heart get put into someone's chest, fibrillate, and then convert to sinus rhythm. It's like watching birth or the Earth being born or a total eclipse. It was just awe-inspiring. How did we get from someone living for 50 hours in the '60s, after a heart transplant, to 80% at 5 years? This is amazing. It's by understanding the risk and understanding the mechanism.
Chistof Koch:
The mechanism. I mean science, this is how science works.
Boris Heifets:
And so that, to me, is the question. If a therapy is truly potent, by definition it carries risk, right? And when you think about the early days of chemotherapy, chemotherapy in 1975 was almost a death sentence in itself. 30 years later, you have the first rationally designed kinase inhibitor. That blew my mind in 1999. Gleevec, that cured leukemia.
And again, you take something that has... It's a powerful... Chemotherapy was powerful and crude. And we learned something and innovated and distilled it down to something highly effective and targeted. I'm not sure that CNS... That psychedelics are going to go that way, but there's a pretty strong track record in every other field of medicine for this approach.
Chistof Koch:
There are also strong motives in the industry to pursue that because that's what the entire medical system is based on. You give one little therapeutic intervention that the FDA approves, that you can then sell to everyone, that works. But in this case, because this is the most complex... You're talking to the most complex piece of active matter in the known universe. And I seriously doubt, having studied my entire life, that any one drug will be a magic bullet that cures whatever existential problems that brain or that mind has.
Boris Heifets:
I'm going to turn that on its head in that I completely agree with you. But how do you, without demonstrating the centrality of... My overall, overwhelming sense from all the work I've done is that we need to center the experience.
Heather Berlin:
My biggest question is whether it's the molecule itself-
Chistof Koch:
Or the experience, or both.
Heather Berlin:
... or you need the psychological experience. And can you isolate the psychological experience so they don't have to even take the drug? Are there other ways to get to that transformative experience?
Boris Heifets:
Yeah. That's what we're trying to develop, is that psychedelics pose really fundamental challenges for randomized controlled trials. Let's start with that for a second.
Heather Berlin:
Right, because you know you're on the drug once you're on it. It's very-
Chistof Koch:
And so why would that be a complication?
Boris Heifets:
So it introduces all kinds of biases. The randomized, placebo-controlled trial was designed for antibiotics and blood pressure medication.
Heather Berlin:
But the power of not knowing whether you're on the drug or not is really to get around the placebo effect thing. There's a certain amount of impact that the drug can have. Just thinking you've taken the drug, that can have an effect. And so-
Chistof Koch:
But probably not for TB, right? That's the logic behind it.
Boris Heifets:
Yeah. There are some things where placebo effect... We should be so lucky to have a cancer placebo effect, right?
Heather Berlin:
Right.
Boris Heifets:
People do not often spontaneously remit just on the strength of their belief, although there are all kinds of stories. But it's important, because think about it from a patient's point of view. You have read Michael Pollan's book, you are fascinated at the potential of psilocybin, you have out-competed 1,000 other applicants to be in the study on depression. You have already won a lottery, right? Now you go into the finale.
Chistof Koch:
And you've already failed two other trials, right?
Boris Heifets:
You've already failed two other trials, and, like, "I think this is going to be it." And so you have an expectation. It's obvious that if I get the drug, I'm likely to improve, because look at what all of these smart people say. And now comes the moment of truth. Your boyfriend, your girlfriend drives you, maybe you fight about it because you've been so persistent in your pursuit. You go through a lot of trouble to get to that room, to that therapist's room. And then you take the drug, and an hour later there's either a moment of confirmation and acceptance and being seen and being in an elite group of people on Earth who've been in a psilocybin trial. Or a moment of betrayal, where why did I spend all of this effort to be in the placebo group?
Chistof Koch:
Because nothing happens to your mind.
Boris Heifets:
Because it's obvious. It's such an obvious psychoactive effect. It's like winning the lottery. What is the effect of winning the lottery? And you tell me, what does that have to do with depression? I guess winning the lottery could be a short-term antidepressant. But that's sort of the heart of it.
Chistof Koch:
So because they've been told and they read that these are wonderful drugs, they were less likely to be depressed afterwards. That's what you're saying. That's what the placebo effect is.
Boris Heifets:
Exactly.
Heather Berlin:
But because they know if they're on the placebo or not, with psychedelics, it's very hard to control for that. So do you have a way that you're trying to get around this?
Boris Heifets:
So again, that's one of the biggest problems facing psychedelic medicine, is identifying a drug-specific effect. It requires some innovative solutions. I want to talk about a couple. One is efforts by David Olson and Bryan Roth, two great chemists, and many others who are re-engineering the molecule itself. They're basically trying to take the trip out of the drug.
Heather Berlin:
Christof's thinking, "That's no fun. Where's the fun in that?"
Boris Heifets:
I already know it.
Chistof Koch:
They want to take the fun out of everything.
Heather Berlin:
I mean, I can read your mind.
Boris Heifets:
This is the science. That, to me, it's crucial, right?
Chistof Koch:
Yes, I agree.
Boris Heifets:
You have to test. How can you not?
Chistof Koch:
Assuming you can do that.
Boris Heifets:
Let's just say for a minute, it's possible, you will get some answer there, is can you just encode resilience biochemically without anybody noticing?
Heather Berlin:
What about giving the psychedelic while somebody is under anesthesia? And they have no experience-
Boris Heifets:
Well, Heather, that happens to be what we did.
Chistof Koch:
Happy that you asked.
Boris Heifets:
I'm so glad you asked. So it requires a lot of different approaches, and this is the one we took. Now, I'm an anesthesiologist. And one, it's hard to escape the idea that you have all these people that come in from all walks of life, many with preexisting depression, PTSD. That's usually not what we're focused on. We're usually focused on getting them through surgery.
And we saw this as an opportunity, is that patients, they're put under general anesthesia, and while they're anesthetized, there's no there there. They're not there for it, right? That's the goal. So what if we gave a psychedelic class drug, like ketamine, during anesthesia?
So it's important to know that this is on a background of general anesthesia, not using ketamine as an anesthetic. We're using drugs like propofol, drugs like sevoflurane. These are standard anesthetic cocktails. And we're getting everyone to pretty even, cruising depth of anesthesia before we give them either ketamine or a placebo.
Chistof Koch:
So they're deep. So if you do a surgical cut, they don't-
Boris Heifets:
That's the goal. They're there for surgery. Now, part of how we were easily able to get approval for this is that ketamine is an anesthetic. It's an anesthetic adjunct. In patients for whom there's what we would call equipoise about, ketamine is kind of... You don't need to give it. There's nothing in the case that screams out, "This patient should definitely get ketamine." We are able to do this trial.
And we ran it like a psychiatry trial. And this is with actual psychiatrists, like Laura Hack and Alan Schatzberg, who helped quite a bit on this study. But we ran a psychiatry trial in the operating room, and they give half a milligram per kilogram over 40 minutes to minimize the psychoactive effects.
Chistof Koch:
But in a regular, awake person, there would be strong psychoactive with his dose, right?
Boris Heifets:
Yes. And that's what we've seen. We've done other... Worked on a trial with Nolan Williams where we're giving ketamine to awake patients.
Chistof Koch:
At this dose?
Boris Heifets:
At this dose. And patients, they'll have what's called... They'll dissociate. They'll get into a dreamy state. They might hallucinate. If you listen to what they say, there is a lot of overlap with psychedelic-like effects. And let's put that on pause for a minute, but that's the trip of ketamine, that we're actually trying to see do you need that in order to benefit from ketamine?
Heather Berlin:
So now you give them this dose, which normally, in a wakeful person, they would have a psychedelic effect, but they're under anesthesia. And you have it placebo controlled, meaning you're going to give them another substance that's not ketamine, or you just give them no ketamine?
Boris Heifets:
We just give them normal saline, a fluid with the same volume. And I guarantee you the patients were not aware. Everyone was blinded in the study.
Heather Berlin:
So they wake up, and what's the measurement? What do you assess?
Boris Heifets:
So again, we want to copy what's been done before. We're not reinventing anything. We're using a standard scale of depression called the Montgomery-Asberg Depression Rating Scale. It's a clinician rated scale. If, let's say, you're my patient, I'll ask you questions. "Tell me about your fatigue levels." Or, "How's your appetite?" And there's kind of standard degrees of-
Heather Berlin:
Of severity, but you're expecting there to be an effect right away, right after the surgery.
Boris Heifets:
That's the beauty of ketamine.
Heather Berlin:
SSRIs, you give a patient, and maybe six weeks later they say you'll feel something maybe. And it's very hard to make the connection between the drug and the impact. But with ketamine, they give it in the psych ER, and it really can knock out suicidality.
Boris Heifets:
And there's a nuance to everything, but essentially, yes. That's the design of this therapy, is that it's rapid acting antidepressant.
Heather Berlin:
So you give them this measure of depression right when they come out of surgery. You don't know who's had it and who hasn't.
Boris Heifets:
So we waited a day. There is a lot of things that happen right after surgery. But again, we're copying other studies where you have... The peak effect, the peak antidepressant effect of ketamine is one to three days after infusion, long after the drug is gone, which is where we started this description. And that's where we're taking our primary measure, is looking at depression scores in the one to three days post-infusion, post-surgery.
Heather Berlin:
And what you found was?
Boris Heifets:
Well, all of the patients who got ketamine did great. 50% response, 30% remission from patients, many of whom had treatment-resistant depression.
Chistof Koch:
Now what about the other patients?
Boris Heifets:
Well, so the placebo group also did great. 50% response, 30% remission.
Chistof Koch:
So it's remarkable. So you think whether or not they got the ketamine, both-
Boris Heifets:
Both groups, on average, showed the same degree of improvement. You could not separate them. The key here is that both were massive, massive improvements. And there's a couple of fine points here because I got a lot of... Wasn't exactly fan mail about the study. But people who looked at the study say, "Are you saying ketamine doesn't work?"
And there are a couple points to bring out about this. And the first point is what was the patient experience like? And you'll see how this is important in a minute, I think. And again, keep in mind this very large placebo effect that we saw, that we were absolutely not expecting.
From a patient, let's say you're coming in for surgery, for 20 years you've been dealing with a lot of trauma, the holdovers from a rough childhood, et cetera. And now you go see your surgeon, and do you think your surgeon is going to ask you about your mood? We can venture a guess to say usually not. It's the rare surgeon that has time, because there are other priorities.
So from your point of view, you're getting something in your email saying, "We care about your mental health and recovery after surgery. Would you be willing to fill out the survey and talk to us?" That's our first contact with the patient a few weeks before surgery.
Then you come in, you get a consent. It's about an hour long, where you hear all about the study. "Ketamine, we think it's an antidepressant in other circumstances. We're wondering whether this has therapeutic value during surgery." Now you come in for a two-hour interview with four of us. A nurse, myself, a research coordinator-
Chistof Koch:
Two hours interview, just as part of the work of this study?
Boris Heifets:
Yes, we want to know everything. And from a patient's-
Heather Berlin:
So you're sort of priming. First of all, they're getting more attention, you're talking about their mood. And you're priming them to this drug might really help your depression.
Boris Heifets:
Exactly. And there have been studies of depression during surgery before, and I don't think they went all out like this. We were looking for a particular type of patient. I was so happy to get each one of them, each of these 40. We learned a lot about all of them. And so two hours where we heard about their trauma, their mental health history, their physical history.
And then the morning of surgery, again, I wanted to make sure things go off without a hitch. In many cases, I held their hands as they went off to sleep. These patients were precious to me. And I was not at all thinking at the time, "My God, what kind of placebo effect I'm engendering?"
And let me stop there for a second. Why was I so blithely unaware of the possibility that we might induce this massive placebo effect? It's because the broader context is surgical anesthesia. Surgery and anesthesia are associated with a higher risk of heart attack, stroke, cognitive dysfunction, kidney injury, lung injury. Actually, all of our literature points to all these things getting worse after surgery.
Heather Berlin:
Nice.
Boris Heifets:
And putting people at risk for opioid use disorder. So that's what I came in with. I was not thinking that placebo would be a problem or that this study would even be about placebo.
Chistof Koch:
So the placebo was really a surprise to you.
Boris Heifets:
It was a big surprise.
Heather Berlin:
This is my question: what is the takeaway here? Is the takeaway that for the effects of ketamine, you don't need the psychedelic effects of ketamine for there to be an improvement?
Boris Heifets:
The takeaway is this: it's in the placebo effect. We can't say much about ketamine in this trial, but what I think we can say something about is all of the trials going on in the psychedelic space. Again, I've painted that picture for you of winning the clinical trial lottery and going through that process and all the confirmation bias that might go along with it. There are a lot of non-drug factors there. So inadvertently, just the structure of this trial, with preparation, a big central event, surgery and anesthesia, and then close follow-up in the aftermath, we had replicated a lot of the key elements of most psychedelic studies and driven a placebo effect that is enormous.
Heather Berlin:
Well, I think in some ways this is really good news. First of all, well, where is this published, this paper?
Boris Heifets:
Nature Mental Health.
Heather Berlin:
So I think everybody should take a look at the paper. But it's a warning to say, "Look, we really need to structure these psychedelic studies in a different way." However, it's really positive to say that, for instance-
Chistof Koch:
Your mind can change your body.
Heather Berlin:
Yes. So we don't need the drugs.
Boris Heifets:
We need something. These patients went through something. I think that's a key part of this.
Heather Berlin:
An experience though. It was an experience.
Chistof Koch:
Yeah, but they need this belief. If they don't have this belief... So you have to tell them that this thing is magical, whether it's a ceremony or a dance or beauty or molecule.
Boris Heifets:
But it's got to be... You can't just tell them. You need good placebo. We had really good placebo. We had the best placebo.
Chistof Koch:
Tell me, what about the... Does the belief that the patient... Because you must have asked the patient, "Did you think you got it or did you think you were in the placebo?" And how does that effect?
Boris Heifets:
So as I said, we weren't expecting this massive placebo effect. And this was in... We started the study in 2019, before a lot of the writing about expectancy had come up. So we didn't ask people until the very end of the study, "Which group did you think you were in?" I will say, this is one of the only, maybe the only, truly blinded study of a psychedelic class drug, so that was a small victory. But when we asked them what they thought they got, nobody knew, first of all. But in talking to them, in my conversations with these patients, if they got better, they attribute it to the ketamine. They said, "Well, I must've been in the ketamine group because I feel better." Which suggests that they had some prior belief. You wouldn't say that you got ketamine unless you believe the ketamine is therapeutic.
Chistof Koch:
But did the people... Surely there must have been some people who believed it, or maybe not, that believed they were on the placebo.
Boris Heifets:
And those are the... Yeah, because they didn't get better. They didn't get better. And they're like, "Well, I must've been in the placebo group." So what that shows, if anything, is that we did a job, unwittingly or not, a good job of instilling a sense of hope that this has the potential for therapeutic benefit.
Chistof Koch:
And I think that's how you conclude in the last paragraph of the paper. This is called [inaudible 00:29:30], the short name of this is hope?
Boris Heifets:
Yes. So there is a dangerous side to this. Not dangerous, but we can draw some of the wrong conclusions from this work. One is that the convention... Placebo is an old word, and it literally means I please.
Chistof Koch:
To please.
Boris Heifets:
Right. So one of the awkward things is if someone gets better after getting placebo, and then you tell them they got placebo, it's more than a little awkward. They're like, "Well, all that stuff I said, well... In the throws of placebo, was that all... It wasn't real." People need to feel seen, need to feel heard. And that idea that placebo is just something that you trick children with, we have to dispense with that idea.
Heather Berlin:
No, I think we need to harness the placebo. I've always said this, harness the placebo effect and use it in medicine.
Chistof Koch:
It's your mind. Yes.
Heather Berlin:
Exploit the placebo effect.
Boris Heifets:
Well, and good doctors do it-
Heather Berlin:
Yes.
Boris Heifets:
... in psychedelic therapy.
Chistof Koch:
That's why you have white coats, that's why you have Dr. Boris Heifets. Well, because if I believe you, just like a shaman, if I believe you are the shaman, then I'm more likely to-
Boris Heifets:
That has to be part of it. And there has to be a strong experience at the center. I had a bar mitzvah when I was 13. My father said, "Today, my son, you're a man." And I can tell you, my voice did not drop, but I felt different. People looked at me differently, they treated me differently. And how does that happen? It's not a person in isolation. It's certainly not a drug effect. It's a door that you walk through that is held up by the collective understanding of the community that surrounds it. And that is a very devilishly hard thing to study with conventional scientific methods.
Heather Berlin:
A lot of it is the power of suggestion. If they come in and they're depressed and they're low, "I'm never going to meet anybody. I'm never going to find anyone." You give them this hope. And they believe you because you have all these credentials and stuff, rather than me just giving my friend some good advice. They take your, "I really feel like you're going to meet someone. I trust that..." And then they start to believe it because someone in a authority position gives them that hope.
It's not about the SSRI they're taking. But studies do show, in conjunction, you get some powerful effects from the SSRI, some from therapy. When they work together, you get this synergistic effect. But I want to just talk about... Because I know there's other research you do, in terms of dreams and inducing dreamlike states with anesthesia, that I really want to-
Boris Heifets:
So going with this theme of experience. In this study that we're just wrapping up, the experience, they all went through something. It's not the experience on drug, but it's the larger experience of being in the study and going through a door, right? Having surgery and coming through the other side.
Chistof Koch:
Any therapy afterwards?
Boris Heifets:
No. Like every other ketamine study, which included no therapy.
Chistof Koch:
And how long did you...
Boris Heifets:
Two weeks.
Chistof Koch:
And so you didn't track... Are these people still...
Boris Heifets:
Not formally. I kept up with some of them. And some of the stories, I'd love to share some of them. It really made me question whether I should be in science or not when I couldn't tell is this woman in the ketamine group? Because how do you get that kind of transformation without something to account for it? Of course, she's in the placebo group.
So there's another way to look at this. Coming back to this theme of preparation and the drug, the day of the dosing, the drug and the trip, and then integration, and really focusing on the drug and the trip. Which you could either take the trip out of the drug, and we've now talked about a couple ways to do that, what if you could take the drug out of the trip? In other words, recreate a psychedelic-like experience without reference to a psychedelic drug itself? That would be a pretty interesting way to test this idea of how special is the serotonin 2A receptor. And there's just some very exciting research.
Heather Berlin:
But now we're talking about how do you create-
Boris Heifets:
Well, how do you regenerate... Exactly.
Heather Berlin:
... hallucinations without the psychedelic?
Boris Heifets:
So wouldn't it be an interesting test if we could induce a psychedelic-like state without a psychedelic, and get some of the same physiology, descriptions of experience, and therapeutic effects? Would that maybe turn on its head the idea that there is a powder at the center of all of these therapeutic effects? And that's, almost by accident, what we've stumbled upon working with anesthesia and dreams.
And I have a colleague, Harrison Chow. He's, I was going to say, an artist. He's an anesthesiologist, but this is the art of medicine. He spent many years in private practice, minor procedures. Patients would come in for hernias or endoscopies, minor stuff, and he would try and make the experience as pleasant as possible.
And he would do this thing where he would watch the EEG monitor and to look for what he thought was dreaming. And then patients would wake up and say, "I had the best dream, I had the best sleep I've ever had." But as you emerge, one of the things that you can notice if you really pay close attention to the EEG, this is brain state monitoring.
Heather Berlin:
So you're watching them as they come them out of anesthesia, and the waves start speeding up and they're getting higher frequency.
Boris Heifets:
Yeah. So when he came to Stanford, my chair put him together with me because he knew I was a psychonaut drug nerd, into non-ordinary states of consciousness, and, "You two should talk to each other and maybe figure something out." It was a great, great partnership. Harrison is really into the idea of making anesthesia more pleasant.
I'm a little bit more scientific, and I was very skeptical at first. So we agreed we're going to get a portable EEG, a SedLine, a couple leads. We have a team, it includes a psychiatrist. We are going to do interviews, diagnostic interviews, and we're going to follow these patients. I want to know, is what you're saying... Are you bullshitting me or is this real? Is there something there?
And not long after, we had our first case. And this is the case of a woman, this was published 2022, where this woman, she had been attacked at close quarters by a relative with a knife. Horrifying. As you might imagine, she'd had nightmares, right? She went to the emergency room and they said, "Go to Stanford, get your hand fixed." And in the intervening time-
Chistof Koch:
The hand got injured-
Boris Heifets:
Yeah, exactly.
Chistof Koch:
... defending herself. So the surgery was to help with her-
Boris Heifets:
Yes. The surgery was for her hand. In the intervening two weeks, she is basically a non-functional human, right? She is hypervigilant, she's having difficulty-
Chistof Koch:
Well, it's PTSD. She has severe-
Boris Heifets:
So due to the timeframe, we call it acute stress disorder, but this is somebody who would... More likely than not, we would be worried she would go on to develop PTSD. So she's in the pre-op area, she's there for her hand, and Harrison finds her. Again, still... That's all she can talk about, and she's really hard to reach. And again, talking about innovations in anesthesia, they put her arm to sleep, she gets a nerve block, and Harrison does his dream thing.
Chistof Koch:
Wait, so is her arm anesthetized, but she is still-
Boris Heifets:
Yeah, her arm was anesthetized. So she doesn't need to be so deeply anesthetized that she can't feel.
Heather Berlin:
When you say this dream thing, it's just that you're controlling the amount of propofol-
Boris Heifets:
And watching the EEG.
Heather Berlin:
... and watching the EEG, and getting her into this sweet spot where he knows that the dreams occur.
Boris Heifets:
Yeah.
Chistof Koch:
How long is this state of dreaming in this patient?
Boris Heifets:
About 10 minutes.
Chistof Koch:
Oh, very brief.
Boris Heifets:
Relatively brief, but there's a lifetime in 10 minutes. So what she says immediately upon waking is, "The nightmare, it was there again. I had the nightmare again, and it was looping just like it always does." But instead of rocketing her into consciousness, which is what a nightmare is, by virtue of this anesthetic suppression, she stays in that state and she actually, in her dream, moves past the attack. She, in her dream, goes to the emergency room, goes to the operating room. She's back home, running errands, with her hand healed.
Chistof Koch:
All in this 10 minutes?
Boris Heifets:
All in 10 minutes. A lifetime in 10 minutes.
Heather Berlin:
Just to go back for a second, just because in terms of therapy, often I'm working with patients who've had trauma. And the idea is to help them work through the emotions, is to sit with the thing that makes them anxious or uncomfortable long enough-
Chistof Koch:
Exposure.
Heather Berlin:
Yeah. Exposure long enough to get through it and resolve it and then move on. But often, when people... As soon as the cortisol comes or whatever, they want to avoid it, and they never get through that. So maybe being in this dream state allowed her to get past the anxiety part of it enough so that her brain was able to process it.
Boris Heifets:
We're thinking along similar lines. So first of all, we followed her for a day, a week, a month, a year. And what is still remarkable to me is she's able to just talk about this attack. No nightmares. Basically, she's functional. She's a functional person who has recovered from trauma.
Chistof Koch:
You're saying, due to a 10-minute dream.
Boris Heifets:
Well, we've done it now about 600 times-
Heather Berlin:
And?
Boris Heifets:
... patients. This is clinical care, this is gentle clinical care, that now we've added an observational study on top of, just seeing what happens when we do this at scale. And the technique isn't perfect. We have somewhere between 60% and 85% hit rate for getting patients to have these vivid dreams. And I can tell you, the things that patients say upon awakening, "This was more real than real. I expected to be somewhere else." Patients are having a very powerful experience.
Heather Berlin:
Very vivid. It's more than just regular dreaming. And do you find that they're less anxious after or less...
Boris Heifets:
Actually, the real clincher, or what was so surprising, is just by chance, two patients that came through the Stanford operating rooms had bonafide PTSD. And in both cases, coincidentally, it was the loss of a child, an adult child, either due to drug overdose or suicide. Again, a horrible thing to live with for years. And as you can imagine, nightmares about trying to save your child, it's really...
We didn't know this before they went to sleep. This all came up in the immediate aftermath. We're putting them into these states for 10 to 15 minutes, they emerge. One of our patients, Mare, and there's a story on the Stanford Med School blog now detailing her experience, she dreamt she re-experienced the birth of her son. Instead of being a traumatic birth, it was joyful. She was reunited with her son and with her family.
And listening... We have a video, also, on my lab website. It still gives me chills, actually, to even listen to, that she says, "Thank you for this." Being able to have that experience. Mare and Edie, the patients who tell us these things, have invigorated a small army of people in the operating rooms, who are now trying... They want to do this. They think-
Heather Berlin:
But then it's transformative. After the fact, then they're less upset about these traumatic events.
Boris Heifets:
She's had nightmares her entire life, especially after this traumatic event. And now what she's telling us, a year later, is that she had not had nightmares.
Heather Berlin:
What this tells me is that however you get to these transformative experiences, whether it's you take MDMA and that allows you to sit with the trauma and work through it and process it, in this drug-induced dream state that allows you to sit with the trauma and process it, or the psychedelic experiences, and even these intense placebo experiences, there is something about the psychological effect of sitting with the anxiety and working through it in however way you can. Psychedelics are a way to get there, but they're not the only way.
Chistof Koch:
This woman, it sounds wonderful, but it's just one of the... You said there's several hundred. Is most patients or 10% or-
Boris Heifets:
Again, we are doing this on the background of providing clinical care. So these patients-
Chistof Koch:
So they all come in again for other types surgeries.
Boris Heifets:
Yeah, they're coming in for thyroid surgeries, plastic surgery, breast biopsies.
Chistof Koch:
But they now always get propofol?
Boris Heifets:
It's a cocktail. But the goal is always the same, is during emergence, we are targeting a state. Whether we use... We've had patients report this with sevoflurane, with propofol, with propofol and remifentanil. Again, this hits at the point it's not the drug.
Heather Berlin:
It's not the drug itself. So that being said though, in terms of what we're starting to learn from the science and from these experiments, is that it's not necessarily the chemical molecule itself that's having the impact on transforming these patients or people who have anxiety and mood disorders. It's the psychological experience that seems to be the most impactful therapeutic here.
Boris Heifets:
And trying to understand what are the bounds, how do we define that? What are the characteristics that need to be present in order for it to be transformative?
Heather Berlin:
At the end of every episode, we ask a Perception Box question. And our question today is, what aspects of yourself are you now grateful for that in the past you struggled with or hated?
Chistof Koch:
I can speak up. I used to stutter as a little child, and I went to logotherapy for six weeks and I just couldn't do, particularly when people were looking at me, like in this scenario. But then I challenged myself and did this on purpose, to get into a situation where I needed to control my language. And I don't know, because it was when I was 9 and 10 and 11, I did the mindfulness training, et cetera. Then I managed to overcome that and use that as a way to learn how to give talks and how to convince people. So I think that this has turned to benefit.
Heather Berlin:
Might've even overcompensated. Sorry.
Chistof Koch:
Thank you.
Heather Berlin:
No, you're not. In jest.
Boris Heifets:
So one of the things... I have a younger brother who's 10 years younger. So for 10 years, I was an only child, and I developed certain... I was very in my own world. And for many years, I would hold ideas and I didn't want to share them until they were perfect, and they would marinate and stew. And one day, during my PhD, something clicked, something clicked being in a lab. And my mentor, Pablo Castillo, really nailed this for me.
In the arguing, the joy of exposing yourself and your ideas, it takes a certain amount of courage or a jump. These are things, my ideas, my dreams, these are things that are really deeply special to me, that I want to hold onto and I want to protect. But what I found very quickly is that by exposing them and talking and really just tearing them apart in a way, some of them didn't survive. And we have this saying in my lab now, that if an idea can survive this room, my office, after talking about it for three hours, there might be something there.
Heather Berlin:
That's the power of discourse, which I think we're losing now a lot of people are... With trigger warnings and safe spaces and whatever.
Chistof Koch:
Yelling.
Heather Berlin:
But to actually be able to have arguments and discourse-
Chistof Koch:
It's also deeply enjoyable to engage in this community of people.
Boris Heifets:
Yeah. Absolutely.
Heather Berlin:
And it shifts your perspective and your ideas. So mine, I think, I don't know if it's more superficial or not. But the first thing that came to my mind is I used to... Being an academic and being a woman, a lot of the time, and this was in the 90s and the early 2000s, just wasn't taken seriously if I was too feminine, wearing makeup, dress, whatever. So I used to dislike my femininity and dress down and not wear makeup. And wear baggy clothes and whatever to be taken seriously at places like Oxford and Harvard and all the...
And there was this unconscious bias and stereotype. And if I would walk in to give a lecture or a keynote, immediately expectations were lower if I was more, let's say, feminized. And so I really tried to hide that aspect of myself. And then as time went on and I got more confident, and I know what I know and I know the science and I had confidence, I didn't have to pretend anymore that I wasn't feminine. And I could wear makeup and dress the way I wanted, whatever, and still be taken seriously, and actually take advantage of those lower expectations. Because if I come in, they're like, "Oh, you're the keynote?" And then they have lower... Rather if someone like Christof comes in, with a German accent, whatever, they're expecting him to say something very intelligent-
Chistof Koch:
And he doesn't.
Heather Berlin:
And then he doesn't, and it's a big disappointment. Whereas I have this great advantage where they have lower expectations and then I can show what I know. So I'm very grateful now for that. But that was a part of myself that I used to try to downplay. And so yeah, that's mine. It's a bit superficial, but I think still meaningful.
Boris Heifets:
That runs pretty deep.
Chistof Koch:
I agree.
Heather Berlin:
Well, I want to thank you, Boris, for being here with us today.
Chistof Koch:
Thank you very much for being with us.
Heather Berlin:
Really, really-
Boris Heifets:
Thank you. Thanks for having me. This is a lot of fun.
Heather Berlin:
... fascinating conversation. So if you'd like to learn more about your own Perception Box, spend some time this week answering the same Perception Box questions that we asked our guest and check out other questions on the website at unlikelycollaborators.com. You could also subscribe to our YouTube channel and watch the show, or listen wherever you get your podcasts. This has been Science of Perception Box, created by Unlikely Collaborators in partnership with Pod People. I'm Dr. Heather Berlin.
Chistof Koch:
And I'm Dr. Christof Koch. Thank you very much.
Psychedelics and the Placebo Effect with Dr. Boris Heifets
Can psychedelics under anesthesia heal trauma? What is the latest research around ketamine, MDMA, and psilocybin? That’s part of what we explore this week on Science of Perception Box. Stanford anesthesiologist Dr. Boris Heifets joins Dr. Heather Berlin and Dr. Christoph Koch to discuss the latest research on the first double-blind study on Ketamine, the placebo effect, and the therapeutic value of anesthesia-induced dreams.
Dr. Boris Heifets, MD, PhD, is a board certified anesthesiologist who specializes in providing anesthesia for neurological surgery. He has practiced at Stanford since 2010. After completing residency training at Stanford, Dr. Heifets completed fellowship training in neuroanesthesiology, also at Stanford. In addition to treating patients, Dr. Heifets directs both clinical research and basic neuroscience. His research group studies how new rapid-acting psychiatric therapies like ketamine, MDMA, and psilocybin produce lasting changes in nervous system function, behavior, and therapeutic outcomes.
Dr. Heather Berlin is a neuroscientist, clinical psychologist, and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
Dr. Christof Koch is Chief Scientist for the Tiny Blue Dot Foundation and the current Meritorious Investigator and former President of the Allen Institute for Brain Science.
Join us for new episodes every Thursday. Follow the show on YouTube, Spotify, Apple Podcasts, Amazon Music, or wherever podcasts are found.
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Boris Heifets:
What if you could take the drug out of the trip? In other words, recreate a psychedelic-like experience without reference to a psychedelic drug itself?
Elizabeth Koch:
Hi, I'm Elizabeth Koch. We all live inside our own personal, private Perception Box, built by our genes and the physical, social, and cultural environment in which we were born and raised. In this podcast, we explore how although the walls of this mental box are always present, they can expand in states like awe, wonder, and curiosity, or contract in response to anxiety, fear, and anger.
I'd like to introduce our esteemed hosts, two incredible and distinguished minds. Dr. Heather Berlin, Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City, and Dr. Christof Koch, Chief Scientist for the Tiny Blue Dot Foundation and the current Meritorious Investigator and former President of the Allen Institute for Brain Science. Welcome to the Science of Perception Box.
Heather Berlin:
Hi, everybody. Welcome to Science of Perception Box. I'm your co-host, Dr. Heather Berlin.
Chistof Koch:
And I'm your co-host, Dr. Christof Koch.
Heather Berlin:
So every week we feature an aspect of the science of Perception Box, highlighting the latest research together with our expert guests. This week we're exploring the powerful research around psychedelics and dream states in the practice of anesthesiology with a researcher and doctor who has been as fascinated about consciousness as we are.
Dr. Boris Heifets is a board-certified anesthesiologist who specializes in providing anesthesia for neurological surgery. He's practiced at Stanford since 2010. In addition to treating patients, Dr. Heifets also directs clinical research and basic neuroscience. His research group studies how new rapid-acting psychiatric therapies like ketamine, MDMA, and psilocybin produce lasting changes in nervous system function, behavior, and therapeutic outcomes. But first, we want to share our own connection to psychedelics. So Christof, how have psychedelics helped you expand your Perception Box?
Chistof Koch:
They made me lose a sense of self. They made me lose my sense of body, of an external world, but there was still consciousness. And they made me lose my fear of death.
Heather Berlin:
Well, that's pretty profound.
Chistof Koch:
Yeah.
Heather Berlin:
So do you think you're a more relaxed person now?
Chistof Koch:
Yes, certainly.
Heather Berlin:
You seem very relaxed. Well, Boris, thanks for joining us.
Boris Heifets:
Thanks for having me.
Heather Berlin:
So how did you become interested in psychedelics as an anesthesiologist?
Boris Heifets:
So I became interested in psychedelics well before I became an anesthesiologist.
Heather Berlin:
Ah, I see.
Boris Heifets:
The question is, how did I become interested in anesthesiology as a psychedelics-
Heather Berlin:
Explorer.
Boris Heifets:
Explorer.
Chistof Koch:
You mean a psychonaut.
Boris Heifets:
Well, I've done some research on the topic before becoming a doctor. When I was towards the end of my PhD training, so I did an MD and a PhD at Einstein in New York, I had this question of, well, how am I going to apply this? What we're doing is we're looking at synaptic responses in brain tissue, we're looking at the inner workings of how circuits function in the brain. And I didn't want to lose that, and I wanted to pick a specialty that would allow me the most access to that kind of thinking and that kind of environment, not to mention this background interest in psychedelics.
I think when I started medical school, my mom told me, "Drop it. You can't have a career studying psychedelics. It's hippie science." This was in 2000, probably good advice. But when it came time to pick a specialty, I was thinking about psychiatry and neurology, neurosurgery, and anesthesiology. And the closest I could get to applied neuroscience was actually anesthesiology. You give a drug and you see its effect on the brain, the body, on consciousness itself. And that, to me, it never gets old.
Chistof Koch:
How do you know their consciousness is gone as compared to they're unable to talk and they're unable to signal that they're still there? How do you know they're not present?
Boris Heifets:
So we have a lot of interviews with patients after surgery that can attest to that. What's remarkable about anesthesia is that it's not like sleep. And when you close your eyes as you are anesthetized for surgery, when you open them, many patients will feel that no time has passed. Which is very different from when you wake up, you kind of have an intuitive sense of how long you may have slept. So that's already one difference just at the level of what the patient experiences.
One of the earliest concerns for anesthesia, as we were developing anesthetic techniques to keep people immobile and pain-free and amnestic during surgery, is there's something called the Brice Questionnaire. What's the last thing you remember before going to sleep? What's the first thing you remember when you wake up? And did you have any dreams during anesthesia? Do you recall anything? And that's basically how we set standards for what depth of anesthesia we use.
Chistof Koch:
How often does it happen that, I guess, depending on the type of anesthesia and the duration, that people do recall something that does relate in some way to something that did happen in the OR?
Boris Heifets:
So it's around one in a 1,000, so awareness under general anesthesia, even with EEG monitors. So we're monitoring brain function, we're getting a sense of the depth, but we're clearly not getting the whole picture because every once in a while a patient will recall something.
Now, I want to put a qualifier on that before nobody ever has surgery again after listening to this podcast. I've seen one case like this, and in an elderly woman, not who I would've expected. Though the thing she said was, "Everything was so far away, everyone was touching me really softly." But she was recalling conversations in the OR. So there's a deep disconnection, but she was able to maintain some sort of input from the real world. So again, that's one in 1,000.
Chistof Koch:
And no pain, right? Because pain is controlled separately.
Boris Heifets:
She didn't complain of pain, she didn't complain... It was a little bit distressing to her because she knew what happened. But she wasn't paralyzed. The thing that I was most worried about is did you feel trapped? And thank God she didn't. And that's, again, advances in anesthesia have allowed us to do surgery without paralysis even, in some cases. So again, that's maybe a topic for another time, but it's a rare complication that we do worry about. And again, that was the early concern of anesthesiologists, is that we want to make sure that consciousness is gone, right? Deep disconnection, disconnected unconsciousness that's reversible at the end of surgery.
Now, in the last 20 years, anesthesia has gotten a lot safer. We've started innovating things like nerve blocks, for example. So now we have a little bit more room to think about how much do I want to sedate this patient? What kind of experience do I want to provide? And that's where things start to get a little bit interesting.
Heather Berlin:
So before we get into the research, can you tell us a little bit about how psychedelics work in the brain and how they can be used as a therapeutic intervention?
Boris Heifets:
Sure. So this is a very hot topic right now. And when we talk about psychedelics, what are we talking about? There's the classic psychedelics: LSD, psilocybin-
Heather Berlin:
The classics.
Boris Heifets:
The classics, the greatest hits. And then there are other drugs that are, I would say, psychedelic adjacent. That a lot of people will identify psychedelic-like properties in these drugs. Drugs like MDMA, which is nearing approval, potentially, for PTSD. Ketamine.
Chistof Koch:
Assisted therapy.
Boris Heifets:
Yes, MDMA assisted therapy, which we're going to return to that point, I hope. And these drugs are not... They don't have the same perceptual effect, but they clearly are acutely psychoactive in a profound way that is very memorable and unmistakable.
And what ties all of these together and what has led to this explosion of research and excitement is that when you provide a space for people to have a powerful psychoactive drug in a safe setting, and just let their mind wander, things come out. If you have PTSD, if you have painful memories, if there are things that you haven't been able to resolve in your life, what people talk about is getting a new perspective.
Whether it be like, "What is going on in my body? Where is this pain coming from?" Or, "Who is this person who's always depressed and pessimistic?" This perspective shift is something that people across these drug classes will talk about. And to me, that's what defines this broad class. They're acutely psychoactive, powerfully so. Their effects are rapid. That perspective shift or however you want to call it, it's rapid.
Chistof Koch:
Change in the Perception Box.
Boris Heifets:
You can put it that way as well. And finally, the effects are durable. This is very different from modern mental healthcare. You don't take these drugs every day. Long after the ketamine or the MDMA or the psilocybin has cleared your bloodstream, you are still feeling those positive effects. This is a sea change in how therapy is delivered. And I want to emphasize again, it is far more complex than just giving someone a drug, putting them in a room while they happen to have their experience.
Heather Berlin:
So it's the synergistic effect between the actual, physical effects of the drug in the brains and this psychological effect or impact.
Boris Heifets:
Well, I would challenge that. I think that's actually one of the biggest debates right now. And it has implications; is it the drug or the trip that's responsible for these therapeutic benefits and the-
Heather Berlin:
Right. Because you get the same benefits without-
Chistof Koch:
Assuming that conceptually, A and B, empirically, experimentally, you can separate those two.
Boris Heifets:
That's exactly it. Right. That's why there's the debate, is right now all we're looking at is correlation.
Chistof Koch:
And so tell us more about this debate.
Boris Heifets:
It boils down to this, is you can think of... The complexity of psychotherapy, you can simplify into three basic stages. There's preparation, which involves setting expectations, building rapport. There's the drug experience itself, a possibly eight hour extravaganza sometimes.
Chistof Koch:
24 hours [inaudible 00:11:37].
Boris Heifets:
Or 48. It depends. The dose is everything. And then there's the integration. Making sense of what happens and trying to incorporate those changes into your life.
Chistof Koch:
Which can take weeks, right?
Boris Heifets:
And in trials, that's how long it takes, is that you have weeks of after-therapy. So the inclination, based on decades of experience in pharma is, well, it's got to be that little crystalline entity in the middle of all of this that's driving these effects. But in reality, as you pointed out, you cannot possibly attribute to one factor the therapeutic change, unless you can independently manipulate them. And this is where the science comes in. I'm going to put in a brief plug for why any of this matters. There are people who believe, not without cause, that it's enough that it works. Why get so bent out of shape about how it works? It's just enough that it does work.
And I would answer to that, is one thing that anesthesia has brought me in contact with is some of the most advanced medicine on Earth. And when I see... One of the most magical moments in residency, and I don't mean to gross you out, but watching a transplanted heart get put into someone's chest, fibrillate, and then convert to sinus rhythm. It's like watching birth or the Earth being born or a total eclipse. It was just awe-inspiring. How did we get from someone living for 50 hours in the '60s, after a heart transplant, to 80% at 5 years? This is amazing. It's by understanding the risk and understanding the mechanism.
Chistof Koch:
The mechanism. I mean science, this is how science works.
Boris Heifets:
And so that, to me, is the question. If a therapy is truly potent, by definition it carries risk, right? And when you think about the early days of chemotherapy, chemotherapy in 1975 was almost a death sentence in itself. 30 years later, you have the first rationally designed kinase inhibitor. That blew my mind in 1999. Gleevec, that cured leukemia.
And again, you take something that has... It's a powerful... Chemotherapy was powerful and crude. And we learned something and innovated and distilled it down to something highly effective and targeted. I'm not sure that CNS... That psychedelics are going to go that way, but there's a pretty strong track record in every other field of medicine for this approach.
Chistof Koch:
There are also strong motives in the industry to pursue that because that's what the entire medical system is based on. You give one little therapeutic intervention that the FDA approves, that you can then sell to everyone, that works. But in this case, because this is the most complex... You're talking to the most complex piece of active matter in the known universe. And I seriously doubt, having studied my entire life, that any one drug will be a magic bullet that cures whatever existential problems that brain or that mind has.
Boris Heifets:
I'm going to turn that on its head in that I completely agree with you. But how do you, without demonstrating the centrality of... My overall, overwhelming sense from all the work I've done is that we need to center the experience.
Heather Berlin:
My biggest question is whether it's the molecule itself-
Chistof Koch:
Or the experience, or both.
Heather Berlin:
... or you need the psychological experience. And can you isolate the psychological experience so they don't have to even take the drug? Are there other ways to get to that transformative experience?
Boris Heifets:
Yeah. That's what we're trying to develop, is that psychedelics pose really fundamental challenges for randomized controlled trials. Let's start with that for a second.
Heather Berlin:
Right, because you know you're on the drug once you're on it. It's very-
Chistof Koch:
And so why would that be a complication?
Boris Heifets:
So it introduces all kinds of biases. The randomized, placebo-controlled trial was designed for antibiotics and blood pressure medication.
Heather Berlin:
But the power of not knowing whether you're on the drug or not is really to get around the placebo effect thing. There's a certain amount of impact that the drug can have. Just thinking you've taken the drug, that can have an effect. And so-
Chistof Koch:
But probably not for TB, right? That's the logic behind it.
Boris Heifets:
Yeah. There are some things where placebo effect... We should be so lucky to have a cancer placebo effect, right?
Heather Berlin:
Right.
Boris Heifets:
People do not often spontaneously remit just on the strength of their belief, although there are all kinds of stories. But it's important, because think about it from a patient's point of view. You have read Michael Pollan's book, you are fascinated at the potential of psilocybin, you have out-competed 1,000 other applicants to be in the study on depression. You have already won a lottery, right? Now you go into the finale.
Chistof Koch:
And you've already failed two other trials, right?
Boris Heifets:
You've already failed two other trials, and, like, "I think this is going to be it." And so you have an expectation. It's obvious that if I get the drug, I'm likely to improve, because look at what all of these smart people say. And now comes the moment of truth. Your boyfriend, your girlfriend drives you, maybe you fight about it because you've been so persistent in your pursuit. You go through a lot of trouble to get to that room, to that therapist's room. And then you take the drug, and an hour later there's either a moment of confirmation and acceptance and being seen and being in an elite group of people on Earth who've been in a psilocybin trial. Or a moment of betrayal, where why did I spend all of this effort to be in the placebo group?
Chistof Koch:
Because nothing happens to your mind.
Boris Heifets:
Because it's obvious. It's such an obvious psychoactive effect. It's like winning the lottery. What is the effect of winning the lottery? And you tell me, what does that have to do with depression? I guess winning the lottery could be a short-term antidepressant. But that's sort of the heart of it.
Chistof Koch:
So because they've been told and they read that these are wonderful drugs, they were less likely to be depressed afterwards. That's what you're saying. That's what the placebo effect is.
Boris Heifets:
Exactly.
Heather Berlin:
But because they know if they're on the placebo or not, with psychedelics, it's very hard to control for that. So do you have a way that you're trying to get around this?
Boris Heifets:
So again, that's one of the biggest problems facing psychedelic medicine, is identifying a drug-specific effect. It requires some innovative solutions. I want to talk about a couple. One is efforts by David Olson and Bryan Roth, two great chemists, and many others who are re-engineering the molecule itself. They're basically trying to take the trip out of the drug.
Heather Berlin:
Christof's thinking, "That's no fun. Where's the fun in that?"
Boris Heifets:
I already know it.
Chistof Koch:
They want to take the fun out of everything.
Heather Berlin:
I mean, I can read your mind.
Boris Heifets:
This is the science. That, to me, it's crucial, right?
Chistof Koch:
Yes, I agree.
Boris Heifets:
You have to test. How can you not?
Chistof Koch:
Assuming you can do that.
Boris Heifets:
Let's just say for a minute, it's possible, you will get some answer there, is can you just encode resilience biochemically without anybody noticing?
Heather Berlin:
What about giving the psychedelic while somebody is under anesthesia? And they have no experience-
Boris Heifets:
Well, Heather, that happens to be what we did.
Chistof Koch:
Happy that you asked.
Boris Heifets:
I'm so glad you asked. So it requires a lot of different approaches, and this is the one we took. Now, I'm an anesthesiologist. And one, it's hard to escape the idea that you have all these people that come in from all walks of life, many with preexisting depression, PTSD. That's usually not what we're focused on. We're usually focused on getting them through surgery.
And we saw this as an opportunity, is that patients, they're put under general anesthesia, and while they're anesthetized, there's no there there. They're not there for it, right? That's the goal. So what if we gave a psychedelic class drug, like ketamine, during anesthesia?
So it's important to know that this is on a background of general anesthesia, not using ketamine as an anesthetic. We're using drugs like propofol, drugs like sevoflurane. These are standard anesthetic cocktails. And we're getting everyone to pretty even, cruising depth of anesthesia before we give them either ketamine or a placebo.
Chistof Koch:
So they're deep. So if you do a surgical cut, they don't-
Boris Heifets:
That's the goal. They're there for surgery. Now, part of how we were easily able to get approval for this is that ketamine is an anesthetic. It's an anesthetic adjunct. In patients for whom there's what we would call equipoise about, ketamine is kind of... You don't need to give it. There's nothing in the case that screams out, "This patient should definitely get ketamine." We are able to do this trial.
And we ran it like a psychiatry trial. And this is with actual psychiatrists, like Laura Hack and Alan Schatzberg, who helped quite a bit on this study. But we ran a psychiatry trial in the operating room, and they give half a milligram per kilogram over 40 minutes to minimize the psychoactive effects.
Chistof Koch:
But in a regular, awake person, there would be strong psychoactive with his dose, right?
Boris Heifets:
Yes. And that's what we've seen. We've done other... Worked on a trial with Nolan Williams where we're giving ketamine to awake patients.
Chistof Koch:
At this dose?
Boris Heifets:
At this dose. And patients, they'll have what's called... They'll dissociate. They'll get into a dreamy state. They might hallucinate. If you listen to what they say, there is a lot of overlap with psychedelic-like effects. And let's put that on pause for a minute, but that's the trip of ketamine, that we're actually trying to see do you need that in order to benefit from ketamine?
Heather Berlin:
So now you give them this dose, which normally, in a wakeful person, they would have a psychedelic effect, but they're under anesthesia. And you have it placebo controlled, meaning you're going to give them another substance that's not ketamine, or you just give them no ketamine?
Boris Heifets:
We just give them normal saline, a fluid with the same volume. And I guarantee you the patients were not aware. Everyone was blinded in the study.
Heather Berlin:
So they wake up, and what's the measurement? What do you assess?
Boris Heifets:
So again, we want to copy what's been done before. We're not reinventing anything. We're using a standard scale of depression called the Montgomery-Asberg Depression Rating Scale. It's a clinician rated scale. If, let's say, you're my patient, I'll ask you questions. "Tell me about your fatigue levels." Or, "How's your appetite?" And there's kind of standard degrees of-
Heather Berlin:
Of severity, but you're expecting there to be an effect right away, right after the surgery.
Boris Heifets:
That's the beauty of ketamine.
Heather Berlin:
SSRIs, you give a patient, and maybe six weeks later they say you'll feel something maybe. And it's very hard to make the connection between the drug and the impact. But with ketamine, they give it in the psych ER, and it really can knock out suicidality.
Boris Heifets:
And there's a nuance to everything, but essentially, yes. That's the design of this therapy, is that it's rapid acting antidepressant.
Heather Berlin:
So you give them this measure of depression right when they come out of surgery. You don't know who's had it and who hasn't.
Boris Heifets:
So we waited a day. There is a lot of things that happen right after surgery. But again, we're copying other studies where you have... The peak effect, the peak antidepressant effect of ketamine is one to three days after infusion, long after the drug is gone, which is where we started this description. And that's where we're taking our primary measure, is looking at depression scores in the one to three days post-infusion, post-surgery.
Heather Berlin:
And what you found was?
Boris Heifets:
Well, all of the patients who got ketamine did great. 50% response, 30% remission from patients, many of whom had treatment-resistant depression.
Chistof Koch:
Now what about the other patients?
Boris Heifets:
Well, so the placebo group also did great. 50% response, 30% remission.
Chistof Koch:
So it's remarkable. So you think whether or not they got the ketamine, both-
Boris Heifets:
Both groups, on average, showed the same degree of improvement. You could not separate them. The key here is that both were massive, massive improvements. And there's a couple of fine points here because I got a lot of... Wasn't exactly fan mail about the study. But people who looked at the study say, "Are you saying ketamine doesn't work?"
And there are a couple points to bring out about this. And the first point is what was the patient experience like? And you'll see how this is important in a minute, I think. And again, keep in mind this very large placebo effect that we saw, that we were absolutely not expecting.
From a patient, let's say you're coming in for surgery, for 20 years you've been dealing with a lot of trauma, the holdovers from a rough childhood, et cetera. And now you go see your surgeon, and do you think your surgeon is going to ask you about your mood? We can venture a guess to say usually not. It's the rare surgeon that has time, because there are other priorities.
So from your point of view, you're getting something in your email saying, "We care about your mental health and recovery after surgery. Would you be willing to fill out the survey and talk to us?" That's our first contact with the patient a few weeks before surgery.
Then you come in, you get a consent. It's about an hour long, where you hear all about the study. "Ketamine, we think it's an antidepressant in other circumstances. We're wondering whether this has therapeutic value during surgery." Now you come in for a two-hour interview with four of us. A nurse, myself, a research coordinator-
Chistof Koch:
Two hours interview, just as part of the work of this study?
Boris Heifets:
Yes, we want to know everything. And from a patient's-
Heather Berlin:
So you're sort of priming. First of all, they're getting more attention, you're talking about their mood. And you're priming them to this drug might really help your depression.
Boris Heifets:
Exactly. And there have been studies of depression during surgery before, and I don't think they went all out like this. We were looking for a particular type of patient. I was so happy to get each one of them, each of these 40. We learned a lot about all of them. And so two hours where we heard about their trauma, their mental health history, their physical history.
And then the morning of surgery, again, I wanted to make sure things go off without a hitch. In many cases, I held their hands as they went off to sleep. These patients were precious to me. And I was not at all thinking at the time, "My God, what kind of placebo effect I'm engendering?"
And let me stop there for a second. Why was I so blithely unaware of the possibility that we might induce this massive placebo effect? It's because the broader context is surgical anesthesia. Surgery and anesthesia are associated with a higher risk of heart attack, stroke, cognitive dysfunction, kidney injury, lung injury. Actually, all of our literature points to all these things getting worse after surgery.
Heather Berlin:
Nice.
Boris Heifets:
And putting people at risk for opioid use disorder. So that's what I came in with. I was not thinking that placebo would be a problem or that this study would even be about placebo.
Chistof Koch:
So the placebo was really a surprise to you.
Boris Heifets:
It was a big surprise.
Heather Berlin:
This is my question: what is the takeaway here? Is the takeaway that for the effects of ketamine, you don't need the psychedelic effects of ketamine for there to be an improvement?
Boris Heifets:
The takeaway is this: it's in the placebo effect. We can't say much about ketamine in this trial, but what I think we can say something about is all of the trials going on in the psychedelic space. Again, I've painted that picture for you of winning the clinical trial lottery and going through that process and all the confirmation bias that might go along with it. There are a lot of non-drug factors there. So inadvertently, just the structure of this trial, with preparation, a big central event, surgery and anesthesia, and then close follow-up in the aftermath, we had replicated a lot of the key elements of most psychedelic studies and driven a placebo effect that is enormous.
Heather Berlin:
Well, I think in some ways this is really good news. First of all, well, where is this published, this paper?
Boris Heifets:
Nature Mental Health.
Heather Berlin:
So I think everybody should take a look at the paper. But it's a warning to say, "Look, we really need to structure these psychedelic studies in a different way." However, it's really positive to say that, for instance-
Chistof Koch:
Your mind can change your body.
Heather Berlin:
Yes. So we don't need the drugs.
Boris Heifets:
We need something. These patients went through something. I think that's a key part of this.
Heather Berlin:
An experience though. It was an experience.
Chistof Koch:
Yeah, but they need this belief. If they don't have this belief... So you have to tell them that this thing is magical, whether it's a ceremony or a dance or beauty or molecule.
Boris Heifets:
But it's got to be... You can't just tell them. You need good placebo. We had really good placebo. We had the best placebo.
Chistof Koch:
Tell me, what about the... Does the belief that the patient... Because you must have asked the patient, "Did you think you got it or did you think you were in the placebo?" And how does that effect?
Boris Heifets:
So as I said, we weren't expecting this massive placebo effect. And this was in... We started the study in 2019, before a lot of the writing about expectancy had come up. So we didn't ask people until the very end of the study, "Which group did you think you were in?" I will say, this is one of the only, maybe the only, truly blinded study of a psychedelic class drug, so that was a small victory. But when we asked them what they thought they got, nobody knew, first of all. But in talking to them, in my conversations with these patients, if they got better, they attribute it to the ketamine. They said, "Well, I must've been in the ketamine group because I feel better." Which suggests that they had some prior belief. You wouldn't say that you got ketamine unless you believe the ketamine is therapeutic.
Chistof Koch:
But did the people... Surely there must have been some people who believed it, or maybe not, that believed they were on the placebo.
Boris Heifets:
And those are the... Yeah, because they didn't get better. They didn't get better. And they're like, "Well, I must've been in the placebo group." So what that shows, if anything, is that we did a job, unwittingly or not, a good job of instilling a sense of hope that this has the potential for therapeutic benefit.
Chistof Koch:
And I think that's how you conclude in the last paragraph of the paper. This is called [inaudible 00:29:30], the short name of this is hope?
Boris Heifets:
Yes. So there is a dangerous side to this. Not dangerous, but we can draw some of the wrong conclusions from this work. One is that the convention... Placebo is an old word, and it literally means I please.
Chistof Koch:
To please.
Boris Heifets:
Right. So one of the awkward things is if someone gets better after getting placebo, and then you tell them they got placebo, it's more than a little awkward. They're like, "Well, all that stuff I said, well... In the throws of placebo, was that all... It wasn't real." People need to feel seen, need to feel heard. And that idea that placebo is just something that you trick children with, we have to dispense with that idea.
Heather Berlin:
No, I think we need to harness the placebo. I've always said this, harness the placebo effect and use it in medicine.
Chistof Koch:
It's your mind. Yes.
Heather Berlin:
Exploit the placebo effect.
Boris Heifets:
Well, and good doctors do it-
Heather Berlin:
Yes.
Boris Heifets:
... in psychedelic therapy.
Chistof Koch:
That's why you have white coats, that's why you have Dr. Boris Heifets. Well, because if I believe you, just like a shaman, if I believe you are the shaman, then I'm more likely to-
Boris Heifets:
That has to be part of it. And there has to be a strong experience at the center. I had a bar mitzvah when I was 13. My father said, "Today, my son, you're a man." And I can tell you, my voice did not drop, but I felt different. People looked at me differently, they treated me differently. And how does that happen? It's not a person in isolation. It's certainly not a drug effect. It's a door that you walk through that is held up by the collective understanding of the community that surrounds it. And that is a very devilishly hard thing to study with conventional scientific methods.
Heather Berlin:
A lot of it is the power of suggestion. If they come in and they're depressed and they're low, "I'm never going to meet anybody. I'm never going to find anyone." You give them this hope. And they believe you because you have all these credentials and stuff, rather than me just giving my friend some good advice. They take your, "I really feel like you're going to meet someone. I trust that..." And then they start to believe it because someone in a authority position gives them that hope.
It's not about the SSRI they're taking. But studies do show, in conjunction, you get some powerful effects from the SSRI, some from therapy. When they work together, you get this synergistic effect. But I want to just talk about... Because I know there's other research you do, in terms of dreams and inducing dreamlike states with anesthesia, that I really want to-
Boris Heifets:
So going with this theme of experience. In this study that we're just wrapping up, the experience, they all went through something. It's not the experience on drug, but it's the larger experience of being in the study and going through a door, right? Having surgery and coming through the other side.
Chistof Koch:
Any therapy afterwards?
Boris Heifets:
No. Like every other ketamine study, which included no therapy.
Chistof Koch:
And how long did you...
Boris Heifets:
Two weeks.
Chistof Koch:
And so you didn't track... Are these people still...
Boris Heifets:
Not formally. I kept up with some of them. And some of the stories, I'd love to share some of them. It really made me question whether I should be in science or not when I couldn't tell is this woman in the ketamine group? Because how do you get that kind of transformation without something to account for it? Of course, she's in the placebo group.
So there's another way to look at this. Coming back to this theme of preparation and the drug, the day of the dosing, the drug and the trip, and then integration, and really focusing on the drug and the trip. Which you could either take the trip out of the drug, and we've now talked about a couple ways to do that, what if you could take the drug out of the trip? In other words, recreate a psychedelic-like experience without reference to a psychedelic drug itself? That would be a pretty interesting way to test this idea of how special is the serotonin 2A receptor. And there's just some very exciting research.
Heather Berlin:
But now we're talking about how do you create-
Boris Heifets:
Well, how do you regenerate... Exactly.
Heather Berlin:
... hallucinations without the psychedelic?
Boris Heifets:
So wouldn't it be an interesting test if we could induce a psychedelic-like state without a psychedelic, and get some of the same physiology, descriptions of experience, and therapeutic effects? Would that maybe turn on its head the idea that there is a powder at the center of all of these therapeutic effects? And that's, almost by accident, what we've stumbled upon working with anesthesia and dreams.
And I have a colleague, Harrison Chow. He's, I was going to say, an artist. He's an anesthesiologist, but this is the art of medicine. He spent many years in private practice, minor procedures. Patients would come in for hernias or endoscopies, minor stuff, and he would try and make the experience as pleasant as possible.
And he would do this thing where he would watch the EEG monitor and to look for what he thought was dreaming. And then patients would wake up and say, "I had the best dream, I had the best sleep I've ever had." But as you emerge, one of the things that you can notice if you really pay close attention to the EEG, this is brain state monitoring.
Heather Berlin:
So you're watching them as they come them out of anesthesia, and the waves start speeding up and they're getting higher frequency.
Boris Heifets:
Yeah. So when he came to Stanford, my chair put him together with me because he knew I was a psychonaut drug nerd, into non-ordinary states of consciousness, and, "You two should talk to each other and maybe figure something out." It was a great, great partnership. Harrison is really into the idea of making anesthesia more pleasant.
I'm a little bit more scientific, and I was very skeptical at first. So we agreed we're going to get a portable EEG, a SedLine, a couple leads. We have a team, it includes a psychiatrist. We are going to do interviews, diagnostic interviews, and we're going to follow these patients. I want to know, is what you're saying... Are you bullshitting me or is this real? Is there something there?
And not long after, we had our first case. And this is the case of a woman, this was published 2022, where this woman, she had been attacked at close quarters by a relative with a knife. Horrifying. As you might imagine, she'd had nightmares, right? She went to the emergency room and they said, "Go to Stanford, get your hand fixed." And in the intervening time-
Chistof Koch:
The hand got injured-
Boris Heifets:
Yeah, exactly.
Chistof Koch:
... defending herself. So the surgery was to help with her-
Boris Heifets:
Yes. The surgery was for her hand. In the intervening two weeks, she is basically a non-functional human, right? She is hypervigilant, she's having difficulty-
Chistof Koch:
Well, it's PTSD. She has severe-
Boris Heifets:
So due to the timeframe, we call it acute stress disorder, but this is somebody who would... More likely than not, we would be worried she would go on to develop PTSD. So she's in the pre-op area, she's there for her hand, and Harrison finds her. Again, still... That's all she can talk about, and she's really hard to reach. And again, talking about innovations in anesthesia, they put her arm to sleep, she gets a nerve block, and Harrison does his dream thing.
Chistof Koch:
Wait, so is her arm anesthetized, but she is still-
Boris Heifets:
Yeah, her arm was anesthetized. So she doesn't need to be so deeply anesthetized that she can't feel.
Heather Berlin:
When you say this dream thing, it's just that you're controlling the amount of propofol-
Boris Heifets:
And watching the EEG.
Heather Berlin:
... and watching the EEG, and getting her into this sweet spot where he knows that the dreams occur.
Boris Heifets:
Yeah.
Chistof Koch:
How long is this state of dreaming in this patient?
Boris Heifets:
About 10 minutes.
Chistof Koch:
Oh, very brief.
Boris Heifets:
Relatively brief, but there's a lifetime in 10 minutes. So what she says immediately upon waking is, "The nightmare, it was there again. I had the nightmare again, and it was looping just like it always does." But instead of rocketing her into consciousness, which is what a nightmare is, by virtue of this anesthetic suppression, she stays in that state and she actually, in her dream, moves past the attack. She, in her dream, goes to the emergency room, goes to the operating room. She's back home, running errands, with her hand healed.
Chistof Koch:
All in this 10 minutes?
Boris Heifets:
All in 10 minutes. A lifetime in 10 minutes.
Heather Berlin:
Just to go back for a second, just because in terms of therapy, often I'm working with patients who've had trauma. And the idea is to help them work through the emotions, is to sit with the thing that makes them anxious or uncomfortable long enough-
Chistof Koch:
Exposure.
Heather Berlin:
Yeah. Exposure long enough to get through it and resolve it and then move on. But often, when people... As soon as the cortisol comes or whatever, they want to avoid it, and they never get through that. So maybe being in this dream state allowed her to get past the anxiety part of it enough so that her brain was able to process it.
Boris Heifets:
We're thinking along similar lines. So first of all, we followed her for a day, a week, a month, a year. And what is still remarkable to me is she's able to just talk about this attack. No nightmares. Basically, she's functional. She's a functional person who has recovered from trauma.
Chistof Koch:
You're saying, due to a 10-minute dream.
Boris Heifets:
Well, we've done it now about 600 times-
Heather Berlin:
And?
Boris Heifets:
... patients. This is clinical care, this is gentle clinical care, that now we've added an observational study on top of, just seeing what happens when we do this at scale. And the technique isn't perfect. We have somewhere between 60% and 85% hit rate for getting patients to have these vivid dreams. And I can tell you, the things that patients say upon awakening, "This was more real than real. I expected to be somewhere else." Patients are having a very powerful experience.
Heather Berlin:
Very vivid. It's more than just regular dreaming. And do you find that they're less anxious after or less...
Boris Heifets:
Actually, the real clincher, or what was so surprising, is just by chance, two patients that came through the Stanford operating rooms had bonafide PTSD. And in both cases, coincidentally, it was the loss of a child, an adult child, either due to drug overdose or suicide. Again, a horrible thing to live with for years. And as you can imagine, nightmares about trying to save your child, it's really...
We didn't know this before they went to sleep. This all came up in the immediate aftermath. We're putting them into these states for 10 to 15 minutes, they emerge. One of our patients, Mare, and there's a story on the Stanford Med School blog now detailing her experience, she dreamt she re-experienced the birth of her son. Instead of being a traumatic birth, it was joyful. She was reunited with her son and with her family.
And listening... We have a video, also, on my lab website. It still gives me chills, actually, to even listen to, that she says, "Thank you for this." Being able to have that experience. Mare and Edie, the patients who tell us these things, have invigorated a small army of people in the operating rooms, who are now trying... They want to do this. They think-
Heather Berlin:
But then it's transformative. After the fact, then they're less upset about these traumatic events.
Boris Heifets:
She's had nightmares her entire life, especially after this traumatic event. And now what she's telling us, a year later, is that she had not had nightmares.
Heather Berlin:
What this tells me is that however you get to these transformative experiences, whether it's you take MDMA and that allows you to sit with the trauma and work through it and process it, in this drug-induced dream state that allows you to sit with the trauma and process it, or the psychedelic experiences, and even these intense placebo experiences, there is something about the psychological effect of sitting with the anxiety and working through it in however way you can. Psychedelics are a way to get there, but they're not the only way.
Chistof Koch:
This woman, it sounds wonderful, but it's just one of the... You said there's several hundred. Is most patients or 10% or-
Boris Heifets:
Again, we are doing this on the background of providing clinical care. So these patients-
Chistof Koch:
So they all come in again for other types surgeries.
Boris Heifets:
Yeah, they're coming in for thyroid surgeries, plastic surgery, breast biopsies.
Chistof Koch:
But they now always get propofol?
Boris Heifets:
It's a cocktail. But the goal is always the same, is during emergence, we are targeting a state. Whether we use... We've had patients report this with sevoflurane, with propofol, with propofol and remifentanil. Again, this hits at the point it's not the drug.
Heather Berlin:
It's not the drug itself. So that being said though, in terms of what we're starting to learn from the science and from these experiments, is that it's not necessarily the chemical molecule itself that's having the impact on transforming these patients or people who have anxiety and mood disorders. It's the psychological experience that seems to be the most impactful therapeutic here.
Boris Heifets:
And trying to understand what are the bounds, how do we define that? What are the characteristics that need to be present in order for it to be transformative?
Heather Berlin:
At the end of every episode, we ask a Perception Box question. And our question today is, what aspects of yourself are you now grateful for that in the past you struggled with or hated?
Chistof Koch:
I can speak up. I used to stutter as a little child, and I went to logotherapy for six weeks and I just couldn't do, particularly when people were looking at me, like in this scenario. But then I challenged myself and did this on purpose, to get into a situation where I needed to control my language. And I don't know, because it was when I was 9 and 10 and 11, I did the mindfulness training, et cetera. Then I managed to overcome that and use that as a way to learn how to give talks and how to convince people. So I think that this has turned to benefit.
Heather Berlin:
Might've even overcompensated. Sorry.
Chistof Koch:
Thank you.
Heather Berlin:
No, you're not. In jest.
Boris Heifets:
So one of the things... I have a younger brother who's 10 years younger. So for 10 years, I was an only child, and I developed certain... I was very in my own world. And for many years, I would hold ideas and I didn't want to share them until they were perfect, and they would marinate and stew. And one day, during my PhD, something clicked, something clicked being in a lab. And my mentor, Pablo Castillo, really nailed this for me.
In the arguing, the joy of exposing yourself and your ideas, it takes a certain amount of courage or a jump. These are things, my ideas, my dreams, these are things that are really deeply special to me, that I want to hold onto and I want to protect. But what I found very quickly is that by exposing them and talking and really just tearing them apart in a way, some of them didn't survive. And we have this saying in my lab now, that if an idea can survive this room, my office, after talking about it for three hours, there might be something there.
Heather Berlin:
That's the power of discourse, which I think we're losing now a lot of people are... With trigger warnings and safe spaces and whatever.
Chistof Koch:
Yelling.
Heather Berlin:
But to actually be able to have arguments and discourse-
Chistof Koch:
It's also deeply enjoyable to engage in this community of people.
Boris Heifets:
Yeah. Absolutely.
Heather Berlin:
And it shifts your perspective and your ideas. So mine, I think, I don't know if it's more superficial or not. But the first thing that came to my mind is I used to... Being an academic and being a woman, a lot of the time, and this was in the 90s and the early 2000s, just wasn't taken seriously if I was too feminine, wearing makeup, dress, whatever. So I used to dislike my femininity and dress down and not wear makeup. And wear baggy clothes and whatever to be taken seriously at places like Oxford and Harvard and all the...
And there was this unconscious bias and stereotype. And if I would walk in to give a lecture or a keynote, immediately expectations were lower if I was more, let's say, feminized. And so I really tried to hide that aspect of myself. And then as time went on and I got more confident, and I know what I know and I know the science and I had confidence, I didn't have to pretend anymore that I wasn't feminine. And I could wear makeup and dress the way I wanted, whatever, and still be taken seriously, and actually take advantage of those lower expectations. Because if I come in, they're like, "Oh, you're the keynote?" And then they have lower... Rather if someone like Christof comes in, with a German accent, whatever, they're expecting him to say something very intelligent-
Chistof Koch:
And he doesn't.
Heather Berlin:
And then he doesn't, and it's a big disappointment. Whereas I have this great advantage where they have lower expectations and then I can show what I know. So I'm very grateful now for that. But that was a part of myself that I used to try to downplay. And so yeah, that's mine. It's a bit superficial, but I think still meaningful.
Boris Heifets:
That runs pretty deep.
Chistof Koch:
I agree.
Heather Berlin:
Well, I want to thank you, Boris, for being here with us today.
Chistof Koch:
Thank you very much for being with us.
Heather Berlin:
Really, really-
Boris Heifets:
Thank you. Thanks for having me. This is a lot of fun.
Heather Berlin:
... fascinating conversation. So if you'd like to learn more about your own Perception Box, spend some time this week answering the same Perception Box questions that we asked our guest and check out other questions on the website at unlikelycollaborators.com. You could also subscribe to our YouTube channel and watch the show, or listen wherever you get your podcasts. This has been Science of Perception Box, created by Unlikely Collaborators in partnership with Pod People. I'm Dr. Heather Berlin.
Chistof Koch:
And I'm Dr. Christof Koch. Thank you very much.
Can psychedelics under anesthesia heal trauma? What is the latest research around ketamine, MDMA, and psilocybin? That’s part of what we explore this week on Science of Perception Box. Stanford anesthesiologist Dr. Boris Heifets joins Dr. Heather Berlin and Dr. Christoph Koch to discuss the latest research on the first double-blind study on Ketamine, the placebo effect, and the therapeutic value of anesthesia-induced dreams.
Dr. Boris Heifets, MD, PhD, is a board certified anesthesiologist who specializes in providing anesthesia for neurological surgery. He has practiced at Stanford since 2010. After completing residency training at Stanford, Dr. Heifets completed fellowship training in neuroanesthesiology, also at Stanford. In addition to treating patients, Dr. Heifets directs both clinical research and basic neuroscience. His research group studies how new rapid-acting psychiatric therapies like ketamine, MDMA, and psilocybin produce lasting changes in nervous system function, behavior, and therapeutic outcomes.
Dr. Heather Berlin is a neuroscientist, clinical psychologist, and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
Dr. Christof Koch is Chief Scientist for the Tiny Blue Dot Foundation and the current Meritorious Investigator and former President of the Allen Institute for Brain Science.
Join us for new episodes every Thursday. Follow the show on YouTube, Spotify, Apple Podcasts, Amazon Music, or wherever podcasts are found.
Love the show? Write us a review on your podcast app, or tell a friend about the show.
Ever wonder why time seems to fly or crawl? From ancient philosophers to modern neuroscientists, the nature of time has captivated human curiosity. This week on Science of Perception Box, we investigate the relationships among time, memory, and perception. Dr. Davachi shares the mechanisms of how the brain encodes and retrieves memories, including why emotions and feelings play a role in our perception of time.
Lila Davachi is a prominent neuroscientist known for her research in the field of memory. She earned her PhD from Yale University in 1999 and currently holds a faculty position at Columbia University, where she leads the Davachi Memory Lab. Her work primarily focuses on understanding the processes of memory encoding, consolidation, and retrieval through behavioral and cognitive neuroscientific methods.
Dr. Davachi has made significant contributions to the understanding of how memories are formed and maintained in the brain. She has published extensively in academic journals, with her research being highly cited within the scientific community. In addition to her research, she is actively involved in teaching and mentoring students in psychology and neuroscience.
Dr. Heather Berlin is a neuroscientist, clinical psychologist and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
Dr. Christof Koch is Chief Scientist for the Tiny Blue Dot Foundation as well as the current Meritorious Investigator and Former President of the Allen Institute for Brain Science.
Join us for new episodes every Thursday. Follow the show on YouTube, Spotify, Apple Podcasts, Amazon Music or wherever podcasts are found.
Love the show? Write us a review on your podcast app or tell a friend about the show.
When was the last time you felt absolutely mesmerized by something beautiful? Whether it’s seeing a breathtaking vista, losing yourself in a piece of music, or being in a crowd cheering for the same team, the feeling of awe can be all-encompassing and expansive. This week on Science of Perception Box, Dr. Dacher Keltner, one of the world’s foremost emotion scientists and a scientific advisor behind Pixar’s Inside Out, shares how we can cultivate more awe in our life and why we need this sometimes overlooked emotion.
Dr. Keltner is a professor of psychology at UC Berkeley and the faculty director of the Greater Good Science Center. He has over 200 scientific publications and six books, including Born to Be Good, The Compassionate Instinct, and The Power Paradox. Dr. Keltner is involved with the education of health care providers and judges and has consulted extensively for Google, Apple, and Pinterest on issues related to emotion and well-being.
Dr. Heather Berlin is a neuroscientist, clinical psychologist and Professor of Psychiatry and Neuroscience at the Icahn School Of Medicine at Mount Sinai in New York City.
Dr. Christof Koch is Chief Scientist for The Tiny Blue Dot Foundation as well as the current Meritorious investigator and Former President of the Allen Institute For Brain Science.
Join us for new episodes every Wednesday. Follow the show on YouTube, Spotify, Apple Podcasts, Amazon Music or wherever podcasts are found.
Love the show? Write us a review on your podcast app or tell a friend about the show.
How can parents embrace science in order to give their children the best possible environment to thrive in? Cognitive development expert Dr. Alison Gopnik joins us to discuss how navigating challenges fosters healthier adults, likening caregiving to being a gardener creating an environment where various ”plants” can thrive in different conditions. Exposing children to diverse environments helps them develop better coping mechanisms, akin to how the immune system strengthens against viruses.
Dr. Gopnik is a professor at the University of California at Berkeley, where she has taught since 1988. She is a world leader in cognitive science, particularly the study of children’s learning and development. She is the author of over 100 journal articles and several books including the best-selling and critically acclaimed popular books The Scientist in the Crib, The Philosophical Baby, and The Gardener and the Carpenter. She is a fellow of the Cognitive Science Society and the American Association for the Advancement of Science and a member of the American Academy of Arts and Sciences.
Dr. Heather Berlin is a neuroscientist, clinical psychologist, and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
Dr. Christof Koch is Chief Scientist for the Tiny Blue Dot Foundation and the current Meritorious Investigator and former President of the Allen Institute for Brain Science.
Join us for new episodes every Thursday. Follow the show on YouTube, Spotify, Apple Podcasts, Amazon Music, or wherever podcasts are found.
We long for love. We die for love. We kill for love. But why do we love? Cohosts Dr. Heather Berlin and Dr. Christoph Koch ask this question to Helen Fisher, PhD. who dedicated her career to researching romantic love. In this episode of Science of Perception Box, we explore how the act of being in love or out of love changes how we view ourselves and the world around us.
Dr. Fisher was a biological anthropologist, Senior Research Fellow at The Kinsey Institute, and Chief Science Advisor to Match.com. She used brain scanning (fMRI) to study the neural systems associated with the sex drive, romantic love, attachment, rejection, love addiction, long-term partnership happiness, and the biological foundations of human personality. She conducted extensive research on the evolution, biology, and psychology of human sexuality, monogamy, adultery, and divorce.
Dr. Heather Berlin is a neuroscientist, clinical psychologist, and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
Dr. Christof Koch is Chief Scientist for the Tiny Blue Dot Foundation and the current Meritorious Investigator and former President of the Allen Institute for Brain Science.
Join us for new episodes every Thursday. Follow the show on YouTube, Spotify, Apple Podcasts, Amazon Music, or wherever podcasts are found.
Love the show? Write us a review on your podcast app, or tell a friend about the show.
What happens when an irredeemable person receives love, gratitude, and respect? After decades of drug and alcohol abuse, chef and television personality Andrew Zimmern learned firsthand.
As a teenager, Andrew Zimmern experienced deep pain when his mother became permanently disabled, and his father enforced a rule to avoid discussing feelings. Without an outlet, that pain grew into resentment and substance abuse. By 14, Zimmern was drinking daily, and his addiction followed him into adulthood, ultimately costing him his career, relationships, and home.
In January 1992, after hitting rock bottom, Zimmern attempted to take his own life. When he woke up, something shifted. For the first time, he asked for help. His friends intervened, sending him to rehab, where he began confronting his emotions and embracing a mindset of learning and giving.
Zimmern rebuilt his life, becoming a celebrated chef, author, and TV personality. Today, he credits that one vulnerable moment with saving his life and inspiring him to live with purpose and gratitude.
About Andrew Zimmern:
Andrew Zimmern is a chef, food writer, and television personality best known for hosting Bizarre Foods on the Travel Channel. A four-time James Beard Award winner, Zimmern has dedicated his career to exploring global cuisines and advocating for culinary diversity. Beyond television, he is a passionate philanthropist, focusing on hunger relief, food sustainability, and social justice. He founded the Andrew Zimmern Project to support food security initiatives and works with organizations like Second Harvest and Services for the Underserved. Through his work, Zimmern strives to create a more equitable food system and inspire cultural appreciation through cuisine.
The one phrase that changed Diana Nyad’s life, and set her on course to become the first person ever to conquer the 110 mile, 53 hour swim from Florida to Cuba.
At 64, Diana Nyad swam 110 miles from Cuba to Florida, facing jellyfish, exhaustion, and tough ocean currents for over 53 hours. But this feat was more than just physical - it was the result of a lifetime of mental endurance.
As a young swimmer, she faced sexual abuse from her coach, which derailed her Olympic dreams and left deep emotional scars. Instead of letting those experiences hold her back, she found a way to channel that pain into something powerful. She talks about developing a "steel trap mind," using her struggles as motivation to pursue her goals.
Diana's journey goes beyond breaking records. It’s a powerful reminder of the human spirit's ability to persevere and heal, no matter the odds. Her swim from Cuba to Florida, completed on her fifth attempt, showcases her incredible willpower and serves as an inspiration to people everywhere.
About Diana Nyad: Diana Nyad is an endurance swimmer, author, and motivational speaker best known for her 2013 record-breaking swim from Cuba to Florida at age 64. Completing the 110-mile journey without a shark cage, she demonstrated unparalleled resilience and determination. Nyad is also a bestselling author, journalist, and co-founder of EverWalk, a fitness initiative promoting community through walking. Her story of perseverance, chronicled in her memoir Find a Way, continues to inspire audiences worldwide.
“I saw that when I believed my thoughts, I suffered, and when I didn’t believe them, I didn’t suffer.”
Author and public speaker Byron Katie shares how she transformed her life after discovering ‘The Work’, a method for identifying the thoughts that cause pain and suffering. By asking herself four simple yet profound questions, she found a way to recover from her agoraphobia, reunite with her family, and begin teaching others how to heal.
Katie’s strategy for ending suffering lies in asking yourself four questions about the thoughts you’re having: Is it true? Can you absolutely know it’s true? How do you react when you believe it? Who are you without the thought?
By asking yourself these questions, Katie explains how you can begin to escape the mentalities that hold you back. Her method shows us that peace doesn’t come from changing the world—it comes from changing how we see it.
About Byron Katie: Byron Katie is an author and teacher who helps people find peace by questioning their stressful thoughts. In 1986, after years of depression, she experienced a life-changing realization that led her to create The Work, a simple process of self-inquiry. Her books, like Loving What Is and A Thousand Names for Joy, have touched millions. Through workshops and talks, Katie shares a path to clarity and freedom, helping people live with more acceptance and ease.
Our cultural lenses can expand our Perception Box or contract it, keeping us closed off to new opportunities. So how do we become aware of the personal influences that shape our perceptions? In this episode of Science of Perception Box, cohosts Dr. Heather Berlin and Dr. Christoph Koch discuss the impact of cultural differences on identity and mindsets with guest Dr. Daphna Oyserman. Dr. Oyserman shares her insights on how small changes in context can significantly affect our mindset and choices, impacting our health and academic performance.
Dr. Daphna Oyserman is a Dean’s Professor of Psychology and Professor of Psychology and Education at the University of Southern California. Dr. Oyserman received a PhD in psychology and social work from the University of Michigan and served on the faculty of The Hebrew University, Jerusalem, before returning to the University of Michigan where she last held appointments as the Edwin J. Thomas Collegiate Professor of Social Work, Professor of Psychology, and Research Professor in the Institute for Social Research.
Dr. Heather Berlin is a neuroscientist, clinical psychologist, and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
Dr. Christof Koch is Chief Scientist for the Tiny Blue Dot Foundation and the current Meritorious Investigator and former President of the Allen Institute for Brain Science.
Join us for new episodes every Thursday. Follow the show on YouTube, Spotify, Apple Podcasts, Amazon Music, or wherever podcasts are found.
Love the show? Write us a review on your podcast app, or tell a friend about the show.
What is the mind? Does the mind exist only in your own Perception Box, or is there a greater connection of consciousness? In this episode of Science of Perception Box, cohosts Dr. Heather Berlin and Dr. Christoph Koch discuss the interconnectedness of the mind, the impact of implicit memories from infancy on childhood attachment, and the wheel of awareness with Dr. Dan Siegel. Dr. Siegel shares his research and practices on healing unresolved trauma, preventing burnout for caregivers and medical professionals, and channeling the Perception Box-expanding power of empathy.
Dr. Siegel is the Executive Director of the Mindsight Institute and Founding Co-Director of the Mindful Awareness Research Center at UCLA, where he was also Co-Principal Investigator of the Center for Culture, Brain, and Development and Clinical Professor at the School of Medicine. An award-winning educator, he is a Distinguished Fellow of the American Psychiatric Association and recipient of several honorary fellowships. He has authored numerous articles and books, including five New York Times bestsellers.
Dr. Heather Berlin is a neuroscientist, clinical psychologist, and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
Dr. Christof Koch is Chief Scientist for the Tiny Blue Dot Foundation and the current Meritorious Investigator and former President of the Allen Institute for Brain Science.
Join us for new episodes every Thursday. Follow the show on YouTube, Spotify, Apple Podcasts, Amazon Music, or wherever podcasts are found.
Love the show? Write us a review on your podcast app, or tell a friend about the show.
Visit unlikelycollaborators.com for more information.
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Humans have a symbiotic relationship with plants. Plants coevolved to suit our desires for nourishment, beauty, and altering consciousness. Journalist Michael Pollan has investigated the human connection to plants. This week on Science of Perception Box, Dr. Heather Berlin and Dr. Christof Koch ask Pollan about modern trends like ultra-processed foods, industrialized agriculture, and consciousness-altering drugs from plants including caffeine, cannabis, and psychedelics.
For more than 30 years, Michael Pollan has been writing books and articles about the places where the human and natural worlds intersect: on our plates, in our farms and gardens, and in our minds. Pollan is the author of eight books, six of which have been New York Times bestsellers. In 2003, Pollan was appointed the John S. and James L. Knight Professor of Journalism at UC Berkeley’s Graduate School of Journalism and the director of the Knight Program in Science and Environmental Journalism. In 2020, along with Dacher Keltner and others, he cofounded the UC Berkeley Center for the Science of Psychedelics.
Dr. Heather Berlin is a neuroscientist, clinical psychologist, and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
Dr. Christof Koch is Chief Scientist for the Tiny Blue Dot Foundation and the current Meritorious Investigator and former President of the Allen Institute for Brain Science.
Join us for new episodes every Thursday. Follow the show on YouTube, Spotify, Apple Podcasts, Amazon Music, or wherever podcasts are found.
Love the show? Write us a review on your podcast app, or tell a friend about the show.
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Jim McKelvey, co-founder of Square, overcame a challenging upbringing marked by social isolation and family tragedy, channeling those experiences into a life defined by action, innovation, and iconoclasm. Though he’s undeniably earned his reputation as a business trailblazer, McKelvey remains uncomfortable with any attempts to mythologize his journey.
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As a child, Bob Stiller felt unmoored. His mother’s death was a loss that fueled anger, insecurity and, as a teenager, lots of partying. He founded rolling paper company E-Z Wider in 1971 and, a decade later, Green Mountain Coffee Roasters.
Sophia Amoruso (aka Nasty Gal) started a tiny online vintage clothing store that quickly turned into a $350 million business. Fame soon followed, but so did all of her insecurities.
Anxiety can make us feel like we’re trapped in our brain. So how do we open the door and gain freedom? This week in the inaugural episode of Science of Perception Box podcast, Dr. Heather Berlin and Dr. Christof Koch invite Dr. Judson Brewer to delve into the roots of anxiety, its impact on our perception, and how curiosity can be the key to lasting change.
Dr. Judson Brewer studies the neural mechanisms of mindfulness. He is the Director of Research and Innovation at Brown University’s Mindfulness Center, where he’s also an Associate Professor at the School of Medicine. Dr. Brewer is a leading expert in the science of self-mastery and breaking habits. His books include Unwinding Anxiety, The Craving Mind, and The Hunger Habit.
Dr. Heather Berlin is a neuroscientist, clinical psychologist, and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City.
Dr. Christof Koch is Chief Scientist for the Tiny Blue Dot Foundation and the current Meritorious Investigator and former President of the Allen Institute for Brain Science.
Join us for new episodes every Thursday. Follow the show on YouTube, Apple Podcasts, Spotify, Amazon Music, or wherever podcasts are found.
Love the show? Write us a review on your podcast app, or tell a friend about the show.
Join renowned scientists Dr. Heather Berlin and Dr. Christof Koch on the Science of Perception Box, where they delve into the Perception Box—a groundbreaking concept developed by Elizabeth R. Koch, that reveals how our beliefs, biases, and neural wiring shape our reality and define how we experience the world.
Through captivating conversations with expert guests like psychiatrist Dr. Judson Brewer, anthropologist Dr. Helen Fisher, and journalist Michael Pollan, the show explores how the Perception Box expands in states of awe, curiosity, and love, and contracts during fear, anxiety, or anger.
From mindfulness and romantic relationships to psychedelics and human connection, each episode uncovers transformative insights into unlocking greater awareness, fostering curiosity, and reshaping how we perceive the world.
New episodes drop every Thursday on YouTube, Spotify, Apple Podcasts, Amazon Music, or wherever you listen to podcasts. Follow the journey and redefine your reality.
Don’t call yourself “a writer,” just write. Ryan Holiday on how the labels you give yourself can hold you back.
Who would you be without all the labels and identities you’ve collected over the course of your life?
Ego, titles, and societal expectations often shape who we think we are—or who we think we should be. Author, and for simplicity's sake, bookstore owner, Ryan Holiday explains the simple question “What do you do?” can turn into a trap, making us cling to roles that don’t really define us. But what happens when you let go of these labels? What if, instead of focusing on the identity of being a writer, you focused on the act of writing itself?
As Holiday got older, he learned that being busy “doing the verb” is far more valuable than obsessing over the noun. It’s easy to get caught up in trying to fit into the “right” categories and titles, but that often means copying, comparing, and losing sight of what really matters.
About Ryan Holiday: Ryan Holiday is a bestselling author, marketer, and one of today’s leading voices in modern Stoicism. He’s known for taking ancient wisdom and making it relatable and practical for everyday life. Before becoming an author, he led marketing at American Apparel. Now, he writes about strategy, self-discipline, and leadership, weaving history into real-world advice.
When a group of first responders were asked to confront the Perception Box question, "What need inside of yourself have you been neglecting?", their raw and honest responses were deeply moving and sparked profound reflection.
This series (a collaboration with Jubilee Media) is designed for communities with shared experiences to spark deeper self-understanding and connection by sharing their answers to specially selected Perception Box questions. This highlights the power of vulnerability and the importance of creating safe spaces for honest conversations.
“I feel like I had to lose my sight to fully gain my vision.” John Furniss on how becoming blind led him to drug abuse, rehab, woodworking, and finally, to a fulfilling life.
John Furniss, also known as the Blind Woodsman, opens up about his journey from a difficult past to finding peace and purpose. After losing his sight as a teenager, John struggled for years to accept his new reality, battling inner turmoil and substance abuse along the way. It wasn't until he discovered woodworking through a vocational rehab program that he found a way to channel his creativity and start healing.
Woodworking became more than just a skill for John; it allowed him to bring the designs he imagined in his mind to life. This craft also led him to meet his wife, Annie, who has been a constant source of love and support. Through his work and his relationship, John found a sense of belonging and a new way of seeing the world. He reflects on how losing his sight actually helped him gain a clearer vision of who he is and what he’s meant to do, ultimately finding peace in embracing his true self.
About John Furniss:
John Furniss, known professionally as The Blind Woodsman, is a skilled woodworker, author, and disability advocate recognized for his meticulous hand-turned creations. After losing his sight at 16, John faced significant challenges adapting to life with total blindness. In his 20s, he found his passion for woodworking through a class designed for the blind, which led to the development of his unique craft.
Today, John’s work has been featured on platforms such as Good Morning America and The Kelly Clarkson Show. He and his wife, Anni, who is also an artist, use their social media platforms to share their work and raise awareness about disability and mental health. John’s expertise in woodworking and his contributions to the art community have established him as a respected figure in his field.
Kaelynn Partlow shares her story about life with autism, ADHD, and dyslexia, and how finding the right diagnosis helped her embrace her neurodivergent identity.
Kaelynn Partlow, an author, autism advocate, and registered behavior technician, shares her own experiences living with autism, ADHD, dyslexia, and more. She talks about how these diagnoses shifted her self-perception from feeling "stupid" to understanding her unique challenges and strengths.
Kaelynn opens up about the misunderstandings neurodivergent people face and the difficulty of connecting in a world that often doesn't accommodate different ways of thinking. She also shares her fears—like wondering if her social difficulties will ever improve—and how she copes with loneliness, especially when not focused on work.
Through it all, Kaelynn emphasizes the value of recognizing your own strengths, even when it’s hard. By taking on challenges and thriving under pressure, she found new opportunities, from public speaking to creative writing. Her story shows that growth often comes from facing fears and redefining success on your own terms.
About Kaelynn Partlow:
In 2015, Kaelynn Partlow joined Project Hope Foundation as a Registered Behavior Technician. She is now a Lead Technician, providing services to middle and high-school-aged clients and contributing to staff training development.
In 2021, Kaelynn was featured on the Netflix series Love On The Spectrum. She has also been a guest on numerous national podcasts and has published several articles, offering insights from an autistic perspective.
With a large following on various social media platforms, Kaelynn uses her reach for autism advocacy, connecting with millions globally. In addition to her online work and role at Project Hope, she is an international public speaker, passionate about sharing tangible strategies for best practices when interacting with individuals on the autism spectrum
Your brain is wired to repeat the familiar. Change this wiring, and it will change your life.
Nicole Vignola, a neuroscientist and organizational psychologist, explains how deeply rooted beliefs can limit our potential and keep us trapped in patterns of thought. These perceptions, often shaped by our upbringing and environment, aren’t necessarily our own—but they can be changed.
Nicole shares how the brain’s natural biases, like negativity bias and confirmation bias, reinforce these limiting beliefs. However, with the right approach, it’s possible to reshape our mental patterns. By practicing metacognition—observing and naming our thoughts—we can start to rewire our perception and create new, empowering narratives.
Our brains are capable of change at any age. By focusing on small wins and challenging automatic thoughts, we can break free from old beliefs and begin using a mindset that better serves ourselves and our futures.
About Nicole Vignola:
Nicole Vignola is a neuroscientist, author and corporate consultant. With a BSc in Neuroscience and an MSc in Organizational Psychology, Nicole works with companies and individuals worldwide, educating them on the science of human optimisation, health and longevity, and how to enable employees to perform better in their daily lives and in turn, bring peak performance to the workplace. Recent clients include Lloyds Bank, Makers Mark and Smeg Ltd.
Expanding your worldview starts with understanding your brain. Stanford neuroscientist David Eagleman explains.
David Eagleman, a neuroscientist at Stanford and host of the Inner Cosmos podcast, explores how our brains shape the reality we experience and why we often accept our perceptions as the only truth. From a young age, we develop our understanding of the world based on limited experiences and biases, which can lead us to form narrow views about what's true.
Eagleman explains that our genetics and life experiences wire our brains in unique ways, meaning that each of us sees the world a little differently. He introduces the idea of "perceptual genomics," which looks at how slight genetic differences influence our perception of reality. He also discusses how our brains naturally create in-groups and out-groups, a tendency rooted in evolution that affects how much empathy we feel for others.
To overcome these biases, Eagleman suggests that we start by recognizing our own prejudices, understanding the tactics of dehumanization, and connecting with others through shared interests. This approach helps us appreciate the diverse realities others experience, ultimately contributing to a more empathetic and understanding society.
About David Eagleman:
David Eagleman is a neuroscientist at Stanford University and an internationally bestselling author. He is co-founder of two venture-backed companies, Neosensory and BrainCheck, and he also directs the Center for Science and Law, a national non-profit institute. He is best known for his work on sensory substitution, time perception, brain plasticity, synesthesia, and neurolaw.
Challenging the loneliness stigma can change your life. Here’s how to start.
From a young age, many of us are taught that being alone means something is wrong, leading to negative thought patterns that reinforce feelings of isolation. Kasley Killam, author of The Art and Science of Connection and an expert in social health, explains how these perceptions of loneliness can shape our experiences and influence our lives.
According to Killam, this stigma around loneliness can trigger a stress response in the body, affecting both mental and physical well being. However, by challenging these narratives and reminding ourselves of how much control we really have, it’s possible to redirect our mindsets. It also helps, she says, to understand the difference between individualistic and collectivist cultures, and how each one can influence the way we interpret and discuss our feelings with others.
For those who have struggled with loneliness or felt trapped in a cycle of negative thinking, this perspective can help us break free. By shifting our thought patterns, we can transform our relationships, enhance our sense of connection, and improve our overall well-being.
About Kasley Killam:
Kasley Killam is a social health expert, author, and advocate focused on strengthening connections and enhancing community well-being. With a background in behavioral science and public health from Harvard University, she is a leading voice on the impact of social relationships on mental and physical health.
As the founder of Social Health Labs, Killam collaborates with organizations to develop innovative solutions for combating loneliness and social isolation. Her work has been featured in major publications, and she is a sought-after speaker on the importance of social well-being in creating healthier, more resilient communities.
Ever wonder why your partner goes Tasmanian Devil in traffic jams while you just shrug? Or why you have such a hard time setting boundaries with parents when your sibling has no problem saying "hell no!" Everyone has something that triggers panic or turns their blood cold…and it all starts with the story you made up about yourself when you were too young to know the difference…your Perception Box Seed Story.
A group of LGBTQ+ individuals courageously answered the Perception Box question, "Who or what have you left behind on your journey to become who you are today?" Their honest and insightful responses were deeply moving.
This series (a collaboration with Jubilee Media) is designed for communities with shared experiences to spark deeper self-understanding and connection by sharing their answers to specially selected Perception Box questions. This highlights the power of vulnerability and the importance of creating safe spaces for honest conversations.
How has Kel Mitchell navigated self-doubt, isolation, and the desire to “hit the off button”? He says it’s all faith, community, and personal forgiveness.
After his debut on Nickelodeon, Kel Mitchell began a life-long career as an actor and comedian. He got married, started a family, and basked in professional success. However, behind the scenes, he faced intense personal hardships that pushed him to the brink, testing his resilience and strength in ways he never imagined.
Kel guides us through the lowest points of his life, showing us how faith in himself and his religion helped him rebuild and achieve a fulfilling existence. He reminds us that blessings can often be hidden in hardships and that mistakes play a crucial role in shaping who we are.
By expressing his pain and opening up to others about the things he was struggling with, he was able to find unity, community, and support from those who had experienced similar drawbacks. Mitchell stresses the importance of understanding others, and how deep relationships can change – and even save – lives.
If you or someone you know is considering suicide, please contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255), text “STRENGTH” to the Crisis Text Line at 741-741 or go to suicidepreventionlifeline.org.
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Kel Mitchell is a two-time Emmy Award-nominated actor, producer, comedian, and youth pastor hailing from Chicago, Illinois.
Mitchell executive produced and appeared in the new iteration of the beloved Nickelodeon series All That, bringing him full circle to the original award-winning show that was his big break. All That was Nickelodeon's longest-running live-action series, with 171 episodes across ten seasons from 1994 to 2005. The franchise paved the way for a number of successful spin-offs, including Kenan & Kel, The Amanda Show, The Nick Cannon Show, and the feature-length film Good Burger, all of which cemented Mitchell's impact on pop culture.
A two-part visualization to help you gain distance from any overpowering emotion so you can respond to the true need of the moment with something closer to calm.
Harvard physician Aditi Nerukar explains how to rewire your brain’s stress response to live a more resilient life.
If you’ve ever heard the phrase “pressure makes diamonds,” this video is for you.
Harvard physician Aditi Nerurkar was working 80 hours a week, and, despite what she was telling herself about resilience, the stress was taking a major toll. She explains how there are two different kinds of stress, aptly named “adaptive” and “maladaptive.” But how can you tell the difference between the two?
Dr. Nerukar explains that healthy, adaptive stress moves your life forward, while unhealthy, maladaptive stress wears you down and diminishes your productivity. When experiencing maladaptive stress, you may find yourself plummeting closer to burnout, or a complete shutdown. To combat these consequences, Dr. Neurkar offers two easily achievable methods for resetting your brain in high-stress situations.
Whether you're navigating a demanding job, balancing multiple life roles, or simply looking to improve your stress management, this information can help you thrive without compromising your well-being. Remember to slow down, take deep breaths, and regularly check in with yourself to ensure your stress remains healthy and manageable!
Neuroanatomist Dr. Jill Bolte Taylor explains the 4 key ”characters” of the brain, and how understanding each can expand your perception of yourself, and the world, forever.
At age 37, neuroanatomist Dr. Jill Bolte Taylor suffered a stroke that would take her eight years to fully recover from. This is how it changed her understanding of the brain.
In this interview, Dr. Jill draws a map of the human brain, explaining how it is comprised of four distinct modules, each serving a unique role in function and personality. This combination of cognitive and emotional components gives rise to the multidimensional characters within each of us.
Are you looking to be more rational, more creative, more forgiving, or perhaps less rigid in your thinking? Dr. Jill suggests that by becoming aware of the four modules of our brains, we can consciously choose to engage specific parts. This awareness allows us to harness the true power of our brains and shape who we want to become, ultimately fostering less anxiety, more inner peace, and a vastly more purposeful life.
Carrie Berk reveals how she transformed her struggle with anxiety and internet fame by changing her perception and finding her true voice as a writer.
Carrie Berk, author, journalist, and social media influencer with nearly 4 million TikTok followers, shares her journey through anxiety, internet fame, and personal growth.
Amid the pandemic and sudden online fame, Carrie faced intense anxiety, receiving harmful threats from strangers and grappling with the pressures of social media. Sharing her most vulnerable moments, including her first heartbreak at sixteen, Carrie emphasizes the importance of authenticity. Through therapy and self-discovery, she learned that while she couldn’t switch off her anxiety, she could change her response to it.
Carrie’s story is a perfect example of the resilience it takes to be a young person in today’s social climate, and proves how powerful self-confidence and inner strength can be.
This group of people who have experienced homelessness were asked the Perception Box question, "In moments of deep solitude, what major concerns and questions about YOU tend to dominate your thoughts?" Their honest answers were deeply moving and insightful.
This series (a collaboration with Jubilee Media) is designed for communities with shared experiences to spark deeper self-understanding and connection by sharing their answers to specially selected Perception Box questions. This highlights the power of vulnerability and the importance of creating safe spaces for honest conversations.
In this episode, a group of formerly incarcerated individuals was asked the Perception Box question, "What are you most afraid is true about you?" Their candid responses were incredibly moving and thought-provoking.
This series (a collaboration with Jubilee Media) is designed for communities with shared experiences to spark deeper self-understanding and connection by sharing their answers to specially selected Perception Box questions. This highlights the power of vulnerability and the importance of creating safe spaces for honest conversations.
Jewel says denying the truth cost her years of her life. This is how she shifted her perception to see truth more clearly and regain her strength.
“My number one job was to be a happy, whole human — not a human full of holes.” Jewel Kilcher, singer-songwriter, and visual artist, opens up about her childhood, the start of her career, and what makes Jewel, Jewel.
After being discovered during a coffee shop gig in the 1990’s, folk singer Jewel began the life-long endeavor of being a performer. Jewel went on to gain worldwide recognition for her talent and creativity. But who is she at her core? What are her greatest fears, her deepest aspirations?
In this interview, Jewel shares the personal struggles and triumphs that have shaped her, the importance of truth on her life and well-being, and the lessons she's learned along the way. Through this conversation, Jewel offers an up-close look into her journey, revealing the experiences and hard-won insights that have shaped her as both an artist and a person.
Experience Jewel’s latest exhibit at the Crystal Bridges Museum of American Art, The Portal: An Art Experience by Jewel ► https://crystalbridges.org/calendar/the-portal-an-art-experience-by-jewel/
About Jewel:
Jewel Kilcher, known mononymously as Jewel, embodies the quintessential story of resilience and artistic integrity. From her humble beginnings in the rugged landscapes of Alaska to her rise as a multi-platinum recording artist, Jewel's journey is a testament to the transformative power of art. Homeless at 18, she honed her craft performing in coffee shops, blending folk, pop, and country influences with her ethereal voice and introspective songwriting.
Her debut album, "Pieces of You," captured hearts worldwide, achieving remarkable commercial success while delivering profound, soul-stirring messages. Beyond music, Jewel's talents extend to poetry and acting, with her literary works and performances reflecting her deep empathy and authenticity.
Jewel's commitment to social causes, including mental health advocacy and her foundation, the Inspiring Children Foundation, underscores her dedication to making a positive impact. In a world often dominated by transient fame, Jewel stands out as a beacon of enduring creativity and compassionate leadership.
Alyssa and her ex-boyfriend Trey have successfully transitioned from lovers to best friends. But can she recreate that same dynamic with her most recent ex, Adal? Alyssa, Trey, and Adal dive deep into their pasts and their relationships with each other by answering a series of thought-provoking Perception Box questions. Watch their honest reflections, uncover their perspectives on love and friendship, and discover what the future holds for this unique trio.
What happens when men shed their armor and embrace their emotions? Men from diverse backgrounds share their stories of overcoming trauma, redefining masculinity, and finding strength in vulnerability. This is a must-watch for anyone seeking deeper connections and understanding.
Emma and Nick both swiped "yes" in person. Now that they have a chance to get to know each other and themselves more deeply by answering Perception Box questions, are they compatible?
Arielle & Ella met on a Nectar dating show. Was it meant to be, or are they destined to be just friends? They will find out when they get to know their true selves and each other by answering Perception Box questions.
Participants are invited to sit down to ask each other Perception Box questions to see if two strangers could sit down and get vulnerable with one another.
This powerful episode features a group of individuals with disabilities opening up about their deepest fears and struggles. Their experiences highlight the unique challenges they face, from concerns about independent living to mental health struggles and navigating social stigma, and ultimately how they can relate to one another.
Michael Oher gained widespread recognition through Michael Lewis's book "The Blind Side" and its film adaptation, which depicted his difficulties in early life and time playing college football. After attending the University of Mississippi, he played in the NFL for the Baltimore Ravens, Tennessee Titans, and Carolina Panthers, winning the SuperBowl with the Ravens in 2013.
Shaka Senghor spent 19 years in prison, 7 of them in solitary confinement. This is how he found true freedom.
Watch the full video here.
Watch what happens when this group of strangers bravely share their unspoken truths. Will these women find connection in the unexpected? Could sharing your secret be the key to unlocking a powerful sense of belonging?
Curious about tools for fostering deeper self-awareness? Check out the latest episode of Tea for Two by Nectar. Former high school sweethearts, Diane & Justin, use Perception Box questions to explore their individual needs and communication styles. Great insights for anyone in a relationship, whether personal or professional.
Hailey and Travis first met on the Nectar channel, now they are going on their first date and things get deep.
Do you ever feel like you have something to prove?
Scientific experts explain how each person's perception is skewed by various factors such as beliefs, biases, and narratives.
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A collection of interviews dedicated to sharing unique perspectives and challenging our preconceived notions.
Jim Lee, President, Publisher, and Chief Creative Officer of DC Comics tells us how his childhood obsession with Superman changed his life.
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Explore how overcoming the limiting beliefs that hold us back, can expand the possibilities of our perception, and open us up to new ways of seeing and being seen.
The Osbournes was MTV’s biggest show – and it almost cost Jack Osbourne his life. Here’s how his family’s reality TV fame stole his childhood, and how he’s been able to heal since.
Meet Jordan and Rana. These two undergrads have been in an exclusive situationship, but are ready to confront where their relationship is going and what might come next.
Tea for Two explores how daters show up in a relationship by first taking a look at their relationship with themselves. Through a series of Perception Box questions, Tea for Two questions, and challenges, these daters get to know each other and themselves on a whole new level. This allows them to dig deeper, uncover more meaningful connections, and figure out if they are ready to be in this relationship.
This is how rejection made executive producer and director Julie Plec an undeniable leader.
Creator of the popular series “The Vampire Diaries,” Julie Plec is proof imposter syndrome never goes away, no matter how big you make it. The writer and producer answered our questions about self-doubt, getting “blacklisted,” and how we can alter our perceptions to better appreciate our successes.
About Julie Plec:
Julie Plec is a creator, showrunner, executive producer and director, most notably responsible for the complete Vampire Diaries Universe (The Vampire Diaries, The Originals, and Legacies), which spanned thirteen years and more than 300 episodes of television.
Plec is co-creator and co-showrunner of the upcoming series Vampire Academy, based on the popular book series, which recently wrapped production in Spain and is debuting September 15, 2022, on Peacock. She is also co-creator of the new series Dead Day, along with her Vampire Diaries partner Kevin Williamson, which was recently picked up to series at Peacock as well, and executive producer of Girls on the Bus, which was picked up straight to series at HBO Max.
Plec is creator and executive producer of Legacies, which recently aired its fourth and final season on the CW, along with serving as an executive producer of Roswell, New Mexico, which recently aired its fourth and final season on the CW as well. In addition, Plec served as executive producer of The Endgame, starring Morena Baccarin and Ryan Michelle Bathé, which recently aired on NBC.
She is currently under an overall deal at Universal Television, where she and Emily Cummins, president of her production company, My So-Called Company, are developing projects across all platforms for the studio. Plec and Cummins recently announced a new project at Peacock, Clifton, along with a slate of several other projects in development.
Along with directing multiple episodes of The Vampire Diaries, Legacies, and Roswell, New Mexico, for which she also directed the pilot, Plec directed an episode of the CW’s hit series Riverdale, and most recently directed an episode of her new series Vampire Academy.
Plec developed and executive produced Containment, which aired as a limited series on the CW in 2016.
She got her start as a television writer and co-executive producer for the series Kyle XY, which she produced for the show’s three-year run. Other television credits include Dawson’s Creek, on which she collaborated with creator/executive producer Kevin Williamson, and The Tomorrow People, on which she collaborated with fellow executive producers Greg Berlanti and Phil Klemmer.
In the early part of her career, Plec worked with both Wes Craven and Kevin Williamson during the run of their hit Scream franchise. She also co-produced Berlanti’s directorial debut film, The Broken Hearts Club.
Your emotions do not reflect an irrefutable truth. Psychologist Kristen Lindquist explains how important that is for connecting across cultures.
When it comes to obtaining an objective understanding of the world around us, emotions may not be as reliable as we think, explains Kristen Lindquist, a professor of psychology and neuroscience at the University of North Carolina at Chapel Hill.
Lindquist explores the concept of "affective realism," a term that describes how our feelings shape our reality, both of which are influenced by cultural nuances. She unravels the connections between emotions, culture, and the brain, challenging the notion that our emotional experiences always mirror objective truths.
About Kristen Lindquist:
Kristen Lindquist, PhD. is a Professor of Psychology and Neuroscience at the University of North Carolina, Chapel Hill. Her research seeks to understand the psychological and neural basis of emotions, moods, and feelings. Her on-going work uses tools from social cognition, physiology, neuroscience, and big data methods to examine how emotions emerge from the confluence of the body, brain, and culture.
Robert Waldinger is a psychiatrist, psychoanalyst and Zen priest. He is Professor of Psychiatry at Harvard Medical School and Massachusetts General Hospital, where he directs the Harvard Study of Adult Development. His TEDx talk on this subject has received nearly 44 million views, and is the 9th most watched TED talk of all time. He is the co-author of The Good Life with Dr. Marc Schulz.
Scott Barry Kaufman talks to Robert Waldinger about the secret to a happy life. Robert shares the recent findings of The Grant Study, which is the longest scientific study of happiness ever conducted. It’s been ongoing for more than 80 years now, and has had high profile participants like US President John F. Kennedy. Robert and Scott get into the details of how they continue to conduct research and how to make sense of both the new and old data. Sure enough, what the study has found consistent is the power of connection. They also touch on the topics of psychodynamic therapy, defense mechanisms, attachment, and psychological research.
Website: www.robertwaldinger.com
X: @robertwaldinger
The divisive gold/blue dress that almost broke the internet in 2015 is a relatable example of how a Perception Box works. How each of us having our Perception Box, own subjective reality, affects the way we experience the world.
Expert James Fadiman explains how psychedelics have the power to expand consciousness, enhance creativity, and deepen our connections to the world.
James Fadiman, a distinguished figure with over six decades in psychedelic research, examines the profound impact psychedelics have on consciousness, creativity, and connectivity.
Fadiman shares insights into how these substances shift perception, offering perspectives that challenge and expand our understanding of reality. He also delves into the scientific underpinnings of psychedelics, their therapeutic potential, and the societal benefits of fostering deeper empathy and open-mindedness. Highlighting the importance of integration post-experience, Fadiman sheds light on the transformative power of psychedelics to not only alter individual consciousness but also to enhance community bonds and personal relationships.
Through a focus on responsible use and the expansion of human awareness, Fadiman's expertise offers a compelling view into the capacity of psychedelics to redefine our interaction with the world and ourselves.
About James Fadiman:
Dr. James Fadiman is a leading scientific expert on the use of psychedelics for personal exploration, healing, and transformation. He has been researching, writing and lecturing on the topic for more than fifty years. His research focuses on exploring the potential of psychedelics to help individuals achieve a more meaningful, balanced and enlightened life. He has written numerous books on the topic, such as The Psychedelic Explorer’s Guide and Your Symphony Of Selves, and is widely considered to be one of the most influential figures in the field.
There are three kinds of memory that all work together to shape your reality. Neuroscientist André Fenton explains.
Neuroscientist André Fenton discusses the intricate relationship between memory, perception, and reality, shedding light on the complexity of human cognition.
Fenton believes memories are not fixed but are continually modified by our experiences and mindsets.
This, in his mind, underscores the importance of humility and empathy in acknowledging the fallibility of our memories and the need to consider different perspectives in our quest for truth.
About André Fenton:
André Fenton, professor of neural science at New York University, investigates the molecular, neural, behavioral, and computational aspects of memory. He studies how brains store experiences as memories, how they learn to learn, and how knowing activates relevant information without activating what is irrelevant. His investigations and understanding integrates across levels of biological organization, his research uses genetic, molecular, electrophysiological, imaging, behavioral, engineering, and theoretical methods. This computational psychiatry research is helping to elucidate and understand mental dysfunction in diverse conditions like schizophrenia, autism, and depression. André founded Bio-Signal Group Corp., which commercialized an FDA-approved portable, wireless, and easy-to-use platform for recording EEGs in novel medical applications. André implemented a CPAP-Oxygen helmet treatment for COVID-19 in Nigeria and other LMICs and founded Med2.0 to use information technology for the patient-centric coordination of behavioral health services that is desperately needed to equitably deliver care for mental health. André hosts “The Data Set” a new web series on how data and analytics are being used to solve some of humanity’s biggest problems.
Nothing is real and everything is an illusion. Neuroscientist Heather Berlin explains why that’s not exactly a bad thing.
Neuroscientist Heather Berlin likens each person's perception to a unique box shaped by their own experiences. Perception, Berlin explains, arises from a blend of internal expectations and external sensory input, creating a subjective experience.
Berlin believes our mental state can also profoundly affect our perception; a pessimistic mindset might skew it negatively, for example. The brain filters information, relying on preexisting schemas that can lead to cognitive biases. She notes that these biases can be altered through changing inputs over time, which can expand our empathy.
Understanding perception's illusory nature empowers us to shape our experiences and find joy despite life's challenges.
About Heather Berlin:
Dr. Heather Berlin is a neuroscientist, clinical psychologist, and associate clinical professor of psychiatry and neuroscience at the Icahn School of Medicine at Mount Sinai in New York. She explores the neural basis of impulsive and compulsive psychiatric and neurological disorders with the aim of developing novel treatments. She is also interested in the brain basis of consciousness, dynamic unconscious processes, and creativity. Clinically, she specializes in lifespan (child, adolescent, and adult) treatment of anxiety, mood, and impulsive and compulsive disorders (e.g., OCD), blending her neural perspective with cognitive-behavioral therapy, mindfulness, and humanistic approaches.
You know Steve-O. Now meet Steve Glover, as the professional stuntman talks to us about pain, insecurity, and never finding contentment.
In this deeply personal and revealing interview, Steve Glover, better known as Steve-O, the daredevil entertainer known for his jaw-dropping stunts and unflinching willingness to face pain, shares the untold story of his journey from a childhood craving for attention to becoming an icon of wild antics and extreme performances.
Opening up about his struggles with alcoholism, the relentless pursuit of fame, and his battles with feeling 'not good enough', Glover offers an introspective look into the complexities behind the laughter and the screams.
With raw honesty, he discusses the pivotal moments that shaped him, the drive to document his existence through stunts, and the liberating power of sharing the secrets he once vowed to take to his grave.
This interview is not just a glimpse into the life of a professional idiot; it's a candid exploration of human vulnerability, the cost of fame, and the ongoing quest for self-acceptance.
About Steve-O:
Steve-O (a.k.a. Stephen Glover) was willing to do whatever it took to become famous, even if it meant stapling his ball sack to his leg. After failing miserably at the University of Miami and couch-surfing with friends, he decided that in order to further his goal of becoming a stuntman he would enroll in Ringling Brothers and Barnum & Bailey Clown College. But it was his relentless attention whoring that ultimately led to working with Johnny Knoxville on a new stunt-based reality show called Jackass.
In 2000, MTV aired the first season and the rest, as they say, is history. Since then, he's had continued success, as a New York Times best-selling author with the release of his memoir, 'Professional Idiot', as well as establishing himself in the world of stand-up comedy. With fourteen years of sobriety under his belt, Steve-O shows no signs of slowing down.
Former SNL star @JayPharoah answers our most challenging questions about life, self-esteem, and changing his mind.
Jay Pharoah is known best for his impressions, but he’s got a lot more going on. The actor, comedian, and rapper sat down with us to talk about embracing triumphs, overcoming setbacks, forgiveness, and the way all of it shapes who you are.
About Jay Pharoah:
Jay Pharoah is an actor and stand-up comedian. With six seasons as a cast member of NBC's Saturday Night Live, Pharoah is best known for his wide array of uncanny celebrity impressions, including President Barack Obama, Will Smith, Denzel Washington, Stephen A. Smith, Kanye West and Chris Tucker, as well as his recurring character, school principal Daniel Frye.
Over 250 million records sold and more than 70 platinum hits later, @JasonDerulo sits down with us to talk about goals, insecurities, and why he still doesn’t feel like he’s “made it.”
Jason Derulo's career flashed before his eyes when he broke his neck in 2012. Despite fearing the worst, he used positive self-talk and daily routines to recover and create hit songs like “Marry Me” and “Talk Dirty.” Overcoming childhood insecurities, he emphasizes the power of self-improvement. Now a global superstar with 250 million singles sold, Derulo prioritizes family time since becoming a father in 2021.
Cindy Gallop answers our questions about sex, identity, and why we need to stop giving a damn.
Cindy Gallop, the founder and CEO of MakeLoveNotPorn, answered our questions about self-worth, the weight of other people’s expectations on women, and hope.
She shares her mission to normalize and destigmatize conversations about sex, including the negative consequences of using pornography as a substitute for sexual education.
Cindy hopes for a world where we’re all unburdened by societal judgments and true equality is achieved.
About Cindy Gallop:
Cindy Gallop is a graduate of Somerville College, Oxford, whose background is over 30 years in brand-building, marketing and advertising — she started up the US office of ad agency Bartle Bogle Hegarty in New York in 1998 and in 2003 was named Advertising Woman of the Year.
She is the founder and CEO of IfWeRanTheWorld, co-action software launched in beta at TED 2010 and subsequently written up and taught as a Harvard Business School case study, which enables brands to implement the business model of the future — Shared Values + Shared Action = Shared Profit (financial and social).
She is also the founder of MakeLoveNotPorn – ‘Pro-sex. Pro-porn. Pro-knowing the difference’ — a social sextech platform designed to promote good sexual behavior and good sexual values, which she launched at TED 2009, and for which she has just raised $2 million to build out MLNP.tv as ‘the Social Sex Revolution’.Cindy recently partnered with AARP on their Disrupt Aging initiative to challenge and change ageism.
Cindy has also published ‘Make Love Not Porn: Technology’s Hardcore Impact on Human Behavior’ as one of TED’s line of TEDBooks.
You can follow her on Twitter @cindygallop.
He co-created one of TV’s funniest shows. He still felt like a failure in his 30s. This is comedian Neal Brennan’s story about conquering toxic self-talk.
We all tell lies to ourselves about ourselves, usually in the form of vicious inner criticism. Neal Brennan, seasoned comedian and one of the brilliant minds behind “Chapelle’s Show,” confronted his inner critic on video for our entertainment.
Despite being instrumental in one of the most successful comedy shows of all time, there was a time when Brennan didn’t think he had much to show for himself, especially not as a solo entertainer. The eventual demise of “Chappelle’s Show” led him down a dark path of self-doubt and, then, rediscovery.
Brennan worked 12-step programs, ventured into the world of psychedelics, and even tried magnetic brain manipulation to break out of his despair. Now, he has a new perspective on the value of going it alone. Turns out, it isn’t quite so bad.
About Neal Brennan:
Three-time Emmy nominated writer, director, producer, and standup comedian Neal Brennan has become a force in the comedy world. An across-the-board talent, Neal has found success in almost every creative vein in the comedy landscape. Hailed by The Hollywood Reporter as “Hollywood’s Comic Whisperer” and lauded by The New York Times as having a “hip-hop and Frontline aesthetic,” he has collaborated with top talent both in front of and behind the camera for three decades.
Neal’s most recent one-man show Neal Brennan: Unacceptable enjoyed a sold-out run in NYC in 2021 with The New York Times offering “Brennan starts off with a regular joke format before turning toward introspection as he exposes his doubts, neuroses and vulnerabilities. And he remains very funny as he does so.” Neal’s critically acclaimed first off-Broadway one-man show 3 Mics also enjoyed a sold-out NYC run in 2016 with musician John Legend serving as Executive Producer with Paste Magazine gushing “It will floor you in the best way possible.” In a break from traditional standup comedy, 3 Mics saw Brennan alternating between three separate microphones; one for traditional stand-up, one for one-liners, and one for short confessional monologues covering everything from managing his depression to his difficult relationship with his father. Both one-man shows were taped as stand-up specials and premiered on Netflix to much fanfare and critical acclaim.
Neal co-created Comedy Central’s legendary Chappelle’s Show, for which he received three Emmy nominations. Together, Brennan and Dave Chappelle wrote and produced virtually every sketch on the show themselves. A longtime writing partner of Chappelle, Neal was a standout speaker in his televised Mark Twain Prize ceremony, wrote on his Emmy-winning 2016 Saturday Night Live hosting turn, and co-wrote the cult hit feature Half Baked. Neal also served as a Creative Consultant and on-air correspondent on Comedy Central’s The Daily Show with Trevor Noah, for which he was personally picked by Noah to be his final guest. He was Executive Producer on Chris Rock’s special Chris Rock: Tamborine, Consulting Producer on Ellen Degeneres’ special Relatable, and collaborator with Seth Meyers on his White House Correspondents Dinner speech. In addition to standup, writing, directing, and producing, Brennan has also directed popular commercials for Sprite, Netflix, Best Buy and Nike.
The Osbournes was MTV’s biggest show – and it almost cost Jack Osbourne his life. Here’s how his family’s reality TV fame stole his childhood, and how he’s been able to heal since.
About Jack Osbourne:
Jack Osbourne is well known for participating in reality TV shows with his celebrity family, like The Osbournes and Ozzy and Jack’s World Tour. Jack has also overcome and dealt with great difficulties in his life, such as dyslexia, drug addiction, an MS diagnosis, depression, various medical scares in his family, and more. His ability to bounce back from these challenges has served as inspiration for others undergoing difficulties in life. Jack uses his platform to advocate for people living with MS.
Jim Lee, President, Publisher, and Chief Creative Officer of tells us how his childhood obsession with Superman changed his life.
Jim Lee is synonymous with DC Comics now, but when he was first charting his path, his family pushed him towards medical school. In this interview, Jim shares how he reasoned with his parents and bought time to pursue his dream of being a comic book artist over the span of a gap year.
About Jim Lee:
Jim Lee, a world-renowned comic book artist, writer, editor and publisher, is currently Chief Creative Officer of DC (DC) and Publisher for the company.
Known for his incredibly detailed and dynamic artistic style, Lee is one of the most revered and respected artists in American comics. A veritable legend in the industry, he has received numerous accolades and recognition for his work, including the Harvey Special Award for New Talent in 1990, the Inkpot Award in 1992, and the Wizard Fan Award in 1996, 2002 and 2003.
Shaka Senghor spent 19 years in prison, 7 of them in solitary confinement. This is how he found true freedom.
The way Shaka Senghor tells his story, he found himself incarcerated long before he officially went to prison for second-degree murder, and he experienced freedom long before completing his sentence at the age of 38.
Senghor ran away from home and got drawn into the crack cocaine trade at the age of 14. After a series of traumatic events, he felt trapped in a narrative that dictated his life could only lead to limited outcomes: an early grave or a prison cell.
In our intimate interview, Senghor shares the three "keys" that transformed his perspective on life and have enabled him to live as a genuinely free man today.
“The Blind Side” only told part of Michael Oher’s story. Now, he tells us the rest.
You might know Michael Oher as the subject of “The Blind Side,” the 2009 movie starring Sandra Bullock and Tim McGraw. The film was based on the true story of Oher, a young Black football player, who gained a second chance at life after being adopted by white parents.
But Oher’s version of the story is a lot different, and it starts long before the Tuohys entered the picture.
In this interview conducted with our partner Unlikely Collaborators, Oher paints a picture of the crack epidemic in the ‘80s and ‘90s, a broken and tumultuous family, and a young boy determined to climb out of it.
About Michael Oher:
Michael Oher gained widespread recognition through Michael Lewis's book "The Blind Side" and its film adaptation, which depicted his difficulties in early life and time playing college football. After attending the University of Mississippi, he played in the NFL for the Baltimore Ravens, Tennessee Titans, and Carolina Panthers, winning the SuperBowl with the Ravens in 2013.
Michael has also written two books: I Beat The Odds and When You’re Back’s Against The Wall, which detail his struggles and successes in life, imparting wisdom on how to overcome adversity. Michael has also contributed to the book Blindsided, where he outlines his experience of early-stage CTE, how he walked away from the NFL, and his urgent recommendations to reform football and make it a safer sport.
Built from the material of your beliefs (aka, the bullshit you tell yourself and collect from those around you over the course of your life), the Perception Box™ has the power to distort your reality and leave you feeling isolated, disconnected, and fearful. By asking sometimes contradictory but always consequential questions, we’ll show you how to understand and work with your Perception Box—how to overcome the limiting beliefs that hold you back, expand the possibilities of perception, and invite in new ways of seeing and being seen.
A guided body awareness mediation to help you get out of your head and into your body. Learn to tune into your body for a heads up on what you’re feeling before you explode. It’s literally your friend on the inside.
Simple, easy, and faster than chasing down that driver that cut you off.
Orin Davis earned the first doctorate in positive psychology, and is a self-actualization engineer who enables people to do and be their best. As the Principal Investigator of the Quality of Life Laboratory, he conducts research on flow, creativity, hypnosis, and mentoring. Dr. Davis consults for companies from startups to multinationals on hiring strategies, culture, innovation, and employee well-being. He is the author of Team Flow: The psychology of optimal collaboration.
Scott Barry Kaufman talks to Orin Davis about the new science of flow. A lot of people are familiar with the concept of flow, but according to Dr. Davis, the experience of it is not very common. They discuss Mihaly Csikszentmihalyi’s work and how Dr. Davis is expanding the research of flow by studying it at a group level. Dr. Davis talks about how we can increase the chances of experiencing flow for both individuals and teams. Orin and Scott also touch on the topics of microflow, hypnosis, absorption, positive psychology, and self-actualization.
Website: https://qllab.org/
X: @DrOrinDavis
Robert Sapolsky is professor of biology and neurology at Stanford University and a research associate with the Institute of Primate Research at the National Museum of Kenya. His research has been featured in the National Geographic documentary "Stress: Portrait of a Killer". At age 30, Robert received the MacArthur Foundation's "genius" grant. He is author of Why Zebras Don't Get Ulcers, A Primate's Memoir, The Trouble with Testosterone and Monkeyluv. His latest book is called Determined: A Science of Life Without Free Will.
Scott Barry Kaufman talks to Robert Sapolsky about life without free will. Humans like the idea of having control over their lives, but Robert asserts that free will is just an illusion. Life beyond free will may sound unpleasant, but Robert explains the profound consequences of this belief in reforming the justice system, meritocracy, and education. Robert and Scott also touch on the topics of philosophy, quantum physics, mindfulness, grit, and responsibility.
LinkedIn: www.linkedin.com/in/robertsapolsky/
For over 40 years, Bob Mankoff has been the driving force of comedy and satire at some of the most honored publications in America, including The New Yorker and Esquire. He is the founder of Cartoon Collections, parent company to CartoonStock.com, the world’s most successful cartoon licensing platform. For twenty years as Cartoon Editor for The New Yorker, Bob pored over thousands of submissions each week, analyzing, critiquing, and selecting each cartoon. In 2005, he helped start the “New Yorker Cartoon Caption Contest.” Bob is the author of numerous books, including his New York Times bestselling memoir, How About Never – Is Never Good For You?: My Life In Cartoons.
Scott Barry Kaufman talks to Bob Mankoff about the psychology of humor. Looking back at his illustrious career as a cartoonist, Bob talks about his early beginnings and the people he's mentored in the field. He explains the anatomy of a joke and reveals his all-time favorite cartoons. While humans are creative creatures, Bob believes that using AI and technology can further augment our intelligence and humor by opening up worlds of possibilities.
Website: www.bobmankoff.com
X: @BobMankoff
Joseph Goldstein is a co-founder and the guiding teacher of the Insight Meditation Society (IMS) along with Jack Kornfield and Sharon Salzberg. He is one of the first American vipassana teachers and has been teaching Buddhist meditation worldwide since 1974. A contemporary author of numerous popular books on Buddhism, his publications include Mindfulness: A Practical Guide to Awakening, One Dharma, Insight Meditation and others.
Scott Barry Kaufman talks to Joseph Goldstein about Buddhism and the impermanence of life. Being too attached to the self can bring suffering. However, this doesn’t mean that we need to forego our identities or self-care. Joseph explains that enlightenment can be achieved when the mind is free from clinging. He talks about the different states that can help us realize the insight of impermanence and selflessness. Scott and Joseph also touch on the topics of mindfulness, compassion, creativity, and wisdom.
Website: www.dharma.org
X: @onedharma
Dan Siegel is a clinical professor of psychiatry at the UCLA School of Medicine and the founding co-director of the Mindful Awareness Research Center at UCLA. Dr. Siegel is also the Executive Director of the Mindsight Institute. He’s authored numerous articles, chapters, and books including the New York Times bestsellers Mind: A Journey to the Heart of Being Human and Aware: The Science and Practice of Presence. His latest book is called IntraConnected: MWe (Me + We) as the Integration of Self, Identity, and Belonging.
Scott Barry Kaufman talks to Dr. Dan Siegel about expanding the notion of the self. Modern culture has taught us that the self is all about individual identity and personal experiences. But Dr. Siegel posits that who we are is not limited to the brain or body. He argues that the self is not isolated, it’s composed of our relationships to other living beings and to the natural world. This expanded view of the self has important implications for the trajectory of humanity. Dan and Scott also touch on the topics of consciousness, neuroscience, quantum physics, and the flow state.
Website: drdansiegel.com
Instagram: @DrDanSiegel
Michael Slepian is the Sanford C. Bernstein & Co. Associate Professor of Leadership and Ethics at Columbia University. A recipient of the Rising Star Award from the Association for Psychological Science, he is the leading expert on the psychology of secrets. He’s authored more than fifty articles on secrecy, truth, and deception. Michael’s research has been covered by The New York Times, The Atlantic, NPR, BBC, The Wall Street Journal and more. He is the author of The Secret Life of Secrets.
Scott Barry Kaufman talks to Michael Slepian about the psychology of secrets. Everyone has secrets that they keep from others—how does this affect our relationships and well-being? According to Michael, maintaining privacy is not the most burdensome aspect. Carrying a secret all by ourselves is what weighs us down. Michael and Scott explore the different categories of secrets and we talk about when to reveal the deepest parts of ourselves and who to reveal them to. Scott and Michael also touch on the topics of personality, morality, trauma, developmental psychology and communication.
Website: michaelslepian.com
X: @michaelslepian
Monica Parker is the founder of global human analytics and change consultancy HATCH, whose clients include blue-chip companies such as LinkedIn, Google, Prudential, and LEGO. Her career has been nothing short of colorful, having been an opera singer, a museum exhibition designer, a policy director, a Chamber of Commerce CEO, and a homicide investigator. She is also a world-renowned speaker, writer, and the author of The Power of Wonder.
Scott Barry Kaufman talks to Monica Parker about the power of wonder. In today’s fast-paced world, most people fail to notice the richness of life. To become more wonder-prone, Monica encourages us all to slow down and pursue meaningful exploration. When we pay more careful attention to the world, we become more empathetic, resilient, and exuberant. Monica shares with her cycle of wonder framework and how we can be more open and present in our daily lives. Monica and Scott also touch on the topics of personality, post-traumatic growth, mindfulness, and education.
Website: www.monica-parker.com
Instagram: @monicacparker
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