The Tim Ferriss Show - #631: In Case You Missed It: September 2022 Recap of "The Tim Ferriss Show"

Starting point is 00:00:00 This episode is brought to you by Five Bullet Friday, my very own email newsletter. It's become one of the most popular email newsletters in the world with millions of subscribers, and it's super, super simple. It does not clog up your inbox. Every Friday, I send out five bullet points, super short, of the coolest things I've found that week, which sometimes includes apps, books, documentaries, supplements, gadgets, new self-experiments, hacks, tricks, and all sorts of weird stuff that I dig up from around the world. You guys, podcast listeners and book readers, have asked me for something short and action-packed for a very long time. Because

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Starting point is 00:01:36 Again, that's tim.blog forward slash Friday. And thanks for checking it out. If the spirit moves you. Optimal minimum. At this altitude, I can run flat out for a half mile before my hands start shaking. Can I ask you a question? and thanks for checking it out. If the spirit moves you. Tim Ferriss Show. which serves as a recap of the episodes from the last month. It features a short clip from each conversation in one place, so you can jump around, get a feel for both the episode and the guest, and then you can always dig deeper by going to one of those episodes. View this episode as a buffet to whet your appetite. It's a lot of fun. We had fun putting it together. And for the full

Starting point is 00:02:39 list of the guests featured today, see the episode's description probably right below wherever you press play in your podcast app. Or as usual, you can head to Tim.blog slash podcast and find all the details there. Please enjoy. First up, bestselling author Dr. Gabor Mate, highly sought after for his expertise on a range of topics that includes addiction, stress, and childhood development. His new book is The Myth of Normal, Trauma, Illness, and Healing in a Toxic Culture. Let me come back to the rage for a second, because I would love to get your advice or had challenges in your marriage, your kids were, at least based on my notes, sort of afraid of you at points because of your rages. What have you learned about rage and anger? How do you relate to it or metabolize it? And I ask

Starting point is 00:03:59 as someone who has a long history of running on anger as maybe a corrosive fuel of sorts. So I would love to just hear you expand on that in any way that makes sense. Sure. So there was a great neuroscientist. His name was Yak Panksepp, P-A-N-K-S-E-P-P, who tragically died a few years ago of cancer. And he distinguished a number of brain systems that we share with other mammals.

Starting point is 00:04:27 They include care. He capitalized these. So C-A-R-E, care. Then something he calls grief and panic. Then fear, lust, seeking, play, and rage. These are all brain systems that we have. They're all necessary for mammalian life. They're all necessary.

Starting point is 00:04:52 By rage he means the anger that arises when our boundaries are being transgressed. If I were to infringe on your boundaries, either physically or emotionally, the healthy response for you is to mount an anger response. No, get out. Stay away. That's healthy. Healthy anger is in the moment. It protects your boundaries, and then it's gone it's not necessary anymore however if your boundaries were infringed as a child but you could not express it it doesn't disappear it gets suppressed it becomes almost like a volcano that's gurgling and bubbling inside, but it's had no expression. Now, why did you suppress it?

Starting point is 00:05:46 Because if you're being, well, you've been very public about this, so I'm sure you'll allow me to mention it, but you've, sometime after you and I talked, you actually publicly acknowledged that you'd been sexually abused as a child. I did. Now, when that's happening to a small child, the last thing you can afford is to be angry. Because if you get rageful at the boundary invasion, you're going to get hurt even more.

Starting point is 00:06:14 So suppressing that rage becomes a survival mechanism. Nothing wrong with it. It's the right thing to do. You don't do it, your brain will do it for you automatically as a way of preserving your life or your relative safety. do. You don't do it, your brain will do it for you automatically as a way of preserving your life or your relative safety. But the rage doesn't go away. What happens then later on as an adult, something triggers you and all of a sudden it just explodes out of you and you have no control over it. Now it's no longer a response, a healthy response to the present moment but it's a response to the past and just as my

Starting point is 00:06:48 hurt and sense of abandonment and enrage was triggered by my wife not picking me up at the airport so a person's rage can be triggered by something relatively minor but all of a sudden this lava flow just explodes out of you. And the difference between healthy anger, and by the way, suppressing healthy anger is also unhealthy for you, we can talk about that, but just as healthy anger expresses itself, does its job, and then it's gone, rage, such as I'm describing, such as the way I used to experience it and probably as used to experience it, the more it explodes, the bigger it gets. That's what happens to me. I've worked with certain therapists who have said, you know, punch a pillow, express the

Starting point is 00:07:32 rage, let it just pass through you like the wind. But that isn't, in fact, what happens with me. And I know I'm not the only one. It actually magnifies and intensifies and extends this feeling. Exactly. Because it recruits more brain circuits into its service. So that's the difference between healthy anger on the one hand, which is an essential boundary defense.

Starting point is 00:07:56 And by the way, so much parenting advice in this culture tells parents to force kids to suppress their anger. Really unhealthy advice. There's healthy anger, then there's that rage that you and I have both experienced. If you're going to punch a human being, and there's a pillow to punch instead, better to punch the pillow. No question about that. But as a technique of dealing with it, that's not how you learn to process that rage, because it needs to be processed. How do you approach the processing? What is a more effective prescription or one possible way?

Starting point is 00:08:30 Well, if I was working with you, I would encourage you to fully experience the body experience of rage, what's happening in your body. And you'll find that it's not just an idea in your head, it's something that dominates your visceral experience of yourself your muscles your breathing your abdomen your entire nervous system and there's ways of just helping you experience it experience it by raising the awareness of that somatic experience? Of being with it. Now, there's a wonderful Buddhist lineage spiritual teacher, meditation teacher called Tara Brach,

Starting point is 00:09:14 who talks about RAIN. Recognize, allow, investigate, and nurture. So you recognize, oh yeah, this is happening to me right now. Okay, I'm going to allow it. Not along in the sense of, I'm going to act it out on somebody else, but I'm going to be with the experience. And then investigate, okay, what is this video all about? And then nurture that little person that had to suppress all that rage. It's a nutshell view of it, but in other words, there's ways of working with it through the body that doesn't involve either suppressing it or acting it out,

Starting point is 00:09:54 but in experiencing it. Next up, Bas Rutten, a Dutch-American actor, former mixed martial artist, kickboxer, and professional wrestler. He was a UFC heavyweight champion and a three-time King of Pancrase world champion. We can't tease the Sweden story without... Okay, so Sweden. What happened in Sweden? We can't tease the Sweden story without... Oh! Okay, so Sweden. What happened in Sweden?

Starting point is 00:10:31 Okay, so understand this. When I'm drunk, I'm a happy drunk. I'm always drowsy partying and, you know, but still, it's stupid because I don't have alcohol under control. But still, I was always a happy guy. When I walked into the bar, it's called the Spy Bar. Very notorious for their bouncers being really bad bouncers.

Starting point is 00:10:47 I mean, the whole Sweden, they love me after this happened. So when I walked in, they recognized me and they said, and you could keep it quiet today, boss. And I thought, that's a weird thing to say. Why wouldn't I? I never get in trouble. I get friends with everybody. So I'm walking around, dancing around. And this one guy wants to give me a drink.

Starting point is 00:11:05 And suddenly a bouncer comes to me, and he says, you have to go. He says, what do you mean? He says, you're bothering the customers. I say, who? Him. I say, he's buying a drink for me right now. So I don't think I'm bothering. Can you ask him?

Starting point is 00:11:17 No, you have to come with us. I say, do it. I'm not bothering anybody. So they grab me. I don't want to fight because I know if I push somebody, it's already going to fight. But I don't want to fight. So I walk with them., it's already going to fight. But I don't want to fight. So I walked with them. And now with the two bouncers, we're at the fire escapes.

Starting point is 00:11:28 And there's this big marble stairs going down. And this guy is a little guy and a big guy behind him. And the little guy is wearing a leather jacket. I remember that. And there's this big guy standing. Croatian guys, Croatian mob, they said. And I'm talking to the guy and he's pointing on my chest the whole time and i said guys i'm going don't worry about it i don't want any trouble can you tell my buddy he's also

Starting point is 00:11:50 bald he's from holland then i'm outside because otherwise he has no clue where i am he says you don't understand he's pushing on my chest the guy does there's no there's no reason to touch me let's let's not do that so then he touched me again i pushed him away i said don't don't touch me stop touching me and right away the guy behind him the tall guy stabs a finger in my eye so i'm going like guys i don't want any trouble and he takes my other eye as soon as that happens i knock him out because what's next he's going to kick the ball he's going to he's going to escalate i mean once you take two eyes so i knocked him out the problem was that these little microphones so now three other bouncers come in and that guy of course he's's out. But while I'm fighting the other bunches,

Starting point is 00:12:29 he starts waking up. So I'm dropping left and right. I put three in the hospital. And then finally I realized eventually I'm going to run out of gas. This is going to go wrong. I got to go down and this is a fire escape. So I need to go down. So I'm running down. I'm going down while I'm fighting and hitting, hitting, hitting, and I'm going down. And I remember, I still to this day, I remember exactly how it looked. It was one of those copper things that you push in to open the door and it was locked. Yeah, I couldn't get out. But till that time, I was still fighting by the rules. I wasn't stabbing eyes. I didn't kick the balls. I didn't hold. I was still kind of just fighting, you know, not to destruct. So now I made up my mind and I turned around and I told myself, I'm going to stab eyes.

Starting point is 00:13:10 I'm going to go all the way. And as soon as I looked at them, they all stepped back. And I felt really powerful for about five seconds because I thought they saw in my face that I meant business. But it wasn't behind me. There was the whole police force standing behind me because they had a call. And that's why they stopped fighting. But they threw me in jail from jail. I went to a jail in the freaking mountain.

Starting point is 00:13:35 You can Google this. I mean, I thought, did I make this up? No, in the mountain, we drive in the tunnel. The tunnel stops in the middle of a mountain. I have to go to an elevator, Two floors up, go out. Three floors up, go out. Four go down. I go like, it's like a movie. I come out of it. It's like a bad wizard

Starting point is 00:13:51 in Harry Potter. Yeah. It was insane. And then they put me in prison. I still couldn't call my wife. Oh, this is always the same. My wife hates this story, but she kind of thinks it's funny on one side or so, but it wasn't funny at the time. When I talked to her before I went into the bar, she says, why are you so happy? I said, honey, I'm just drunk and I'm just having a good time. She says, no, no, no. You're

Starting point is 00:14:13 there with two Swedish blonde girls, aren't you? I go, you know me, honey, for me right now, alcohol counts. That's my only folks. Okay. I got to go. So then two days, she didn't hear anything from me. And now I call her. And by the way, they wouldn't give me my first phone call. It was the guards who knew me who gave me their cell phone, and I wasn't allowed to call. Dude, they gave me a TV. I had a VCR. They gave me cookies. I was playing cards

Starting point is 00:14:36 with the guard. It was hilarious. But still, it was not fun because I was in jail, and they told me I was going to be six to nine months in jail because apparently one of the cops of one of the bouncers was a cop. But he didn't say he was a cop. So, well, if he attacked me, well, yeah, I'd knock you out as well. You're saying like the, you said the

Starting point is 00:14:51 cop of one of the bouncers, like the father of one of the bouncers or the brother of one of the bouncers? No, no, no. One of the bouncers was a cop, off-duty cop. Oh. Apparently in Sweden they need one law enforcement person to be there as well but he got the same treatment because if he attacks me i got him so i called my wife and she's freaking

Starting point is 00:15:11 out now and i go honey come i don't have a lot of time i have some good and some bad news and what do you want to hear first and she says the good news i say i didn't have sex with two swedish girls and she goes what's the bad news I said I'm in jail he goes you think that's funny I go yeah so thankfully I had some good guys there who were pretty powerful guys who convinced the bad people to take the charges back but otherwise I would have been there six to nine months that's what they wanted to give me for no reason. Then we find out, and you can Google this, they put people in jail for four years for nothing. There was a guy who went on, one of those guys for the bouncers,

Starting point is 00:15:53 he went on a big show, like an Oprah kind of show in Sweden, and he was crying on the show. They said it to me. He said that they put an actress in jail for four years and she didn't do what they said. Their boss told him to do these things. He felt so bad because they were the mafia bouncers. That's what they called them.

Starting point is 00:16:10 They put in the Swedish post, they put a picture of my street, a self-defense DVD. And then below it said that one of the bouncers said, we were so happy the police came because we couldn't handle him. My salesman threw the roof over in Sweden and I became their hero because everybody had trouble in that bar. And now they finally had somebody who could give it back, you know, but still it was a very, now I'm here and I can talk about it with a smile.

Starting point is 00:16:38 But at that time, if you think you're going to be there for six or nine months for something you didn't do, you know, try to convince it's five against one, you know, nobody's going to be there for six or nine months for something you didn't do, you know, try to convince. It's five against one. You know, nobody's going to believe me. So, yeah, that was the sweetest story. So, prior lifetime. Prior lifetime.

Starting point is 00:16:56 You see, now it's time to take the rosary. And now it's rosary. Next up, Kevin Rose, serial entrepreneur, world-class investor, and self-experimenter. I did one of those full-body MRI scans called Pranovo. Yeah, we should talk about this. This is something I need to get on. Yeah, you know what? Honestly, it was like, I don't know if it was my mom getting cancer. I think I did it before that,

Starting point is 00:17:26 but like, I was just one of those things where I got to this stage in life where I had a couple of little girls and I'm like, you know, Tia was telling me, he was like, Hey, you know,

Starting point is 00:17:36 you can do these or at the age now or make sense. See if anything shows up. They can detect it's something like 80% of cancers at stage one, which is amazing. Yeah. And so I was like, okay, let's do it. So I went and did it two years ago, came back, you know, all the standard stuff like, oh, we see this here, but you know, that's normal law.

Starting point is 00:17:55 Like this is a little bit weird. You have an extra vertebrae, which I actually do, which is weird. So a little vestigial tail. Yeah, exactly. A bunch of shit like that. Ladies. A little vestigial tail. Yeah, exactly. A bunch of shit like that. So I do that. And then I go for year two and I go and get the scan again.

Starting point is 00:18:17 And they call me up and they're like, yeah, it turns out you have a little brain aneurysm, a little small brain aneurysm. And I'm like, what the fuck? Like, this is crazy. Okay, tell me more. And then after the fact, like a month later, or not a month later, but a few weeks later, my doctor calls them and says,

Starting point is 00:18:32 hey, what did we see on the first scan? They found it on the first scan as well. It hadn't changed, which is great. And it's super tiny. It's the smallest. My doctor said if they hadn't been using the latest tech, they wouldn't even have detected it at all because it was so small. So it's only one millimeter and they don't treat them till they get to seven millimeters yeah so it's like it's totally fine you want to keep your blood pressure low and all

Starting point is 00:18:52 that but it's also it's weird because in some sense like you want to detect those stage one cancers but there's a lot of false positives not that this is a false positive it's something to pay attention to certainly changing my dietary actions in terms of keeping sodium low and like lowering my blood pressure yeah but it's something you should do which is why we're having croissants and coffee exactly well i mean that's like i missed my you know it's it's like i mean was that i would imagine that to be terrifying yeah it's 45 minutes so it's fast they not the procedure the review of the results yeah i mean you go through it and i have a couple spots on my brain and they they told me you're allowed one per decade and so like you're fine you have you know two or three or whatever that's fine i'm like okay

Starting point is 00:19:36 this still doesn't sound good like don't worry yeah it's like a bruised apple but that's fine yeah and then they're like they're like your lymph nodes this is the first scan they're like your lymph nodes are really swollen on the left side i'm like cool like what does that mean and they're like did you get your your covid vaccine on that side i'm like yeah i did they're like okay that's why and then that would turn out to be fine and then you know they found like some other shit like there's a little bit of like a a little a little tail no there's a little bit of like a little a little tail no there's a little like like I have this little tiny bulge in my right nut sack that it's

Starting point is 00:20:10 just it's kind of like the little string thing that connects to the sack kind of bulge out a little bit and they're like that's totally normal it's not cancer you're fine blah blah so like you know it's just like cool oh my god I can't wait until our random shows when we're in our 60s and 70s.

Starting point is 00:20:28 It's just going to be a litany of injuries and prostate complaints. Oh, my God. So let me just rewind. So I'll make sure. No, just make sure I'm hearing you correctly. So were you pissed that they did not? If it hadn't changed. Yeah.

Starting point is 00:20:45 That they didn't spot it the first time around? I think it was so small that they just, they have different, it's not a radiologist, whoever it is that reviews it. It's probably a radiologist. I think it is. I think the first one was like, this is so insignificant, I don't even need to call it out. And the second one called it out for, and they were just like, and then they compared

Starting point is 00:21:02 the notes and it was fine. This is the story I haven't told. Friend of mine went in, had a scan. They found a growth in his brain, non-cancerous, a decent size, operated,

Starting point is 00:21:14 removed it. He's fine, but he didn't even know he had it. And he was just going in for, for a thing and it was growing. Yeah. And it saved his life most likely. Yeah. That's,

Starting point is 00:21:23 that's wild. And so it's shit like that and the radiologist when i talked to him he said the number he goes i don't really drink he goes but the number of bottles of wine i get in the mail from people they're like you saved my life because you found this at stage one or stage two i don't know it's just one of those things where get your diagnostics folks and i mean do it more i hesitate to say this but like don't don't push out the interval. If you're supposed to get something every five years, if anything, get it more frequently.

Starting point is 00:21:49 Don't push it out. So I have recently had the opposite experience with a friend of mine who went in for a routine exam, stage four cancer terminal. Holy shit. And I just spent several days with him. And not because I don't want to give specifics just in case people like triangulate stuff, but it's metastasized. And at this point, surgery,

Starting point is 00:22:16 at least some types of surgery don't make any sense. And man, if you want a proof point for what someone can do with decades of meditation practice, he is incredibly upbeat. He's super happy. He is as productive as he can be. He's spending a lot of time with loved ones, of course, but he is consciously choosing of all the decision trees, a path of gratitude and not naive optimism, but optimism in the sense of looking at everything as the glass half full. And I was so inspired by this because I'm going through some hard stuff myself and to see someone in those circumstances able to demonstrate that

Starting point is 00:23:14 just blew my mind. And I've spent, I know him well enough and we've had enough interactions. I know it is not an act. It is not an act. And I'm really impressed because that's not automatically the case. I mean, there are people, including famous, famous meditators who are world-famous teachers who on their deathbeds or in the process of going through hospice, just say over and over again to

Starting point is 00:23:38 their closest friends, like, I don't want to die. I don't want to die. I don't want to die. And they're afraid, which is understandable. I might be that person. I mean, certainly I have no confidence that I would end up responding the way my friend is responding, but it's been incredibly inspiring. Wow. Yeah. And I mean, it's certainly sad in its own way,

Starting point is 00:23:56 but a real gift that he's also giving those around him. It's incredible. How are you doing with dealing with all that? You mean with, with his situation? It mean with with his situation being a friend it's having a friend go through something like that you know uh are you gonna see him again do you think before he passes or is it something i would like to i would like to i mean it's i don't know how long the time horizon is it's it's uh it may not be that long. I am doing well with it because of how he is able to choose to respond to this unfolding story.

Starting point is 00:24:37 Of course, it's sat on a number of levels, but we all have a one-way ticket, as far as we know. My dad, before he passed, said there's no lease on life he just like wanted to remind me of that like yeah it's like you know it's coming for all of us yeah yeah absolutely and it's and it's not something you want to think about all the time right but if you think about it none of the time you also have problem and this this has been a very strong reminder for me it's like yeah get it together you know like when i had don't dick around too much like have fun don't take

Starting point is 00:25:12 everything seriously but also realize that like every moment you have like this not to get all cheesy but it's like these are precious amazing moments yeah everybody's healthy yeah i think about that with my girls every day dude the kids next up travel writer rolf potts his newest book is the vagabond's way 366 meditations on wanderllust, Discovery, and the Art of Travel. Are there any other books or thinkers, writers, movies, doesn't really matter, anything at all that has had an impact on your ability to maybe extend your perception of time, slow the passage of time, increase your savoring of time, anything like that. I mean, you mentioned the scent of time. I'll throw one out there and buy some time. I read a novel. It was gifted to me by my brother who has a very high bar. And it took

Starting point is 00:26:17 me several attempts to get through the first hundred pages because it's very dense. And you can't put it down after 13 pages and pick it up for seven pages two days later and then read another 12 pages. That will never work. You have to kind of get the balls in the air and juggle so that your short-term memory is doing some work. But that novel, once you get, if you get to The Talking Fish, I'll only leave it at that, you'll realize, oh, okay, this is about to get very strange indeed. And that book had a profound impact on my way of perceiving the world in time for a few weeks. It was a very, very cool experience. Are there any other books, writers, thinkers, experiences that people might be able to

Starting point is 00:26:58 look to themselves that have changed your experience of time or your ability to slow down? I've been weirdly obsessed with time ever since I met this guy in a monastery in Massachusetts on my first vagabonding trip. I was like 23. This dude, wherever he is, thank you, whoever you are, he just left the Navy. He was in the contemplation room of a monastery. And I didn't want to become a Trappist monk, but it's like the only place where I could stay for free. And I was a dirt bag and I wanted to stay there. And this guy, he was just out of the Navy. He wasn't necessarily going to become a monk, but he was really interested in monasticism.

Starting point is 00:27:29 And he had this skull and crossbones on his arm. And that's where I learned the phrase memento mori. I had no idea what memento mori, remember death, is, the philosophical idea of remember death. And I've been thinking about it ever since. You know, actually one of the inspirations for me as a traveler, you know, for Vagabonding and up to the new book is just the idea of that life doesn't necessarily reward you in time.

Starting point is 00:27:52 My grandfather was a Kansas farmer. He worked really hard from age 15. He dropped out of school, took over the farm when his dad died, worked his ass off. And then when he got to retirement age, his wife, my grandmother got Alzheimer's disease and he took care of her for the rest of his life. And so it was a really heartbreaking thing when I was young. But I realized that time isn't just given to you in a rational way in life. You have to grab time as you are allowed to grab it.

Starting point is 00:28:18 And so there's great writing about time. Is it Oliver Berkman? I think you've quoted other people. Yeah, 4,000 Weeks, I think. 4,000 Weeks, yeah. No, I haven't finished that book, but I always read like 10 books at once. The philosophy of time and the idea of time and now the scent of time is something that I've always sort of obsessed about. And actually, one of my favorite filmmakers is Richard Licklater, and time is sort of one of the things he experiments in as a filmmaker.

Starting point is 00:28:46 And I love Before Sunrise because it's about a guy who meets his true love on a train in Austria. Well, I met my wife the one time I wasn't traveling, but that's still a very meaningful movie to me because they talk so much about time in that trilogy. And they talk about journaling, which is something I know you talk about quite a bit, but is not done as much anymore as it was in the 90s when that movie was first made. And just the idea that Selene, that character in Before Sunrise, is talking about coming to this city as a teenager and writing in her journal and basically having a conversation with herself based upon what she wrote in that journal. And Richard Linklater has some other, you know, their boyhood is about, very specifically about time and aging and things like that.

Starting point is 00:29:30 But I saw before Sunrise of Brown the time that I left that monastery with the Navy guy with the tattoo who taught me about memento mori. And so I've thought about that. And I think it's really important to be cognizant of time and just the idea that the moment is what we have. And there's so many ways to embrace time, but maybe as an obsessive traveler, it always puts me into this thought experiment of how time is playing out and how I'm making use of it. Next up, Dr. John Crystal, chair of the Department of Psychiatry at Yale University and a leading expert in the areas of alcoholism, post-traumatic stress disorder, schizophrenia, and depression. formed at all that ketamine, instead of a million other interventions or pharmacological tools, might be useful for repairing the structural damage of stress or alleviating depression? Was it something that was observed in the field? For instance, one of the rumors that I've heard is that veterans who are administered this anesthetic seem to

Starting point is 00:30:53 experience less PTSD that was somehow recorded in the field and that led to hypothesis generation and use of ketamine. That seems pretty tenuous. I don't know if that's true, but how did it go from anesthetic to, of all the things we could choose, we're going to mess around with ketamine? First off, I love hearing stories about how I and Dennis came up with ketamine for depression. It's one of my, like, people, you know, it's like, oh, that's a great idea. To be clear, this isn't specific to you. It's just, I'm so fascinated by the Genesis stories of these things. I think they're important. So I'd love to hear the real story as opposed to the Santa Claus version. So the real story is not related to depression at

Starting point is 00:31:46 all. It's related to schizophrenia. So it so happens in the great cosmic universe of coincidence that a friend of my dad's in Detroit and his family was a friend of our family. And we went on vacation together. I remember intertubing down a river in northern Michigan. I grew up in Michigan, intertubing down a river with his daughter. We were maybe 10 or 9 or 10 at the time. His daughter is now is named Joan Luby. She's now an endowed professor, an expert in child psychiatry at Washington University in St. Louis. Anyway, this fellow's name was Elliot Luby. And in 1959, he published a paper that was the first time phencyclodine or Cernal was given to a human being. This happened at the Lafayette Clinic in Detroit, an entity,

Starting point is 00:32:45 a building which no longer exists, unfortunately, an extremely, extremely generative place in its era. And he said, if you gave Cernal, which was the company name for Phencyclidine PCP Angel Dust, if you gave it to people, it produced something like schizophrenia in them. The thing was, that's 1959. And the mechanism, the fact that it blocked the NMDA glutamate receptor wasn't identified until the mid-1980s or in 83, 84. So it was this fascinating observation, which couldn't go anywhere scientifically. But they did research, and this is going to bring us to other topics that we'll probably talk about, in which they compared the effects of phencyclidine to the effects of LSD in people. Good old psychomimetic.

Starting point is 00:33:48 Yeah. Just unbelievably courageous and creative, trailblazing psychopharmacology at a time when they just had no idea what was happening in the brain, the neurobiology. And in the early 60s, another trailblazing scientist also associated with that group was a guy named Ed Domino, who was a pharmacologist. Great name, too. Yeah. My cousin, Tom, I apologize for mentioning his name, who was a medical student at the University of Michigan, brought me to sit in one of his classes, who was a medical student at the University of Michigan, brought me to sit in one of his classes when I was applying to medical schools.

Starting point is 00:34:30 And it just happened to be Ed Domino. And my friends, my cousin and his friends, when Ed Domino came up to talk, sang a bit of the Van Morrison song, Domino, which you may be familiar with. Anyway, unforgettable to me because Ed became a very dear friend and colleague over the years. But Ed was the first to give ketamine to animals and humans because it was a shorter acting, safer version of a small structural modification in the phencyclidine chemical structure that made it possible to be shorter-acting, more manageable, easier to control. And for what reason was he administering the ketamine in those particular studies? For anesthesia. For anesthesia, got it.

Starting point is 00:35:22 There was a fellow, Corson, who was working with him on some of those studies. So there's a line that I love. I love portentous lines in scientific literature. I think it's the last line in the Watson and Crick discovery of DNA where they say, it has not escaped our notice that the elucidation of the structure of DNA may have relevance for the transmission of genetic traits or something like that. Something unbelievably understated. papers on ketamine, maybe the first paper that Ed Domino wrote, which was, when you give ketamine to humans, we notice that sensory information can get to sensory cortex unimpeded, but is altered or blocked in its transmission to association cortex. We call this dissociation and this process dissociative anesthesia or something like that. And wow, what a profound cast-off sentence, right? Buried in the discussion section of a paper in an anesthesia journal.

Starting point is 00:36:38 But really what happened was that this group of pioneers had an incredible tool, but no conceptual framework to use it to generate real deep scientific insight. And that's because they were 30 years ahead of the field. And, you know, it wasn't even known that there was a binding site for phencyclidine. So, first studies published in 1959, it wasn't even known that there was a binding site for phencyclidine. So first studies published in 1959, it wasn't even known that there was a binding site for phencyclidine. Now by binding site, you mean a receptor that it could... Some kind of something that where the drug act in a... They didn't know that it acted in a specific way at a specific target in the brain. What that target was, they didn't yet know until the early 1980s that it was a glutamate receptor. But they just didn't even What that target was, they didn't yet know until the early 1980s that it was

Starting point is 00:37:25 a glutamate receptor. But they just didn't even know that there was a binding site for fencyclating until a landmark paper in 1979 from Steve and Suzanne Zukin. So it was darkness, right? It was like the middle ages of neuroscience. And so they had a brilliant insight, but they couldn't take it anywhere because there was no framework for it. So around 88, 89, I joined the faculty in 88 at Yale. And I wasn't sure what I was going to do. And my boss said to me, Dr. Charny said, well, you can be the chief of the schizophrenia program or the deputy chief of the PTSD program. And I said, well, I like the idea of being the chief. That's how I went into the field of schizophrenia research. And so I found myself as a new, completely inexperienced schizophrenia researcher, setting up a research program related to the neurobiology and treatment of schizophrenia.

Starting point is 00:38:38 And it happened to be just at that time that Clozapine, which is an antipsychotic medication, that's a little bit more effective than other antipsychotics, was introduced. And I've been raised studying monoamine pharmacology. That's what I knew. That's really what I had anticipated studying. I treated patients with Clozapine, and I thought it was a pretty good medication. But I didn't want my legacy after 40 years of schizophrenia research to be that he figured out why clozapine was a little bit more effective than other antipsychotic medications. So I felt like I just had to go out of the box. And this is where my father's legacy really had a big impact.

Starting point is 00:39:25 It's like, well, if you could do anything, what would you do? And it was like, well, I don't want to study these few cells contributing to dopamine or norepinephrine. I want to study the main information highway of the brain. And just a few years before, they figured out that drugs like ketamine, PCP, blocked this receptor for glutamine. And so what brought me to ketamine was really the effort to probe glutamate synaptic function in higher cortical circuits as a way of understanding the cognitive impairments, negative symptoms, and other aspects of schizophrenia. So our path in our institution, my path, was the development of a research program on glutamate psychopharmacology, developing

Starting point is 00:40:19 circuit and mechanistic hypotheses. And one of my collaborators in those days was a pharmacologist named Bita Mokadam. And in 1997, she published a paper that showed that ketamine released glutamate in the brain at the very same doses that we were using, the equivalent of the very same doses that we were using to produce changes in cognition and psychosis related to schizophrenia. And, you know, that line of research has its own story because we began using the ketamine administration as a platform for trying to identify novel alternatives to antipsychotic medication for the treatment of schizophrenia. And that has had its own life and story, and maybe someday we'll talk about that. But one of the things Bita found, which turned out to be profoundly important for the antidepressant story, was if you give it at the sub-anesthetic dose that we use to study cognition, it releases glutamate.

Starting point is 00:41:28 If you give it at anesthetic doses, it depresses glutamate, and it's not antidepressant at those doses. And if you give it at even a little bit lower level, it doesn't stimulate the glutamate release. There's this tiny, narrow window where it's producing dissociation, psychosis, and a number of the other effects that we're really interested in where it works. And it turns out that that little narrow dose window is the dose range where it works for the treatment of depression. We just stumbled on that because it was optimal. You know, the thing was, we couldn't give higher doses to people because we needed them to perform cognitive tests and be able to answer our questions. When we gave people much higher doses of ketamine, they would have pretty interesting experiences,

Starting point is 00:42:16 but they couldn't answer any of our questions. So it wasn't any good for me as a research tool. I mean, I remember one person that we gave this higher dose of ketamine to who couldn't answer a lot of our questions, but he was holding onto the bed really tightly. And I said, well, that's interesting. Why were you holding onto the bed? He said, well, basically, the dress, the blue in the dress of the interviewer had become outer space. The white polka dots in her dress had become planets and solar systems. And his bed was flying among the planets and the, you know, the outer planets.

Starting point is 00:43:00 And he was afraid that if he let go of the bed that he'd be cast adrift in outer space and not make it back. Well, that was really fascinating. Seems reasonable. Yeah. It was really, really interesting, but useless. I couldn't get him, he couldn't do any tests. He couldn't perform anything. So what that essentially did was create the upper bound of the dosing that we were using with ketamine. And then the lower doses just turned out to be completely ineffective and have repeatedly been shown to be so in single doses in antidepressant trials. So that's how we got to ketamine. And that's how we got to the dose of ketamine and the route of ketamine that we use in the treatment studies. Because what we did was to adapt the dose and the duration of administration. Like you could have said, why 40 minutes? Well, because ketamine is such a short-acting drug, we administer it for 40 minutes

Starting point is 00:44:00 to give us a time window where people are having the subjective effects of ketamine where we can test behavioral incognition. That's why we had the slow infusion in the initial study. And we just imported that into depression. And that has become the standard treatment infusion paradigm for racemic ketamine administration for the Treatment of Depression. Last but not least, Dr. Suresh Muttakamaraswamy, Associate Professor at the School of Pharmacy, University of Auckland.

Starting point is 00:44:47 What I would like to just make note of really quickly is that I feel the LSD microdosing study that you just finished gathering data for is a really important first of its kind, and please poke holes in this if I'm getting any of it wrong, for a number of different reasons, but I'd like to highlight one of them. And one of them is placebo control in psychedelic studies or studies involving psychedelics, where it's incredibly difficult to have placebo controls at larger doses with something like psilocybin or LSD, because it is tremendously obvious to anyone who has taken it that they've taken it. And if they haven't taken it, it's very clear that they have not taken it. And there's going to be expectancy effects. And generally,

Starting point is 00:45:29 people are going to come in knowing on some level what psychedelics are or believing that they do and having done some reading and so on. So you have placebo effects. We won't even get into nocebo effects, which people should read up on because that's also something worth looking at. But in the case of microdosing, it seems like you really can begin to apply placebo controls. And just for people listening, could you describe how you thought about that and whether you decided on passive or active placebo? For this study, we went with an inactive placebo just because because no one ever done lsd microdosing before we wanted a rent for in the community we wanted an inactive control so that when we looked at safety and like physiological measures of safety we had a really we've not actually done anything to these people we We haven't given them any drug. This is just pure. So we had a very pure safety group to look at.

Starting point is 00:46:27 And in terms of whether people are able to detect the effects, some are, some aren't. So we were around the threshold. This was at around 10 micrograms? Yes, about 10 micrograms in male volunteers. So there was quite a heterogeneity, though, actually. We saw that some participants were particularly sensitive to it and we had to reduce doses for some

Starting point is 00:46:50 participants and some hardly noticed. So there's quite a variability in people's response and that's interesting in and of itself. It suggests to me that we're probably, when we move on to the next phase and actually want to look at a clinical population and run like a, for example, a depression trial, we may need to start looking at lightly active placebos because we're now interested in the clinical outcome, not just sort of like, can you do it? What do people experience? then probably some kind of light placebo, the little bit of, I wouldn't say deception, but just ambiguity in the information that we provide to participants might be enough to get us over the top in terms of blinding the study successfully, unlike psychedelic studies, which aren't blinded at all. And this is a real methodological problem that the field has to try to conquer in some way. And we're working on it. I just want to jump in for a second. So I would say also that the fact that placebo controls are so difficult

Starting point is 00:47:49 is, I don't want to say a feature and not a bug, because it does present, just from the standpoint of rigor and publication, a whole lot of challenges. But the fact that this effectively entire class of drugs has so much trouble with placebo controls is very interesting in and of itself. I've written a whole mess of paper on this topic. Yeah, I mean, it's fascinating that it's so hard. Do you have any, and you don't have to give away your secrets, but anything on the short list for potential active placebos that you would use in such a case?

Starting point is 00:48:22 Niacin, something else? Niacin's not a great option that's um yeah a vitamin so actually niacin was used in the 1960s and it's been determined even in 1960 that niacin is a poor control for society but people used to use it for some reason and i'm not sure why skin flushing i mean maybe some type of subjective experience so that people think it's doing something yeah so it's added to a lot of dietary supplements as well just we're getting into the weeds here but what i would say is actually what the compound is isn't as important as what the participant thinks it's going it's their belief about what they're receiving that's the important thing because blinding clinical trials is really

Starting point is 00:49:00 important to prevent expectancy instances because if a person goes into a clinical trial thinking they're going to get psilocybin, they do get psilocybin, and if they think it might make them better, they work out that they've had it, and they go, ah, and maybe that over-accentuates their clinical response, which we would call a confound. So that's potentially a problem.

Starting point is 00:49:19 But what's important is it's not the compound itself. It's what the participant believes that they've had. And so it's not as much potentially around what the actual active placebo is, but what you tell the participant about the active placebo and the information that you provide them. Because you're not trying to manipulate their physiology. You're trying to manipulate their beliefs about what they're having. So I think these are subtle things that we need to really think about

Starting point is 00:49:43 in our experimental science. This is why I really enjoy doing research in this area, because these are fascinating problems. And it's a really like fascinating area to try and work out these scientific problems. I reckon we can do it. I'm not, you know, give me another 10 or 15 years and I might give up. But right now, I think, you know, we can totally crack it if we put our brains to it as a scientific discipline. It's a really exciting time to be, for me, certainly observing, watching to the extent that I can, supporting the ecosystem and a really exciting time for people like you to be doing the research.

Starting point is 00:50:18 It's really kind of a blue sky opportunity. And the payoffs, as I think we established very early on in the conversation, are potentially huge if we look at the trend lines of various diagnoses and illnesses and the costs, both on a personal level, familial level, and societal level. And now here are the bios for all the guests. Today's guest is Dr. Gabor Mate. You can find him online at drgabormate.com. That's G-A-B-O-R-M-A-T-E.com. On Twitter, at drgabormate. On Instagram, at gabormatemd. Dr. Mate is a renowned speaker and bestselling author. He's been on the podcast before, and it was a very popular episode. He is highly sought after for his expertise on a range of topics that include

Starting point is 00:51:08 addiction, stress, and childhood development. Dr. Mate has written several bestselling books, including the award-winning In the Realm of Hungry Ghosts, I highly recommend, subtitled Close Encounters with Addiction, When the Body Says No, Exploring the Stress-Disease Connection, and Scattered, How Attention Deficit Disorder Originates and What You Can Do About It. He has also co-authored Hold On to Your Kids, Why Parents Need to Matter More Than Peers. His works have been published internationally in nearly 30 languages. His new book is The Myth of Normal, subtitled Trauma, Illness, and Healing in a Toxic Culture. My guest today, why would I be so excited?

Starting point is 00:51:49 This is Sebastian Rooten, better known as Boss Rooten. You can find him on Twitter and elsewhere at Boss Rooten MMA. He's a Dutch-American actor, former mixed martial artist, kickboxer, and professional wrestler. He was a UFC heavyweight champion and a three-time King of Pancras world champion. We're going to talk quite a bit about that. Finishing his career on a 22-fight unbeaten streak with a strike accuracy of 70.6%, the highest ever recorded by Fight Metric. Rutten was co-host of Inside MMA on AXS TV. That's A-X-S from 2007 to 2016. And he has been a color commentator in several MMA organizations, including Pride Fighting Championships, another thing that we will spend some time on.

Starting point is 00:52:29 He has appeared in numerous television shows, movies, and video games as an actor and continues to be involved in MMA through his coaching and publishing of instructional materials. Boss became a naturalized American citizen in the late 1990s, and in 2015, he was inducted into the UFC Hall of Fame. We'll link to all of the social as well as the O2 Trainer, which we're going to get to. You can find that on Instagram at O2LungTrainer, and we'll link to YouTube, Facebook, and other places. This is another edition of The Random Show with my friend Kevin Rose. Who's Kevin Rose? He's a technologist,

Starting point is 00:53:08 serial entrepreneur, world-class investor, self-experimenter, and all-around wild and crazy guy. You can find him at Kevin Rose on Twitter. I'll keep it short at that. Have my friend Rolf Potts here. Rolf Potts, who is Rolf? Rolf is the author of the international bestseller Vagabonding, subtitle, An Uncommon Guide to the Art of Long-Term World Travel. That was one of the two books I traveled with in the years preceding the writing of The 4-Hour Workweek. His newest book is The Vagabond's Way, 366 Meditations on Wanderlust, Discovery, and the Art of Travel. He has reported from more than 60 countries for National Geographic Traveler, The New Yorker, Outside, The New York Times Magazine, and Travel Channel. Many of his essays have been selected as notable mentions in the Best American Essays, the Best American

Starting point is 00:53:56 Non-Required Reading, and the Best American Travel Writing. He is based in North Central Kansas, I love how specific that is, where he keeps a small farmhouse on 30 acres with his wife, Kansas-born actress, Kristen Bush. My 2014, God, how old are we getting? Rolf, we're going to talk about that. My 2014 interview with Rolf can be found at tim.blog slash Rolf. We cover a lot of ground in that interview, including a lot of background with vagabonding. We're probably not going to revisit all of that. And we get into all sorts of nooks and crannies. So that is a self-sustaining, independent episode. We're going to try to cover some new ground in this one. You can find Rolf on Twitter and Instagram at Rolf Potts. That's R-O-L-F-P-O-T-T-S.

Starting point is 00:54:42 And you can also find everything Rolf at rolfpotts.com. My guest today is the incredible John Crystal. Dr. John Crystal is the Robert L. McNeil Jr. Professor of Translational Research, Professor of Psychiatry, Neuroscience, and Psychology, Chair of the Department of Psychiatry at Yale University, and the Chief of Psychiatry and Behavioral Health at Yale New Haven Hospital. Dr. Crystal is a leading expert in the areas of alcoholism, post-traumatic stress disorder, schizophrenia, and depression. His work links psychopharmacology, neuroimaging, molecular genetics, and computational neuroscience to study the neurobiology and treatment of these disorders. And he is very fluent, well-versed in many other things,

Starting point is 00:55:26 but he is best known for leading the discovery of the rapid antidepressant effects of ketamine in depressed patients. He co-directs the Yale Center for Clinical Investigation, CTSA, NIAAA Center for Translational Neuroscience of Alcoholism, and Clinical Neuroscience Division of the National Center for PTSD. Dr. Crystal is a member of the U.S. National Academy of Medicine, co-director of the Neuroscience Forum of the U.S. National Academies of Sciences, Engineering and Medicine, fellow of the American Association for the Advancement of Science, and editor of Biological Psychiatry, one of the most selective and highly cited journals in the field of psychiatric neuroscience. He's the co-founder and chief scientific officer of Freedom Biosciences, which you can find at freedombio.co, a clinical stage biotechnology

Starting point is 00:56:09 platform developing next-generation ketamine and psychedelic therapeutics that just recently emerged from stealth in August of 2022. And without further ado, let me introduce the main attraction and the guest of the hour, and that is Dr. Suresh Mutukumaraswamy. I will here forward refer to him as Suresh. Suresh is an associate professor of psychopharmacology at the University of Auckland, and he completed his PhD in psychology at the University of Auckland in 2005, after which he joined the newly established Cardiff University Brain Research Imaging Centre as a postdoctoral fellow. While at Cardiff, he started research work with the psychedelics and psychedelic compounds in 2011 in collaboration with two

Starting point is 00:56:53 very well-known names, Professor David Nutt and Dr. Robin Carhart-Harris, investigating the neuroimaging correlates of the psychedelic drugs psilocybin and LSD. In 2014, Suresh received a prestigious Rutherford Discovery Fellowship and returned to the University of Auckland where he works in the School of Pharmacy at the Faculty of Medical and Health Sciences and leads the Auckland Neuropsychopharmacology Research Group. Suresh's main research interests are in understanding how therapies alter brain function and behavior and in testing methodologies to measure these changes in both healthy individuals and patient groups, particularly in depressed patientsologies to measure these changes in both healthy individuals and

Starting point is 00:57:25 patient groups, particularly in depressed patients. And of course, this session will have a focus on mental health, so we will delve into that. At the University of Auckland, he has conducted clinical trials in depressed patients involving ketamine, scopolamine, and transcranial magnetic stimulation, TMS. He has received several Health Research Council of New Zealand research grants to support this work, including a grant to investigate the effects of microdoses of LSD on brain and cognitive function. Suresh has published 117 papers and his work has received more than 8,000 citations. take off. And that is Five Bullet Friday. Would you enjoy getting a short email from me every Friday that provides a little fun before the weekend? Between one and a half and two million people subscribe to my free newsletter, my super short newsletter called Five Bullet Friday. Easy to sign up, easy to cancel. It is basically a half page that I send out every Friday to share

Starting point is 00:58:21 the coolest things I've found or discovered or have started exploring over that week. It's kind of like my diary of cool things. It often includes articles I'm reading, books I'm reading, albums, perhaps, gadgets, gizmos, all sorts of tech tricks and so on that get sent to me by my friends, including a lot of podcast guests. And these strange, esoteric things end up in my field, and then I test them, and then I share them with you. So if that sounds fun, again, it's very short, a little tiny bite of goodness before you head off for the weekend, something to think about. If you'd like to try it out, just go to tim.blog.com slash Friday, type that into your browser, tim.blog.com slash Friday, drop in your email, and you'll get the very next one. Thanks for listening.

The Tim Ferriss Show - #631: In Case You Missed It: September 2022 Recap of "The Tim Ferriss Show"

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