Addiction (featuring Dr. Marcelo Wood)

26:42So your epigenome controls how your genes are turned on and off and regulated. And here's the crazy part. your DNA gets these little chemical modifications. The protein that helps compact the DNA gets little modifications. That whole collection of modifications is called your epigenome. Every epigenetic modification is a metabolite. So our diet, our experience, our sleep, our stress, the pesticides that we eat in our food, all get integrated into that platform. And that's how we adapt within our lifespan, right? So there's evolutionary adaptation that takes eons. And then there's within-organismal adaptation to your life experience.

27:30And the crazy thing is people think that the epigenome can also be a source of heritable experience. That you could pass it on to people. Right. So things that your grandparents experienced would be epigenetically inherited by you. and it can skip generations. So these are all things that people don't understand. The phenomena have been observed, they exist, but we don't understand the mechanism. So if my grandparents had some like amazing transformational chocolate bar a hundred years ago, that could have been somehow encoded and passed down to me and led to me appreciating chocolate even more?

28:05Potentially. And so where they've shown that to be true is with odors associated with fear responses. And so that you can track within a species, but across generations. A grandchild of a grandparent that had an odor associated with a terrifying experience, they'll be weary of that odor for no reason. They've never experienced the fear component. Wow. But we don't know how that works. I remember I had read about, I think it was Michael Meaney's experiments on how moms treated their babies and how that impacted the way they responded to stress for the rest of their lives. And I learned about that right before I got pregnant.

28:43And every time I got stressed out, I was like, no, I'm going to ruin my daughter. And then that stressed me out even more. And it was this like feedback. And eventually my husband was like, you got to here's some ice cream. Calm down. And I was like, all right. And I'd feel better. But all right, let's take a break. And when we get back, we'll unpack epigenetics a little bit more.

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31:03That's why millions of families use Brilliant. Brilliant is the online math tutor that's visual and interactive. Unlike other tools, it never hands your kid the answer. It helps them actually understand math and think for themselves. On Brilliant, students get hands-on with concepts until they make sense, and Brilliant sees their work. So when they get stuck, it knows how to help. It asks just the right questions to get them unstuck or gives visual cues by sketching on their screen. It helps students reason through every problem step by step. Students can build stronger foundations or move ahead as fast as they want, from fractions all the way to calculus.

31:38Brilliant even helps them set goals and keeps them motivated so you don't have to. Brilliant was built by experts from MIT and Harvard and is trusted by millions of parents and teachers. Sign up today at brilliant.org slash tutor and get 20 % off for back to school. That's brilliant.org slash tutor.

32:07And we're back, and let's start with a question from Daniel. So this idea of epigenetics and remembering things, does that mean that, for example, if somebody lives next to a bunch of very nice bean eaters, that their children and their children's children might have a particular response to the aroma of digested beans. Fear response? Honestly, I don't know. Yeah. That's hilarious though. That was a joke question, but I wanted to say more about this sort of state of the art of knowledge about where this information is stored. Because in the case of genetics, it's obvious, it's the DNA, that's where it's stored.

32:47In the case of epigenetics, you pointed to molecular fingerprints and the sort of information around the genome. Like, what is the context in which this can be written and read and impact, you know, the behavior and the life of a creature? Yeah. And so, where this is happening physically is on the DNA itself. So, DNA can obtain a modification called methylation. So, the DNA gets methylated. And that's just a little tiny chemical group that gets added to DNA. And that tiny, tiny little chemical group can absolutely change gene expression. It can shut it down, or in some cases, it can help turn it on.

33:27So an excellent example of this is going back to pregnancy, Kelly. When a mom is pregnant, she'll frequently be prescribed supplemental folic acid. Right? And so a lot of moms will take supplemental folic acid. And the reason is folic acid is a methyl donor. That little chemical group that gets added to DNA, it's a methyl donor. And so folic acid supplementation prevents spina bifida. And so you have normal spinal cord development and whatnot when you've supplemented. You prevent any potential harm from malnutrition or not having enough of the right type of nutrients for that epigenetic mechanism to be engaged.

34:10Another example of that is with rheumatoid arthritis. When you have severe rheumatoid arthritis, you get put on a drug called methotrexate. It's an anti-inflammatory, helps people quite a bit. But usually insurance companies require people to be on it for a couple of years before they get moved on to biologicals like antibodies, which work better. So methotrexate, one of the problems is it causes memory formation problems. And the reason is methotrexate is affecting that DNA methylation pool. And so people that are on methotrexate will frequently supplement with folic acid for their memory. So these epigenetic mechanisms are heavily used during development, and they're also heavily used by our adult brain past development.

34:57And those physical entities exist on the DNA itself, as well as the proteins that the DNA wraps around to get in, compacted into the nucleus of a cell. Is there ever a good reason for your brain to be less good at forming memories? Or is this always just you have a deficit of something you need, and that's why you have the problem and you have to take folic acid. Brilliant question. So for the longest time in my lab, we were obsessed with trying to understand how are long-term memories formed and how do they persist? And we thought, if we can answer that question, we can understand things like PTSD, addiction, et cetera.

35:34And after about 10 years of work, we realized that we had accidentally discovered the opposite. We had discovered enzymes that control epigenetic machinery that prevent you from encoding everything. Huh. And we found out by accident because when we mess with those enzymes, animals can encode subthreshold learning events. Learning events that would not be encoded into long-term memory are perfectly encoded into long-term memory. Huh. And persistently. And so when you modulate the epigenetic machinery, you absolutely massively control learning and memory. Wow. And again, that's what drugs of abuse do as well.

36:15And so going back to what you asked with the memory, our brain is very selective at what it encodes. And we do not want it encoding everything. We want it to encode the most important things that happen to us. For example, if you're crossing the street and you're jaywalking and you almost get hit by a car, your brain will instantly encode that event. It will release a stress hormone. the stress hormone, immediately engages the epigenetic machinery, adjusts it so that you kick on gene expression that allows your neurons to change their structure and function, and they encode everything that you experienced that day.

36:55What kind of car almost killed you, what you were wearing that day, what you had for breakfast, whoever remembers that, unless you eat the exact same thing like I do every single breakfast, what street it was, what time of the day, you encode all that. It's a flash memory. But normally that doesn't happen. Normally it's very difficult for us to encode things. So like med students going through organic chemistry, it's awful trying to memorize all that organic chemistry. Your brain isn't designed to do that. It doesn't want to do that. So it takes repetitive spaced out training to be able to encode things like that.

37:30It is awful. Totally agree. You took organic chemistry as a physicist? Why did you do that to yourself? I didn't take organic chemistry because it is awful. Oh, I see. But I think you're saying that it's good to be able to forget things. Otherwise, we'd be like awash in a bunch of boring details. Yeah. And we should be remembering the important stuff. That's the answer to Kelly's question, is that there's a lot of our lives that are forgettable, unfortunately. Yeah. We would not be able to give the right salience to things, whether good or bad. Everything would be the same. And this is something I don't think I understood.

38:04you're saying essentially that our personalities and our memories are not just encoded in our neural structure. Like, you know, as a physicist who thinks about machine learning and training and stuff, I think about networks learning and all that is encoded in the weights and the structure of the network. You're saying it's more than just the neurons and the structure and the relationships in our brain. There's this whole chemical overlay, this epigenetic overlay that also affects our behavior because it affects our memory. That's like totally brand new knowledge to me today. Wow. I remember a while ago reading a yeast genetics paper.

38:39And so people studying yeast gave yeast a particular food source. The yeast would use that food source and then it engages transcription factors for the metabolic machinery to use the food source. And then you take the food source away and there are all these epigenetic modifications that remain. And so yeast geneticists would call that short-term or long-term memory, depending on how long those chemical modifications on the epigenome lasted. So then, well, why? Why would a yeast care about that or a yeast geneticist care about that? It's because that type of molecular memory then allows a yeast that has experienced the food source once, they experience it a second time, their metabolic machine is ready to use it immediately, and they can out-compete a naive yeast.

39:24Wow. And so it gives them an adaptive advantage. And so that's an epigenetic molecular memory that then allows that yeast to have an adaptive advantage. So I promise I'm going to get us back to addiction. But first, I have to ask you a crazy sounding question, which is, so then if you read science fiction novels where they're like scanning people's brains and uploading them to the cloud to live forever, are you thinking, you also got to scan their epigenetics, otherwise it's not the same person? Oh, absolutely. Absolutely. Yeah. Okay. You two need to collaborate on a sci-fi novel. So to bring us back to addiction, is the connection here, so you mentioned that people who manage to get themselves off of drugs of abuse years later can get triggered.

40:10Is that epigenetics making that happen? In part. In part, for sure. Okay. So we know that drugs of abuse and consistent use can change the circuitry in a very persistent way. And we can measure those changes in all sorts of ways. So we know that happens. We know it's persistent. And one of the only ways that cells can change their function and maintain that difference is through epigenetic regulation. And that's what we see in development. When we develop and our bodies develop, certain parts of our body take on a specific function like the liver or the kidney and forevermore stay that function.

40:47And so that's what's happening to the reward system. It's experienced this drug of abuse for who knows how long. It's adapted and changed persistently. and that fundamental change then puts the brain at risk to relapse. Either due to experience the drug again, like having a drink after being sober for decades, seeing a cue or a context for a cocaine user that can be a rolled up dollar bill, it can be a snow-capped mountain, can trigger somebody with cocaine use disorder. You mean because they did cocaine on a snow-capped mountain once before or because a snow-capped mountain looks like it has cocaine on it?

41:25It reminds them of the powder. Wow. Yeah. Wow, fascinating. So then in your view, is addiction biological? Is it psychological? Is there even a distinction? Is all of psychology just biological? Yeah, so I think it's a mix of that. You know, I spend most of my time studying it at a molecular and epigenetic level, but there's absolutely a psychosocial component to it. As humans, we are very social animals. And one thing that in neuroscience still drives me insane is in neuroscience, we always study an individual brain, right? Always. Whether it's animal research, human research, it's an individual brain.

42:06But our brains never evolve to work individually. Our brains evolve to interact with other brains. Always. They're always interacting with other brains. And that's the success of a species. And so with addiction, it's not only the chemical component and the molecular component, but there's a very large social component to it as well. And it has a genetic component as well. So the heritability of addiction is the same as diabetes, hypertension. The genetic risk is similar to those diseases. But people argue with addiction being a disorder or a disease because you can have addiction be part of your life for quite a long time and then become abstinent and never, ever return to that drug of abuse.

42:59And that can't happen with Alzheimer's disease, right? Right. Or Huntington's disease. If you have that disease, you don't just stop all of a sudden. It doesn't just go away. It will always be there. So people get into these arguments of disease or not disease, et cetera. So then is there a distinction in your mind between things that are habit-forming and things that are addictive? Like you just said that you can have addictions, which then you just walk away from. So for example, I eat chocolate regularly. I don't think I'm addicted to chocolate. I've gone for periods without doing chocolate.

43:33Doing chocolate. Not doing chocolate. Doing chocolate. Hitting chocolate. without my chocolate dealer coming to my house. So is there a distinction there between habit forming and addiction? People also say, for example, marijuana is not addictive, it's habit forming. Is that a meaningful distinction? What does it mean? Well, yeah, I have trouble with splitting hairs like that because people use these terms in different ways. But I think undoubtedly part of the circuitry in the mesolimbic pathway that is the reward circuitry, there's a habit component. And we know from experiments that you can adjust those habit mechanisms to transform into compulsive drug taking.

44:21And so although habits and habit formation might be part of it. That's all it is. It's just part of it. And it might be in series with developing a compulsive disorder, but it might not be. There's so many different components to this. It's hard to tell what's a stronger driver in one person versus another person. So you're saying it is possible to have a healthy relationship with chocolate and also to have chocolate every day. I think so. I want a scientific blessing for my chocolate habit here. Having the same chocolate problem. I want to believe in that too. So now that you've gone into all of this nuance to explain to us that like that social stuff also matters, but I'm going to still try to go back and simplify things for a second.

45:13So we've been trying to look at how addiction impacts the brain. Where are we in our ability to use like medications to try to tinker with the brain to like undo the damage that's been done? Like, you know, five years from now, will we be giving drug addicts a bunch of folic acid or withholding folic acid because it was like an epigenetics thing or yeah. So where are we in being able to give people medications to help with this kind of stuff? Yeah. So there are several approaches. There are pharmacological approaches. So for example, with opioid addiction, a frontline medication is naloxone. And that's an inhibitor.

45:51It binds to the receptor and it blocks the opioid from being able to hit the receptor. And so you can prevent someone from odine. You can rescue their breathing. That's why it's a frontline defense. But then longer treatment, there's buprenorphine and methadone, which also hit those receptors. They give a little bit of the euphoria, but they're much, much safer. And so other countries use those much more than the United States for treatment of opioid addiction. Things like cocaine, there's almost nothing out there for cocaine. People are trying to use your own immune system to fight cocaine use disorder and methamphetamine use disorder, where you can get your immune system to create antibodies against the drug, and then the drug can't bind the receptor or the transporter or whatever, whatever its mode of action.

46:41So that's been somewhat successful. People are using electromagnetic stimulation in the brain. That's been successful for like antidepressant resistant depression. And it works in addiction in some areas. Wait, are you talking about like zapping people's brains? Yeah. Wow. And my, again, very limited understanding is that we don't really understand why that works. It's just kind of like a thing we've tried on people and we've seen that it kind of does work. Or do we understand why applying electric shocks to the brain can help in this situation? I don't know enough about that area. I'd be afraid to speculate too much on the mode of action, how it works, how persistent it works.

47:23That's what I would want to know. We can see short-term effects, but how do those short-term effects really translate into long-term? did that one or very specific dosing of electromagnetic stimulation cause long-term effects or was it just temporary? I can totally see a mechanism for temporary. I don't understand exactly how it'd be specific for long-term, but maybe that's known. I don't know. Okay. So electromagnetic stimulation, I think there was at least one more thing you were going to tell us about. Chocolate therapy. Wasn't it chocolate therapy? Oh yeah. Sorry. That was There's actually the cognitive behavioral therapy.

48:00So using social groups, social support, those are huge. And then there's also, and this is controversial in the United States, but using monetary reward in place of drug to stay clean. Wow. And that kind of management works extremely well. Paying people not to take drugs. Exactly. And you can, just saying it makes you understand why a lot of people are against it. I can imagine if you factor in the cost of supporting somebody with an addiction, if you could just give them that money and they'd stop, that might be better for everybody. Right. No, the money's peanuts to run those programs compared to the over$1 to$4 trillion that costs just the United States to deal with addiction.

48:44Wow. A year. Well, it's a similar argument for universal basic income or universal healthcare. Preventative costs are always smaller. Exactly. Well, our listeners had questions about coffee and sugar and a couple other addictive stimulants. And so let's take a break. And when we come back, we'll get to their questions.

49:23Reach for the sky. Get your Skypot protein soda now at Target or Walmart. Ever wanted to try an Olympic and Paralympic sport? Try fencing. It's fast, competitive, and even offered at the NCAA level. Find a beginner class near you at try fencing.org. That's try fencing.org. Get the feeling you should maybe get out more, see and do more. Totally normal. So is staying stuck. Because finding out what and where just seems hard. A Do More subscription brings you concerts and comedy, sports and museums. For seven scrawny bucks a month, you get at least one pair of tickets to something great. Discover new bands, laugh, learn, do more.

50:05And right now, Do More makes interesting and adventurous easy. Because your first month's free at DoMoreStuff.com slash free. Aging is real. And so are the benefits of adding vital proteins, collagen, peptides to your daily routine. Because around the age of 30, your body needs backup to keep your collagen up to help support healthy hair, skin, nails, bones, and joints. Available in the classic collagen peptides, collagen and protein shakes, and new Vital Proteins Collagen Sparkling Waters. So you can stay vital, stay you. Visit vitalproteins.com to learn more and where to buy. These statements have not been evaluated by the Food and Drug Administration.

50:40This product is not intended to diagnose, treat, cure, or prevent any disease. A big part of parenting today is figuring out which technology will help your kid and which might hurt them. especially when it comes to learning. That's why millions of families use Brilliant. Brilliant is the online math tutor that's visual and interactive. Unlike other tools, it never hands your kid the answer. It helps them actually understand math and think for themselves. On Brilliant, students get hands-on with concepts until they make sense, and Brilliant sees their work. So when they get stuck, it knows how to help.

51:09It asks just the right questions to get them unstuck, or gives visual cues by sketching on their screen. It helps students reason through every problem step by step. Students can build stronger foundations or move ahead as fast as they want, from fractions all the way to calculus. Brilliant even helps them set goals and keeps them motivated so you don't have to. Brilliant was built by experts from MIT and Harvard and is trusted by millions of parents and teachers. Sign up today at brilliant.org slash tutor and get 20 % off for back to school. That's brilliant.org slash tutor.

51:53All right, we're back. And so one thing that I'm dying to know is we've been talking about drugs of abuse, but how do drugs of abuse differ from something like my addiction to scrolling on Instagram or my addiction to coffee in the morning or Daniel's massive addiction that's apparently all he thinks about to chocolate? You mean very healthy, habit-forming behavior. That's right, yes. Yes. Yeah. So, and this, I won't probably speak too much because I don't know enough about natural things like sugar, etc. Drugs of abuse have an absolutely outscaled effect on the neurotransmitter systems and the circuitry in the brain.

52:33things like sugar people say oh you become addicted to sugar and we continuously escalate our sugar intake and and yeah sugar is a problem in our american diet but the impact on metabolism as a whole is massive and so trying to then parse out okay what changed in the whole milieu of metabolism from increasing sugar and compulsive sugar intake that led to more is really hard to pinpoint. Other things like gambling, social media, there was a huge lawsuit that I think Meta just lost for social media and trapping adolescents into social media addiction, right? So there must be aspects of that that are true.

53:25It's definitely true for gambling, These things, social media, gambling, they also release that neurotransmitter. And one reason is because of something called prediction error. So dopamine in your brain is not really thought of as, oh, it's a pleasurable molecule, the pleasure molecule. People mislabel it that way. Oh, you had this amazing meal. We released all this dopamine. That's why it tastes so good. That's not really it. It's the increase in dopamine is a motivation seeper. it tells us and motivates us to go get it. And so with gambling and social media, the dopamine is acting as a prediction error in that you got a better than expected reward.

54:11And so for gambling, you know, you're going to lose a lot, but every once in a while, you're going to hit. And when you hit that high is awesome because your prediction error, you kept expecting, you know, lose, lose, lose, lose. But when you hit and you hit big, it's a massive bonus, like, oh, dopamine, so much release. It's going to drive us to go do that again because it was great. It was a great experience, right? Social media, when people post something that goes viral, same thing. All of a sudden, attention, people saying great things about you, blah, blah, blah, and people get addicted to that and keep pursuing it.

54:50And that can be very detrimental, especially in teenagers where the whole reward circuitry, the learning and memory circuitry in a teenager is still evolving. There's a very complex hormonal kind of control of how the brain is continuing to develop during adolescence. And that's when we're hitting all these kids with pretty bad diets in some cases, social media constantly. Unfortunately, all the news people see is fantastical and blown out of proportion and clickbait, right? It's either amazingly incredible or it's horrific and world-destroying, right? That's how our media is pitched to us now so that we'll actually click on it.

55:36And so when the brain starts to see all of this, it gets confused. The neurotransmitter, all it is is a prediction error. It can't assess value of what you're looking at and what you're doing, really. Right. And that's where all those social constructs, psychosocial behavior, your support group, your family, your friends, that's where all that becomes really, really important. It helps your brain and that collection of brains figure out how to respond to these things. Wow. So when you say the dopamine is the prediction error and that it's not like the reward, it's the thing that motivates you to go back and like put down another 20 bucks on blackjack.

56:15Yeah. Because it's anticipating the occasional big hit. Right. I see. And then we keep pursuing that big hit. Mm-hmm. Yeah. And it's the same thing that thrill seekers do, extreme skiing. I grew up doing extreme skiing. Cool. And I just kept looking for that bigger cliff, more inclined just to get that rush. And you start pursuing more and more dangerous things until you start breaking bones. And then you get either too old or you stop or you die. I am way less exciting. For me, the big hit is when a goat post comes up on Instagram. And I'm like, goats! That's what's exciting for me. But I stay here.

56:59Did you break bones? I got pretty lucky, but I'm 54 years old right now and I damaged my MCL in January. I hit a tree in March, but I still love to ski. So it's all good. Good luck. You learn how to fall. So maybe that's a good transition to studies of how we avoid or leave addictive behaviors. So when Marcelo has been skiing and getting that fix of that thrill of like, wow, I just did something stupid and survived, and then you stop doing it. You were talking earlier about the basic mechanisms of addiction involve obviously the reward and then the habit formation, but then the sort of desensitivity to it.

57:43Is it that last part that's crucial for the difficulty of leaving the addictive behavior? Yeah, I think as the brain kind of switches to this compulsive approach, it's battling one, the anhedonia, the lack of reward for natural rewards and the normal things that you do that should be pleasurable, like the goats, right? That's a natural, normal thing that should be fun. That's right. And I don't know what's wrong with people that don't like goats. Obvious evolutionary benefits. There are some crazy people out there. Yeah, yeah. So your brain starts to battle that. And then your brain has also changed the levels of receptors and all these compensatory things that lead to tolerance and sensitization, incubation of craving.

58:35The longer you're away from something, the more you crave it. That's a wild mechanism. And so it really becomes important trying to find how you normalize those things. How do you get back to normal rewards being stimulating again? And time and time again, one of the most important things is social interaction. That means more to your brain than most other things. But it gets harder and harder for us to do that. So like, for example, in the pandemic, addiction and overdose deaths skyrocketed. Wow. Because we were isolated. We're socially isolated. So it was a very scary problem when thinking about addiction.

59:15Now that things have normalized a bit more, it's gotten better. But this is also one of the concerns about our online lives and how fake our online lives can be. It all comes back down to trying to find normal pleasures be rewarding. And can you maintain that? And for some people, that's exercise. Exercise is great. Getting into that habitual exercise starts to re-transform how your brain responds. And exercise affects all the epigenetic machinery as well. It affects how your metabolism reacts. And so you can use those things to help modify. And so somebody who's become addicted to coffee in the morning and then stops coffee and gets headaches, your advice is, even though you don't feel like going to speak to anybody now because you're miserable, what you really should do is go talk to your neighbors.

1:00:06Yes. Although coffee and headaches are a bit different mechanism. Do we understand that mechanism? Because I think our listener wanted to know why they get a headache when they try to wean themselves off coffee. Yeah, I remember looking this up a long time ago. I don't quite remember, but it does have to do with vasoconstriction and caffeine and vasoconstriction. But I can't remember the exact mechanism. Okay. So when you're not having your coffee at the right time, miss it by a couple hours, you start to get a headache. It's because the blood pressure in your brain has changed. That makes sense.

1:00:41Feels all the more imperative then to get coffee. If you're like, oh my gosh, the pressure in my brain is increasing. I need to go get coffee. And so now I will never be late for my coffee again. What do you think is the future of this field? What do you think we're going to be able to do in 15 or 30 years that we can't do today to help people with addiction? Yeah, so I think two or three things might be incredible. One is trying to understand who will develop addiction and who will not. How do you help people self-identify that they have the genetics or the behavioral psychosocial environment where they really are much more high at risk and to be educated in that.

1:01:26Yeah. Education goes a long way in addiction. Two is for things like epilepsy, there are some incredible closed loop circuit devices that as soon as someone's hippocampus is about to have a seizure, the device starts to register the neuronal spiking and then dampen it down so the person doesn't seize. And so as we identified the reward circuitry that triggers relapse and the cell types and the firing patterns, those types of mechanisms could theoretically be used so that as someone's brain starts to trigger relapse, that device shuts it down and prevents it. Wow. And then the third science fiction, but this is working in other domains, is - Robotic goats?

1:02:13No. Okay. CRISPR editing. And so we now know, for example, in sickle cell anemia, you can do CRISPR editing and it's quite successful. So you mean changing people's genes, basically gene therapy. Right. Wow. It's endivo gene therapy within the organism. And there are ways that that is starting to evolve dramatically in science. And so is that a future for addiction therapy? Maybe, but it's, like you said, it's 15, 20, 30 years out there. I can't see any way that could ever go wrong. So that sounds great. No, never, never. I like it when you're the wet blanket, Daniel It's usually my job It's very refreshing when you take Take up the torch All right, well, Marcelo Thank you very much for being on the show I had a ton of fun Thank you for putting up with Living Next to Daniel That must be a lot of fun A real rollercoaster And I assume whenever there's a problem Well, now I know where I can get my chocolate That's right, yeah, I was going to say I assume whenever there's like a neighborhood level problem If you just bring Daniel enough chocolate He'll get on your side, it sounds like.

1:03:20That's a bean. That counts as a bean. That's right. Okay. All right. Well, thank you very much for joining us. All right. Appreciate it. Thank you, Marcelo. That was wonderful. Thank you. Whoa. That was super interesting. I'd never heard of the epigenome before. So, understanding how the human body becomes accustomed to drugs makes sense in that context, but I still don't think I understand the withdrawal part of my question. If I don't drink coffee, my withdrawal symptom is a headache. If a person addicted to a more serious drug abstains, then they could experience significantly more extreme effects than a headache.

1:03:53I'd love to understand what's causing that. Phrased differently, why, as a coffee drinker, does my brain's blood pressure change and give me a headache if I skip caffeine for the day? Thank you, Daniel, Kelly, and Dr. Marcelo Sweetwater-Wood for an incredible episode. What a great deep dive into a fascinating topic. work yeah listen to the episode it seems that nobody's addicted to sugar and it's just a habit that is a strong habit not quite sure where the dividing line between addiction and a strong habit would be but uh as a follow-up question i wonder if uh the addiction or strong habit to ketones might be anorexia i don't know anyway very interesting episode thank you very much cheers bye

1:04:44Thanks, everybody, for listening. Please go and do us a favor and rate the show on whatever podcast app you're using. It really helps people find us. Daniel and Kelly's Extraordinary Universe is edited by the amazing Matt Kesselman. He really is a wizard. You can also find us online on Blue Sky, Instagram, and XDNKUniverse. Come engage with us. You can email us at questions at danielandkelly.org. We really do want to hear from you. And you can find our website, www.danielandkelly.org, where you'll also find an invitation to join our Discord, where everybody comes and talks about the amazing universe.

1:05:24And we also have the most amazing moderators. This is an iHeart Podcast. Thanks for joining us. One last thing before you go. You know that feeling when feedback, notes, and data are coming in from every direction? ChatGPT work can make sense of it all, turning scattered inputs into ready-to-review work. With your permission, work in ChatGPT can gather context from apps and files, summarize incoming messages, rebuild decks, and help finalize high-quality documents for your team or clients. Stay in control as you move from a goal to polished work faster with ChatGPT work. Download the ChatGPT desktop app today and take on your most ambitious work.

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