welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology at Stanford School of Medicine my guest today is Dr John Cruz Dr John Cruz is an mdphd 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 Aderall rlin viance modafanil 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 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 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 cost to 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 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 uh 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 I'll just start out by saying that like most things in neuroscience and Psychiatry we 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 how we diagnose ADHD and that is there are 18 different 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 um being easily distracted the impulsive and hyperactive ones are cutting people off in conversations blurting things out running around um fidgeting the definitions themselves were designed with a child population in mind because until roughly the mid90s it was Dogma that this was
a dis neurodevelopmental disease of childhood and that every child who had it outgrew it that is dramatically wrong um 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 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 in excessive amount of time in 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 um traits that are displayed in multiple Realms of life um they have to cause again distress or
dysfunction they have to be to an extent that's beyond what a normal person does and what's strange is often DD has a stigma it's not a real diagnosis partly because there isn't some the fancy word is pathon neonic 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 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 stigma and questioning you know isn't this just normal behavior carried to an a ridiculous extent 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 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 uh play a sport or to work where sure there are multiple things you can do in those environments but they're more constrained in terms of the the different sides of oneself the different activities that one tends to um engage in is that is that common yeah so I'll back up a little bit that like of our other mental health or psychiatric conditions there's clearly both a biological component ADHD and clearly a social environment or the nature and nurture question isn't which is it it's always both
so at ADHD we know there's a very strong genetic component the heritability factor is around 08 which is about as strong as the heritability factor for height or for schizophrenia so does that mean that if you're an identical twin and your twin has ADHD that there's a sort of essentially a point8 probability that you'll have it as well or is this through I mean heritability is a little more technically sophisticated and it's about the variance due to sure but it's high likelihood so this tends to run in families but but again it has a social
it 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 the official how we categorize it in term or diagnose it in terms of symptoms we most often are understanding at 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 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 um working in a work office environment part of the problem is if you're in a 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 hallway you know Larry is your how far along are
you on this cating 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 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 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 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 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 mental health figure 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 going to go up we know anxiety is 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 Uncle Joe just died from coughing his lungs out from Co you know PTSD it's easy to see or depression you've just lost your job and whole industry you know you're 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 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 and you know this the media has jumped all over this not only have ADHD diagnosis gone up considerably but also um prescription stimulant have shot up dramatically in the last few years 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
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body panel about three to four times a week and I use the ju handheld light both at home and when I travel if you'd like to try juv you can go to juv spelled jv.com huberman juv is offering an exclusive discount to all hubman lab listeners with up to $400 off ju products again that's ju spell jv.com huberman to get up to $400 off I'm fascinated by this relationship between of optimal structure and difficulty or at least optimal structure versus having some um margins for exploration at one's job I realize it's very difficult to throw
out uh kind of pan statements about what sorts of work and professions are going to be best for people with ADHD but um in your clinical observation can you perhaps point us to kind of clusters of professions where people with ADH h d tend to gravitate toward because they they have sufficient or even hyper uh proficiency there like would we say like the creative arts where you know as long as they can get themselves to to uh to the theater um they tend to do well when um improv I'm I'm using extreme kind of almost
silly examples but those are professions indeed versus um a job where people have quote unquote Banker hours where it's you know 9 to5 I could see that being an advantage also being very difficult and of course or accounting where you know literally uh decimal points matter and and every every digit counts so are there sort of clusters I'm going to step back and answer I'll get to your answer but I'm going to 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 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 en well maybe a few people enjoy it but most of us aren't CPA is Art 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 doing in their basketball playoff game look at this cool cat video oh I'd rather do something else so regarding career work I think the most important thing is that it's that's interesting to you so I we can talk about Realms of work or certain um career paths but if it's not compelling to you if it's not interesting to you it's it's going to be hard to work at it even if it's structurally maybe a better support for you does that carry over to other domains of life do you see for instance that
people with ADHD are um have a harder time with parenting um not that um 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 um I think of this word importance driven is just kind of like really dutiful like it's it's it you do it because you're supposed to do it part of how the field like actually in the 90s started becoming aware that adults could have ADHD is that all these clinicians who were 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 and 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 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 kids's brain is working differently but actually it might not be that differently it might be exactly 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 spec identifying specific careers is it is a society we've long cherished or valued 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 interest change so for many people with ADHD the best career is actually not one 50-year career it's 10 fiveyear careers or five 10e careers and part of it is as 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 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 normos Centric bias to that is what you should strive for and if you are changing careers you 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 their 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 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 appointment still involved in a bit of research but I'm in a second career now is MH um and I imagine there'll be a third um we can talk later if you think I have ADHD or not um I certainly consume a lot caffeine and we'll come back to the idea the relationship between um uh levels of caffeine consumption and uh Poss possible ADHD
we'll see we're seeding the discussion for later on that we hear pretty often that social media and scrolling um X or scrolling Instagram or Tik Tok is quote unquote giving people ADHD um are there any data either clinical or otherwise that suggests that the mere practice of look looking at you know 10,000 different contexts or even you know you know 15 videos in for a minute while standing at the bus stop is somehow creating um more a distractability in other domains of life yeah so I'd say there's a lot of good Neuroscience research or neuros
pychological 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 that you are you train yourself to overreact to any new distraction 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 have been people writing about you know the question you're asking that the Neuroscience are brains getting more distracted are we becoming you know it's not just distracted you know immersion in this media world or social media cell phone however you want to break it
down it's not all bad it's not just that concentration is worse so you know detecting visual items in the environment being there's some things that people become more Adept at whether that's actually a good thing to be more Adept at um 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 and but all the books that talk about that say well this is just sort of everyday stuff this has nothing to do with ADHD and there's lots of wonderful ADHD books out there and they say ADHD is this discret 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 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 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 ditsy 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 to it so a kid who has ADHD their life expectancy is about 10 years shorter than their non-adhd peers that is the same extent of
cutting off life is having diabetes or having major depression is that because of um 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 also 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 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 her 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 is lots of people feel really bad but we know having guns and households increases the right of likelihood someone's going to 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 um 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 how does that make any sense and it wasn't huge but since suicides 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 kids 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 very interesting I I didn't realize that ADH carried this um lifespan liability um and 10 years is certainly significant 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 your earning potential I mean ADHD isn't just an academic cognitive problem it isn't just who's going to jump through the hoops and get through school it isn't just who's turning in their reports or um doing their work on time in the work it's also having social implications and in all those areas it's having measurable detrimental significant impacts on people's lives my understanding and and you'll see how this weaves
into the previous uh 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 um I I don't know if I have ADHD or not I I suspect if I it's rather mild or I just feel lucky that I uh 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 5pm on
because that was the only way people could reach me and I certainly am familiar with the it's it's almost a druglike effect of dropping into 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 the feeling of pleasure just everywhere from head to toe after doing 20 minutes of focused work or 30 minutes of focused work is 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 um they're just much higher thresholds it just takes more fear of a deadline or fear of a consequence or excitement about the activity uh is is that true 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 focus on attention deficit hyperactivity disorder and it's very clear as your 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 if it's a situation that's appropriate
to be sustaining it 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 hyperfocus as one of their superpowers and that is where they're getting so absorbed in their work that they are you know so busy coding that actually everyone else in the office is left and it's only when the janitor is coming and emptying the garbage cans at 11:00 p.m. that oh
my God I'm where is everyone I'm still here because I was so intently working on the project some people strongly resist the idea that Flo and I'm going to butcher the CH chck uh CHS Mah yeah no one can pronounce his name even fewer can spell it so we're okay yeah my reading of when I sort of delved into this I think hyperfocus 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 hyperfocus looking at us beautiful flower people don't describe that so it it needs the right amount of challenge it can't be too easy it can't be too hard has to be something important and interesting to you um and involves you know Oblivion not just to time but also to lots of space going around you um so I think they are pretty close if not the same phenomena flow in hyperfocus and some people with ADHD and I think some who are ones
who learn what situational factors or what internal factors can help get them into that state but but many of them still struggle with it showing up when they don't want to be hyperfocused on something or or have trouble engaging it when it would be useful to I sometimes use the absent-minded Professor excuse um but only uh half jokingly there there's a photograph that I love of the great Oliver Sachs the neurologist turn writer man who mistook his wife for his hat Awakenings and so forth um people may be familiar with Oliver's work and and it's
a photograph of Oliver at a train station lots of bodies moving around um him some blurry so there's motion there and he's standing there with um I think he's got his pipe in his mouth um and he's writing outside the train station his bag has fallen to the floor some items are coming out and he's he was a known and self-professed um meth methamphetamine addict for a great portion of his uh medical and um writing career um and you know sort of alluded to the idea that he had these Tendencies and I I raised this
as an example because I see that photo and I see somebody who's in hyperfocus in a very dis um busy environment but he wrote I spent a lot of time with his work and his autobiography Etc and talk 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 actually became a distraction it was as if somebody
in here was speculating um uh about diagnosis but that there's something about external anchors and internal anchors and that you know 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 morning certain environments for afternoon certain environments having returned 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 um identify sort of best conditions for them and how important is circadian uh time here I know you have and of course I mentioned in the introduction that you a lot of background in in circadian biology which I think brings in a a really additional and unique Dynamic to to your understanding of ADHD 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 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 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 in 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 and with scheduling what I tell people is before you slot in your work or your homework or your school or 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 a it's it's intial 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 if they were just so the four Essentials I say are sleep eating exercise or some amount of movement because again with the hyperactivity there's 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 I put all those in the same slot maybe they shouldn't and all those need to be in place um 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 two different real life tests um the office I had was an old Victorian home so was a home office 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 45 Hartford the office is at 45a the entrance is at the end of the driveway and I actually did the data on it um the only people who ever showed up at the front door the home door were the people with ADHD now everyone it wasn't um it was specific for ADHD it wasn't completely sensitive 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 asks 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 4:00 yesterday
and I just realized I hadn't eaten all day ding ding ding ding ding 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 and it's not that everyone at the ADHD does that but either either not getting the right interos receptive cues from your body or not paying attention to them is something that's been measurable in people with ADHD so having a regular meal schedule 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 Tac who really lamented now I have to work for 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 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 um never really ends it just sort of uh sort of fragments into the rest of the day that can be one variation mhm but it's it's often just completely forgetting or being oblivious to or I mean the other ways ADHD is canl 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 you know an executive function problem interestingly it's not one of the 18 symptoms in our official checklist so 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 stronger and are harder to regulate and that's nowhere acknowledged in our official diagnostic symptomatology I'd like to
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plus a year supply of vitamin D3 K2 with your order of ag1 again go to drink a1.com huberman to claim this special offer so we've got sleep eating exercise or movement and relaxation maybe um before we start talking about some medications and some other factors that modulate ADHD if we could maybe step through each of those and um you could share with us some of your favorite tools that you um give your patients um and that you teach online um 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 um I'm curious about your um favorite go-to tools we were talking about a few of these before we started so sleep um Regular to bed in wakeup times 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 till 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 my PhD research was on circadian rhythms we had Realms of data back then so this was 40 30 plus years ago we had every bit as much data then that that the timing of sleep was as important as a duration and yet every Public Service Announcement just says
get your eight hours s you know 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 Chon chronotype where they're maybe more effective or functional later in the day a tendency to stay up um for many years now we've actually known that there's a this is strongly genetically controlled so we do have you know there are genetic markers affecting sleep timing that are over represented strongly in the ADHD community so some of it is you are pushed that
way but some of it is the nature of ADHD that if you you know procastinating is part of ADHD if you procastinate you're going to push things off till the end of the day um some people the end of the day is better time to work because there's fewer distractions you know if everyone else is asleep finally no one's going to 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: a.m. till 10:00 a.m. every day I'd say go for it if you can be consistent with it um so what are the things that help with getting regular sleep one thing paradoxically for many people is actually being on stimulant medications MH 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 and alertness or energy or because they're being more productively ener expending 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 we don't know the mechanism by which it works there's there's lots of plausible and overlapping ones but again daytime alertness medications can help can I run something by you in that context before we jump back um I don't consistently take stimulants except caffeine and I limit my caffeine intake to prior to 2 p.m. and
I stack it pretty heavy in the early part of the day but on occasion I'll take 25 to 50 milligrams of Wellbutrin which uh you know better than I is um slightly dopaminergic but certainly triggers uh noradrenergic release so um epinephrine norepinephrine stim 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 rapid eye movement sleep it's extremely consistent so from that I um sort of uh 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 1 to 3 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 uh 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 you know H and with stimulants um epinephrine Spike early
and throughout the day um with better rapid eye movement sleep at night does that logically hold for you it's just a story but you know I was going to say both those 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 you know 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 you're not doing it every day so those potential issues aside I I'll jump into insomnia and Matthew Walker talks about some of this to me maybe the biggest finding in insomnia sleep medicine in 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 systems 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% probably more of people who have insomnia problems is a failure of the daytime arousal system to shut off properly so normally we have these two mutually inhibitory systems wakefulness arousal system and a sleep sedation system and usually when one turns on the other turns off the 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 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 bedtime you know having thinking about this ahead of time and two eliminating any stimulate I mean one so exercise I'm
a big fan of I'm a marathon runner I know you're heavily into exercise as well um exercising too late in the evening can Elevate body temperature disrupt falling asleep so physical arousal we don't want to be doing a lot of late in the day and emotional intellectual cognitive arousal too so the biggest single tool in Modern Life is do not have your phone in your bedroom and that's hard for lots of people to do but if it's there you're going to be checking it I mean Studies have been 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 it 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 if you are on the same page and can have a partner or 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 cyli S I mean there are other box breathing and other techniques that help someone relax so we know cylic sing engages a parasympathetic nervous system our rest and digest system 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 you there already makes it easier um I know you have videos about cyclic sing and I do too I mean my own experience which
I was sharing with you before we started talking was not only does cylic sing help me f asleep better it actually help me stay asleep throughout the night better 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 um somewhere for me typically around 10: p.m. somewhere between 10: and 11:00 p.m. is my typical bed time but then I consistently wake up uh at uh
you know 3: 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 in the bedroom um but as we were also talking about before we uh turned on the microphones um this idea that our bladders get smaller as we age is is complete nonsense right so that can't be the explanation why people wake up uh more in the middle of the night as as they get
older yeah I mean some might I mean some it may be a prostate issue you know clearly that isn't accounting for half the population but I think it's much more the neurologic interation 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 so how much cyclic sighing are you doing before sleep and how long before sleep is the cyclic sighing done so when I read your paper with spel 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 relax that I do I you seem like a pretty mellow dude I I haven't ever taken the time to do it which I'm embarrassed by so I said read the paper I can do 5 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 again I slept really well till I was around 40 and not so well the next 20 years both the mostly with the trouble falling asleep even though I knew 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 would have and it was clear
so I do about 5 minutes and much more than 5 minutes I tell people and I might be doing it a little slower than most count out about 20 or 25 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 5 minutes and then you're woken up you're reversing or mitigating some of the benefit benef 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 and we know the exhalation has to be longer I was trying to find is you know is anyone systematically you know is a 4-second exhalation better than 10 versus 6 and those studies would be so simplistic and easy to do but you know there's lot lot 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 oh delighted to hear that it's worked so well for you I I'm 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 physiologist in the 19 data point that I I shared with you is that prior to trying cyclic sighing at night time 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 fantastic so we're talking about sleep you mentioned earlier um 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 yeah um 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 um exercise aside from encouraging people to not exercise too late in the day
um certainly not um caffeine and exercise late in the day are there any data about specific types of exercise being better for um ADHD independent of effects on sleep I realize they're hard to tease apart yeah there's a few studies looking acute aerobic exercise part of it is that it's hard to study people when they're exercising during many exercise 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 anyone 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 being able to switch of 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 today I get my workout in the gym in or I feel better or that you know the week
I took off from that was a big mistake but I would say identifying at what's the most valuable or what's the best duration I've 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 is there a relationship between ADHD and addiction because of the impulsivity component 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 27.4 3% well it might have been in that study but that's looking at one population at one said 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 drugs people with ADHD have a rate that's almost double and it's higher in men than in women double almost double almost 40% risk and that's for substance abuse not behavioral addictions 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 and I should say the stimulant themselves do have a small potential for addiction but putting kids on stimulants pretty much normalizes their rate of addiction problems so half it protects them this is a really important point that I think maybe we just hover on for a second um because I think many people including myself assume that well if you
we're you know putting these kids on amphetamines of which you know many of the medications for ADHD are that were creating kids that are addicted to amphetamines or to a hypers stimulation period but you're telling me it's actually protective to put kids with real ADHD on medication for ADHD I can say not absolutely every study has found this but several large metaanalyses have gone back and most of them have found this fairly dramatic benefit to being on stimulant 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 um it seems to be that it's not just the impulsivity traits but some of the inattentive ones too you know if your teachers 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 the classmates who are stoners at this age or XY or 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 I have this model in my head that is um perhaps completely wrong maybe partially wrong um 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 um use dopamine and epinephrine and norepinephrine um at least to some extent and we know that people with ADH are capable of focus as you said it's a it's a
failure to direct that Focus maintain Etc 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 distractability that you know they might have ad DHD so what I'm imagining here is that the threshold to get dopamine epinephrine and norepinephrine released is either much higher or more complicated um for people with ADHD and so what they're seeking is these catacol amines these three chemicals dopamine epinephrine norepinephrine and that if they're given a
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 um 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 it seems to me that the model of ADHD that we hear about is that you know people can't focus um 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 I have this model in mind now that what we are all seeking is to have portions of our day where we are directing our Focus towards meaningful Bill the things that are you know generative in our life work school relationships Etc and that whether or not it's pharmacology or exercise or or what have you that it's it's just about getting into this plane of of Consciousness and I say that in no woo or abstract terms is is that right I mean are what we really talking about here is
a failure to access enough of these neuromodulators and 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 mean I'm 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 the day um 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 that 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 um let's talk about the medications since uh you raised those um and you know the first one I ever heard about was Rin MH um let's start with Rin um how often is rlin used nowadays and what is rlin doing um neurochemically and what are your thoughts on rlin as a a useful drug for childhood and adult ADHD and
I'm happy to repeat those questions so rlin is or generic methylphenidate and there's dozens now of slow release versions and there's even a patch a skin patch instead of an oral 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 neopine phrine driven fight or flight arousal system so by the loosest criteria caffeine's a stimulant um albin's a stimulant even though we classify it as an anti-depressant um some of the decongestants
are stimulants but more often when we're talking ADHD medicines we're using stimulant more specifically for amphetamine based products like Aderall and viance 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 rlin a full stimulant so the neurop pharmacologists 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 but in addition to that amphetamine is a pretty potent to a 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 well buttin is that's
one of the comp you know it's and so so why I would further say if you look at the efficacy data how well do these work in resolving ADHD symptoms all the metaanalyses lump Aderall products amphetamine and methylphenidate products here and say you know they're here CU they work better this is you know success in reducing ADHD symptoms and allar stratera at motine Wellbutrin I use symol toot mfil guanosine 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
methyl fenity is actually closer to the pack below it's that amphetamine products are Head and Shoulders above everything else methylphenidates usually at the top the rest of the crowd but if you just looking at the the data objectively there's a clear decision point so in terms of efficacy amphetamine products are stronger um but in terms of some of the side that you know the 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 the 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 um with amphetamine adderal products and that'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 police are spying on them I mean if you drink too much alcohol you can be bat crazy as 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 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 at The 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 empet iine 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 marijuana causing a similar picture so now we're studying this a little more but with amphetamine induc 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 much higher higher risk of this for I can get into it if we need to reasons in my population in 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 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 um and so I'll go into I think a couple different reasons one is I worked with a lot of HIV positive men and
we know HIV particularly in the days before we had effective antivirals is a virus that goes to the brain and effect you know there's a HIV induced dementia so probably some of these people had brains that were compromised because of that and were 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 um so it's a cousin but methampetamine we know has higher rates of psychosis higher rates of addiction um is tends to be
more re wording 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 them phetamine IND 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 stimulant and then had a full-blown psychotic episode where he his data 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 pay phone and because Rhode Island's so small he was actually calling from out of States so was a federal crime he got thrown in federal prison for this 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 she 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 the broader range of stimulant dosages and 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 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 and all of them knew enough to lie about this past so they didn't tell me about you know they don't they presented all of them also had ADHD you know they presented with ADHD they'd say I'd been on stimulus 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 20s calling me from inside the psychiatric hospital to try to get me to prescribe more adoral to him and not only that he had convinced his impatient psychiatrist that this was a good idea that this was important to treating his ADHD and helping him retain his job wow so these are as you said um 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 it feels like a manic High the dopamin high dopaminergic State yeah and and I and you th 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 overtly enjoying it they weren't having a
great time they weren't saying I'm going to 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 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 you know psychological suppression
of it or physiologic they're 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 I have 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 I'd like to take a quick break and thank one of our sponsors element element is an electrolyte drink that has everything you need and nothing you don't that means the electrolytes sodium magnesium and potassium in the correct ratios
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sample pack with the purchase of any element drink mix again that's drink element spelled l MNT so it's drink element.com huberman to claim a free sample pack what are the options for people that think that they may have ADHD let let me phrase it differently someone comes in and you they have you know let's say an adult they have five of the 18 um what 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's 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 adderal viance um Etc versus the I realize you put riddle in at the top of the bottom Cloud um well be riddlin um modafanil uh you mentioned simala which cluster do you go to first 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 nonstimulants 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 on disability from Medicare I also worked with people who are on Medicaid in the city's Insurance before Obamacare happened so I 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 I'll I'll jump back that 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 anti-depressants 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 anti-depressants seem to work equally well
we don't have potent anti-depressants and nonent 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 list 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 um but there's a more linear dosage results relationship do you worry about um strain on uh the heart with amphetamine products um 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 uh you know is it true that um that stimulant based medications for ADHD can quote unquote weaken the heart 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 a 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 neopine so Wellbutrin simala um modafanil it's less clear and we can get into that when we talk about
modafanil but clearly methylphenidate amphetamine on average increase at therapeutic doses increase heart rate a few points increased blood pressure a few points but part of that obscures that probably 80% of people don't have any change and maybe 20% have 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 um usually related to the neurologic wiring of the heart who are particularly vulnerable to dropping dead from a stimul and almost every year there's you know a well-trained athlete either professional player more
often a high school or college player College you know who will take cocaine take Rin take prescription stimulant and drop debt of a heart attack um the risk of that so uncommon this is 15 years ago when Aderall X came out the Canadian government was worried enough about this risk that they banned ader are for almost a year and because they have a comprehensive medical system they could look more extensively at the numbers and this is looking at kids the percentage of kids who Dro Dead with Aderall was Tiny and not just tiny it was
lower than the kids who aren't on Aderall who dropped outad of a heart attack so part of it is if you're in this rare genetic condition almost always there's family member numbers or you've had some other near-death or synap 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 even the Cardiology associations have said 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 metaanalysis that came out earlier this year on so most the studies looking at more serious other than just mild hypertension or mild elevation of heart rate um haven't found much but most of them only looked 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 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 out and there they found measurable statistically significant increase in risk that increased during the first 3 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 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 we don't know whether potentially more people are getting into more trouble so if somebody presents as um having ADHD as an adult and they've never touched stimulants and they're uh would you
start them on rlin Wellbutrin or ader or something in theol viance Cloud thanks for bringing me back to your question sure um and and I'm going to jump it you through in the sort of qualifying phrase never been on any stimulant in their life or tried it or something not consistently well what I would say is Lots these drugs are fairly common in our society both illicitly and listly 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 STS once or
twice and that itself is valuable clinical data you know if they felt too to 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 to do for you so my presentation is is usually you know Aderall is likely to be the most strongly effective or I more often are using viance these are the other options but Aderall also has again greater R rare but risk for these bad problems what you
know does that scare you some people are petrified they're not going to go anywhere near that some people say yeah that's 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 C reasons I absolutely would not I mean my worry again I I saw more of it than
I think most people in a higher rate with amphetamine psychosis but a friend from college was just trying to refer a friend's son who's 27 and had a psychotic episode on 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 psychi rist kept him on adderal I absolutely again the 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 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 um from the traditional press um and then ironically they're now putting out information that is essentially speaks to the same I'm not saying this happens in everybody but there's certainly a a possibility there would you say that if
somebody is a regular high THC cannabis user that they are at greater risk to developing Psych is if they're taking these stimulant form ADHD meds 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 THC there's some risk is it you know Reaper Madness at 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 yeah especially as I understand we had an expert from the Cannabis research community on in in edible form in particular it's harder for people to control the dosage whereas um when people use inhalation as as a means to deliver it seems like they they kind of find the right plane without going overboard more often than with Edibles in any case one other big factor is that CBD actually seems in some studies to have an anticho 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 and I'm sure you've highlighted that a big problem with this whole industry is even in Colorado which three years ago is the state with the most close regulation and inspection and almost a majority of what the label say don't correlate with what you're really getting so um 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 um 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 and there's not a lot of data on marijuana it's the one I've actually changed my mind from reading what was out there 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 it help them and what I would tell them is the
data we have and these are from everyday users is that there are measurable you know the the characteristic of the classic Stoner has a grain of truth to it so measurably lower motivation poorer organiz ation 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 over the years so I had a handful of people would swear it worked better for them than stimulants it worked better 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 it's harder to evaluate how objective they were but there's some research that suggests there is some sub segment and I don't think it's a 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 and what I was going to say is there's probably at least
7 or 80 other psychoactive components to marijuana not most of them as in high a concentration as the THC or CBD but they're out there maybe they are more important even at lower concentrations I've heard this that for some people uh cannabis can help them focus and um I'm certainly not one of those but uh it it certainly is interesting um as long as we're on cannabis um excuse me as long as we're discussing cannabis neither of us are on cannabis to my knowledge um maybe I could just ping you for kind of the relationship
between um various compounds that people use that are available over the counter um or with you know sort of online um access to these compounds and ADHD symptoms specifically and then at some point I'd like to return to the uh the amphetamine based uh drugs so let's just start with nicotine so these days there's increased use of nicotine pouches gums not just smoking vaping dipping and snuffing um and it's certainly a stimulant um and certainly a lot of people in particular young males are using it more often this 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 uh category um 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 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 yeah so there's some well done research
showing nicotine is helpful for improving some of the executive functions sustained detention and I'm not sure which which 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 that actually is moderately unique and and I hate
people who 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 anxi so nicotine again seems to be both calming and helping alert or Focus people um 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 and if 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 sensation I have some people who feel that it's been a important and useful part of their regimen um 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 did my di my toe not my anything else into the snuff um looked into it there's no you know clinical research showing does this help or not help 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 torine Alpha GPC theanine you know so tyrosine so you know things that are thought to generally amplify the production or release of neuromodulators like dopamine aoine and so forth and so the
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 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 Angy higher levels of jitteriness higher levels of cardiac toxicity if you were to use it at a equivalent dose but most people are using at a substantially lower dose and the ADHD experts sort of historically have fallen into two different camps some of them have said it's going to interact with the 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 stimulant and non-stimulant ADHD medications and as long as you know it's part of the picture and trying to be constant with your dosage or aware of it then fine and maybe it helps you get away with the 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 exper 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
but lots of people have the experience go to their local Starbucks or something and say whoa that's 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 7 billion stores around the country everything's automated and precise they must be Starbucks isn't you know they control for the aromaticity they how many minutes each Bean is cooked which side it gets flipped over on they're not controlling for caffeine intake which is wild to you and me so a
University of Florida study and this is several years ago now went into a Florida 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 wow and that's Starbucks who knows what smaller so so one is you may think you know what you're and maybe you know the the bane of coffee Drinkers and maybe Sanka 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 very interesting I mean I um as I've said several times in this podcast I think caffeine is a wonderful drug mostly because I love the things that comes in yamate being my you know preferred source of 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 it doesn't seem to um have a very um pervasive effect and and dosing it on an empty
stomach versus after eating it's it I mean I'm not that precise about it but I don't see it as a very um reliable stimulant it's more to get to a plane of just normaly 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 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 your favorite newscast in the morning as you're drinking it that all is adding to its effect in terms of combining with other over-the-counter things there is some study looking at caffeine and 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 found across a pretty broad range of alanine 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 maybe more detrimental eleanine certainly is being added to a lot of caffeine containing drinks because it seems to take the Jitters of and um the Assumption being that people can consume more of that um that drink as a consequence there's a tiny bit of evidence so suggest it it may both you know dampen down you know help with anxiety but it may directly have some beneficial cognitive executive function benefits itself yeah this is um in keeping with the green tea hypo hesis which I believe green
tea is enriched for theanine um you are somebody who uh quite refreshingly to me has talked not just about prescription drugs and behavioral tools for ADHD but also um 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 um depression you those studies were starting to come out we were talking about those studies um 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 um
from good clean sources including fish oil um is mostly beneficial or beneficial um what about fish oil um for ADHD in particular and what threshold dosages are um are relevant here so just as with the 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 looked at the first few studies with fish oil and kids didn't show any benefits at all and then subsequently there have been several studies that looked at benefits and again in 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 so and I haven't looked closely enough to know you know where their 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 is a possible issue with big big big doses of fish oil I mean most of the recommendations are in the range that 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
for or a health benefit um and there the recommendation is usually Target about a th000 milligrams of EPA of eicosapentanoic acid a day um if you're seeing some benefit but it feels like that there's more room for improvement so this is my mod I tell people then you could probably double it reasonably I mean some of the dramatic there were dramatic stud looking at fish oil for Mania people hospitalized with it but and they use dosages as high as 7,000 milligrams a day to treat Mania yeah and it I that study I think it was
a Harvard area um Clinic that was doing it the results were so dramatic that they ethically had to stop the study before its intended completion because the the benefits seem to be so robust in the fish oil group compared to the UN that it was unethical to not put everyone on fish oil that's a lot of fish oil that's a lot of yeah you probably need to get it in liquid form to make it um you know so it wasn't so expensive but I I find this recency effect incredible that you me you know which
you mentioned a few moments ago that um and I think this is helpful for people to hear certainly it is for me you know we hear um you know studies over the years have explored fish oil for cardiac benefits and then more recently as I understand you know these are not sh 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 um cardiac and ADHD I think it's really important um we hear this with alcohol too I've
been involved in this debate I you know I I don't care if people drink one way or the other provide they take care of themselves and others 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 like 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 Al alcohol use that seems to be the highlight and then everything else is forgotten and the inverse is also true
um one would think that the meta analyses would include all as many good studies as possible but I think it's important to that people hear that that's not always the case just because there's a metaanalysis doesn't mean that it included all the relevant studies so I'm just restating thank you um I make it a point to try and get 1 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 support well-being um including cardiac function 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 cost the mammal bird Reptile Kingdom the Omega-3s are found in about a 2:1 ratio of EPA to DHA iOS pentanoic acid toosa hexanoic acid and what I tell people is I think Mother Nature is probably smarter than any Harvard Professor if and the Brain particularly is high
in brain membranes of DHA so I don't see some people seek out EPA purified or sole you know only EPA Brands um 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 a th milligrams of EPA but don't worry that you're getting about 300 400 milligrams of DHA and probably that's better for you I'd like to take a quick break and acknowledge one of our sponsors matina matina makes loose leaf and ready to drink yerbamate now I've often discussed yate's
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perfectly well at night no problems if you'd like to try matina you can go to drink maa.com huberman right now matina is offering a free one PB bag of loose leaf yamon tea te and free shipping with the purchase of two cases of their cold brew yerbamate again that's drink maa.com huberman to get a free bag of yamate loose leaf tea and free shipping you're one of the first people that I ever heard discuss the gut microbiome and ADHD um this is me giving you credit for being way ahead of your time I 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 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 MH I I think nowadays we hear
about the gut microbiome I may have actually heard the words got microbiome first from you um gosh yeah that would be well over that would be almost 20 years ago remarkable um so gut microbiome what do we know about the gut microbiome and supporting it in ADHD 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 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 yeah only to the extent of trying to have a varied diet and eating at somewhat regular interval intervals but not not more specifically great right um if that's where we're at that's where we're at um before we go back to some drugs um I want to ask about behavioral tools for ADHD um I've seen some of the literature claiming that um certain video games might actually be useful for training Focus um I've managed to find a
few papers that talk about um 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 so I'll start for by stepping back a little bit and broading it broadening it I 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 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 50 years ago um maybe longer 60s I think late anyway on the surface it's a horrible match for 8 HD because we know it requires lots of repetitive boring homework doing the same thing of it 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 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 behaviors changing your brain has changed that that's only place that thoughts and behaviors come
from but there have been at least two groups Mary Santos at in New York and um the Harvard Group by blanking on as for saffron and and some other Ramsay at Pennsylvania developed 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 going to do um 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 importance driven you may have a task I mean you probably have 17 task lists one's new your coffee one's at the grocery store one you of one it's having one
Consolidated list because if it's everywhere then it's nowhere and two is the simplest um triaging or or organizing approach is having the things that are both urgent and um important so they have to happen today those get in the a category the things that are important but aren't as urgent are the B category and all the other things are the C and one of the temptation that people with ADHD have is 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 so that and and there's much more to it so that CBT approach
can work with um decreasing procrastination it can re 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 um modules on even extending your concentration time so 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 does something when the FDA
approves devices basically they're saying it's not going to kill anyone it might help I mean it might help tremendously but it's having the FDA in premature for that doesn't guarantee that or mean that at all do you recall if the study of that device uh or the study that video game has a conflict of interest was it run by the company yeah 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 oh is this Adam gazelle's group I
think so yeah he's I should just say that I've um followed his work for some years he he's he's a neuroscientist I know people who have been in his lab um he's known for doing very very high quality and stringent work 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 and talking about neuro feedback because there's lots and lots of neuro feedback companies across the country that are making lots and lots of money and there's a article in the American Journal of psychiatry in the last year I'm not remembering which group did it and it was another non a failure to find a significant impact from neuro feedback 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 because
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 and the evidence is we are rewiring our brains so maybe anything pushing 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 I've made it a point to put social media on a old phone um 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 air drop it onto that phone and this has helped tremendously in segregating that activity and limiting it um 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 that on because it's one of the things that's really allowed me to restrict my social media time um and yet still be you know in keeping with the
fact that I think social media has its uses I post there Etc um yes so getting back to the scheduling I mean what I recommend to people and one of my weak I don't know the specific apps but there are apps that will help shut you out of Facebook or Discord or Tik Tok or whatever it is if 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 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 well um but still consuming content so I make it a point to read from an actual physical book a bit each day or night um also because I was raised doing that and writing by hand is just sort of in keeping with the way
that my brain was um was wired so maybe that's more specific to me and my generation but um 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 um but that's a good sign for preserving I'd like to talk about some compounds that are not so typical meaning um some people may have heard of these but most people probably haven't and they are somewhat novel to me um the first one is uh
guanosine um what is guanfacine and and why is it sometimes used for ADHD so guanosine and a related drug called clodine which can be confused with clopin and others so clonidine and guanosine are both Alpha 2 agonists so they work on a subset of the neopine phrine 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 neopine phrine Alpha 2 receptor really quickly and for people who Skip a dose with their blood pressure medication or stop abruptly it's not uncommon to have um rebound hypertension and not just mild but way higher than what you're being originally treated for to dangerous levels guanosine leaves The receptors more slowly and there have 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 um the rebound hypertension does not seem to be nearly as common with Gant facine and that's part of why the research has moved more towards the guant vine um so there's extensive work by I'm going to blank on her Amy ardan AR that's she's a Yale oh um arston arston thank you yeah and her lab and related Labs have shown that quanin effects seem to deal with strengthening synaptic Connections in prefrontal circuitry so unlike most of our drugs which are just boosting norepinephrine Andor dopamine and work quickly
and I'll throw in this because we didn't really touch this most of the ADHD experts still say stimulants amphetamine rlin work quickly immediately because I boost dopamine right away and our drugs like stratera which is atomoxetine or syala or Wellbutrin Works slowly for ADHD because they're anti-depressants and anti-depressants work slowly there's still people saying this 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 is dopamine get reuptake get blocked by
will buin or by adom oxidine stratera or by simala within minutes to hours of taking it so you would expect if you're boosting norrine 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 St you I could tell I took it and I walked out of your office and I mean one guy I have who love simola said I took it in your office and I wasn't
sure it was working and I got downtown to work 15 20 maybe 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 um so jumping back to Guan facine seems to work slowly so the synaptic strengthening building and it seems to be the nor the alpha
receptors that are on um neurons that receive glutamate is our primary input the Alpha 2 receptor is modulating how glutamate is actually working and it's actually a an MDA glutamate receptors not the more common in the brain ample glutamate receptors no that's an important point I'll just quickly throw in if I may that the um nmda the N methylaspartate um glutamate receptors are the ones that typically are associated with synaptic plasticity um although you know so are you know the ampa receptors can do that too but what um Dr Cruz is referring to is the
fact that guanosine you know indirectly modulates those Pathways so um the longer duration to get the effect it sounds like could be at least partially explained by a real um change in in neural wiring as opposed to with uh you use simbala and Wellbutrin as examples of a fast changes in neur neurotransmitters neurom modulators that led to this um very quick effect in this patient that left your office got downtown and was already experiencing effect um put differently sounds like guanosine um and clonidine not to be confused with clopin clonidine um could help ADHD but
might take longer for the effects to manifest than the other drugs that y we typically hear about yeah so most often it takes 2 3 four weeks be and because it I mean with the stimulants you see effects right away it's reinforcing it and stimulant often in addition to having effects on concentration attention other you know do Boost energy for most people do boost mood for most people and can improve sleep if they're not taken too close to sleep yeah Guan Fine's most common side effect tends to be sedating so most people take it at
nighttime which is like why are you taking a s ating nighttime medication for your ADHD it's because it helps it works slowly indirectly so in tun of the the brand name extended release guanosine was approved in kids because again most of the research on ADHD is still in kids um for treating ADHD as a solo agent it clearly works in adults as well and even before intun was approved there were a handful of studies with either immediate release guanosine or extended release guanosine in the studies so far the the um 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 bedtime and again because it's my impression and it probably don't have a and that's big enough to do a rigorous study is the sedating effects are Rel to the night time and people are feeling okay during the daytime 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 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 and what clinics tend to it looks like most people who are on Guan facine are on it in combination with either a stimulant or a norepinephrine or dopamine promoting agent let's talk about modafanil and our
modafanil by extension uh we hear about modafanil a lot in communities like the tech community and communities where people are trying to quote unquote cognitively enhance what is modafanil what does it do what doesn't it do how might it be useful for ADHD so we're going to jump back to your issue with the recency in science and how to incorporate things when so mno 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 205 maybe 35 years ago and at the
time all the research showed that it was an orexin receptor antagonist wait antagonist Agonist um works on the orexin the hyperr orexin system right so boosting activity but not working like all our stimulant alerting drugs which are working on primarily norepinephrine systems so it was called the non-stimulant stimulant 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 you know so I stick with the orexin
because that's where I was taught so orexin getting back to the the sleep wake in the brain and arousal as I describe it there's two ways to wake up in the morning 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 lawn mower someone snoring an earthquake if you're in LA 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 maao worked it was waking you up but not overstimulating over Revenue 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 US military because they have a big investment and wanting people to be alert and ready to kill 247 but not being hyperactive trigger happy jittery like stimulants can do and this you know particularly in the early days this is really dating
me of the Afghan war we Dro 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 the military has relied on traditional stimulants to keep people people able to fight around the clock and they wanted an agent that would keep you alert awake but not revved up not agitated and I'd say there's some good evidence that that's really sort of how modao works or performs so mno was called provigil for pro vigilance
and then when they were using losing their US Patent like many drugs the provil is a Ric mixture of left and right-handed versions of the same mol molecule they found that the our modol the right-handed version was the one that's doing most of the good stuff and has a longer halflife than the combined version so they got a new patent for armaano which is new vigil um so that's that's the only difference between the two they're the same active ingredients as far as we can tell so and when it got approval in the US it
was approved for narcolepsy where people are falling abruptly asleep during the day so it keeps 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 were 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
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 as helpful um on the other hand there's one study and I'm forgetting the principal investigators it was at Brown University where they used some very clever sophisticated approach to try to sort out motivation versus pure cognitive functioning and their claim and and it was a very well done
study they were comparing it directly to an amphetamine product their claim was that modafanil was the one that was actually boosting cognitive functions and not just boosting motivation whereas it most of amphetamines benefit for ADHD when we say it helps me concentrate it helps me sustain 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 Ridin 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 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 attacking into the orexin system is serving as a signal kind of like a panic attack does that there's something weird something different or being revved up and it 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 overr you 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 even though I've never tried modafanil provigil that people that I know who have and I know one who has for treatment of um real narcolepsy so he's narcoleptic um but others who have uh Tak it for ADHD and for work focus and cognitive enhancement um people who take modafanil and arodo really like it they I don't know if it has any reinforcing property but today is 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 a kind of a dependence form I mean it is a cont controlled substance because some people are worried about the potential and there was a woman Olympic 20 15 years ago who is ADM and said she had narcolepsy I don't know the 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 decade at least before it came to the US and they didn't see any rates of substance abuse or problems I mean
it's clearly does not have the on any tests or animal studies the propensity that the amphetamines do and I'd say it's to me not the concluded subject whether there's any potential for addiction with it what about within the category of adderal viance 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 um very non-clinical um 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 uh for you to be able to chime in about um like drug holidays you know taking weekends off or U and things of that sort 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 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 2 cm not big but measurably and consistently found there for kids who are routinely on the stimulants for their growth years um and taking breaks that last for several months like taking it off during the summer result in overcoming that decrement and 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 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 work days 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 down time has diminished in many communities and again whether there's actual benefits to that or not other than for
the 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 has really studied it rigorously sort of related to that you as the question about short acting versus is long acting and 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 with high doses with a long you know extended release version that may actually be more of a risk but but I'd say there's more concern I think in the basic science Community from the immediate realis and there's a tiny bit of data but part of it overall is that a we talked earlier
about global rates of addiction to any substance that we have fairly good data on because of CDC track it but in terms of very specifically who gets addicted to Aderall who gets addicted to ridin there's so little data and most people just sort the same numbers that oh maybe two 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 anyone who did use their drug exactly as prescribed which means
if you're taking a short acting rlin and it says take it one every or six hours apart during the day and you acknowledge taking it on one day eight hours difference you're classified as a misuser by those studies I mean it's a I'm 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 add I mean we should be worried about addiction but we shouldn't be overreacting or creating pretending it's a problem and among those where
that I would say is not addiction 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 a 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 6 to 8 Hour range we'll get benefit some shorter some an immediate release lasts all day 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 3: that afternoon you could take it at 2: 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 um 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 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 crashing as I go off of it or many people who wen't aware that it was actually elevating mood to any extent feel oh my God I'm crashing and I'm crying and cranking and miserable now 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 and most of them go out much more gradually at the end of the day the one I like the most or for a long acting amphetamine product is viance and viance was designed as a slow release product it was designed specifically to be unattractive to drug abusers so viance chemically links a dexamine molecule to line 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 prod drug you have the listex amphetamine your red blood
cells actually need have an enzyme that Cleaves cine and leaves you with free active dexamphetamine and that's the slow release mechanism is how quickly your red blood cells can do it and they have limited capacity to do that so although they designed it to be a 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 um and also towards the end of the day one of the the best in terms of
not falling off abruptly um 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 to make more Dexter amphetamine available almost invariably when I'll ask you know how did this compar to your Aderall xar or tohan or they'll say smooth smooth they're getting it they're not feeling too
Jarred too ruged up yeah we don't really have a language for these things right um hence the uh uh bad speed um language before cracked out bad speed smooth um because what we're talking about here is the Gestalt of the subjective experience of all these uh neural and and uh chemical mechanisms um very interesting thank you for sharing that I know that there are a lot of listeners and and viewers who have tried these things or are considering or you know at one point use them and um a lot has evolved D in in this
uh realm of chemistry for ADHD but that's very helpful before we wrap up I 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 find slice time when our arousal is high that's what presumably gives people the kind of slow motion effect in you know High very stressful environments versus when we're relaxed our frame rate on Life Goes
Down And um 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 uh they together read read a book about ADHD and something in there read something like this that people without ADHD keep track of time whereas people with ad DHD 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 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 good question um so I'd say there's two different angles and I think I me the one that's easier to objectively measure is putting people in a lab and I mean there's a simple test a time perception test and you interrupt them
after 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 or consist sorry consistently inconsistent so it's not that they perpetually under estimate or overestimate but they are estimating incorrectly much more often than people without ADHD so there's something at a basic time processing level that's abent there but there's also getting you know the real world aspect of not paying attention to cues or not noticing other people who left the room or not regist you know being distracted which compounds
the 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 was this person who the session before we had been talking that her boss was giving her threatening notices CU she had come in two hours late one day and she had all sorts of good excuses of why she could could 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 said and then I asked well when do you act when is the expectation this is pre-co pre-working from when is the expectation you're there when do you usually show up oh well office starts at 9: and I'm usually there by 9:15 9:20 that's not late and 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 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 you know 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 there are some research groups
um I think it's mainly a Danish group who's feeling that ADHD is primarily a circadian rhythm disruption that that's the central neurologic issue at play and there's interesting I got to do work in the ' 80s on bright light therapy for winter depression which has a me 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 re synchronize internal rhythms which are out of sync in ADHD whether that's exactly the same thing you were getting at but certainly if you have I mean even though we have a sort of Master Clock in the Supra asmatic 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 thank you for those
reflection ctions 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 I'm looking forward to your upcoming book however long it takes um I'm sure it'll be spectacular you know when you talk about ADHD you're able to do it from so many um different angles behavioral supplement based nutrition
life and organizational life organizational um aspects and of course the medication the pharmacology the neuroscience and the ways that those different nodes um interact with one another because of course they do so I just want to be um 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 here to educate us thank you so much thanks I'm Gob smacked so 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 zeroc cost way to support us in addition please click follow for the podcast on both Spotify and apple and on
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