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

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My cybernetic organism, living tissue over metal enough scalar. Hello, boys and girls, this is Tim Ferris. Welcome to another episode of the Tim Ferris Show, where it is my job to deconstruct world class performers of all different types, to tease out the routines, habits, and so on that you can apply to your own life. This is a special in between episode which serves as a recap of of the episodes from the last month. 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 wet your appetite. It's a lot of fun. We had fun putting it together and for the full list of the guests featured today, see the episode's description probably right below where we 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 Best selling 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 at least Here of some of your learnings over The last decades. Because I recall from our first conversation

That You know, in your forties, you're a successful doctor. You're a driven workaholic. You 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 as someone who has a long history of running On anger as a 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's a great neuroscientist. His name was Jack Pacsep, P 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. They include Care. So you C A R E care.

Then something really call he calls grief and panic. Then fear? Lost? Seeking Play.

And rage. These are all brain systems that we have. They're all necessary for mammalian life. They're all necessary. By which 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. 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 you. But it's had no expression. And why did you suppress it? 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 Some time after You and I talked, you actually publicly Acknowledge that you'd been sexually abused as a child.

Yeah, I did. No 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 Bundary Invasion. You're gonna get hurt even more. 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. But the race 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. No, 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 Hurt and sense of abandonment and unrage. 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 it's

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 explores, the bigger it gets.

That's what happens to me. I've worked with certain therapists who've said, you know, punch a pillow, express the 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.'Cause it recruits more brand circuits. Into its service.

So that's the difference between Healthy anger on the one hand, which is essential boundary defense. 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 gonna punch a human being And there's a pillow to punch instead, better to punch the pillow.

You know, no question about that. But as a technique of dealing with it, no, that's not how you learn to process that rage'cause it needs to be processed. How do you approach the processing? What is a more effective

prescription or one possible way. 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. Yeah, I have done an The 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. Wonderful spir uh Buddhist lineage spiritual teacher, meditation teacher call Tara Brah, who talks about rain.

Recognize Hello. Investigate and nurture. So you recognize Oh yeah, this is happening to me right now. I'm okay.

I'm gonna allow it. Not Along it in the sense of I'm gonna act it out on somebody else. But I wanna be with the experience.

And then Investigate, okay, what is this video 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. But in experiencing it. Next up

Boss Rutin A Dutch American actor Former mixed martial artists. Kickboxer. and professional wrestler.

He was a UFC heavyweight champion. And a three time King of Pancras. World champion. We can't tease the Sweden story without Okay Okay, so Sweden. What happened in Sweden? Oh okay, so

Yeah. Understand this. When I'm drunk, I'm a happy drunk. I'm always drowned partying and you know but but still it's it's stupid because I don't have alcohol in the 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. I mean the whole Sweden

They love me. After this happened. So when I walked in, they recognized me and they said And you couldn't 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 uh this one guy wants to give me a drink 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 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? No, you have to come with us. I said, Do it. I'm not bothering anybody. So they grabbed me. I don't want to fight because I know if I push somebody, it's already gonna fight. But I don't wanna fight. So I walk with them. And now with the two bounces where the fire escapes. And there's this big marble stairs going down. And this guy's a little guy and a big guy behind him.

And the little guy's wearing a leather jacket, I remember that, and there's this big guy's thing. Croatian uh guys, Croatian mob they said. Yeah. And um I'm talking to the guy and he's pointing on my chest the whole time. And I say, Guys I w I'm going. Don't worry about it. I don't want any trouble. Can you tell my body? He's also 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 again. 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, staps a finger in my eye. So I'm going like guys, I don't want any trouble and it takes my other way. As soon as that happens, I knock him out because what's next? He's gonna kick the ball, he's gonna he's gonna escalate. I mean once you take two eyes.

Should I knock them up? The problem was they had these little microphones. So now three out of punch is coming. And that guy, of course, he's out, but while I'm fighting the other bouncers, he starts waking up. So I'm dropping left and right every way. I put three in the hospital and uh finally I realized eventually I'm gonna run out of gas. This is gonna go wrong. I gotta 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 and hitting and hitting and I'm going down. And I remember I still say I remember exactly how it looked. That was one of those copper things that you push in to open the door. And it was locked. Uh Yeah, I couldn't get out. But till that time I was still fighting by the rules. I wasn't stabbing ice, I didn't kick the balls, I didn't all I was still kinda just

Fighting. You know, not to destroy. So now I made out my mind. And I turned around and I told myself I'm gonna stab eyes, I'm gonna go all the way. And as soon as I looked at them They all step back.

And I felt really powerful for about Five seconds because I thought they saw in my face. Then I meant business. But it wasn't behind me. There was the whole police force was standing behind me because they had a pole and that's why they stopped fighting. But they threw me in jail.

Uh from jail I went to a a jail in the freaking mountain. 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, go I go like this like a movie, I gotta come out of it. It's like uh you're like a bad wizard in Harry Potter, yeah. And then it put me in prison. I still couldn't call my wife.

Oh, this is always say my wife hates this story, but she kinda thinks it's funny on one side or so, but it wasn't funny at the time. When I talked to her when I 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's just no no no, you're there with two Swedish blonde girls, aren't you? I go, You know me, honey. But me right now, alcohol counts. That's my only focus. Okay, I gotta go. So then two days she didn't hear anything from me. And now I pull it.

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 T V, I had a V CR, they gave me cookies, tea, I was playing cards with the guard, it was hilarious. But but still it was not fun because I was in jail and they told me I was gonna be six to nine months in jail because apparently one of the cops Of one of the bosses was a cop.

But you didn't say he was a cop. So well if you attack me, well yeah, I'd knock you out as well. You're saying like the you said the The cop of one of the bouncers. The like the father of one of the bouncers or the brother one of the bouncers? No no no one of the bouncers was a cop. Of Do die Cup. Apparently in Sweden they need.

Or 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 call my wife and she's freaking out now. And I go, honey, calm. I don't have a lot of time. I have some good and some bad 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 are 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 uh one of those guys for for the bouncers? He went on a big show, like an opera 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 call them. 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. through the roof over in Sweden and I became their hero because everybody had trouble in that bar. And now they finally had somebody who Who g give it back?

You know? But still. It was a very s now I'm here and I can talk about it with a smile, but at that time If you think you're gonna 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 gonna believe me. So uh yeah, that was the sweetest story. So So prior lifetime. Prior lifetime.

No it's now take the rosary and it's not. Next up Kevin Rose. Serial entrepreneur? World class investor

And self experimenter. I did one of those full body MRI scans called Perdomo. Yeah. Yeah, we should talk about this. This is something I need to get on. Yeah, I 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, but like

It was just one of those things where I got to the stage in life where I I had a couple of little girls and I'm like, Uh, you know Tia was telling me. He was like, Hey, you know, you can do these you're at the age now or it makes sense. See if anything shows up. They can detect it's something like eighty percent 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 it you know, that's normal, la like this is a little bit weird. You have an extra vertebrae, which I actually do, which is weird. So oh uh little vestigial tail. Yeah, exactly. A bunch of shit like that. So uh I I do that and then I go for year two. Then I go and get the scan again. And they call me up and they're they're like

Yeah, it turns out you have a little brain aneurysm. A little s little small brain aneurysm. And I'm like I'm like, what the fuck? Like this is crazy. Okay, tell me more. And Then after the fact, like a a month later, Or not a month later, but a few weeks later, my doctor uh calls them and says, Hey, what what do we see on the first scan?

They found it on the first scan as well. It hadn't changed. Which is great. Yeah. 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 that, but

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. But It's something you should do. Which is why we're having croissants and coffee tomorrow. Exactly. Well, I mean that's not my document. Yeah.

It's forty five minutes, so it's fast. Yeah they not the procedure. The review of the results. Yeah, I mean you go through it and I have a couple of spots on my brain and they they tell me you're allowed one per decade. And so they're like, You're fine, you have, you know, two or three or whatever, that's fine. I'm like, Okay, this still doesn't sound good. 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 they're like, Did you get your your COVID vaccine on that side? I'm like, Yeah, I did. And 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 bit. No, no, there's like a a little like Like I have this little tiny bulge in my right nut sack. It's just it's kinda like the the little stringy thing that connects to the sack. Kinda bulged 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 little shit like that. Cool. Oh my God. I can't wait until our random shows when we're like in our sixties and seventies. It's just gonna be a list of injuries and prostate complaints. Exactly. Oh my god. So

So let me just rewind. So make sure well just make sure I'm hearing you correctly. So were you pissed that they did not? Yeah. That they didn't spot it first time around. I think it was it was so small that they just they have different it's not a radiologist, whoever it is that reviews it. It's probably radiologist. I think it is. I think the first problem was was like, This is so insignificant, I don't even need to call it out.

And the second one called it out for for and they were just like and then they compared the notes and it was fine. This is the story I haven't told him. Went in, had a scan. They found a growth in his brain.

Non cancerous. Decent size. operated, 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 and it saved his life, most likely. Yeah. That's that's wild. And so it's shit like that. And the the radiologist when I talk 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 that are 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 get your diagnostics, folks. And I mean do it more f 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. Don't push it out. So I've 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 uh spent several days with him and Not to have cancer. 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, 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

Up beat. 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? Just blew my mind. And I've spent I know'em well enough and we've had enough interactions. I 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 their closest friends, like I don't wanna die, I don't wanna die, I don't wanna 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 it's certainly sad in its own way, but A real gift that he's also giving those around him. It's incredible. How how are you doing with dealing with all that? Uh w you mean with with his situation. Being a friend is 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 we've got to do? I'd like to I would like to. I mean it's I 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. Of course it's sat on a number of levels, but

I mean, we're all we all have a one way ticket, as far as we know. You know. My my dad before he passed said there's no lease on life. He just like wanted to remind me of that. 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 a problem. And this this has been a very strong reminder for me. It's like, Yeah.

Get it together. You know, like Too much. Like have fun. Don't take 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. Three hundred and sixty six meditations on Wanderlust.

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 a novel. It was gift to me by my brother who has a very high bar, and it took me several attempts to get through the first hundred pages because it's very dense. And you can't put it down. after thirteen pages and pick it up for seven pages two days later and then read another twelve pages. That will never work. You have to kinda 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 and time for a few weeks. It was very, very cool experience. Are there any other Books, writers, thinkers, experiences. That

People might be able to 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 vagabond trip. I was like twenty three. 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 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 dirtbag and I wanted to stay there. And this guy, he was just out of the Navy.

He wasn't necessarily gonna become a monk, but he was really interested in monasticism, and he had this skull and crossbones on his arm. And that's where I learned the phrase memento mori. I did I had no idea what mementum more, remember death is, the philosophical idea of memordeath. And I've been thinking about it ever since. You know, actually one of the the inspirations for me as a traveller, you know, for vagabonding and up to the new book is just the idea of Life doesn't necessarily reward you in time. My grandfather was a Kansas farmer. He worked really hard from the age fifteen. 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 that was a really heartbreaking thing when I was young, but I realized that you sort of Yeah. 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. And so there's great writing about time. Is it Oliver Berkman? I think I think you've quoted other people I've I've started four thousand four thousand weeks. Four thousand weeks, yeah. No, I've I haven't finished that book, but it's

I was read like ten 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, who at time is sort of One of the things he experiments in as a filmmaker and I love before sunrise because it's about who a guy who meets his his true love, you know, on on a train in 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, you know, which is something I know you talk about quite a bit, but is not done as much anymore as it was in the nineties when that movie was first made. And just the idea that Celine, 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 Linklard has some other you know, their boyhood is about very specifically about time and aging and things like that. But I saw before Sunrise Around 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 it's 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's always puts me into this thought experiment of how time is playing out and how I'm making use of it.

Next up Doctor 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. How was the hypothesis formed?

At all. That Cademine. 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 seemed to experience less PTSD that was somehow recorded in the field, and that led to hypothesis generation and and use of ketamine.

That Seems pretty tenuous. I don't know if that's true, but how did it go from And aesthetic to Of all the things we could choose. We're gonna

Mess around with ketamine. First off, I love hearing stories about how I and uh Dennis came up with ketamine for depression. I just want my like people. I I 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 the genesis. stories of these things. I think they're important. So I'd love to hear the

The real story as opposed to the Santa Claus version. So the real story Is not related to depression at all. It's related to schizophrenia. So it so happens. In the

Great cosmic Universe of coincidence. The 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. Inter tubing down a river.

with his daughter we were maybe ten or nine or ten at the time. His daughter is now Is named Joan Luby. She's now an endowed professor in an expert in child psychiatry at at Washington University in Saint Louis. Anyway. This fellow's name was

Elliot Louby And in nineteen fifty nine. He published a paper. That was the first time Fencyclade. or certain was given to a human being.

This happened at the Lafayette Clinic in Detroit, uh an entity, a building which no longer exists, uh unfortunately. An extremely Extremely Generative place in its era. And he said If you gave Cernal.

Which was the company name for pencycladine P C P Angel Dust. If you gave it to people It produced something like schizophrenia in them. The thing was That's nineteen fifty nine.

And the mechanism The fact that it blocked the NMDA glutamate receptor wasn't Identified until the mid nineteen eighties or In eighty three, eighty four. So

It was this Fascinating observation. Which couldn't go anywhere scientifically. But they did research and this is gonna bring us to other topics that we'll probably talk about. In which they compared

The effects of Pencycladine. to the effects of LSD in people. Mm-hmm. Good old psychometic. Yeah. Just

Unbelievably courageous and creative trailblazing psycho pharmacology. At a time when they just had no idea what was happening in the brain, the neurobiology. And In the early sixties. Another.

Trailblazing scientist also associated with that group was a guy named Ed Domino. Who was a pharmacologist Great name too. Yeah. My

Cousin. Come. I apologize for mentioning his name. Who is a medical student At the University of Michigan.

brought me to sit in one of his classes when I was applying to medical schools. And it just happened to be Ed Domino. And my friends, my my cousin and his friends Ed Domino. came up to talk saying a bit of the Van Morrison

Song Domino. Uh which you which you may may be familiar with. Anyway. Unforgettable to me because Ed became a very dear friend.

And colleague uh over the years. But And Cadomine.

Two. Animals and humans. Because it was a shorter acting Safer version of a Small structural modification.

In the Thencyclodine 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. There was a A fellow Corson, who was working with him on some of those studies.

So there's a line that I love. I love Portentious lines. In scientific literature. I think it's the last line in the Watson and Crick discovery.

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.

The first papers on ketamine May maybe the first paper. Yeah.

Yeah. 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 Block in its transmission to association cortex. We call this dissociation And this Process dissociative anesthesia, something like that.

And Wow. What a profound cast off sentence, right? Buried in the discussion section of a paper in an anesthesia journal. 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 Thirty years. ahead of the field.

And You know, it wasn't even known that there was a binding site. For Fancyclade. So

First studies published in nineteen fifty nine. Wasn't even known that there was a binding site for fencycladine. 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, but At a specific target in their brain. What that target was They didn't yet know until n the early nineteen eighties that it was a glutamate receptor. But in incyclining until uh landmark paper in nineteen seventy nine from

Steve and Suzanne Zucan. So It was Darkness, right? It was like The Middle Ages.

Of neuroscience. And so they they had a brilliant insight, but they couldn't take it anywhere because there was no Framework for it. So

Around eighty eight eighty nine. Join the faculty in eighty eight. Uh yeah. And

I wasn't sure what I was going to do. And my boss said to me, D Doctor Chinese 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. Okay. 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 neurobiol and treatment of schizophrenia. And It happened To be just at that time that clozopine, which is an anti psychotic medication that's a little bit more effective than other

And to psychotics. 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 clozepene and and I thought it was a pretty good medication. But I didn't want my legacy after forty years. of schizophrenia research to be that He figured out why clozepine was a little bit more effective than other antipsychotic medications.

So I I I felt like I just had to Go out of the box. And This is where my father's legacy really

had it had a big impact. 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, P C P blocked this receptor for glutamine.

And so What brought me to Cademy 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 Might. Was The development of a research program on glutamate.

Psychopharmacology. Developing Circuit and mechanistic hypotheses. And one of my collaborators in those days. Was

A pharmacologist named Beta Mogadum. And in nineteen Ninety seven. She published a paper That showed

That Ketamine released glutamate in the brain. Yeah. 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 Cadmine administration as a platform for trying to id identify novel Alternatives to antipsychotic medication for the treatment of schizophrenia. And and that has had its own life and story in. Maybe some day we'll We'll talk about

Yeah. One of the things Beta 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. Yeah. Release glutamate. If you give it at anesthetic doses, it depresses glutamine, and it's not antidepressant at those doses. And if you give it a little bit more.

At even a little bit lower level. It doesn't stimulate the glutamate release. There's this tiny narrow window. Where it's reducing dissociation, psychosis, and a number of the other effects that we're really interested in. Where it works. And

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. 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 too. Who

Couldn't answer a lot of our questions. But he was holding on to the bed really tightly. And um and I said. Well, that's interesting. Why were you holding on to 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 and the uh You know, uh the outer planets. And he was afraid that if he let go of the bed that he'd be cast adrift in outer space and and not make it back. Well That was really fascinating. Seems seems reasonable. Yeah. Was really, really interesting. But Useless. I couldn't get him t 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 have repeatedly

uh 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 forty minutes? Well Because ketamine is such a short acting drug. We administer it for forty minutes. To give us a time window.

Where people are having The subjective effects academy 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 Academy administration for the treatment of depression. Last but not least.

Doctor Suresh Mutakamaraswami. Associate Professor at the school of pharmacy University. of Auckland.

What I would like to just make note of Really quickly is that I feel the L S D microdosing study that you just Yeah.

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 uh one of them is placebo control. Yeah. 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 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 gonna be expectancy effects and generally people are gonna come in knowing on sub level what psychedelics are or believing that they do and having done some reading and so on. Right. We won't even get into no SIBO 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. Pasebook. Control. And uh 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 had ever done L S D microdosing before. We wanted a rant for In the community, we wanted a 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 haven't given them any drug. This is just pure so we had a very pure safety group to look at. And In terms of analyst With the people are you know Able to detect the effects. Summer, summer. So we are around the threshold.

This was at around uh ten micrograms? Yeah, about ten micrograms in male volunteers, so There was quite a heterogeneity though, actually. We we saw that some participants were particularly sensitive to it and we had to reduce doses for some participants. And some hardly notice. 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 wanting 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. 'Cause we're now interested in the clinical outcome, not just sort of like can you do it. What do people experience if we're wanting to kind of try to fool people a bit better? Then Probably some kind of light placebo.

The little bit of I wouldn't say deception, but just ambiguity. in and the information that we provide to participants might be enough to get us over the top. In terms of blinding the studies 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 wanna jump in for a second. So I would say also that the the fact that placebo controls are so difficult 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 read a whole mess of paper on stomach so I mean it's fascinating that it's so hard. Do you have any you don't have to give away your secrets, but anything on the short list for potential active placebos that would you you would use in such a case? Niacin

Nia Niacin's not a great option. That's um yeah a vitamin. So actually niacin was used in the nineteen sixties and it's been determined Even in nineteen sixty that niacin is a poor control for size. People used to use it for some reason, and I'm not sure why. Skin flushing. I mean maybe subtype of sub subjective experience so that people think it's doing something. Yeah, so it's added to a lot of dietary supplements as well. We're getting into the weeds here, but what I would say is actually what the compound is isn't as important. Is what the participant thinks it's going it's their belief about what they're receiving. That's the important thing because Blinding in clinical trials is really important to prevent expectancy. Because if a person goes into a clinical trial thinking they're gonna get side side and they do get side side and and if they think it might make them better, they work out that they've had it and they go, Oh And maybe they're over ex insurite.

over accentuates the clinical response, which we would call a confound. So that's potentially a problem. So 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 in the Because

You're not trying to manipulate your 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 in our experimental designs. You know, this is why I really enjoyed doing research in this era, 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 I'm not you know Give me another ten or fifteen 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 the ecosystem and a really exciting time for people like you to be doing the research. 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 cost first. 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 Dr Gabor Mate.com. That's G-A-B-O-R-M A T E dot com on Twitter at DR Dr. Gabor Mate on Instagram at Gabor Mate M D. 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 addiction, stress, and childhood development. Doctor Mate has written several bestselling books, including the award winning In the Realm of Hungry Ghosts. I highly recommend. Subtitle 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. I My guest today. Why would I be so excited? This is Sebastian Rutin. Better known as Bos Ruten. You can find him on Twitter and elsewhere at Bos Ruten MMA. Is a Dutch American actor, former mixed martial artist, kickbox, and professional wrestler. He was a UFC heavyweight champion and a three time

King of Pancras world champion. We're gonna talk quite a bit about that. Finishing his career on a twenty two fight unbeaten streak with a strike accuracy of seventy point six percent, the highest ever recorded by Fight Metric. Ruton was co host of Inside MMA on Axis TV. That's AXS from two thousand seven to two thousand sixteen, and he has been a color commentator in several MMA organizations, including Pride Fighting Championships, another thing that we will spend some time on. 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 nineteen nineties, and in two thousand fifteen he was inducted into the UFC Hall of Fame. We'll link to all of the social as well as the O two trainer, which we're gonna get to. You can find that on Instagram at O2 Lung Trainer and we'll link to YouTube, Facebook, and other places.

Yeah. This is another edition of The Random Show with my friend Kevin Rose. Who's Kevin Rose? He's a technologist. 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.

I 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 four hour work week. His newest book is The Vagabond's Way, three hundred and sixty six meditations on wanderlust,

Discovery and the art of travel. He has reported from more than sixty 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 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 thirty acres with his wife. Kansas born actress Kristen Bush. My 2014 God. How old are we getting? Rolf, we're gonna talk about that. My two thousand fourteen 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 gonna 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. And you can also find everything Rolf at RolfPots.com.

Yeah. 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, 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, and NIAA Center for Translational Neuroscience of Alcoholism and Clinical Neuroscience Division of the National Center for PTSD. Doctor Crystal's a member of the US National Academy of Medicine, co-director of the Neuroscience Forum of the US 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 is the co founder and chief scientific officer of Freedom Biosciences, which you can find at freedombio.co, a clinical stage biotechnology platform developing next generation ketamine and psychedelic therapeutics, that just recently emerged from Stealth in August of twenty.

22. I And without further ado, let me introduce the main attraction and the guest of the hour, and that is Dr. Suresh Mutu Kumara Swami. I will hear Forward referred 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 Center as a postdoctoral fellow. While at Cardiff, he started research work with the psychedelics. And psychedelic compounds in twenty eleven in collaboration with two very well known names, Professor David Nutt and Dr. Robin Carhart Harris, investigating the neuroimaging correlates of the psychedelic drugs psilocybin and LSD. In twenty fourteen, Suresh.

received a prestigious Rutherford Discover Fellowship and returned to the University of Auckland, where he works in the school pharmacy at the Faculty of Medical and Health Sciences, and lead 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 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. Hey guys, this is Tim again, just one more thing before you 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 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 slash Friday. Type that into your browser, Tim.blog slash. Friday, drop in your email and you'll get the very next one. Thanks for listening.

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