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Dr. John Krystal

lines on the record: 207
first: 2022-09-29
most recent: 2022-09-29
sittings or episodes: 1
sources: podcast

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“At the time that I was studying ketamine, I was interacting regularly with this broader group of people. Ronduma was at Yale, George Agageni and Yale, Eric Nessler, Dennis Charney, obviously my collaborator and mentor, and many other people. So one of the things that was really striking was when we had made this finding with ketamine and shared the results with Ron, I had the feeling that Ron thought that it was more important than we did. So, you know, he would say this is like the most important finding in fifty years, and we would say, what? And so he was really highly motivated to try to understand how ketamine worked. And his own research was in the area of the basic neuroscience of stress and antidepressant activity. He was the first to show that antidepressants stimulate”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“And it's, I think, related to the abuse academy. It says ketamine, and it's got a picture of a horse. Just say nay, N-E-I-G-H.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“So, first, I have to tell you about a cartoon that I saw about ketamine related to its use as a horse tranquilizer, which is the cartoon says”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“By giving a single dose academy is we're not making random new connections in the brain. That would be a bad thing. The brain is not chaotic structure. And we don't want to make random connections because that would make things worse in theory. I mean, that's what you get with epilepsy, a growth of inappropriate connections in parts of the brain. What we do is overcome whatever intrinsic resistance there is to recovery in the brain, to give a brief pulse of academy and enable a restoration of the brain's intrinsic capacity to develop and maintain structural connectivity. And we think that is a part of the story of how ketamine works in the brain. That insight happened around 2010, and that was really fundamentally important in terms of drawing.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Stress related behaviors, impairments in cognition, difficulty solving problems, difficulty regulating emotions, etc. All of these behavioral changes that we associated with the emergence of stress-related changes in animals and depressions in people, that loss of connections between nerve cells and the brain are a part of that series of events. And that within 24 hours of a single dose, these brain connections could go back. What a profound new way of thinking about what we're doing in the brain. And one of the things that's maybe a subtle point, but to me profound is I view depression treatment as about thinking about how we restore behavioral and emotional resilience and how we can tap into the brain's intrinsic capacity for resilience to promote behavioral resilience. So what we've done”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“It produced rapid and profound biochemical, electrophysiological, and structural change in the brain within twenty four hours. And this builds on an idea that really came first from the pioneering scientist Bruce McEwen, who is just another wonderful person and scientist who was based at the Rockefeller University, that if you stress animals, severe stress over a period of time, long period of time, that not only do they have behavioral changes, but that those behavioral changes are associated with the loss of the synaptic connections in the brain, that the circuits involved in the regulation Lose a small percentage of the synapses, but enough to have profound functional and behavioral consequences.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“And showing that psychedelic drug changed the activity rate of these serotonin neurons, giving one of the first neural signatures of psychedelic drugs in the brain as well. So it's really kind of life goes full circle in a way that George Agagenian and Ron Dooman together showed that if you give a dose academy to stressed animals,”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Just an incredible trail blazing scientist, remarkably brilliant and talented neuroscientist and a wonderful person, colleague, and friend. And he did this study in collaboration with George Agaganian. Now, for those in the psychedelic world, you may be familiar with it name. But George Agagenian and Danny Friedman, who was his mentor around 1960, 1958, 1959, 1960, the early 1960s, did some of the first studies to implicate serotonin signaling in the mechanism of action of psychedelic drugs. And George was the first person, the first physiologist to record the activity of serotonin and nerve cells in the brain.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“which is somewhere in between'97 I guess is the first presentation, and the early 2000s that I started to hear about its use already in clinical practice, which doctors can do because it's an FDA-approved drug. And the other key turning point. I think for the field came in two thousand ten, with the work of my late colleague Van Duman, and Ron was”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Are you talking about? I've already started using ketamine in my clinical practice, and I'm having great results, and I would like go pale, and I would freeze, and I would say, well, it's still an experimental procedure. We don't have enough evidence to really adopt it yet in clinical practice, but that's really what happened.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“And the first paper of a study that tried to replicate those ketamine effects came out in 2006. And that was because Dennis Charney had moved to NIMH. He had built a program, he and Hussein Mangi and Carlos Serati designed and executed a study to replicate the initial finding. And you know what? They found basically exactly what we found. And then more and more groups started to replicate that work and found the same thing over and over again. And people started to believe it. And something really remarkable happened, which is that I started to give talks and I would describe how we gave ketamine as this research procedure and it produced these antidepressant effects. And now what we need are definitive trials because we really have preliminary evidence, but we really need definitive trials. And then psychiatrists would tell me from the audience, what are”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Exactly. But it happened over and over and over in this pilot study. And we didn't really know exactly what to make of it. And we started sharing the findings with people. You know, science is just wonderful because the dominant mode of interaction in science is skepticism. So we would present these data and we'd say, no, people got a dose acetamine and the next day they were several of them were better. And they'd say, right. Skepticism overall. And it took a long time for other groups to even try to replicate that ketamine finding. We presented the first results for the first time in 1997.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“What? And okay, we know that these kinds of things happen. You know, you give somebody a glass of tea and the next morning a cup of coffee, a really good croissant. And the next day they really feel better. Fantastic. But we don't really, we didn't really think with the first...”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“And then the day test day went on, and within a couple of hours people said, you know, I'm feeling a little better. We thought, right, you're feeling a little better. Great, fantastic. And then we sent them home. And then we called them the next day. Did you have any bad effects from your ketamine exposure? Do you have any hangover? Do you have any lasting effects? Did you sleep okay last the night before? And they said, you know what? My depression's all better And we said.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Mechanisms in the brain. So we thought well let's try that. So by that time I had been studying for at least five years. I had been studying ketamine to try to understand its role in synaptic signaling in disorders, problems, cognitive processes, behavior, other things related to schizophrenia. And we thought, well, we can use ketamine to probe the integrity of glutamate synaptic signaling. That's been what I've been working on for the last five years. Let's bring that into testing depression. And we designed a study, and we gave ketamine to depress patients. And ketamine did transiently produce some cognitive impairment and some changes in things like that lasted an hour or so. And then those effects went away. And, you know, we saw nothing special. Ketamine has the same kind of... In depression as it does in healthy subjects.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“The function of the cerebral cortex and limbic system is essentially a dynamic tension, like yin and yang, between factors driving excitation, the magnitude of excitation, and the timing of excitation and the spatial dispersion of activity in the brain and GABA balancing and inhibition. And we thought, well, gee, how can we tap into signaling through the main information highway of the brain? And it's really remarkable, isn't it? Serotonin is maybe a couple of percentages of the synapses in the brain. Glutamate is 90%. Psychiatry has been studying depression for 50 years by that point. Put all of its chips on serotonin and opinephrine to 2% and completely ignoring the 98% of the”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Consequence of that small conceptual shift because the cortex in the limbic system are predominantly driven by different chemical messengers than serotonin and arbiniferin. Serotonin and arpinephrine tune and modulate the activities of the higher brain centers, but it pulled us to think about the intrinsic circuit mechanisms of the cortex and limbic system and to try to approach those circuits directly with pharmacology. These higher brain centers predominantly use two neurotransmitters, glutamate, which accounts for something like 90% of the synapses of the brain. The main information highway the brain, ninety percent of the synapses, the main excitatory driver for And Gavit, which is the main inhibitory transmitter of the cortex.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“A really weird turn of phrase, but yeah, let's turn this problem upside down. If depression isn't a disorder of these really simple and few serotonin cells in the brain, then maybe it's a disorder. That has a major part of its biology in the parts of the brain that are responsible for regulating emotion, for processing reward, for making plans, for interpreting the world. In other words, the higher cognitive centers like the cortex, cerebral cortex, and the higher emotional centers in the limbic system. And there was a profound”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Probably was just that idea itself was probably flawed from the start. But like all conceptual crises, it was incredibly stimulating in terms of creative thought about what the alternative ideas about depression were. And so in those days, when these experiments were going on, Dennis Charney, who was now my boss, as well as my collab writer, his office was upstairs on the ninth floor. He had a really good view of Long Island Sound, and I had a little office on the eighth floor. You know, I would go up at the end of the day and we would talk about science and all the things that are going on. And we wrestled with this. This is one of the things that we wrestled with a lot. If it wasn't serotonin simply, what could it be? And the answer was that we came to was, let's turn it on, let's turn the brain on its head.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Conceptual crisis like the philosopher Thomas Kuhn would say You come to a point where you have a body of theory and then you have a single experiment which in a fundamental way challenges the idea that this idea that depression is simply a disorder of the very primitive and very few number of serotonin cells that live in a very primitive part of the brain the mid-brain and a little bit of the brain stem that these primitive cells could be the cause of this pervasive syndrome of cognitive behavioral etc etc impairment”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“The other thing thou say just before moving on because there's a tendency to want to make the world simple. Either it's all serotonin or it's no serotonin. But as I said, would the most complex structure in the universe really work in such a simple minded way that it had to be everything or nothing? Probably not. And there are brain scan studies in depression involving positron emission tomography, the work of people like Ramin Parsi and others that do find some changes in the regulation of certain serotonin receptors that may be intrinsic to the biology of depression. So I'm not in any way arguing for a really simple minded idea of depression. But I do want to highlight that these monoamine depletion studies were a”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“The world is really complicated, and maybe we'll come back to it. And what's complicated is that serotonin does have a lot of acute effects in the brain. And a single dose of prozac does change some things. So, for example, Catherine Harmer at the University of Oxford in the United Kingdom has done a large number of studies to show that some of the negative biases that people have when they're depressed go away, at least transiently, with a single dose of prosaic. So it's not that there aren't some acute effects and that those effects aren't related to depression. It's just that the simple-minded idea that low serotonin equals depression, normal serotonin equals healthy life, that idea is, we knew pretty much from the start, couldn't possibly be true as it was initial.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Associated with serotonin synapses really underlay the antidepressant effects as an initial and in some ways ongoing mechanism of action for the SSRI antidepressants like prosaic. But when you depleted serotonin in healthy people, you did not make them depressed. So there had been an idea floating around that depression was a manifestation of a pure deficit in serotonin, lower serotonin, you get depressed. Take a prozac, you get undepressed. We knew that idea was wrong right from the start because you take a tablet of prozac, you do not get undepressed from a single tablet of prozac. It can happen extraordinarily rare and it usually doesn't last when that occurs.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Basic question, but we didn't know. So what Pedro did was to deplete the body of serotonin using this tryptophan depletion technique, which involved giving all the other amino acids, tryptophan restricting, and then giving all the other amino acids to drive protein synthesis and use up all the free triptophan so it couldn't be used to make serotonin. Dropping the serotonin levels and producing a brief relapse of depression. And so you could show that the antidepressant effects of drugs like prozac dependent on the ability of the brain and on an ongoing way to have a big supply of serotonin. And that was really important. And it really supported mechanistic ideas that had already been underway in a series of pioneering laboratories around the country, including the Laboratory of George Agageni at Yale, that at neuroadaptapations”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Research going on in psychiatry. And what they figured out, building on the work of an alum, a graduate of our department who moved to McGill, Claude de Montigny, they developed a strategy for depleting the body of serotonin. It builds on the idea that tryptophan, which is the precursor for serotonin, is an essential amino acid. So if you deplete the body of free tryptophan, then the body all over the body you can't make any more serotonin. And you can drop the level of serotonin in the blood and in the body and in the brain. And we could use that technique, Pedro Delgado really led the clinical projects in those days. We could use that technique to ask first the question, which is such a fundamental question, but had not yet been answered, is serotonin necessary for the antidepressant effects of prozac? Couldn't be a more”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“So the brain is perhaps the most complex structure in the entire universe. And you're trying to draw inferences about what's happening in certain connections by whether when you give a drug, does the cortisol level go up? Does the prolactin level go down? So it's really rough and ready neuroscience. And it's a little bit like Ptolemaic astronomy in the sense that you have no understanding about really how the universe is constructed and yet remarkably the Ptolemaic astronomers could build elaborate explanatory systems to explain how the planets were moving in relation to each other. And that's really where psychiatry was in the 80s. And this was the leading edge of mechanistic research, in other words, the first in some ways kinds of mechanistic”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“My colleagues, the people that I trained with and have had my career with, in particular my mentor Dennis Charney, with whom we did the first ketamine study, you know, they spent their careers trying to figure out what was the role of these chemicals serotonin and norpinephrine in depression and antidepressant treatment. And this was an era of real creative psychopharmacology research. It's before CAT scans, before MRI, before FMRI, before PET scans, before any of that. And they had to use pharmacology and measuring neuroendocrine responses and behavior as a way to try to figure out what was going on in the brain.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“In lots of really things that people really enjoy eating, these kinds of foods have a lot of tyranny. So they're really great drugs, but they do, you have to be a little careful with them.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“You recall, these monominatious neighbors cause a form of release of norepinephrinephrine serotonin and prevent their breakdown. So anything independent of the drug increased the release of norepinephrine and serotonin, had the potential to produce massive increases in norepinephrine and serotonin in the body. And so the problem you get in if you have a massive increase in norepinephrine is you can get big increases in blood pressure that can be life-threatening. And if you get a big increase in serotonin, you can develop something called a serotonin syndrome, which can also be very serious medically. It raises body temperature and creates a stress on the system. And the thing was that the kinds of things that most commonly were a problem is that there's a compound in aged cheese, in wines.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“So the way that monoamine oxidase inhibitors work is by inhibiting an enzyme called monoamine oxidase, which is involved in the breakdown, the metabolism of the chemicals norpinephrine and serotonin. And so when you give a monoamine oxidase inhibitor, you raise the level of serotonin norpinephrine in the synapse, the space between nerve cells, and you increase the stimulation of the receptors for those chemicals. And in that way, they're a little bit like the SSRIs, which instead of preventing the breakdown, they prevent cells from taking up out of the synaptic space these same chemicals. The monoamain oxidase inhibitors also release a bit norepinephrine serotonin so that they release a little bit and they prevent the uptakes. They're actually powerful antidepressant. They have some side effects and risks that have limited their use in modern clinical practice. But in the era in which I trained were very commonly prescribed.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“A drug that prevented the breakdown of norepinephrine and serotonin to chemicals that have been implicated in depression. And it's a great story because the first monoamine inhibitor given to depressed patients was given accidentally because it was a treatment for tuberculosis. And they discovered that the tuberculosis patients, their tuberculosis was getting better, but so was their depression. And so that's how they discovered that first antidepressant. Then they discovered through a similar, a little bit accidental path the tricyclic antidepressants then much later in the 1980s, the SSRIs, which are like the tricyclic antidepressants but act in a more narrow and specific way in the brain to block serotonin reuptake.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“If you don't mind, I might track the historical story because it really takes us from Serotonin hypothesis to what's really exciting. And I told you this before, and I really believe that this is the most exciting scientific time in the entire history of the field of psychiatry. You know, that we have been operating in some ways in the dark with not a very good understanding of what's happening in the brain for the last 60 years. And the sunlight is really just beginning to penetrate into our understanding of the brain in ways that are relevant to thinking about the biology and treatment of depression and other kinds of issues. So the serotonin story, the serotonin hypothesis really emerged from the appreciation of the effectiveness of antidepressant medications. The first antidepressant that we had, which was discovered in 1957, which makes it one year older than I am, was a drug called”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Respond to multiple different kinds of medications, electro convulsive therapy is sometimes the only treatment that will work.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Has restricted the availability of certain what are so called gold standard or definitive treatments. And one of those would be electric convulsive therapy. Now electric convulsive therapy, we know is somewhat controversial in areas. It's obviously a treatment that has both medical and in some cases cognitive risks for patients. On the other hand, What's often appreciated, and one of the reasons I mentioned the medical risks of depression is that depression, when untreated, has medical and cognitive risks at all that have to be balanced against the risks and benefits of these treatments. But the number of sites that administer electric convulsive therapy has been progressively decreasing in this country, which means that access to this treatment has become progressively limited, even though for people who fail to”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Worked really hard over a long period of time to get to the point where they're only a five. And there is justifiably a sense of accomplishment and investment in that new status quo. But what there is, though, is a failure to say, have I exhausted all possible outcomes to go from a five out of ten to a 2 out of 10? And the answer is in most cases the possible outcomes have not been explored. And this is really important. We have to keep pressing because not only is there a possibility of adding another kind of treatment that would be making the patient better, but there is also the possibility that we might need to remove a medication that's interfering with resilience and recovery. The other thing is that we are in a country which”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“One of the reasons is the invisibility of inadequate responses. So what can happen is that people will start treatment. Maybe they start treatment with psychotherapy and maybe the treatment is somewhat helpful for them, but it hasn't worked entirely. And then maybe they then add a medication to the psychotherapy. And maybe that medication is somewhat helpful, but not entirely. The person has gone from an eight out of ten to a five out of ten. So they're substantially better than they started off, but they're substantially symptomatic. And in ways that take a toll on them, their social relationships, their work productivity. So why is it invisible? It's invisible because both the doctor and the patient have worked”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Basically brief questionnaires that people can complete to give us some semi quantitative idea about how people are doing, but those outcome measures aren't routinely applied in clinical practice, and so that as a field, when we look at our healthcare systems, there's no data on outcomes for the clinical interventions or much less data on outcomes. Some healthcare systems like the VA have started to embed clinical ratings into clinical care. But it's not a situation where the field has been held accountable for the outcomes. And the field hasn't been held accountable for outcomes. The insurance companies have not been held accountable for the outcomes. The country has not been held accountable for outcomes. And that has been particularly problematic for depression for a number of reasons.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Reasons why that tends to happen a little bit more in psychiatry than in some other aspects of medicine. One of them is that there's just inadequate support for psychiatry, mental health treatment generally. So it's a scarce resource and people often essentially take what they can get. And that speaks to the inadequacy of our national approach to making sure that people have access to effective health care. A second thing is We don't measure outcomes in clinical practice in any kind of routine way. In other words, if you have a heart attack, then you get scans and they measure the EKG, the electrical activity of the heart. Maybe you have a stress test. Maybe you have an echocardiogram to measure the ability of your heart to contract. Well, where are those tests in psychiatry? Those tests to the extent that we have them”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“In other words, they would say things like, well, the patient wasn't adequately engaged in treatment, they didn't engage in psychotherapy, they weren't a good psychotherapy candidate, they didn't blah blah blah. And while it's true that people engage in treatment with varying levels of motivation and understanding and things like that, we would never say for heart attack, for heart disease, well, you know, they had a heart attack, but they weren't very motivated to be in treatment, so what could we do? We would never say that. We would always say, well, let's look at the illness. Let's try to optimize the treatment. And if people aren't responding, let's do something about that. for the fact that our treatments don't always work as effectively as we'd like them to be. Now there are some underlying”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“So psychiatry has struggled with what to do with partial response and non-response for all psychiatric disorders. And I'm embarrassed to say that there is a strain of a history in psychiatry. When patients didn't get better that they blame the patient.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Illnesses where inflammation is a process worse. If you have untreated depression, on average, it shortens your life not by suicide, it still shortens your life by about five years. And if you have depression in the context of medical illnesses, it makes the medical outcomes worse. Not only the psychological outcomes, but the medical outcomes worse. Depression is a disorder of the spirit, if you will, the brain, but also the whole body. And that's one of the reasons why, number one, it's one of the most disabling conditions that we have in the world. And two, it's from a medical point of view, it's also urgently important that people are treating their depression.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“But one thing that's really important for people to understand that they often don't understand is the medical part of depression. And when I say medical part is that we understand, yes, medical depression is a state of emotional experience. And yes, it's a altered way of brain function, but it's a brain function of an embodied brain. In other words, depression is a state that affects your entire body. Medical factors like inflammatory processes in the body related to obesity, cardiac disease, arthritis, asthma, a variety of things that cause inflammation in the body, increase your risk for depression. And if you have depression, it makes inflammation worse. And that means it makes all of those medical”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Ever since. And there's another kind of depression that we also see, which is people who have the capacity to see good and bad, but who cannot constrain the way in which they react. So something good happens, they can react in a normal way to it. But something bad happens to them and they spiral downward in a very negative way beyond their control to despair and hopelessness and extreme distress. That is not the typical profile of traditional melancholic depression, but as a kind of reactive depression, one of the things that we appreciate about depression is that can be a very heterogeneous thing, that there's a whole array of different kinds of depression, and we're just at the early stages of sorting that out.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“And I mentioned a sapping of energy, loss of appetite, a decrease interest in activities a kind of withdrawal this state was deemed by the Greek hypocritic doctors as a kind of fundamental negative mode of being that they thought was connected to black bile, which in Greek had the name Melon for black colia for bile, and then has been known as melancholic depression”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“People often describe feeling blue when they're depressed because the contrasts in the world, their visual experience of the world is as if the normal contrasts are blunted and colors seem duller and things that are exciting and rewarding seem blander and a kind of sapping of life's essence. This kind of depression is associated with a loss of energy, a loss of concentration, difficulty sleeping, waking up early in the morning, tossing and turning, in difficulty relaxing and feeling comfortable, being overcome with pervasive intrusive, recurring thoughts on negative things like a terrible person, I let people down over and over and over, ruminating on these negative, horrible ideas”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Mode of being that invades every aspect of one's life and experience of the world. It affects the pattern of your thinking, in other words, instead of, as you say, seeing the world as a mixture of risk and opportunity, you see the negative in everything that you engage. It affects the way you make judgments. Instead of being able to make judgments based on reasonable risk reward kinds of decisions, everything's colored by the negativity. What people often don't appreciate about depression is that it goes beyond sadness for many people it can be a complete blunting of emotional experience and people describe sometimes the loss of feeling. One of the people that we treated with ketamine said that she was just amazed to have feelings again after her depression began to lift.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“So, I think that people think that depression is like having a bad day. And everybody's had a bad day. And everybody's had a few bad days. And I think that some of the confusion about depression has to do with the way in which we throw depression around as a term like I spilled my coffee and I'm depressed about that. Now, yeah, that is a disappointment, right? But it's not that kind of experience isn't what we're talking about when we talk about depression. When we talk about depression is more about the experience that you're talking about. The way that depression can be a pervasive”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“Is an enormous gift that comes out of this kind of nurturing developmental experience. And so much of what he dealt with in treating people who had been traumatized in psychoanalysis and in psychotherapy was the way that early life traumas disrupt that and create a feeling not of optimism and the potential for things to work out, but the opposite, that in the expectation that the world is a dangerous threatening place and that failure lurks around the corner, and so creating the very constraints on creativity and motivation, deadening hope, deadening creativity, constraining opportunities that people are putting this cage on themselves as a consequence. Of the disruption of the sense of safety and possibility that is a natural byproduct of a nurturing childhood experience.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“I want to reassure you that he was like a normal person, and so he would never talk about the omnipotent interjected object at the dining room table. You can imagine people have all kinds of ideas about what psychoanalysts talk about over dinner, and mostly it was just pretty much bread and butter things. The second thing is that I think about that he believed that the parent child interaction was fundamental to all human resilience and that in that kind of nurturing, supportive interaction lay the root of optimism. And that having a sense that no matter what is happening around you, that there's still the possibility that things will work out okay.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source
“In the way that he developed his career profoundly impacted me in my thinking in the things that I thought were important in what I ended up pursuing in the way that I pursuing them. The other thing about my father was he was profoundly curious and would read religious, he would read history, he would read neuroscience, he would read philosophy, he would pursue almost any field that he thought had any relevance to what he was thinking about. And that perspective also was normally incredibly impactful for me and has influenced the way I approach everything that I do.”
2022-09-29 · The Tim Ferriss Show · #625: Dr. John Krystal — All Things Ketamine, The Most Comprehensive Podcast Episode Ever · IDENTIFIED FROM THE TRANSCRIPT · source