A (3:24)

Good to meet you, Andrew.

B (3:26)

Addiction is a big topic, but I think for a lot of people it gets slotted into one small drawer. But if we were to compare it to say, mental illness, many, many things, depression, manic, bipolar, ocd, and on and on. How do you parse this thing that we call addiction in thinking about how best to possibly treat addiction, Especially when it comes to trying to treat addiction en masse at the level of policy, which we'll also talk about today. So put simply, how do you frame addiction and how should people think about it?

A (4:01)

Yeah, it's hard because it's a word. Unlike say, you know, maybe it's a little like schizophrenia where people say like, oh, you know, he's a schizophrenic person. What they actually mean is, you know, he's a person with different moods and that sort of thing. Addiction is even more like that. It's in common parlance, people say, you know, I'm addicted to, you know, a TV show, or I'm addicted to my phone or that sort of thing. But, you know, it's not just stuff you do a lot, you know, which we sometimes, you know, colloquially call addiction. It's the persistence of doing something that is harmful. So like the classic animal study, you know, is, you know, James old study with rats done in the 50s, showing that you could give a rat the opportunity to give itself brain stimulation, which they enjoy, and that they would continue to do that even as they were starving to death next to a pile of food pellets or run out of water while they were next to water. That is what it was. It's not the doing the things over and over or even being compulsive about things, it's doing them to the point of destruction. When you would normally any other behavior, you would think, well, you would just stop doing that. But people don't. And that's the sine qua non of addiction.

B (5:12)

I've tried to create a definition for addiction, which is that it's a progressive narrowing of the things that bring one pleasure. That it doesn't happen all at once. Like someone doesn't take heroin once and then stop doing everything else. It tends to be progressive. I suppose it could be overnight. But is that true? I'm happy to revise the definition.

A (5:33)

Yeah, no, that is true. So you see, the other types of rewards, particularly natural rewards, start to fall away from the person's life. So I'll sacrifice my relationship with my parents or my spouse or my friends. I will stop going to work, which would normally generate the things I needed to eat, or I'll give up my housing for the sake of this substance. And then you become not only more physically dependent on it, but essentially you're psychologically dependent on it because it's the one thing left that is still rewarding. Everything else has been stripped away. And that makes it easier to understand why people would still hang onto it in that situation when it feels like, look, it's the only time I feel good is that moment when I take that hit.

B (6:18)

These days, there are a lot of industries that are addiction for money, basically, industries. And we're gonna talk about all of them. Nicotine, alcohol, cannabis, social media, all of these. But for the time being, do you think that there is truly something to the genetic bias for becoming an addict? And is it very substance or behavior specific? Let's start with maybe alcohol, for example.

A (6:47)

Yeah, yeah, that's a great question. So let me start by just getting rid of one myth where we say people are born addicted. You'll sometimes read, if mom was addicted to fentanyl, then the baby is born addicted. That is not possible because a fetus has no association between their behavior and the exposure to the drug. So they can be physically dependent, meaning they'll go through withdrawal upon birth, but they're not addicted. But you can have Risk from birth in your genes and the estimation of how much of that is shared. It's actually quite a bit. We look at studies where kids were adopted out of families with parents who were addicted to alcohol. Much higher likelihood of developing an alcohol problem, even if they were raised by teetotalers, for example. How big is that? It varies across studies. It varies across substances, but it's large. It might be like 0.3, 0.4, 0.5 for most of them. And you can imagine that the same gene, some might be specific and some might be more general. So here's an example of a specific one. If you are born into a group like Han Chinese are, and you lack the enzyme or don't have much of a particular enzyme that is used to metabolize alcohol, it is just a less enjoyable experience to drink. You can't break it down to acetaldehyde and acetic acid and all that sort of thing. And so that one is. But that wouldn't lower your risk for anything else, but at least specific for alcohol. But other genes for things like impulsivity, that would put you at risk for across substances. Being sensation seeking, you're going to try more drugs. That means it's more likely that you're going to get exposed to one. Another thing we see happening, which is really fascinating and poorly understood. I, of course, know doing what I do. Lots of people are in recovery. And I've known people and had people in my studies who have been, say, clean and sober in their sense for 20 years. And then all of a sudden they develop a very strong sexual compulsion or they gain 30 pounds because they're just eating and eating and eating. And it's like, you know, the underlying diathesis, whatever it is, has found a new phenotypic expression because it was never actually resolved. What was resolved was the particular set of behaviors that went with the addictions they had when they got into recovery.

B (9:14)

When it comes to alcohol, I've heard it said that there's a subset of people with, I guess nowadays they call it alcohol use disorder. Can we just call it alcoholism today?

A (9:24)

Sure.

B (9:24)

Okay. Sometimes people will lash back at me if I refer to someone as an alcoholic. But I have enough friends who are alcoholics. That joke is only on them, by the way, who are recovered. So I can make the joke. Cause they're impressive recovery stories. And they all just say, just call it what it is, which is alcoholism. There's just so much splitting of names now. I don't want to put you in a position of saying something that's going to offend anyone. Whereas I can do that.

A (9:50)

No, this is worth getting into. So use disorder is a much broader spectrum thing. So if you diagnose someone with alcohol use disorder, it can be mild, moderate or severe. And the people at the mild end, everyone at AA would laugh at this is a person who occasionally drinks too much, has some harms, but basically life is still put together. And people at AA would be like, you gotta be kidding me. That's your problem. It's only when you get up to the severe end where we see the things that looks like addiction, so they aren't actually the same thing. Addiction and use disorder. Use disorder is broader and it was there to sort of move alcohol like other health behaviors that you might start addressing, particularly in primary care. So just like we would like doctors to intervene when someone is 15 pounds overweight and has moderate high blood pressure so that they don't later develop a more serious problem. That was the idea. Well, let's have a lower severity problem that a doctor might, while the person still has a fair amount of control, advise you, hey, you know, if you could just cut back a bit now, you could avoid a lot of suffering later. That's where that came from. But I'm comfortable talking about addiction. It's a good word. It's scientifically meaningful, and it's something the public understands.

B (11:03)

Yeah. And if you go to an AA meeting, they go around the room saying, I'm so and so and I'm an alcoholic. They don't say, I'm so and so and I have alcohol use disorder.

A (11:12)

Oh, that's right.

B (11:14)

So many people who are in recovery define at some level of their identity, not their total identity as an alcoholic. It's actually an important part of the 12 step recovery process, which is. Which we'll talk about in any case. Not to split hairs here, but I'm grateful that you're willing to embrace that nomenclature. And thanks for clarifying why it was split. Because sometimes these clinical and naming things are split because of quote, unquote, sensitivities. We don't want to offend, et cetera. And we don't want to offend. Okay, so alcohol, I've heard it said that there's a subset of people, somewhere around 8 to 10% for whom they. They drink alcohol. And they experience it very differently. They experience it more as a, for lack of a better term, kind of a dopaminergic energizing experience. And this could relate to tolerance, but that they have a very different experience subjectively. Of alcohol than most everybody else who can build up tolerance? Anyone can build up tolerance. And then it takes longer to get into the sedative effects, the depressive effects of alcohol. But I've heard it said that this 8 to 10% are particularly susceptible to becoming alcoholics because they drink and they feel spectacularly good, and they can keep drinking in a way that many other people either pass out, blackout, crash their car, end up in jail, or dead. And so in some sense, this 8 to 10% may be at greater risk than everyone else.

A (12:46)

Yeah. So Mark Schuchat, who's a superb psychiatrist who's based in Southern California for most of his career, did some wonderful studies of male children of alcoholic fathers. And one of the things he showed is that when given alcohol, their body sway is less at a level you can't even perceive. But he could measure that body sway. Yeah, like how much they moved, like how hard the alcohol hit them. And they had fewer hangovers the next day. And then you might think, well, that's great. It doesn't hit you that hard, but you can drink a lot. Like, no, that's the problem. Because someone else would get the signal of like, whoa, I'm feeling kind of dizzy here. I must have had too much to drink. Or the next morning, they get up and go, oh, God, I'm never doing that again. They don't get that signal. It's less punishing, more rewarding. And you see that across drugs, and this is almost surely genetic. How much people like different drugs varies enormously. I'll be personal about this. So I had an injury, I broke my ulna, and I had to take Vicodin for the pain afterwards. I find taking opioids so unpleasant. I feel bound up, miserable, groggy, that I just took one and said, pain is better than this. I have worked with people clinically who say, the first time I had an opioid, it was like a hole in my chest. Had been there my whole life, filled up for the very first time. That has everything to do with genes. There's no learning history there. Right. But there's something, you know, I'm just wired differently for that particular drug than people who get in trouble with it is. And these don't necessarily go in groups. So someone can, you know, hate opioids, but, you know, love cannabis or love alcohol. And that, of course, is going to change their risk. How could it not?

B (14:41)

This is such an important point, and I didn't realize that it extended to things outside of alcohol, because oftentimes When a discussion starts to surface about addiction and whether or not zero is better than any, whether or not things can be done in moderation, I think this is actually a big unspoken point of friction, because some people really can drink five or six drinks.

A (15:02)

Oh, yeah.

B (15:03)

And then the next day, they're at work, hammering away, and they're gonna say, listen, my life's going great.

A (15:08)

Yep.

B (15:09)

And, you know, liver markers are still within range. Eventually they'll decline. You know, they'll get worse. But the conversation becomes very difficult to have because it's high. It sounds like it's highly individual, how people will react. And there are the behavioral impacts. Like, for instance, I've heard the statistic that one of the greatest risks for becoming an alcoholic is if your first drink is before the age of 14. So I find that some people will have their first drink, like you said, and it's like a magic elixir for their physiology. And there are very few things that can get somebody like that to stop drinking, except the risk of losing everything. And sometimes even then.

A (15:51)

Sometimes even then.

B (15:52)

And so maybe alcohol is the best template for talking about this, because it's socially acceptable in most places for adults anyway.

A (16:00)

It's legal, it's marketed, it's legal, it's marketed.

B (16:02)

And. And yet how does one know whether or not they have a predisposition? Because those people might want to avoid using something. Because our colleague Anna Lembke has said that you can't get addicted to something that you've never done or taken.

A (16:19)

Yes, that is the most helpful advice. So I can never tell you if, in this game of Russian roulette, the bullet will not be in your chamber. For sure. I can say you're less likely for this, more likely for that. But the only way to determine that a substance will not damage your life is to never use it in the first place. There's always going to be some risk. There's been a lot of work on genotyping to try to figure out, could I tell people what their genetic risk is for alcohol? And nothing is as good as just saying, your parents alcoholic? Yeah. Or no. And if they were, that's like the most useful bit of information. Or does problem drinking run in your family? That kind of is crude a question as it is, that's more useful than anything we have from SNPs or anything like that.

B (17:04)

Does it cross sex? So, like, if a daughter has a father who's alcoholic, does it cross sex as readily as it goes from, say, father to son or mother to daughter?

A (17:15)

No, I mean, there is still risk there for sure. But the father to son link is the strongest one you see in genetic studies. Now, of course, in a sense, it's hard, right, because men drink more than women do, I mean, in our culture anyway. And they drink to excess more than women do anyway, whether they've got an alcohol problem or not. So if you think this is some sort of unfolding process, then men carrying risk would be more likely to have that risk realized through the behavior than a woman would. Where there's still a fair amount of women who don't drink or drink, hardly any. So it's sort of like the thing. If you had all the genetic loading for cocaine in 1800, it didn't matter there was no cocaine. If you had all the genetic looking for alcohol and you've never drank, then it's really irrelevant.

B (18:05)

I'd like to take a quick break and acknowledge one of our sponsors, David. David makes a protein bar unlike any other. It has 28 grams of protein, only 150 calories and 0 grams of sugar. That's right, 28 grams of protein and 75% of its calories come from protein. That's 50% higher than the next closest protein bar. These bars from David also taste amazing. Right now, my favorite flavor is the new cinnamon roll flavor, but I also like the chocolate chip cookie dough flavor and I also like the salted peanut butter flavor. Basically, I like all the flavors. They're all delicious. Also, big news. David bars are now back in stock. They were sold out for several months because they are that popular, but they are now back in stock. By eating a David bar, I'm able to get 28 grams of protein in the calories of a snack, which makes it very easy for me to meet my protein goals of 1 gram of protein per pound of body weight per day and to do so without eating excess calories. I generally eat a David bar most afternoons and I always keep them with me when I'm away from home or traveling because they're incredibly convenient to get enough protein. As I mentioned, they're incredibly delicious. And given that 28 grams of protein, they're pretty filling for just 150 calories. So they're great between meals as well. If you'd like to try, David, you can go to davidprotein.com huberman Again, that's davidprotein.com huberman Today's episode is also brought to us by BetterHelp. BetterHelp offers professional therapy with a licensed therapist carried out entirely online. I've been doing therapy for many years now, and I can tell you that it's a lot like physical workouts. There are days when I want to do it and there are days when I don't want to do it. But every time I finish a therapy session, I come away feeling much better and knowing that the time was very well spent. Typically, when I finish a therapy session, I come away with at least one valuable insight or perspective on something that I'm working through, whether that's with work relationships or my personal life, or just simply my relationship to myself. There's just so much benefit that comes through effective therapy. And with BetterHelp, they make it very easy to find an expert therapist who can provide you with the benefits that come from effective therapy. With over 30,000 therapists, BetterHelp is one of the world's largest online therapy platforms, having served over 5 million people globally. And it works with an average rating of 4.9 out of 5 for a live session based on over 1.7 million client reviews. Also, because BetterHelp is done entirely online, it's extremely time efficient. There's no driving to a therapist's office looking for parking, et cetera. If you'd like to try BetterHelp, you can go to betterhelp.comhuberman to get 10% off your first month. Again, that's betterhelp.comhuberman women are drinking more or less now.

A (20:41)

Women, unfortunately. You know, in the late 90s, early aughts, the alcohol industry figured out that women had more money but they weren't drinking the way men were. So they engaged in a long term campaign to try to increase women's drinking. So things like mommy wine juice and those mommy wine chats online and all that, that was really engineered by them. Even some of the ones that look organic online were engineered by the industry and it worked. Women's drinking went up a lot and the damage per drink is more for women for most things than it is for men, partly due to body size, but also partly probably due to some hormonal things. And so it's been a exploitation, as I see it, of women. And I notice a lot of young women now, like undergraduates I talked to re evaluating that, like looking at their mom's experience and saying I don't think I want to do that. And I'm really encouraged by that. Not that I want to to control the decisions we make, but I don't want them making them just because the industry slickly marketed to them. Because the industry's sole interest is always Going to be to generate profit. And you do that with addiction because something like what? 10% of our country drinks about half the alcohol. Yeah. You're shocked.

B (22:03)

10% of the country drinks half the alcohol, United States.

A (22:06)

So if you're running the industry, you want that group to be as big as possible. You do not make money off people who have half a bottle of wine on special occasions. You make your money on the people who drink the equivalent of multiple bottles of wine every single day. So you have fundamentally these industries, the more addiction there is, the better off they do financially.

B (22:31)

Wow, there's a lot there. The statistics say that drinking is at an all time low in the United States right now.

A (22:38)

At least some statistics. Yeah, some statistics. Something seems to have changed and this may have something to do with this new generation. There's less risk behavior in lots of things over the last 10 years. So less cutting class, less chance of dropping out of high school, fewer unwanted pregnancies, all that stuff. So that generation will probably be a drier generation than their parents were.

B (23:05)

Is cannabis use higher in that group? Everyone likes to just default to. Well, cannabis is up, so alcohol's down. Implying that you have to do something, that people have to be using some sort of mind altering substance.

A (23:17)

Yeah. With the legalization of cannabis, we certainly have seen a lot more use and a lot stronger products, but youth use really has only changed pretty slightly. So the growth has really been among adults, including adults who probably stopped at some point and have now gone back in later life to using cannabis.

B (23:35)

We'll get back to cannabis, but I want to parse the alcohol stats a bit more also as it relates to women. Maybe we can just either put to rest or not this argument that some amount of alcohol, typically it's red wine, is couched this way, is more beneficial for you than not drinking at all. My read of the data, and we covered this in a long episode on alcohol a few years ago, was that zero is better than any. And that two per week. Two drinks per week. And that's getting very specific about ounces for, you know, spirits versus two per week is sort of the upper limit for adult non alcoholics that don't want to incur any additional health risk. The cancer risk, very clear. The disruption to sleep, which probably cascades into other things, inflammation, et cetera. But is zero better than any is too safe for non alcoholic adults? Because every week it seems I see a new article that says zero is better than any. No, wait, it turns out there's some benefit from two drinks per week. And I'm getting, frankly I'm not tired of it, but it's almost getting funny.

A (24:49)

Yeah.

B (24:49)

The extent to which the. It's traditional media not to poke on them but they just keep flip flopping. And then the questions that always come up are, well, did the alcohol industry sort of encourage this study? Because if we're honest, there's a lot of advertising of alcohol in traditional media outlets.

A (25:07)

Oh absolutely. So statement against interest because I like red wine, I would love to believe it is healthy. It's not. And the whole thing about red wine per se, by the way, never made any sense. Like why would there be a benefit to red wine that wasn't in other alcoholic beverages? And it came from a 60 Minute story. I think it was in the 90s, it was about why do French people, why do Mediterranes look like it's the red wine. Red wine cells exploded. You know, this is so great.

B (25:35)

Resveratrol was an argument.

A (25:36)

Yes, that's right. You know, there's such trace amounts that were just like ludicrous, you know, in a grape skin. And so that was just spread and it was just so great for the industry. It's better for you than not drinking. And you know that's just not true. You know, it's when you look at, they would look at studies and say, well look, the non drinking group have higher mortality than the low drinking group and famous they call it the J shaped curve like that. Problem is non drinkers include people who are inalcoholics. Anonymous. That's why they don't drink. They had a wretched experience with alcohol and so they've had different kinds of damage to their bodies. Maybe their health isn't as good, they're not going to live as long as. But it's not that they would be better off if they went back to drinking. Things would go to hell basically for them. And that just got marketed and spread and it's not true. There might be some cardiac benefit, okay. But we don't get to live our lives as single organs. We have a whole body. You have to weigh that. If that is true and it is wobbly, but if that's true, it's smaller than the cancer risk. So your net is you're not going to get any mortality gain from mortality reduction from drinking alcohol. If you have two drinks a week and by a drink I mean like a 12 ounce beer, a 1 ounce shot or a glass of wine, a 4 ounce glass of wine, you have slightly higher risk, but it is very, very, very small. And it's not the kind of thing, if I were giving health advice to the country, that would not be on my top 10 things to be, you know, really frightened about. I think it's very small. It's just not good for you. That's what science has overturned. The industry message that this is will extend your life and you'll be more healthy if you drink than if you don't. There's no way we can establish that as being true.

B (27:29)

You said it very clearly. But I'm going to just repeat it because I think it's super important for people to take note of that. The cardiac benefit is less than the cancer risk. And I think that's a very important way to view these stats. The episode that we did about alcohol had a lot of different responses. There's obviously a selection bias in the responses. Many people gave up drinking who I later learned wanted to quit drinking. They didn't like it. The downstream effects of the disruption to sleep from alcohol and so on, probably part of the effect. It was very interesting as it relates to women because many people, including some members of my family, really like their post work glass of wine or want a drink to just kind of mark an end to the day and relax. My observation was that many women who stopped drinking either because of that discussion about alcohol or others that they had heard did so when they learned that women have a particular risk to cancer as it relates to alcohol. Meaning if the breast cancer risk and other hormone, ovarian cancer, hormone related cancers and so forth, not always hormone related. But the moment that the it's probably best to avoid alcohol entirely conversation moved into women's specific health. It had a very potent impact which is interesting in its own right. And it speaks to what's perhaps required to override some of the marketing. Because let's be fair, it's nice to relax with friends. And if people think relaxing with friends is easier to do over a glass of wine or two, then that's a great, not just marketing scheme. It's also somewhat true for them until there's counter evidence. And so what I'm really getting at here is, you know, how is it that people should frame what they know to be risky versus the other benefits of alcohol that clearly exist, like helps people relax, it's social, they stress less and so on and so forth.

A (29:30)

You know, as I mentioned, I'm someone who drinks wine and I know that it is, you know, on average, you know, it's not healthy. Why do I do that? It's like, well, because it creates other things, particularly with exactly that situation. Getting together with friends is enjoyable. Enriching good food is enriching good food. And a good wine tastes good, and I value those things. And there are many other decisions we make like that, where we endure some risk because we care about something else. It's dangerous to, you know, for someone my age to, you know, hike up a mountainside, probably, but if the view is spectacular, I can say, oh, I'm gonna accept that risk. And maybe I'm more prone to twist my ankle or something, but this is just really beautiful. That's okay. I think what the place we got an alcohol that was bad was needing an explanation to stop. So how often have you ever said to someone at a party or seen someone say at a party, why are you drinking? I've never heard that, but I've certainly heard a million times, why aren't you drinking?

B (30:37)

If you don't drink at parties or you refuse an offer of alcohol, people think there's something wrong with you.

A (30:44)

Yeah. And you have an explanation like, well, I got an exam tomorrow morning, or, I've got a cold or something. It's like, you shouldn't need an explanation. But people do feel that social pressure. And so that's one way health information can work. Why didn't the person just quit beforehand? Because they may not have had an explanation that worked in their circle. And now you can say, well, I see those data on ovarian cancer, and I decided to quit drinking. And that is health is a reason people still accept, I think, as legitimate for changing behavior. You can make that because cancer is scary. And that may be why people quit. Same thing happened when first Surgeon General smoking thing came out. Everybody smoked. You had to sort of fit in at work. You had to smoke. And when that came out, there were a lot of people who just quit immediately. They clearly were capable of quitting, wanted to quit, but they needed some to tell everybody. Why are you not smoking anymore? Why don't you carry cigarettes anymore? I can't bum one off you anymore. It's like, that's why.

B (31:49)

Why do you think people who drink feel uncomfortable about people not drinking around them? When people would ask me if I wanted to drink and I'd say no, and they'd say, why? They often say that I would say the truth, which is, I'll say anything that's on my mind without drinking. You don't want me to drink, because then I'll tell you everything that's on my mind.

A (32:08)

Oh, that's good.

B (32:10)

It's true. I mean, like, I will tell people what I'm thinking. I don't need to, like, loosen up. I'm pretty relaxed in social settings. I don't have much social anxiety. But I realize some people might have trouble with social anxiety.

A (32:22)

Yeah, you know, I spent a little time in Japan when I was a young man and there's this, you know, culture of getting going out after work, like the salaryman going to work and someone getting really, really drunk and everyone's drinking and you're vulnerable with each other and then you know that I will. It's like a trust exercise, like that falling backwards thing, except it is that we're all drunk and if someone weren't doing it, it's like, why are you not undergoing any. So we're all going to be vulnerable and you're not. Are you going to exploit us in some way? Or I'm going to say I think I hate the boss. And then you're going to repeat that at work because you're the one person sober enough to remember I said that. I think that is a real thing that people have anxiety about. Or I can imagine. What if a man and woman are on a date and the guy keeps giving drinks to the woman and doesn't drink himself? Like, you know, what is the natural thing to think? Are you trying to get me drunk? Are you going to take advantage of me? Because you're going to be with it and I'm not because I'm going to be drunk. So those kinds of fears may be in the soup, but I don't think so. Maybe that's rational at some level, but I don't think that should drive our sort of routine social interaction with our friends. It should just be a non issue of what do you want? And if I want sparkling water, I just give you a glass of sparkling water. And don't say, why aren't you drinking this intoxicating beverage? You shouldn't need to explain it to me.

B (33:48)

The trust piece is super interesting. So is the vulnerability piece. A couple thoughts about this, and they're just editorial thoughts, so forgive me. But one is for years I thought how crazy it was I would go to these meetings with doctors and scientists who ostensibly were working on issues related to health. And everyone would just get trashed at the bar. And I wasn't into that and I wasn't judgmental. I actually kind of liked it because by the third day of the meeting, I'm cranking and they're all just. I can tell they're all just Bleary. And they're also aging much faster than I am. They would get the tenured look, as we would call it, or as I would call it, like you see them in five years. I'm like, what happened to you? You aged 15 years. And these people tended to drink a lot, both at meetings and outside meetings. Alcohol was paid for, often by the meeting fees. This gets a little. I'm not trying to point a finger here. And then a lot of the stuff that happened at meetings that turned out cost people jobs was always alcohol related.

A (34:43)

Yeah.

B (34:44)

In the instance of the man and woman on a date drinking or a group of people at work drinking together in Japan, it sounded like it was men getting drunk with other men.

A (34:52)

It was men, yes.

B (34:53)

In my mental picture of the male female dynamic in drinking, I'm going to simplify this. If she drinks, it makes her vulnerable. If he drinks, it makes him more stupid and impulsive. And so in the world where she's drinking and he's not, you gave the example that perhaps he would take advantage of her. If he's encouraging it, certainly there's that picture in one's mind. He also can get her home safely. If he's drinking, he can't get her home safely. And he might say or do something really dumb. So I feel like no matter how the math is arranged, it always ends up drinking ends up being kind of a bad idea. I mean, not trying to be judgmental here because I don't judge what people do. Do as you wish, but know what you're doing is my philosophy. But I just don't see a world where drinking with your co workers or drinking on a date with somebody that you don't know very well, male or female.

A (35:47)

Right.

B (35:48)

For either of them, it's just like a lack of safety all around. It just seems like a bad idea.

A (35:54)

As women move into more professions that may have changed that norm of, you know, everybody goes out and gets drunk because the consequences aren't the same. And, you know, I know a lot of, you know, professional women friends. I don't want to do that, you know. You know, I don't want to be around the boss when he's drunk, you know, and so let's have a Christmas lunch together at work instead of, you know, drinks afterwards. So I definitely see that, I think, in the dating. Now, of course, I haven't thankfully had to worry about dating for 40 years. But what I think most people would say is just the anxiety is intense for some people and alcohol is anxiolytic and so it's probably that. That people are sort of feeling they're too nervous and whether they should or they shouldn't, that's just, I think probably in the soup. One of those benefits people care about. And there are people, it has to be said, who are more socially engaging when they've had a drink than when they haven't because they're kind of wound up. People, when they relax, some other stuff comes out and they may seem more appealing.

B (37:04)

It's interesting. We could dissect it a number of ways, but I think that's enough contour for people to be able to think about whether or not they have a genetic predisposition. Understand that 0 is better than any. If we hear about some cardiac benefit, to weigh that against the cancer risk and not just take it as an independent piece of information. And then to think about vulnerabilities of other people's actions and vulnerabilities of one's own actions and words. If drinking. And then people can make an informed decision.

A (37:35)

That's kind of how I A good.

B (37:36)

Summary, how I feel about it. Again, do as you wish, but know what you're doing is like the purpose here. Let's talk about cannabis a bit, because eventually I'd like to weave back to how industries impact use and abuse. Cannabis when I was growing up was illegal. You go to jail for it. People still smoke pot. It happened. The idea was that it was much less potent. We can talk about that. But now it's a whole industry.

A (38:05)

Yes.

B (38:06)

And the edible industry has contributed to this greatly because it bypasses the. The blowing of smoke, the smell, and a number of other things. So what are your thoughts about cannabis as something that can be used, quote, unquote, recreationally, medicinally, and its potential for abuse? And then let's talk about how those things have been amplified or reduced by the fact that it's essentially legal or decriminalized. So what are your thoughts on cannabis?

A (38:38)

Yeah, so whenever I talk about, I make a distinction between sort of old and new cannabis. So if you go back to the 80s and 90s when, as you mentioned, it was illegal everywhere, the THC content that's the principal intoxicant would be 3, 4, 5%, something like that, on average. And now studies of legal sales show the average product is about 20%. That's dramatically stronger. The other point is how people use it is different, perhaps related to that high potency. Jonathan Calkins pulled together a lot of really interesting data that got a lot of polarization play. And it showed that about 40. I think it's 42% of people who use cannabis use it every day or almost every day. That is also different. So if you go back in the past, the more modal user might have been once or twice a week. So you put those things together. So you take somebody what was like an 80s pot smoker, well, on weekends I'd smoke a joint at 5%. But now if it means every day I'm consuming 20%, you quickly realize their brain exposure is dramatically higher, about 65 times higher between the modes of those two experiences. And so what does 65 times mean? Well, it coincidentally is also the potency difference between a coca leaf and cocaine. That is 65 times two. So it's a big difference. And as you know, dose makes the poison. So it is just a really different drug than what was back there. And this is very hard to get across to parents because their view is like, ah, I smoked weed, you know, who Cares if my 15 year old is using it? It's like that's kind of saying you drank low alcohol beer and you're not concerned that your 15 year old is guzzling vodka. That's kind of the difference. And it's just a bigger deal than it used to be. Even when you take away the fact that you have an industry really pushing it, just the drug is stronger, more addictive. Does it have any medical applications? Almost surely. The cannabinoid receptor system evolutionarily is one of the oldest in the history of Homo sapiens. It is both in the brain, but it's also in the body. There are clearly going to be some applications for pain. Many people would say they spontaneously get relief. It's hard to tell always what that means because sometimes that's just relief from withdrawal. But probably some type of medical applications for pain will come out of this plant. We do have some out of the cbd, which is the non intoxicating part, is a medication that is used in seizure disorders in kids. So there'll be some other things like that for sure. And it's easier to study this than it has ever been before. About 2020, Congress changed the way research works, so it's a lot simpler to do it. So we'll figure those things out, but it is just a more dangerous drug than it was. When I was a young person, I.

B (41:44)

Had a guest on the podcast who's a cannabis researcher, runs an animal lab and we invited him on because I had released a solo episode about cannabis or touched on some of the risk for psychosis in young Men and made some points about, frankly, concerns about cannabis because of the high THC content. He was not happy with the things I said. He made that clear on social media. So, by the way, this isn't the way to get invited on the podcast, but we invited him on and I think we had a very fruitful discussion where he clarified a few things for me. And one of the things that he claims is that despite the higher THC content, that there's a distinct difference between smoked versus edible cannabis, whereby people who smoke cannabis, even the high THC cannabis, are very good at gauging the kind of level of high so that they don't go into paranoid modes, they don't surpass the plane of high that would make them feel paranoid or put them into a psychotic episode. But that people who take edibles, because it's harder to gauge where you're at if you can just swallow an edible or even nibble on an edible, often surpass the level at which they would be comfortable, meaning at which there's a psychotic episode or there's paranoia. So he was making this kind of soft argument for the fact that the elevated THC levels in cannabis are not such a problem because people are essentially taking less to offset the difference.

A (43:17)

Yeah, I think there's no evidence for that at all. And people are surprisingly bad, even experienced pot smokers, at judging in lab studies of how strong different cannabis is. I don't agree with that part, but I do agree we should think about the edibles differently because of the onset is different through the gut. So when you smoke anything, you get that, that goes very efficiently to the brain. But when you eat something, you know, it takes a while to have its effect. And so particularly when these products came out and a lot of people were new to them, they would bite down on one piece of whatever the bar, the cookie or whatever. Five minutes later, I feel the same, take another bite, still feel the same, and then just eat the whole thing. And then it would all hit them like a train. And that does happen. The other thing that is true is that a lot of these products are not well made or they're not up to like, the standards of, like, you would have a cookie, you would never open up a bag of chocolate chip cookies in the United States and find all the chocolate chips at one end and just dough and the rest. But that does happen with cannabis products in legal markets. And so if you just bite on the wrong part, you're getting the, you know, the whole enchilada, so to speak, because it's not evenly blended through and there's some people who've gotten to got into trouble on that as well.

B (44:39)

Interesting. What about the psychosis risk?

A (44:43)

Yeah, so I was very skeptical of this literature for years. Not to say that the science was bad, but just like it seemed to me, there'd be lots of ways to explain it. And I'm a lot less skeptical now candidly because in the old studies they would be, those were men who had used cannabis in teen years and then they would have higher rates of, of psychotic disorders in adult. These were studies based on like Swedish registries because everybody has to register for the military, you know, and they would track people. And it's quite amazing data. So it is a whole national data that's good. But there's lots of reasons that could come about, you know, could be a common factor between those two things, you know. But the evidence has gotten stronger as the drug has gotten stronger. And again we got it got to realize people are using it much more intensely. So if this effect is there, it's much more plausible that it would be from a much stronger drug used every day could generate higher rates of psychosis. It's hard to test this because it's a rare thankfully condition, but I think there is probably something there. I am sad to say, I wish there weren't, but there probably is something there. I would not use cannabis if I had any first degree relatives with any schizophrenia, schizoid personality, anything in the psychiatric, bipolar disorder. I would not personally recommend that for anybody. I think that's probably quite risky.

B (46:14)

What about the cardiac risk and other health risks? I've heard recently that there's a direct risk of cannabis even if it's not smoked or vaped on.

A (46:24)

Cardiac health, I'm not sure of that of non smoked cannabis in the heart. I mean I haven't looked at that literature so I don't know the answer to that. I realize there's one point I should touch on that you also raised earlier about first drinking, which is everything is different when the brain is plastic and our brains are most highly plastic when we're young. And so a lot of these effects, the worst things are going to be because people start when they're in teen or late single digit. That's where addictions overwhelmingly start. And that is where if there is a psychotic risk, it's almost surely then during that period of brain development before people get their first psychotic break, which tends to be around 18, 19, 20, 21. I'd worry about it less for anything Initiating a substance when you're 50 is far less likely to end you up with an addiction or some other terrible thing than when you're young.

B (47:27)

I'm sure everyone knows at least one person or has heard of one person who's very productive in their life, healthy family, job, et cetera, high energy, who uses cannabis. In my observation, they are the rare exception. And there are a lot of examples of people who use cannabis who don't really go anywhere in life. They don't go through the normal developmental progression of finding a job that can sustain them. Right.

A (48:00)

Of.

B (48:02)

Organizing their life, their relationship life, their professional life. And clearly there are other aspects to life, but those are key ones. Right, and what are the data on high THC or just frequency of cannabis use as it relates to life progression? Failure to launch, we call it now typically it's guys that young men that fail to launch. And I want to be clear, not for political reasons, but I want to be clear, when I say fail to launch, I don't mean that every kid has to go to college and you know, be a, you know, varsity athlete or any of this, but just moving out of one's home, eventually getting a regular job, keeping the job, hopefully having healthy relationships of various kinds and being self sustaining. That's what I'm talking about.

A (48:49)

Yeah, absolutely true. I mean, for example, I did Ezra Klein's show. He's obviously a very successful guy and he mentioned that he sometimes uses cannabis edibles.

B (48:56)

He has that look. No, I'm just kidding. Sorry, Ezra, just tease it.

A (48:59)

Yeah, I mean, so yeah, and there are very, very, very successful people who use cannabis for sure. Overall though, I mean, I'll steal a phrase from Jonathan Calkins. It's like we have performance enhancement drugs. It's kind of a performance degrading drug. So it's not fentanyl. Your odds of your death being directly traced to it are extraordinarily low. But it does, with regular use, undermine certain things that you need to succeed in the modern world, like short term memory and concentration and being able to keep track of details. And for some people also, it undermines their sort of motivation to do much of anything. I mean, the couch lock is a real thing. I know families in Palo Alto, where I'm from, very achieve y place who had straight a, a straight a son doing everything, starring on a sports whatever, who six months later was just smoking cannabis all day and had no interest in, in the team he used to star on. And the math he used to be great at. And like, that's Pretty frightening. And all those things are not conducive to succeeding again in a modern world. If maybe back in an agrarian society it didn't matter because everything was on muscle power. Right. But to succeed in this society, you have to be able to do those things. And you are in competition. If you want a job computer coding, you're in competition not just with the smartest kids in your neighborhood, you're in competition with the smartest kids who are in Mumbai and in Tokyo. And if you can't focus or you're just slower and you can't remember things or you have trouble making sure you keep track of time, that is going to put you at a disadvantage. And you can end up that stereotype of living in mom's basement. That unfortunately is true of a chunk of people who are heavy users of cannabis.

B (51:03)

Yeah, I worry a lot about examples of so and so is very high achieving and they use cannabis. I had a friend growing up who desperately wanted to be a professional golf player and he would cite all these professional golf players who were heavy drinkers. He ended up just being good at the heavy drinking part.

A (51:19)

Yeah.

B (51:20)

Sadly, I think he turned his life around at some point. But these examples of people who can use very addictive substances and are open about that and are very high achieving, I think there's a real detriment to that messaging. Now, of course you don't want people to cloak their reality, but it's complicated.

A (51:41)

Yeah. And it also has policy risks too. I mean, when you make up the rules, you know, your laws and regulations, to think, well, you know, I'm accomplished, I'm able to use this, so that must mean it's pretty safe. It's like that just doesn't follow logically. The fact that you occasionally, you know, take a snort of cocaine or whatever and you're still a state senator, that doesn't prove that that would be safe for everyone. And you know, we know people have different levels of risk, they have different social capital, they have different incentives in their lives. And you can't overgeneralize from a sort of a lucky life or a costed life. Sometimes you can do more of that than you can when there's not many nets sort of between the person and the ground.

B (52:31)

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A (54:25)

Patrick.

B (54:25)

Patrick Kennedy, excuse me, who's been very open about his own recovery. So many gems in that talk. We'll put a link to it and we'll touch on some of those things again. But just such an important conversation. And, you know, it came up in that discussion that many industries are industries of addiction, alcohol, cannabis, gambling. Nowadays. I was thinking about what you guys were talking about. And nowadays it's very difficult to look at any industry and not see it that way at some level.

A (54:55)

They talk about it themselves that way. You know, they, they'll, if you get together with app developers, they'll say, how do we make this more addictive? You know, so it's, it's. And it is good for business. There is no customer like an addicted customer. So of course that's going to be appealing if you're trying to sell something.

B (55:09)

I guess the question is healthy addictions or adaptive addictions or things that fall outside the progressive narrowing of the things that bring you pleasure. Because a kid getting quote unquote addicted to a learning app that carries over into a number of things one hopes in school or even social media. I've learned a lot from YouTube videos. Heck, I even watched that YouTube video of you and Patrick on YouTube. So there's this double edged blade piece. But when it comes to alcohol and cannabis, what you told us earlier, getting women to drink more by making it seem like an important part of being a woman in the United States to drink, that sounds diabolical. Yeah, convincing people that cannabis is gonna make them more creative and it's not as bad as alcohol, that to me is very diabolical. And I worry about this, well, it's not as bad as alcohol argument because I mean, shooting yourself in the head is way worse than stabbing yourself in the head.

A (56:09)

Well, alcohol also kills about 150,000Americans a year. So if that's our bar, we should have hand grenades in the drugstore. That would kill tens of Thousands, but not 150,000. We should legalize drunk driving because that only kills 10,000 people. I mean, that's just a crazy thing to set as the. Well, as long as it kills less than 150,000 people a year, it sounds great to me. That doesn't make any sense. I mean, I am clear economically. I am a capitalist. I'm glad we have companies. I love living in Silicon Valley. I love all the things people create there. And I think that is an important part for society to work, to have a private sector. And at the same time you have to regulate addictive goods, temptation goods, very intelligently and tightly because you can't count on the sort of rational consumer to protect themselves like you can when you're dealing with cabbage or lettuce, which nobody ever overdoses on. But we do see people burning down their lives over all these drugs. And for that reason to protect those people, but also to protect the rest of us from the consequences of that. That's why you need things like advertising restrictions. That's why taxes to which people are people, even heavy users respond to price. That's a really important tool to regulate them. I would do much more with cannabis, particularly. Just some of the promotion is so naked and a lot of it is in place where kids are exposed particularly. And this has just Been a long term fight. We had it with the tobacco industry. Almost any nasty thing you could say about the tobacco industry turned out to be true. I mean, they did work to make it more addictive. They worked to defeat any type of health regulation. They were marketing to kids, all that stuff. So those are the economic incentives. And so you should not be naive if you work in this space about what the financial incentives are. If you're making an addictive product more addiction is good for your bottom line. So us on the other side have to say, all right, we're going to put in laws and regulations so that that is harder to achieve. Never going to get rid of all of it, but you can make it a lot, lot harder. Gambling is a great example. I mean, I'm just amazed that we have just given up on any restrictions on gambling now. I mean, when I was a kid, Pete Rose was not allowed to go into the hall of Fame because he had once placed a better on his own team. He wasn't even doing anything corrupt, but he bet on his own team would win. He was kept out of the hall of Fame. Now you can't watch a sporting event without having gambling ads shoved in your face. Like that's an example of something that should just not be the case. That is terrible for anyone who's trying to quit gambling. It's terrible for a lot of young men particularly. But not just young men are just ruining themselves economically over sports gambling. And we don't need this, we can do without it.

B (59:06)

Gambling thing's a real concern. We had a guest on this podcast who's a self admitted gambling addict. And a friend of mine who treats gambling addicts said it's among the worst of the addictions because they live with the reality, it's true that the next time really could change at all. And he said eventually they get addicted to the shame of losing. They just get so winning becomes a thing of the distant past. I mean, this sounds crazy to the rest of us, but it's fascinating and disturbing. And gambling addicts will say that every addiction is gambling.

A (59:44)

Yeah, that's good. That's good. There's a tremendous book, Addiction by Design. And I'm afraid I'm gonna mispronounce the the name of the person wrote. I think it's Scholl, but I'm not sure. But I know the title edition by Design about gambling. And she profiles people who play video poker, many of whom work in the casino. They basically get paid and then they go pay the casino back by giving it away. But some of them will take a toothpick and bend it and force the BET button down and they won't even touch it. They'll just sit there and watch in kind of a dissociative state as it just runs and runs and runs until their money is gone. You know, that's like, you know, it's really like zombification of this stuff. And that tech has been perfected to be addicted. If you. I do go to Las Vegas like once every couple years. I just find not for Gamma, but I just enjoy the sort of pageantry and the food and all that. It's very hard to see dealers at tables anymore because dealers don't give the perfect timing of reinforcement that machines can do. And you know, they don't. You know, you have to wait for your reward and all that kind of thing. And you wait till you find out. And there's a social component. Well, that all slows down the process. Whereas a machine can give you exact timing between your press the button and then you get your reward or your win or your loss. And you can just go infinitely 24 hours a day, unlike, a dealer never gets tired. And so all the casinos like chopped up dealers, tables, and now you're just playing with the machine.

B (61:07)

Incredible. I don't want to spill off into too many anecdotes on my side, but I will share something that was shared by a previous guest on the podcast you may find interesting. Michael Easter is at a university out in Las Vegas, and he got access to one of these. He wrote the Comfort Crisis about getting outdoors, getting away from things and basically carrying weight on your back and walking as a therapy of sorts, an important one to do regularly. But he got access to one of these research casinos, and it turns out that slot machines used to be a small fraction of the income of casinos. Now it's 80% or more. And he said that that came about because a father who worked for the casino industry was at home watching his kids play video games. And he realized that the kids weren't playing to win. They were playing for the novelty of what was on the next screen. And the kids didn't realize this, but it became clear to him. So now, and I think this will help people. This is why I'm taking the time to share this once again. Now, if you play a slot machine, you think you're trying to win, hear the ching, ching, ching, ching, ching, ching, and the bells go off and you won. You think that's the dopamine reward. But they figured out that unlike the old rotor machines, where you have some cherries and bells and stuff, in the electronic landscape, you could have an infinite amount of novelty through novel combinations. So now they figured out that people will play to win 50 cents on the dollar, so they lost 50 cents. Right. And they know that rationally, or they could know that rationally, but they'll continue to play until it's all gone, as long as you give them novelty. So people aren't even really playing for the money anymore. They think they are. They're actually just being stimulated with enough novel combinations that their bank account gets drained, the house takes it all.

A (63:02)

Yeah. Yeah.

B (63:03)

When I heard that, it changed my view of gambling because I always thought it was about winning money and leaving. It's actually more about playing, and it's more about the novelty that's introduced in each quote, unquote, hand or spin. And the. I think knowing that carries over, certainly, to sports and the excitement that you're feeling about the potential that you could win, but that it's a novel combination of things might prevent, hopefully, somebody from becoming a gambling addict or might help people realize that what they're addicted to, if not already shame, might actually just be the novelty. And that's why they're losing all their money.

A (63:42)

Yeah, there's an industry term for that, LDWs, losses disguised as wins. So, you know, you put in a dollar and you get 100 credits, and then you pull the thing and it does its thing, and then it goes like, dit, dit, dit, dit, duh. You've matched this way. You've won 10 and it goes off, and you've matched that way. 20. Oh, my God. I won a guy. 40. I won 40. 20, and 10. With all these exciting things, I just lost 30% of what I put in, but it feels like a win. And they realized, as you say, people will keep playing even while objectively, they're just pouring money down a sewer.

B (64:20)

So glad I'm not addicted to gambling. But I could see how I could be. Even though I would like to say I couldn't be, I could see how I could be because the brain is just so prone to these kinds of things. We all have these circuits.

A (64:35)

Absolutely. And it's interesting, too. You know, casinos are one of the few places where you can still smoke indoors and you get free drinks. And so it's really like absolute dense pack of addictions. And a huge number of people, problem gamers, are problem drinkers and also are addicted to cigarettes. And so when I go to Las Vegas it's almost like an anthropology experience. I just look at all this and like, wow. And there was a story in Shull's book, which I just found amazing, with a bunch of people playing, playing, playing, playing. And somebody had a heart attack at one of the machines, fell over on the floor in a group of them and none of them even reacted. They just kept playing as this person died.

B (65:17)

What a metaphor for society. Well, I just decided if I'm ever going to Las Vegas, I'm going with you.

A (65:22)

Okay.

B (65:22)

Sorry to invite myself, but you seem like a safe person to go.

A (65:25)

I'm pretty safe, yes. You may win or lose five bucks and that'll be the end of it.

B (65:30)

So industries that drive this stuff. Okay. Alcohol, cannabis. It's going to be very interesting to see what happens with cannabis now and going forward. Is it the case that in states where it's legalized or decriminalized that the state collects its taxes on it?

A (65:46)

Yeah, it depends. Those are different regimes. And this is a really important point to get into when you think about policy. So decriminalization is about the user. And that's to say, look, we're not going to punish you for using pot. Okay. And that is a pretty popular. It's been a popular policy for a long time and doesn't seem to really affect use that much. Maybe a little bit, but not a lot. Legalization is making the production processing, marketing and sale legal. Bringing in a corporation, and that is fundamentally different because the corporation is going to have very smart people who are good at selling and they will increase consumption of the product. At this point, I don't know the exact state count, but most people in the United States, population wise, have access at this point to a recreational cannabis. And virtually every state, I believe, has something if it's not recreational, it's medical or there were these due to hemp. There was sort of a way mistake they made in regulation. There's a way to process hemp that you can make these like Delta 8s and Delta 9s. So even in states that are prohibited, there's quite a bit of like, you know, hemp laced beverages which are quite strong.

B (66:59)

Is cannabis a gateway drug? We were told that when we were in school.

A (67:03)

Yeah. So all drugs are gateway drugs. The lie in that was that cannabis had some unique role that was gonna lead you to use heroin use. But the truth is anything like if you're a teenager and you start smoking or you start drinking or you start using cannabis or stealing prescription opioids from your parents or whatever that will increase your likelihood of progressing to other substances for multiple reasons. One, you might like it say, okay, well, I guess I'm converted to electro, let me try some others. Two, your social networks may change, so you're around other people who do this, and so you're comfortable with them, they're comfortable with you. And they're also more likely to have something else you might want to try. And then the third thing is it could be some brain sensitization going on that makes drugs more rewarding. And there is some interesting work with identical twins in different states, which seem to suggest that you could be starting some unfolding process when you expose a young brain to it. So all those processes is how gateways work. The lie was that it was just cannabis. And this actually fits with the general lie I would say is that alcohol is a drug and we pretend that it isn't. So you mentioned people getting drunk at science conferences or health conferences. I have seen conferences, political events where people spend all day demonizing drug users and talking about the threat of drugs and how evil drugs are and how we have to destroy all drugs and then they all go to the bar and get drunk as if they are not drug users. Not wanting to admit that alcohol is a drug is a very useful for the industry, but it was also just useful politically because you could say, well, the big threat to kids is cannabis, when it's much more likely a kid was going to get in trouble with alcohol than with cannabis.

B (68:53)

These days there's a lot of discussion about psychedelics, broad category of drugs. Lsd, psilocybin, MDMA is an empathogen, not a psychedelic, but somehow it's been lumped into it. M methyl, it's a methylenedioxy, methamphetamine, mdma, Ecstasy, folks, it's methamphetamine with some modifications. So it's not a psychedelic, it's an empathogenic. But it gets lumped with that. Ketamine gets lumped with it. Dissociative anesthetic. It's not a psychedelic. So if we're gonna have a conversation about psychedelics, I wanna be really clear. Maybe we just put psilocybin and LSD on the table and then talk about the empathogens and ketamine and all the rest separately, because so often these get lumped and it leads to a lot of confusion. I know several people who feel they've benefited tremendously from doing clinical work, meaning with a guide in safe setting, et cetera, on high dose psilocybin, maybe only Two or three times total. And that's it for treatment of depression. Sometimes for alcohol issues and other issues. I'm not talking about microdosing. They do a high dose, 2 to 5 grams. A lot of addicts who use other things are interested in or currently using or considering using psilocybin, LSD less so as a means to get over their addiction. I'd like your thoughts about that and your thoughts about these compounds specifically.

A (70:28)

Yeah, I mean, they're exciting in part because we haven't really made much progress in pharmacotherapy in the last 20 years for lots of things for depression, for addiction. So the thought that these might work, and I think they're other than the GLP1s, one of the. Probably say the second. I'd say put my second bet on that. I put my first one in GLP1 agonist. There is an awful lot of hype, but real things can be hyped. So the fact that there are a lot of extravagant claims being made. And also, again, talking about industry, you know, there are people who are hoping to make a huge sum of money on these medications, but there's also something there. You know, you could look at different pilot studies, you know, small trials. They are encouraging. And I'm glad that, you know, it's a lot easier now to do these types of studies. You know, we just had my friend, Dr. Todd Korthas, down to Stanford. You know, he's from Oregon. You know, Oregon is doing these things. Probably similar experience to what your friend had, where you get. You have preparation with a trained person, you get the medication and then you do the integration session afterwards. And there are people would say it's transformative for them. There are also people who have very bad experiences on them, too, though, it has to be said. And that's why we don't just say, all right, let's just use this as our frontline.

B (71:54)

You mean during the psychedelic experience?

A (71:56)

Experience end afterwards or afterwards, like flashbacks. You know, you're driving along and then you have a flashback, you know, that is both upsetting, depending on what you're doing at the time, you know, could carry some risk to it. We don't know that well how well these or exactly how these drugs work. You know, sort of serotonin kinds of drugs. The one thing we do know good, though, keeping on the topic of addiction is thankfully, you know, there's no evidence that people get addicted to psilocybin or to LSD if they have abuse potential. It's extremely, extremely slight. So I've Always worried about them far less as a class of drugs than I do. Things like stimulants, which I know, and alcohol.

B (72:41)

My read of the literature, and this might have been updated since, is that there is zero evidence that microdosing psilocybin has any benefit.

A (72:49)

Yeah, I think that's too silly.

B (72:53)

There is solid evidence that in a clinical setting, as you pointed out, and thank you for pointing it out, we're talking about at least two or three talk sessions without psilocybin, then a psilocybin journey that's typically two guides for safety purposes. Now, that's kind of how it's being explored. So they're to avoid exploitation conditions because there has been some exploitation, mainly in the MDMA trials, but and then follow up that it's been somewhere between 60 and 70% of people who go into that sort of thing with major depression that hasn't been resolved by other approaches get either significant relief or full remission after two full versions of what I just described at fairly high dosages. When I think about the negative impacts, certainly there's the quote unquote, bad trip phenomenon. What I've observed quite a lot, and I hear from a lot of people in this psychedelic space, is that post MDMA for trauma, post psilocybin for major depression and addiction issues, there's the. Not euphoria, but the feeling that something significant has changed in the weeks and months afterwards, and then some period of time later, a significant sudden drop in mood and that frightens them and that they're able to recover from, but that it's a real thing, a real trough. And this, by the way, is separate from the very well known trough that comes two days after MDMA use. We could talk about that. But you get high and then there's a low, you know, very well explained.

A (74:28)

As with stimulants.

B (74:29)

As with stimulants. Right. I'm divided on this psilocybin to treat addiction thing. It seems very precarious because of the lack of kind of standardization of how this would be done outside a clinical trial. It's hard, you know, I mean, you hear about some. You hear Shaman practitioner guide, and there's no. Because it's illegal. There's no Yelp reviews for these people. There's no board that's overseeing it.

A (74:57)

Well, there is an Oregon. That's actually what Todd was presenting at, which is. Yeah. Because you. It is legal.

B (75:03)

It's legal. Not just decriminalized.

A (75:05)

Correct. Yeah. Okay.

B (75:06)

Because in Oakland and California, it's decriminalized. Psilocybin is decriminalized.

A (75:10)

Yeah, Oakland's very different. In Oregon, you actually, you are licensed by the state to do this.

B (75:15)

Ah, I see.

A (75:15)

So yeah, so that's what we'll find out. I mean, to me this is like pretty probably this is case where it's easy to be a scientist. Sometimes it's annoying to be a scientist. Makes life harder, makes it easier. It's like, I don't know if this works. It's really important to figure out if it works. We have really good methods to do that. So let's spend the dollars to get good people to do those studies. And this is the NIDA view National Institute on Drug. They are funding quite a few studies of this sort and I imagine niaaa, which is the Alcohol Institute is doing it also. I say good because to me it's really. I think people get a little scared of these drugs and they sort of like think, well you can't use them in medicine. It's like, well, we use lots of things in medicine that are a lot riskier than this. Right. It's just a question of what is the effect on the patient, what is the balance?

B (76:05)

Electric shock treatment.

A (76:06)

Oh Yeah, I mean, OxyContin, there's all kinds of things. Right. But we figured that out by running really good research and that's what this area needs. And I'm glad it's getting the investment. It's getting a fair amount of philanthropic investment too. Another important thing is that the people doing the studies are at equipoise. So there's been some bad work in this area over the last 50 years or so because of. It was people who were super enthusiastic to the point that they weren't careful and critical about what the evidence said and they sort of overclaimed what they found because they believed in themselves, maybe because they'd had very positive experiences themselves. And just like that is not in the long run a good way to do science. You really want people who design a good study and then let the chips fall where they may and then tell us all and then we can decide. But they don't. They're not, you know, shouldn't be a spin doctor. That's not good.

B (77:02)

Fun little factoid. And then another note about psilocybin. I was curious as to why there's so few studies about LSD and a colleague of mine who works in this space, he runs clinical trials at ucsf, said, oh, it's very straightforward. Most of the studies on LSD, clinical trials, that is, are done in Switzerland, because the LSD trip can last up to 13 hours and they'll work very long hard hours. In the United States, it's hard to get the, the staff to come in two hours before a four to eight hour psilocybin session and then make sure that the person is okay enough and taken care enough to go. So I'm not suggesting we extend work hours any more than we already have, but it's kind of interesting that I mention it because sometimes practical issues drive the science. It's just as simple as that.

A (77:49)

Yeah, it will drive also healthcare system. So if it took that long to do, the odds that this would ever be scaled up in the health system are pretty low. Right. So there are real reasons why if you can do something in less time, you do it.

B (78:06)

And there is a movement now, meaning a solid effort in laboratories to figure out whether or not there are non hallucinogenic, non psychedelic experience related compounds within these compounds. Meaning the psychedelic experience may not actually be critical to the antidepressant effect.

A (78:26)

Right? No. So that's one of the interesting things about ketamine. Like if you blocked, you know, our late great friend Nolan Williams, you know, was looking at like, if you could block like say with some kind of naltrexone molecule, block the, you know, the blinking lights and the visions and all that stuff, would it still have the same effect? That is a great question, you know, for scientists to figure out. Now some people say, but I like that part, it's like, okay, but a lot of people find that actually pretty upsetting. But if, you know, they could take ketamine and not have that kind of vivid dissociation stuff and they were depressed and helped them, that would be a good medicine to have, right?

B (79:01)

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A (82:11)

Plasticity, which we have naturally the most when we're young, is absolutely a two edged sword. So if you try to learn French at my age, it's just really, really hard to pick up that new. Whereas if you grow up speaking it or you try to learn it as a second language teenager, you're going to have much more capacity to get it and retain it. That's true. It's also true that if you start smoking cigarettes in my age, you probably will not get addicted. And if you start smoking cigarettes when you're 13, you almost certainly will. Is that true? Yes, same thing. Plasticity. Almost all addictions start when people are young, you know, and you can, I mean, you think of this as a learned, you know, it is a, you know, it's maladaptive learning, but it is learning, you know, that you, you know, you acquire those things and you stay all the way through. It's why, you know, sometimes older people, I can remember getting mad like shows they like got canceled and people were watching them. I remember the show because my parents watched it. Dr. Quinn, Medicine Woman. Well, why? Because old people watched it and advertisers don't want to pay for old people. The advertisers want young people, want lifetime users. That's right. And to instill those habits when people are young is how you get them to do it for 50 years. You can't really persuade many people my age to start eating Cheerios or Frosted Flakes or whatever. But you start it when people are young. And that just underscores the point you're making of like plasticity isn't good or bad. It's this capacity the brain has and it can be used in very different ways.

B (83:41)

Maybe it explains why despite some minimal effort, I can't get addicted to TikTok. It just, it's aversive to me. Thank goodness.

A (83:49)

But maybe if you'd started when you were 13, it didn't exist then. But you know, if it did, you might have, you might have found it far more engaging and picked up that habit.

B (83:59)

Chances are, I mean, based on what I observe and knowing myself. You mentioned ketamine. Ketamine's an interesting one. A not a psychedelic dissociative anesthetic has some proven benefit for depression. Although maybe transient but high abuse potential. And here in Los Angeles, not six months goes by without hearing about some famous person dying of ketamine. Which means that a lot more non famous people are dying of ketamine and we're not hearing about it.

A (84:26)

That's a good point. Yeah. And I don't know if you can post articles, but we did a review, Todd Corsa and some other colleagues of the potential therapeutic effect of this whole drugs. And the thing about ketamine that struck me, yes, it is FDA approved for treatment resistant depression. So it is approved. There's a lot of negative trials for depression. I mean, it didn't like vault over the efficacy thing. It cleared it. There are some positive trials and I can say I know a couple people whose judgment I trust said it was very, very valuable to them in a deep depression. But I didn't view it as quite the knockout I thought it was going to be before I read all these studies. And then you do have that problem. It is addictive. So we have a lot of people getting addictive. And then also the bladder damage you get from it, you get Young people with 60 year bladders from ketamine and like that is most urologists have seen this. Now why is someone at 25 coming in with this? It's like because their bladder's been damaged by ketamine. So those are significant side effects. So it would not be the thing I would jump to if I had treatment resistant depression, which has got to be said is a terribly challenging condition to deal with. I'd be far more likely to actually do the same protocol that Nolene Williams developed with our because the effects of that for treatment resistant pressure are so much clearer in my view. And the downsides are, as far as I can see, virtually nil.

B (85:49)

Thanks for bringing it up again. Tms, Transcranial magnetic stimulation is a non invasive brain stimulation that can either activate or decrease neural activity in specific brain areas. Very good data on this. How soon will that be available to folks in all parts of the country.

A (86:05)

And the world, in our country, I mean, RTMS for depression is approved and so you can get it at clinics that have this technology. These are big, expensive machines. So I'm sure there's lots of places where they're not local, but yeah, it's covered. I think Medicare actually covers it. Whether they cover the specific protocol that Nolan did, I'm honestly not sure because there was a lower intensity one. And Nolan's genius was to compress this treatment so people would come in five days in a row and have 10 minutes on, 50 minutes off. I believe that's the rate all day long, five days with a theta burst setting for the RTMS. And I've seen some people's lives just absolutely changed by that. And you can see. I mean, it's a trial, it's a good trial. Unlike with psychedelics, you really can fool people that they're getting RTMs. You know, it's always tough to interpret psychedelic research because everybody knows when they've gotten a psychedelic drug.

B (87:09)

The people in the control experiment know they're in the control experiment.

A (87:12)

That's correct, but not true. In rtms, you can put these coils on the head. I've actually tried it. And it feels like something's happening, and it's just a sham. And when you ask people again, guess which condition they're in, they can't guess. So this is really some good science. And that's where I would go next if I were. I would look at the Saint Protocol is the name of it. Maybe we can. I don't know if we can put.

B (87:33)

Yeah, we have links. We'll put links to any papers, any outlets. You know, I hear from a lot of people with depression issues. People have become very wary of SSRIs because of the side effect profiles, probably also because of what they've heard. I remind people that SSRIs have been very, very helpful to the community of people who suffer from true ocd, not like, oh, they're OCD people who have debilitating levels of obsessions. Excuse me, and compulsions. So I don't like to demonize any common.

A (88:05)

No, we shouldn't do that. There's lots of people who benefit from SSRIs, there's no question.

B (88:08)

But maybe TMS would be something where people would want to explore. But as long as we're on SSRIs, do SSRIs make people shoot other people or themselves?

A (88:18)

No, No, I don't believe that. The mass shooting thing, I mean, it doesn't fit the data where mass shootings are. I mean, there was just a mass shooting in Australia. That is so rare that you see these in developed countries other than the United States. That was their first mass shooting in 30 years. There's plenty of people take SSRIs in Australia. Why weren't there mass shootings Europe? Did many people take SSRIs? They don't have the level of mass shootings. So I don't think that is the explanatory variable. I mean, I think the explanatory variable is that it's extremely easy to get high powered weaponry in our country. And, and it's harder pretty much in the rest of the developed world.

B (88:54)

Not pushing back for sake of pushing back. But I've seen data, I don't know how solid the data are that something like 70 plus percent of the prescription drugs for depression are consumed by the United States. So that the relative percentages of the population, maybe that's a better way to frame it. Taking SSRIs is much, much higher in the United States than it is, say in northern Europe or in Australia. So yes, they take SSRIs, but at a much lower frequency.

A (89:24)

Yeah, but you would, you would not go 30 if there were significant risks. You wouldn't go 30 years without a mass shooting in a country, Australia, where does it have 25, 30 million people in it? I mean, you know, even at a lower rate there would be. The disparity is so huge in where mass shootings occur that that's just not going to be the, you know, the likely explanatory variable.

B (89:43)

What about suicide?

A (89:45)

There is some worry about adolescents on SSRIs. This has been a really hard fought, you know, debated issue for years. And it's tough because depression of course raises suicide risk. Right. So by definition, if someone's getting an ssri, they already have some risk present. I think there's some legitimate worry with teenagers. I would say it's non zero, but to be honest, it's, it's not completely in my wheelhouse, so I'm just gonna leave it at that. There are people who've worked on this much more deeply than I can still, though I would say there are many teenagers on these medications who benefit from them also. There's no doubt about that.

B (90:25)

Yeah. And folks who are interested in this, I'm working on an episode with a guest about some of these long term effects of SSRIs that some people seem to experience. There is a cohort of people out there, this is one of the great things about the Internet who have rallied together and saying, hey, we have the same constellation of symptoms. We don't have any bias against the medical industry, but we were prescribed SSRIs in our teen years and early 20s. And there's a constellation of mainly sexual side effects and mood related side effects that don't seem to resolve even after coming off. We also see this with finasteride, which was used to treat baldness. And our colleague Michael Eisenberg came on here and said, look, the data aren't really there, but I hear from a lot of young guys who are given these anti hair loss drugs and they come off the drugs and they're still experiencing debilitating sexual side effects. And so it is true that the medical profession sometimes takes 10, 20 years to catch up to what many people are experiencing.

A (91:28)

That is true.

B (91:29)

So I'm not trying to make an anti SSRI statement here, but I think there is, there are people walking around out there that are convinced one way or the other that SSRIs mess them up pretty bad and they have loud voices and so I think that's where the concern comes from.

A (91:44)

Yeah, I honestly don't know what the evidence is in that particular case. I will say just something very general about medications, how we approve them. They're approved on short term trials. I mean if you look at the typical trial for opioids and pain, it's like nine weeks or 12 weeks and there's lots of medications and opioids are a good example. That doesn't necessarily mean that taking them for a year gives you the same effects because for example, you become tolerant to them or you might become addicted to them and all that. And that is a general just challenge of how we regulate these medications. There are post marketing studies that are done, but particularly if something is a complicated and rare from a widely used medication, it's hard to figure that out. I mean doctors will make reports that get aggregated up, but that's hard to figure out.

B (92:40)

Before moving on from the discussion about psychedelics, our late and indeed great colleague Nolan Williams. Sadly he passed a few months ago. We may talk about that later, maybe not. Either way, I'll put a link to his information because he's a critical figure in this general space around the treatment of depression because of his work on tms, the SAINT protocol as it's referred to, as well as ibogaine, which is a very unusual psychedelic. But he was running trials on veterans mainly taking ibogaine out of country, illegal in the United States. So he had to do it out of country. It's a 22 hour long psychedelic experience. You have to be heart rate monitored. Nobody does this recreationally and nobody should do it recreationally. Sometimes it was followed up with dmt, sometimes no. But from my last discussion about Nolan before he passed, it seemed like the data were very encouraging, such that people who had veterans who had PTSD and or addiction issues would do ibogaine once under this intense supervision, sometimes followed by DMT and would experience a total remission of everything bad. Frankly, they're back to life. And it was pretty striking, at least the way it was being described. So much so that I was anticipating that ibogaine would be the first FDA approved psychedelic, in part because it's not the kind of thing you can just do hanging around with your friends and you wouldn't want to. It involves a lot of scary experiences in there that one works through. What are your thoughts about the ibogaine work and ibogaine as a potential first through the legal door of psychedelics?

A (94:27)

Yeah. So Nolan and I were office neighbors and I really liked him. He was a huge loss. I think he was one of the great psychiatrists of his generation. There's enormous respect for him as a person and as a scientist. And I miss him every day when I walk by his office. I think what he is really fascinating in part because he did the important thing. He imaged people. Anur imaged them before and afterwards. And he was able to see a lot of these changes. And why does that matter? Because, you know, people, you know, there's certain experiences people might have described very enthusiastically and think they're really different, but they aren't in fact different. But he actually documents that is different. So I think that was really groundbreaking and it's sad he's not going to get to continue that work. The thing says this is an open label trial with no control group. So that's what we have so far. So now the thing is to do a proper trial. And see there is a lot also of sort of ceremony around this. It's sort of like, as a colleague might describe it, it's like the final mission for the soldiers. They go down into Mexico, they do this. There's a lot of camaraderie. There's a lot of other good stuff packed around it. And so is that part of the therapeutic experience or is it entirely a chemical experience? That's the thing you would find out in a trial. You would have sort of, you do all that other stuff, but you wouldn't have the ibogaine at the end. And absolutely worth studying. And newer hands will have to pick this up, but I really hope people will.

B (96:00)

Yeah, I'm very curious as to where that work is going to go now. That. Because it really was Nolan spearheading that work. But there are people who are working hard to keep it, you know, going forward. Stimulants. I'm a heavy caffeine user.

A (96:17)

Okay.

B (96:17)

My caffeine tolerance is insanely high. I mean, people have teased me online. There's no way that's true. 800 milligrams a day of caffeine. Child's play, meaning when I was a kid, I've got a photograph of me drinking yerba mate. My father's Argentine alt, the gourd, which is fairly stimulatory, although nice even flat ride. You know, you can tell I like stimulants by the way I talk about them. When I was 3 or 4 years old, 800 milligrams of caffeine, no big deal. You know, a gram of caffeine a day, that's kind of like where I'm nearing my limit. I can drink caffeine all day long. I stop around 2pm so I can sleep well. Not a problem. I think 90% of the world uses caffeine. Adult world use caffeine is caffeine. I'm asking this for my own reasons. Is caffeine addictive? Is it dangerously addictive? It makes me more productive. I love life on caffeine. I can handle life without caffeine if I have a flu or cold. Otherwise I'm not interested in finding out what life without caffeine is like.

A (97:18)

I'm probably the worst person to answer this because I love coffee and as I like to say, I don't have a problem with coffee. If I had to choose between coffee and my children, I can make that decision, but I would really miss them. I knew that was an okay joke to say because my sons laughed when I told it to them. But yeah, it's a stimulant, so it's rewarding and it is potentially addictive. But so what would you see if someone were addicted? Someone come in and says, I'm drinking so much, I'm retching, I'm having shooting stomach pains, I can't sleep. Are you gonna stop? And if, you know, I've actually never met in a while, but perhaps there are some people say, no, I can't seem to stop using it. I was like, okay, that would be addictive. But I've never met a true what I consider a coffee addict person because it's not that intense of a stimulant. And the things you can GI symptoms, things like that, that would be the main thing or, or jittiness and sleeplessness. But almost everybody who experiences those seems to quit. Or at least everyone I've met seems to quit more generally on stimulants. I have to say this is the biggest disappointment of my career in the addiction field. I started my career in the late 80s and going into the Lower east side of Detroit, which Was very rough. Crack cocaine was everywhere. And the treatment offering two people who were addicted to crack cocaine then in the late 80s is not very different from what it is today, which is almost 40 years later. No pharmacotherapy at all, no evidence of anything that works in pharmacotherapy. A lot of psychotherapies that don't really seem to work very well and groups and stuff like that which have very most modest effects. I'm talking about therapy groups. That's not a lot of development. A lot of people have tried, I mean they've tried all kinds of medications for stimulants and just not been able to succeed. The only thing that seems to work is contingency management which are these things where you. Steve Higgins I think was the first person to do this where he showed against the idea that people have no control on addiction, which is in fact rare. They have impaired control, but not no control. He started experimenting with people who are addicted to, to cocaine, saying well, you're coming into treatment. How about tomorrow we'll do urinalysis when you come in and if it's a negative urinalysis, the first day we'll give you two bucks. And the day after we'll give you four bucks. And the day after we'd give you eight bucks. The day after gives you 16 bucks. And he found out people stopped, they wanted those rewards and that's managing a contingency. You can use that to change stimulant users behavior. Also for other things like well, if you come in there's some kind of reward or if you fill out a job application there's some kind of reward that is the only thing that really looks good for stimulant use disorder. And it's fine as a behavioral technology and I'm glad to say it's been expanded a lot. You can do it under. It's covered by insurance now in most places. But it's just disappointing to me that if you transform. Took Keith 20, 25 back to late 80s and talked to those same people I was meeting coming into treatment. They said wow, what new things happen for people like me over the Next in the 40 years, man from the future. And I'd say I'm sorry, basically nothing. And that is really disappointing.

B (100:45)

What about all the prescription stimulants? Adderall, Vyvanse? I feel very lucky that those didn't exist when I was in high school and college and graduate school. Probably in part because I like caffeine enough that I worry that I might have liked them I've never taken any of the things I just mentioned. Yeah, back then we had ephedra and ephedrine pills and things like that that were sold over the counter and that, that always felt too stimulatory. Nowadays I would say yes. At least half of my friends with male children, those children are on amphetamines for the treatment of adhd and they start them young and then they call me because I have a network, not because I can treat, but not a clinician. But then they call me because they're worried about the growth stunting effects. They're worried their kids aren't going to achieve maximum height. Then they're worried that their kids aren't sleeping or eating. And then so all the classic symptoms of stimulant addiction and general sets of issues. So what are your thoughts about Adderall, Vyvanse and similar?

A (101:55)

Those are tough calls for parents. There are kids whose lives are transformed positively by riddle, who cannot sit still, cannot do their homework. And it is transformative. They're at the same time, I would say over prescribed, maybe example drug that sometimes is both under prescribed and over prescribed. There's probably people who could benefit are not getting them and there's a lot of people who are getting them that, you know, I think there's just less tolerance for some variations in how all our brains worked in medicalizing everything. And I noticed that a lot, which makes parents anxious. You know, your kid has his thing and all that as opposed to could be. Well, you know, he is kind of an active kid or he doesn't pay that much attention, but he doesn't have an illness that needs to be medicated. I worry about that just very generally I worry like a kid can't be shy anymore. They have to be on the spectrum, you know, or you know, and carry a diagnostic label. And I think there's, you know, a lot of that going on unfortunately. And I sympathize with the parents. I'm not judging any of them because, because I know those calls are really, really tough to make. And again, I know some kids whose lives are meaningfully transformed by them. So that's tough. That's tough.

B (103:17)

Tell me if you disagree with this and forgive me for citing previous guests, but because I'm not an expert. But I hosted a psychiatrist on here who's expert in ADHD and his claim is that non treated ADHD poses a much greater risk for addiction than treating ADHD with substances that in non ADHD folks are addictive. In other words, if a kid or adult has ADHD and doesn't medicate, they're at much greater risk of abusing drugs. If you do medicate, they're at much lower risk because it lowers the impulsivity.

A (103:50)

Yeah, that could well be true. It's not my core area, but it could well be true. There is a very high rate of ADHD among people in adulthood. You see, you're alcohol addicted, which doesn't seem to be a coincidence. So that could well be true.

B (104:08)

So when you look out on the landscape of energy drinks and nicotine has made a big comeback. Big comeback. Interesting stimulant, because it's both a stimulant, but it also relaxes you to some extent. I tried it for a bit, the gum stuff. Despite my caffeine tolerance, I'm very sensitive to drugs. So I can do like 2 milligrams of nicotine gum. And I notice it gave me spasms in my throat when I wasn't taking it. And I was told that's because the muscarinic acetylcholine stimulation. So your throat starts spasming, then you feel like you need it. It's actually a physical sensation. Then the oral health folks tell me that it's bad for gum disease. And the skin folks, this always gets typically women, but here in la, men and women, it definitely ages skin faster because of the vasoconstriction in the skin. So it makes you look older even though you're not smoking at the oral nicotine. But here I just have to pepper with what I've heard. We have a Nobel prize winning colleague, I'll just name him. It's Richard Axel at Columbia who told me long ago and many times, nicotine is protective against Parkinson's and Alzheimer's, which is why he chews or did chew tons of nicorette per day. So what's the deal? Nicotine seems like it has some benefits. It might make you look older, it might. Maybe you need to take better care of your teeth. It's a stimulant, but highly habit forming and addictive. So what's your view on nicotine as an industry and as a substance?

A (105:35)

Yeah, I mean, it's a poison. If you consumed all the nicotine in a carton of cigarettes, it would kill you. I mean, you know, that's remarkable. That is so popular because of that. It is exactly the reason you say it's both. I feel sharper and then, yet I feel relaxed at the same time. I think a lot of people who use it are mistaking the treatment of withdrawal for a drug benefit.

B (106:02)

Can you elaborate on that?

A (106:03)

Yeah, sure. So let's say you smoke when you sleep. Obviously you're not smoking, and the nicotine blood level goes down and you wake up, feel jittery and jangly and all that, and you have your. For a cigarette, it feels great. Because that doesn't mean, wow, cigarettes are really good for you. Look, you smoke and you feel really good. What you're doing is just the withdrawal that makes you agitated and angry and annoying goes away. And you attribute that. Well, it's the use of the nicotine, but it could just be you are dependent on this drug. And what you actually need to do is persist through the days where you will feel cognitively sludgy and maybe a little bit keyed up and all that, but then once you go through the withdrawal, you won't need it to get to that point. I think there's a lot of people, like, that happens with cannabis a lot, too. I mean, a lot of people say, I can't sleep without it. It's like, yeah, well, one sign of cannabis withdrawal is sleeplessness. So are you sure that you've got a sleep disorder that you're treating and not that you basically just are trapped in a cycle of withdrawal and medicating? Withdrawal happens to opioids too, is another example. People think my pain's coming back and it's like my injury, it's like, well, it could be, but it could also be you're dependent on opioids.

B (107:10)

What's your advice to those people? To ride it out.

A (107:12)

There are treatments that can make, you know, withdrawal easier from different types of drugs. But, yeah, I mean, if you can get past that point, you could be free of using it at all. And wouldn't that be nice to do? It's definitely worth running the experiment.

B (107:27)

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A (110:10)

Off, you would say, wow, I'm so glad you told me. This is something that tens of millions of people experience and many of them stay silent about it. And therefore, people feel. And you may feel that you are strange or this is shameful or an odd experience when it is really an extremely common experience. You're saying that so the person doesn't feel embarrassed and they feel comfortable talking about it. The other thing Is you convey optimism. There are probably. Surveys give something like 24 million Americans are in recovery. We just don't notice them because someone in recovery looks like anybody else. We notice them when they're actively addicted, but not when they're in recovery because they sort of returned and they just look like, oh, that's just a school teacher, that's an accountant, that's a police officer, whatever. But that there's a lot of reason for rational hope. And in the particular case you're talking about, when someone's just starting to worry and it's early stage, the odds that they will recover are dramatically higher. So, you know, it's much, much easier to sort of pull out before you've burned your life down around you. So it's tough when people come in and you say, all right, well, do you have family support? Well, my family doesn't talk to me anymore. Okay, do you have at least a safe place to live? No, I lost my. I'm sleeping on a couch right now. Well, at work or, you know, I lost my job. That's tough for the person to rebuild everything. But if you still have those resources, there's still people who love you and your life, you still have a meaningful role where you're contributing, and you also have some accountability that's going to help you make that behavior change, whatever it is. I would say that about any behavior change, not just one connected to substances. And then what do we do when we work with people? Well, we always think about motivation. It's hard. This may seem strange, but someone says, I want to quit smoking. A good clinician will say, why would you want to do that? You think like, well, that's dumb. You aren't supposed to say, yeah, good, great, good. It's like, well, if you don't want to do it, it doesn't matter what I think. Right. And also, there's quite a few people. If you push on it, they actually become less likely to do it. If you sort of nag them to say, so tell me, what do you want to get out of this? Because it's work. I mean, I'm happy to work with you, but what is it? What are your motives? And that's reflecting on that, like, well, here's the thing. All my clothes stink, and I hate the way. So you would enjoy and help them elaborate. So you would get up and your clothes would smell really good, and you'd feel good about something. Yeah, yeah, yeah. And I'm spending a lot of money. Say, how much are you spending? Whatever it's 2,000 bucks a year. So if you had 2,000 bucks because you hadn't smoked in a year, what would you buy for yourself? What would be something you'd really enjoy? Tell me about it. And sort of helping them build up in their own mind, because again, this is about them, not you. What do you get? Because this is going to be tough and maybe I want to do it today, but in three days I'm going to be in withdrawal and I'm going to feel like I want to go back and I need to think about, wait a minute. If a year without smoking I get that $2,000 trip to Cancun I've always wanted to take. So that helps motivate them. And then we used to do some sort of behavioral analysis of where do you use? How much do you use? What do you use? Are there cues to use often? For many people there are. And also to non use, Are there places where you would never use. Oh, I'd never use, you know, I never. At my mom's house. Huh. Okay, that's good to know. Maybe you could visit your mom more often or I never smoke on a holy day and whatever my religion is. Oh, okay. So let's talk about that. How do you get through that day? What are the techniques you use there that we could try on other days? And also, what are the things that get you in trouble? You know, like, I'm trying to quit drinking. Well, what if I went into your house and opened up the cabinet, what would it be? Well, there'd be like, you know, 20 different types. So could that go somewhere else? Could you give that away so that it's behaviorally harder for you to, you know, get this, you'd have to go down the street and go to a liquor store. That kind of thing help people and stuff like that. And then, you know, there's often practical skills in learning that, like how do I manage a social interaction without alcohol, for example? Or what do I do for fun? You may think like that. Or how do I hang out with my friend who loves to drink and explain to him why I can't drink anymore? Those kinds of things as well. And that's what the therapist does. The other thing that's really important is that like any other, anytime you're making a behavior change, this is maybe seem like incredibly simple, almost dumb advice, but hang out with other people who are trying to make the same change. You want to start jogging, join a jogging group. You know, you want to stop drinking. I would suggest go check into an AA meeting or one of the other fellowships. We have life ring recovery or smart recovery. Having other people on the same journey is good for us. I mean, everything shows that no matter what you're doing, I'm losing weight, I'm exercising, I'm more whatever. I'm quitting smoking because it gives you two things. It gives you support, but it also gives you some accountability. Say, hey, you were going jogging and Tuesday you weren't there. What's up? Are you going to be part of this group or not? And that is helpful for people, the combination of the two. So all those things we encourage people to do.

B (115:25)

That's wonderful to hear some concrete questions that one would ask because I think people have heard of just quit. I think a lot of people who aren't familiar with addiction as a chemical, brain circuit, hormonal, full body, full brain issue, but mostly a brain circulation.

A (115:44)

Sorry. It almost makes you laugh. Just think like it's like someone's going to say, my God, why didn't I think of that before? Thanks, doctor. And stamp on a cigarette and walk out.

B (115:51)

Yeah, it's wild, right? I mean, this addiction used to be looked at as a character defect. And certainly addicts have character defects, But I would argue at no greater rate than nonexistent.

A (116:04)

Everybody has character defects.

B (116:05)

Everybody has character defects, exactly. And part of the reason I think it was viewed as a character defect is that a. Addictions vary and susceptibility to them varies. So if it's been easy for me to quit drinking alcohol and I wasn't aware of what addiction is, I might look at somebody who's having a hard time quitting drinking and just think, well, just quit. I did it. You can't this kind of thing and just swap whatever substance or behavior for alcohol there and then. I think the other reason is that oftentimes, sadly, addicts hurt people around them in their addiction. This is, you know, they lose money that wasn't theirs, they harm themselves or others psychologically or physically. And I mean, I know drug addicts that it had to come down to their kid getting into their drugs and almost dying before they finally quit. And even at that time, they were concerned that they might not be able to quit even though they adore their children and wife.

A (117:10)

Yep.

B (117:11)

Fortunately, that person is still sober some years later. But it's like, you can imagine from the outside, you can come up with some pretty good character defect arguments when you observe that kind of thing. But when these people get sober, it's spectacular how the real person seems to emerge, which points to the fact that the addiction masks something about who they truly are, not the other way around.

A (117:40)

I don't agree with that. And I think you're right that a lot of the explanations from addiction come from people who are hurt and angry with good reason. They had an addicted parent and that was hard for them, or their marriage is disintegrating and so they're mad, and so they're gonna have a certain amount of venom in how they explain this sort of understandably. And in addiction, people do things they would not otherwise do. I mean, like, you're saying lying about lots of things that there's no. They normally wouldn't lie about. Like, I promise I'll show up to the baseball game and watch you play your game. Or, you know, yeah, I'm going to save up some money and we're going to get that, you know, the plumbing fixed, but I'm actually spending it on drugs, those types of things. And, you know, that hurts people. And it's very important to acknowledge that because sometimes the language about the message that sometimes government public health people have given about addiction is a disease sounds scolding to people who've been harmed by addicted people. Like, I'm saying, we don't feel sorry for you. We feel sorry for this person. They're ill. And it's almost like, how dare you be angry at your mother? She was ill. It wasn't her fault. It's like, it still hurts. It doesn't. If someone who has dementia goes on an angry rant and says a lot of nasty things, it still hurts. It's still scary. The fact that it's a disease doesn't change your experience as a person. And so I'm always trying in public messaging to acknowledge that the pain is enormous. It's really tough to live with an addicted person. It's hard.

B (119:14)

It's a complicated problem from a public health. And just psychologically, I mean, we're in the wake right now of Robert Reiner and his wife being killed by stabbing, which is seems additionally violent and horrible by their son. It seems he's been charged anyway, who was an addict. And the photos of him that are going up make him look quite angry and deranged, frankly. It's gonna be interesting to see how that shapes people's views of addicts and addiction and the fact that he was supported by his parents for a long time in that addiction. They even made a movie together, which wasn't a very good movie and everyone knew it. It was sort of. Of like, it felt like a desperate attempt to rescue his son through his profession. And it just descended as tragically as it possibly could. And then we have this quote unquote homeless problem, which is perhaps also an addiction issue in part. Thanks for mentioning that. Addicts are in pain, but the people around them are in a lot of pain. Also, be interesting if in the future, addiction could be framed as. As like a context as opposed to like a person. But it's hard to separate the behavior from the person.

A (120:29)

That's right. If you grow up with an addicted parent as a kid, you know, you won't understand all that anyway. Right. You just know, like, you're wanting love and attention and you're not getting it. And that's a very common experience to grow up with an addicted parent. And that can generate lifelong negative feelings about it to people. And again, I say understandably, even if you do eventually come to the view that, yeah, dad had a disease or mom had a disease, you still didn't get what you wanted at the time. And so there'll be grief and sadness about that.

B (121:01)

Asking why would you want to quit? Is very interesting.

A (121:06)

Seems strange, doesn't it? Yeah.

B (121:07)

And I wanna talk for a moment about the carrots and the sticks. The sticks are kind of obvious in most cases. Well, if I wasn't smoking, I wouldn't have to pay for cigarettes. I wouldn't smell bad, I wouldn't cough so much. The carrots are often a little more cryptic and probably harder for people to think about, for the addict to think about if they're very far into their addiction. Recently I observed some spectacularly enormous, frankly, weight loss achievements of some famous people. Country music singer Jelly Roll. Forgive me, that's his name. I didn't nickname him that. That was his name. He was a giant man. He was close to in excess of like £400 or something. Lost over £300. And he's a transformed human being. The way he talks about what he's doing. He's running 5Ks and half marathons. I mean, he's a completely different person. But for somebody who's still stuck in the very large body, they can't imagine those carrots because they've never really lived in them. And so how do you make a. A carrot motivation, a positive motivation feel real for a patient in a way that it can really pull them forward as opposed to just all the stuff that they're not going to feel because you have to be pretty close to losing it all for the sticks to really matter.

A (122:29)

Yeah. So all People to some extent discount future rewards to some. We buy the five dollar latte instead of putting it our retirement, even though if we did that every day we would have a million dollars when we were 65. And in addiction they do it even more. So in addiction, if you ask people about what about something, would you take $5 today or $20 tomorrow? They're more likely to say $5 right now, almost as if tomorrow doesn't exist. So this really is a problem. And you can't really say to people, if you get in recovery after like five years, you're probably going to. I bet you'll meet a nice person and you'll, you'll get married and settle down and then you'll go back to school and get. That's all like fantasy camp kinds of stuff, right? So you have to, it's okay to have those long term goals sometimes those are very motivating. But you want to focus on things that are immediate because that's the world they're living in. A world of immediacy that you know. For example, you will have more money every day you know you will not. If you're using an illegal drug, you're. Your risk of arrest will drop to zero immediately. Once you stop engaging in these transactions. You will feel physically better very, very quickly than you feel right now. And social reinforcement really matters too. This is one of the geniuses of the people who developed the 12 step fellowships. The fact that you get literal status by how many days you have not or years, you have not used the substance and you get respect. And we care about those things for very good reasons. They've been central to the survival of the species. I've always thought it was clever of AA to have the one day at a time concept which maybe seems like hokey, like a slogan, but you can't suddenly quit drinking for the rest of your life. It's not here yet. And that just seems inconceivable. But can you not drink today? Not drink today and go to a meeting and get some reward for that? Yeah, you can probably do that. And so just do that every day and then you will have 30 years eventually. But you don't have to wait for all those rewards because it's very, very, very few people can do that. And of the ones who really can, they're probably not very prone to addiction. People who are think that far ahead all the time and have extremely high self control, so they'd be less likely.

B (124:52)

And what about the addictions where people either believe or it's actually true that it helps them be more functional in other areas of their life. Less social anxiety with two or three drinks, you know, taking prescription stimulant and get your work done. Maybe they are true adhd, but, you know, not revealing anything, you know, that isn't already known. I mean, stimulants raise levels of alertness. Alertness is a prerequisite for focus. And you're out the gate whether it's caffeine or people who are taking. And I think even on our dear Stanford campus, I would bet that there are students who are not prescribed Adderall, Vyvanse and other stimulants that take them in order to get work done. It's a very competitive place and they're driven and no one wants to feel tired when you got work to do.

A (125:39)

So this is also part of when you look at motivation. So some people think what you do is you say, drugs are bad. Look at all these things that's ruining you. You know, it does this, it's hurting you this way, that way, this way. In effect, you're kind of telling the person they're an idiot, right? If you actually do that. So you get them to articulate, well, clearly you like some things about it. What are they? And put them on the table. Well, you know, it's just like my friendship group has always drunk and I would just love those hunting trips. We all get shit faced together and it's real fun. Okay, so that'd be one thing you could do. What else? Tell me. And you're not framing this as a struggle between you, as the punishing force that's gonna deny that this person has enjoyed something about this or gets something out of it socially. And you say, so this is what we need to decide. These are the costs and these are the benefits. It's your life, not mine. Do you wanna go for this or not? And you acknowledge the grief of those things. Like, man, I used to be so much closer to my college buddies, and now I had to skip our annual trip for the first time because I was afraid I would relapse. Like, wow, that is a real cost. I mean, that has to be grieved. And there are many things like that. I know people with relationships where one person nagged the other to quit drinking, and then when the person got sober, left them because they changed a lot in ways that they didn't like. And it turned out there were certain aspects of of person, their drinking problem that worked for that other person, whether it was, well, I had more control over the checkbook because you were always drunk and I got to make my spending decisions by myself or I didn't have to. I find now that we're talking more, I realize I don't like a lot of things you say. I didn't know that before. And that's all real. I mean, those kinds of things happen. Drugs always work in some crude sense. I don't mean necessarily beneficial, but they have some function. Right. And you got to figure that out because that will change if this drug use changes. Yeah.

B (127:38)

The partner example is interesting because there's this whole notion of codependents teaming up with or partnering up with addicts. This is why things like codependents Anonymous and.

A (127:47)

Yeah, I think that's a bit overstated, honestly, but I think so. Yeah, yeah, yeah. One of the really interesting studies was done by Ruth Konkai, who was my colleague for a while, and it was about women who were married to alcoholic men and did all the things that fit the codependent thing. But then when the men got sober and they went back and studied them a year later, the women looked exactly like women of men who had never been alcoholic. So a lot of the things that are attributed to the personality of the codependent person is actually reaction to addiction. They're hyper responsible. They have to be because the mortgage won't get paid. They're placating. Well, they have to be because they've got this volatile person, potentially dangerous person. That's where a lot of that comes from. And I think it was a bit unfair. I mean, obviously there are people who have bad taste in partners, there's no doubt about that. But maybe a bit unfair to not appreciate. A lot of things families do are more reactive than something that was pre existent and fit with an addiction.

B (128:45)

That's a really important point because I think most people think the addict codependent pairing is almost like a prerequisite. And it actually reminds me of this whole literature, which I think is an important literature that became popular about, you know, avoidant attachment versus anxious attachment and this idea that people always pair up along these dimensions. But the studies that have been carried out subsequent to those naming categories is that put each of those people in a different context and they behave very differently. And, you know, you can. So we're more plastic in our psychologies, in our romantic pairings than perhaps we assume.

A (129:25)

And it's also true that, you know, there are people who 10 years into addiction find they're not married to the person they married, you know, because that person has Changed an awful lot. So, you know, maybe they were originally pretty social, pretty competent, pretty honest. And then after 10 years of heroin use or whatever, they are none of those things. And it feels like to the marriage person, like, this is just not the person I married in the first place. That's why we don't match. Not because I picked the wrong person.

B (129:54)

But that person changed in keeping with that. And the original question, which was different stages of addiction perhaps requiring different approaches. There's this idea, perhaps, trying to remove my neuroscientist lens here, but I believe I'll just be open about this. I believe that at some point, if you use certain substances long enough, the brain has changed significantly enough that the opportunity for recovery is different depending on whether or not you go to a meeting. Which certainly works for, let's just say, all of the addictions early on, probably most of them in the middle. But I know a few ex heroin addicts. They're different. They're still different even though they're sober. I knew them before. Now, it's not a perfect experiment because there was time, et cetera, but we know that certain drugs actually kill neurons. Certain drugs. Certain drugs rewire the reward circuitry, and the person is different. It's not to say that they shouldn't quit. They should. But it's harder to imagine sitting down with someone who's been using heroin or methamphetamines for a number of years and say, all right, let's think about how you're losing. Let's see what you could win in this circumstance. I mean, I hope that's the case, but it seems like they're rewired. They're a different beast.

A (131:17)

Yeah, well, that is fundamental to the understanding of the disorder. That is a change in the brain. And there's, you know, you can call it disease, you can call it disorder. I often think of it as deeply maladaptive learning. You know, I'm like that rat who really, really believes the most important next thing for me to do is to consume this powder. And when I'm ignoring all the things that I am evolved to do instead. So it's definitely true. You see these changes, and you can observe them in the brain, and it's amazing you can even predict things that the person can't even report on. So we did some work, myself, Claudia Padula, Brian Knutson, and Kelly McNiven up at the VA in Menlo park of people who were in a residential program addicted to methamphetamine. All of them off methamphetamine while they're in the residential thing and then giving them, imaging them and showing them cues of meth associated things like the pipe or the powder and all that and asking them how much do you like that? What do you feel towards that? Well, independent of that, there's also nucleus accumbens activation that you can see. And that predicted who relapsed. Not what they said, but what there was going on in their brain. They didn't even necessarily know it.

B (132:36)

We should say nucleus accumbens is a critical node within the dopamine reward circuitry of the brain that underlies the path to addiction and many other things that initially feel good.

A (132:47)

Yeah, yeah, that's right.

B (132:48)

So the brain was report could nucleus accumbens. Let's just put in dopamine activation proxy. So levels of dopamine activation, so to speak. We're being neuroscience y here not technically precise. Levels of dopamine activation predicted whether or not the person would relapse better than their own self report of the subjective feeling of whether or not they would relapse.

A (133:10)

I crave this, I like this, I want this. And it helps explain why addicted people sometimes get unfair rap in terms of, well, they lie about what their desires are. I really, really want to stop using. Well, I would assume if they're in a residential program for 28 days, they do in fact want to stop using. But they don't have complete insight to what's going on on the inside of brain like anyone else's. So those two people would both say, I really, really want to do this. And one goes out and relapses and the other doesn't. It doesn't necessarily mean the one who relapsed lied. It may just be I didn't realize how deeply my brain has been changed. And it's pretty hard for me, given the neighborhood I live in, to walk around and see no one using drugs ever. To see no illusions to drugs in TVs or movies. To see no pipes, to see no powders. And I'm going to relapse because I have rewired my reward system.

B (134:09)

So in 12 step one, they talk about your addict brain or one's addict brain. That's my addict brain. That's your addict brain talking. That's not you. I think this study that you refer to, I think pinpointed the addict brain is at least in part nucleus accumbens dopamine reward circuitry activation.

A (134:26)

Q elicited.

B (134:26)

Yes, Q elicited. So something that anticipates or predicts the use.

A (134:32)

Yep, that's right. And you think, particularly when you get into legal products, that is a hugely important thing. I mean, when you can, it's very hard to watch TV and not see an ad for beer, for example.

B (134:42)

Or pharmaceuticals.

A (134:43)

Or pharmaceuticals, yes. Right. And it's depending where you are around cigarettes. You know, this is very driven by class, but there's still a lot of neighborhoods where quite a few people smoke. And it's pretty hard to get through the day without being exposed to the Q, the smell of tobacco smoke or the smell of cannabis smoke for that matter. And so Q elicited. You know, craving is going to be a driver of relapse. And you. And that is clearly something that you were not born with. That is something that you learn through a repeated exposure of your brain to a pretty powerful drug.

B (135:17)

So for folks listening who pick up their phone and find themselves scrolling social media knowing they have other things to do or playing video games knowing there are other things they really need to do and feel like they quote, unquote, can't stop, stop. I think what you're pointing to really represents the divide between that inner voice that we think of as us telling us, why am I doing this? I know I shouldn't be doing this, but I feel like I'm compelled to do it almost in a kind of automaton kind of way.

A (135:45)

It is extremely common experience just in life. I know I shouldn't eat that. Ho ho. I've been trying to lose weight, but I'm tired today and I'm going to have it. Just the fact that we have a contradiction between our idealized self in our own head and our behavior that's probably just being a person. But when it gets to the point that I'm actually, I'm going to flunk this exam, which is important to me, not to flunk. If I don't start studying and I'm on my third hour of scrolling through TikTok and I know and I'm not, then you start to worry, right? Because now you're going to do damage to yourself for the purpose of consuming this brain candy, which has no nutritive value at all, but is clearly seductive.

B (136:25)

I'm out of the lab these days, but if I were to go back into the lab, I'd want to team up with clinicians like you and some of our engineering bioengineering friends and develop something which would be similar to what Nolan and company developed for depression. Right? Brain stimulation. Not just willy nilly, but of particular brain areas and circuits to try and undo major depression. Wouldn't it be wonderful if there was a brain stimulation device that could tweak the reward circuitry in the presence of a cue that predicted methamphetamine for the amphetamine addict or alcohol for whatever process behavioral addictions and wouldn't eliminate the ability to experience reward, but would eliminate essentially the bad addiction or tamp it down. Tamp down the rewarding properties of the bad addiction and at the same time do an experiment, a parallel experiment where you ramp up the reward circuitry and in the presence of a something that cued for positive behavior, because I don't think you can just tamp down reward circuitry. This is one of the challenges I have with the, you know, okay, obviously abstinence is going to be critical, but for somebody that has a nucleus accumbens, and we all do, it's going to want to latch onto something. And I've seen so many addicts pivot to the next thing sometimes. It's a healthy thing. Many ultra runners are addicts.

A (137:53)

I've met people like that too.

B (137:54)

You can't go to a 12 step meeting, and this is somewhat cultural also, but you can't go to a 12 step meeting and not see people with lots and lots of tattoos if they have issues with, and I'm not demonizing tattoos, but if they have issues with drugs or alcohol, typically smoking will pop up in its place. They need something, we need something. And ideally it would be, you know, school and family and connection and community and public service. Great if we could, you know. But a device that could help tune the specificity of reward I don't think is outside the realm of possible. I'm thinking like a Stanford guy now. We like to engineer everything, but why not? It's being done for ocd, it's being done for depression, it's being done for ptsd. It's being done for so many things. I mean, after all, it's plasticity that we're after.

A (138:43)

Yeah, I mean, you're right. One of the challenges is addiction is it's not like it's introduced something new into the body. It's working on the very system we use to negotiate life. It is the thing we use for learning, acquisition of knowledge, acquisition of skills. So it's, it's not like if we just didn't have that, we would be better off. We wouldn't be better off. We couldn't survive without it. The only neurosurgery patient is at West Virginia University who had a very uncontrollable addiction and got not exactly sure the nature of the implant. If it's a stimulating implant that's happened once it was covered, people want to read about it. Lenny Bernstein, a friend of mine at Washington Post interviewed that patient and the team. But I think that is likely that we will see something like that. I suspect we will see more RTMs, trans magnetic stimulation because it's not so invasive, not so expensive and not so risky. We're about to start led by Greg Salem who's a really good psychiatrist. A multi site study with RTMS to the dorsolateral prefrontal cortex for people who are cannabis use disorder, addicted to cannabis. There are lots of people working on these protocols for alcohol, for cocaine. Doesn't always work. Saying RTMS is almost like saying we put them on pills because there's what brain region at what intensity, all that kind of stuff. But that is a way to intervene far more directly to the brain than talk therapy for example. So I think that is certainly possible in implants made possible this particular case with somebody who was very very very had tried everything on earth and still couldn't stop. And interestingly even with the implant still needs medications, goes to lots of 12 step meetings. It didn't just make it disappear. Cancer. Though we haven't talked about GLP1 Agnes. If we want to get into that that is maybe something that would have the lasting effect on changing what one wanted.

B (140:51)

I definitely want to talk about GLP1s. I think just before we pivot there, when I think about the quote unquote homeless problem living in California. You can't but see this. I think of it as at least you tell me where my numbers are off 50% an addiction problem either first or also.

A (141:12)

In this economy.

B (141:13)

Yeah, yeah. I mean those folks aren't going to go to 12 step meetings. Yeah, maybe. Maybe I would love for them to. They live outside my door and I talk to some of them and they're not going to 12 step meetings, no way. And many of them are. Their brain circuitry is altered. Maybe it was altered before. This is not all homeless people. In fact, I don't even know if homeless is the right word. And I'm not going to the unhoused thing like they're homeless. Okay. They don't have homes. You know, I don't think we need to split hairs with the naming. Many of them have serious substance abuse issues and or mental health issues that may have stemmed from that. I'm not asking to solve the whole problem here in five minutes or less. But how do we wrap ourselves around the legislature? I know you've been involved in things related to this. How do you get somebody on the street to understand what's going on and rescue themselves?

A (142:13)

Yeah, so first off, yeah, it is a very high rate of substance use and mental illness. Higher now than in other periods because unemployment is low. When the economy is really terrible. There are a lot more people who don't have anywhere to live, who are, you know, just need a job basically. You know, they're not, they didn't fall out of housing or family, they just need work. But since, you know, unemployment is historically quite low now, so who's left are the people who cannot, even when we're near full employment, cannot find a shelter. And those tend to be people who have problems like mental illness, like addiction. You can do some things, and we've good evidence you can do some things by combining housing, nice housing that people would want with recovery culture. So there's a model called Oxford House which is run by the people who live there and they all contribute a bit to the rent and they have a culture which is basically, you can't fight, you can't be violent and you can't use substances or bring them in, but otherwise that's it. And they have sort of recovery communities like 10,000 of those things, those kind of things have really good evidence of benefit. So some people will, for that leave the streets and live there and make that trade. You can't use your drugs anymore, you can't drink anymore, but, but you can't at least have a nice clean place with nice people who like you and will support you, that can help people. Some people, in my opinion, have to. It will be a court mandated thing and there's two mechanisms for that. If someone is so impaired that they're gravely disabled and imminent threat to themselves or others, you can, through the civil commitment process, make them go to treatment. If someone has committed a crime, and many people do, like grab someone's iPhone, knock them over and run away and get caught, that is a different type of leverage we can do through things like drug court where you say, look, you shoved that person, you assaulted them, you stole their phone, we could send you to jail for this, but we don't want to send you to jail. Instead, if you will comply with this treatment regimen, you will not have to serve the penalty for that and we'll expunge your record at the end. Those kinds of things are going to be necessary for some people. Now there are many people who are uncomfortable with that, like, are you going to use pressure to put someone into treatment? Isn't that really unethical? Well, if someone with Alzheimer's disease wanders away from a nursing home, we go find them and we bring them back whether they want to or not, because we assume that the disease is affecting their judgment. So if they think they can survive out there, they're wrong. And so we take them back whether they want. Well, the same thing is true, absolutely true of addiction. It dramatically changes our judgment, impairs our judgment, and without pressure, many people will not stop using. There's a study, I like to quote, by Doug Poulson and colleagues of people seeking help for alcohol treatment. And why this is a good one is because alcohol is legal. Right. So it's not the war on alcohol made them go. Alcohol is legal. But. But he asked all of them, has anyone leaned on you basically to quit drinking in the past year? And 91% of them said yes. The wife said, I'm moving out with the kids if this continues. The boss said, you show up drunk one more time, you're fired. My lawyer said, this is your third drunk driving arrest. You better get into treatment. So the judge might take some mercy on you. They're pressed in, in a way. You don't have to press people to seek care for, say, chronic pain. Chronic pain sucks. Everyone was happy to leave chronic pain, but people are ambivalent about giving up substances because, again, it's rewarding. That's why people do it. And so that press is necessary. And so we're going to have to do that with the sort of criminally involved, homeless, addicted population. We're going to have to get comfortable with protections for. Sure, protections for civil rights need to give them quality care, but to push them into treatment where they can regain their reason and then make better decisions for themselves.

B (146:14)

I know you've been involved in legislature, and it's always nice when I guess I can say you did that under a Republican administration and a Democrat. A Democratic administration. So we don't have to get into partisan politics here. Two administrations, opposite sides of the aisle. Your goal there was to get better legislature as it relates to addiction and treatment of addiction, correct?

A (146:37)

Yeah. Yeah.

B (146:38)

So where are we at? What do we need?

A (146:40)

Since like 2008 up to the present moment has been the best addiction treatment policy we've had as a country. And that was because 2008 is when parity legislation came in. This means, like Blue Cross, Aetna and all those, when they cover stuff, they have to cover mental Health and addiction too, at a comparable level. And those laws have expanded to cover more and more people on the private side then on the public side. The expansion, particularly of Medicaid has become the backbone of a substance use treatment system. Like in places where I'm from West Virginia, I happen to know it's the biggest spender of the addiction treatment system that is good, that has made treatment better, quality, easier to access. And because Medicaid is a mainstream healthcare player, it helps integrate addiction care better into the rest of the healthcare system.

B (147:27)

So excuse me for interest, but practically speaking, so somebody's got a son or a daughter who's got an opioid issue or an alcohol issue and they want help, if they have insurance, they can go to a treatment center and it will mostly or completely be covered by insurance.

A (147:42)

It depends on the plan. I want to promise anyone in particular, but here's what used to be legal. It used to be a plan could say your co payment for an outpatient visit is five bucks unless it's mental health or substance use. In that case it's 25 bucks. Or you're allowed to have up to, you know, six months of hospitalization a year unless it's mental health and substance use and you're allowed to have 14 days. Those kinds of things, which made very skimpy benefits, are now illegal in almost all plans.

B (148:09)

Interesting.

A (148:09)

So the odds as a mom or dad when you open up the plan today that whatever you got through your work or wherever will give your kids something that they need is just way, way higher than it's ever been before. And that was due to advocacy in changing the law and changing the regulations because obviously covering care costs money. Insurers don't like to cover care, they have to, but they also don't want to. And so keeping the pressure on, they have to follow the law. So in that sense, we're in a better place on the private side. The challenge on the public side will be the contraction of Medicaid. So you know, the budget bill that was passed this last year takes about a trillion dollars roughly out of Medicaid over the coming years. And you know, number of people on Medicaid have substance use problems. So how they will get substance use care and other care that they need is not entirely clear. So I'm quite, I'm worried about the impact of that, especially on low income Americans who are dealing with addiction.

B (149:12)

What are the options for people without insurance and, or who don't want to go to a treatment facility? I'll just be direct about this. What's your opinion? What are the data on 12 step programs? Because 12 step programs have this phenomenal aspect to them, which is they're happening every day and night online and in person. It is anonymous. Every city, all over the world. If you go to a meeting, you don't like it, you leave, you find a different meeting. You don't have to pay for it. You can donate to support. I mean, there's just so many things about 12 step that make it arguably the most accessible addiction treatment program ever. And if anything, it's growing right now. But what are your thoughts? Does it work? Is it a cult? What's the upside? What's the downside?

A (150:00)

It is not irrelevant that, that those programs were designed by people who have the problem and therefore understood what it is, what you need when you've got that problem. So I think about this like where I am in Palo Alto. Let's say some engineer wakes up in Palo Alto on a Saturday morning with his 20th or 30th or 40th beastly hangover of the year and says, what am I doing? I've got a great. I've got this great life. I have this $200 million one bedroom condo that I really like and. And I'm messing with my life. I'll call. Let's call Stanford psychiatry department and try to get some help. Well, they're closed on the weekend. You'll get a message, then on Monday you can call back and then you'll get on a waiting list and eventually you might get in. So for a condition characterized by ambivalence and impulsiveness, I want to quit now. Two hours later, I don't. That's like, this healthcare system's the worst possible design. Whereas how is AA design? Be like, I'd like to go to aa. You can go on the AA website, look in the area. Oh my God, there's like 15 meetings today. And not only are there 15 meetings, but there's like a women's meeting, a men's meeting, a spiritual focus meeting, an LGBT meeting. And you can just go. And that moment you have at this moment, I want to change. You can just follow through and then you can get immediate reward, social reward, for taking positive steps towards it. The treatment system will never be that good at sort of being that accessible. And of course, no health insurance, no paperwork, no pre approval. That's amazing. Does it actually work when people get there? So I started my career, I didn't really know anything about addiction. My first job, I took it Because I was literally flipping burgers. And there was a job that paid another dollar an hour in the medical school where I didn't have to wear a costume, a Wendy's outfit. So that's why I got into the addiction field. And that's the truth. So I didn't know anything about it. And I met, while I was on this job, I met some people, said they were in aa and I thought they were like the people who get your car battery for you on a cold. That's what I think of when I think of aa. And I didn't know what AA was. And they explained it to me and I talked to my mentors about it. And my mentors were professors in medicine. And they were very dismissive. They're like, well, they don't have doctors, they don't have medications. It's kind of folk medicine. Bit of professional snobbery there. But I wasn't so far along in my education that I was incapable of learning. So I thought, well, will you take me? Can I go? And they're like, well, you can't go to a closed meeting. But there are these openings. Okay, because I want to see this. And I was so impressed with just the authenticity and the caring and the warmth and the wisdom really just made me think, maybe there is something here. And so I started doing research on it, as a number of other people were at that time. And it just keeps coming out really, really good in studies. And so finally, a few years ago, me, John Kelly and Marika Ferri did what's called a Cochrane Collaboration review. This is the creme de la creme, most rigorous review of evidence in medicine as a method. And looked at all these studies of Alcoholics Anonymous done by different people with different viewpoints in different cities, in different countries even, and it came out extremely well relative to very good therapies like the one I was trained to do, like cognitive behavioral therapy, motivational enhancement therapy on abstinence outcomes. If you ask, like, do people stop entirely AA and also 12 step facilitation kinds of counseling to help people get into AA was winning by 50%. Higher rates routinely of that. And then when you looked at other outcomes, like did the person at least cut their drinking or reduce the damage of drinking or less dependent or better family functioning, whatever it was as good as that's amazing for something that's free, anyone still left saying, hey, it doesn't work. Often people think there's no evidence. There's a ton of evidence. There's randomized trials, there are quasi Experimental studies. There are healthcare utilization studies. It's amazing. And so I always say to anybody, whether it's a patient or just a person I care about, if you want to stop drinking, that'd be a place to try. There's really no harm to it. Right. If you go to a bad movie, you're out in the evening and 15 bucks you go to a bad AA meeting, you're just out in the evening. It's not like a high risk endeavor to just give it a go. And there are some alternatives too, by the way. There are smaller. But if you live in an area like San Francisco Bay Area where there's more choices. There's also like Smart Recovery and Women for Sobriety. And I'm forgetting some of the other names, but choices. If you don't like particular AA model but that experience of mutual support. People are on the same journey with me. They're further along the same journey and they're doing well. At Spire's Hope they'd given me useful information. All of that is really potent and that's why it survived and thrived as an organization. Why 195 countries or something have AA in it?

B (155:08)

Just want to mention if people are interested in aa and this is. It's not like I've been sent here to advocate for aa, but they have. Keith mentioned open meetings. If you look up, an open meeting is one that anyone can go to. Even if you are not an addict and you're just curious or you have a different addiction and you want to go to an AA meeting. Because the AA meetings tend to be more established and there are more of them than the other letter Anonymous meetings for gambling and other sorts of addiction. I've been to many meetings. I'm super impressed by how AA can do what it does. It's just a shining example of humans self organizing into something that keeps going, doesn't walk around with a basket. There's no GoFundMe, no tax dollars, no tax dollars. They just, they, they stay out of politics. It's. It's really cool. And I know some people that couldn't get sober any other way that did it. I'm curious what the data are on the other addictions that are treated through the 12 step model. So Narcotics Anonymous, Overeaters Anonymous, Gamblers Anonymous. There's so many of them now.

A (156:20)

Yeah.

B (156:21)

And I imagine there aren't as many studies, but the model is pretty much the same. So I wonder how they hold up.

A (156:30)

I was very interested in this question for the drug groups. There's Very little on gambling and sexual addicts, those things. So the other big pool of data we have, to extent we have one is on the nac, Cocaine Anonymous, Narcotics Anonymous. There were a couple things, interesting one is it's harder to get people into those groups. So we were looking at studies where there was what's called 12 step facilitation counseling. So where you're in there, you've got somebody who knows the program is introducing you to it, encouraging you to go and then talking about how did the meeting go and did you get a sponsor and all that kind of stuff. And the uptake was much lower. So if you do that in an alcohol program, you get these doubling or tripling of the rate of patients going into aa. And the effect was much, much smaller with the illicit drugs to get people to attend ca. We don't know why, but it wasn't as easy to get people in. Definitely there were correlations pretty consistently that people who were going longer were doing better. But the evidence wasn't quite as strong from external validity, I'm sorry, internal validity point of view. In other words, they're not the same kind of trials, randomized trials that we like to have, you know, when we draw inferences. So I characterize the evidence on 12 step groups for drugs as positive, encouraging. I would certainly try it, you know, certainly not harmful, but it's not as strong. I don't feel, I feel comfortable saying AI no positively has a causal effect on alcohol. I have no doubt about it and I'm less sure about that whether that's true for the maybe in Andrew's case, but on average it was harder to, to demonstrate that effect.

B (158:11)

I was being somewhat facetious when I asked whether you think AA is a cult, but one of the reasons why sometimes people will call it a cult is I'm just going to be very blunt here. Is that often? Not always, but often enough, I should say people who get into AA, discover sobriety in the AA community or other 12 step communities will talk a lot about it and how much it's changed their life and they've got a new set of people they hang out with and in the name of sobriety. And that can be, if it's not handled correctly, it can be seen as somewhat of a separator by people around them. That's one. There will always be instances where certain groups are not in a healthy dynamic, but I would say 95% of the time it seems to be healthy dynamics. But there's this other piece that I think sometimes gets Gets tucked away and no one wants to talk about. Which is that a critical component of 12 step is that the addict acknowledge that they're not in control of everything. They certainly can't control other people, but perhaps they can't even control their own mind. And they have to have a higher power in notion. And I think some people interpret this to think that one has to suddenly become formally religious, either Christian or just, or to believe in God as an entity. And, and. But my understanding is that 12 step. Well, I know because I've been to a lot of meetings. 12 step hinges on the acknowledgement of some sort of higher power. But people can self assign what that higher power is. Some people say God, some people say Jesus Christ, some people will say nature, some people will say the universe, some people will say the collective. So I think that's not discussed often enough. And then people will say, well I don't want to go 12 step because it's going to be a bunch of Jesus freaks coming at me and I'm going to have to do a bunch of other things and what's happening.

A (160:07)

Yeah, so there's a lot there in those questions. So in the cult thing. Well, I wouldn't call it a cult. Cults do two things that AA doesn't do. One is cults take everybody's money. AA literally won't let you give them money. I mean it's amazing they've survived authorization Rockefeller off the money. They said no, we should limit that. That's would be too grandiose. So it's very, you know. And they're perpetually broke by design. They have just enough to keep going past the hat. They can give it if you want.

B (160:29)

To or not, you don't, but if you don't, you are not looked down upon.

A (160:32)

Yes, they give away the literature, so they don't do that. The other thing is they don't stop anybody from leaving literally any meeting. You can literally stand up and say I'm go get drunk, bye. And that's different than a car.

B (160:43)

You just can't show up drunk. This is important, the desire to quit drinking or the other behavior. And you can't show up intoxicated.

A (160:52)

They will usually let people sit as long as they're quiet if they're drunk, rather than throw them out. If they start talking and drunk, then that's a different thing. But usually they will. And relapse is a normal part of recovery. And nobody knows that better than people in aa. I mean they appreciate that even though they don't want to hear from a drunk person, obviously. But then the religious thing, yeah, they got the word God there, right. And so there are people who just have had bad experiences and just that word is a repellent to them. It doesn't really, in a sense, it doesn't even matter if they know how the organization defines it. They just like, look, I was, I went to Catholic school. I hated Catholic school. I hate religion. And this sounds like religion, so I don't want to go. Some of those people might be happier than in programs like Smart Recovery, which doesn't have that component to it. But yeah, it is incredibly flexible in terms of how it's hard. That's why it's really a spiritual, not religious organization. It is, it says in the text, the 12 steps are but suggestions. Okay. Can you imagine that in a Christian church saying Jesus was the son of God or maybe he wasn't. Who knows? It's really up to you, right? That's what in a religion. No, he was, period. That's non negotiable point. Aa, everything is negotiable other than what you believe. It's what you do. Go to meetings, stay sober. They don't really care. My friend Barry Rosen passed away too young, unfortunately, was an addiction psychiatrist. He said would say to people, look, the God in AA can be anything. It could be Buddha, it could be Jesus, it could be your group, it could be the doorknob.

B (162:37)

It could be.

A (162:38)

It just can't be you, you narcissistic sob. And that's what they were really concerned about with the people who found it, is that it was the hubris, the ego of, I am in control and I don't need any help. I am the God, basically. And breaking that belief, it's like, no, you're whipped. You have lost your control. Out of the subject. And admitting that is the critical point. How you end up explaining the spiritual part is really up to you, but that part is non negotiable. Why else would you be there if you thought, no, I can still control my drinking? They would say, well, then you shouldn't come here because we can't. That's why we're here.

B (163:18)

Bill and Bob, the founders, were good psychologists. They understood the juxtaposition of the narcissism and the shame that is addiction.

A (163:26)

Yeah, yeah. They were really great Americans. I mean, they changed it, changed the country.

B (163:33)

Before moving on from this again, if you're curious, you can go to an open AA meeting if you want to. It's interesting. And when they go around the room. And people say, I'm so and so, I'm an alcoholic. Some people say, I'm so and so, and I'm their first name only, of course. And they're an addict. If you're a visitor, you just say, you could say nothing. You could say, pass. No one would pay much mind to it. Or you could say your name and just say, I'm just here to learn. And I've seen that a number of times. And it's. It's usually family members of addicts or family members that want someone in their family or a friend to go to 12 step. And this is an interesting little trick tool. Sometimes it's easier to get someone to go to 12 step if you yourself have gone. And if you're not an addict and you want someone to go saying, I went, yeah, and I'll go with you. Right. I mean, this sounds very kind of hokey on the one hand, but. And I've seen the incredible things that 12 step can do. It's so awesome. It's free. How many things are completely free, accessible all the time. It's like wild. It's a wild invention.

A (164:35)

It's the closest, by John Kelly. My friend who did the review said it is the closest thing we have to a free lunch in public health.

B (164:41)

Speaking of lunch, let's talk about GLPs.

A (164:43)

Okay.

B (164:45)

I'm struck by how many people have lost a lot of weight who couldn't lose weight previously. I'm also delighted, thrilled, so, so relieved that I don't have to look at these stupid arguments online anymore about whether or not obesity was the consequence of some other thing besides over consumption of calories relative to caloric expenditure. You know, there's no blame in that statement, but, like, people were going back and forth and back and forth, and the laws of thermodynamics apply. We now know, thanks to glps, if you eat less than you burn, you lose weight. It's just very hard for people who are very overweight to eat less and burn more. And it runs against all the evolutionarily hardwired circuitry of desiring overconsumption. So here we are at a time where there are these peptides that people can take to lose significant amounts of weight. The cost on those peptides is coming down now through the compounding pharmacies. And people are taking half doses. People, by the way, people are sharing their glp. People are splitting them. Not supposed to do that. It's illegal. That's not a suggestion. It's incredible how low a Dose of GLP is required for people to get the desired effect. And people are picking up on this. The pharmaceutical companies hate this, but people are getting them through compounding pharmacies. They're extending their dosages, they're sharing their. Don't share prescriptions, but they're doing it. And people are just losing weight easily. Some are losing muscle, and everyone gets inflamed about that. But you can do some resistance training to offset that. And they're awesome weight loss drugs.

A (166:23)

Yeah, they're amazing.

B (166:25)

I'm not on them, by the way, but I would take them if I needed them.

A (166:28)

Yeah. And they may have other benefits too. We haven't fully figured out. So I'm extremely interested in their effects on substance use. I have a friend who's addiction psychiatrist. She said what my patients desire is they want not to want. So which is different than, like, I want to conquer my desire. Like, I just wish I didn't desire this drug as much as I do. And I link that with something a friend of mine said to me over lunch. A friend of mine who I noticed had lost a lot of weight. And I said, wow, you've lost a lot of weight. He goes, yeah, I'm on GOP's. And he said, I used to spend all day not eating, and now I don't think about it. It was effortful all day long. Don't eat, don't eat, don't eat, don't eat. And now that voice is just gone. And so what if we could do that for, say, cocaine or alcohol? They are sort of in the same kind of family of behaviors. And there are some interesting studies. Now, to be clear, there's some studies that are negative. Nothing ever works out perfectly for everybody. But when I look through animal studies, small trials, and opportunistic epidemiological studies. So like, when you go through the hospital, here's There's 10,000 people who had a diagnosis of cocaine use disorder. And let's see if the ones on jlps went to the emergency room less. Something like that. None of these. They're vulnerable to different kinds of selection effects. But still, I see this pattern, particularly with semaglutide, which is the GLP that is in wegavy and ozempic and alcohol drops in alcohol use. And the other thing I think is perhaps important and why I'm working now with the VA and Novo and a philanthropist to do something like this, is that alcohol is the most like, eating of drug behaviors. Right. So to the extent these drugs create a sense of satiety and fullness. Right. To me, that seems more likely to change. You know, swallowing something, a drink versus, say injecting myself or snorting a powder. And it's eating like behavior. And so that's why I was optimistic. At least that's where I want to start. If that works, it'd be fantastic because we have. If you have a drinking problem, you're about 70% more likely to also be overweight. And Americans are already pretty overweight. Just think of the two for benefit of this, for transforming people's lives, lose 30 pounds and stop your diet drinking problem. And last one you mentioned, my dear friend Anna Lemke, my colleague, she said, what's great is their patients. I don't really want to stop drinking, but, you know, I just love losing weight. So, you know, because I've been overweight my whole life. And so I will take the Ozempic here in the addiction clinic. Not because I'm that motivated for the addiction part, but boy, when it comes with this other thing I really value, then I'm going to do it. And then they get the benefit. You know, they stop their drinking, cuts back. So. So it's really thrilling. Another nice thing is these are old drugs. They've been around like 20 years. People don't realize that. And millions and millions of people have taken them. So that makes it less likely that there's some awful side effect that doesn't show up for 10 years to them. So there's just a lot of potential upside here. And I think the next couple years of science in this area are going to be super exciting.

B (169:50)

What aspect of alcohol craving is sugar craving?

A (169:55)

I don't think very much. I mean, maybe some. I mean, certainly the lore is when you're hungry, when do you are likely to relapse? In fact, AAP would say this. Hungry, angry, lonely, tired. And some people feel that way, like if they actually. They also sometimes feel this way about carbs. When they are short of carbs, they want a beer. So maybe it's something in the there. But I don't think that's the fundamental thing that is the driver. I think it's more the subjective effect of consuming.

B (170:27)

There's a movement toward removing advertisements for pharmaceuticals on television, online. I mean, on television. Does anyone watch television anymore?

A (170:39)

That's a good question.

B (170:40)

I don't know what effect it's going to have now that so few people watch television. But what are your thoughts on that? I mean, and of course there are medications for hives and allergies. And all these things. So it's a broad category, but I'm specifically thinking of things that have an addictive potential.

A (170:53)

The Lancet commission on Stanford, Lancet commission that I led, you know, partnership between Lancet and the medical school. That was one of the points we made, is that there's only two countries on earth that have television ads all the time, which is us and New Zealand. I have no idea why New Zealand, but. And when people from other countries come here, that's always a jolt to them, like, you know, come, go to your super bowl party and like, God, all these ads for Ask your doctor about this. Ask your doctor about this. Ask your doctor about this. I think it can create, I can't prove this, but I think it can create a sense that everything is perfectible if you just bully your doctor enough. And that is just not the truth. So that's the downside, I think, to worry about them, particularly for like, we don't have, thankfully, OxyContin ads on television, but we do have bank shot commercials. So by that I mean there was one actually in the super bowl of an ad for opioid induced constipation. So who is that really for? I mean, that's a way of bringing up the subject of are you on opioid painkillers? But mostly we don't have that. And I think that's good. You know, we need opioids, clearly, and we. And you know, they're. I've worked in Hospice for 10 years. No one needs to tell me how incredibly valuable they are. But at the same time, you know, over promotion was clearly part of what triggered the opioid crisis. And by that I don't mean tv, I mean everything. I mean people, you know, gifts and, you know, other types of promotions, gifts to schools that weren't separated enough from the industry. All those things we highlighted in the Lancet Commission.

B (172:42)

Social media probably doesn't have its own 12 step yet. It probably will soon. Social media is here to stay. Let's be blunt. I'm sure there's been discussions in the past about television is ruining society, and now everyone's staring at a box in the evening. I mean, this has happened multiple times throughout history. But do you see true social media addicts or video game or YouTube addicts? Do you ever observe intervention working? What does that look like? Given that it's not quite like eating, meaning you have to eat at some point, but to tell a young person or an older person, but to tell a young person, look, you can't ever Be on social media isn't reasonable. It's like saying you're not going to talk to your friends unless they're standing right in front of you and it's not going to work.

A (173:34)

So I will quote a perceptive Stanford freshman who said to me, I hate social media, I think it's bad for my mental health, but I have to be on it because everybody else is. And that is really tragic. And I think lots of people are in there. And I read another study on the plane coming here of how much would you have to, how much would you demand if you had to leave social media? And people will say a certain money. But you say if everybody else were leaving it, the same people would say I would pay money to be one of them. So that is why things like the Australian social media ban are gonna be really interesting because it's not really an individual punishment, you're not being exiled from the party. It's more of life is going to happen in person for teenagers. And so that will make that real life more appealing than being online. So I'm really fascinated. I mean we don't know what's gonna happen. Really fascinated to see what happens. We do see all across the country more people coming in with these types of problems, like feeling like they can't stop looking at their phone or games or pornography is a really big one, you know, deliver through these media. And of course there are now gambling apps you can use on your phone and that kind of thing. And really have extremely difficult lives. I mean they really have become absolutely consuming for them. We don't know yet what the natural course is of this because it's new. So what is the five year course of social media? That's really literally impossible to answer at this moment. For what portion of people is a developmental thing that they will get out of? For example, if you go into a college campus you will see a lot of people drinking at levels that would qualify them for some level of alcohol use disorder. And a huge number of them, five years later will be married and have a job and drink very little. I mean there are those kinds of maturing out effects. Is there a maturing out effect on social media or not? For me it was easy to. I used to do a lot of X and then I stopped or just do a teeny bit. Now that was particularly easy. But of course I had 40 years of my brain not touching it. Will that be as easy for whatever the most popular kids probably TikTok or Instagram or something. If you've been Doing that again, thinking in that plastic neuroplasticity from the time you were 8, 9, 10, 11, 12. Is it developmental when you're 25, will you be ignoring your kids or will you not have kids because you don't have sex, because you don't have a date, because you're in all day looking at the phone like, what will that course be? We don't know that yet.

B (176:19)

Yeah, I see a lot of adults addicted to social media. I don't know if I'm addicted. I don't think so. Because if I say I'm not, sounds like an addict, right? So I'm just going to say I don't think so. But I found great benefit to taking an old phone when I upgraded my phone, which I do far too seldom. But I finally upgraded my phone and I took my old phone and I put X and Instagram on that phone. And it remains much of the time in a supermax prison lockbox that you can't code out of. So you put like one day or 19 hours or something, you click that and you'd have to saw it open and that wouldn't even work. And it's very helpful because once it's locked away and there's no opportunity to look at it, if people send me things, I can't open it on my other phone and the impulse to pick it up is blocked. It's very useful portable box, and it doesn't require. I mean, the box costs 30 bucks. I'm sure I recovered more than that in work output and recreation output and just hanging out with my girlfriend and not looking at my phone.

A (177:23)

Yeah, I know other people who've done things like that or switched back to a dumb phone to avoid the constant Bing notification. Da da da da. Or there's also software you can get that will suppress a lot of that stuff unless you specifically go in and enter a code and say, bring it all to me. And those are useful things. It's so new that we haven't got a lot of social norms about it. But think of something like drinking before noon. There's no law against drinking before noon, and yet a huge number of people abide that norm. And like, oh, well, it's not noon. And we might over time evolve some kinds of things about social media. I would hope. Like things that we all find sensible, like don't do social media at the dinner table would be, I think, a good one. Or don't do social media in a restaurant or whatever. I hope we'll do something because you can't solve this problem just through individual clinical medicine. That's crazy. I mean, there has to be some. Just like we've built a lot of norms around alcohol. We've built norms don't drink and drive. That's one that most people now broadly find believable. Building some about social media I think is going to be sort of the task of this generation that has grown up with them.

B (178:39)

Yeah, I have three real life examples of young guys whose parents I know who essentially contacted me because different situation for each. But I'll just describe the overlap. Each one of them was looking like a failure to launch, graduated high school, was not highly motivated to go off to college or went to community college, then stopped doing that was working, then lost their job or they were not in a career path that was gonna sustain them independently. YouTube or video game enthusiasts to say the least. And all were convinced they had adhd. All medicated by now, happy to say, with some explanation of reward circuitry. And Ana's book, giving them Ana's book Dopamine Nation and obviously really hard work on their part is really what did it. All three of them in higher education situations, great universities, off medication, they all had to quit video games or YouTube for some extended period of time and recapture their attentional capabilities and most importantly, recapture their sense that they have agency in the world, that they can make things happen for themselves. Yeah, not incidentally. All of their parents are reasonably high achieving and none of them have patterns of addiction that would have predicted any of this. So there is a way to escape the vortex of this stuff. But I mention those stories because I think a, they're success stories and I'm proud of those guys. But oftentimes it's multifactorial. I can't say, oh, it's the medication or oh, but the medication didn't rescue them OR oh is YouTube or oh is video games, is. There's a sort of a pattern of progressive languishing that's set in this context of media. They weren't talking to me about porn, although I suspect that was in the backdrop of some of these cases. And they're kicking butt right now. All three of them in healthy relationships, working hard, working out happy, which is the most important thing. I mean, one kicked cannabis, the other doesn't drink. The other one can drink, it seems, without any issues. I mean, when I think about what they have to deal with relative to what I had to deal with growing up when we didn't even really understand what addiction was, there's just so many more things coming at them to impair them. It's like they've unshackled themselves from five or six different ball and chains.

A (181:03)

That's great. And the point you make, too, about there's so many pathways out of this. You see that everywhere. Many, many pathways to recovery. I mean, I know people who, like a dear friend of mine just tried to quit smoking for years and years and years and felt totally defeated by it until he saw his baby as soon as he was a father. He's just like, man, I got to stay around for this beautiful being and quit that day. There's changes in the homo racial system because of life changes that. I have another friend, a dear friend who was going to prison, which is a terrible thing. You think, how would anybody benefit from being in prison? But he said, I just needed many, many months off of methamphetamine for my brain to heal. And I sort of realized, wow, that was really crazy. And he didn't get any treatment. It was just being away from the drug for an extended period. And there's an infinite number of stories because this is a condition experienced by tens of millions of people, right? So there's going to be lots and lots of pathways out. That is one thing, by the way, surprises a lot of people of people who had a substance problem and are now doing well in big representative surveys. Very few of them actually went to see anybody like Stanford Psychiatry. That is an unusual pathway to go through addiction treatment. People change in all kinds of ways for all kinds of reasons.

B (182:30)

One of our team members here has been open about this, so I feel comfortable saying it. He managed to kick alcohol and a pre almost lifelong alcohol and cannabis addiction. Didn't go to meetings, but made the decision and lost a bunch of weight, too. He was already super productive. You know, he was doing well enough. That wasn't a forced thing, but he was just tired of, you know, tired of being tired, as they say. And he flipped the switch in one day. Has never gone back. And I remember asking him recently, I was like, wait, did you go to meetings? He's like, no, I went to the gym. He found a replacement behavior. He got healthy. He kept doing all the other things he was doing. And I don't want to take the words out of his mouth, but he's gone on a few podcasts talking about the relationship with his kids, improving tremendously professionally and his relationship to himself, and broke a long family line of alcoholism. I mean, I think that's what sometimes people forget, is that you can break the chain in one generation, which is really spectacular.

A (183:28)

Yeah. Genes are risk. They're not destiny. And that's very important. Even if you come from 100 generations worth, that doesn't mean that your life is necessarily going to come out that way. And you're raising another point too, about what is beautiful for a lot of people about recovery is then you start acquiring more reasons not to use that you didn't have at the moment you started because you. You burn those relationships out or you'd never form them because you have been living in your mom's basement, smoking cannabis and being online all day. And then you start to get like, oh, wow. Having a job where I'm respected and I feel important is nice. Getting paid is nice. Being mentally present instead of high all the time is nice. And then it just makes it easier month by month, year by year, to just live the rest of your life that way.

B (184:17)

There was a question that I forgot to ask earlier.

A (184:20)

Okay.

B (184:21)

And it's a somewhat of a touchy subject.

A (184:23)

Okay.

B (184:25)

I've observed and I've heard that sometimes the smarter the person is or the more intellectual they tend to be, or ideas oriented, the worst 12 step works for them. Whereas people who just kind of go, okay, like chop wood, carry water, I can do that. Follow step one, follow step two, follow step three, step four is pretty uncomfortable. Do that. Okay, fine. That one's harder than the other ones. And they just kind of do it. They don't overthink it. I've observed this quite a lot, and I don't want to get into notions of iq. I think it's just some people have this prefrontal cortex that lets them see five different strategies simultaneously. Other people are like more plug and chug. And neither is better or worse is just different. And I have observed that for people who just kind of like, ratchet into the work and don't overthink it. What's this about? Is it a cult? What do they want? But there's this one instance, like, will I ever drink it? They don't think about it too much. They just do the steps and they're out.

A (185:29)

That is what AA asks. I mean, I want expressions. Is your best thinking got you here? In other words, keep it simple. Like, you don't have to, you know, do a philosophical Critique of the 12 steps. You just have to, don't drink, go to meetings. Don't drink, go to meetings. It's that, you know, and it is an action program, whereas. So it's different in that sense from a lot of psychotherapy styles, which are, you know, more intellectual and analytical, you know, and less focused on. You're actually going to do certain behaviors. And so if you dislike that, yeah, I can see why AA would bother you. That said, AA is just not one thing. So you can find, I'm sure, within a few miles of where we are sitting, you can find an AA meeting over a gas station with guys who are smoking tobacco and have jailhouse tattoos who are talking about the steps. And you will find meetings with professionals who will talk about angst and things like that. And you sort of find your own people. And I've known some very intellectual people, like professors, who go to an AA meeting with other people like that, and they're still working the steps and all that, but they are also. They're going to talk about Kierkegaard. And again, AA is like, fine, you talk about Kierkegaard. Just remember, don't drink, go to meetings, talk about whatever you want. And you need to find your peeps. And that's also why when people are thinking of going, I say, think of this like dating. You wouldn't go in one day, say, I didn't like that person. I guess I'm going to be alone the rest of my life. You go on a group of dates, right? So pick some different meetings at different times of day and different places, and they will be different. And then go back to the one that felt like home.

B (187:16)

Speaking of carrots, there's no wisdom like the kind of wisdom you can get from a really good share from someone at an AA meeting that you thought when they stood up and started their share, that you had nothing in common with this person. You, you are from two different universes, and inevitably there's some kernel of truth for you or something that you disagree with, and therefore you have insight. It's a spectacular thing, really.

A (187:43)

Yeah. And they were very conscious about that. If you read, it's called the Big Book, actually just aclog, synonymous. But it was called the Big Book because it was printed on cheap paper. So it was sort of fat, pulpy. This was back in the depression. It says flat out, this book is mostly stories. And we tell stories in the hopes that something in them will catch you and say, gosh, that life is like mine, and look where he or she is. Boy, I wish I were there. Well, they're kind of like me and they got to that good spot. Maybe I can get to that good spot. And so it's a conscious and very, I think, clever organizational strategy to tell people you know there's a place for you here. There's people like you here.

B (188:24)

I want to ask you about death.

A (188:26)

Okay.

B (188:29)

You worked in hospice.

A (188:32)

Great experience.

B (188:33)

As Americans, we're not comfortable talking about death. It evokes sadness, fear. But I think there's a lot to learn about it from hearing about someone who's been close to it a lot. And one can't live very long without losing someone. And we're all gonna go eventually. And that's, you know, hard truth. But why did you go into hospice? And then what did you learn about in hospice that has informed your sense of life and death?

A (189:09)

Yeah, so I loved being a hospice counselor. I did it for about 10 years. And there's so many beautiful things about it. First off, when I tell people, they go like, oh, God, that must be really depressing. Hospice staff were the most upbeat people I've ever worked with. Optimistic, compassionate, seeing everything. And in a way, I could sort of understand it because it's accepted. The person's going to die. Like, so what's the worst that could happen? Right? You don't think, like, oh, if I say the wrong thing, maybe in our session, it'll take an extra three months to develop more trust. Like, they're not going to be alive that long. We've accepted the worst, right? And so then we can just do well and help this person have a good death and help their family have a good death and work through their grief experience. And so they're just very upbeat. And so I never found it depressing at all. I did it partly because I'd shifted to doing more research, and I just missed taking care of patients. And I thought I wanted to obvious thing have been, well, why didn't I just do more addiction? I thought I'd just do something different. And the other part was I was scared of death. And I don't like being afraid. I'm a counterphobic person. I am not brave, but I'm afraid of being afraid. So I do things that look brave. So when I. And I know about phobia, like, the most basic thing is exposure, you know, reduces fear and anxiety. Running away from things makes them scarier. So I thought, like, all right, I'm scared. I'm scared of death. So how do I solve that problem? I'm going to spend as much time around death as I can. And it's a very intimate experience. You're in people's homes. It's not like when they're sitting in your office, but people's bedroom could have, like, what Is that. Well, that's my. I was a high school baseball player. We won the Nationals. Or. What's that? That's my wedding picture. That's my wife and I, 40 years ago. It is very intimate and sweet, And being the last friend somebody ever makes is an incredible honor. And I always felt that when I had to say goodbye, I had been honored by them in that way, the last friend they made. So I just found it profoundly moving experience, and it took away that fear. And then I was able to help other people get free of that fear, because when you've been around it for a while and then the family comes in and they're scared, or maybe sometimes doctors are scared of death. You can be the person who says, this is what's going on. This is what your mom, your dad, your uncle is going through. Here's what's going to happen, likely. Here's how long he's likely to live. Here's what we're doing for him. And then that helps them, because you are radiating that acceptance that they need to come to, which is hard. So I'm just so glad I did that. And I really would recommend that to anybody who wants to give back to community, but also just come to a place of peace with dying. The way to do that is to be with the dying, not to run from them.

B (192:32)

You got me, man. Maybe it's because we both know. Nolan, I think I just got. I was just feeling your feelings. Death is the way you describe it, as heavy, and you wove some lightness in there, which clearly. I'm not a hospice worker. I don't have that relationship to death. But thank you for sharing that. I think it is a universal experience. And being in there with people, alongside them, clearly something that I think many people, young and old, run from. It's like, yes, yeah, there's something there.

A (193:16)

And we can in this society. You know, I've been. I've done work in developing countries. You can't not see death. People die on the street, literally. And so there is less, oddly enough, there is more death and less fear than there is in our advanced technological society, where death is hidden and denied. So Americans, I find, are much more terrified of it than people I met in Iraq, for example. So that's why you really have to make an effort, because to get past those norms and those structures, if you want to be in companionate connection to people who are dying.

B (193:58)

I didn't anticipate asking what I'm about to ask, but it's been on my mind A very long time. And it's directly related to the two major topics we've covered, which are addiction and death. I've heard it said by a gambling addict that all addiction is gambling of some sort. You know, am I going to get trouble this time? Am I going to get fired this time? And I've thought a lot about addiction, and I've wondered if all addiction is an attempt to escape our fear of death. And this is not an attempt to get philosophical or deeply psychological. But, I mean, it's a weird thing. We don't know what other species think, but it's a weird thing that the portions of our brain that let us think into the future and plan and build technologies, and that made us the curators of the earth and not like the house cats or the elephants or something, can logically know that we're going to die someday. And if we really drop into that feeling, for most people, it is scary. It's really scary and really sad. And I think if any of us dropped really deeply into that and we've created any sort of connection to anything or anyone, it's deeply terrifying. And one thing I can say about addiction is that the states of being high, whatever the thing is for that person, they have a timelessness to them. You're out of the real world, where you're operating in the real world as if you had superpowers. I mean, in one's mind. And so I wonder whether or not the fear of death is something that addicts in particular are running from. And that raises the question, is embracing death as a very real thing overcoming that fear, the counterphobia? Do you think that perhaps could be used to help treat addiction or avoid it?

A (196:00)

Wow, that's a really interesting idea. I mean, I think very broadly speaking, a lot of heavy substance use is some desire for oblivion, to get away from unpleasant truths. And I think one of those is death and suffering. But I think it's broader than that. So it could be, I just can't be in this PTSD anymore, or I can't. You know, I was sexually abused as a child, and I just need to stamp out those visions and those memories for an hour, you know, and step outside them. My marriage has disintegrated, and I'm miserable, and my spouse and I hate each other. And this is the one moment where I am above that or unconcerned about that. Oftentimes there's something awful and frightening or humiliating or painful that this is the escape from. And they do provide that, at least in the Short term, the high term costs are hard, but in the short, short term, everything could be falling down around you. And if you're high on a stimulant, you can still feel euphoria, at least for that brief moment. And what can be tough about recovery is when you stop using, those things are not gone. You're still going to die. If your marriage is bad, your marriage is bad. If you were abused, you were still abused. And that is enough to. To persuade some people never to stop. Because it's a lot harder to actually deal with those things head on than avoiding them through intoxication.

B (197:53)

Thank you so much for this discussion. You shed so much light on substances, routes to sobriety, stages of addiction. Very interesting work on the GLPS 12 step. We'll provide links to all these resources and papers, if you're willing. Before we walked in here, I solicited X of all places for questions about addiction.

A (198:22)

Oh, sure.

B (198:22)

So thanks to you, most of the questions that were asked are already answered, material covered before. But there were three that I think are worth touching in on that weren't. And the first one is, are men getting addicted to things more than women or are they just showing up for help more often?

A (198:43)

Men are larger consumers of addictive substances in every culture on earth and are overrepresented in all the major addictions. Opioids probably four men to every one woman. Alcohol probably about 60, 40. It used to be higher, but women have been drinking more. The one thing you see in clinics that is close, the one is prescription medication that those are a little closer to 50, 50, but otherwise it's predominantly male.

B (199:15)

Why the relationship between addiction and lying? And not just lying about the addiction. Anna Lembke, our colleague, has talked about this before. Is there overlapping circuitry there?

A (199:25)

No, I don't think so. I think it's just you end up in these situations that are possible to cover over without lying. So you know where you know you were supposed to. Dad, you were supposed to pick me up after school. Where were you? I was drunk. Right. But I don't want to say that. So I say, oh, the car. I had car trouble, couldn't do it. Or the boss. What happened to the money for the. Yeah, it was an unexpected tax bill because I'm not going to say I stole it. And so I think that is why. The other thing, of course, is sometimes we make addicted people lie. I always point this out to residents that if you watch how doctors sometimes ask people about their substance use, it's absolutely clear the correct answer If I say you don't drink, do you? Or you don't use drugs, do you? Or some look. And so. And when you're addicted, you get very good at reading people. Like, what is this person going to say if I tell them that I use methamphetamine? And sometimes they lie, not because they want to, but because they know they'll get a negative reaction from the person.

B (200:28)

Asking the other question was about relapse. Is it the case that relapse can occur just as easily when things are going well as opposed to when they're going poorly? What do you see in your clinic?

A (200:40)

Yeah, I mean, people relapse in both ways. I mean, it's a friend of mine in college, I remember his dad, after years and years of drinking, got sober and just miraculously got an extremely high paying, respected job despite incredibly erratic work history, and immediately relapsed, went out and drove the wrong way on a highway and killed himself. And just think like, how could you know everything was going right? But you see that a lot. It's sort of like, I got money in my pocket, I'm happy, I know I'm okay now, the problem's behind me. And so I'm going to do what I always did and then be shocked that I got the same result I always did. You see that? Broadly speaking, though, relapse is most likely in times of stress, whether that's transitory stress like spat with the spouse or with the boss, or I'm just really exhausted, didn't sleep well, a couple nights in a row, that kind of thing. Or something bigger like maybe my kid's addicted also and I'm dealing with that and that makes me more likely to relapse.

B (201:51)

Last question is from me, I'm just curious. You're a dad of two college aged boys. What advice did you give them or do you give them about addiction? Not assuming that they're particularly prone, but just they're in life and to be in life now means that you're prone to addiction, period.

A (202:11)

I can hear them rolling their eyes even from Southern California because they, they said like, oh, another talk about addiction. So I talk to them a lot about fentanyl because I've known so many families where kids like them say like nice family, middle class kid have died from fentanyl that they took in the form that it looked like something else. And this happened in college campuses, happening in high school, you know, these printed pills that look exactly like an Ativan or an Adderall. I think I'm going to try that. And you don't realize you're taking fentanyl and you die. So I always warned them about that, like never to take anything. You can't know what it is. If you didn't personally acquire it, you can't know what it is. And then the other thing I told them is the point that you can make these decisions yourself, but the only thing I can tell you is you will never get addicted to something that you choose never to, to use. That is your maximal point of control. And what happens after that point, what you started using is something I can't know. More importantly, something you can't know.

B (203:22)

Thank you. Well, Dr. Keith Humphries, thank you so much for coming here today.

A (203:29)

Thank you. I really enjoyed the discussion.

B (203:31)

I mean, it's obvious to everyone that you have immense knowledge about this area. And the fact that you have not just knowledge, but that you're a clinician and you help people get into and through recovery and stay sober in all these different dimensions is itself amazing. But I think I'm certain I'm not alone in saying that what's so awesome about the work you do and you is that it? And that became evident today is that you combine incredible expertise with incredible compassion for people. That's. You didn't have to say it. It's just in every aspect of, of what you shared. And, you know, it's an honor to have you here. It's an honor to be colleagues and to meet you finally. But mostly I'm just grateful that we were able to create an environment where you could share your knowledge and your compassion. And I'm certain that it's gonna help a lot of people understand themselves, understand people around them and hopefully take action if they need to. So thank you so much.

A (204:27)

Thank you, Andrew. It was a real pleasure to be on your show.

B (204:30)

Thank you for joining me today for my discussion with Dr. Keith Humphries to learn more about his work, please see the links in the show. Note capt. If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero cost way to support us. In addition, please follow the podcast by clicking the follow button on both Spotify and Apple and on both Spotify and Apple. You can leave us up to a five star review and you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. For those of you that haven't heard, I have a new book coming out. It's my very first book. It's entitled An Operating Manual for the Human Body. This is a book that I've been working on for more than five years and that's based on more than 30 years of research and experience and it covers protocols for everything from sleep to exercise to stress control, protocols related to focus and motivation, and of course I provide the scientific substantiation for the protocols that are included. The book is now available by pre sale@protographsbook.com there you can find links to various vendors. You can pick the one that you like best. Again, the book is called Protocols An Operating Manual for the Human Body. And if you're not already following me on social media, I am Huberman Lab on all social media platforms. Platforms. So that's Instagram X threads, Facebook and LinkedIn. And on all those platforms I discuss science and science related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the information on the Huberman Lab podcast. Again, it's Huberman Lab on all social media platforms. And if you haven't already subscribed to our Neural Network Newsletter the Neural Network Newsletter is a zero cost monthly newsletter that includes podcast summaries as well as what we call protocols calls in the form of one to three page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You Simply go to hubermanlab.com Go to the menu tab in the top right corner, scroll down to newsletter and enter your email. And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for Today's discussion with Dr. Keith Humphries. And last but certainly not least, thank you for your interest in science.