Improve Focus With Behavioral Tools & Medication for ADHD | Dr. John Kruse

My guest is Dr. John Kruse, M. D., Ph. D., a psychiatrist specializing in treating people with attention-deficit/hyperactivity disorder (ADHD). We discuss the many stimulant and nonstimulant ADHD medications available, covering both their potential benefits and risks. We also explore behavioral approaches to managing ADHD, the key role of maintaining a consistent sleep-wake schedule, and the impact of exercise, fish oil supplementation, and video games on ADHD. Additionally, we examine the genetic and environmental factors contributing to the rise in adult and child ADHD diagnoses and offer various options to consider if you or someone you know is struggling with focus. Read the full episode show notes at hubermanlab.com. Thank you to our sponsors AG1: https://drinkag1.com/huberman Eight Sleep: https://eightsleep.com/huberman Joovv: https://joovv.com/huberman LMNT: https://drinklmnt.com/huberman Mateina: https://drinkmateina.com/huberman Timestamps 00:00:00 Dr. John Kruse 00:02:11 Attention-Deficit/Hyperactivity Disorder (ADHD) 00:05:37 Genetics & Environment; COVID Pandemic & ADHD Diagnoses 00:11:43 Sponsors: Eight Sleep & Joovv 00:14:26 ADHD, Interest & Careers 00:20:40 Social Media & Distractibility; ADHD & Lifespan Effect 00:27:39 Hyperfocus, Flow States 00:33:45 Tools: 4 Essential Behaviors for ADHD; Regular Meal Schedule 00:41:06 Sponsor: AG1 00:42:21 Tool: Regular Sleep Timing; Stimulants & Sleep 00:48:06 Insomnia; Tools: Bedtime Structure, Exercise, Phones, Breathing 00:52:30 Nighttime Waking Up; Cyclic Sighing 00:56:35 Exercise; Addiction, Risk, Kids & Stimulants; Catecholamines & Focus 01:04:32 Ritalin, Stimulants, Amphetamines; Amphetamine-Induced Psychosis & Risks 01:16:46 Sponsor: LMNT 01:18:03 Adult ADHD & Medications; Stimulants & Cardiovascular Risk? 01:26:06 Adult ADHD Medication Choices, Psychosis, Cannabis 01:33:49 ADHD Symptoms, Nicotine; Caffeine, Energy Drinks, L-Theanine 01:43:28 Fish Oil, Cardiac Effects & ADHD, Tool: Fish Oil Dose, EPA vs DHA 01:49:38 Sponsor: Mateina 01:51:04 Gut Microbiome 01:52:56 ADHD & Cognitive Behavioral Therapy (CBT), Tool: Task List System 01:57:52 Video Games, Neurofeedback, ADHD Benefit?, Tool: Technology Restriction 02:02:26 Guanfacine, Clonidine, Hypertension, Effects & Timeframe 02:10:13 Modafinil, History & Forms, Dependence 02:19:02 Drug Holidays; Short- vs Long-Acting Drugs, Addiction, Vyvanse 02:28:56 Time Perception, ADHD, Circadian Rhythm Disruption, Phototherapy 02:35:39 Zero-Cost Support, YouTube, Spotify & Apple Follow & Reviews, Sponsors, YouTube Feedback, Protocols Book, Social Media, Neural Network Newsletter Disclaimer & Disclosures Learn more about your ad choices. Visit megaphone.fm/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Andrew D. Huberman?

  Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life.

• 0:09Andrew D. Huberman?

  I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. John Cruz. Dr. John Cruz is an MD, PhD, and practicing psychiatrist who specializes in the treatment of ADHD in both kids and in adults. As you'll see during today's episode, Dr. Cruz is among the world's top experts in understanding the various treatments for ADHD and tools for helping to overcome non-clinical issues with focus and attention. We, of course, discuss the drug treatments for ADHD. So those include Adderall, Ritalin, Vivance, Modafinil, Wellbutrin, basically all the drugs that are used to treat ADHD. And we cover their relative advantages and disadvantages. We also talk about the use of caffeine for focus

• 0:53Andrew D. Huberman?

  and how caffeine can interact with those various drugs. Dr. Cruz also educates us on how specific behaviors, like our sleep timing, so not just the amount of sleep we get, but when we sleep, as well as our meals, our exercise, how all that can shape our levels of attention and focus. And that, of course, is relevant not just to people struggling with attention and focus or who have ADHD, but to everybody. Dr. Cruz isn't just a psychiatrist. He also has a background in circadian biology research. And he offers the intriguing idea that ADHD and other deficits in focus may, in many cases, be the consequence of a misregulated circadian rhythm. He tells us how to test that idea and potentially how to fix it. By the end of today's episode, you'll understand what stimulants do, the possible origins of ADHD in both kids and adults,

• 1:38Andrew D. Huberman?

  and both the behavioral and drug treatments and non-prescription approaches to overcoming brain fog and focus challenges. So by the end of today's episode, you'll be armed with a ton of new knowledge and you'll have a lot of practical tools you can apply. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-costed consumer information about science and science-related tools to the general public. In keeping with that theme, this episode does include sponsors. And now for my discussion with Dr. John Cruz. Dr. John Cruz, welcome. I'm glad to be here today. Let's talk about ADHD.

• 2:17Andrew D. Huberman?

  And probably best if we start off by just kind of laying out what it is. Is the H is the hyperactivity component always in there? Childhood ADHD, adult ADHD, maybe if you would, just give us the top contour of this. And then we can get into ways to combat ADHD depending on different circumstances, different needs, this sort of thing.

• 2:41Speaker 01

  I'll just start out by saying that like most things in neuroscience and psychiatry, we have some definitions and we have lots of different thoughts and frameworks to approach things. So I'll start with our diagnostic category or how we diagnose ADHD. And that is, there are 18 different symptoms. Nine of them are hyperactive, impulsive. Nine of them are inattentive. So the inattentive ones are things like forgetting to follow through on things, losing items, being easily distracted. The impulsive and hyperactive ones are cutting people off in conversations, blurting things out, running around, fidgeting.

• 3:24Speaker 01

  The definitions themselves were designed with a child population in mind because until roughly the mid 90s, it was dogma that this was a neurodevelopmental disease of childhood and that every child who had it outgrew it. That is dramatically wrong. Some kids do, most kids don't. The latest work suggests that most adults fluctuate in time with the severity of their ADHD symptoms. So jumping back to the definition. So we have these 18 different symptoms. As an adult, you need to have at least five of them. And when we say have them, all of these are things that normal people can display at

• 4:09Speaker 01

  any time. So any of us might interrupt someone, might have trouble sitting, might have trouble attending to a task. But to meet the criteria, these have to be displayed. An excessive amount of time in an or to an excessive degree, to the extent that they're causing some dysfunction or distress and that they have to be displayed in multiple realms of life. So if it's only at work that you have trouble completing your task, you know, that might have something to do with your boss or uncomfortable chair or something. So these have to be traits that are displayed in multiple realms of life. They have to cause, again, distress or dysfunction.

• 4:50Speaker 01

  They have to be to an extent that's beyond what a normal person does. And what's strange is often ADHD has a stigma. It's not a real diagnosis, partly because there isn't some, the fancy word is pathognomonic, you know, some classic symptom that's characteristic exactly of that. So with schizophrenia, we have hallucinations. Most people aren't having hallucinations. If you have those, you know, you might have schizophrenia or a drug effect, but that's unusual. Again, with ADHD, they're all usual behaviors. It's just to an unusual extent. So the diagnosis comes under a lot of stigma and questioning. You know, isn't this just normal behavior

• 5:34Speaker 01

  carried to a ridiculous extent?

• 5:37Andrew D. Huberman?

  So you mentioned that there can be a lot of environmental dependence. One thing that I and I know a lot of people wonder about is with the advent of more people working at home and certainly during lockdowns, kids were at home for school as well. But is it the case that when somebody with ADHD is in their home environment where there are typically, you know, more options of things to do, that the symptoms get worse? As opposed to when they go to, say, a restaurant or to school or to play a sport or to work, where sure, there are multiple things you can do in those environments,

• 6:20Andrew D. Huberman?

  but they're more constrained in terms of the different sides of oneself, the different activities that one tends to engage in? Is that, is that common?

• 6:30Speaker 01

  Yeah, so back up a little bit. Like of our other mental health or psychiatric conditions, there's clearly both a biological component to ADHD and clearly a social environment. The nature and nurture question isn't which is it, it's always both. So with ADHD, we know there's a very strong genetic component. The heritability factor is around .88, which is about as strong as the heritability factor for height or for schizophrenia.

• 6:55Andrew D. Huberman?

  So does that mean that if you're an identical twin and your twin has ADHD, that there's a sort of essentially a .8 probability that you'll have it as well? Or is this through the...

• 7:07Speaker 01

  Yeah, I mean, heritability is a little more technically sophisticated and it's about the variance due to gen...

• 7:13Andrew D. Huberman?

  Sure.

• 7:14Speaker 01

  But it's high likelihood. So this tends to run in families. But again, it has a social... It's you're not just a brain in the world, you're a brain interacting with the world. And with ADHD, we like to frame it as both structure is important and demands are important. So one of the aspects of ADHD, separate from the official how we categorize it or diagnose it in terms of symptoms, we most often are understanding it this day and age as a problem with executive functions of the brain. How the brain's working memory works, how selective attention works or doesn't work, how emotional regulation is working or not, how impulse control is working.

• 7:57Speaker 01

  And essentially, the ADHD brain is less able to provide the structure it needs, so it's more reliant on an optimal structure in the outside world. So getting the home versus working in an office environment, part of the problem is if you're in a traditional office environment, you know, you're starting a specific time. Everyone else is doing their work at a certain time. You know, when you go to lunch is clear. You may have people checking in or seeing you in the hallway, you know, Larry is your... How far along are you on this coding project? Are you going to be ready for it on time? When you're home... You don't get any of that reinforcement. You don't have any of that structure.

• 8:41Speaker 01

  So, I mean, structure is a Goldilocks issue. It's not just more structure is always good. Because if you put or impose too much structure on someone, so most people with ADHD are really lousy assembly line workers. They don't want to be just picking up one bolt, screwing it on the side of the Lexus or whatever, and watching the car move down the line. That's too stultifying, too limiting, too structured. So you need the optimal amount of structure. And with COVID and working from home and kids being at the home, so one thing it created is less structure for the day, but it also increased the demand side of the equation. So the cognitive demand, not only did you have to manage your own time and schedule

• 9:26Speaker 01

  now, in addition to doing your work, you had to schedule it, but you might have had screaming kids in the other room, or you might have had your partner who wants to use that room for, you know, their quiet meetings some of the time when you're trying to do it. So the demands increased for many people and the structure decreased. And that was sort of a, um, what's a perfect storm for creating more ADHD. And what's really interesting from a mental health perspective, at the very start of the COVID epidemic, public mental health figures said, you know, we know if this is a massive epidemic and we're going to have to do quarantine and people, we know depression's

• 10:07Speaker 01

  going to go up, we know anxiety's going to go up, we know alcohol and substance abuse is going to go up, we know PTSD and domestic violence is going to go up. They claimed suicide would go up. That was incorrect, and we can get into that, but I think there's an ADHD reason why it didn't go up. Nobody that I heard was mentioning that ADHD would go up. And part of it is because partly to hold on to its legitimacy as a real psychiatric diagnosis, both many patients and many researchers in the field hold so strongly to, this is a biological condition, why would it change? You know, I mean, we can understand why PTSD, more people are being traumatized.

• 10:51Speaker 01

  Uncle Joe just died from coughing his lungs out from COVID. You know, PTSD, it's easy to see. Or depression, you've just lost your job in your whole industry, you know, a restaurant worker, that's not coming back. So we could easily relate stories as to why these other conditions were going to go up, but there was no prediction, again, mostly because I think the defensiveness of the ADHD community and not wanting to acknowledge as much that there's a real nurture component and not just a nature component. And yet, what we've seen, just looking at prescriptions and, you know, this, the media's

• 11:30Speaker 01

  jumped all over this, not only have ADHD diagnoses gone up considerably, but also prescription stimulants have shot up dramatically in the last few years.

• 11:42Andrew D. Huberman?

  I'd like to take a quick break and thank our sponsor, Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. Now, I've spoken before on this podcast about the critical need for us to get adequate amounts of quality sleep each night. Now, one of the best ways to ensure a great night's sleep is to ensure that the temperature of your sleeping environment is correct. And that's because in order to fall and stay deeply asleep, your body temperature actually has to drop by about one to three degrees. And in order to wake up feeling refreshed and energized, your body temperature actually has to increase about one to three degrees. Eight Sleep makes it very easy to control the temperature of your sleeping environment by allowing you to program the temperature of your mattress cover at the beginning, middle, and end of the night.

• 12:24Andrew D. Huberman?

  I've been sleeping on an Eight Sleep mattress cover for nearly four years now, and it has completely transformed and improved the quality of my sleep. Eight Sleep recently launched their newest generation of the Pod cover called the Pod 4 Ultra. The Pod 4 Ultra has improved cooling and heating capacity. I find that very useful because I like to make the bed really cool at the beginning of the night, even colder in the middle of the night, and warm as I wake up. That's what gives me the most slow wave sleep and rapid eye movement sleep. It also has snoring detection that will automatically lift your head a few degrees to improve Your airflow and stop your snoring. If you'd like to try an 8Sleep mattress cover, go to 8sleep.com/huberman to save up to $350 off their Pod4 Ultra.

• 13:06Andrew D. Huberman?

  8Sleep currently ships in the USA, Canada, UK, select countries in the EU and Australia. Again, that's 8sleep.com/huberman. Today's episode is also brought to us by JOOV. JOOV makes medical-grade red light therapy devices. Now, if there's one thing that I have consistently emphasized on this podcast, it is the incredible impact that light can have on our biology. Now, in addition to sunlight, red light and near-infrared light sources have been shown to have positive effects on improving numerous aspects of cellular and organ health, including faster muscle recovery, improved skin health and wound healing, improvements in acne, reduced pain and inflammation, even mitochondrial function, and improving vision itself. What sets JOOV lights apart and why they're my preferred red light therapy device

• 13:50Andrew D. Huberman?

  is that they use clinically proven wavelengths, meaning specific wavelengths of red light and near-infrared light in combination to trigger the optimal cellular adaptations. Personally, I use the JOOV Whole Body Panel about three to four times a week, and I use the JOOV handheld light both at home and when I travel. If you'd like to try JOOV, you can go to JOOV, spelled J-O-O-V-V dot com slash huberman. JOOV is offering an exclusive discount to all Huberman Lab listeners with up to $400 off JOOV products. Again, that's JOOV, spelled J-O-O-V-V dot com slash huberman, to get up to $400 off. I'm fascinated by this relationship between optimal structure and difficulty,

• 14:33Andrew D. Huberman?

  or at least optimal structure versus having some margins for exploration at one's job. I realize it's very difficult to throw out pan-statements about what sorts of work and professions are going to be best for people with ADHD. But in your clinical observation, can you perhaps point us to clusters of professions where people with ADHD tend to gravitate toward because they have...

• 15:04Andrew D. Huberman?

  Sufficient or even hyper proficiency there like would we say like the creative arts where you know as long as they can get themselves to to to the theater they tend to do well when improv I'm using extreme kind of almost silly examples but those are professions indeed versus a job where people have quote unquote bankers hours where it's you know nine to five I could see that being an advantage also being very difficult and of course or accounting where you know literally decimal points matter and and every every digit counts so are there sort of clusters?

• 15:36Speaker 01

  I'm gonna step back and answer I'll get to your answer but I'm gonna to frame it two different ways first one is and I didn't come up with this but I think it's one of the most insightful quips about ADHD is that non ADHD brains are importance driven you know if you know you have to move your car because you'll get a parking ticket you go out and move it if you know taxes need to be paid in April you know it's a boring thankless job nobody and well maybe a few people enjoy it but most of us aren't CPAs are you take care of it the ADHD brain in contrast is an interest driven brain so they know yeah yeah yeah I should be doing my taxes but hey look at how the Warriors are

• 16:16Speaker 01

  doing in their basketball playoff game look at this cool cat video oh I'd rather do something else so regarding career or work I think the most important thing is that it's interesting to you so I we can talk about realms of work or certain career paths but if it's not compelling to you if it's not interesting to you if it's it's gonna be hard to work at it even if it's structurally maybe a better support for you.

• 16:48Andrew D. Huberman?

  Does that carry over to other domains of life do you see for instance that people with ADHD are have a harder time with parenting not that kids aren't super interesting but you know some of their activities might be less interesting to parents than others versus people who are just I think of this word importance driven as just kind of like really dutiful like it's it's it you do it because you're supposed to do it.

• 17:14Speaker 01

  Part of how the field actually in the 90s started becoming aware that adults could have ADHD is that All these clinicians who are having ADHD clinics for kids were starting to notice, wait a minute, this parent is showing up 20 minutes late to pick up his kid. Wait a minute, the parent didn't fill the prescription, so the kid went for two weeks without the medication. They started becoming more aware of ADHD in adults by seeing that the adults who were parents of these kids, and again, there's a strong genetic connection, had ADHD. So there are certainly wonderful, loving, supportive, nurturing parents with ADHD, but

• 17:59Speaker 01

  studies that have looked at, you know, trying to find some objective measures. Are things more likely to be forgotten, misplaced, mislaid, go off track with an ADHD family? Absolutely. And one of the more powerful sets of interventions for kids with ADHD, separate from medications, is family-based training that helps get the whole family, one, to understand how the kid's brain is working differently, but actually, it might not be that differently. It might be exactly how dad or mom's brain is working, but to help them function as more consistent parents. So the other bias, I'd say again, before identifying specific careers, is that as

• 18:43Speaker 01

  a society, we've long cherished or valued, you know, the guy who worked 50 years for Eastman Kodak Company and got the gold watch at the end was sort of the epitome of what you should strive for in a career. But if you're interest-driven and your interests change, so for many people with ADHD, the best career is actually not one 50-year career, it's 10 five-year careers, or five, 10-year careers. And part of it is, is the whole work world has become more fragmented and, you know, upheaval is the name of the game and break things quickly is the motto of Silicon Valley. Not, I didn't phrase that quite right, but the message, I think, is still there.

• 19:29Speaker 01

  We're accepting more that many career trajectories are going to look not like just one beautiful arc, but I think there's a sort of a normo-centric bias to that is what you should strive for, and if you are changing careers, that's a bad thing. And yet, lots of people who do worthwhile things in life, and often because of their more varied experience, they're bringing more to what they're doing. So I think we need to value that and embrace that as an option and accept that maybe for some people, that is an optimal career path.

• 20:06Andrew D. Huberman?

  I can relate. I mean, I spent 20-plus years training to become a bench scientist and run a lab, and then now I still teach and hold my appointments, still involved in a bit of research, but I'm in a second career now-ish, and I imagine there'll be a third. We can talk later if you think I have ADHD or not. I certainly consume a lot of caffeine, and we'll come back to the idea, the relationship between levels of caffeine consumption and possible ADHD. We're seeding the discussion for later on that. We hear pretty often that social media and scrolling X or scrolling Instagram or TikTok

• 20:48Andrew D. Huberman?

  is quote-unquote giving people ADHD. Are there any data, either clinical or otherwise, that suggests that the mere practice of looking at, you know, 10,000 different contexts, or even, you know, 15 videos for a minute while standing at the bus stop, is somehow creating more distractibility in other domains of life?

• 21:14Speaker 01

  Yeah, so I'd say there's a lot of good neuroscience research or neuropsychological data that the more time you spend immersed in social media, and it's the constant, it's the barrage of information and... And not just the volume of information, but that you are constantly being interrupted. And that most of these interruptions are intentionally designed to attract your attention. And that the more people practice thinking that way, or being in the world that way, yes, it's harder to sustain attention for long periods of time.

• 21:54Speaker 01

  That you are, you train yourself to overreact to any new distractions. So, so the core elements of some of the executive functions that are impaired in ADHD, we are all becoming more ADHD-like. So that, that's the thesis of the book that I've been working on that's still several months from going anywhere, but I call it Attention Deficit World. And one of the things that's been frustrating is that there's been this huge disconnect. There've been people writing about, you know, the question you're asking, that the neuroscience, our brains getting more distracted, are we becoming, you know, it's not just distracted. You know, immersion in this media world, or social media, cellphone, however you wanna

• 22:38Speaker 01

  break it down, it's not all bad. It's not just that concentration's worse. So, you know, detecting visual items in the environment, there's some things that people become more adept at. Whether that's actually a good thing to be more adept at, people do multitask more quickly or switch in and out of it, they're still not doing as well on that task if they had no distractions and just focus solely, but they're multitasking better than people who don't immerse themselves a lot in the internet. So there's a whole literature and popular books and attention. We know everyone's getting a little more distracted. But all the books that talk about that say, well, this is just sort of everyday stuff.

• 23:22Speaker 01

  This has nothing to do with ADHD. And there's lots of wonderful ADHD books out there, and they say, ADHD is this discreet condition, even if they acknowledge it's on a spectrum of severity, but that it's really serious stuff and we don't, you know.

• 23:40Speaker 01

  Just because you forgot your homework, or you left your car keys, or you can't remember where you parked your car. Everyone does that, and we want to make sure that you respect that ADHD is a serious and potentially disruptive condition. And when I say serious, and I'm going to go on this tangent for a little bit, the caricatures of ADHD is, you know, oh, there's the squirrel. You know? It's silly. It's people are distracted, ditzy, late, doing things that we make fun of in society. And we ignore that many of these things can have a more serious repercussions inside. So a kid who has ADHD, their life expectancy is about 10 years shorter

• 24:25Speaker 01

  than their non-ADHD peers. That is the same extent of cutting off life as having diabetes or having major depression. Is that because of accidents? Addiction, injury? Almost all of it is two factors, and they're almost equally. One is accidents, so motor vehicle accidents, you know, if you're driving distracted, you're more likely to be involved in accidents. But it's also, you know, the kid who's probably being more daring with the tractor on the farm, or daring the bull, or, I mean, all sorts of accidents, not just motor vehicle accidents. And the other is suicide. And some of the suicide is because there is an overlap with depression and anxiety and other factors.

• 25:10Speaker 01

  But I'm convinced, and not many people are looking at this angle, some are. With suicide, we focus so much on the despair, the misery, that someone hates their life. I mean, but there's lots and lots of depressed people who don't kill themselves. The other really important element to suicide is impulsivity.

• 25:31Speaker 01

  Is lots of people feel really bad, but we know having guns in households increases the rate of likelihood someone's gonna shoot them. Accessibility to tools that you can quickly use to kill yourself, which shows if you slow down the thinking process, if you give people more time, if they are less impulsive, they are less likely to kill them. They still might be miserable. And that's, that's my explanation for why, even though during COVID lockdowns, and we did see increases in depression, we did see increases of PTSD, we did see increases in domestic abuse and battering, and we saw actually a decrease in suicide during that time.

• 26:16Speaker 01

  How does that make any sense? And it wasn't huge, but since suicide's been going up every year prior to that, it's pretty clear and blatant in the data and remarkable. And my claim is so many more people were at home, you know, your kid's not around to play with the gun or find the gun, or, you know, you know what's going on, or poison, or hanging themselves from the door, or whatever else they might do.

• 26:40Andrew D. Huberman?

  Very interesting. I, I didn't realize that ADHD carried this lifespan liability, and 10 years is certainly significant.

• 26:52Speaker 01

  There's also the middle ground. So I, I sort of mentioned that the caricature is sort of the silliness and the trivial of being late for your friends at the restaurant, or forgetting your car keys. And the extreme is death, but in between, we know ADHD measurably derails education, disrupts social relationships, impacts your likelihood of your earning potential. I mean, ADHD isn't just an academic cognitive problem. It isn't just who's gonna jump through the hoops and get through school. It isn't just who's turning in their reports, or doing their work on time in the workforce. It's also having social implications, and in all those areas, it's having measurable detrimental, significant impacts on people's lives.

• 27:39Andrew D. Huberman?

  My understanding, and you'll see how this weaves into the previous question in a moment. My understanding is that people with ADHD have the ability to focus quite intensely on things that really capture their interest. I don't know if I have ADHD or not. I suspect if I do, it's rather mild, or I just feel lucky that I went through the educational system at a time when there were no smartphones. I'm really grateful for that. I actually used to unplug the phone in the laboratory where I was a PhD student so that I could just do experiments from 5:00 PM on, because that was the only way people could reach me. And I certainly am familiar with the, it's almost a drug-like effect of dropping into

• 28:24Andrew D. Huberman?

  an activity. Sometimes people call it flow, but for me, it just is dropping into an activity. Did some early morning writing this morning, and gosh, the feeling of pleasure just everywhere from head to toe after doing 20 minutes of focused work or 30 minutes of focused work is so striking to me. And yet, I like, I think most people, find it difficult sometimes to just get rid of all the distractions, unless there's a deadline, which is one of the reasons I love deadlines. So, the question is this: is it true that people with ADHD can in fact focus, but that somehow whatever neural or neurochemical thresholds are there to allow them to drop into focus, they're just much higher thresholds?

• 29:05Andrew D. Huberman?

  It just takes more fear of a deadline, or fear of a consequence, or excitement about the activity? Is that true?

• 29:13Speaker 01

  Yeah, so I'll back up a little bit, and I maybe should have said this when we were talking about diagnosis and what is ADHD. And many people think it's a horrible title, because it focuses on attention deficit hyperactivity disorder, and it's very clear as you're enumerating here, it's not a deficit of attention. If it's a deficit at all, it's a deficit of control over attention. And with attention, there's at least three different realms where we're controlling it. I mean, one is we direct attention, so if something's important going on over there, there, so we have to be able to shift it. Two, you have to be able to sustain it. So, if it's a situation that's appropriate to be sustaining it.

• 29:54Speaker 01

  And three is you need to shift out of it if it's inappropriate to stay in it. And in all three of those realms... People with ADHD have less volitional control over their attention. So many people in the ADHD who experience it describe hyper-focus as one of their superpowers. And that is where they're getting so absorbed in their work that they are so busy coding that actually everyone else in the office has left and it's only when the janitor is coming and emptying the garbage cans at 11:00 PM that they say, "Oh, my God, where is everyone?" "I'm still here," because I was so intently working on the project.

• 30:35Speaker 01

  Some people strongly resist the idea that flow, and I'm going to butcher the Chik...

• 30:40Andrew D. Huberman?

  Chiksumahai. Yeah, no one can pronounce his name. Even fewer can spell it. So we're okay.

• 30:47Speaker 01

  My reading of, when I sort of delved into this, I think hyper-focus is exactly a flow state because people are describing the same lack of awareness of time, lack of, and it's always, I mean, it's a task that's somewhat challenging and engaging and interesting. It's not just that, you know, if it were just about enjoyment or bliss, you could hyper-focus looking at a beautiful flower. People don't describe that. So it needs the right amount of challenge. It can't be too easy. It can't be too hard. It has to be something important and interesting to you.

• 31:25Speaker 01

  It involves oblivion, not just to time, but also to lots of space going around you. So I think they are pretty close, if not the same phenomena, flow and hyper-focus. And some people with ADHD, and I think some are ones who learn what situational factors or what internal factors can help get them into that state, but many of them still struggle at showing up when they don't want to be hyper-focused on something or have trouble engaging it when it would be useful to.

• 32:03Andrew D. Huberman?

  I sometimes use the absent-minded professor excuse, but only half-jokingly. There's a photograph that I love of the great Oliver Sacks. Neurologist turned writer, man who mistook his wife for his hat, awakenings and so forth, people may be familiar with Oliver's work. And it's a photograph of Oliver at a train station, lots of bodies moving around, him, some blurry, so there's motion there. And he's standing there with, I think he's got his pipe in his mouth, and he's writing outside the train station. His bag has fallen to the floor, some items are coming out.

• 32:42Andrew D. Huberman?

  And he was a known and self-professed methamphetamine addict for a great portion of his medical and writing career. And, you know, sort of alluded to the idea that he had these tendencies. And I raise this as an example because I see that photo and I see somebody who's in hyper-focus, in a very busy environment. But he wrote, I've spent a lot of time with his work and his autobiography, et cetera, and talked to people who knew him. And it seemed that he was constantly seeking novel environments where there was a lot of stimulation, and somehow that allowed him to drop into these tunnels of focus. Whereas when he spent a lot of time alone, there were bouts of focus, but the quiet

• 33:27Andrew D. Huberman?

  actually became a distraction. It was as if somebody in here were speculating about diagnoses, but that there's something about external anchors and internal anchors, and that finding that sweet spot is really about knowing ourselves and where we work best at particular times. And this is something I'd like to transition into here, is talking about the fact that there isn't just one environment that works for somebody. It seems like it's often the case that it's certain environments for mornings, certain environments for afternoons, certain environments having return from vacation. You can probably see where I'm going with this. What are your thoughts on people trying to, with ADHD or not, trying to identify sort

• 34:11Andrew D. Huberman?

  of best conditions for them? And how important is circadian time here? I know you have, and of course, I mentioned in the introduction, that you have a lot of background in circadian biology, which I think brings in a really additional and unique dynamic to your understanding of ADHD.

• 34:27Speaker 01

  So many people come to me as a psychiatrist for ADHD are primarily focused on medications. And we still know that the stimulants are the... Single most powerful, I mean, in terms of extent of symptom reduction overall, and in terms of the percentage of people they help, they're our most potent tool. I mean, the medicine's not going to change everything, and you need to be focusing on your life as well, and I always start with scheduling. And many people with ADHD find scheduling anathema, that that's, you know, like the slaves on the galley ship being told you have to row, stroke, stroke, stroke. And what I tell them is that the part of you that's going to help make the schedule

• 35:12Speaker 01

  that works for you, isn't some evil taskmaster trying to make you do what you don't want to do. It's actually the wisest, smartest, nicest, kindest part of you that's identified, what are your lifetime, what are your bigger goals? How are we going to match what you're doing in the minute to line up with those bigger goals? So, and this analogy isn't perfect, but the best one I've come up with, so rather than the guy on the Viking ship, the person, you, the part of you that's making your schedule, is a mother hen who's sort of counting all the chicks and making things aligned and nestling down and hunkering around you and taking care of you and nurturing you.

• 35:54Speaker 01

  And with scheduling, what I tell people is before you slot in your work, or your homework, or your school, or externally derived tasks, I tell people, you need to have the four basics. And sleep is far and away the biggest basic, particularly for, it's essential for all of us, but it's particularly critical for ADHD, and there's particular reasons why it's a particular challenge for people with ADHD. But I'm trying to think if I can imagine a counter example. I would say, all the successful people I know with ADHD have found some way to try to regularize their sleep compared to what it would be if they were just...

• 36:35Speaker 01

  So, the four essentials I say are sleep, eating, exercise, or some amount of movement, because again, with the hyperactivity, there's people who can sit at a desk for 12 hours, not even getting up to, for a bathroom break, or to eat, or anything. That's not just bad, I mean, that's bad for your brain, bad for your body. And then the fourth thing I put in is... A miscellaneous category of me time, relaxation, meditation. I put all those in the same slot, maybe they shouldn't. And all those need to be in place. We can talk more about sleep, but I'll just say a little bit more about the eating component. One of my, so we have our diagnostic criteria for ADHD, but I had, over the years,

• 37:20Speaker 01

  two different real-life tests. The office I had was in an old Victorian home, so it was a home office. The office itself was at the entrance was at the end of a short but very steep driveway. So it's a separate door. And I would always explain to every new patient, the exact same thing, you know, there's a house at forty-five Hartford, the office is at forty-five A, the entrance is at the end of the driveway. And I actually did the data on it. The only people who ever showed up at the front door, the home door, were the people with ADHD. Now, everyone, it wasn't, it was specific for ADHD, it wasn't completely sensitive.

• 38:04Speaker 01

  So some of the ADHD people got it right. But never did anyone who was coming in for OCD, or depression, or PTSD, show up at the front door. And I gave the instructions at the same time. And sometimes I didn't know beforehand that the person was coming in for ADHD, because they didn't know. But if they showed up at the front door, that always made me, you know, uh-oh, I better make sure I ask specific detailed questions about the ADHD possible component. So the other sort of real-life diagnostic test I had, if someone during the evaluation would say something like, or in a subsequent session, oh, it was four o'clock yesterday, and I just realized I hadn't eaten all day. Ding ding ding ding ding.

• 38:48Speaker 01

  That's, I mean, I have people who died, I have people who have, you know. Fasting regimens or others, but they're not forgetting to eat. And it's not that everyone at the ADHD does that, but either either not getting the right intero receptive cues from your body or not paying attention to them is something that's been measurable in people with ADHD.

• 39:11Andrew D. Huberman?

  So having a regular meal schedule.

• 39:12Speaker 01

  So having a regular meal schedule. And again, getting back to the COVID in workplace, if you're, you know, I had lots of people in tech who really lamented, now I have to work from home, they were giving me lunch, a healthy, nice lunch each day at work. They're scrambling to to even use the home, you know, meal delivery systems because getting that organized and set up is just too overwhelming for them. And again, these are bright people who are succeeding in most parts of their life.

• 39:42Andrew D. Huberman?

  Are these people with ADHD sometimes also starting a meal, taking a few bites and then going back to work and then like the meal never really, never really ends, it just sort of, sort of fragments into the rest of the day?

• 39:55Speaker 01

  That can be one variation, but it's often just completely forgetting or being oblivious to, I mean, the other ways ADHD is can play a role is I was meaning to have breakfast before I left the house, but always when it's time to leave the house, you forget that you hadn't done this and the kids' shoes need to be tied and, oh, do I need a new toothbrush? I better go check upstairs before I go out because I'm going to the CVS store. I mean, time management is a problem with ADHD, an executive function problem. Interestingly, it's not one of the 18 symptoms in our official checklist.

• 40:36Speaker 01

  So our official checklist is sort of a crude clinical attempt to map out a lot of the aspects of ADHD, but it misses a lot. So there's emotional regulation problems. We know something like 60% of people with ADHD acknowledge having that emotions explode or come up bigger or stronger and are harder to regulate. And that's nowhere acknowledged in our official diagnostic symptomatology.

• 41:06Andrew D. Huberman?

  I'd like to take a quick break and thank our sponsor AG1. AG1 is an all-in-one vitamin, mineral, probiotic drink with adaptogens. I've been taking AG1 daily since 2012, so I'm delighted that they're sponsoring this podcast. The reason I started taking AG1 and the reason I still take AG1 is because it is the highest quality and most complete foundational nutritional supplement. What that means is that AG1 ensures that you're getting all the necessary vitamins, minerals, and other micronutrients to form a strong foundation for your daily health. AG1 also has probiotics and prebiotics that support a healthy gut microbiome. Your gut microbiome consists of trillions of microorganisms that line your digestive tract and impact things such as your immune system status, your metabolic health, your hormone health, and much more.

• 41:50Andrew D. Huberman?

  So I've consistently found that when I take AG1 daily, my digestion is improved, my immune system is more robust, and my mood and mental focus are at their best. In fact, if I could take just one supplement, that supplement would be AG1. If you'd like to try AG1, you can go to drinkag1.com/huberman to claim a special offer. They'll give you five free travel packs plus a year's supply of vitamin D3K2 with your order of AG1. Again, go to drinkag1.com/huberman to claim this special offer. So we've got sleep, eating, exercise or movement, and relaxation. Maybe before we start talking about some medications and some other factors that modulate

• 42:32Andrew D. Huberman?

  ADHD, if we could maybe step through each of those and you could share with us some of your favorite tools that you give your patients and that you teach online. Realizing, of course, that each one of those is a vast topic that could, we could do entire, we have done entire podcasts on, but I'm curious about your favorite go-to tools. We were talking about a few of these before we started. So, sleep, regular to bed and wake-up times?

• 43:01Speaker 01

  Matthew Walker, in his great book on sleep, one of my favorite things about it is he really emphasizes this point, that quality sleep isn't just about eight hours. It isn't just duration. It's getting quality sleep. And the timing of your sleep is every bit as important as the duration. So if you're used to sleeping midnight to 8:00 a.m. and you're staying up dancing or partying until 4:00 a.m. and you say, "Oh, it's a weekend. I can sleep until noon." You may still get those eight hours, but they're not restorative to the same extent as if you had slept at your regular time. And it's, I mean, my PhD research was on circadian rhythms. We had realms of data back then.

• 43:43Speaker 01

  So this is 40, 30-plus years ago. We had every bit as much data then that the timing of sleep is as important as the duration. And yet, every public service announcement just says, "Get your eight hours of sleep." Now, why are we leaving out this other piece? We've known for decades that people with ADHD have a strong propensity to being night owls, to have a different chronotype, where they're maybe more effective or functional later in the day, a tendency to stay up. For many years now, we've actually known that this is strongly genetically controlled. So we do have, you know, there are genetic markers affecting sleep timing that are overrepresented strongly in the ADHD community.

• 44:28Speaker 01

  So some of it is you are pushed that way, but some of it is the nature of ADHD, that if you, you know, procrastinating is part of ADHD. If you procrastinate, you're gonna push things off till the end of the day. Some people, the end of the day is a better time to work because there's fewer distractions. You know, if everyone else is asleep finally, no one's gonna come in and interrupt your work or ask what your thoughts on this project are. But again, getting regular sleep and regular and sufficient doesn't mean it has to be what I'd say normal. You know, if it works for you, if you can build your career and your social life around sleeping from 2:00 a.m. till 10:00 a.m. every day, I'd

• 45:10Speaker 01

  say, go for it if you can be consistent with it. So what are the things that help with getting regular sleep? One thing, paradoxically, for many people is actually being on stimulant medications. So stimulants do have, as a side effect, some people have insomnia, some people stay up later, but more people with ADHD tend to, either because it's the drug is wearing off at the end of the day and there's some crash in alertness or energy, or because they're being more productively expended energy and are more tired at the end of the day, or it's just helping synchronize circadian clocks by getting a consistent start early in the day.

• 45:50Speaker 01

  We don't know the mechanism by which it works. There's lots of plausible and overlapping ones, but again, daytime alertness medications can help.

• 46:00Andrew D. Huberman?

  Can I run something by you in that context?

• 46:02Speaker 01

  Sure.

• 46:03Andrew D. Huberman?

  Before we jump back, I don't consistently take stimulants except caffeine, and I limit my caffeine intake to prior to 2:00 p.m., and I stack it pretty heavy in the early part of the day. But on occasion, I'll take 25 to 50mg of Wellbutrin, which you know better than I, is slightly dopaminergic but certainly triggers noradrenergic release, so epinephrine, norepinephrine, stimulant, it's a stimulant. On the days when I take that, which again is very rare, and I track my sleep every night, I notice a significant improvement in my sleep and significant increase in my

• 46:46Andrew D. Huberman?

  rapid eye movement sleep. It's extremely consistent. So from that, I sort of reverse engineered the major effect being norepinephrine. Epinephrine, I decided, well, I would do something else that I know raises epinephrine, which is I'll do a cold plunge first thing in the morning of one to three minutes long. And the effect isn't quite as strong, but on those same days when I do that... Clearly adrenaline raising activity. I also see a, for me, a significant increase in my rapid eye movement sleep and the quality of sleep later that night. So I think there really is something to this epinephrine, obviously going hand in hand with stimulants.

• 47:28Andrew D. Huberman?

  Epinephrine spike early and throughout the day with better rapid eye movement sleep at night. Does that logically hold for you? It's just a story.

• 47:37Speaker 01

  Yeah, I was gonna say, as both of us have some science background, so I'd say, I'm glad it works. And what's hard to sorting out is why it's working is, one, is potential placebo effect. You're doing it because you're thinking or hoping it works. Good. And two, I'd say maybe even more importantly than the placebo effect, is the days that you're deciding to do this, there's something different about those days to begin with because they're not doing it every day. So those potential issues aside, I'll jump into insomnia. And Matthew Walker talks about some of this.

• 48:17Speaker 01

  To me, maybe the biggest finding in insomnia sleep medicine of the last 20 years is that almost everyone who has a problem with insomnia doesn't have a problem with sleep. Huh? What? That does sound like I'm contradicting myself. What I mean is, the sleep system's intact, it's there, it's waiting to arrive and put you to sleep each night. What the problem, and this is from the sleep researchers, with at least 90% of, probably more, of people who have insomnia problems, is the failure of the daytime arousal system to shut off properly. So normally, we have these two mutually inhibitory systems, a wakefulness arousal system and a sleep sedation system.

• 49:02Speaker 01

  And usually, when one turns on, the other turns off. And with Most people's problem with insomnia, it isn't that sleep is weak or insufficient or not there. It's sitting, it's waiting there, it just can't land on the landing pad because you're too aroused or too awake. I mean, maybe that helps the arousal system to turn off better at the end of the day, if it's gotten more fully engaged during the day, I don't know, but it feeds back more into some of the non-medication approaches to helping with sleep, and that is doing everything you can, again, not just to force sleep or push it, because that doesn't work very well, it's getting rid of arousal, it's dampening arousal. So for people with ADHD, one is, you know, deciding on what's a reasonable

• 49:47Speaker 01

  bedtime, you know, having, thinking about this ahead of time, and two, eliminating any stimulation or, I mean, once, so, exercise, I'm a big fan of, I'm a marathon runner, I know you're heavily into exercise as well. Exercising too late in the evening can elevate body temperature, disrupt falling asleep, so, physical arousal, we don't want be doing a lot of late in the day, and emotional, intellectually, cognitive arousal too. So, the biggest single tool in modern life is do not have your phone in your bedroom. And

• 50:29Speaker 01

  that's hard for lots of people to do, but if it's there, you're gonna be checking it, I mean, studies have even shown, even if you're not checking it, if it's there, you're thinking about it, or looking at it, just having it away, out of sight, is better than having it visible and turned off. Two is using, if you have someone you're sharing a bed with, or family members, using them to help reinforce, yes, and it's really helpful to talk about this ahead of time, because the exact same words can either be sounding like a nag, or someone trying to exert their power over you, rather than, with people with ADHD, we know, need reminders, they know, they need some of that external structure. And

• 51:13Speaker 01

  if you are on the same page and can have a partner, your kid, or someone else present, "Hey Dad, shouldn't you be turning off the computer and heading to bed right now?" That can be helpful. Again, it can be destructive if it's not done in a Framework where both people are on board and it's not fair to make the other person responsible for your own behavior. But lots of people are usually happy to help the person with ADHD be more organized in their life. So we were also talking a little bit before, one of my favorite tools for falling asleep is actually cyclic sighing. I mean, there are other box breathing and other techniques that help someone relax. So we know cyclic sighing engages the parasympathetic nervous system, our rest and digest system.

• 51:58Speaker 01

  I mean, one of the things that happens normally in the transition every night when you fall asleep is you're going from primarily sympathetic tone to primarily parasympathetic tone. So anything that is strengthening or putting in there already makes it easier. I know you have videos about cyclic sighing and I do too. I mean, my own experience, which I was sharing with you before we started talking was not only does cyclic sighing help me fall asleep, but it actually helped me stay asleep throughout the night better.

• 52:30Andrew D. Huberman?

  That's a remarkable thing because many people, including myself, have very little trouble falling asleep, especially given how I stack caffeine in the early part of the day and then stop in the afternoon. It allows me to fall asleep within seconds. Somewhere for me typically around 10:00 PM, somewhere between 10:00 and 11:00 PM is my typical bedtime. But then I consistently wake up at, you know, three in the morning, usually get up, use the restroom and then go back to sleep, most of the time without too much trouble, provided there isn't a lot of stress in my external life and provided the phone is not in the bedroom. But as we were also talking about before we turned on the microphones, this idea that

• 53:13Andrew D. Huberman?

  our bladders get smaller as we age is complete nonsense, right? So that can't be the explanation why people wake up more in the middle of the night as they get older.

• 53:22Speaker 01

  Yeah, I mean, some might, I mean, some it may be a prostate issue. Clearly that isn't accounting for half the population, but I think it's much more the neurologic innervation of our bladder. You know, all our nerves start functioning not quite as well. And they're just getting the signal that I really need to urinate right now when pretty clearly, most of those people don't. They could wait, but the signal is arriving that says you have to, and it's believable, and you don't want to deal with it if it's, you know, you don't want to not listen to it if it is right, so.

• 53:56Andrew D. Huberman?

  How much cyclic sighing are you doing before sleep? And how long before sleep is the cyclic sighing done?

• 54:02Speaker 01

  So when I read your paper with Spiegel and others, January, for years, I've said, I don't have a meditation practice. Most people think I'm sort of so chill or relaxed that I do.

• 54:13Andrew D. Huberman?

  You seem like a pretty mellow dude.

• 54:15Speaker 01

  I haven't ever taken the time to do it, which I'm embarrassed by. So I said, read the paper, I can do five minutes a day of cyclic sighing. And I tried, and it was, some days I was getting it in, and many days I wasn't getting it in till bedtime, which is the, I slept really well till I was around forty and not so well the next twenty years, both mostly with the trouble of falling asleep, even though I knew of relaxation techniques and others. So I wound up just consistently doing it to do it more for the general health, and I do have slightly elevated blood pressure and relaxation, and to see what effect it would have. And it was clear.

• 54:58Speaker 01

  So I do about five minutes, and much more than five minutes, I tell people, and I might be doing it a little slower than most, count out about twenty or twenty-five reps of it. And if you lose track, doesn't matter, just go back to the lowest number, because again, everything we're trying to do is decrease arousal. If you have a timer on it, and you do it for five minutes, and then you're woken up, you're reversing or mitigating some of the benefit of doing it. So I, my recommendation is do it for five minutes, about, but do it by counting reps, and. Don't focus, or, you know, if it's six minutes, if it's four. I mean, there's so many aspects of this.

• 55:41Speaker 01

  And we know the exhalation has to be longer. I was trying to find, you know, is anyone systematically, you know, is a four-second exhalation better than 10 versus six? And those studies would be so simplistic and easy to do. But, you know, there's lots of variables that we can play with to see what's optimal. I don't think we know at all what's optimal, but we know what's good enough to work.

• 56:03Andrew D. Huberman?

  Oh, delighted to hear that it's worked so well for you. I, as people know, I'm a huge fan of the physiological sigh. And I take no credit for having discovered it. It was discovered by physiologists in the 1930s.

• 56:14Speaker 01

  So throughout the data point that I shared with you is that prior to trying cyclic sighing at nighttime, I was waking up virtually every single night, once a night, to urinate. And in the 18 months, 20 months since I've been doing it, I think it's been a total four times that I've woken up during the night to urinate.

• 56:34Andrew D. Huberman?

  Fantastic. So we're talking about sleep. You mentioned earlier encouraging people with ADHD or who think they might have ADHD to keep a somewhat regular eating schedule, or at least to make sure that they're eating.

• 56:48Speaker 01

  Yeah.

• 56:49Andrew D. Huberman?

  And to not let their meals get fragmented into starting a meal, then finishing it later. Like have, for some people, it's breakfast, lunch, and dinner. For some people, like myself, it's lunch, snack, dinner. Whatever it is, keeping a regular schedule. Exercise, aside from encouraging people to not exercise too late in the day, certainly not caffeine and exercise late in the day. Are there any data about specific types of exercise being better for ADHD, independent of effects on sleep? I realize they're hard to tease apart.

• 57:24Speaker 01

  Yeah, there's a few studies looking at acute aerobic exercise. Part of it is that it's hard to study people when they're exercising during many exercises. I mean, you're not going to wire someone up when they're swimming, for example. So there's not a lot of studies in any one approach and there's so much diversity that often it just gets lumped together. So there do seem to be some acute effects of measurably improving some of the executive functions associated with better attention from acute exercise. And there seem to be some more general or longer term benefits from people who are consistently actively exercising, having, you know, being able to concentrate longer,

• 58:07Speaker 01

  being able to switch attention more appropriately or effectively. And there's a huge body of sort of clinical literature of patients reporting, you know, I know I feel much more alert the day I get my workout in the gym in, or I feel better, or the week I took off from that was a big mistake. But I would say identifying what's the most valuable or what's the best duration. I ran through the data about a year or two ago and it's, I would say that we can't make any conclusions and I would say at some level, try it and see what works for you and that's what's important. It isn't what works for everyone.

• 58:47Andrew D. Huberman?

  Is there a relationship between ADHD and addiction because of the impulsivity component?

• 58:55Speaker 01

  Yes, and, and so the answer is, and these are really rough statistics, I actually, one of my pet peeves is people who quote, oh, the rate of this is 27.43%. Well, it might have been in that study, but that's looking at one population, at one set it. So I use ballpark figures. The ballpark figure is Americans in the last 20 years, more than that, about 20% of Americans run into some addiction, substance addiction problem, either alcohol or drugs. People with ADHD have a rate that's almost double that, and it's higher in men than in women.

• 59:33Andrew D. Huberman?

  Double?

• 59:34Speaker 01

  Almost double, almost 40% risk.

• 59:36Andrew D. Huberman?

  And that's for substance abuse and not behavioral addictions?

• 59:39Speaker 01

  Yeah, that's substance abuse and that's looking at abuse and we can get into the related topic of what's misuse and versus abuse and I have pet peeves there. However, kids who are put on stimulant medications when they're young, and I should say the stimulants themselves do have a small potential for addiction.

• 1:00:00Speaker 01

  But putting kids on stimulants pretty much normalizes the rate of addiction problems.

• 1:00:06Andrew D. Huberman?

  So it protects them.

• 1:00:08Speaker 01

  It protects them.

• 1:00:09Andrew D. Huberman?

  This is a really important point that I think maybe we just hover on for a second. Because I think many people, including myself, assume that, well, if you were, you know, putting these kids on amphetamines, of which, you know, many of the medications for ADHD are, that we're creating kids that are addicted to amphetamines or to a hyperstimulation period. But you're telling me it's actually protective to put kids with real ADHD on medication for ADHD?

• 1:00:39Speaker 01

  Yeah, I can say not absolutely every study has found this, but several large meta-analyses have gone back and most of them have found this fairly dramatic benefit to being on stimulants as a kid in terms of specifically reducing substance abuse risk. And some of them that have looked at this, when I said it was a yes and, it seems to be that it's not just the impulsivity traits, but some of the inattentive ones too. You know, if your teacher's lecturing about the risks of alcohol or this and this and you're zoning out at the window and looking at the plane flying by, you have less pertinent information on the topics. You may be less attentive to the negative effects that other kids are seeing among

• 1:01:22Speaker 01

  their classmates who are stoners at this age or X, Y, or Z. So it seems that both inattentive sets of ADHD symptoms and the impulsive, you know, thrill-seeking, not weighing the consequences as heavily are all contributing to this heightened risk.

• 1:01:42Andrew D. Huberman?

  I have this model in my head that is perhaps completely wrong, maybe partially wrong. And it goes something like this, that we know that the neural circuits involved in executive control and directing attention and maintaining attention and avoiding distraction, this kind of thing, use dopamine and epinephrine and norepinephrine.

• 1:02:08Andrew D. Huberman?

  At least to some extent. And we know that people with ADHD are capable of focus. As you said, it's a failure to direct that focus, maintain, et cetera. So I've heard from you before this discussion that, you know, people that, you know, tend to drink lots and lots of caffeine or who can drop into an activity but have a lot of distractibility that, you know, they might have ADHD. So what I'm imagining here is that the threshold to get dopamine, epinephrine and norepinephrine released is either much higher or more complicated for people with ADHD. And so what they're seeking is these catecholamines, these three chemicals, dopamine, epinephrine,

• 1:02:49Andrew D. Huberman?

  norepinephrine, and that if they're given a medication that puts them in that range where they're getting it, then they're good. They can stop seeking it, so to speak. And I'm raising this now because we're talking about addiction. Addiction is a, you know, pursuit of things essentially. And I guess what I'm saying is it seems to me that the model of ADHD that we hear about is that, you know, people can't focus, you know, their dopamine circuits are all out of whack, and then you put them on this dopaminergic drug and, you know, basically you get them addicted to that tunnel vision or something. But I have this model in mind now that what we are all seeking is to have portions of

• 1:03:31Andrew D. Huberman?

  our day where we are directing our focus towards meaningful build, the things that are, you know, generative in our life, work, school, relationships, et cetera. And that whether or not it's pharmacology or exercise or what have you, that it's just about getting into this plane of consciousness. And I say that in no woo or abstract terms. Is that right? I mean, are we really talking about here is a failure to access enough of these neuromodulators? And these medications, which we're about to talk about, are really about putting us in the realm where those neuromodulators are just more accessible? I'll just say, I can go with that. Okay. Well, you're the expert. I mean, I'm putting this together based on kind of what we're talking about. Like, getting enough sleep, to me, is a way of being able to have enough arousal during

• 1:04:15Andrew D. Huberman?

  the day. You know, exercise or these medications, just different ways of being able to access arousal. Like, if you don't sleep, you can't access arousal during the day. So, okay, well, I'm going to hold that model in mind, and I'm going to keep testing it to try and destroy it as we go forward.

• 1:04:33Andrew D. Huberman?

  Let's talk about the medications, since you raised those. And, you know, the first one I ever heard about was Ritalin. Let's start with Ritalin. How often is Ritalin used nowadays? And what is Ritalin doing neurochemically? And what are your thoughts on Ritalin as a useful drug for childhood and adult ADHD? And I'm happy to repeat those questions.

• 1:04:58Speaker 01

  So Ritalin is, or generic methylphenidate, and then there's dozens now of slow-release versions, and there's even a patch, a skin patch, instead of a neural version. Our definition of what a stimulant is, is really squishy and vague. In its broadest sense, it's any drug that has an effect in the body, like the sympathetic nervous system, which is a norepinephrine-driven fight-or-flight arousal system. So by the loosest criteria, caffeine's a stimulant, well, but it's a stimulant, even though we classify it as an antidepressant. Some of the decongestants are stimulants.

• 1:05:41Speaker 01

  But more often, when we're talking ADHD medicines, we're using stimulant more specifically for amphetamine-based products like Adderall and Vyvanse. And again, there's a host now of newer branded extended-release forms, and methylphenidate. And we lump the two together, probably most ADHD experts agree with, and this is where I'm going to be disagreeing with most of them. I don't consider Ritalin a full stimulant. So the neuropharmacologists differ a little bit, but amphetamine is a strong dopamine and norepinephrine reuptake blocker. So it prevents what's already been released from being taken back up, so more is available longer.

• 1:06:21Speaker 01

  But in addition to that, amphetamine is a pretty potent, let's just say, vesicle manipulator. So it's actually forcing a bigger release from the vesicles when they're synaptically released. So it's not just that the signal lasts longer and is stronger because of that, it's a bigger signal. Depending on what study you look at, most of the studies suggest that methylphenidate is actually a pretty weak vesicular manipulator, and some studies don't find any impact there at all. Which means if methylphenidate is basically a norepinephrine and dopamine reuptake inhibitor, that's what wellbutrin is, that's one of the, you know, it's.

• 1:07:04Speaker 01

  And so why I would further say, if you look at the efficacy data, how well do these work in resolving ADHD symptoms? All the meta-analyses lump Adderall products, amphetamine and methylphenidate products here and say, you know, they're here because they work better. This is, you know, success in reducing ADHD symptoms. And Alvar, Strattera, alomoxatine, wellbutrin, I use simbolatlot, modafinil, guanfacine, all these other things are down here as less effective. But if you actually look at any of the plots that I've looked at and separate out, methylphenidate is actually closer to the pack below.

• 1:07:49Speaker 01

  It's the amphetamine products are head and shoulders above everything else. Methylphenidate's usually at the top of the rest of the crowd, but if you're just looking at the data objectively, there's a clear decision point. So in terms of efficacy, amphetamine products are stronger. But in terms of some of the side, you know, the side effect that I worry most about, it's not at all common, but it's one of the horrible ones is amphetamine induced psychosis. Now that we're finally looking at that a little more closely, because for years ADHD experts have said, yeah, it's really rare, let's not look at it at all, let's not pay attention, move along, you know, don't look.

• 1:08:33Speaker 01

  With amphetamine Adderall products, and it's probably dose dependent, but it's close to one out of 500 people. And what's, I'm going off on a tangent here, but I'll keep following it because it's an important tangent. It's only one out of 500 people. That's uncommon, but this is a really bad condition because, so amphetamine induced psychosis is a schizophrenic-like picture. Usually someone is really paranoid, really worried that their friends are manipulating them or the police are spying on them. I mean, if you drink too much alcohol, you can be batshit crazy, and that's a highly technical term there. You can be out of touch with reality, you can be hallucinating, you can be saying all sorts of nasty things.

• 1:09:15Speaker 01

  But if it's alcohol induced, you fall asleep at the end of that night, you wake up the next morning, you may feel horrible with a hangover, you're not hallucinating, you're not psychotic anymore. Hopefully, you're regretting what you did, probably not remembering much of what you did. People will let you know. With amphetamine induced psychosis, on the other hand, classically and characteristically in what I've seen clinically, it continues for days, weeks, or months after stopping the medication, which means we are, we've changed someone's brain and we don't have lots and lots of data and it's actually only come to us because people are concerned about

• 1:09:56Speaker 01

  marijuana causing a similar picture. So now we're studying this a little more. But with amphetamine induced psychosis, about, and these are again rounding from different studies, about 20%, if you look 20 years out, about 20% of those people are in a permanent psychotic state still. So again, it's uncommon, but it's such a bad outcome that we really should be alerting people to it. And I've been, I saw a much higher risk of this for, I can get into it if we need a reasons in my population in San Francisco. But I've had people coming from all the most prominent ADHD clinics over the years who just moved to the area.

• 1:10:38Speaker 01

  And when I'd say this, give this as my introduction to, you know, I'm happy to continue on this, but are you aware, to a person, they said, no one ever told me that. Now, maybe they have ADHD and weren't listening, but it's so uniformly consistent that they didn't hear or know that that was a side effect. And one in 500 isn't a trivially small number. No, it's not trivial. And I mean, why I got alerted to it is my rate in San Francisco is actually higher than one out of 100. And so I'll go into, I think, a couple of different reasons. One is I worked with a lot of HIV positive men, and we know HIV, particularly

• 1:11:19Speaker 01

  in the days before we had effective antivirals, is a virus that goes to the brain and affect, you know, there's a

• 1:11:26Speaker 01

  HIV-induced dementia, so probably some of these people had brains that were compromised because of that, more vulnerable. Two, a high incidence of methamphetamine. So methamphetamine, street speed, is a chemically different molecule than amphetamine, has an extra methyl group, and an extra methyl group can mean a lot. So it's a cousin, but methamphetamine, we know, has higher rates of psychosis, higher rates of addiction. This tends to be more rewarding, but again, in that population, and many of them would hide that history from me, but I think that the very first person I had with amphetamine-induced

• 1:12:04Speaker 01

  psychosis, a guy in his 40s, HIV positive for years, this was back in early, mid 90s, was able to finish school in his mid 40s, get a good-paying job in two years on stimulants, and then had a full-blown psychotic episode where his dad had died of a heart attack 10 years earlier. He was threatening his mom because he believed his mom had poisoned her. He flew over to Rhode Island where she was living. He was making threats from a payphone, and because Rhode Island's so small, he was actually calling from out of state, so it was a federal crime. He got thrown in federal prison for this.

• 1:12:44Speaker 01

  And, and he stayed psychotic for months after he wasn't using any, but it later turned out, he had had a psychotic episode 10 years earlier on street meth, which he lied about when I did the evaluation. So the other high-risk group I had was, I was known in San Francisco as someone who worked with adults with ADHD at the early stages of recognizing ADHD, so, and I was comfortable with a broader range of stimulant dosages than many providers are. So I had people who had, and they were all young, white males, straight males, who had history, and I don't know how many, how many of those demographics are relevant, but who

• 1:13:26Speaker 01

  had histories of taking stimulants, having a psychotic episode, again, being really paranoid, all, and again, the numbers aren't huge, but at least five people with this general profile. But even though they were paranoid, even though they were severely impaired enough that each of them wound up in a psychiatric inpatient hospital, which is pretty hard to get into in this day and age, or even 20 years ago, they all liked something about the experience enough that they all wanted to get back on, and all of them knew enough to lie about this past. So they didn't tell me about, you know, they presented, all of them also had ADHD, you know, they presented with ADHD, they'd say, I'd been on stimulants

• 1:14:10Speaker 01

  before, and, you know, I'm not working with that doctor because my insurance changed, or they had moved to the area. So they, they gave plausible histories, and most of those, within a month or two of restarting it, wound up back in the psychiatric hospital. I had one guy, bright computer programmer, late twenties, calling me from inside the psychiatric hospital to try to get me to prescribe more Adderall to him. And not only that, he had convinced his inpatient psychiatrist that this was a good idea, that this was important to treating his ADHD and helping him retain his job.

• 1:14:52Andrew D. Huberman?

  Wow. So these are, as you said, straight, white males who have psychotic episodes on their ADHD meds, and continue to seek those meds because they, quote unquote, like the experience. It feels like a manic high, the dopaminergic state.

• 1:15:14Speaker 01

  Yeah, and you put the word mania in there, manic, and lots of people define this as amphetamine induced mania rather than psychosis. I don't, because one is uniformly, and maybe other people are seeing more, that these people were paranoid, they were worried, they were anxious, they were delusional, but they weren't.

• 1:15:39Speaker 01

  Overtly enjoying it, they weren't having a great time. They weren't saying, "I'm gonna party with all you friends and I'm only worried about the people there." And yes, they were talking more loudly, they were sleeping less, which is, could be characteristic of mania, but there was no positive affect that I or police reports, or often families give you extensive history of everything that was going on, that there was nothing euphoric they were describing about it. I mean, I think the second piece is how much of they, it's unclear how much they actually remember or recall, or either through psychological suppression of it, or physiologic, they're

• 1:16:24Speaker 01

  in a different enough state, it didn't register properly, it's not clear. But they tend not to recall the paranoia, and by paranoia, it's persecutory delusions. You know, people who assaulted family members, thinking that they were being spied on, manipulated, when they were the parents trying to take care of their kids.

• 1:16:45Andrew D. Huberman?

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• 1:17:26Andrew D. Huberman?

  in about 16 to 32 ounces of water when I wake up in the morning, and I drink that basically first thing in the morning. I'll also drink a packet of Element dissolved in water during any kind of physical exercise that I'm doing, especially on hot days when I'm sweating a lot and losing water and electrolytes. There are a bunch of different great tasting flavors of Element. I like the watermelon, I like the raspberry, I like the citrus, basically I like all of them. If you'd like to try Element, you can go to drinkelement.com/huberman to claim an Element sample pack with the purchase of any Element drink mix. Again, that's drink Element, spelled L-M-N-T, so it's drinkelement.com/huberman to claim a free sample pack. What are the options for people that think that they may have ADHD? Let me phrase it differently.

• 1:18:09Andrew D. Huberman?

  Someone comes in and you, they have, you know, let's say an adult, they have five of the 18, um, well, uh, criteria. Um, they, they meet the criteria for ADHD. Do you tend to, well, after telling them about sleep, food, exercise and relaxation, after that squared away, if the decision is to medicate, do you just, and assuming they're not on any other medications, which cluster in this, um, two sets of clusters that you described before, the amphetamine type, the Adderall, Vivance, um, et cetera,

• 1:18:49Andrew D. Huberman?

  versus the, I realize you put Ritalin at the top of the bottom cloud, um, Wellbutrin, Ritalin, um, Modafinil, uh, you've mentioned Cymbalta. Uh, which, which cluster do you go to first?

• 1:19:04Speaker 01

  I mean, some of this is just individual style rather than intellectually thinking one is better or not. And my style is usually to listen as closely as I can to what the patient wants. That doesn't mean agree with them, but to, to explain in as much detail as I can what I perceive the risks and the likelihood of those are and what I perceive the benefits to be. Um, for years, just statistically, I had many more people who are on non-stimulants than stimulants compared to the general ADHD population. And that's even accounting for, by many variables, I had, I've always worked with a lot of people who are in disability from Medicare.

• 1:19:45Speaker 01

  I also worked with people who are on Medicaid and the city's insurance before Obamacare happened. So I've worked with, not entirely, but a skewed, more dysfunctional, more severely afflicted population, which again, you would think would be a better match for the more powerful drugs. Um, I would, I'll jump back, but this actually is a situation where we have more powerful drugs. So often when I treat people with depression, they'll try one or two or three antidepressants and say, well, give me something that's more powerful. And with depression, Maybe we can put ketamine out of the picture, and I know this is a side issue, but all of our antidepressants seem to work equally well. We don't have potent antidepressants

• 1:20:30Speaker 01

  and non, if they got FDA approved, it works in a certain range of likelihood. But with the stimulants, amphetamine based products really are more powerful and more so than with depression or many of our other conditions where it's more a categorical, this will help or not, as long as you're above a threshold, there's a more linear relationship. If you, if a little bit of wellbutrin helps, a lot is likely to help more. I mean, you might start getting more side effect issues and there may be good reasons to not keep going up, but there's a more linear dosage results relationship.

• 1:21:09Andrew D. Huberman?

  Do you worry about strain on the heart with amphetamine products? Just even if it's relatively low dose over time, just, you know, the, just the strain on the calcium channels and on the, on, on the heart, you know, is it true that, that stimulant based medications for ADHD can quote unquote weaken the heart?

• 1:21:31Speaker 01

  When you use that term, I was, I was talking with Rob beforehand about running marathons, and when I ran the 100th anniversary of the Boston Marathon, they had some of the medical literature from the previous decades, and one of the medical warnings was, you know, maybe you could do one or two marathons in your life, but don't do more than that because your heart will wear out. And, you know, I've run 100 and my heart, I think, is still beating, so we know things we thought we know at one point. Common cardiovascular effects of not just the stimulants, but the non-stimulants that are affecting norepinephrine, so wellbutrin, Cymbalta, modafinil, it's less clear, and we can get into that when

• 1:22:14Speaker 01

  we talk about modafinil, but clearly methylphenidate, amphetamine, on average, increase at therapeutic doses, increase heart rate a few points, increase blood pressure a few points. But part of that obscures that probably 80% of people don't have any change and maybe 20% have a, maybe a more slightly significant change. So we know that there's some impact there. We know there's some people with extremely rare genetic underlying conditions, usually related to the neurologic wiring of the heart, who are particularly vulnerable to dropping dead from a stimulant. Almost every year, there's, you know, a well-trained athlete,

• 1:22:59Speaker 01

  either a professional player, or more often a high school or college player, college, you know, who will take cocaine, take Ritalin, take prescription stimulant, and drop dead of a heart attack. The risk of that's so uncommon, this is 15 years ago, when Adderall XR came out, the Canadian government was worried enough about this risk that they banned Adderall XR for almost a year. And because they have a comprehensive medical system, they could look more extensively at the numbers, and this was looking at kids. The percentage of kids who drop dead with Adderall was tiny,

• 1:23:42Speaker 01

  and not just tiny, it was lower than the kids who aren't on Adderall who dropped dead of a heart attack. So part of it is, if you're in this rare genetic condition, almost always there's family members, or you've had some other near-death or syncopal episode where you passed out. So history-taking of the individual and family history. And if you're at all worried or concerned, you can do EKGs, which detect most of those electrical abnormalities. But the cardiology, and lots of my colleagues practice maybe a more conservative, cover-your-ass-medicine approach, where everyone has to have an EKG before they're on a stimulant. But even the cardiology associations have said,

• 1:24:27Speaker 01

  "That seems to be a waste of resources. Absolutely do a thorough history. Absolutely do a thorough family history. If there's anything of concern, or if the patient's anxious about it, get an EKG. But other than that, these should be generally safe for most people's hearts." So there was a meta-analysis that came out earlier this year on... So most of the studies looking at more serious, other than just mild hypertension or mild elevation of heart rate... Haven't found much, but most of them only look, you know, a year out or a year of treatment. Do we see rates of heart attacks? Do we see rates of strokes? Do we see rates

• 1:25:06Speaker 01

  of dangerous arrhythmias? And in general, they're looking at a young population where these events are really uncommon anyway, and most of them didn't find any evidence of problems in a year or two out. The more recent study looked as long as 14 years out, and there they found measurable statistically significant increase in risk that increased during the first three years of being on a stimulant and increased at a much lower rate for the next 10 years, sort of plateaued out, but still measurably higher than people with ADHD who weren't on a stimulant. But the absolute rate is still really, really

• 1:25:48Speaker 01

  low. So for most people, it's not a risk. I mean, on the other hand, if you start these medicines when you're 10 or 20 and maybe on them for 60 years, we don't have, we don't know whether potentially more people are getting into more trouble.

• 1:26:05Andrew D. Huberman?

  So if somebody presents as having ADHD as an adult and they've never touched stimulants and they're, would you start them on Ritalin, Wellbutrin, or Adderall, or something in the Adderall, Vivaance cloud?

• 1:26:19Speaker 01

  So thanks for bringing me back to your question.

• 1:26:22Andrew D. Huberman?

  Sure.

• 1:26:23Speaker 01

  And I'm going to jump at, you threw in that sort of qualifying phrase, never been on any stimulant in their life or tried it or something.

• 1:26:31Andrew D. Huberman?

  At least not consistently, yeah.

• 1:26:32Speaker 01

  What I would say is lots, these drugs are fairly common in our society, both illicitly and licitly. I mean, we know lots of kids, lots of adults with ADHD share their medication. Lots of people have tried these things, even if it's just once or twice. And that itself is valuable clinical data, you know, if they felt too revved up from it, you know. So if they have, I try to find out what dose was it? What did it do for you? What good things did it do for you? What bad things did it do for you? So my presentation is usually, you know, Adderall is likely to be the most strongly effective, or I more

• 1:27:13Speaker 01

  often are using Vivaance. These are the other options. But Adderall also has, again, greater rare, but risk for these bad problems. What?

• 1:27:24Speaker 01

  Does that scare you? Some people are petrified. They're not going to go anywhere near that. Some people say, yeah, I'm not that concerned about it. And most people do come in with some friends at work, family members, X, Y, or Z. You know, they think they know what the drug is likely to have as an effect on them. And I tend to, at least as a starting point, listen to that. And now, I mean, there are certain reasons I absolutely would not. I mean, my worry, again, I saw more of it than I think most people on a higher rate with amphetamine anger psychosis. But a friend from college was just trying to refer a friend's son,

• 1:28:08Speaker 01

  who's 27 and had a psychotic episode on marijuana, and does have ADHD and is in bed depressed and not going to work, and is being evaluated by two New York City doctors. But the psychiatrist kept him on Adderall. I absolutely, again, the likelihood of recurrence seems so high that if you have a family history of schizophrenia or psychosis, or you've had any experience of it, I would not prescribe a stimulant, an amphetamine-based stimulant.

• 1:28:44Andrew D. Huberman?

  Could we go so far as to say, and I suspect the answer is no, but because nowadays we're hearing more about the possibility, I want to highlight possibility, of high THC cannabis-causing psychotic episodes. This is something I've stressed on this podcast, on social media. I took a lot of heat for this from the traditional press. And then ironically, they're now putting out information that essentially speaks to the same. I'm not saying this happens in everybody, but there's certainly a possibility there. Would you say that if somebody is a regular, high THC cannabis user, that they are at greater risk to developing psychosis if they're taking these stimulant form ADHD meds?

• 1:29:27Speaker 01

  Yeah, I mean, you could actually play that both ways. I mean, you could claim that if they've already been on an agent without developing psychosis, then maybe they're more impervious to that as a potential side effect. Or where you were coming more from is if we're already on one agent that's pushing them that direction, why the heck would you ever add another that could also? I mean, my approach clinically would be more, what do you think the marijuana is doing for you? And might it be more helpful to just clear that out of the picture before we add anything new onto it? But depending on what they say or don't say. So my reading of the data is very clear that there is some, I mean, there's, even at low

• 1:30:11Speaker 01

  THC, there is some risk. Is it, you know, Reefer madness that everyone who puffs a joint is freaking out? Clearly not. But again, it's much more potent than it was 10 years, or that was 70 years ago, I guess.

• 1:30:25Andrew D. Huberman?

  Yeah, especially as I understand, we had an expert from the cannabis research community on in edible form in particular. It's harder for people to control the dosage. Whereas when people use inhalation as a means to deliver, it seems like they kind of find the right plane without going overboard more often than with edibles in any case.

• 1:30:44Speaker 01

  Well, one other big factor is that CBD actually seems in some studies to have an antipsychotic effect. So, you know, maybe strains of marijuana 50 years ago that had a, whatever nature thought was a more balanced view, had less of a risk. But now that you can get pure THC products, and I'm sure you've highlighted that a big problem with this whole industry is even in Colorado, which three years ago was a state with the most close regulation and inspection and...

• 1:31:14Speaker 01

  Almost a majority of what the labels say don't correlate with what you're really getting. So this is not a well-regulated industry, even though states are trying to regulate their industries, so you may not know what you're getting. CBD, again, may have some protective effects, so getting pure and higher potency THC may be particularly undesirable. So in my own YouTube podcast series, I've researched lots of subjects, and most of them, I wind up saying, "We don't have a lot of data on it, and there's not a lot of data on marijuana." It's the one subject I've actually changed my mind from reading was out there.

• 1:31:57Speaker 01

  And for years, I would tell people, because being in San Francisco, even before the wave of legalization, lots of people were using it, lots of people felt to help them. And what I would tell them is, "The data we have," and these are from everyday users, "is that they are measurable, you know, that the characteristic of the classic stoner has a grain of truth there." So measurably lower motivation, poorer organization of thought, lower energy are strongly correlated with daily marijuana use. Why would anyone with ADHD want any of that going on? That seems like a perfect misfit, or accentuating what's not working right.

• 1:32:39Speaker 01

  Over the years, though, I had a handful of people would swear it worked better for them than stimulants, it worked better for them than the non-stimulant alternatives. Clearly not everybody. And when I looked at the data, there is actually some tiny studies, you know, there are some that are funded by marijuana organizations, so that doesn't mean they're wrong, but...

• 1:33:03Speaker 01

  It's harder to evaluate how objective they were. But there's some research that suggests there is some subsegment, and I don't think it's eight people with ADHD in general, but some subset of that population who may actually do better. And most of the time, they were looking at marijuana rather than pure THC. And what I was going to say is there's probably at least seven or 80 other psychoactive components to marijuana. Not most of them is in a higher concentration as a THC or CBD, but they're out there. Maybe they are more important even at lower concentrations.

• 1:33:38Andrew D. Huberman?

  I've heard this, that for some people cannabis can help them focus. And I'm certainly not one of those, but it certainly is interesting. As long as we're on cannabis, excuse me, as long as we're discussing cannabis, neither of us are on cannabis, to my knowledge. Maybe I could just ping you for kind of the relationship between various compounds that people use that are available over the counter or with, you know, sort of online access to these compounds and ADHD symptoms specifically. And then at some point, I'd like to return to the amphetamine based drugs. So let's just start with nicotine.

• 1:34:23Andrew D. Huberman?

  So these days, there's increased use of nicotine pouches, gums, not just smoking, vaping, dipping and snuffing. And it's certainly a stimulant and certainly a lot of people, in particular, young males, are using it more often. The traditional media is now trying to create this kind of picture of nicotine being part of the kind of wellness and fitness community, but in my observation, many, many more people outside of the, that category are using it. So. What in your experience happens when somebody with ADHD, let's assume they're not medicating in any other way, starts dabbling in nicotine use?

• 1:35:05Andrew D. Huberman?

  And let's assume they're going to do this in ways that do not cause cancer, because the smoking, dipping, vaping, snuffing part is what causes the cancer. Let's just talk about the compound nicotine.

• 1:35:15Speaker 01

  Yeah, so there's some well-done research showing nicotine is helpful for improving some of the executive functions of sustained attention. And I'm not sure which which are the executive functions, but they help people focus, be sharper, do better. There was actually a major pharmaceutical company who was developing a nicotine receptor product specifically for ADHD. And they abandoned that several years ago. And I haven't been able to find word as to why that was abandoned, whether there was some other side effect. It's worth throwing out there that although nicotine in many ways acts like a stimulant, it actually is moderately unique.

• 1:35:59Speaker 01

  And I hate people who's unique means one of a kind. So I can't say I can't modify it in any way. Unusual, maybe not the only one. Unusual in that it both arouses people and reduces anxiety simultaneously. Not too many, most of our stimulants are again banging away at the sympathetic nervous system. And that's banging away on good arousal and bad arousal. So nicotine again seems to be both calming and helping alert or focus people. And as you know, as long as they're taking it in a way that's not clearly detrimental to their health, which smoking and vaping and probably chewing are, well, not probably, definitely are.

• 1:36:44Speaker 01

  And if it's affordable, because some of these products are pretty pricey, at least the chewing gums or the Nicorette that was used for helping people with smoking cessation. I have some people who feel that it's been an important and useful part of their regimen. I have some people. Small numbers who prefer it to any other medications. And almost no, again, other than sort of the basic neurophysiology showing that it can have beneficial effects on executive functions, there's no research, at least as of a year or two ago, whenever I dipped my toe, not my anything else into the snuff,

• 1:37:26Speaker 01

  looked into it, there's no, you know, clinical research showing, does this help or not help?

• 1:37:31Andrew D. Huberman?

  What about caffeine and in particular, energy drinks? These days, there's just seems to be an explosion of drinks that include caffeine, but also fairly high dosages of things like taurine, alpha GPC, thienine, you know, so.

• 1:37:49Speaker 01

  Tyrosine.

• 1:37:50Andrew D. Huberman?

  Yeah, tyrosine, so, you know, things that are thought to generally amplify the production or release of neuromodulators like dopamine, acetocalline and so forth.

• 1:38:00Speaker 01

  So epidemiologists say that the most widely used psychoactive substance on this planet, and I thought it was alcohol for years, but it's actually caffeine, because lots of groups outlaw alcohol, who won't outlaw caffeine. So lots and lots of people use it, and this is a gross oversimplification, but this is what I tell people. Even though it's the most widely used, if you used it as an equivalent dose to our stimulants, I mean, essentially, we're using it at a lower dose level, it's a pretty lousy stimulant. I mean, separate from that it's working primarily on adenosine and indirectly working on dopamine, but associated with higher levels of andrioidy, higher levels of jitteriness, higher levels

• 1:38:45Speaker 01

  of cardiac toxicity, if you were to use it at an equivalent dose. But most people are using it at a substantially lower dose. And the ADHD experts sort of historically have fallen into two different camps. Some of them have said.

• 1:39:02Speaker 01

  It's gonna interact with your stimulant or other medications. It's complicated. We don't want it messing up the picture. Stay off of it. And the other half say, it's a stimulant. You know, lots of people are using it with these other stimulants, you know, both full-blown stimulants and non-stimulant ADHD medications. And as long as you know it's part of the picture and you're trying to be constant with your dosage or aware of it, then, fine, and maybe it helps you get away with a lower dose of the prescription. The one little piece I'd add in there is that often you don't know what dose you're getting. So people have the common experience, as I was saying earlier, I've only had three cups of coffee in my whole life, so this is all anecdotal or research, not personal experience data.

• 1:39:47Speaker 01

  But lots of people have the experience, go to their local Starbucks or something and say, whoa, that feels way stronger than usual. And then invariably they say, oh, that must just be me. I'm more anxious already, I'm jacked up, or... Because they think Starbucks, you know, seven billion stores around the country, everything's automated and press ice, they must be... Starbucks isn't, you know, they control for the aromaticity, they... how many minutes each bean is cooked, to which side it gets flipped over on. They're not controlling for caffeine intake, which is wild to you and me. So, University of Florida study, and this is several years ago now, went into a Florida

• 1:40:29Speaker 01

  Starbucks, bought the same drink every day for three weeks, and compared the caffeine content, the highest day compared to lowest days, was a three-fold difference.

• 1:40:40Andrew D. Huberman?

  Wow.

• 1:40:41Speaker 01

  And that's Starbucks. Who knows what smaller... So, so one is, you may think you know what you're giving, and maybe, you know, the bane of coffee drinkers, and maybe senka in a teaspoon that you're dissolving may be the most consistent there, or... But one of the risks with caffeine and with pretty much any over the counter drug is you may not know what dose you're getting.

• 1:41:05Andrew D. Huberman?

  Very interesting. I mean, I, as I've said several times in this podcast, I think caffeine is a wonderful drug, mostly because I love the things it comes in. Yerba mate being my, you know, preferred source of caffeine, but also coffee. And it certainly increases my focus. It's a narrow plane, though. You know, two sips too many and I can start feeling myself veer toward more lack of focus. It doesn't seem to have a very pervasive effect. And dosing it on an empty stomach versus after eating, it's, I mean, I'm not that precise about it, but I don't see it as a very reliable stimulant. It's more to get

• 1:41:48Andrew D. Huberman?

  to a plane of just normalcy for me, given how much I've been drinking it since I was a teen, really. I think most people are similar. They drink it to feel normal.

• 1:41:57Speaker 01

  Yeah, there's lots of, well, and there's also lots of cultural and habitual, you know, if it makes, gives you your warm fuzzies or puts you in the right mode, or you're sure, you think you're more alert, or you're listening to your favorite newscast in the morning as you're drinking it. That all is adding to its effect. In terms of combining it with other over the counter things, there is some study looking at caffeine and L-theanine together. And having some, at least in a tiny handful of studies, some measurable beneficial effect on, I think it's mostly kids that have been looked at, and nothing dangerous

• 1:42:37Speaker 01

  found across a pretty broad range of L-theanine dosages. But it's, I'm not aware of any good research done with adding all the other things that are currently being added to it. And some logically may be doing something, some may be irrelevant, some may be more detrimental.

• 1:42:55Andrew D. Huberman?

  L-theanine certainly is being added to a lot of caffeine containing drinks because it seems to take the jitters off. And the assumption being that people can consume more of that, that drink as a consequence.

• 1:43:07Speaker 01

  Yeah, there's a tiny bit of evidence that suggests it may both, you know, dampen, you know, help with anxiety, but it may directly have some beneficial cognitive executive function benefits itself.

• 1:43:20Andrew D. Huberman?

  Yeah, this is in keeping with the green tea hypothesis, which I believe green tea is enriched with theanine.

• 1:43:29Andrew D. Huberman?

  You are somebody who, quite refreshingly to me, has talked not just about prescription drugs and behavioral tools for ADHD, but also, actually, I think years ago, you were the first person to first share with me the data about fish oil and the EPA omega-3s for depression. Those studies were starting to come out, we were talking about those studies. And nowadays, I think, while there's still a little bit of controversy out there about fish oils, I think most everybody believes that getting high-quality omega-3s from good, clean sources, including fish oil, is mostly beneficial or beneficial. What

• 1:44:11Andrew D. Huberman?

  about fish oil for ADHD in particular, and what threshold dosages are relevant here?

• 1:44:20Speaker 01

  So, just as with the fish oil for cardiac benefits, you know, there was a time period where the first few large, and they were pretty large, well-done studies showed benefits for cardiovascular health. The more recent studies with fish oil haven't shown an effect or benefit. And strangely to me, and not very scientifically, the cardiology community sort of looks at the more recent ones and say, "Okay, that's what it is." Well, you have to reconcile all the data in the pool. The ADHD fish oil story is a little the opposite, and it's been, it's almost everything with ADHD, it's been kids that have been most strongly

• 1:45:00Speaker 01

  looked at. The first few studies with fish oil in kids didn't show any benefits at all, and then subsequently, there have been several studies that looked at benefits. And again, and the field jumps to the second set without reconciling, "Well, how do we, you know, do a good meta-analysis with everything in there?" Or, and I haven't looked closely enough to know, you know, were there methodological differences, dosage differences, population differences that matter. I'd say unless you're taking so big a dose that you're probably at risk for heavy metal poisoning, which...

• 1:45:36Speaker 01

  Is a possible issue with big, big, big doses of fish oil. I mean, most of the recommendations are in the range that it seem. And I'd say that depression has been the most consistent field and not. That doesn't mean every study there has been positive either, but the most consistent field for a mental health benefit or a health benefit.

• 1:46:00Speaker 01

  And there the recommendation is usually target about a thousand milligrams of EPA of icosapentanoic acid a day.

• 1:46:10Speaker 01

  If you're seeing some benefit, but it feels like that there's more room for improvement. So this is my motive. I tell people, then you could probably double it reasonably. I mean, some of the dramatic, there were dramatic studies looking at fish oil for mania. People hospitalized with it, but and they use dosages as high as 7,000 milligrams a day.

• 1:46:32Andrew D. Huberman?

  To treat mania?

• 1:46:33Speaker 01

  Yeah. And that study, I think it was a Harvard area clinic that was doing it. The results were so dramatic that they ethically had to stop the study before its intended completion because the benefits seem to be so robust in the fish oil group compared to the, that it was unethical to not put everyone on fish oil.

• 1:46:54Andrew D. Huberman?

  That's a lot of fish oil.

• 1:46:55Speaker 01

  It's a lot of, yeah.

• 1:46:56Andrew D. Huberman?

  You probably need to get it in liquid form to make it, you know, so it wasn't so expensive. But I find this recency effect incredible that you meant, you know, which you mentioned a few moments ago that, and I think this is helpful for people to hear. Certainly it is for me. You know, we hear, you know, studies over the years have explored fish oil for cardiac benefits and then more recently, as I understand, you know, they, these are not, have not been demonstrated and there seems to be a focus on the recent studies as if the old ones don't exist. That's essentially what you described for both cardiac and ADHD. I think it's really important. We hear this with alcohol too. I've been involved in this debate. I, you know, I don't care if people drink one way or the other, provide they take care of themselves and others.

• 1:47:41Andrew D. Huberman?

  And if you're an alcoholic adult, don't drink. And if you're a kid, don't drink. But, you know, people want to drink a few drinks a week. I don't have a problem with it. But it's remarkable that every time a study comes out showing a mild benefit of moderate alcohol use, that seems to be the highlight and then everything else is forgotten. And the inverse is also true. One would think that the meta-analyses would include all, as many good studies as possible, but I think it's important to understand that people hear that that's not always the case. Just because there's a meta-analysis doesn't mean that it included all the relevant studies. So I'm just restating. Thank you. I make it a point to try and get one to two grams of EPA per day, just as a general mood. You know, I'm not clinically depressed, but just to support my mood, to support focus, to

• 1:48:26Andrew D. Huberman?

  support well-being, including cardiac function.

• 1:48:28Speaker 01

  So the other thing that I think is understudied with the fish oil issue is that, and it's a Harvard guy who has a proprietary brand of purified EPA that pushes it. So in nature, whether you're a whale, or a human, or a butterfly, or a, maybe not insects, I'm not sure, that across the mammal, bird, reptile kingdom, the omega-3s are found in about a two to one ratio of EPA to DHA, acysapentaenoic acid to docosaxanoic acid. And what I tell people is, I think Mother Nature's probably smarter than any Harvard professor. And the

• 1:49:08Speaker 01

  brain particularly is high in the brain membranes of DHA. So I don't see, some people seek out EPA purified or sole, you know, only EPA brands. That, to me, doesn't make a lot of sense. So I would, I would say, we can still count or do the numbering based on about 1,000 milligrams of EPA, but don't worry that you're getting about 300, 400 milligrams of DHA, and probably that's better for you.

• 1:49:37Andrew D. Huberman?

  I'd like to take a quick break and acknowledge one of our sponsors, Mateina. Mateina makes loose leaf and ready to drink yerba mate. Now, I've often discussed yerba mate's benefits, such as regulating blood sugar, its high antioxidant content, the ways it can improve digestion, and its possible neuroprotective effects. It's for all those reasons that yerba mate is my preferred source of caffeine. I also drink yerba mate because I simply love the taste. And while there are a lot of different choices out there of yerba mate drinks, my personal favorite, far and away, is Mateina. It's made of the highest quality ingredients, which gives it a really rich, but also a really clean taste, so none of that tannic aftertaste. In fact, given how absolutely amazing Mateina tastes and their commitment to quality, I decided to become a part owner in the company last year.

• 1:50:21Andrew D. Huberman?

  In particular, I love the taste of Mateina's canned zero-sugar cold brew yerba mate, which I personally helped develop. I drink at least three cans of those a day now. I also love their loose leaf Mateina, which I drink every morning from the gourd. So I add hot water and sip on that thing and I'll have some cold brews throughout the morning and early afternoon. I find it gives me terrific energy all day long and I'm able to fall asleep perfectly well at night, no problems. If you'd like to try Mateina, you can go to drinkmateina.com/huberman. Right now, Mateina is offering a free one-pound bag of loose leaf yerba mate tea and free shipping with the purchase of two cases of their cold brew yerba mate. Again, that's drinkmateina.com/huberman to get a free bag of yerba mate loose leaf tea and free shipping.

• 1:51:04Andrew D. Huberman?

  You're one of the first people that I ever heard discuss the gut microbiome and ADHD.

• 1:51:12Andrew D. Huberman?

  This is me giving you credit for being way ahead of your time. I don't know how you are receiving praise, especially on camera and with microphones, but I just want to say that, you know, it was over a decade ago that I heard from you about EPA and fish oil for depression and other things, about circadian rhythms, an area that I'm familiar with, and just the critical importance of circadian health for everything that we're talking about today and more, and on and on. And so, you know, again, thank you for raising these points, even if they turn out to be minor effects. I think nowadays we hear about the gut microbiome. I may have actually heard the words gut microbiome first from you.

• 1:51:57Andrew D. Huberman?

  Gosh, yeah, that would be well over.

• 1:52:01Andrew D. Huberman?

  That'll be almost 20 years ago. Remarkable. So gut microbiome, what do we know about the gut microbiome and supporting it in ADHD?

• 1:52:11Speaker 01

  I'm going to kind of pass on that by just saying it's complicated and probably important and so many variables that it's hard to know what's really valuable in a day-to-day, real, human living perspective.

• 1:52:27Andrew D. Huberman?

  Do you do anything to support your gut microbiome? Just in with your knowledge of of a of the relationship between gut and mental health? Does it impact your behavior at all in terms of choices?

• 1:52:42Speaker 01

  Yeah, only to the extent of trying to have a varied diet and eating at somewhat regular interval intervals, but not not more specifically.

• 1:52:52Andrew D. Huberman?

  Great. That's where we're at, where that's where we're at. Before we go back to some drugs, I wanted to ask about behavioral tools for ADHD. I've seen some of the literature claiming that certain video games might actually be useful for training focus. I've managed to find a few papers that talk about focus and meditation tasks that kids in particular, but adults may be able to get better at. I mean, are any of these brain training games to get people better at focusing? Are any of them known to be worthwhile according to like real data or clinical observation?

• 1:53:33Speaker 01

  So start first by stepping back a little bit and broadening it, broadening it, I'll get to the video game things. But one of the effective approaches that helps with symptomatic reduction with ADHD is cognitive behavioral therapy. So that's a form of talking therapy. And my quick overview of it is that it focuses on

• 1:53:56Speaker 01

  Actions, thoughts and feelings and that humans can have direct control of their actions and thoughts, not too much over their feelings, but all three are affecting each other. And the traditional CBT was developed by Aaron Beck to treat depression, probably fifty years ago, maybe longer, sixties, I think, late sixties. Anyway, on the surface, it's a horrible match for ADHD because we know it requires lots of repetitive, boring homework, doing the same thing. It involves introspection of being aware of what you're doing already, looking at those patterns, looking at what the triggers, you know, to see if you can see triggers for them.

• 1:54:38Speaker 01

  And then doing lots and lots of repetitive homework, which, and, and when it's successful for depression or PTSD or other venues, we know it actually changes brain wiring and brain chemistry. So lots of people still think talking therapies are sort of up here doing something and chemicals and medications are really changing the brain. If your thoughts are changing, if your behavior's changing, your brain has changed. That, that's the only place that thoughts and behaviors come from. But there have been at least two groups, Mary Solantos in New York and Harvard Group, I'm blanking on his first, Safran and, and some other, Ramse at Pennsylvania, developed

• 1:55:21Speaker 01

  approaches using CBT techniques specifically designed for people with ADHD to help overcome some of those hurdles and barriers. And both of them encourage actually the use of medications in combination with it. So, because many people with ADHD are too unfocused, too unable to sit down and do it. But these are approaches, and both approaches are amazingly similar, although devised completely independently. At the core of both of those approaches is having a system of scheduling each day. That doesn't mean micromanaging each minute, but it's having the essentials in place, having blocks of time that you know what you're gonna do.

• 1:56:02Speaker 01

  And having a task list in combination with that and ways of learning to prioritize and move things up or down and again with ADHD being interest driven rather than importance driven, you may have a task, I mean, you probably have seventeen task lists, one's New York Coffee, one's at the grocery store, one, you know, one, it's having one consolidated list, because if it's everywhere, then it's nowhere, and two is the simplest triaging or organizing approach is having the things that are both urgent and important, so that have to happen today, those get in the A category, the things that are important but

• 1:56:46Speaker 01

  aren't as urgent are the B category, and all the other things are the C, and one of the temptations that people with ADHD have is, oh, I need to be productive, uh, uh, you know, it's fun to go buy shoelaces, and that's on my list, so I'll go to buy shoelaces, because then I can cross something off my list, but I didn't move the car, I didn't do my taxes, I haven't done my homework, you know, all the important things remain undone, so it's a system for getting done what's really needed to be done, and, you know, eventually, if, if your shoes don't work, the shoelaces will move up to that A category, but for most people, they're not really there, and it's not a good use of your time to do them first.

• 1:57:27Speaker 01

  So that, and, and there's much more to it, so that CBT approach can work with decreasing procrastination, it can help with structuring your own workspace, given that you probably have much more trouble doing that and not doing it spontaneously, it's how to eliminate distractions, and modules on even extending your concentration time. So, the answer with the video games, there is one product that's actually been FDA approved for use in ADHD, and the really important thing to remember there is the FDA's system for addressing medications is much more rigorous, much more thorough, you have to demonstrate it really works and

• 1:58:12Speaker 01

  does something, when the FDA approves devices, basically, they're saying it's not going to kill anyone, it might help.

• 1:58:22Speaker 01

  I mean, it might help tremendously, but having the FDA in primature for that doesn't guarantee that or mean that at all.

• 1:58:28Andrew D. Huberman?

  Do you recall if the study of that device or the study of that video game has a conflict of interest, was it run by the company?

• 1:58:36Speaker 01

  Yeah. Yeah, so almost all of them have been run by the company. I mean, it's good people at UCSF who are at least partly involved in it.

• 1:58:44Andrew D. Huberman?

  Oh, is this Adam Gazelli's group?

• 1:58:46Speaker 01

  I think so.

• 1:58:47Andrew D. Huberman?

  Yeah, he's, I should just say that I've followed his work for some years. He's a neuroscientist. I know people who have been in his lab. He's known for doing very, very high quality and stringent work.

• 1:58:58Speaker 01

  Their product and some of the others can clearly show you get better at their product and you get better at tests that look exactly like their product. But in terms of real world, how much is this really helping ADHD symptoms on a day-to-day basis? Not a lot of data at all. So again, that doesn't mean it doesn't work. And I'm going to go sideways in talking about neurofeedback because there's lots and lots of neurofeedback companies across the country that are making lots and lots of money. And there was an article in the American Journal of Psychiatry in the last year, I'm not remembering

• 1:59:37Speaker 01

  which group did it, and it was another non, a failure to find a significant impact from neurofeedback. And again, I'm not saying it doesn't have an effect, but I've had lots of people saying, writing me, should I keep spending hundreds of dollars each week as my insurance isn't covering this? And the doctor's saying, oh, maybe 20 more episodes will retrain your brain. So this gets back to a topic you brought up earlier. How much are we retraining our brains with immersion in social media?

• 2:00:14Speaker 01

  And the evidence is we are rewiring our brains. So maybe anything pushing in an opposite direction, or maybe this is reinforcing some of the bad things we don't want. It's we're in a messy world without clear answers yet.

• 2:00:30Andrew D. Huberman?

  I've made it a point to put social media on an old phone.

• 2:00:35Andrew D. Huberman?

  So those apps are only on that phone. I don't even know the number to that phone. If I need to post something, I airdrop it onto that phone. And this has helped tremendously in segregating that activity and limiting it. It also means that if people send me something which would otherwise direct me to social media, it's much more difficult for me to go look it up. It's helped tremendously. I just pass it on because it's one of the things that's really allowed me to restrict my social media time. And yet still be, you know, in keeping with the fact that I think social media has its uses. I post there, et cetera.

• 2:01:08Speaker 01

  Yes, so getting back to the scheduling, I mean, what I recommend to people. And one of my weaknesses, I don't know the specific apps, but there are apps that will help shut you out of Facebook or Discord or TikTok or whatever is. If you can't exert your own willpower, which again is harder to do if you have ADHD. And if the app approach doesn't work, the next level up is there are all sorts of companies making lock boxes and physical devices where you can lock yourself out of your device for certain hours of the day. And I think that's a good idea for lots of people.

• 2:01:45Andrew D. Huberman?

  I do too. And I think it also helps, at least in my experience, to do things that are very different than social media as well, but still consuming content. So I make it a point to read from an actual physical book a bit each day or night. Also because I was raised doing that and writing by hand. It's just sort of in keeping with the way that my brain was was wired. So maybe that's more specific to me and my generation. But I find that when I'm doing those other activities, when I go on to social media, it feels more like a departure from the rest of life as opposed to the other way around.

• 2:02:22Speaker 01

  But that's a good sign for preserving.

• 2:02:26Andrew D. Huberman?

  I'd like to talk about some compounds that are not so typical. Meaning, some people may have heard of these, but most people probably haven't. And they are somewhat novel to me. The first one is guanfacine. What is guanfacine and why is it sometimes used for ADHD?

• 2:02:46Speaker 01

  So guanfacine and a related drug called clonidine, which can be confused with clonopin and others. So clonidine and guanfacine are both alpha 2 agonists. So they work on a subset of the norepinephrine system. They're both originally anti-hypertensive for lowering blood pressure. And it was actually studies first in clonidine that suggested this could be helpful with people with ADHD. And I think it was just a serendipitous initial discovery. It wasn't seeking out its mode of action to see if that really worked. One difference between the two of them is clonidine jumps off the norepinephrine alpha 2 receptor really quickly.

• 2:03:28Speaker 01

  And for people who skip a dose with their blood pressure medication or stop abruptly, it's not uncommon to have rebound hypertension. And not just mild, but way higher than what you're being originally treated for, to dangerous levels. Guanfacine leaves the receptors more slowly. And there've been formal studies trying to see if this is a problem or issue there. And particularly given that people with ADHD forget their medication or run out and don't fill it in time or just don't remember to take it. The rebound hypertension does not seem to be nearly as common with guanfacine. And that's part of why the research has moved more towards the guanfacine.

• 2:04:13Speaker 01

  So there's extensive work by, I'm going to blank on her name, Amy Arden? Ar, that's, she's at Yale.

• 2:04:21Andrew D. Huberman?

  Oh, um, Arnston.

• 2:04:22Speaker 01

  Arnston, thank you, yeah. And her lab and related labs have shown that guanfacine's effects seem to deal with strengthening synaptic connections in prefrontal circuitry. So unlike most of our drugs that are just boosting norepinephrine and or. Dopamine and work quickly, and I'll throw in this because I didn't really touch this. Most of the ADHD experts still say stimulants, amphetamine, Ritalin, work quickly, immediately because they boost dopamine right away. And our drugs like Strattera, which is atamoxetine, or Cymbalta, or Wellbutrin, work slowly for ADHD because they're antidepressants and antidepressants work slowly. There's still people saying this.

• 2:05:07Speaker 01

  And for 25 years, I've been saying, this is just wrong from one, a basic neuroscience point of view, and wrong from don't you ever talk or listen to patients. So neuroscience view, how quickly does dopamine get, reuptake get blocked by Wellbutrin, or by atamoxetine, Strattera, or by Cymbalta, within minutes, hours of taking it? So you would expect, if you're boosting norepinephrine or dopamine availability right away, you should see effects right away. And if you ask patients who these drugs work for, and they don't work for anybody, all the ones I've worked with say, you know, work just like the stim. You know, I could tell, I took it and I walked out of your office.

• 2:05:49Speaker 01

  And I mean, one guy I have who loves Cymbalta, said, I took it in your office and I wasn't sure it was working and I got downtown to work, 15, 20, maybe a half hour later. And there was this guy coming at me on, with this, on a skateboard on the sidewalk. And I know in my normal ADD state, I would have just been flooded and not be able to process. And I could just step out of the way. So, you know, it worked that quickly and dramatically. So that's the aside. So jumping back, guanfacine seems to work slowly. So the synaptic strengthening, building, and it seems to be the nor-, the alpha 2 receptors

• 2:06:30Speaker 01

  that are on, neurons that receive glutamate as their primary input, the alpha 2 receptor is modulating how glutamate is actually working and it's actually a, an MDA glutamate receptor, not the more common in the brain AMPA glutamate receptors.

• 2:06:50Andrew D. Huberman?

  No, that's an important point. I'll just quickly throw in, if I may, that the NMDA, the N-methyldeaspardate glutamate receptors are the ones that typically are associated with synaptic plasticity, although, you know, so are, you know, the AMPA receptors can do that too. But what Dr. Cruz is referring to is the fact that guampicine, you know, indirectly modulates those pathways. So the longer duration to get the effect, it sounds like could be at least partially explained by a real change in neural wiring as opposed to with, you use Cymbalta and Wellbutrin as examples of fast changes in neurotransmitters, neuromodulators that led to this very quick effect in this patient that left your office,

• 2:07:35Andrew D. Huberman?

  got downtown and was already experiencing effect. Put differently, sounds like guampicine and clonidine, not to be confused with clonopin, clonidine could help ADHD but might take longer for the effects to manifest than the other drugs that

• 2:07:51Speaker 01

  Yeah.

• 2:07:51Andrew D. Huberman?

  we typically hear about.

• 2:07:52Speaker 01

  Yeah. So most often it takes two, three, four weeks. And because it, I mean, with the stimulants, you see effects right away. It's reinforcing and stimulants often in addition to having effects on concentration, attention, other, you know, do boost energy for most people, do boost mood for most people.

• 2:08:11Andrew D. Huberman?

  And can improve sleep if they're not taken too close to sleep. Yeah.

• 2:08:14Speaker 01

  Guampicine's most common side effect tends to be sedating. So most people take it at nighttime, which is, why are you taking a sedating nighttime medication for your ADHD? It's because it helps, it works slowly indirectly. So Entuniv, the brand name, extended release guampicine was approved in kids, because again, most of the research on ADHD is still in kids, for treating ADHD as a solo agent.

• 2:08:42Speaker 01

  It clearly works in adults as well. And even before Entuniv was approved, there were a handful of studies with either immediate release guanfacine or extended release guanfacine. In the studies so far, the results aren't distinguishable. You know, they both seem to work. So clinically, because it's much cheaper, I actually use immediately release form. And all at bedtime. And again, because it's my impression, and it probably don't have a N that's big enough to do a rigorous study, is the sedating effects are relegated to the nighttime and people are feeling okay during the daytime.

• 2:09:24Speaker 01

  I mean, some of the rationale with the extended release is you're sort of smearing it over a longer time, so it should be less sedating. But depending on the time curve and how it works, you could actually wind up with being more uniformly sedated day and night with the extended release. So I've seen good results in some people. I've had many who either didn't work or they didn't perceive a result because again, some part for some people of the stimulant benefit is I can feel it, I know it's working. So the majority, at least in terms of prescription searches and what clinics tend to be, it looks like most people who are on guanfacine are on it in combination with either a stimulant

• 2:10:09Speaker 01

  or a norepinephrine or dopamine promoting agent.

• 2:10:13Andrew D. Huberman?

  Let's talk about modafinil and our modafinil by extension. We hear about modafinil a lot in communities like the tech community and communities where people are trying to quote unquote cognitively enhance. What is modafinil? What does it do? What doesn't it do? How might it be useful for ADHD?

• 2:10:36Speaker 01

  So we're going to jump back to your issue with the recency in science and how to incorporate things. When so modafinil was a drug developed by a French company and approved there and used for decades for maybe a decade before it came to the US 25, maybe 35 years ago. And at the time, all the research showed that it was an orexin receptor. Antagonist. Antagonist, agonist. Works on the orexins. The hypocretin-orexin system, right. So boosting activity, but not working like all of our stimulant alerting drugs, which are working on primarily norepinephrine systems. So it was called the non-stimulant stimulant.

• 2:11:21Speaker 01

  Now, most of the pharmacology literature refers to it as a dopamine-acting drug. And there's, some people are debating whether it's orexin that it's working via or dopamine. I haven't seen anything that, to me, means, gives a clear consensus. So I stick with the orexin, because that's where I was taught. So orexin, getting back to the sleep-wake in the brain and arousal, as I described, but there's two ways to wake up in the morning. One way is the normal way, that you just wake up. And the other is being alarmed by an alarm clock, your neighbor, starting their lawnmower,

• 2:12:03Speaker 01

  someone snoring, earthquake, if you're in L.A. or Hawaii, being startled out of sleep. That wakefulness system is a sympathetic nervous system. The orexin system is the more natural, normal waking system. And it isn't arousing you, isn't, it's waking you, but it's not agitating you. Again, the claims originally was that this is how modafinil worked. It was waking you up, but not overstimulating overrevenue. So that the, other than being developed by this French company, the entity that spent most research funds looking into what this does or doesn't do was the U.S. military.

• 2:12:43Speaker 01

  Because they have a big investment in wanting people to be alert and ready to kill 24/7, but not being hyperactive, trigger-happy jittery like stimulants can do. And this, particularly in the early days, this is really dating me of the Afghan War, we dropped bombs on Canadian troops by accident, you know, friendly fire scenario things. And the investigation, the pilot and the crew there blamed their trigger-happiness on being revved up by methylphenidate. So for years, militaries relied on traditional stimulants to keep people able to fight around the clock.

• 2:13:24Speaker 01

  And they wanted an agent that would give you alert, awake, but not revved up, not agitated.

• 2:13:31Speaker 01

  And I'd say there's some good evidence that that's really sort of how modafinil works or performs. So modafinil was called ProVigil for provigilance, and then when they were using, losing their US patent, like many drugs, the ProVigil is a racemic mixture of left-handed and right-handed versions of the same modafinil molecule. They found that the armadafinil, the right-handed version, was the one that's doing most of the good stuff and has a longer half-life than the combined version. So they got a new patent for armadafinil, which is new vigil. So that's, that's the only difference between the two. They're the same active ingredients, as far as we can tell.

• 2:14:16Speaker 01

  So, and when it got approval in the US, it was approved for narcolepsy, where people are falling abruptly asleep during the day, so keep them alert and awake there. It also got approval for circadian sleep shift work disorder, where because you're on a shift schedule, you're sleeping weirdly. And it got approval for daytime sleepiness from sleep apnea. But even at that time when it was approved, there were dozens of studies that showed, regardless of why you're sleepy, whether it was sedating medication, whether you had lupus or MS, whether you had some other condition, it works pretty well for keeping people alert and awake.

• 2:14:57Speaker 01

  So more than keeping alert and awake, there does seem to be evidence that it helps with some of the executive functions of attention, concentration. My clinical experience with it, it tends to be, again with the amphetamine on top, many fewer people describe it as being helpful or as helpful. On the other hand, there's one study, and I'm forgetting the principal investigators, it was Brown University, where they used some very clever, sophisticated approach to try to sort out motivation versus pure cognitive functioning. And their claim, and it was a very well-done study, they were comparing it directly to an amphetamine product.

• 2:15:41Speaker 01

  Their claim was that modafinil was the one that was actually boosting cognitive functions and not just boosting motivation, whereas that most of amphetamines benefit for ADHD when we say, it helps me concentrate, it helps me... Sustained focus, it makes me less distracted. Their feeling, their analysis was that the stimulant was mostly working on motivation. It's a controlled substance, but not nearly, not the same schedule as amphetamine and Ritalin, so it's easier for some prescribers to prescribe. Even though it's the non-stimulant stimulant, and I'd say most people do experience, you

• 2:16:23Speaker 01

  know, I feel more alert or awake or better, but I don't feel revved up. About 10 to 15% of people that I've worked with and others have written about it, so I don't think it's unique, will feel revved up when they take it the first few times. And invariably, the people I've worked with have said, "This feels like bad speed." Including people who haven't too, who never even took speed. So I don't know why they came up, I mean, it's just weird that people come up with the same terms. But it's, I mean, my interpretation is that for some people, this novel substance primarily maybe tacking into the orexin system is serving as a signal, kind of like a panic attack

• 2:17:05Speaker 01

  does, that there's something weird, something different, we're being revved up, and that it's, I think, secondarily triggering the sympathetic system. Because for most of those people, within a few trials, within a few days, they no longer had that over-rev effect. And again, the important piece for alerting people to that is if they're expecting taking this, "I'm not going to feel over-roused and over-agitated," and they do, then they're even less prepared and more freaked out.

• 2:17:36Andrew D. Huberman?

  Even though I've never tried modafinil provigil, that people that I know who have, and I know one who has for treatment of real narcolepsy, so he's a narcoleptic, but others who have, take it for ADHD and for work focus and cognitive enhancement.

• 2:17:56Andrew D. Huberman?

  People who take modafinil and are modafinil really like it. They, I don't know if it has any reinforcing property, but today's the first that I've heard that has this dopaminergic aspect. But they seem to really like it and rely on it. Have you seen a kind of a dependence form?

• 2:18:12Speaker 01

  I mean, it is a controlled substance because some people are worried about the potential. And there was a woman, an Olympic athlete, 20, 15 years ago, who was, had modafinil and said she had narcolepsy. I don't know, but was disqualified from the Olympics because of it. Whether it has any real performance enhancing effects is not clear. You know, it was available in France for a decade, at least before it came to the US, and they didn't see any rates of substance abuse or problems. I mean, it clearly does not have the, on any tests or animal studies, the propensity that the amphetamines do.

• 2:18:53Speaker 01

  And I'd say it's, to me, not a concluded subject, whether there's any potential for addiction with it.

• 2:19:01Andrew D. Huberman?

  What about within the category of Adderall, Vivance, and the stimulant-type treatments for ADHD? I don't want to say what are your go-to favorites, because that's, that makes it sound very non-clinical. But, you know, what are the general trends that you've observed and that others have observed clinically or in any studies about preference for long, long-acting drugs versus shorter-acting drugs? And maybe this is also a good opportunity for you to be able to chime in about, like, drug holidays, you know, taking weekends off or things of that sort.

• 2:19:40Speaker 01

  Maybe I'll start with that. So, for decades, particularly starting with kids, the, the dogma has been, taking breaks from stimulants is a good idea because it will decrease the likelihood of developing addictions, it will decrease tolerance, and...

• 2:19:58Speaker 01

  Not a lot of rigorous research, but one of the known side effects of stimulants for kids is growth suppression. So height winds up being about two centimeters, not big, but measurably and consistently found there for kids who are routinely on these stimulants for their growth years. And taking breaks that last for several months, like taking it off during the summer, result in overcoming that decrement in height. I looked, and I still haven't, whether there's any lower rate of addiction, whether there's any lower rate of developing tolerance. There's nothing that shows clinically. I mean, it may be true.

• 2:20:43Speaker 01

  The other recommendation when I started out was, and this is before the internet, before constant plugged into everything, and before kids had soccer practice and violin lessons and 400 activities, is that kids should take it during the workdays and not take it during the weekends and not take it during the summers. And now, and for many years, we've lived in a world where little Johnny has soccer practice and ballet and piano and has 42 things to get to, where he's supposed to be performing and focused and behaving. So the sort of excuse you could have downtime has diminished in many communities. And again, whether there's actual benefits to that or not,

• 2:21:27Speaker 01

  other than for the height decrement, which again, there is evidence that taking long breaks, but probably not short breaks, mitigates that. I haven't seen any evidence clearly showing a benefit. That doesn't mean it's not there. Nobody's really studied it rigorously. Sort of related to that, you asked the question about short acting versus long acting. And

• 2:21:55Speaker 01

  There's differences in the realm of what's clinically helpful or useful, and then there's the issue of risks or side effects. So again, one of the claims is that part of what makes a drug more addictive is not just the level it reaches, but how quickly it's going in and out, and that the short-acting drugs may predispose someone to higher rates of addiction. There are, at least occasionally, some people arguing on the other side that saturating the receptors for longer periods of time, but high doses with a long, you know, extended-release version, that may actually be more of a risk. But I'd say there's more concern, I think, in the basic science community from the immediate release.

• 2:22:37Speaker 01

  And there's a tiny bit of data, but part of it overall is that, we talked earlier about global rates of addiction to any substance. That we have fairly good data on, because the CDC tracks it. But in terms of very specifically, who gets addicted to Adderall? Who gets addicted to Ritalin? There's so little data, and most people just sort the same numbers, that, oh, maybe 2% to 3% of kids run into trouble, and it's not common, and that's it. Or they study a much broader question, and that's the issue of misuse combined with abuse. And misuse, by the research definitions, means

• 2:23:18Speaker 01

  anyone who didn't use their drug exactly as prescribed. Which means if you're taking a short-acting Ritalin, and it says, "Take it one every six hours apart during the day", and you acknowledge taking it on one day, eight hours difference? You're classified as a misuse by those studies. I mean, I'm being maybe a little ridiculous, because most of the exceptions aren't that narrow. But there's a big blurring in the research, particularly coming from the people who are worried about addiction. I mean, we should be worried about addiction, but we shouldn't be overreacting or creating, pretending it's a problem among those where that, I would say, is not addiction.

• 2:24:03Speaker 01

  That's not abuse. That's not using it as directed. But people with ADHD, by their very nature, are not going to use things as directed, either because they forgot, or... Weren't organized enough to get it on time, or forgot what you said in the office, even though you wrote it down, because they lost the sheet of paper it's written down on. So getting back to patients' experience of it. So the advantages of the immediate release is they tend to work quickly, you can feel it going in. It's easily, most people, there's a lot of individual variability, but let's say in the six to eight hour range, will get benefit. Some shorter, some immediate release lasts all day.

• 2:24:46Speaker 01

  But you know when it's on, you know when it's off. If you forget to take your medicines in the morning, but you know you have a presentation at three that afternoon, you could take it at two and still be able to sleep that night. So it allows more flexibility, it allows more pinpointing of optimizing it for points the day you want to be using it. Some people philosophically say that in itself is wrong or bad, that you should be absolutely steady and constant, because what we're trying to do is be consistent and reproducible. And others would say, we're trying to treat individuals who have different demands on them and have different patterns during their day. So there are different philosophies about what's better or worse.

• 2:25:30Speaker 01

  One of the big downsides of the immediate release, though, is not only does it go in quickly, it tends to go off quickly. And most people, not all, but most, experience some withdrawal as it's going off. And although, when we're using this for ADHD, we focus on the cognitive executive function benefits, the focus, the attention, the concentration, and people can experience that. Many people who weren't even aware of it increasing their energy feel, my energy's crashing as I go off of it. Or many people who weren't aware that it was actually elevating mood to any extent feel, oh my god, I'm crashing and I'm crying and cranky and miserable now.

• 2:26:10Speaker 01

  And with the extended release versions, most of them go in more gradually, so it can be harder to detect. They last a longer period of the day, and most of them go out much more gradually at the end of the day. The one I like the most, for a long-acting amphetamine product, is Vyvanse.

• 2:26:31Speaker 01

  And Vivance was designed as a slow-release product. It was designed specifically to be unattractive to drug abusers. So Vivance chemically links the dextroamphetamine molecule to lysine, one of the amino acids. It's a basic component of proteins and 20 essential amino acids. And if you snort it or inject it, you have an inactive pro-drug. You have the list dextroamphetamine. Your red blood cells actually need, have an enzyme that cleaves the lysine and leaves you with the free active dextroamphetamine. And that's the slow-release mechanism is how quickly your red blood cells can do it.

• 2:27:15Speaker 01

  And they have limited capacity to do that. So although they designed it to be an anti-drug abuse drug, it actually turns out to be one of the sort of most consistently evenly entering the body. For some people, it goes in so slowly that they say, I don't feel it. And also towards the end of the day, one of the best in terms of not falling off abruptly. The potential downside is again, that the capacity of the red blood cells is limited. So at some point, for most people, because that's a rate-limiting step, when you're adding more and more, you're actually extending the duration of time more than you're getting a bigger peak because your, your red blood cells just aren't cleaving it fast enough

• 2:27:59Speaker 01

  to make more dextroamphetamine available. Almost invariably, when I'll ask, you know, how did this compare to your Adderall XR or to Hancear, they'll say, smooth.

• 2:28:11Andrew D. Huberman?

  Smooth.

• 2:28:13Speaker 01

  They're getting it, they're not feeling too jarred, too revved up.

• 2:28:16Andrew D. Huberman?

  Yeah, we don't really have a language for these things, right? Hence the bad speed language before, cracked out, bad speed, smooth.

• 2:28:29Andrew D. Huberman?

  Because what we're talking about here is the gestalt of the subjective experience of all these neural and chemical mechanisms. Very interesting. Thank you for sharing that. I know that there are a lot of listeners and viewers who have tried these things or are considering or, you know, at one point used them. And a lot has evolved in this realm of chemistry for ADHD, but that's very helpful. Before we wrap up, I want to make sure that I ask you about something that's been on my mind a lot in general, but in particular as it relates to ADHD, which is time perception. And I'm basically obsessed with time perception. I've long been fascinated by the fact that we can fine slice time when our arousal is

• 2:29:14Andrew D. Huberman?

  high. That's what presumably gives people the kind of slow motion effect in, you know, very stressful environments versus when we're relaxed, our frame rate on life goes down. And it's all very dynamic. It's important our brains are able to do that. But someone recently told me the following. Her partner has ADHD and she said that the big rescue to their relationship came when they together read a book about ADHD. And something in there read something like this, that people without ADHD keep track of time, whereas people with ADHD don't, but they do know the difference between now and not now. But they're not tracking time. They know that what they're doing in the moment is not what they're going to be doing

• 2:29:59Andrew D. Huberman?

  later or what they did in the past, but they're not tracking time the same way. And I think this ties back to this interest-based attention system. What do we know about time perception in ADHD? And by extension, do you think that these drugs are working in part to change time perception?

• 2:30:17Speaker 01

  Good question. So I'd say there's two different angles. And I think, I mean, the one that's easier to objectively measure is putting people in a lab and there's a simple test, a time perception test, and you interrupt them after a certain period. I mean, say you're going to be estimating how long you're You're left without interruption. And people with ADHD measurably are they're inconsistently inconsistent. Consistently inconsistent. Consistently inconsistent. So it's not that they perpetually underestimate or overestimate, but they are estimating incorrectly much more often than people without ADHD.

• 2:30:57Speaker 01

  So there's something at a basic time processing level that's aberrant there. But there's also getting, you know, the the real world aspect of not paying attention to cues or not noticing other people left the room or not regis-, you know, being distracted, which compounds a situation. And I mean, it's also interesting to the extent to which many people aren't. So I often ask, even though it's not one of the 18 symptoms, are you chronically late to them? And particularly people who show up late to my office time after time. So one of my favorite quotes is this person who the session before we had been talking

• 2:31:41Speaker 01

  that her boss was giving her threatening notices because she had come in two hours late one day and she had all sorts of good excuses of why she couldn't get out the door. And I we were talking, you know, are you regularly late? No, no, no. And I said, well, why was the boss so upset? I'd say, and then I asked, well, when do you, when is the expectation? This is pre-COVID, pre-working. When is the expectation you're there? When do you usually show up? Oh, well, my office starts at nine and I'm usually there by nine fifteen, nine twenty. That's not late. In her mind, it wasn't late. So, you know, and so when you ask a question, are you routinely late? You're going to get meaningless information on your little checklist unless you know what that means to the individual.

• 2:32:26Speaker 01

  So the second part of the question, I'm sure it's been done and I don't have the answer. Whether stimulants or other drugs measurably improve time perception in that laboratory situation of just can you estimate how much time has elapsed? I I should know that, but I don't have that on top of my. And the more global question of how central that's sort of the time aspect of organization of thoughts and attention is to. The content of disorganization, I mean, there are some research groups, I think it's a Danish group, who's feeling that ADHD is primarily a circadian rhythm disruption,

• 2:33:10Speaker 01

  that that's the central neurologic issue at play. And there's interesting, I got to do work in the early 80s on bright light therapy for winter depression, which has a measurable impact as strong as medication. But there is one or two studies done on individuals with ADHD without any seasonal depression, without any depression at all, and just those same bright lights showing them, you know, a dose of bright lights early in the morning, measurably improved a broad range of ADHD symptoms. And the claim was that that was working because it was helping resynchronize internal rhythms which are out of sync in

• 2:33:53Speaker 01

  ADHD. Whether that's exactly the same thing you are getting at, but certainly if you have, I mean, even though we have a sort of master clock in the supra chiasmatic nucleus, we also have clocks throughout our body and they're talking and interacting and ostensibly synchronized and working with each other. But it could well be that for many people they're not, and that getting that to work is essential.

• 2:34:18Andrew D. Huberman?

  Thank you for those reflections. And really, I want to say thank you on behalf of myself and everyone listening and watching for doing the work you do. You were invited here today because you have an absolutely encyclopedic understanding and knowledge of ADHD and the clinical treatments. And I've watched your YouTube channel and we'll provide links to all your various resources. I'm looking forward to your upcoming book, however long it takes. I'm sure it'll be spectacular.

• 2:34:48Andrew D. Huberman?

  When you talk about ADHD, you're able to do it from so many different angles, behavioral, supplement-based, nutrition, life and organizational, life organizational aspects, and of course, the medication, the pharmacology, the neuroscience, and the ways that those different nodes interact with one another, because of course, they do. So I just want to be absolutely clear how grateful we are for you for sharing all this knowledge. A lot of people struggle with attention issues, regardless of whether or not they have a full-blown ADHD or not. A lot of people have been treated for it. Some people are still wondering if they should be or not. And so today's discussion was nothing short of spectacular. So on behalf of everybody, I want to just thank you for doing what you do and for coming

• 2:35:32Andrew D. Huberman?

  here to educate us. Thank you so much.

• 2:35:35Speaker 01

  Thanks. I'm gobsmacked, so.

• 2:35:38Andrew D. Huberman?

  Thank you for joining me for today's discussion with Dr. John Cruz. To learn more about his work, please see the links in the show note captions. If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific, zero-cost way to support us. In addition, please click Follow for the podcast on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review. If you have questions for me or comments about the podcast, or guests for topics you'd like me to consider for the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. For those of you that haven't heard, I have a new book coming out. It's my very first book.

• 2:36:20Andrew D. Huberman?

  It's entitled Protocols: An Operating Manual for the Human Body. This is a book that I've been working on for more than five years, and that's based on more than 30 years of research and experience. And it covers protocols for everything from sleep to exercise to stress control, protocols related to focus and motivation. And of course, I provide the scientific substantiation for the protocols that are included. The book is now available by pre-sale at protocolsbook.com. There you can find links to various vendors. You can pick the one that you like best. Again, the book is called Protocols: An Operating Manual for the Human Body. If you're not already following me on social media, I am Huberman Lab on all social media platforms. So that's Instagram, X, formerly known as Twitter,

• 2:37:04Andrew D. Huberman?

  Facebook, LinkedIn, and Threads. And on all those platforms, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the content on the Huberman Lab podcast. Again, that's Huberman Lab on all social media platforms. And if you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a zero-cost monthly newsletter that includes podcast summaries, as well as what we call protocols, in the form of one to three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You simply go to hubermanlab.com, go to the menu tab in the top right corner, scroll down to newsletter, and

• 2:37:48Andrew D. Huberman?

  enter your email. And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. John Crews. And last, but certainly not least, thank you for your interest in science.