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Peter Attia MDPeter Attia MD

321 – Dopamine and addiction: navigating pleasure, pain, and the path to recovery

View show notes here: https://bit.ly/4eZjTB7 Become a member to receive exclusive content: https://peterattiamd.com/subscribe/ Sign up to receive Peter's email newsletter: https://peterattiamd.com/newsletter/ Anna Lembke is the Chief of the Stanford Addiction Medicine Dual Diagnosis Clinic and author of Dopamine Nation: Finding Balance in the Age of Indulgence. In this episode, Anna dives deep into the biochemistry and neurobiology of addiction, exploring the critical role of dopamine and the prefrontal cortex. She shares her framework for diagnosing and treating addiction, providing real-world examples involving alcohol, gambling, cannabis, social media, and more. Anna outlines the risk factors for addiction, including inherited and nurture-based risks, explores the rise of addictions in younger generations, and discusses effective ways to address these issues with children. Additionally, she touches on healthy coping strategies, the evolution of the “marshmallow experiment,” and provides insights into GLP-1 agonists as a possible tool for addiction treatment. Finally, she reflects on the value of 12-step programs and how she navigates the emotional challenges of her work. We discuss: 0:00:00 - Intro 0:01:11 - The role of dopamine and the prefrontal cortex in addiction 0:12:18 - The clinical definition of addiction and the behavioral criteria for diagnosing it 0:16:44 - Assessing alcohol use: patterns, risks, and addiction diagnosis 0:21:38 - Applying the addiction diagnosis framework using gambling as an example 0:25:48 - Exploring addiction variability: how nature, nurture, and access shape individual vulnerability and drug of choice 0:43:33 - How abstinence from addictive behaviors can help reset the brain’s reward system and improve mental health 0:54:29 - Safely abstaining from addiction substances, drugs needing medical supervision, and other key considerations 1:02:40 - Transitioning from abstinence to long-term recovery: tools and considerations 1:13:18 - Exploring behavioral addictions like sex addiction, and the gender differences in addiction patterns 1:19:13 - Factors contributing to the increasing levels of addiction across the world 1:30:21 - How online pornography can affect young boys' developing brains and lead to addictive behaviors, and strategies for parents to address this issue 1:43:05 - The link between social media use and declines in mental health, potential solutions, and protective measures 1:53:32 - How exercise affects brain chemistry, the role of dopamine and endorphins, and how exercise can become addictive 1:57:04 - Cold-water immersion for mood regulation, and other healthy coping strategies 2:04:47 - The “marshmallow experiment”: how broken promises affect behavior and trustworthy environments help children develop self-control 2:09:30 - Can GLP-1 agonists be useful in treating addiction? 2:17:57 - The benefits of 12-step programs 2:24:14 - Why understanding a patient’s story is essential for meaningful psychiatric care -------- About: The Peter Attia Drive is a deep-dive podcast focusing on maximizing longevity, and all that goes into that from physical to cognitive to emotional health. With over 90 million episodes downloaded, it features topics including exercise, nutritional biochemistry, cardiovascular disease, Alzheimer’s disease, cancer, mental health, and much more. Peter Attia is the founder of Early Medical, a medical practice that applies the principles of Medicine 3.0 to patients with the goal of lengthening their lifespan and simultaneously improving their healthspan. Learn more: https://peterattiamd.com Connect with Peter on: Facebook: http://bit.ly/PeterAttiaMDFB Twitter: http://bit.ly/PeterAttiaMDTW Instagram: http://bit.ly/PeterAttiaMDIG Subscribe to The Drive: Apple Podcast: http://bit.ly/TheDriveApplePodcasts Overcast: http://bit.ly/TheDriveOvercast Spotify: http://bit.ly/TheDriveSpotify Google Podcasts: http://bit.ly/TheDriveGoogle Disclaimer: This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. I take conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit my website where I keep an up-to-date and active list of such companies. For a full list of our registered and unregistered trademarks, trade names, and service marks, please review our Terms of Use: https://peterattiamd.com/terms-of-use/

Anna LembkeguestPeter Attiahost
Oct 14, 20242h 32mWatch on YouTube ↗

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EVERY SPOKEN WORD

  1. 0:00 – 1:11

    Intro

    1. AL

      The, the interesting thing for me about treating addiction is that it is a biopsychosocial disease, right? There's a biological component, psychological, and a deeply embedded social and, and cultural component, such that, for example, workaholism is really celebrated in our culture, and we have many, many workaholics, and you and I might even be in that category. And yet there are so many social rewards, monetary, uh, you know, social validation, um, you know, you name it, um, that, that this compulsive engagement in the work that we do, um, we may not ever identify as problematic unless we begin to look at s- more subtle manifestations or harms, like opportunity costs. Like because I'm spending all this time working, I really don't know my children, right? Or because I'm spending all this, this time working, I'm not cultivating friendships or not investing in, um, you know, my, my partner or in my health or, or whatever it may be.

    2. PA

      [upbeat music] Hey everyone, welcome to The Drive podcast. I'm your host, Peter Attia.

  2. 1:11 – 12:18

    The role of dopamine and the prefrontal cortex in addiction

    1. PA

      Anna, thank you so much for making time to sit down with me today. I've been looking forward to this for, for quite a while, months actually. Um, so thank you for, uh, for humoring me and talking about a subject that you, I know, talk about a lot.

    2. AL

      Well, thank you for inviting me. I'm delighted to be here. Um, I actually hadn't realized that you were a fellow Stanford grad, so that was fun to learn.

    3. PA

      I know. I feel like we were passing each other briefly, right? Because I think you graduated two years before I started, but then you were in your residency while I was in med school, so the probability that we ran into each other in the cafeteria or, uh, going through the hall is, is probably pretty high.

    4. AL

      Yes, it's perfectly possible that I scutted you out as a medical student and made you go do things that, you know, I didn't want to do. [laughs]

    5. PA

      [laughs] I, I always tell people, like, I have the fondest memories of medical school, but there are certain things that I still remember, and I can't believe they were the case. And one of them is that for a school as, as, uh, as fancy and prestigious, that do you recall we didn't have a bathroom in the library?

    6. AL

      Ah, I didn't-

    7. PA

      Do you remember that fact?

    8. AL

      Yes. I, I, as you, uh-- It could be I did not spend as much time in the library as I should have.

    9. PA

      [laughs]

    10. AL

      Um, I do remember that we had our anatomy classes in trailers.

    11. PA

      In trailers, yep.

    12. AL

      Right.

    13. PA

      I remember that. Yeah.

    14. AL

      Yes.

    15. PA

      Um, well, we ended up studying mostly in the business school library, which was really fancy-

    16. AL

      Yeah

    17. PA

      ... had bathrooms, um, and didn't have business students in it because-

    18. AL

      Right

    19. PA

      ... of reasons that are probably obvious. So anyway, um, [laughs] anyway, great to sit down with you. So there, there's actually a lot I wanna, I wanna talk about with you. Some of it is, uh, the substance of what you've written about in Dopamine Nation, uh, and, and I'd love to probably start there, but there's so much other, you know, material I'd love to cover with you if, if our time permits. But, um, obviously one of the things that anyone who's familiar with you, um, thinks about is this role of dopamine and understanding addiction. This clearly plays into a big part of your clinical practice as a psychiatrist. Um, but I also realize that terms get thrown around quite loosely, and sometimes it can just be helpful for people to understand, uh, a little bit of, of what we describe as, as the semantics. So I, I'd like to actually start with an understanding maybe of some of the biochemistry and the neurobiology of dopamine, and then I wanna also talk about what an addiction really is. Um, but this word dopamine is, is something everyone has heard of. Um, but tell us a little bit about the molecule, how it works, um, and maybe even some of what the supporting cast of other neurotransmitters look like that factor into these pathways that, that obviously play an important role in our evolution and our, our existence.

    20. AL

      Yeah. Great place to start. Thank you for setting the stage. So dopamine is a neurotransmitter, so it's a chemical that we make in our brains. Neurotransmitters are the chemicals that allow for fine-tune modulation of the neural circuits that make us who we are. You might think of the brain as a collection of wires. Uh, those wires are neurons. They send electrical impulses, one to the other, but the neurons don't actually touch end to end. There's a little gap between them called the synapse, and that gap is bridged by molecules called neurotransmitters. There are many different neurotransmitters in the brain. Um, they have many different functions, but dopamine has become, uh, kind of the common currency for measuring pleasure, reward, and motivation. It's not the only neurotransmitter in- involved in that process, obviously, uh, but it is the final common pathway for all reinforcing substances and behaviors. So whether the substance is primarily, um, you know, modulating our serotonergic system or norepinephrine or the nicotinic system or the endogenous opioid system or the endogenous cannabinoid system, the final common pathway for all of those chemical cascades is to release dopamine in a dedicated part of the brain called the reward circuitry, which consists of the prefrontal cortex, that's that large gray matter area right behind our foreheads, and then these deeper limbic or emotion brain structures like the nucleus accumbens and the ventral tegmental area. We're always releasing dopamine at a baseline tonic level, uh, but when we do something that's pleasurable or reinforcing or that our brains consider salient or important for survival, so in, in some cases it might even be an aversive stimulus, um, then temporarily we will increase dopamine firing above baseline. That generally feels good to us, which is how we tell our brains, "Oh, this is important. I should approach, explore, and consider doing this again." So broadly speaking, that, that's dopamine's function. It's not its only function, by the way. So dopamine is also really important for movement. As you know, Parkinson's disease, which is a movement disorder, is characterized by a decrease or a depletion of dopamine in a different part of the brain called the substantia nigra. Um, and one of the ways that we treat Parkinson's is to actually give people L-DOPA, which is a dopamine precursor. Why do we give them L-DOPA and not dopamine? Because dopamine itself actually can't cross the blood-brain barrier, so we give them a precursor that crosses the blood-brain barrier and then, um, you know, binds to dopamine receptors in the substantia nigra, allowing for more fluid movements in people with Parkinson's. Unfortunately, uh, L-DOPA, uh, transformed to dopamine also binds dopamine receptors in the reward pathway, which is why about a quarter of folks with Parkinson's who get treated with L-DOPA end up with, uh, addictive disorders that are usually, uh, reversible when you stop the L-DOPA and tend to be, um, dose-dependent, so the more L-DOPA, the more likely the sex addiction, shopping addiction, or whatever the compulsive behavior.

    21. PA

      Okay, a lot there, um, and many questions, but one of them is the role of the prefrontal cortex. Now, again, I think people listening to us probably, um, have heard about the prefrontal cortex. Uh, it comes up a lot when we talk about dementia. It talks-- It comes up a lot when we talk about higher order cognitive function, uh, judgment centers. Um, but it is also something that I believe, and I could be wrong on this, but I believe this is a part of the brain that is more developed in our species than in others. Um, so I, I guess a, a question then would be around the, um, addictive potential of our species versus others. Are we more susceptible to what we're about to talk about as addiction, um, with a larger prefrontal cortex, or is it not as simple as just the anatomic size of this part of the brain?

    22. AL

      So, um, so I guess to back up for a second, the, the prefrontal cortex has many roles, but when we think about its role in, um, addiction or other appetitive disorders, it actually has a stop function. So if you think about-

    23. PA

      Hmm

    24. AL

      ... um, you know, if you, if you analogize to a car, the prefrontal cortex, um, acts like the brakes on the car. It allows for delayed gratification. This is where we have the control centers. Uh, it allows for appreciating future consequences. Uh, it's-- it lights up when we're engaged in autobiographical narrative, and of course, narrative is part of the ways that we, um, actually, uh, create metacognitive awareness to inform future decisions. So having a, a very robust prefrontal cortex is potentially protective against addiction.

    25. PA

      Hmm.

    26. AL

      Um, people who have cognitive or attentional disorders, who are thought to have a disorder of the prefrontal cortex, for example, attention deficit disorder, are at higher risk to develop addictive disorders. So essentially, again, if you think of this as like the car analogy, the prefrontal cortex is the brakes, the nucleus accumbens is the accelerator. The nucleus accumbens is deep, you know, deep in the brain, is rich in dopamine-releasing neurons, and that likes-- acts like the accelerator on the car. So addiction is a problem either with too little on the brakes, too much on the accelerator, or some combination thereof. In terms of whether or not, um, humans are, are more likely to get addicted than animals, I would say no. Um, what, what's remarkable, um, about this reward circuitry is how incredibly conserved it is over millions of years of evolution and across species. So, y- you know, neuroscientists used to talk about, uh, the lizard brain or the triune brain. They're, they're not typically using that, that phraseology so much anymore, but what they were getting at was that if you look at the nucleus accumbens ventral tegmental area, um, it, it's amazingly unchanged across species over millions of years of evolution. It's really, you know, our reflexive, uh, approaching pleasure and avoid- avoiding pain is, is what has kept us alive, you know, for, for so, uh, so, so many, many generations on the planet. Um, and so it's a very basic primordial structure that all living organisms or, or, you know, more advan-- well, not even ad- advanced, even primitive organisms have. Uh, you know, even the most primitive nematode or worm will release dopamine in response to food in its environment, which then dopamine allows it to locomote toward food. It's probably no coincidence that the same neurotransmitter involved in movement is also involved in pleasure, reward, and motivation because prior to about five hundred years ago, if you wanted to get a reward, you had to work for it. That's no longer true, which is one of the reasons our brains are, um, so confused today. So I would say, you know, to, again, to just sort of try to answer your question, um, you could almost make the opposite argument that because we have these large frontal lobes that can sort of reason and appreciate future consequences, human beings might be even more capable of getting out of the cycle of addiction than, um, other organisms. I mean, it is miraculous that even people deep in the most severe addiction can find somewhere within themselves the capacity to stop using. I mean, this is-- it's really, really remarkable. Um, and, and, you know, I'm-- it seems to me almost a miracle in my clinical work when I get people who have been in severe addictions for decades who somehow find it within themselves, either through some logical reasoning or some spiritual surrender or some combination, to actually get into recovery.

    27. PA

      There's so

  3. 12:18 – 16:44

    The clinical definition of addiction and the behavioral criteria for diagnosing it

    1. PA

      much I want to talk about on that front, um, but I, I think I'll, I'll still try to, um, get some of the more basic, uh, stuff out of the way just to make sure when we get there, it-- we have a, we have the foundation to understand some of the incredible stories you've shared. So, um, l- let's take a moment to now maybe technically define an addiction. Uh, I'm sure everybody once in a while has said, "Man, I'm addicted to Netflix," and, "I'm addicted to chocolate," and, "I'm addicted to this." But how does one truly define an addiction in a clinical setting?

    2. AL

      Yeah, so when I use the term addiction, I, I'm referring to a form of psychopathology, not the more common colloquial casual use of, you know, I'm addicted to Netflix. Although, you know, you could argue that we actually are addicted net- to Netflix, um, and we'll probably get there. So the diagnosis of addiction is based on what we call phenomenology. These are patterns of behavior that repeat themselves across individuals with unique temperaments, demographics, time periods, geographic locations. Um, there is no brain scan or blood test to diagnose addiction, although we know that addiction is characterized by distinct brain changes. We're just not at a state of the art where we can diagnose it based on that. So it's still based on patterns of behavior that can broadly be summarized as the four C's plus tolerance and withdrawal. So the four C's are out of control use, compulsive use, cravings, and continued use despite consequences. Now, as you can imagine, that phenomenology is going to be a judgment call, right? And it's going to be based on both that individual's subjective endorsement of having those kinds of issues, plus the observation of other people around them. Which is to say, if you went to 10 different psychiatrists, you might get 10 different diagnoses. And that is true for all mental health disorders. So we, we don't have any brain scans or blood tests to diagnose any mental health disorder. The entire DSM, or Diagnostic and Statistical Manual of Mental Disorders, which is our kind of codification of different buckets that we put people in for different forms of psychopathology, is completely based on phenomenology. Um, so you have the four C's, and then you have tolerance and withdrawal. So those are very clear evidence of physiologic changes. Psychological changes are also physiologic changes, but here we're talking about more obvious manifestations of it being, um, say, a physical, chemical body reaction. Tolerance is the phenomenon of finding that the drug stops working over time, um, and that we need more and more to get the same effect or more, more potent forms. And, and, and tolerance is overcome by using more, using more often, or overcoming tolerance by changing the delivery mechanism instead of, you know, orally ingesting, maybe smoking or injecting, or, um, overcoming tolerance by changing slightly the chemical combination or moiety or combining drugs together so that the brain sees something that's similar but slightly novel. And then in addition to tolerance, there's the phenomenon of withdrawal, which is to say, when I cut back, um, or stop using, my, my body reacts in a very predictable fashion, which is most often the opposite of whatever the intoxicant causes. So if I'm taking a stimulant like cocaine or meth or nicotine or caffeine and I try to stop using, my withdrawal phenomenon will, will feel like sedation, lethargy, inattention. If I'm using a sedative, uh, like alcohol, uh, then my withdrawal phenomenon will be restlessness, uh, um, jitteriness, uh, maybe even seizures, maybe even life-threatening seizures in the case of alcohol and benzodiazepines. And also keep in mind that the universal symptoms of withdrawal from any addictive substance are anxiety, irritability, insomnia, dysphoria, and craving. And I always like to mention that because I'll have, like, cannabis users or alcohol users come in and say, "Well, you know, I don't have any withdrawal, so therefore I'm not addicted." Well, did you feel anxious? Did you feel restless?

    3. PA

      [laughs]

    4. AL

      Were you unable to sleep? Uh, were you in craving mind? Uh, because those are all the actions, so to speak, that our brain takes to get us to try to use again.

  4. 16:44 – 21:38

    Assessing alcohol use: patterns, risks, and addiction diagnosis

    1. PA

      So I wanna use just two examples and walk, you know, viewers and listeners through them. So, um, let's start with a chemical one, and let's just pick alcohol because of its ubiquity. So let's go s- through how a person might be evaluating the four C's and tolerance withdrawal. So I come to you and I say, um, I, you know, "I'm here because people around me think I drink too much." What, what are sort of the questions we go through to probe that?

    2. AL

      Yeah, great. So we've developed a kind of framework that, um, relies on gathering data in a way that's not threatening and sort of factually based, starting simply with data. So we would ask people, "What do you drink? How much and how often?" Um, when we try to quantify that specifically with alcohol, we, we bring it down to what we call the standard drink. A standard drink is one 12-ounce bottle of beer, a five-ounce glass of wine, or one to one and a half ounces of hard liquor. So that's one standard drink.

    3. PA

      Yep.

    4. AL

      We use something called the timeline follow-back method because it tends to be more reliable than a sort of general gestalt where we say, "Okay, how much did you drink yesterday? How much did you drink the day before that and the day before that and the day before that?" Until we get seven days, we add it all up, and then the person goes, "Oh, wow, I'm drinking 21 standard drinks in a week." That's very useful information for me as a healthcare provider, but also for that individual themselves because when we're chasing dopamine, we have a funny way of not being very good self-observers and losing track. So we simply gather the data, then we ask people to tell us why they drink. What, what is it? What is the positive thing that they get out of it? As well as trying to hint a little bit at tolerance, um, which is to say, is it still working for them the way that it used to? Um, I should also mention when we're gathering data, we're also looking for binge patterns. So some people can go a long time without drinking, but then they'll have, let's say for an adult male, a binge is considered five or more standard drinks in a sitting. A sitting is a single day. Um, for w- for an adult female, it's four or more standard drinks, uh, in a sitting, and when we find that pattern, that's also very concerning. Let me just say that the really nice thing about alcohol is that these questions are based on epidemiologic studies showing that for an adult male who drinks more than 14 standard drinks per week or more than four on any given day, or an adult female who drinks more than seven standard drinks per week or more than three on any given day, there's a much higher risk not only of having an alcohol addiction, but also developing al- all cause morbidity and mortality, so pancreatitis, heart disease, um, you know, cancer, injury, accident, and death. So it's very nice to have that data to back that up. But anyway, we, we start there, is just, uh, uh, to say that. Um, and then we, then we probe, you know, and why do people drink? People drink for all kinds of reasons, but broadly speaking, they drink to have fun or to solve a problem. That problem can be anything from social anxiety to loneliness to boredom and everything in between. So we really explore that with patients. And then next we, um, you know, we, we ask about problems. Like, are you having, you know, what are the problems that you have noticed? Interpersonal problems, work problems, health problems, the simple problem of tolerance, that it's not working for you the way that it used to. Um, are you having mental health problems, depression, anxiety, insomnia, inattention? Um, and we kind of go through those, and then based on that, um, you know, we begin to see a picture that nudges us toward thinking that, yes, this person has what we call an alcohol use disorder. Um, and again, you can see it's quite judgmental and contextual, right? Depending upon the culture. But one of the things that often happens is people will normalize their use by affiliating with other people who drink heavily. So they'll say, "Well, you know, you may think that's a lot, but my fraternity brother Joe drinks way more than I do." It's like, well, yes, but in, in the general population, you're in the one percentile, um, in terms of even just the amounts that you drink. And we know that just based on amounts, you're at higher risk for all cause morbidity and mortality, even separate from our diagnosing an addictive disorder.

    5. PA

      Okay, so what about-- And, and you also already addressed the withdrawal, and of course, um, I, I'm sure many people are quite familiar with the medical complexity of alcohol withdrawal and how, um, things like DTs can become an actual physiologic risk to mortality if a patient isn't withdrawn safely from alcohol using things like benzodiazepines. Um, and as, as discussed earlier, of course, tolerance is, is clear with, with alcohol. Um,

  5. 21:38 – 25:48

    Applying the addiction diagnosis framework using gambling as an example

    1. PA

      what if we talk about something like gambling? How does the, the framework work for something like that? In other words, for a person to have a gambling addiction, is, is the sine qua non of that, that they basically must be financially creating chaos in their lives? Or as long as they're, you know, you know, if a person loses a million dollars a year in gambling, but they make 10X that, and it's not actually impacting their life in other ways, is, you know, how do you sort of ferret out whether or not this is, this is pathologic?

    2. AL

      Yeah. Great question. And I would say when you think about the four, four Cs, control, compulsion, craving, and consequences, plus tolerance and withdrawal, um, none of those is a sine qua non. And in fact, you can have no tolerance and no withdrawal and still meet criteria for an addiction. Um, just a little footnote there.

    3. PA

      Mm.

    4. AL

      People can actually have physical withdrawal from behavioral addictions like gambling, where they have headache, nausea, vomiting-

    5. PA

      Mm

    6. AL

      ... insomnia. But for, for gambling disorder, um, theoretically, you know, you could have somebody who was gambling a lot and had, you know, no control issues, meaning that they could set a certain amount that they were gonna spend, and they, and even if that was a very large amount, they adhered to that amount. Um, when they decided to cut back or abstain for a period of time, they were able to do that. Um, they could have no craving, no reported cravings, although, again, we're not the best judges often of ourselves when it comes to this disease process. They could have, as you highlight, no consequences because they're making money, although generally, you know, with pathological gambling, that almost never works out that way. The house wins. Um, so then you have to get into the more subtle factors of compulsive use. So what does it mean, compulsive use? It means a lot of mental real estate occupied with thinking about using, getting the drug-

    7. PA

      Mm-hmm

    8. AL

      ... maybe covering up drug use because other people don't approve. Um, finding that other things are less salient, so a kind of narrowing of our focus on that particular activity, a loss of joy in other things that we used to find pleasurable. Um, so this kind of, and a level of automaticity, right? Like I- I'm just sort of immersed in this. And then I think a kind of a, a qualitative judgment about the attachment Which is to say feeling like if I don't have this activity as an outlet, I can't function, right? Even on just a mental level, even if objectively, you know, everything looks great on paper in terms of my life. Like I'm so deeply immersed in this kind of addiction vortex that I'm thinking about it all the time. I'm organizing my life around it. I don't feel like there are other things that I can do or take joy in. When I try to decachect or de-- you know, attach myse-- uh, remove some attachment, I, I get anxious, I get irritable, I can't sleep. Um, and again, you know, these are-- the, the interesting thing for me about treating addiction is that it is a biopsychosocial disease, right? There's a biological component, psychological, and a deeply embedded social and, and cultural component such that, for example, workaholism is really celebrated in our culture, and we have many, many workaholics, and you and I might even be in that category. And yet there are so many social rewards, monetary, uh, you know, social validation, um, you know, you name it, um, that, that this compulsive engagement in the work that we do, um, we may not ever identify as problematic unless we begin to look at s- more subtle manifestations or harms like opportunity costs. Like because I'm spending all this time working, I really don't know my children, right? Or because I'm spending all this, this time working, I'm not cultivating friendships or not investing in, um, you know, my, my partner or in my health or, or whatever it may be.

    9. PA

      Well, that's--

  6. 25:48 – 43:33

    Exploring addiction variability: how nature, nurture, and access shape individual vulnerability and drug of choice

    1. PA

      a, a big part of what I wanted to, to chat about was, was actually this idea of why different individuals, uh, become addicted to very different stimuli-

    2. AL

      Yeah

    3. PA

      ... even if the final common pathway is comparable, right? So even if, um, you could put all of us into whatever it is we use, fMRI or whatever type of scan that we might use to, to pick up on, um, the areas of the brain that, that undergo excitation, uh, why is it that for one individual, alcohol becomes the thing, uh, whereas for another person, it becomes an opioid? And, and by the way, are there clusters where for certain people, chemicals really are the problem, whether it be, you know, opioids, alcohol, cocaine, and yet for others it's more behaviors? And I, and I'll share with you, um, just as an example of why this is a question that is on my mind so often. So I, I've shared this story publicly before, but, um, when I was actually in medical school, I suffered a really, really, uh, debilitating back injury and, um, uh, uh, to make a very long story short, uh, through, through some, some, some errors in the part of the medical system, uh, I ended up on a r- a really, really, uh, high-- uh, at the time, very high doses of, of, of oxycodone and OxyContin and, um, predictably went through the escalation of those doses until at one point I was up to a, a three hundred milligrams a day of OxyContin. So, um, I'm sure you can put that in the context of, of the patients that you see, uh, and I'm sure you've seen patients higher, but that's a, that's a pretty staggering dose. That's a dose that if you or I split it right now, we would be dead. Uh-

    4. AL

      Right

    5. PA

      ... so, so just for context to people. So, so after several, oh, I don't know, probably six months of being on such a, you know, again, enough oxy to kill a, a horse, um, I just decided I wanted off. Um, and I was-- it was a very strange wake up moment where I realized I wasn't even taking it because I was in pain anymore. I was taking it because I wanted to escape how depressed I was that I was debilitated. So I just decided to stop cold turkey. And I, at the time, was dating an anesthesiology resident, and she was like, "You are effing crazy. You're going to die. We need to put you on nortriptyline and ten other drugs to taper you off." And I said, "No, I'm doing this cold turkey," which I did, and I proceeded to spend the next two weeks in hell. Um, but this is the point of the story. It's not-- it's nothing that I said so far. The point of the story is I'm no more inclined to struggle with an opioid than any other person at-- for reasons I don't understand. In other words, after that experience, I was quite afraid of opioids, and I assumed I was addicted. But maybe ten years later when I had a really bad tooth condition and nothing was touching the pain, I finally succumbed and took Percocet. And then after two days when the tooth was addressed, I stopped taking the Percocet and there was no issue. And my came to conclu-- I, I ca- I concluded from that experience that this was not a willpower thing that allowed me to quit. This was just a, a luck thing. There's something physiologically about me that was not becoming addicted to that substance, um, and that's why I was able to stop cold turkey. In other words, there-- I, I wasn't morally superior to the opioid addict. I was lucky. Um, and my question is why? [chuckles] What explains this difference? Because there are clearly areas like work where I'm not so lucky, um, and, and, and where the addiction is indeed real and where the struggle is daily.

    6. AL

      Okay, so a lot there to unpack. Um, why don't we just start with your interpretation of your experience, which is, yes, I got physiologically dependent on opioids in medical school, but ultimately, I'm not a person who's going to be addicted to opioids. Um-

    7. PA

      Well, I thought I was, but it didn't appear to be the case based on subsequent use patterns.

    8. AL

      Right.

    9. PA

      Yes, yes.

    10. AL

      Right. You, you ultimately decided, you ultimately decided, "Oh, I, I'm actually-- this is not an inevitable problem for me." And but I recognize that especially given what you went through, that it could be an i- an inevitable problem for some- somebody else, right?

    11. PA

      Right. Yeah.

    12. AL

      Okay. So let's start with risk factors for addiction. Um, so risk factors for addiction can broadly be, um, placed into three separate buckets, which I call nature, nurture, and neighborhood. The inherited or inborn risk for addiction based on family and twin studies is about 50 to 60%. So this is, for example, based on studies showing that if you have a biological parent or grandparent addicted to alcohol, you are at increased risk of getting addicted to alcohol than the general population, even if raised outside of that alc- alcohol using home, right? So these are really nicely carefully done studies.

    13. PA

      So, so high heritability is determined by twin concordance basically?

    14. AL

      Yeah. A- and family studies, right?

    15. PA

      Okay.

    16. AL

      Looking back in family trees, looking at, um, kids who were adopted into non-alcohol using homes who developed alcohol use disorder at higher rates because they had a biological parent or grandparent. So th- th- that-- those are those studies. Um, and for a long time, you know, people have talked about the quote unquote "addictive personality." "Oh, I'm-- I have an addictive personality. Whatever I do, I take it to the extreme. I'm, I'm gonna get addicted." Um, you know, that's a kind of colloquial use, but it g- gets to the heart of this idea that yes, people come into the world with different vulnerability to this tendency to take to the extreme the pursuit of certain types of highly reinforcing substance behaviors once discovered in the environment, okay? Um, it's also probably true that we each have different what, what, what are called drugs of choice. So-

    17. PA

      Hmm

    18. AL

      ... even with people who are, you know, poly substance users, which by the way is more, more common than not today. People use a lot of different substances and behaviors. They'll still tell you, "But, you know, my pr- my preference is opioids," or, "The thing I really wanna do is smoke a cigarette," or, "Alcohol is my go-to." Um, and th- interestingly, there's very little science on the concept of drug of choice 'cause I, I looked pretty hard for that and I couldn't find very much. Um, but it is a really important one because what it means is that here we have the phenomenon of access intersecting with drug of choice to increase the risk for certain individuals. Let me explain what I mean. One of the-- So we've got the na- th- let me back up. So we've got the nature, right?

    19. PA

      Mm-hmm.

    20. AL

      The inherited risk. By the way, that probably goes along with co-occurring mental health disorders. People with mental health disorders are at increased risk of developing addictive disorders, and addiction is probably a complex polygenic phenomenon. Then we have risk factors based on nurture, so this is the way that we're raised, early childhood development, parents that model maladaptive addictive, uh, behaviors or that explicitly or implicitly condone substance use or other addictive behaviors. Those kids are more likely to develop addiction in adulthood, especially if there's trauma, if there's, uh, negative attachment. Um, whereas kids who are raised in a, in a home where patients are modeling healthy, uh, adaptive coping strategies, where they have a good attachment to their kids, where there's not sexual, physical, or emotional abuse, those kids are, um, protected, right? Or relatively protected. Nobody's completely protected. You can have the perfect childhood and still end up addicted. And then we have what I call neighborhood risk factors, and these get to the key of access. So one of the biggest risk factors for addiction is simple access to that drug. If you live in a neighborhood where drugs are sold on the street corner, you're more likely to try them and more likely to get addicted. If you go and get medical care at a place where people liberally prescribe opioids, benzodiazepines, stimulants, your brain will be exposed to those drugs, will change in response to those drugs, and you are at increased risk of getting addicted to those drugs. Um, now in your case, the risk of access, um, was ultimately what got you initially hooked, but probably other innate protective factors that you have allowed you to not end up, um, with a serious addiction, probably in, in terms of genetic protective elements, maybe had having to do with the way that you were raised. I don't know you, so it's hard for me to judge. But essentially, you know, that's kind of how, how we think about it.

    21. PA

      But what's interesting, and I guess this is the part that's most mo- most curious to me is I am cl-- I mean, if I'm being brutally honest and take a, an honest stock of my life, there are clearly things where I behave in very addictive ways today. So, uh, and, and let's just acknowledge that the neighborhood for those things is high, right? Like, I mean, online shopping. Like my wife describes me as an e-shopaholic.

    22. AL

      Mm-hmm.

    23. PA

      And she can tell my stress level by the number of Amazon packages that come to the door. So when I'm under low stress, we'll go a week without a package. When I'm under high stress, three packages a day. To be clear, it's not breaking the bank. I'm buying stupid, irrelevant trinkets, but it's this dumb little escape I have where, oh my God, I, I need a keychain. I wonder what kind of keychains they have on e-- Amazon. Da, da, da, da. Oh, look, I gotta-- You know? So it's-- And I am-- I fully acknowledge that there are real-- that, that is a true addiction. Now I'm fortunate in that the consequences of that addiction are minimal. But I'm, but I'm, but I, but I'd like to believe I'm at least wise to the fact that, um, that there's a, that there's just a, a general good luck that is permitting Amazon to be my pusher as opposed to someone selling illicit drugs. And th- a- and I wonder why. That, that's the thing. I wonder w- why because This, to me, speaks to, like, w- we're all addicts potentially.

    24. AL

      Right.

    25. PA

      Why are some people unlucky in that the addiction is, it turns out to either kill them or destroy the quality of their life and their relationships?

    26. AL

      Right. So l- l- let me, let me answer that in a, in a couple of different ways. First of all, thank you for sharing the online shopping addiction. A- as you know, in my book, Dopamine Nation, I talk about how I got addicted to romance novels. Now, granted it was a minor addiction, and I was able to, once I recognized it, um, you know, change those behaviors without having to get professional help. Um, which, again, brings us back to this concept of drug of choice and how it intersects with access. Because what's so challenging about the world today is that not only do we have more access to more potent forms of traditional drugs, including alcohol, but all the other drugs that have been around for millennia, but we also have brand-new drugs that didn't exist before, all of the online digital media, online shopping, pornography, the drugification of the romance novel, et cetera, et cetera.

    27. PA

      Y- you, you described this, Anna, sorry to interrupt, in a way that I loved so much. I wrote it down. "We are cacti living in a rainforest." I mean, it's just such a beautiful way to describe the bizarre existence of the human in this, in this condition relative to 10,000 years ago and, and, and for-

    28. AL

      Yes

    29. PA

      ... millennia.

    30. AL

      Yes. And I'd love to take credit for that metaphor, but I can't. That's Dr., uh, Finn Kane from Johns Hopkins-

  7. 43:33 – 54:29

    How abstinence from addictive behaviors can help reset the brain’s reward system and improve mental health

    1. AL

      Yeah, and I think it's great for people to hear that you have some degree of incontinence around this behavior. Um, you know, Aristotle talked about what, what he called wide-eyed incontinence. Why it is, why is it that I do what I do not want to do? Because really that's at the heart of addictive behaviors, and I, I'm, I'm guessing that people look to you as a sort of paragon of self-discipline. So it's, uh, very nice, I think, for people to recognize that even you have arenas in which you, you know, you are incontinent in this regard. Which by the way, is really hard to admit, um, in our culture because we're all supposed to be, you know, have it together and have all this kind of self-control. But really, um, almost all of us now have some, some space in our lives where we're over-consuming either a substance or be- or behavior, um, even if it's only mildly problematic that, that we'd like to change. Um, and I guess since I have seen people with very severe and life-threatening addictions be able to get into recovery and maintain recovery for decades, um, I think that we can all look to those individuals as, um, guides for the rest of us and, and not sort of, um, be overly fatalistic about our own capacity to change these behaviors. I think we can change these behaviors. And I would also suggest that, um, to do so is not just important for our own mental health, but it's also important for the planet. So our consumptive behaviors really do, you know, affect everything around us.

    2. PA

      Some of the stories in your, in your book, Dopamine Nation, uh, as, as I'm reading them, I'm thinking to myself, "Well, if she included this person, there must be a happy ending." But, but as I'm reading it, I'm thinking, "There's no way this person is getting out of this alive." I mean-

    3. AL

      [laughs]

    4. PA

      ... the, like, some of the addictions that you-- Some of the, the clinical stories that you write about, and I assume outside of changing names and maybe genders in a few places, these are probably very accurate accounts of the, of the-

    5. AL

      Yeah

    6. PA

      ... of the individuals you worked with. Um, uh, I mean, I really had, had a lot of empathy for these people. Um-

    7. AL

      Yeah. Good, good. That's good

    8. PA

      ... again, may- maybe, maybe because anybody reading it who themselves has an addiction, even a quote unquote-

    9. AL

      Right

    10. PA

      ... "benign one," realizes that, that, that's devastating. But, but there are a couple that, that, you know, I think are, are, are interesting and, and worth talking about. So, so let's talk about the young woman who, um, whose parents sort of talk her into coming to see you because she's basically smoking pot around the clock. Uh, or not even smoking it. I mean, she's consuming it in every form that THC is imaginable, right?

    11. AL

      [laughs] Right.

    12. PA

      Um, and now of course, by her own reckoning, this is purely, um, a logical coping tool for her anxiety. This is-

    13. AL

      Right

    14. PA

      ... there's nothing pathologic about it. She's not suffering any ill consequences of it. Maybe te- tell her story and, and, and the, and, and kind of a little bit of the work you, you did with her. And, and the reason I wanna use that as one of the examples is you talked about neighborhood a second ago.

    15. AL

      Mm-hmm.

    16. PA

      And it's a very controversial topic right now, which is, for example, the legalization of marijuana. Um, and, and truly, it's something I find myself divided on, right? Because on the one hand, I think the criminalization, um, of marijuana has led to a lot of destruction in people's lives. Um, but at the same time, it's hard to avoid the, um, the, the, the knowledge that you've, you've shared, which is, look, the more available and ubiquitous a substance is, the more likely it is to be abused. Case in point, alcohol and tobacco. Um, and, um, so, so, so I'd like to kind of explore that a bit with you and also explore this idea of marijuana as a gateway drug, the, the so-called gateway drug to, to, to drugs that maybe people would argue are quite harmful, even if they believe that THC consumed in any amount is not. So, so maybe we'll start with the story of that young woman and, and kind of explore that a bit more.

    17. AL

      Yeah. So this young woman-- First of all, all of the patients, uh, that I talk about in the book are patients who were very longtime patients of mine, who I knew very well, and who I asked for their permission to share their stories using a pseudonym. Uh, so this, this was a young woman, uh, very typical for the types of patients that we will see now, who came in not looking for help with her cannabis use, but looking for help with her anxiety and her depression. And, you know, 20 years ago, the first thing I would have done for a patient like this was prescribe an antidepressant or an anxiolytic, maybe even some Xanax or some Klonopin, uh, and referred her for psychotherapy. My practice has changed, um, very much in the last two decades because of what I've learned from patients in recovery and the ways in which, um, repeated use of highly reinforcing substances and behaviors actually changes our hedonic or joy set point and creates, exacerbates, and drives depression and anxiety such that now the first intervention that I'll do with a patient like this is to actually ask them to abstain from their drug of choice for four weeks as a way to reset those reward pathways, uh, to see whether or not that alone will address the anxiety and depression. And in the majority of my patients, if they are willing and able to do that, they feel so much better after that, uh, you know, abstinence trial or dopamine fast that there's not even an indication after that, uh, to, to prescribe an antidepressant or an anxiolytic or necessarily do psychotherapy. I'm, I'm happy to talk about sort of how that hedonic set point gets changed from the perspective of neuroscience, if that would be helpful.

    18. PA

      Yeah, I think that would be great.

    19. AL

      Okay, so to me, one of the most interesting findings in neuroscience in the past 75 years is that pain and pleasure are co-located in the brain and work like opposite sides of a balance. So if you imagine that deep in these limbic structures in nucleus accumbens, the area that's rich in dopamine-releasing neurons, there's something like a teeter-totter, um, a central beam on a fulcrum that in a very simplified way represents how we process pleasure and pain. When we experience pleasure, it tips one way. Pain, it tips the other. There are certain rules governing this balance, and the first and most important rule is that the balance wants to remain level. Um, and that level balance is what neuroscientists call homeostasis, such that with any deviation from that level position, which is the definition of biological stress, our brains will work very hard to restore a level balance. So for example, um, my patient uses cannabis through the endogenous opioid system that ultimately leads to the release of dopamine in the reward pathway. Her pleasure-pain balance tilts to the side of pleasure, and then her brain says, "Oh, that was good. Let's do that again." But remember, uh, the balance wants to return to the level position, so it does that by adapting to that increased dopamine by down-regulating dopamine transmission and production, not just to baseline levels, but below baseline levels. I like to imagine that as these neuroadaptation gremlins hopping on the pain side of the balance to bring it level again, but the gremlins like it on the balance, so they stay on, uh, until the balance is tilted an equal and opposite amount to the side of pain. That's the hangover, the come down, the blue Monday, or just that state of craving. Now, if after that initial use my patient doesn't smoke again, those neuroadaptation gremlins get the message that their work is complete. They hop off the balance, and homeostasis is restored. Craving goes away, and she goes on with her day. But if she continues to use that substance, in her case cannabis, repeatedly over time, ultimately what happens is those gremlins on the pain side of the balance start to accumulate. They get bigger. They get stronger. Now they're camped out there. And now essentially we're, we're entering addicted brain. Now when she uses cannabis, that initial deviation to the side of pleasure is weaker and shorter in duration, but that after response to pain gets stronger and longer, and ultimately she ends up in a kind of chronic dopamine deficit state below her natural dopamine baseline, where she is experiencing the universal symptoms of withdrawal from any addictive substance, which are, again, anxiety, irritability, insomnia, dysphoria, and craving. When she uses cannabis, that temporarily counteracts those gremlins on the pain side of the balance, and she feels better, so she thinks to herself, "I'm self-medicating my anxiety with my medical marijuana." But in truth, all she's really doing is just adding more gremlins to the pain side of the balance. So the intervention is to have her abstain from her cannabis long enough so that those neuroadaptation gremlins get the message they need to hop off the pain side of the balance so that, uh, you know, healthy levels of dopamine firing can, can be restored. This is obviously a vast oversimplification of a very complex process, but it gets to the heart of homeostasis, a level balance, and allostasis, which is our brain's ada- adapt-- attempt to adapt to these highly reinforcing stimuli for which it was not evolved, right? I mean, the definition of a intoxicant is that it releases a lot of dopamine all at once in the brain's reward pathway. Our brains were evolved for us to have to work very hard to find a tiny little, you know, jolt of dopamine and then essentially do that again and again to s- to stay alive. So, you know, the intervention for her is to ask her, uh, to abstain and to let her know that she's going to feel worse before she feels better, more depressed, more anxious. Um, maybe she'll have other signs of physiologic withdrawal, which indeed her case-- in her case she did. She had vomiting, which really shocked her because she thought that was a sign for her, a physical sign that she had become dependent on or addicted to the cannabis. But as I say to patients, if you can just get through about the first 10 to 14 days of feeling worse after you give up your drug of choice, by the time you make it to about week three or four, you will feel better, less craving, less anxious, less depressed, better able to sleep. And that's so often a revelation for people because they have become convinced that their drug of choice is, quote-unquote, "self-medicating" their depression or whatever it is. So, so that, that, that, that was the intervention with her. That, that's our general early intervention that we do. Um, in terms of-

    20. PA

      Uh, just a couple questions there, Anna, before we go on.

    21. AL

      Yeah. Mm-hmm.

  8. 54:29 – 1:02:40

    Safely abstaining from addiction substances, drugs needing medical supervision, and other key considerations

    1. PA

      Which drugs or chemicals, I suppose, can you not safely just do that with? So for example, in the case of cannabis, um, the, the pain that she experienced was not life-threatening, and therefore she didn't need anything to cope with withdrawal. We've already discussed how that would not be the case with ethanol. So if somebody came into your office, um, and they're having six drinks a day and they acknowledge, you know, go through the steps to acknowledge, 'Hey, this is problematic,' and they agree to want to stop, you wouldn't be able to just say, "Hey, leave your office. Uh, don't drink and I'll see you in four weeks." There's a very good chance they would be dead due to the cardiovascular side effects. So there you would have to put them on other drugs. Um, what are the other dependencies for which you wouldn't just have the liberty of stopping cold turkey?

    2. AL

      Okay, so let, let me just say that that's a very good point to qualify, um, this intervention, but it, it's not necessarily true that for somebody with an alcohol addiction you couldn't do this intervention. It would depend on how severely physiologically dependent they were and whether or not they were at risk for life-threatening withdrawal or delirium tremens or seizures. Most people who are addicted to alcohol, um, actually won't have life-threatening withdrawal-

    3. PA

      Right

    4. AL

      ... and could do this. Um-

    5. PA

      H- how do you determine that, by the way? 'Cause I, I don't-

    6. AL

      Yeah

    7. PA

      ... I, I, you know, we used to be very blunt about this in residency. Like, because I was a surgical resident, when we operated on people who appeared to drink a lot based on our intake assessment, which is subjective, uh, we would just usually run an ethanol drip in them for safety. But I-- There, there was no-- I don't think there was any real, uh, you know, insight into whether that was really necessary or not. So how would you evaluate that with a patient?

    8. AL

      The biggest predictor of how someone is going to withdraw from alcohol is past withdrawal. So we will ask them, "When was the last time you stopped drinking? For how long? And what was your symptomatology?" Uh, it's not, you know, fail-safe, and of course, as people age, they lose neuroplasticity. Uh, their risk of having some kind of more difficult or even potentially life-threatening withdrawal increases. It also increases over the drinking career, especially as their-

    9. PA

      Mm

    10. AL

      ... liver is p- is compromised or pancreas is compromised. But really, you know, you look at past withdrawal, how long ago was that? And it, it, it is really interesting, and we don't understand why this is, that some people who drink enormous quantities for decades can stop and have-

    11. PA

      Mm

    12. AL

      ... minimal withdrawal, and other people who have had much shorter drinking careers, um, will go into delirium tremens or have life-threatening seizures. So we're not at all cavalier about it, and for any patient that we remotely suspect might have, um, a serious withdrawal, we would recommend, uh, medical monitoring, um, probably or possibly inpatient monitoring. So we take it very seriously, um, and we don't just recommend this early intervention for, for somebody who is at risk. But I can tell you most people who, who, um, are addicted to alcohol will not have life, life-threatening withdrawal from alcohol. The other major category is basically, um, are benzodiazepines, which is alcohol in pill form. They work on the same or similar GABA receptors. And so people can have life-threatening withdrawal from benzodiazepines, which is why for many individuals, we will, um, recommend a medically monitored slow taper, uh, or a more rapid inpatient detox. We used to think that opioid withdrawal, although extremely painful, was not life-threatening. But in the last twenty years, as we've been helping people decrease the very large doses of prescription opioids they've been given, uh, by their doctors, we have noticed that especially in older people and people with serious medical comorbidities, cardiac comorbidities, for example-

    13. PA

      Mm

    14. AL

      ... the stress is just too much, um, and that those individuals, again, need to be slowly, uh, tapered down. But the general ones that we worry about and have to screen for is alcohol, benzodiazepines, and, and now, um, concern for opioids. I would say the other category of individual in which we would not recommend this dopamine fast or abstinence trial, um, is individuals who have repeatedly tried to stop on their own and been unable to. That would just be a lesson in frustration. Those are individuals that we would recommend to a higher level of care, like a day treatment program or a residential treatment program.

    15. PA

      Mm-hmm.

    16. AL

      Also, especially with opioid use disorder, opioid addiction, we are finding that some people, even with long periods of abstinence, um, never get out of that state of craving and really can't move on with their lives, which is why we will prescribe opioids, uh, to treat opioid addiction in some cases. And for example, medications like buprenorphine or methadone maintenance are evidence-based interventions for opioid addiction. Seems counterintuitive to give a patient with an opioid addiction an opioid, but they're very unique opioids. They have a long half-life, which means it gets people out of this repeated cycle of intoxication, withdrawal, drug seeking, et cetera. Um, it gets them out of that state of craving, and if you think back to this pleasure-pain balance, we're not getting folks with opioid use disorder high by giving them opioids. We're just allowing them to level, uh, their pleasure-pain balance, go back to baseline homeostasis, which then frees up their energy and creativity to, um, engage in other aspects of their recovery.

    17. PA

      If someone's listening to us now, Anna, and, you know, by the end of this podcast they've become convinced that maybe they're drinking too much and they'd like to try this dopamine fast, um, do you recommend that they speak with their doctor before doing it? Is this something that a person can safely try if they're aware of what side effects might prompt medical attention? We certainly don't want to discourage people from reducing their alcohol intake if that is indeed problematic, but at the same time, we want to be responsible in how we do that. So what, what advice would you have for somebody listening who's saying, "Hey, you know what? These, these three or four drinks I'm having every single day, I could-- I'd be better off without"?

    18. AL

      Yeah. So I mean, um, if, if, if I think if the individual has any concern about a serious medically dangerous withdrawal, um, from alcohol or from benzodiazepines or from opioids, uh, they, they should consult a medical specialist. But the majority of people who use these substances have taken periods on the order of days or maybe even weeks when they have stopped, so they have a pretty good sense of, number one, whether they can do it, and number two, what kind of reaction their body will have. Um, so I do think that this is an experiment that most people can try, um, without medical supervision, especially if they're in a position to either not be able to afford it or have access to somebody who's trained in addiction medicine. We have far fewer addiction medicine providers in this country than we have, uh, you know, the need, uh, to address the problem. So I think as an early intervention, it can be a, a nice experiment even just to see if they can do it. You know, sometimes we think we have some degree of control, and then it turns out we don't have, uh, you know, we don't have what-- the degree of control that we, we thought we had. Um, it's also just, you know, a very interesting experiment for those who are not addictive to get a sense of deep understanding and empathy for the problem of addiction. Because even just giving up something like online shopping or romance novels or video games or what have you, um, and to observe ourselves going through withdrawal can be enlightening. Um, and you know, as you experience with the, the opioid withdrawal, um, in that medical setting, kind of give you a great deal of sort of empathy and, and healthy respect for the phenomenon of addiction.

  9. 1:02:40 – 1:13:18

    Transitioning from abstinence to long-term recovery: tools and considerations

    1. PA

      Yeah. Going back to that, uh, the point about neighborhood again is really, really clear, uh, which is, uh, it's very difficult to kick a habit if you go right back into the environment in which that habit was, was rife. So i-in the case of this patient, for example, um, she comes back after four weeks. Um, it's been a transformative experience in that she's, she's gone through very painful withdrawal. Um, you, you prepared her for it by telling her it was going to hurt a lot and that she needed to sit in the pain effectively. Um, and when she comes back, the anxiety is gone. Um, so one, how do you now help her with this next phase of recovery? And, you know, how difficult a set of choices does that person need to make if indeed their social circle basically fed into that addiction? I mean, to me, as hard as that four-week abstinence program is, it might be what follows that's actually harder.

    2. AL

      Yeah, you're absolutely right. So if the patient is able to abstain for four weeks, they come back. We ask them how, how it went, um, and we kind of make a pros and cons list. What was good about not using? What was, what was bad about not using in those four weeks? Um, we typically-- When the patient feels better, and again, about eighty percent of folks feel, feel better. Twenty percent don't, and that's also really useful information 'cause it tells us that something else is driving this, and then we explore that. Um, for, for this case, you know, the feeling better, we-- on the pros side, people will talk about, "I was more productive. I had more time. I was able to be more present. I felt physically better. I was less anxious, less depressed, slept better," et cetera, et cetera. So there's really a, a nice long list of things that they gained from stopping using. And what I think is so powerful about this intervention is that the person has their own experience. I'm no longer in the role of having to persuade them that not using or using less will make them feel better. They have experienced it for themselves. On the cons list, like what was bad about not using, you already anticipated the-- pretty much the top one, which is, "I couldn't hang out with my friends 'cause all my friends use, um, and I really like my friends, and I want to go back to hanging out with them." So that, that poses a serious dilemma. The other major con that people endorse is just simple boredom. All of a sudden, people are left with lots of time and wondering, uh, what to do with it. But I like to talk a lot with patients about boredom being kind of the, the midwife of, of creativity. Um, and then we essentially, uh, talk about next steps. And the first time around, most patients want to go back to using their drug of choice, but they want to use differently. They want to use in moderation. So I support them in that goal, even if I'm thinking to myself, "This is a really bad idea. I don't think they're gonna be successful." Why do I support them in that goal? Because, again, this is experiential learning. I can talk till the cows come home. Until they experience it for themselves, it's not really gonna take. But also, I've discovered that I'm a very bad predictor of who's going to be successful and who isn't. I've had patients who definitely meet criteria for alcohol use disorder, serious alcohol addictions, who have been able to go back to using alcohol in moderation, uh, after, uh, an extended period of absence. So-

    3. PA

      What, what fraction do you think, uh, fits that description? Um, where-- A-and again, we'll talk about it through the lens of chemicals maybe and as opposed to just behaviors. But, um, is that, is that a minority of people who are able-

    4. AL

      Oh, absolutely. It's a small minority. It's a small minority. It's, it's, it's definitely less than ten percent. May-maybe, maybe even hovering closer to one percent.

    5. PA

      So these people are clearly anomalies, but just out of the, you know, the curiosity of exploring the end user, what is it about an individual that allows them On the one hand, to have met complete criteria for a true addiction, whether it be to alcohol or another substance, to go through a period of detoxification and emerge from that and say, "You know what? It's true, I used to drink six drinks a day, and I would blackout drink and binge drink, and it was ruining my life. DUIs all day long," like all of the above, "But now I'm gonna become a social drinker. I'm gonna have a glass of wine with dinner every night. That's it." And, and th- if there's the one in 100 who can do it, how are they doing that?

    6. AL

      They're doing it with a lot of hard work. So it, it doesn't come just like that. It's not like you abstain for a while, you reset your reward pathways, you're, you're good to go. In fact, quite the contrary, um, once we've created those kinds of addiction circuits, even though we can get them to quiet down, they're very easily reignited, not just by exposure to our drug of choice itself, but to reminders of the drug of choice. So what I talk a lot with patients about is the specificity of the plan for how they will consume. The more specific, the better, and this is all in the spirit of self-binding strategies. Self-binding strategies are very, very important-

    7. PA

      Mm

    8. AL

      ... in a world where we're constantly being titillated and invited to consume and told that that's the good life. Uh, what do I mean by self-binding strategies? Those are both literal and metacognitive barriers that we put between ourselves and our drug of choice so that we can press the pause button between desire and consumption. So for a patient with, uh, you know, a drinking problem, that might look like not having, uh, any alcohol in the house, right? A very simple and obvious self-binding strategy. That might look like, um, pledging to never drink alone, but only with friends on special occasions, making sure that I don't now fill my schedule up with many different special occasions-

    9. PA

      [laughs]

    10. AL

      ... which happens, right? Uh, that can look like making sure that I, um, am very cognizant of how much I'm drinking and keep it to no more than two standard drinks on any given drinking ca- occasion and track it carefully and write it down so that I don't get into that state of sort of blurry denial where I can tell myself it was r- only one drink when it was really five. Um, that might even look like taking medication. So we have medications like naltrexone, which is an opioid receptor blocker. Alcohol works in part through our endogenous opioid system, and by blocking the opioid receptor, we essentially make alcohol less reinforcing. So people who will take naltrexone will say, "When I'm taking naltrexone," at least the ones for whom, whom it works, "I can look at a six-pack of beer, and I just want to drink two. I don't want to drink the whole six-pack." And that's really a revelation-

    11. PA

      Mm

    12. AL

      ... uh, for these people because before, you know, it was just like, "I really wanna drink the whole six-pack." So, you know, self-binding strategies can be, again, at the, like, literal, uh, physical barrier level. It can be at the chemical barrier level. It can be at a kind of interpersonal accountability level. It can be at a spiritual level, um, so, um, wanting to live in accordance with one's values or a greater good and seeing their use as, or their excessive use as, um, um, contrary to living according to those values. So really getting at it from all different angles. Uh, and, and people with the most severe addictions ultimately really need to kind of get a totally different orientation on their lives, um, in the sense that they, they really need to inculcate, um, a philosophy about life that, you know, allows them to maintain their recovery. Um, a- and, and by that, I mean, like, living recovery principles in all aspects of their lives. So that's things like, um, telling the truth in all situations. A lot of people in recovery have taught me that, uh, if they start to lie, even about little things like why they were late for a meeting, that is a potential for them to tip over and relapse. So it's, it's a very interesting, um-- It's like a recovery mindset/lifestyle/philosophy. It has to become bigger than just the substance itself.

    13. PA

      Ye- yeah. It's, um-- One of the things that strikes me as noteworthy as you describe the effort that would have to go into, uh, dipping your toe back in the water is at least maybe ha- the patient consider the cost of that, right? In terms of, look, if you, if you really wanna go back to having a couple of drinks here and there, then the systems you have to put in place to do that as opposed to the systems you might have to put in place to just adhere to complete abstinence might not, you know-- Think of the opportunity cost of doing that. That's a lot of energy that could go into living a fuller life in other ways. Is it really worth having a couple of drinks a week or whatever it is that you've agreed to? Um, but d- do you, do you sort of ever have that discussion, or do you think that that's just up to them to figure out?

    14. AL

      Oh, no, no. So that's a very common discussion. You, you, you, you... So basically, the, the typical outcomes that we see after the dopamine fast or the abstinence trial is, first, the abstinence violation effect, where people say, "I'm gonna go back to using in moderation," and immediately they're plunged into a binge episode even worse than what was there before. And then, you know, then there's the discussion of, "Gee, maybe moderation is really not possible." Or people who are able to achieve moderation but who ultimately decide it's so effortful and so much work that it's essentially not worth it. There's this famous, uh, you know, AA lingo, uh, "One drink is too many and two is never enough," which kind of captures that very well, uh, this idea that You know, stopping at two doesn't actually get me what I'm looking for, uh, but, but does in fact kind of, uh, reignite those addiction circuits such that it's very difficult to stop at two, and I want to keep drinking. And those people will, you know, often ultimately decide that abstinence is, uh, not only better for them, but also easier.

  10. 1:13:18 – 1:19:13

    Exploring behavioral addictions like sex addiction, and the gender differences in addiction patterns

    1. PA

      So let's talk a little bit about some of these behavioral addictions as well. You-- I, I think of all the stories in your book, uh, the one that I, I'm not sure what it is about the character, but it, it, he certainly invites enormous sympathy is-- I think his name is Jacob.

    2. AL

      Yeah.

    3. PA

      Um, and, uh, look, uh, everybody's heard of sex addiction and sort of, uh, has a, has an understanding of what it is, but, but it's not necessarily what, what you describe in Jacob, right? His sex addiction is not the, the, the one that you would think of when you're watching a TV show that features someone who's a sex addict. Um, so w- maybe tell briefly the story about Jacob and, and describe the, the pathology there and, and what, what is, what is the addiction giving him that maybe a gambling addiction wouldn't give a gambler or an alcohol, uh, an alcohol addiction doesn't give the alcoholic? Uh, the-- again, what was the pleasure he was seeking, um, relative to, to maybe what I would normally think of as a sex addict is, is seeking many partners, for example?

    4. AL

      Ah, interesting. Okay. So there are, I mean, many different ways that, um, sex addiction can manifest. Sometimes when people get addicted to sex, they, they compulsively seek out partners. But many people addicted to sex now are addicted to pornography and compulsive masturbation. Um, it's very hard to get numbers o-on any of this, but I would say the majority of cases that we see are, are not in fact people who are having sex with other people. They're, they're people who are spending enormous amounts of time, um, looking at pornography, masturbating, and of course, that's so easy to do now given the advent of the internet and online pornography. Um, in the case of my patient, Jacob, you know, he, he started out with pornography and compulsive masturbation, but he is an engineer and ultimately, um, made-- you know, built a masturbation machine that escalated over time, uh, as his addiction progressed, as addictions will progress, uh, such that he was ultimately hooking himself up to the internet, letting strangers in chat rooms manipulate this machine, you know, in a way that was really very dangerous and potentially life-threatening, which he was fully aware of and yet struggled to stop the behavior. Ultimately, you know, when the behavior was discovered by his wife, she left him, um, you know, and he considered ending his life. So wh-when people say, "Oh, you can't really get addicted to sex the way you can, uh, with drugs and alcohol," I would just invite them to be a fly on the wall in, in the work that we do. We are seeing more and more, um, uh, men o-of all ilk coming in with really devastating, um, what we, what we broadly classify as, as sex addictions. This is compulsive masturbation or the pursuit of orgasm in, in many different ways.

    5. PA

      Well, and, and, and you, you mentioned this as, as primarily a male problem. Why do you think that is?

    6. AL

      Well, I mean, I, I think there's enough evidence to show that men in aggregate have a higher sex drive than women. Um, you know, a-any teenage boy, um, you know, the, the joke about how much of a teenage boy's brain is occupied with thinking about sex, it's a, like ninety-nine percent. I mean, you know, I, I, I d- I'm sort of loathe to kind of speculate too much about that. Um, but, um, it's just, it's just the truth. I mean, that's what we're seeing. We're not seeing women coming in with, um, with sex addictions the way we are with, as with men. Occasionally, we'll see that, but it's quite rare. Although there are data emerging showing that more and more women are consuming pornography. So, um, you know, what, what's been interesting to see, uh, in the modern era, the ways in which certain demographic groups that were previously relatively immune to certain types of addictions, uh, that's no longer the case. So for example, with alcohol use disorder, you know, genera- for generations, the ratio of men to women with an alcohol addiction was five to one.

    7. PA

      Hmm.

    8. AL

      Thirty years ago, it was two to one. Today, among millennials, it's one to one. We are now seeing young women presenting with alcohol use disorders pretty much as often as we see men. So who knows, you know? With enough time, it could well be that this is not necessarily, um, a biological phenomenon and really just a sociocultural one. Certainly, in part, it's probably social, sociocultural.

    9. PA

      Are men in general more prone to addiction? Because obviously you've stated now that men are-- effectively make up all of the, or most of the, uh, patients who suffer from various forms of sex addiction. I'm just gonna guess, knowing nothing about it, that the same is probably true with gambling. Um, so, so w-what are the addictions, maybe stated the other way, where women disproportionately make up the patients?

    10. AL

      The only one that I have seen data for where women, um, outstrip men is for benzodiazepines.

    11. PA

      Hmm.

    12. AL

      So sedatives like Xanax, Valium, Klonopin.

    13. PA

      Okay. So if we take all addictions together, men have a greater problem with addiction than women, I would guess, just based on the simple fact that in most cases, men outstrip women. So how much-

    14. AL

      The one, the one, the one sort of new wrinkle there is just social media addiction, where we're seeing-

    15. PA

      Hmm

    16. AL

      ... more women and girls.

    17. PA

      Okay. So do you think that that fits more into nature, nurture, or neighborhood as the driver?

    18. AL

      Um, it's probably both. You know, it's, or, or both. We have three things, so I guess it's a combination of all three things,

  11. 1:19:13 – 1:30:21

    Factors contributing to the increasing levels of addiction across the world

    1. AL

      I think.

    2. PA

      Very interesting. Okay. So, um, let's go back to maybe some of the things that, some of the itches that are being scratched with these different addictions, right?

    3. AL

      Mm-hmm.

    4. PA

      So you talk about, I think it's called loss dysphoria. Is that what you referred to as, um... Or no, no, I'm sorry, loss chasing?

    5. AL

      Oh, yeah.

    6. PA

      Is that what the gambler-

    7. AL

      Mm-hmm

    8. PA

      ... is looking for?

    9. AL

      Yes.

    10. PA

      Now, that was a very, that was, that was, I had never thought of that before. Can you explain what that is, and is that, does that phenomenon expand beyond the gambling addiction? Is there an analog to that in other forms of addiction?

    11. AL

      Yeah, great question. Um, so loss cha- chasing is a, is a, is a phenomenon that's been o- observed in pathological gamblers where they will report that when they are deep in an episode of gambling, they actually want to lose.

    12. PA

      Hmm.

    13. AL

      And the reason they want to lose is because the losing allows them to justify staying in the game longer, which is, I think, very revealing because it shows that on some level, a gambling addiction isn't really about being addicted to money. It's about being addicted to the pursuit of money or the game itself or the trance-like state that people can get into when they're deep in their addictive behaviors, which I would argue applies to every single addiction under the sun. Um, so for example-

    14. PA

      Hmm

    15. AL

      ... sex addiction is not really about sex. It's about self-soothing. It's about escape. It's about numbing. It's about relieving tension. Um, and I would say that that's true for, for all addictive behaviors. Interestingly, there's been some work using brain imaging looking at dopamine levels in pathological gamblers' brains compared to healthy control subjects who are gambling. And what the researchers found is that when pathological gamblers are winning, there, there will be an increase in dopamine transmission in the reward pathway, and the same will be true for healthy control subjects. But the difference comes when they're losing. Uh, when healthy control subjects lose, there's n- no increase in dopamine transmission, but pathological gamblers will actually have an increase in dopamine transmission when they're winning, which is-

    16. PA

      When they're losing

    17. AL

      ... you know... Well, sorry, yep. But pathological gamblers-

    18. PA

      Yep

    19. AL

      ... will have an increase in dopamine transmission when they're losing, um, which maps very nicely on to this, uh, this subjective experience of, of loss chasing. And it looks like the, um, the do- the, the dopamine in a pathological gambler, dopamine is released at the highest level when the chances of winning and losing are equal. So it's that place of uncertainty-

    20. PA

      Hmm

    21. AL

      ... in the gambling state that is, uh, on some level the most appealing state, uh, for the pathological gambler.

    22. PA

      Is there, just from a, a population prevalence standpoint, you've already alluded to the fact that a- addictions to social media are probably really, really on the rise, um, [clears throat] for the obvious reason that they're, you know, s- didn't exist 20 years ago. Um, we, we, we certainly know from an availability, i.e. neighborhood access phenomenon, that opioid addiction is clearly on the rise. Um, I would assume that marijuana is also on the rise for the same reason. Is that, is that a fair assumption?

    23. AL

      I haven't looked at the latest data. So certainly, um, overall in the last 20 years, Americans are using a lot more cannabis than they were previously, and they're using more potent forms of cannabis. And what we're seeing in particular is that there's a subset of individuals who use cannabis who are using very, very large quantities. So a generation ago, 30, you know, 20, 30 years ago, people who used cannabis, uh, were still mostly using it recreationally on the weekends with friends. Now what we're seeing is a, a very hardcore group of individuals who use cannabis every day, all day, dabbing highly potent forms, vaping, getting very, you know, high levels in their brain. So these are the kinds of trends. In other words, the increased access is going to harm a subset of the most vulnerable individuals who will be most likely to use it in very potent forms in very large amounts.

    24. PA

      Yeah, which really raises kind of a, a challenging societal question, right? Which is, do you punish all of the people for whom the increased access has potentially made life better, both in terms of the actual use of the drug and, and certainly the decriminalization of it, which has, has probably made many lives better. Um, but it's clearly made some lives worse. And, um, you know, I'm glad I'm not the person responsible for making those decisions 'cause those are very difficult decisions. I, I don't know how one makes a decision if you're trying to put the good of society, uh, uh, at, at the top of the priority list when, when it's, th- there, there are, you know, these conflicting, um, outcomes. What about other things like, uh, well I guess you've alluded to the fact that it sounds like sex addiction is also on the rise?

    25. AL

      Very hard to get numbers-

    26. PA

      Okay

    27. AL

      ... on sex addiction, but I can tell you based on, you know, 25 years of clinical practice, it's on the rise, at least in terms of help-seeking individuals. And my sense, um, is that since the advent of the internet, especially the, the smartphone which makes, you know, online pornography and chat rooms, et cetera, so easy to access, dating apps I would put in the category of sex addiction, um- I think that we are dealing with an enormous problem in ever younger age groups, and that our-- what we see is really just the tip of an ice- of the iceberg of a, a kind of a rampant, um, compulsive consumption of pornography among men and boys.

    28. PA

      Uh, I want to come right back to that, but just to close the loop on this, what about gambling, uh, benzos, uh, other, uh, cocaine, things of that nature? Where, where do we-- where is the trajectory and trend line on those things?

    29. AL

      So with gambling, um, the, the-

    30. PA

      I assume online gambling is just another thing that's, you know.

  12. 1:30:21 – 1:43:05

    How online pornography can affect young boys' developing brains and lead to addictive behaviors, and strategies for parents to address this issue

    1. PA

      to go back to what you talked about with res- with respect to porn and young kids, young boys in particular. So anybody listening to this who has young boys is probably aware of and concerned about this. So I, I, I always think Bill Maher does the best job talking about this. He says, "Look, you know, for, for people of our generation, uh, pornography was like, you know, finding a raggedy old Playboy magazine in the woods, and, and, and, and there's no question that you were obsessed with looking at that. But it didn't warp your sense of sex, right?" Like, it, it, it didn't pervert you to the point of potential pathology. And yet, um, in it-- t- today, yeah, any- anything on your smartphone can basically do just that. And, and is there an argument to be made that the impact of that is differentially worse in a sort of prepubescent/in puberty brain than it is in, you know, uh, a mature, you know, an adult? I mean, is, is there a difference in the impact? What are the data on that? And then ultimately what I'm really asking is what, what can parents do to, to educate their kids? Because I think it has to come down on some level to education, right? I mean, i- if you think about this through the lens of alcohol, um, you know, I, I... What a parent says and does probably matters more in terms of modeling, I would hope, than just, you know, a draconian rule set that says, you know... Uh, anyway, so, so, so, so tackle those questions in any order you see fit. But, but basically, what, what is a parent to do in this day and age to try to raise, uh, boys in particular, uh, to be, you know, sexually healthy people when they, when they get older?

    2. AL

      Okay, great. So let me, let me start at the beginning of your series of questions. So, so first of all, um, o- one of the things that's been very interesting to me in treating patients with sex addiction is to see how tolerance manifests. Many of these individuals start out with kind of run-of-the-mill legal types of engagement with pornography or what have you, but over time, as their brain adapts to those rewards, they develop tolerance. They need more potent forms to get the same effect, and they find themselves a year, two years, five, 10 years later then engaging in highly deviant or violent or pedophilic pornography or engaging with, um, you know, sex workers, illegal activities. Um, and so I think th- that is, that is important because when we're trying to distinguish like a paraphilia from a sex addiction, I think, um, many psychiatrists are not recognizing that the way that that person presents at sort of their end-stage sex addiction might really be 100% due to tolerance. And if you can get them out of that addiction cycle, their preference for this illegal activity, uh, you know, really might not be there. Um, in terms of the developing brain, so we do believe that children and adolescents are more vulnerable to these highly reinforcing stimuli, and that the earlier that folks are exposed, the more likely they are to develop an addictive process. We base that on analogy with substances 'cause we know that the earlier that kids start using substances, the more likely they are to develop a substance use disorder in their lives. We speculate that that is because adolescents still are developing the connectivity between the frontal lobe and those deep, uh, you know, limbic structures, the emotion part of the brain, um, and that adolescence is characterized by a period of pruning, where the brain essentially cuts back on those neuronal circuits and dendrites and axons that are being used least often and myelinates those circuits that are used most often. Myelination is what makes the conductivity faster and more efficient, such that by the time we're about age 25, we've essentially created the neurological scaffolding that will serve us for our adult lives. So that means if young people are engaging in maladaptive coping strategies and strengthening those circuits, it's not impossible, but it's harder to change, uh, you know, once they re- reach 25 or early adulthood. So the key for parents to realize-

    3. PA

      Hmm

    4. AL

      ... is that while they still have some modicum of control over how their children and adolescents are engaging with the internet, I s- I recommend that they exercise that control to limit access, as well as educating, um, and having open discussions about, um, the potential harm there. What, what is the potential harm? Again, these images are highly reinforcing. You know, we were wired to find mates and partner, and that's what allows us to propagate the species, which is how we've been able to survive. But what pornography essentially does is it hijacks these reward pathways with very potent images that are made all the more reinforcing by the fact that, um, the individual can control them in the moment. So with very little work that is required in real relationships, they can now just go right to the money, so to speak, or the reinforcing aspect. Plus, orgasm is the release of neur- a bunch of neurotransmitters all at once, um, which feels, you know, really good for many people. I want to highlight that not every, uh, you know, y- boy or man is actually drawn to pornography or sex. Um, so it's, it's again, we have this interindividual variability. But for young, for, for boys and men for whom that is a potent reinforcer, it is the medium itself of the internet, the easy access, the potency, even dating apps. You know, the, the, the idea of dating apps is that we're going to be matched with a partner, but what can happen is people get just addicted to the match, right? The confetti of the match, and then they want to have the pursuit and the match again, and it's not even necessarily leading to any kind of, um, intimacy beyond that, or if it is, it's just leading to hookups, which are about the sex. Um, so for parents out there, you know, I really recommend that a child under 13 not have unsupervised access to the internet. Um, if, if, if they must have some kind of phone device, have it be a light phone or a flip phone, and then once they get to the point where they do have data and access to the internet, um, have a lot of open discussions about pornography. Um, and they can be really, really awkward discussions. I'm a mother to two, um, boys, and both of, you know, both of my sons, we have, um, try to have open quite awkward discussions about pornography

    5. PA

      Yeah, yeah. T- t- tell me about that because it's, uh, like it's been really easy to have discussions with our daughter about, uh, illicit drug use because it's a biochemistry discussion, and the risk is really obvious. In other words, um, you know, I, I had a guy by the name of Anthony Hipolito on the podcast who's a local sheriff here in the Austin area whose work focuses entirely around fentanyl toxicity and fentanyl-laced drugs. So there, there are kids all over here that are dropping dead from laced Ambien, laced Xanax, uh, you know, cocaine, whatever the drug is that seems to be spiked with fentanyl. So, so having the discussion with, with our daughter about that is really quite easy, right? Which is-- But, but what are, what are your coaching points for... And I'm asking this honestly for myself just as much as the listeners, right? My boys are pretty young, you know, seven and 10. Um, but w- you know, th- that's gonna be a discussion to have soon. W- w- how are you making the case to a 13-year-old or 14-year-old that, "Hey, you know, you're gonna be over at your friend's house one day, and you're gonna be playing sports, and all of a sudden, you know, he's gonna say, 'Hey, come and, come and look at this.'" 'Cause maybe in their household, it's not gonna be as policed as it is in our household. What's the case you're making?

    6. AL

      Yeah, so this is where I really encourage parents to try as much as possible to just be curious. Think of themselves-- Actually, one, one, uh, kind of metaphor I heard once, which I thought was really good, is pretend like you're a journalist-

    7. PA

      Hmm

    8. AL

      ... and you're just trying to get the story. Um, and just ask them, you know, "What, what did you think about that?" You know, uh, it's very easy as a parent to get dysregulated in even speaking about these things or imagining our child engaging with these images, but it is the reality, so we have to go there. You know, "What, what did you think about that? Um, you know, is that something that you have started using yourself, um, you know, to, you know, masturbate or get as an escape or release? Um, you know, how is that working for you? How do you, how do you feel afterward?" I think really zeroing in on how do you feel afterward can be very instructive because usually there's a pretty hard comedown, as well as a feeling of like, "Wow, that didn't actually do for me what I was hoping that it did, and I kind of am feeling bad about that experience." So again, um, you know, and this gets into the whole quagmire of sort of sexual liberation and this argument nothing's wrong with pornography, nothing's wrong with m- masturbation. You know, so people are gonna come to this with different value systems, and I, and I respect that.

    9. PA

      Yeah. What, what, what do the data say? I think it's-- We, we can put our feelings aside for a moment. I think the real question here is, [clears throat] are there data to tell us that, that one approach is healthier than the other? And then obviously, what are, what are the clinical anecdotes that, that probably are more valuable than just our, our, our, our built-in beliefs, right?

    10. AL

      Right. Well, I mean, the, the data that we have is that men and boys, and actually women now too, are spending m- a lot more time consuming pornography. And young people in particular are m- much less likely to go out and actually have sex with other people and be in relationship. Now, whether or not those things are causative or correlative, you know, we don't know. Um, but we could certainly make an argument that all the time that men and boys are spending engaging in pornography is actually becoming a substitution for real-life engagement, either with their spouses or partners, or other people that they might meet. And in clinical care, what we see with behavioral addictions, including sex addiction, is that the phenomenology is identical to drug and alcohol addiction. People start out for fun or to solve a problem. If it works for them, they repeat that behavior. They go back again and again. Over time, it tends to work less well. They need more potent forms or larger quantities to get the same effect. And then at some point, in severe cases, they're marshaling all their available resources in order to do that activity or consume that drug. So, you know, this is a n- very new problem. We don't have a lot of good data. People are not rushing forward saying, "I have a sex addiction. Let me tell you all about it." In fact, it's very common in clinical care that we'll have a man come in and say in the first one to two to three visits that he's here for some reason that's not really the reason that he brought him, brought him in. He's really here for a s- sex addiction, but it's so difficult for him to talk about that. So, you know, this is, like, highly stigmatized because at the same time that we have this incredible access to pornography, we also have a culture and a climate in which men and boys are really seen as sexual predators. So, um, i- it's, it's a very potentially uncertain and dangerous environment for them to be trying to cultivate in real-life relationships, right? It's a, it's a risky environment. And so all of that, I think, is contributing to this kind of retreat from engagement and instead a kind of a self-soothing through this medium.

    11. PA

      So

  13. 1:43:05 – 1:53:32

    The link between social media use and declines in mental health, potential solutions, and protective measures

    1. PA

      let's talk about sort of a very near cousin of that, which you've already alluded to, which is social media. Now, this is in the, in the me-- This is, you know, th- this is the forefront of everybody's attention right now. There's a, uh, a, a book out about this by J- by Jonathan Haidt, um, that talks a lot about this. Um, and, and you know, I, I had dinner with Jonathan several months ago before the book came out, and it was, it was wonderful to sit down with him and, and sort of have this discussion about everything. Um- And I, and I posed a question to him that, um, you know, and I don't, I don't want to speak for him, but I, I think it's safe to say he didn't really have a great answer for. Um, but I think it is the jugular question. And it's interesting that since the book has come out, uh, there have been folks in the medical establishment that have, um, have, have come out and argued the opposite side of, of his. And so the question I posed to Jonathan was, "Jonathan, it's very clear here that the correlation between social media and declining mental health a-amongst young people in particular is overwhelming." Um, but I said, "How compelling are the data, and what would need to be done to demonstrate causality?" Because if, if you have causality, it becomes much easier to have a discussion about policy and action, right? So, um, once causality could be unambiguously established for tobacco use and cancer, um, which really occurred in the late '60s-- And by the way, it was-- it didn't occur through RCTs, right? It occurred through a very careful application of the Bradford Hill criteria, um, coupled with some mechanistic and, and, and animal research. Obviously, no one could do the RCT to demonstrate the harm of tobacco and, um, uh, and with respect to, to, to cancer. But nevertheless, once causality was established, the, the, the, the die was cast for the monotonic decrease in tobacco consumption that has occurred over the last fifty years. Um, and, and when causality is missing, it becomes very difficult to make the case for it. So there, there's, there's-- I've read all these arguments that-- And again, these are the minority arguments, to be clear. I think the majority of people believe that, you know, if they're even thinking of it that way, they believe there is causality. Um, but the minority argument is, look, there are a lot of reasons that young people are too anxious today. Um, social media might be one of them, but it's far from the only one. These people would argue that we've catastrophized everything in the world, right? We've got every young person thinks that by twenty thirty, uh, the, the climate is gonna have eroded to the point where it, the world will be uninhabitable, um, even though, of course, that's not true. But nevertheless, there, there are enough people who, who have catastrophized so many things in terms of, um, o-o-of, of the future of this planet that, that maybe that's, that's part of the reason. And, um, and, and anyway, they just go on and on and on. So, so I guess my question for you, as a person who I know thinks about this deeply, is do you think we have causal evidence, um, that, that will pin, uh, what seems intuitive to many of us, right? Which is social media probably is a net negative. It has some benefits, but it's got a lot of negatives at, at least for a vulnerable population. Um, or, or do we think that we just haven't got that causal bullet and that really there's, you know, we're looking at two things that have gone up over the same period of time that are correlated, but, but, you know, getting rid of social media is not going to fix the mental health of young people. So, so how do, how do you-- Sorry for the long question, but, but how do you think about that?

    2. AL

      Well, I'll start at the end. Um, I don't think anybody who thinks there's a causal harm from social media thinks that we should get rid of social media. That, that anyway is an impossibility. I think what we're talking about is harm risks-

    3. PA

      Yeah, sorry, sorry. I should, I should just be-

    4. AL

      Yeah

    5. PA

      ... clear there. And, and, and Jonathan doesn't think that either, right?

    6. AL

      Right.

    7. PA

      I think Jonathan's argument is maybe, maybe people should not be using social media while they're young. Um, but-

    8. AL

      Right

    9. PA

      ... but anyway, yes. So, so I just wanted to make sure I wasn't putting words in anybody's mouth on that front. Yeah.

    10. AL

      Okay. Yeah. Great. Um, yeah. So I mean, let, let's look at the different types of evidence. One of the most important types of evidence in medicine is empirical evidence. This is observation and subjective experience. And we have plenty of empirical evidence to show that young people, and I'm gonna focus on young people because, you know, when you, when you think about a policy intervention, I really think we're, we're thinking about how to direct that to young people. Um, that young people endorse that they feel addicted to social media, not, not all, but many, and that they use it more than they would like, and that it's adversely affecting their mental health. That is a powerful piece of evidence. Now, you could, you could say there's, you know, could, uh, there's cultural stimulation or stimulated reporting. Sure. But we have loads of young people now who are endorsing that. We also have a lot of observational evidence that is showing many of the Bradford Hill criteria, starting with a dose-dependent response. We know that the more people, the more time that people spend on social media, the more likely they are to experience anxiety, depression, insomnia, inattention, et cetera. Um, now you could argue, well, chicken and the egg. Maybe those were individuals who were vulnerable or already had depression, anxiety, which made them want to self-medicate by using more social media. But I think the strongest evidence, uh, against that is the, um, the evidence that we have on another Bradford Hill criteria, which is experimentation. When we intervene in these cases of depressed and anxious individuals and take social media away for a period of time or even limit use, people are feeling less depressed and anxious. And that is a very powerful piece of evidence to me, but not even the only one. Other Bradford Hill criteria, you have biological plausibility. Does it even make biological sense that engaging with social media could change the brain and in ways that are potentially harmful and, and beneficial. Sure. I mean, it's, you know, that's the organ that we're using to consume social media. Uh, so it's completely biologically plausible. We also know that when people are doing activities that engage in, for example, social validation, that releases dopamine in the brain's reward pathway. And what is social media if not a slop, slot machine for validation?

    11. PA

      Mm.

    12. AL

      You have, um, you have strength of association. So yes, these are correlative phenomenon, but study after study after study is showing similar findings. Yes, there are exceptions. Uh, but in general, you know, the, the, the powerful studies that we have are st- are showing the strength of association. And then you have temporality. Now, temporality is hard to, to get because usually, meaning that which one comes first. Are people using social media a lot and then get depressed and anxious, depressed and anxious, and then using social media? Um, and of course our natural retrospectoscope will want to rationalize and explain, um, certain irrational behaviors. But I mean, we can often get pretty good reports of temporality subjectively in an individual clinical case, but also epidemiologically, and this is Jonathan Haidt's work, right? He's saying, look, if you look at when, um, for example, social media became widely available on college campuses, it didn't happen uniformly. Some college campuses, uh, got social media up and running much earlier than others, and you see on those campuses where it was widely available and used, worse mental health outcomes. So to me, um, you know, the weight of the evidence makes it more likely than not that social media is causing mental health harms, especially in youth. And so earlier you asked me, what can parents do? 'Cause to me, you know, pornography, that, that, that begins to fit into social media as well. Um, what can parents do? I don't think it should be solely up to parents. Parents need help, right? Schools need to get smartphones out of the schools so that, uh, adolescents can actually have the liberty and freedom to concentrate on learning, because these devices, the way that they hijack the reward system, make it almost impossible for children to learn and almost impossible for teachers to teach. Uh, you know, you, you analogize to, to alcohol. We have lots of laws that limit a child's access to alcohol. We have federal funding for highways that are tied to drinking age limits in those states. The age of 21 is universal in every state now. Why? Because people wanted those dollars to build their highways. We should be doing that. We should be offering federal and state funding to schools that actually, um, make sure-

    13. PA

      Right

    14. AL

      ... that from the top down, uh, kids are not looking at their smartphones and that they have some tech-free spaces and some opportunities for both socializing and learning that don't rely on the internet and rely on technology. What are we hearing from schools, mostly private schools, uh, that are eliminating smartphones? That the schools are noisy again because kids are actually interacting with each other. So lots and lots of empirical evidence, um, that's also, yes, consistent with our intuition that, gee whiz, there's a problem here, we need to do something about it, which isn't the same thing as saying, um, "Social media's bad, and nobody should be on social media, and it's all evil, and it's the devil."

    15. PA

      Mm-hmm.

    16. AL

      And that's what people said about TV, and that's what they said about radio. You know, this is on a very different scale, the way that the algorithms learn what we've done before, um, making these media so potently addictive. You only have to walk through an airport to see the ways in which we've all, you know, stopped engaging with our surroundings.

  14. 1:53:32 – 1:57:04

    How exercise affects brain chemistry, the role of dopamine and endorphins, and how exercise can become addictive

    1. PA

      I want to talk about something we haven't talked about yet, but that gets often lumped in the category of addiction, which is exercise. Um, so maybe let's start with the brain chemistry of, of exercise. I think people have heard the term endorphins, but what exactly is an endorphin? Is that sort of a, a, a, an irrelevant, uh, topic here, and is it-- does this really boil down to dopamine again?

    2. AL

      I would say yes and yes. So endorphin is an endogenous opioid. We make our own opioids. Thank God we do. Um, otherwise, we wouldn't be able to cope with physical pain. Exercise is actually immediately toxic to cells. Strange. Why would something that is toxic to cells be ultimately healthy for us? And the evidence is overwhelming that, uh, exercise in moderation, uh, depending upon that person's fitness level, um, is, is healthy. Essentially, what's happening is that as the body senses injury, we upregulate production of our own feel-good neurotransmitters, like dopamine, but also serotonin, norepinephrine, endogenous opioids. That's the runner's high. If you look back at this metaphor of the pleasure-pain balance, we saw that when we press on the pleasure side, the gremlins of neuroadaptation hop on the pain side as a way to bring us in balance ultimately again. The same thing happens with painful stimuli. When we do things intentionally that are physically or mentally challenging for us, our body senses injury, upregulates feel-good neurotransmitters, and those gremlins actually go over and hop on the pleasure side, so we get our dopamine indirectly by paying for it up front. And you see this, for example, with studies that have looked at ice cold-water immersion-

    3. PA

      Mm

    4. AL

      ... noting that dopamine levels gra- rise gradually over the latter half of the immersive ice cold-water bath. And then interestingly, those dopamine levels, and serotonin and norepinephrine, stay elevated for hours afterwards before going back down to the baseline levels of dopamine firing, which is amazing, because what that says is we never go into that dopamine deficit state. We get our dopamine indirectly by paying for it up front, and that process is relatively more immune to the problem of addiction because we had to work first to get it. Um, whereas intoxicants cause that sudden upward spike of dopamine followed by dopamine free fall, that dopamine deficit state, that state of craving before going back to the, the level position. Now, are there certain personalities that can get addicted to exercise? Absolutely. Um, we do see this in clinical care, and I think we also see it, you know, again, just in our culture. We've also drugified exercise, made it more potent, made it possible to do it in more extreme conditions. Um, we've social media-fied it so that now people are comparing themselves not just to their immediate neighbor, but to people all over the world. We've quantified it down to the nth degree. We're constantly measuring ourselves, our heartbeats, our breathing, our sleep. Um, many people actually get kind of addicted to those numbers or quantifications. Now they're pursuing a certain numerical outcome. Dopamine is probably ultimately quite sensitive to numerification. Um, and when we intervene for an exercise addiction, we intervene similar to the way that we intervene for other addictions. We ask people to abstain from that particular exercise for a period of time, try to reset reward pathways, and then when they go back to using, using in a way that's not harmful or self or other destructive.

  15. 1:57:04 – 2:04:47

    Cold-water immersion for mood regulation, and other healthy coping strategies

    1. PA

      This idea, by the way, that both exercise and cold are, for the most part, healthy ways to experience pleasure because the pain comes first and you have to do the work to get the pain to experience the pleasure. Um, I, I think it's safe to say that that, that's probably how the majority of people would experience that. You do write about a fellow in your book who, uh, you m- maybe took the cold plunge thing a little too extreme. But I would argue in his context, it might have been the lesser of two evils, right? Because ultimately this became, uh, uh, uh, I, I think a, a more well-adapted coping mechanism to an otherwise maladaptive addiction. Would you say that's fair?

    2. AL

      I do. I agree with you. So this was an individual addicted to alcohol and cocaine who got into recovery, um, experienced a lot of dysphoria, and discovered that taking an ice cold shower in the morning that was recommended to him by, um, a trainer or a coach was actually, um-- made him high. It, it gave him the, the kind of response, uh, that he often got from drugs. So he began doing daily ice cold shower, and then over time got himself, uh, like, um, a cooler and, you know, would submerge himself in ever colder temperatures and then got a motor to circulate the water. So he was breaking the ice off in the morning. At some point kind of realized, "Oh, wait a minute, I think, you know, my tendency to take things to extreme may be operating here." But yes, absolutely, I agree with you. Ultimately, this was a, a healthy, a healthy coping strategy. Um, and ultimately, you know, in, in a really-- which really speaks to what is a healthy coping strategy. Uh, it's something that we also do with other people. So he started doing it with his family, with, uh, social groups. People would come over, over for ice cold water bath parties. You know, much better than having people over, um, you know, to, to snort some lines or, you know, whatever the case may be. Um, so yes, and we have lots of patients who, when they get into recovery from drugs and alcohol, will often discover sports and, and, you know, endurance athletes to, to-- in order so that they can still have that striving and that goal and the endorphins. We just have to make sure they don't continue to do it to the point of, you know, personal injury.

    3. PA

      You know, I discovered something, uh, m- m- several years ago, which was, um, if I took an ice cold shower, uh, and I-- when I was very upset, angry, uh, the, the mood would reverse quite quickly and, and I kind of attributed that to stimulation of the vagus nerve. Um, a- again, it had to be like my head had to be immersed in cold water. It could, it could have even presumably been dipping my head in a cold water sort of stimulating, uh, the dive reflex. Um, but like others who enjoy cold plunging, which I do very, very much, um, I, I, I would completely share that experience. It is a absolutely mood-lifting experience. And when people ask me, which I get asked, as you can imagine, all the time, um, you know, "Is, is cold plunging kind of an elixir of longevity?" Um, having looked at the data very carefully, um, I can say that the answer appears unlikely. I, I see no evidence that cold immersion, um, alters any of the hallmarks of aging with the one possible exception being a reduction in inflammation. Uh, so-- But, but that's never translated to a clinical benefit vis-a-vis disease in the way that I do think that there is benefit to sauna, right? So I do think if you look at the sauna literature a- and run that same Bradford Hill c-criteria, uh, along with the experimental data which are included, that, that there really is probably causality between the benefits of sauna and disease prevention. So again, I don't see that with cold, um, but [clears throat] my m- my use of it personally just stems from the mood elevation. And if it-- You know, so, so s-- believing that it has no benefit on my ability to reduce the risk of cancer, heart disease or dementia, uh, just the mood elevation alone for me seems to be reason enough. So, um, I was-- I enjoyed the story of that gentleman. [chuckles]

    4. AL

      Yeah. Yeah. Yeah. That's interesting. I didn't know that about the data with sauna or even longevity relationship, uh, with ice cold water plunges. But in terms of a mood modulator and a, a replacement behavior, because I do think that ultimately we are strivers, right? We, we want to experience intense emotions and, and it's not that we can just sort of not have goals and not have emotions. We, we want that kind of intensity, and certainly many of my patients, um, have reported similar types of positive responses to ice cold water plunges. Um-

    5. PA

      Which by the way, I don't notice with sauna. So, so-

    6. AL

      Yeah

    7. PA

      ... with, with, with extreme heat, which I also enjoy greatly, um, it's a different sensation, and I'm, I'm curious, do you think that there's something about cold that produces more pain? I mean, I guess it does feel much more painful. Um, i- is that-- is it simply come down to the pain?

    8. AL

      I, you know, it, I don't think we know. I, I do think that the immediate response is going to be some kind of hormetic response, hormesis being this Greek term that means to set in motion. We're setting into motion our own, uh, regulatory healing response in response to injury. Um, and the, the branch of science called hormesis is, uh, looking at the ways in which toxic or noxious stimuli actually makes us more resilient over the long run. So, um, yes, I think that it's an immediate hormetic response, and let me just say we see this being beneficial, not just in people struggling with addiction or looking for alternative sources of dopamine, but also when people get immediately dysregulated. So you noted that when you get angry, it's helpful. So when we have patients who are very dysregulated, overwhelmed by their emotions, can't reregulate, we say, "Stick your face in an ice cold water bath. Plunge your hands in an ice cold water bath." So, and it really, really works for some people.

    9. PA

      Mm-hmm.

    10. AL

      Um, there, there's also interesting work looking at cold more broadly and what it does to neurons, and it turns out that cold is one of the, uh, most potent stimuli for neurogenesis. So very interesting looking at like mice brains a- after expo- exposing the mouse to extreme cold, or the effect of hibernation in extreme cold, and finding that cold, uh, uh, initially causes a sort of like, not neuronal death, but if you look at the brain slices, it looks almost like these dendritic, you know, tree-like neuronal structures sort of die out, you know, in response to cold. But then very quickly afterwards, you get a spring-like regrowth, um, and amazing neurogenesis. So who knows? Maybe the repetitive use of cold on some level is causing or facilitating, um, human n- n- neurogenesis as well. I don't know. Um, I would love though to see more broadly in the field of neuroscience, people look at this concept of drug of choice 'cause it's so interesting. Cold, for example, does absolutely nothing for me. It, I don't, I don't enjoy the experience, but I also don't get benefit afterward.

    11. PA

      Mm-hmm.

    12. AL

      Um, I sure wish I did 'cause it's a nice, easily accessible kind of a tool. Um, but for many people, including you, it's, it's very potent, and that's great.

    13. PA

      You

  16. 2:04:47 – 2:09:30

    The “marshmallow experiment”: how broken promises affect behavior and trustworthy environments help children develop self-control

    1. PA

      write about, um, a very famous experiment that I'm sure everyone listening to this has heard, which is the marshmallow experiment, and most of us who are parents did the marshmallow experiment on our kids with the real hope that they would be able to refrain from eating the marshmallow, uh, because of how we believe it might predict better success later in life. But you also write about a revised version of that experiment, which I think is actually a little more interesting. Um, do you mind just explaining both the original for those who might not be familiar with it and, and also of course the revised version and, and above all else, what it is that that tells us about being parents?

    2. AL

      Yeah. So, um, the original marshmallow experiment was conducted at Stanford, and it looked at kids between about the age of two and five, um, and it put them-- the kid, the child was placed in a room, uh, with nothing in the room except for a table, a chair, a little plate, and on that plate, a single marshmallow. And the researcher said to the child, you know, "I'm going to leave the room, um, and I'll be back in fifteen minutes. If you can go the whole fifteen minutes without eating a marsh- eating this marshmallow, when I come back, I will give you a second marshmallow, so you'll get two." And the whole point of it was to really measure delayed gratification and a child's ability to delay gratification. And the, the most significant finding was very simply that older children were better able to delay gratification than younger children, so that this is a, a skill or a capacity that children will develop with age. But even within a single age co- cohort, there were differences. Some children were better able than others to wait the full fifteen minutes or just wait longer before eating that first marshmallow. And what they then did, and this part of the study is a little bit controversial, but what they then did was followed those kids prospectively, some, in some cases all the way through college and later, and sort of looked at their life outcomes. And the claim was that the kids who, within their age cohort, were able to wait longer for the marshmallow, i.e. delayed gratification, were also more likely to graduate high school, graduate college, and go on to have sort of successful lives, so to speak. So the variance on the marshmallow experiment that, that I learned about i- in, in my researching for this book was that they decided to do, um, um, uh, another version in which they divided the groups of kids into two groups, and in addition to the plate and the marshmallow, there was also a bell that they could ring. Uh, and they told one group, um, "If at any point in these fifteen minutes you'd like me to return for any reason, just ring this bell and I'll come back." Uh, so they told, told that to both of those groups. But in one group, when the child rang the bell, the researcher came back, and in the other group, uh, when the child rang the bell, the, the researcher didn't come back until the full fifteen minutes were over. So in other words, one, one, one group of children was told the truth and another group of children was lied to. And, um, what they discovered was that the children who were lied to were much more likely to eat that marshmallow before the full fifteen minutes were up. And I, it's just, to me, it's such a powerful paradigm for the importance of truth telling and to not only to teach our kids the importance of telling the truth, but to model that for our kids and actually be truthful and show up when we said we were going to show up, because it looks like what happens when we're living in an environment where people cannot rely on other people around them, especially adult caregivers, to do what they said they were gonna do, that we essentially go into a kind of survival mode where we just feel like, "Nobody's gonna take care of me. I gotta take care of myself. I better eat this marshmallow now because if they're not gonna come back in the room, maybe they're also not gonna bring me a second marshmallow-

    3. PA

      Mm

    4. AL

      ... if I wait the full 15 minutes." And that can really breed, um, within a family dynamic, a very toxic kind of interpersonal family system that I think does increase the risk of addictive behaviors later on, because what we'll often see in patients with severe addiction is not only that they had a, a parent or caregiver who was addicted, but that they had lived in a house where lying was rampant, where people almost never showed up.

    5. PA

      Right.

    6. AL

      When they said they were gonna show up, never did what they, they said they were going to do. Um, so it's, it's very interesting to me how something like telling the truth can be such a powerful shaper of appetitive control.

  17. 2:09:30 – 2:17:57

    Can GLP-1 agonists be useful in treating addiction?

    1. PA

      Speaking of appetitive control, you, you note how individuals who have had gastric bypass, um, while quite successful in, uh, curbing appetite and ultimately food consumption, and therefore being a great tool for managing obesity and type 2 diabetes, are prone to higher rates of alcoholism. Uh, can you say a little bit more about that? And, and, and ultimately what I want to really talk about is this new class of drugs that have been introduced, uh, GLP-1 agonist, but let's just set the stage on the, uh, on the gastric bypasses.

    2. AL

      Yeah. So about a quarter of individuals undergoing gastric bypass for obesity, which you might conceptualize as food addiction, um, in certain vulnerable individuals, um, will go on to develop an alcohol use disorder after their gastric bypass, and that's probably operating on multiple levels. One level on which it's operating is that alcohol becomes immediately a much more potent drug for them because through the gastric bypass, they essentially have a kind of a dumping syndrome where they get the equivalent of many more drinks because it immediately goes into the duodenum and is absorbed. So they get, [lips smack] um, you know, where they can have one drink and immediately feel their effects. And, and part of potency is not just how much dopamine it's released, but how quickly it's released, um, which is why, for example, you know, injecting is so potentially addictive because it's basically right to the brain. Um, so alcohol becomes a very potent drug for them, but also because of the problem of cross addiction, where when people give up one addictive substance or behavior, they are vulnerable to switch that addictive tendency over to another substance or behavior. And so unless we're directly addressing the problem of the behavioral addiction itself at the same time that we're addressing, uh, the obesity and doing the, the, the bypass surgery, folks are gonna be vulnerable to that.

    3. PA

      Yeah. So, so, so what has been your experience clinically with the significant increase we've seen in the use of GLP-1 agonists and the expansion in use from, uh, type 2 diabetes to obesity to overweight to, you know, basically anybody? Um, [clears throat] on the one hand, there have been a lot of reports that GLP-1 agonists not only curb appetite, which is the desired outcome, but may in fact also curb desire and maybe even pleasure. And that would actually suggest that unlike a gastric bypass, an individual who uses a GLP-1 agonist to achieve their weight loss goals might also have another benefit in that it might curb other maladaptive behaviors such as alcohol consumption. Um, so just kind of curious as to what you've seen as the, as the field is still quite nascent in our understanding, but, but obviously you're, you, you're probably the canary in the coal mine for some of these things.

    4. AL

      Yeah. So I mean, these are really fascinating drugs, and what we are seeing clinically is individuals with food addiction and individuals with alcohol addiction, alcohol use disorder, which by the way, is closely linked to food addiction because alcohol is caloric, so we've got both mediated through the carbohydrate system. Individuals with, at least in the cases where, where we have experimented off-label, uh, with the semaglutide, the GLP-1, um, you know, drugs, [lips smack] um, these individuals have tried almost everything to get their addiction under control, and I would say more, we have more experience with treatment-refractory alcohol use disorder, including trying medications, right? Medications like baclofen, um, medications like, uh, naltrexone, medications like Top-

    5. PA

      I, I didn't know about baclofen, so tell me, baclofen the muscle-

    6. AL

      Yeah

    7. PA

      ... relaxant is used to treat-

    8. AL

      Yes

    9. PA

      ... alcohol disorder?

    10. AL

      Yeah. So there are more placebo controlled trials in Europe than here in the US. It's not FDA approved for that indication. It's not first line for us, but we will sometimes use bac- baclofen, sometimes u- we'll use gabapentin.

    11. PA

      What doses of, of baclofen and now gabapentin are, are necessary to produce that effect?

    12. AL

      Well, gabapentin we usually, I, I will say I, I'm using less gabapentin than I used to.

    13. PA

      Mm-hmm.

    14. AL

      Because we've been s- seeing people actually get physically dependent, in some cases addicted to gabapentin.

    15. PA

      Mm.

    16. AL

      But typically we'll use the 600 milligrams three times a day to help people withdraw from alcohol and in some cases, um, maintenance, although less of that. I don't use baclofen often enough to tell you what the dose is.

    17. PA

      Okay.

    18. AL

      I, I have to look it up. Um, but, but those are, those, I would say more often we're using naltrexone, the opioid receptor blocker, which can be very nice because, uh, many people's goal is moderation, not just abstinence, and naltrexone's been helped, been shown to help not just with abstinence but also re- reducing drinks on drinking days. So that's very nice. We, we use that almost as first line. We use Antabuse, disulfiram, which is the one that's a deterrent. If you drink on it, you'll get sick. People don't usually like to go to that first line, but it, it works when people take it. We use things like topiramate.

    19. PA

      It should be pointed out that if patients do use that and drink through it, they are actually increasing the toxicity of alcohol gram for gram-

    20. AL

      Yes

    21. PA

      ... because they're experiencing more acetaldehyde, which is the, obviously the toxic mediator.

    22. AL

      Yes, exactly. So you really have to be careful who you prescribe it to, and it has to be somebody who ca- can really be committed to not drinking o- once they've taken that medication. Um, we also use topiramate, which is a seizure medication which was first discovered off-label to be helpful for binge eating disorder and, um, later was shown to be helpful for alcohol use disorder. But the bottom line is, when we have a case of a patient who has tried these various medications, who's been involved in Alcoholics Anonymous, who's tried psychotherapy, who's gone to rehab, who's done it all, um, in that rare instance, because it is off-label and because it's so new, and so we, we're conservative with medications, we will occasionally, we have occasionally recommended semaglutide or the GLP-1, um, drugs. And, um, in one case in particular, it was very striking the extent to which this individual with treatment-refractory alcohol use disorder endorsed the complete cessation of alcohol craving-

    23. PA

      Hmm

    24. AL

      ... um, with, uh, semaglutide. And, you know, it's, it's very moving to see that in an individual who has struggled so long and so hard, uh, to battle their addiction, and then there's this drug that seems to, um, just suddenly turn off all the noise for them.

    25. PA

      Was that patient at all overweight?

    26. AL

      Yes. And so that's how we could justify it, right?

    27. PA

      I see.

    28. AL

      Because, uh, uh, he, he, we were giving it to him for being overweight, for, um, not having type 2 diabetes, but being at risk for type 2 diabetes.

    29. PA

      I see.

    30. AL

      Um, but, but the, our real agenda was the alcohol.

  18. 2:17:57 – 2:24:14

    The benefits of 12-step programs

    1. PA

      the best job I've ever encountered of describing 12-step programs, um, which I think people tend to have very polarizing views of, right? So you've got people who view these things as, you know, the best things in the world, everybody should be in a 12-step program, even if they've got just the mildest inclination towards addiction. And then you've got another group of people who say it's a cult, it's re- you know, it should never be a part of addiction recovery. And I, I think, um, you very eloquently, I think, describe both sides of this and, and, and I think land in a very reasonable position, which is, which is actually quite favorable for a given individual and maybe not for all individuals. Do, do you mind just saying a little bit about that? Because I know that, um, there are many s- 12, tw- 12-step programs out there. Um, I, I've been to many meetings myself and have, have actually always found them to be remarkable, um, even when the, the topic at hand is not something that I particularly share the addiction for. But where I've always found it amazing is in the sharing, um, and in the, um, something that you described as the pro-social shame, right?

    2. AL

      Right. Right.

    3. PA

      So, so maybe, maybe say a little bit about, um, your, your view on 12-step programs in, in, in the, in the, in the help, uh, of those who, who are struggling with addiction and, and, and what pro-social shame means and why it's an important part of recovery.

    4. AL

      Yeah. So, um, I always like to say there are many ways to the top of the mountain, uh, and everybody is going to take their own path, but we have clear evidence for things that work, and at the same time there's, again, enormous inter-individual variability. So what works for one person may not work for another, but it would be good if all persons had access to all the different options so that they could explore what works for them. Um, 12-step groups are not a treatment per se. They're not professionally led. These are peer recovery groups where people are helping other people struggling with the same problem and they intentionally eschew affiliation with any kind of political, um, agenda. There's no monetary, um, there's no fee structure. They, they don't involve themselves in, in money. All of, all of that incredibly wise, recognizing that we humans are, um, so vulnerable to, um, kind of mismanaging and asserting our own agendas, uh, in these kinds of endeavors and sort of keep it free and accessible and everywhere, um, is just makes the bar for admission much, much lower, which increases access. So even if you're talking about an effect size that may not be as large as some kind of professional mediated treatment, the, the simple fact that it's free and it's in every church or synagogue basement, uh, in the world, uh, or, or, or community center equivalent, uh, makes it already a very potent intervention. Um, I think it's, it's also important to acknowledge that for, uh, people with more extreme forms of addiction, um, that the 12-step groups may work even better than individual or group psychotherapy that's professionally led.

    5. PA

      Hmm.

    6. AL

      And I refer folks to the, the, the Cochrane review by John Kelly and Keith Humphreys and co-authors that really reviews the evidence and clearly shows that 12-step are an evidence-based treatment or effective intervention for people who actively participate. For reasons that I don't entirely understand, the, the press and the media and sort of the culture has been very 12-step bashing of late. I don't know quite where that comes from. Um, I, I do think that it's important not to force people to go to 12-step or to say that's the only way to do it. Um, but, but you don't wanna also then, you know, malign or get rid of something that's clearly very effective. Why does 12-step work when it does work? I think one of the main, um, sources of efficacy is, again, easy access, low bar for participation, and it may be one of the few places left in modern society where people can show up and be their fully flawed and broken selves and be entirely accepted for that. Not just accepted, but where our brokenness becomes a positive social good. Um, this may not even be true anymore in faith-based organizations where people are sometimes get so caught up in proving the, uh, the bounties of believing that they are then loathe or reluctant or even discouraged from disclosing the ways in which their life is not working out. I have a very good friend who's a, a theologian and a devout Christian who of late has stopped going to his church and instead is going to 12-step meetings. He does not in fact have an addiction, but he gets so much, um, nourishment from this coming together of people who can talk freely about their mess-ups and their greed and their, their, the mistakes that they've made and their, you know, shameful, um, guilt-ridden types of behaviors and come out, you know, on the other side feeling better for it, less ashamed, um, more motivated to change those behaviors. Um, a- and plus, you know, it, it, the whole sponsorship s- program is so powerful, right? Where you get a sponsor, you work the steps.

    7. PA

      Hmm.

    8. AL

      People can call their sponsors any time of the day, uh, any day of the week. You can't do that with me. Like, if you call me at midnight on a Saturday, I'm not gonna get that message till Monday, and depending upon the, you know, the, uh, the clinical acuity, I might not return that call till Tuesday. That's not true for a sponsor. You can call a sponsor in the middle of the night and that sponsorship bond, that person will-- might, might even come over to your house. You know what I'm saying? So to me, it's just a very remarkable social movement, definitely not for everybody, but incredibly potent and powerful, especially in a world that is, in general, conspiring against our mental health.

  19. 2:24:14 – 2:32:01

    Why understanding a patient’s story is essential for meaningful psychiatric care

    1. PA

      You write about something so eloquently, and it really reminds me of a close friend, Paul Conti, and I, I don't know if you and Paul ever-

    2. AL

      Oh, yeah

    3. PA

      ... overlapped when he was doing his residency at Stanford. But, um, Paul always talks about the patient's story, the patient's story. And so I was really, uh, um, touched by how you, you really wrote about the same thing, right? Which is we've pathologized mental health so much down to [clears throat] , you know, history of present illness, review of systems. And, um, you've talked about your own journey as a psychiatrist and your own evolution away from [lips smack] the traditional training where at the end of the day, you've gotta come up with a DSM-IV or DSM-V code. You have to be able to come up with a label. And so you're interacting with a person and you're, you're in the mode of what's the label? What axis is this person? What's the diagnosis? And you talk about now how you teach residents to just put that aside and listen to the story of the person. Um, what, what is it in your journey that, that led you there? Um, and, and how, how difficult or how easy is it to be training other psychiatrists in that, in that school of, of thinking?

    4. AL

      Yeah. I mean, what comes to the mind immediately about w- what in my journey led me to do that is gonna sound super selfish, but it was the realization that I was not engaged or interested in this person. I could not capture my own empathy for them unless I knew the story. Uh, you know, the, the sort of, as I say, the mini autobiography of their lives. What had transpired in their early life? What were the major milestones? How did they end up where they are today? Who was in their life? What were the, you know, the major influences? I mean, it, narrative is so powerful. As you know, our brains are wired for story. Our prefrontal cortex is activated when we listen to narrative. We learn through narrative. I mean, narrative is such, um, a powerful mechanism for so much of what we do. I think Foucault said something like, uh, "Narrative is the only way we can measure lived time," which I think is really powerful, and it's also one of the primary ways to get at causality. Of course, we can tell ourselves stories that aren't true a- and come up with causal relationships that aren't based in fact.

    5. PA

      Hmm.

    6. AL

      But when we're telling true stories, it is the way that we, um, understand what led to what led to what. Um, so, [smacks lips] uh, and it's also just much more interesting and more fun. A- and that's, I, I see that as a psychiatrist's job. That's the data, right? What, that is our, that's our bread and butter. You know, the, the cardiologist gets the EKG, the, the surgeon's cutting and sewing and, and we deal in story, and we must deal in story. And when we have new fellows, we have addiction medicine fellows, um, you know, they come from many different specialties. We have family medicine doctors, emergency medicine doctors-

    7. PA

      Hmm

    8. AL

      ... uh, pediatricians, psychiatrists, and it's so hard for them to let go of that kind of structured categorization, chief complaint, history of present illness, past medical history. But I just say, "Trust me on this. Trust me."

    9. PA

      Hmm.

    10. AL

      Start with their story. Say, "Tell me the story of your life, um, where you were born, who raised you, what you were like as a kid, major milestones, memories that you remember-

    11. PA

      Hmm

    12. AL

      ... that were impactful or important. Um, all the way up into the present day. Who do you live with? Who are the important people in your life? What do you care about? What are your goals and dreams?" If we don't do that, w- we end up with a kind of a, you know, a laundry list of symptoms that is not actually a person.

    13. PA

      Anna, when you think back over your career, you know, you've, you've written about what are undoubtedly a lot of the amazing success stories, right? People who seemed on the, on the brink of, of death in some cases, and, and if not death, outright destruction of their lives and relationships. Um, but I have to imagine that there's a graveyard, too, of people that you haven't been able to help. Um, how, how have you coped with that?

    14. AL

      It's a great question, and it's very timely, uh, 'cause I just had clinic yesterday, and I had a, an interaction with a patient that was really not good, and the patient was very angry at me. Um, the key, I think, for me, is to just stay curious, to just continue to wonder about this person, what shaped them, um, what their motives might be, and how all of that might inform how we can help them. So to, to stay in this empathic professional stance, um, to look at myself, right? So if a patient criticizes me or the treatment, g- what, what is potentially correct about that? Um, how have I messed up? Um, how can I make amends? Um, so really trying to walk a path of humility. Um, you know, the longer I've practiced psychiatry, believe it or not, in some ways the less I think I actually understand about the brain and, um, how people change. Um, I mean, at some really core level, it is a great mystery. Um, so just trying to stay humble and curious and empathic, um, and then also go home and forget about it for a while and, uh, make sure I take care of myself and my family.

    15. PA

      Yeah, the further you get from shore, the deeper the water gets, uh-

    16. AL

      Yes [laughs]

    17. PA

      ... for sure. W- when, when you lose a patient, which I'm sure you do, right? I'm sure there are many patients-

    18. AL

      Yeah

    19. PA

      ... where it's not just that they're angry at you in clinic, it's that they succumb to their addictions, uh-

    20. AL

      Yeah

    21. PA

      ... physically succumb, literally die.

    22. AL

      Right.

    23. PA

      Um, i- i- is that something where [clears throat] you've accepted the fact that that's going to happen, but the, it's the pri- the, you know, being attached to that patient and suffering the pain of their loss is the price you pay to be a better doctor, or is there a way to, uh, create a boundary and never let yourself, uh, hurt in the, in, in that situation?

    24. AL

      One of my early mentors and supervisors said something to me that I'll never forget. He said, "Anna, the reason that the work that we do works when it does work is because we actually love our patients and the emotions are real." We have to come to the therapeutic encounter with our own physical, mental, sexual needs met so that we are there 100% for the patient's needs, but the emotions are real. The relationship is real.

    25. PA

      Hmm.

    26. AL

      We have to care about these folks. So I think that is a deep truism, and, um, when, when, you know, when my, when, when, when a patient dies, it is devastating. It's absolutely devastating, and the guilt is enormous. Um, you know, the kind of what ifs, if only I had done that, if only we had been more present or more proactive or whatever it is. You j- you kind of can't get away from that.

    27. PA

      This has been a, a fantastic discussion. Um, I, I really appreciate the work you're doing. Your writing is exceptional, um, and, and, and I certainly appreciate it, uh, and, and obviously just appreciate your, your time today. Thank you very much.

    28. AL

      Oh, well, thank you. It was a lovely interview. I enjoyed meeting with you. Thank you for your important work, and, uh, yeah, it was, it was a pleasure to talk with you.

    29. PA

      Thank you. [upbeat music]

Episode duration: 2:32:01

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