In an era where mental health challenges such as ADHD are increasingly recognized and addressed, the dialogue surrounding effective treatment strategies grows more critical. In a recent episode of Andrew Huberman’s YouTube series, renowned psychiatrist Dr. John Kruse, M.D., Ph.D., shares his insights on harnessing behavioral tools and medication to enhance focus and manage ADHD symptoms. This discussion is not only timely but also essential for those seeking to navigate the complexities of ADHD treatment. However, as with any health-related discourse, it is vital to separate evidence-based recommendations from misconceptions. In this blog post, we will fact-check the insights shared in this episode, providing clarity on behavioral strategies and pharmacological options for ADHD. Join us as we delve into the facts and provide you with a clear understanding of the discussed topics.

Find a fact check of this transcript on CheckForFacts

Transcript:

[00:00:00,000]: Welcome to the Huberman Lab Podcast where we discuss science and science based tools for everyday life

[00:00:08,779]: I’m Andrew Huberman and I’m a professor of neurobiology and ophthalmology at Stanford School of Medicine

[00:00:15,000]: My guest today is Dr John Cruz

[00:00:17,120]: Dr John Cruz is an MD PhD and practicing psychiatrist who specializes in the treatment of ADHD in both kids and in adults

[00:00:25,879]: 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

[00:00:37,400]: We of course discuss the drug treatments for ADHD

[00:00:40,000]: So those include Adderall Ritalin Vyvanse Modafinil Welbutrin basically all the drugs that are used to treat ADHD and we cover their relative advantages and disadvantages

[00:00:50,959]: We also talk about the use of caffeine for focus and how caffeine can interact with those various drugs

[00:00:55,979]: 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

[00:01:08,720]: And that of course is relevant not just to people struggling with attention and focus or who have ADHD but to everybody

[00:01:14,660]: Dr Cruz isn’t just a psychiatrist

[00:01:16,440]: 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

[00:01:28,300]: He tells us how to test that idea and potentially how to fix it

[00:01:31,519]: 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

[00:01:45,019]: 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

[00:01:51,699]: Before we begin I’d like to emphasize that this podcast is separate from my teaching and research roles at Stanford

[00:01:57,260]: 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

[00:02:04,279]: In keeping with that theme this episode does include sponsors

[00:02:07,800]: And now for my discussion with Dr John Cruz

[00:02:11,360]: Dr John Cruz welcome

[00:02:13,800]: I’m glad to be here today

[00:02:15,300]: Let’s talk about ADHD and probably best if we start off by just kind of laying out what it is

[00:02:24,580]: Is the H is the hyperactivity component always in there

[00:02:28,740]: 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

[00:02:41,419]: I’ll just start out by saying that like most things in neuroscience and psychiatry we have some definitions and we have lots of different thoughts and frameworks to approach things

[00:02:51,600]: So I’ll start with our diagnostic category or how we diagnose ADHD and that is there are 18 different symptoms

[00:03:00,880]: Nine of them are hyperactive impulsive

[00:03:03,399]: Nine of them are inattentive

[00:03:05,119]: So the inattentive ones are things like forgetting to follow through on things losing items being easily distracted

[00:03:15,619]: The impulsive and hyperactive ones are cutting people off in conversations blurting things out running around fidgeting

[00:03:24,240]: But the definitions themselves were designed with a child population in mind because until roughly the mid 90s it was dogma that this was a neurodevelopmental disease of childhood and that every child who had it outgrew it

[00:03:42,639]: That is dramatically wrong

[00:03:45,979]: Some kids do most kids don’t

[00:03:49,520]: The latest work suggests that most adults fluctuate in time with the severity of their ADHD symptoms

[00:03:56,779]: So jumping back to the definition so we have these 18 different symptoms

[00:04:01,380]: 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

[00:04:10,479]: So any of us might interrupt someone might have trouble sitting might have trouble attending to a task

[00:04:17,279]: But to meet the criteria these have to be displayed in excessive amount of time 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

[00:04:33,339]: So if it’s only at work that you have trouble completing your task that might have something to do with your boss or an uncomfortable chair or something

[00:04:41,220]: So these have to be traits that are displayed in multiple realms of life

[00:04:47,700]: They have to cause again distress or dysfunction

[00:04:50,980]: They have to be to an extent that’s beyond what a normal person does

[00:04:56,820]: And what’s strange is often ADHD has a stigma it’s not a real diagnosis partly because there isn’t some the fancy word is pathognomonic some classic symptom that’s characteristic exactly of that

[00:05:11,760]: So with schizophrenia we have hallucinations

[00:05:14,720]: Most people aren’t having hallucinations

[00:05:16,839]: If you have those you might have schizophrenia or a drug effect but that’s unusual

[00:05:22,320]: Again with ADHD they’re all usual behaviors it’s just to an unusual extent

[00:05:26,799]: So the diagnosis comes under a lot of stigma and questioning isn’t this just normal behavior carried to a ridiculous extent

[00:05:37,040]: So you mentioned that there can be a lot of environmental dependence

[00:05:41,779]: One thing that I and I know a lot of people wonder about is with the advent of more people working at home and certainly during lockdowns kids were at home for school as well but is it the case that when somebody with ADHD is in their home environment where there are typically more options of things to do that the symptoms get worse as opposed to when they go to say a restaurant or to school or to play a sport or to work where sure there are multiple things you can do in those environments but they’re more constrained in terms of the different sides of oneself the different activities that one tends to engage in

[00:06:27,739]: Is that common

[00:06:29,980]: Yeah so back up a little bit

[00:06:31,619]: Like all of our other mental health or psychiatric conditions there’s clearly both a biological component to ADHD and clearly a social environment or the nature and nurture question isn’t which is it it’s always both

[00:06:44,279]: So with ADHD we know there’s a very strong genetic component the heritability factor is around 0 8 which is about as strong as the heritability factor for height or for schizophrenia

[00:06:55,799]: So does that mean that if you’re an identical twin and your twin has ADHD that there’s a sort of essentially a 0 8 probability that you’ll have it as well or is this through the

[00:07:07,239]: Yeah I mean heritability is a little more technically sophisticated and it’s about the variance due to genetic but it’s high likelihood

[00:07:16,279]: So this tends to run in families but again it has a social you’re not just a brain in the world you’re a brain interacting with the world

[00:07:25,779]: And with ADHD we like to frame it as both structure is important and demands are important

[00:07:32,279]: So one of the aspects of ADHD separate from the official how we categorize it or diagnose it in terms of symptoms we most often are understanding 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

[00:07:57,760]: 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

[00:08:09,339]: So getting the home versus working in an office environment part of the problem is if you’re in a traditional office environment you’re starting a specific time

[00:08:22,640]: Everyone else is doing their work at a certain time

[00:08:25,420]: When you go to lunch is clear

[00:08:27,200]: You may have people checking in or seeing you in a hallway

[00:08:31,399]: Larry how far along are you on this coding project

[00:08:34,099]: Are you gonna be ready for it on time

[00:08:36,020]: When you’re home you don’t get any of that reinforcement

[00:08:40,460]: You don’t have any of that structure

[00:08:42,020]: So I mean structure is a Goldilocks issue

[00:08:44,400]: 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

[00:08:55,859]: They don’t wanna be just picking up one bolt screwing it on the side of the Lexus or whatever and watching the car move down the line

[00:09:03,640]: That’s too stultifying too limiting too structured

[00:09:07,400]: So you need the optimal amount of structure

[00:09:10,299]: 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

[00:09:22,719]: 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 but you might’ve had screaming kids in the other room or you might’ve had your partner who wants to use that room for their quiet meetings some of the time when you’re trying to do it

[00:09:38,000]: So the demands increased for many people and the structure decreased and that was sort of a what’s a perfect storm for creating more ADHD

[00:09:52,140]: And what’s really interesting from a mental health perspective at the very start of the COVID epidemic public mental health figures said we know if this is a massive epidemic and we’re gonna have to do quarantine and people we know depression is gonna go up

[00:10:08,960]: We know anxiety is gonna go up

[00:10:10,780]: We know alcohol and substance abuse is gonna go up

[00:10:13,400]: We know PTSD and domestic violence is gonna go up

[00:10:17,020]: They claimed suicide would go up

[00:10:19,099]: That was incorrect and we can get into that but I think there’s an ADHD reason why it didn’t go up

[00:10:25,239]: Nobody that I heard was mentioning that ADHD would go up

[00:10:29,460]: And part of it is because partly to hold onto 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

[00:10:47,500]: I mean we can understand why PTSD more people are being traumatized

[00:10:51,119]: Uncle Joe just died from coughing his lungs out from COVID

[00:10:54,820]: PTSD it’s easy to see or depression

[00:10:57,900]: You’ve just lost your job and your whole industry

[00:11:00,640]: You’re a restaurant worker that’s not coming back

[00:11:03,359]: So we could easily relate stories as to why these other conditions were gonna go up but there was no prediction again mostly because I think that 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

[00:11:25,799]: And yet what we’ve seen just looking at prescriptions and the media has jumped all over this not only have ADHD diagnosis gone up considerably but also prescription stimulant sort of shot up dramatically in the last few years

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[00:14:26,599]: I’m fascinated by this relationship between kind of optimal structure and difficulty or at least optimal structure versus having some margins for exploration at one’s job

[00:14:41,059]: I realize it’s very difficult to throw out kind of pan statements about what sorts of work and professions are going to be best for people with ADHD but in your clinical observation can you perhaps point us to kind of clusters of professions where people with ADHD tend to gravitate toward because they have sufficient or even hyper proficiency there

[00:15:07,940]: Like would we say like the creative arts where you know as long as they can get themselves to the theater they tend to do well

[00:15:16,219]: When in improv I’m using extreme kind of almost silly examples but those are professions indeed versus a job where people have quote unquote banker’s hours where it’s you know nine to five

[00:15:25,659]: I could see that being an advantage also being very difficult then of course or accounting where you know literally decimal points matter and every digit counts

[00:15:35,039]: So are there sort of clusters

[00:15:37,080]: I’m going to step back and answer I’ll get to your answer but I’m going to frame it two different ways first

[00:15:44,239]: 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

[00:15:53,080]: You know if you know you have to move your car because you’ll get a parking ticket you go out and move it

[00:15:57,179]: If you know taxes need to be paid in April you know it’s a boring thankless job

[00:16:02,419]: Nobody well maybe a few people enjoy it but most of us aren’t CPAs of art

[00:16:07,219]: You take care of it

[00:16:08,599]: The ADHD brain in contrast is an interest driven brain

[00:16:12,739]: 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

[00:16:18,679]: Look at this cool cat video

[00:16:21,000]: Oh I’d rather do something else

[00:16:23,400]: So regarding career or work I think the most important thing is that it’s interesting to you

[00:16:30,919]: So we can talk about realms of work or certain career paths but if it’s not compelling to you if it’s not interesting to you it’s going to be hard to work at it even if it’s structurally maybe a better support for you

[00:16:49,679]: Does that carry over to other domains of life

[00:16:51,419]: Do you see for instance that people with ADHD have a harder time with parenting

[00:16:58,539]: Not that kids aren’t super interesting but some of their activities might be less interesting to parents than others versus people who are just I think of this word importance driven as just kind of like really dutiful

[00:17:12,079]: You do it because you’re supposed to do it

[00:17:15,219]: Part of how the field 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

[00:17:33,520]: Wait a minute the parent didn’t fill the prescription so the kid went for two weeks without the medication

[00:17:40,140]: They started becoming more aware of ADHD in adults by seeing that the adults who were parents of these kids and again there’s a strong genetic connection had ADHD

[00:17:51,560]: So there are certainly wonderful loving supportive nurturing parents with ADHD but studies that have looked at trying to find some objective measures are things more likely to be forgotten misplaced mislaid go off track with an ADHD family absolutely and one of the more powerful sets of interventions for kids with ADHD separate from medications is family based training that helps get the whole family one to understand how the kid’s brain is working differently but actually it might not be that differently

[00:18:27,560]: It might be exactly how dad or mom’s brain is working but to help them function as more consistent parents

[00:18:36,719]: So the other bias I’d say again before identifying specific careers is that as 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 interests change so for many people with ADHD the best career is actually not one 50 year career

[00:19:08,540]: It’s 10 five year careers or five 10 year careers and part of it is the whole work world has become more fragmented and upheaval’s the name of the game and break things quickly is the motto of Silicon Valley

[00:19:24,640]: I didn’t phrase that quite right but the message I think is still there

[00:19:29,819]: We’re accepting more that many career trajectories are gonna look not like just one beautiful arc but I think there’s a sort of a normocentric bias to that is what you should strive for and if you are changing careers that’s a bad thing

[00:19:47,839]: Lots of people who do worthwhile things in life and often because of their more varied experience they’re bringing more to what they’re doing

[00:19:57,239]: 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

[00:20:06,639]: I can relate

[00:20:07,819]: 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 ish and I imagine there’ll be a third

[00:20:24,759]: We can talk later if you think I have ADHD or not

[00:20:27,420]: I certainly consume a lot of caffeine and we’ll come back to the idea the relationship between levels of caffeine consumption and possible ADHD

[00:20:37,740]: We’re seeding the discussion for later on that

[00:20:40,060]: We hear pretty often that social media and scrolling X or scrolling Instagram or TikTok is quote unquote giving people ADHD

[00:20:51,880]: Are there any data either clinical or otherwise that suggests that the mere practice of looking at 10 000 different contexts or even 15 videos for a minute while standing at the bus stop is somehow creating more distractibility in other domains of life

[00:21:15,179]: Yeah so I’d say there’s a lot of good neuroscience research or neuropsychological data that the more time you spend immersed in social media and it’s the constant it’s the barrage of information and 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 train yourself to overreact to any new distractions

[00:22:00,860]: So the core elements of some of the executive functions that are impaired in ADHD we are all becoming more ADHD like so 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

[00:22:23,640]: There have been people writing about you know the question you’re asking that the neuroscience our brain’s getting more distracted or are we becoming you know it’s not just distracted

[00:22:33,420]: You know immersion in this media world or social media cell phone however you wanna break it down it’s not all bad it’s not just that concentration’s worse so you know detecting visual items in the environment there’s some things that people become more adept at whether that’s actually a good thing to be more adept at people do multitask more quickly or switch in and out of it they’re still not doing as well on that task if they had no distractions and just focused solely but they’re multitasking better than people who don’t dimmerse themselves a lot in the internet so there’s a whole literature and popular books in attention

[00:23:13,560]: We know everyone’s getting a little more distracted but all the books that talk about that say well this is just sort of everyday stuff

[00:23:22,140]: This has nothing to do with ADHD and there’s lots of wonderful ADHD books out there and they say ADHD is this discreet condition even if they acknowledge it’s on a spectrum of severity but that it’s really serious stuff and we don’t you know 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 wanna make sure that you respect that ADHD is a serious and potentially disruptive condition and when I say serious and I’m gonna go on this tangent for a little bit the caricatures of ADHD is you know oh there’s the squirrel

[00:24:04,380]: It’s silly it’s people are distracted ditzy late doing things that we make fun of in society and we ignore that many of these things can have a more serious repercussions inside

[00:24:19,160]: So a kid who has ADHD their life expectancy is about 10 years shorter than their non ADHD peers

[00:24:26,919]: That is the same extent of cutting off life as having diabetes or having major depression

[00:24:33,299]: Is that because of accidents addiction injury

[00:24:37,320]: Almost all of it is two factors and they’re almost equally

[00:24:41,079]: One is accidents so motor vehicle accidents you know if you’re driving distracted you’re more likely to be involved in accidents but it’s also you know the kid who’s probably being more daring with the tractor on the farm or daring the bull or I mean all sorts of accidents not just motor vehicle accidents and the other is suicide and some of the suicide is because there is an overlap with depression and anxiety and other factors but I’m convinced and not many people are looking at this angle some are with suicide we focus so much on the despair the misery that someone hates their life but there’s lots and lots of depressed people who don’t kill themselves

[00:25:25,720]: The other really important element to suicide is impulsivity is lots of people feel really bad but we know having guns in households increases the rate of likelihood someone’s gonna shoot them

[00:25:41,959]: 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 themselves

[00:25:55,119]: They still might be miserable and that’s my explanation for why even though during COVID lockdowns 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

[00:26:16,760]: How does that make any sense

[00:26:18,139]: And it wasn’t huge but since suicide’s been going up every year prior to that it’s pretty clear and blatant in the data and remarkable and my claim is so many more people were at home you know your kid’s not around to play with the gun or find the gun or you know what’s going on or poison or hanging themselves from the door or whatever else they might do

[00:26:41,639]: Very interesting

[00:26:42,899]: I didn’t realize that ADHD carried this lifespan liability and 10 years is certainly significant

[00:26:51,959]: There’s also the middle ground so I sort of mentioned that the caricature is sort of the silliness and the trivial of being late for your friends at the restaurant or forgetting your car keys and the extreme is death but in between we know ADHD measurably derails education disrupts social relationships impacts your likelihood of your earning potential

[00:27:14,760]: I mean ADHD isn’t just an academic cognitive problem

[00:27:19,160]: It isn’t just who’s gonna jump through the hoops and get through school

[00:27:22,239]: It isn’t just who’s turning in their reports or doing their work on time in the work world

[00:27:28,380]: It’s also having social implications and in all those areas it’s having measurable detrimental significant impacts on people’s lives

[00:27:39,199]: My understanding and you’ll see how this weaves into the previous question in a moment my understanding is that people with ADHD have the ability to focus quite intensely on things that really capture their interest

[00:27:54,619]: I don’t know if I have ADHD or not

[00:27:57,100]: I suspect if I do it’s rather mild or I just feel lucky that I went through the educational system at a time when there were no smartphones

[00:28:06,859]: I’m really grateful for that

[00:28:08,579]: I actually used to unplug the phone in the laboratory where I was a PhD student so that I could just do experiments from 5 p m

[00:28:14,359]: on because that was the only way people could reach me and I certainly am familiar with the it’s almost a drug like effect of dropping into an activity

[00:28:25,139]: Sometimes people call it flow but for me it just is dropping into an activity

[00:28:29,220]: Did some early morning writing this morning and gosh the feeling of pleasure just everywhere from head to toe after doing 20 minutes of focused work or 30 minutes of focused work is so striking to me and yet I 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

[00:28:50,860]: So the question is this

[00:28:52,860]: Is it true that people with ADHD can in fact focus but that somehow whatever neural or neurochemical thresholds are there to allow them to drop into focus they’re just much higher thresholds

[00:29:05,759]: It just takes more fear of a deadline or fear of a consequence or excitement about the activity

[00:29:11,899]: Is that true

[00:29:13,920]: Yeah so back up a little bit and I maybe should have said this when we were talking about diagnosis and what is ADHD and many people think it’s a horrible title because it focuses on attention deficit hyperactivity disorder and it’s very clear as you’re enumerating here

[00:29:29,480]: It’s not a deficit of attention

[00:29:31,459]: 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

[00:29:40,959]: I mean one is we direct attention

[00:29:42,879]: So if something’s important going on over there or there so we have to be able to shift it

[00:29:47,100]: Two you have to be able to sustain it

[00:29:50,059]: So 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

[00:30:09,120]: 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 so busy coding that actually everyone else in the office has left and it’s only when the janitor is coming and emptying the garbage cans at 11 p m that they say oh my God where is everyone

[00:30:30,120]: I’m still here because I was so intently working on the project

[00:30:35,019]: Some people strongly resist the idea that flow and I’m gonna butcher the check check

[00:30:42,019]: Cheek sum a hi

[00:30:43,019]: Yeah no one can pronounce his name

[00:30:45,259]: Even fewer can spell it so we’re okay

[00:30:47,459]: 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

[00:31:05,459]: It’s not just that you know if it were just about enjoyment or bliss you could hyperfocus looking at a beautiful flower

[00:31:14,420]: People don’t describe that

[00:31:16,439]: So it needs the right amount of challenge

[00:31:18,519]: It can’t be too easy it can’t be too hard

[00:31:20,800]: It has to be something important and interesting to you

[00:31:25,120]: It involves you know oblivion not just to time but also to lots of space going around you

[00:31:33,860]: So I think they are pretty close if not the same phenomena flow and hyperfocus

[00:31:41,399]: 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 many of them still struggle with showing up when they don’t want to be hyper focused on something or have trouble engaging it when it would be useful to

[00:32:03,319]: I sometimes use the absent minded professor excuse but only half jokingly

[00:32:08,780]: There’s a photograph that I love of the great Oliver Sacks the neurologist turned writer man who mistook his wife for his hat awakenings and so forth

[00:32:18,699]: People may be familiar with Oliver’s work

[00:32:20,939]: And it’s a photograph of Oliver at a train station lots of bodies moving around him some blurry

[00:32:29,220]: So there’s motion there

[00:32:30,540]: And he’s standing there with I think he’s got his pipe in his mouth and he’s writing outside the train station

[00:32:38,680]: His bag has fallen to the floor some items are coming out

[00:32:42,180]: And he was a known and self professed methamphetamine addict for a great portion of his medical and writing career

[00:32:52,540]: And it sort of alluded to the idea that he had these tendencies

[00:32:57,139]: And I raise this as an example because I see that photo and I see somebody who’s in hyper focus in a very busy environment but he wrote I’ve spent a lot of time with his work and his autobiography et cetera and talked to people who knew him

[00:33:12,280]: 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

[00:33:22,220]: Whereas when he spent a lot of time alone there were bouts of focus but the quiet actually became a distraction

[00:33:29,639]: It was as if somebody in here were speculating about diagnoses but that there’s something about external anchors and internal anchors

[00:33:37,879]: And that finding that sweet spot is really about knowing ourselves and where we work best at particular times

[00:33:44,839]: 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

[00:33:52,899]: 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

[00:34:01,680]: You can probably see where I’m going with this

[00:34:03,939]: What are your thoughts on people trying to with ADHD or not trying to identify sort of best conditions for them and how important is circadian time here

[00:34:16,540]: I know you have and of course I mentioned in the introduction that you have a lot of background in circadian biology which I think brings in a really additional and unique dynamic to your understanding of ADHD

[00:34:28,180]: So many people come to me as a psychiatrist for ADHD are primarily focused on medications

[00:34:33,759]: And we still know that the stimulants are the single most powerful

[00:34:39,019]: 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

[00:34:47,139]: I mean the medicine’s not gonna change everything and you need to be focusing on your life as well

[00:34:52,040]: And I always start with scheduling

[00:34:55,059]: And many people with ADHD find scheduling anathema that that’s you know like the slaves on the galley ship being told that you have to row stroke stroke stroke

[00:35:07,340]: And what I tell them is that the part of you that’s gonna help make the schedule that works for you isn’t some evil taskmaster trying to make you do what you don’t wanna do

[00:35:18,999]: It’s actually the wisest smartest nicest kindest part of you that’s identified

[00:35:24,480]: What are your lifetime what are your bigger goals

[00:35:27,379]: How are we gonna match what you’re doing in the minute to line up with those bigger goals

[00:35:31,899]: So and this analogy isn’t perfect but the best one I’ve come up with so rather than the guy on the Viking ship the person you the part of you that’s making your schedule is a mother hen who’s sort of counting all the chicks and making things aligned and nestling down and hunkering around you and taking care of you and nurturing you

[00:35:54,240]: And with scheduling what I tell people is before you slot in your work or your homework or your school or externally derived tasks I tell people you need to have the four basics

[00:36:08,800]: And sleep is far and away the biggest basic particularly for it’s essential for all of us but it’s particularly critical for ADHD and there’s particular reasons why it’s a particular challenge for people with ADHD

[00:36:22,879]: But I’m trying to think if I can imagine a counterexample

[00:36:26,379]: I would say all the successful people I know with ADHD have found some way to try to regularize their sleep compared to what it would be if they were just so the four essentials I say are sleep eating exercise or some amount of movement because again with the hyperactivity there’s people who can sit at a desk for 12 hours not even getting up for a bathroom break or to eat or anything

[00:36:50,680]: That’s not just bad I mean that’s bad for your brain bad for your body

[00:36:55,539]: And then the fourth thing I put in is a miscellaneous category of me time relaxation meditation

[00:37:03,620]: I put all those in the same slot maybe they shouldn’t

[00:37:06,559]: And all those need to be in place

[00:37:09,799]: We can talk more about sleep but I’ll just say a little bit more about the eating component

[00:37:14,360]: One of my so we have our diagnostic criteria for ADHD but I had over the years two different real life tests

[00:37:23,220]: The office I had was an old Victorian home so it was a home office

[00:37:28,020]: The office itself the entrance was at the end of a short but very steep driveway so it was a separate door

[00:37:34,760]: And I would always explain to every new patient the exact same thing

[00:37:40,520]: There’s a house at 45 Hartford the office is at 45A the entrance is at the end of the driveway

[00:37:47,679]: And I actually did the data on it

[00:37:52,819]: The only people who ever showed up at the front door the home door were the people with ADHD

[00:37:58,539]: Now everyone it wasn’t it was specific for ADHD it wasn’t completely sensitive so some of the ADHD people got it right

[00:38:06,659]: But never did anyone who was coming in for OCD or depression or PTSD show up at the front door

[00:38:13,140]: And I gave the instructions the same time and sometimes I didn’t know beforehand that the person was coming in for ADHD because they didn’t know

[00:38:20,919]: But if they showed up at the front door that always made me you know uh oh I better make sure I ask specific detailed questions about the ADHD possible component

[00:38:32,500]: So the other sort of real life diagnostic test I had if someone during the evaluation would say something like or in a subsequent session oh it was four o clock yesterday and I just realized I hadn’t eaten all day

[00:38:47,140]: Ding ding ding ding ding

[00:38:48,360]: I mean I have people who diet I have people who have fasting regimens or others but they’re not forgetting to eat

[00:38:56,900]: And it’s not that everyone with ADHD does that but either not getting the right intero receptive cues from your body or not paying attention to them is something that’s been measurable in people with ADHD

[00:39:11,199]: So having a regular meal schedule

[00:39:13,020]: So having a regular meal schedule and again getting back to the COVID in workplace if you’re you know I had lots of people in tech who really lamented now I have to work from home they were giving me lunch a healthy nice lunch each day at work

[00:39:27,799]: They’re scrambling to even use the home

[00:39:30,612]: you know meal delivery systems because getting that organized and set up is just too overwhelming for them

[00:39:37,552]: And again these are bright people who are succeeding in most parts of their life

[00:39:42,892]: 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 ends it just sort of fragments into the rest of the day

[00:39:55,252]: Yeah that can be one variation

[00:39:57,312]: But it’s often just completely forgetting or being oblivious to it

[00:40:02,292]: Or I mean the other ways ADHD can play a role is I was meaning to have breakfast before I left the house but always when it’s time to leave the house you forget that you hadn’t done this and the kid’s shoes need to be tied and oh do I need a new toothbrush

[00:40:20,112]: I better go check upstairs before I go out because I’m going to the CVS store

[00:40:25,192]: I mean time management is a problem with ADHD and an executive function problem

[00:40:31,872]: Interestingly it’s not one of the 18 symptoms in our official checklist

[00:40:36,212]: So our official checklist is sort of a crude clinical attempt to map out a lot of the aspects of ADHD but it misses a lot

[00:40:45,792]: So there’s emotional regulation problems

[00:40:48,912]: We know something like 60 of people with ADHD acknowledge that emotions explode or come up bigger or stronger and are harder to regulate

[00:41:00,272]: And that’s nowhere acknowledged in our official diagnostic symptomatology

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[00:42:21,432]: So we’ve got sleep eating exercise or movement and relaxation

[00:42:27,932]: Maybe before we start talking about some medications and some other factors that modulate ADHD if we could maybe step through each of those and you could share with us some of your favorite tools that you give your patients and that you teach online

[00:42:44,772]: Realizing of course that each one of those is a vast topic that we could do entire

[00:42:48,552]: We have done entire podcasts on but I’m curious about your favorite go to tools

[00:42:54,932]: We were talking about a few of these before we started

[00:42:57,192]: So sleep regular to bed and wake up times

[00:43:01,872]: 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

[00:43:12,052]: It isn’t just duration

[00:43:13,472]: It’s getting quality sleep

[00:43:15,572]: And the timing of your sleep is every bit as important as the duration

[00:43:19,152]: So if you’re used to sleeping midnight to 8 a m

[00:43:22,192]: and you’re staying up dancing or partying until 4 a m

[00:43:25,832]: and you say oh it’s a weekend I can sleep until noon

[00:43:28,972]: 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

[00:43:36,692]: I mean my PhD research was on circadian rhythms

[00:43:41,052]: We had realms of data back then

[00:43:43,752]: So this was 40 30 plus years ago

[00:43:47,952]: We had every bit as much data then that the timing of sleep was as important as the duration

[00:43:53,452]: And yet every public service announcement just says get your eight hours of sleep

[00:43:58,532]: Why are we leaving out this other piece

[00:44:01,452]: We’ve known for decades that people with ADHD have a strong propensity to being night owls to have a different chronotype where they’re maybe more effective or functional later in the day a tendency to stay up

[00:44:14,892]: For many years now we’ve actually known that this is strongly genetically controlled

[00:44:20,172]: So we do have you know there are genetic markers affecting sleep timing that are overrepresented strongly in the ADHD community

[00:44:28,192]: So some of it is your push that way but some of it is the nature of ADHD that if you you know procrastinating is part of ADHD

[00:44:36,632]: If you procrastinate you’re gonna push things off till the end of the day

[00:44:41,052]: Some people the end of the day is a better time to work because there’s fewer distractions

[00:44:46,252]: You know if everyone else is asleep finally no one’s gonna come in and interrupt your work or ask what your thoughts on this project are

[00:44:53,992]: But again getting regular sleep and regular and sufficient doesn’t mean it has to be what I’d say normal

[00:45:02,092]: You know if it works for you if you can build your career and your social life around sleeping from 2 a m

[00:45:08,092]: till 10 a m

[00:45:09,312]: every day I’d say go for it if you can be consistent with it

[00:45:14,532]: So what are the things that help with getting regular sleep

[00:45:18,192]: One thing paradoxically for many people is actually being on stimulant medications

[00:45:23,412]: 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 the drug is wearing off at the end of the day and there’s some crash in alertness or energy or because they’re being more productively 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

[00:45:50,532]: We don’t know the mechanism by which it works

[00:45:54,412]: There’s lots of plausible and overlapping ones but again daytime alertness medications can help

[00:46:00,212]: Can I run something by you in that context before we jump back

[00:46:04,772]: 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

[00:46:14,792]: But on occasion I’ll take 25 to 50 milligrams of Welbutrin which as you know better than I is slightly dopaminergic but certainly triggers noradrenergic release

[00:46:29,692]: So epinephrine norepinephrine it’s a stimulant

[00:46:33,912]: 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

[00:46:48,272]: It’s extremely consistent

[00:46:49,872]: So from that I sort of reverse engineered the major effect being norepinephrine

[00:46:56,392]: Epinephrine I decided well I would do something else that I know raises epinephrine which is I’ll do a cold plunge first thing in the morning of one to three minutes long

[00:47:05,712]: And the effect isn’t quite as strong but on those same days when I do that clearly adrenaline raising activity I also see for me a significant increase in my rapid eye movement sleep and the quality of sleep later that night

[00:47:20,572]: So I think there really is something to this epinephrine obviously going hand in hand with stimulants epinephrine spike early and throughout the day with better rapid eye movement sleep at night

[00:47:34,932]: Does that logically hold for you

[00:47:36,792]: It’s just a story but you know

[00:47:38,332]: I was gonna say as both of us have some science background so I’d say I’m glad it works

[00:47:45,232]: And what’s hard to sorting out as why it’s working is one is a potential placebo effect

[00:47:50,552]: You’re doing it because you’re thinking or hoping it works good

[00:47:54,542]: 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

[00:48:06,492]: So those potential issues aside I’ll jump into insomnia and Matthew Walker talks about some of this

[00:48:17,732]: 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

[00:48:29,532]: Huh what

[00:48:30,252]: That does sound like I’m contradicting myself

[00:48:32,612]: What I mean is the sleep system’s intact

[00:48:36,012]: It’s there it’s waiting to arrive and put you to sleep each night

[00:48:40,112]: What the problem and this is from the sleep researchers with at least 90 or probably more of people who have insomnia problems is the failure of the daytime arousal system to shut off properly

[00:48:52,072]: So normally we have these two mutually inhibitory systems a wakefulness arousal system and a sleep sedation system and usually when one turns on the other turns off

[00:49:05,092]: 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

[00:49:17,692]: I mean maybe that helps the arousal system to turn off better at the end of the day if it’s gotten more fully engaged during the day I don’t know but it feeds back more into some of the non medication approaches to helping with sleep and that is doing everything you can again not just to force sleep or push it because that doesn’t work very well it’s getting rid of arousal it’s dampening arousal

[00:49:42,432]: So for people with ADHD one is deciding on what’s a reasonable bedtime having thinking about this ahead of time and two eliminating any stimulation or I mean once so exercise I’m a big fan of I’m a marathon runner I know you’re heavily into exercise as well

[00:50:05,972]: Exercising too late in the evening can elevate body temperature disrupt falling asleep

[00:50:12,252]: So physical arousal we don’t want to be doing a lot of late in the day and emotional intellectual cognitive arousal

[00:50:21,652]: 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 gonna be checking it

[00:50:35,252]: I mean studies have even shown even if you’re not checking it if it’s there you’re thinking about it you’re looking at it just having it away out of sight is better than having it visible and turned off

[00:50:46,792]: Two is using if you have someone you’re sharing a bed with or family members using them to help reinforce yes and it’s really helpful to talk about this ahead of time because the exact same words can either be sounding like a nag or someone trying to exert their power over you rather than what people with ADHD we know need reminders

[00:51:10,112]: They know they need some of that external structure and if you are on the same page and can have a partner your kid or someone else present hey dad shouldn’t you be turning off the computer and heading to bed right now that can be helpful

[00:51:25,212]: 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

[00:51:42,052]: So we were also talking a little bit before one of my favorite tools for falling asleep is actually cyclic sighing

[00:51:48,132]: I mean there are other box breathing and other techniques that help someone relax

[00:51:52,772]: So we know cyclic sighing engages the parasympathetic nervous system our rest and digest system

[00:51:59,232]: 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

[00:52:09,312]: So anything that is strengthening or putting you there already makes it easier

[00:52:15,752]: I know you have videos about cyclic sighing and I do too

[00:52:18,932]: I mean my own experience which I was sharing with you before we started talking was not only does cyclic sighing help me fall asleep better it actually helped me stay asleep throughout the night better

[00:52:29,832]: 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

[00:52:41,452]: It allows me to fall asleep within seconds

[00:52:45,832]: Somewhere for me typically around 10 p m somewhere between 10 and 11 p m is my typical bedtime

[00:52:50,852]: But then I consistently wake up at three in the morning usually get up use the restroom and then go back to sleep most of the time without too much trouble provided there isn’t a lot of stress in my external life and provided the phone is not in the bedroom

[00:53:07,372]: But as we were also talking about before we turned on the microphones this idea that our bladders get smaller as we age is complete nonsense right

[00:53:17,612]: So that can’t be the explanation why people wake up more in the middle of the night as they get older

[00:53:22,692]: Yeah I mean some might I mean some it may be a prostate issue

[00:53:27,832]: Clearly that isn’t accounting for half the population but I think it’s much more the neurologic innervation of our bladder 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

[00:53:46,792]: They could wait but the signal is arriving that says you have to and it’s believable and you don’t wanna deal with it if it’s you don’t wanna not listen to it if it is right so

[00:53:56,932]: How much cyclic sighing are you doing before sleep and how long before sleep is the cyclic sighing done

[00:54:02,292]: So when I read your paper with Spiegel and others January for years I’ve said I don’t have a meditation practice most people think I’m sort of so chill or relaxed that I do

[00:54:13,692]: You seem like a pretty mellow dude

[00:54:15,732]: I haven’t ever taken the time to do it which I’m embarrassed by so I said read the paper I can do five minutes a day of cyclic sighing and I tried and it was some days I was getting it in and many days I wasn’t getting it in till bedtime which is I slept really well till I was around 40 and not so well the next 20 years mostly with the trouble of falling asleep even though I knew of relaxation techniques and others

[00:54:45,892]: So I wound up just consistently doing it to do it more for the general health than I do have slightly elevated blood pressure and relaxation and to see what effect it would have and it was clear so I do about five minutes and much more than five minutes I tell people and I might be doing it a little slower than most count out about 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

[00:55:19,152]: If you have a timer on it and you do it for five minutes and then you’re woken up you’re reversing or mitigating some of the benefit of doing it

[00:55:28,632]: So my recommendation is do it for five minutes about but do it by counting reps and don’t focus or if it’s six minutes if it’s four

[00:55:38,952]: I mean there’s so many aspects of this and we know the exhalation has to be longer

[00:55:44,912]: I was trying to find is anyone systematically is a four second exhalation better than 10 versus six

[00:55:51,912]: And those studies would be so simplistic and easy to do but there’s lots of variables that we can play with to see what’s optimal

[00:55:58,712]: I don’t think we know at all what’s optimal but we know what’s good enough to work

[00:56:03,832]: I’m delighted to hear that it’s worked so well for you

[00:56:06,592]: As people know I’m a huge fan of the physiological sigh and I take no credit for having discovered it

[00:56:11,512]: It was discovered by physiologists in the 1930s

[00:56:13,652]: So throughout the data point that I shared with you is that prior to tricyclic sighing at nighttime I was waking up virtually every single night once a night to urinate

[00:56:25,932]: And in the 18 months 20 months since I’ve been doing it I think it’s been a total of four times that I’ve woken up during the night to urinate

[00:56:34,812]: Fantastic

[00:56:35,972]: So we’re talking about sleep

[00:56:37,492]: You mentioned earlier encouraging people with ADHD or who think they might have ADHD to keep a somewhat regular eating schedule or at least to make sure that they’re eating and to not let their meals get fragmented into starting a meal then finishing it later

[00:56:53,892]: Have for some people it’s breakfast lunch and dinner

[00:56:56,272]: For some people like myself it’s lunch snack dinner whatever it is keeping a regular schedule

[00:57:03,532]: Exercise aside from encouraging people to not exercise too late in the day certainly not caffeine and exercise late in the day are there any data about specific types of exercise being better for ADHD independent of effects on sleep

[00:57:21,952]: I realize they’re hard to tease apart

[00:57:24,292]: Yeah there’s a few studies looking at acute aerobic exercise

[00:57:29,612]: Part of it is that it’s hard to study people when they’re exercising during many exercises

[00:57:34,772]: I mean you’re not gonna wire someone up when they’re swimming for example

[00:57:39,332]: So there’s not a lot of studies in any one approach and there’s so much diversity that often it just gets lumped together

[00:57:46,252]: 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 attention more appropriately or effectively

[00:58:12,392]: And there’s a huge body of sort of clinical literature of patients reporting you know I know I feel much more alert the day I get my workout in the gym in or I feel better or you know the week I took off from that was a big mistake

[00:58:26,192]: But I would say identifying at what’s the most valuable or what’s the best duration

[00:58:33,052]: I ran through the data about a year or two ago and 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

[00:58:45,832]: It isn’t what works for everyone

[00:58:48,312]: Is there a relationship between ADHD and addiction because of the impulsivity component

[00:58:55,392]: Yes and so the answer is and these are really rough statistics

[00:59:00,392]: I actually one of my pet peeves is people who quote oh the rate of this is 27 43

[00:59:07,332]: Well it might’ve been in that study but that’s looking at one population at one set of so I use ballpark figures

[00:59:14,032]: The ballpark figure is Americans in the last 20 years

[00:59:18,217]: More than that about 20 of Americans run into some addiction substance addiction problem either alcohol or drugs

[00:59:27,477]: People with ADHD have a rate that’s almost double that and it’s higher in men than in Double

[00:59:33,957]: Almost double

[00:59:35,117]: Almost 40 risk

[00:59:36,417]: And that’s for substance abuse not behavioral addictions

[00:59:40,057]: 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

[00:59:49,417]: However kids who are put on stimulant medications when they’re young and I should say the stimulants themselves do have a small potential for addiction but putting kids on stimulants pretty much normalizes their rate of addiction problems so it cuts them in half

[01:00:08,197]: It protects them

[01:00:09,077]: This is a really important point that I think maybe we just hover on for a second because I think many people including myself assume that well if you were putting these kids on amphetamines of which many of the medications for ADHD are that we’re creating kids that are addicted to amphetamines or to a hyper stimulation period but you’re telling me it’s actually protective to put kids with real ADHD on medication for ADHD

[01:00:39,097]: Yeah I can say not absolutely every study has found this but several large meta analyses have gone back and most of them have found this fairly dramatic benefit to being on stimulants as a kid in terms of specifically reducing substance abuse risk and some of them that have looked at this when I said it was a yes and it seems to be that it’s not just the impulsivity traits but some of the inattentive ones too

[01:01:06,537]: If your teacher’s lecturing about the risks of alcohol or this and this and you’re zoning out at the window and looking at the plane flying by you have less pertinent information on the topics

[01:01:17,817]: You may be less attentive to the negative effects that other kids are seeing among the classmates who are stoners at this age or X Y or Z

[01:01:26,357]: So it seems that both inattentive sets of ADHD symptoms and the impulsive thrill seeking not weighing the consequences as heavily are all contributing to this heightened risk

[01:01:42,497]: I have this model in my head that is perhaps completely wrong maybe partially wrong and it goes something like this that we know that the neural circuits involved in executive control and directing attention and maintaining attention and avoiding distraction this kind of thing use dopamine and epinephrine and norepinephrine at least to some extent

[01:02:10,657]: And we know that people with ADHD are capable of focus as you said it’s a failure to direct that focus maintain et cetera

[01:02:18,537]: So I’ve heard from you before this discussion that people that tend to drink lots and lots of caffeine or who can drop into an activity but have a lot of distractibility that they might have ADHD

[01:02:32,837]: So what I’m imagining here is that the threshold to get dopamine epinephrine and norepinephrine released is either much higher or more complicated for people with ADHD

[01:02:43,497]: And so what they’re seeking is these catecholamines these three chemicals dopamine epinephrine norepinephrine and that if they’re given a medication that puts them in that range where they’re getting it then they’re good they can stop seeking it so to speak

[01:02:59,877]: And I’m raising this now because we’re talking about addiction

[01:03:03,117]: Addiction is a pursuit of things essentially

[01:03:07,317]: And I guess what I’m saying is it seems to me that the model of ADHD that we hear about is that people can’t focus their dopamine circuits are all out of whack and then you put them on this dopaminergic drug and basically you get them addicted to that tunnel vision or something

[01:03:25,657]: But 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 a meaningful bill the things that are generative in our life work school relationships et cetera and that whether or not it’s pharmacology or exercise or what have you that it’s just about getting into this plane of consciousness

[01:03:48,397]: And I say that in no woo or abstract terms

[01:03:51,237]: Is that right

[01:03:52,377]: I mean are we really talking about here is a failure to access enough of these neuromodulators and these medications which we’re about to talk about are really about putting us in the realm where those neuromodulators are just more accessible

[01:04:04,677]: I’ll just say I can go with that

[01:04:06,917]: Okay

[01:04:07,197]: Well you’re the expert

[01:04:08,297]: I mean I’m putting this together based on kind of what we’re talking about like getting enough sleep to me is a way of being able to have enough arousal during the day

[01:04:17,057]: You know exercise or these medications just different ways of being able to access arousal

[01:04:23,017]: Like if you don’t sleep you can’t access arousal during the day

[01:04:25,677]: So okay well I’m going to hold that model in mind and I’m going to keep testing it to try and destroy it as we go forward

[01:04:33,637]: Let’s talk about the medications since you raised those

[01:04:38,257]: And you know the first one I ever heard about was Ritalin

[01:04:42,277]: Let’s start with Ritalin

[01:04:44,197]: How often is Ritalin used nowadays and what is Ritalin doing neurochemically

[01:04:51,017]: And what are your thoughts on Ritalin as a useful drug for childhood and adult ADHD

[01:04:56,317]: And I’m happy to repeat those questions

[01:04:58,317]: So Ritalin is or generic methylphenidate and then there’s dozens now of slow release versions and there’s even a patch a skin patch instead of an oral version

[01:05:09,597]: And our definition of what a stimulant is is really squishy and vague

[01:05:15,877]: In its broadest sense it’s any drug that has an effect in the body like the sympathetic nervous system which is a norepinephrine driven fight or flight arousal system

[01:05:27,237]: So by the loosest criteria caffeine’s a stimulant well butyrin’s a stimulant even though we classify it as an antidepressant

[01:05:37,797]: And some of the decongestants are stimulants

[01:05:41,017]: But more often when we’re talking ADHD medicines we’re using stimulant more specifically for amphetamine based products like Adderall and Vyvanse and again there’s a host now of newer branded extended release forms and methylphenidate

[01:05:54,477]: 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

[01:06:03,307]: I don’t consider Ritalin a full stimulant

[01:06:07,157]: So the neuropharmacologists differ a little bit

[01:06:09,997]: But amphetamine is a strong dopamine and norepinephrine reuptake blocker

[01:06:16,057]: So it prevents what’s already been released from being taken back up so more is available longer

[01:06:21,557]: But in addition to that amphetamine is a pretty potent let’s just say vesicle manipulator

[01:06:27,417]: So it’s actually forcing a bigger release from the vesicles when they’re synaptically released

[01:06:33,077]: So it’s not just that the signal lasts longer and is stronger because of that

[01:06:37,857]: It’s a bigger signal

[01:06:39,777]: Depending on what study you look at most of the studies suggest that methylphenidate is actually a pretty weak vesicular manipulator

[01:06:48,677]: 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 Welbutrin is

[01:07:01,477]: That’s one of the components

[01:07:04,377]: And so why I would further say if you look at the efficacy data how well do these work in resolving ADHD symptoms all the meta analyses lump Adderall products amphetamine and methylphenidate products here and say they’re here because they work better

[01:07:25,937]: This is success in reducing ADHD symptoms

[01:07:29,217]: And Alvar Stratera ethylmoxetine Welbutrin I use Cymbalta a lot modafinil guanfacine all these other things are down here as less effective

[01:07:40,557]: But if you actually look at any of the plots that I’ve looked at and separate out methylphenidate is actually closer to the pack below

[01:07:49,057]: It’s the amphetamine products are head and shoulders above everything else

[01:07:54,077]: Methylphenidate’s usually at the top of the rest of the crowd

[01:07:56,637]: But if you’re just looking at the data objectively there’s a clear decision point

[01:08:02,777]: So in terms of efficacy amphetamine products are stronger

[01:08:08,177]: But in terms of some of 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

[01:08:19,897]: Now that we’re finally looking at that a little more closely because for years ADHD experts have said yeah it’s really rare

[01:08:26,597]: Let’s not look at it at all

[01:08:27,617]: Let’s not pay attention move along don’t look

[01:08:34,077]: With amphetamine Adderall products and that’s probably dose dependent but it’s close to one out of 500 people

[01:08:40,437]: And what’s I’m going off on a tangent here but I’ll keep following it because it’s an important tangent

[01:08:45,597]: It’s only one out of 500 people

[01:08:47,697]: That’s uncommon but this is a really bad condition because so amphetamine induced psychosis is a schizophrenic like picture

[01:08:55,837]: Usually someone is really paranoid really worried that their friends are manipulating them or the police are spying on them

[01:09:02,697]: I mean if you drink too much alcohol you can be batshit crazy as that’s a highly technical term there

[01:09:08,637]: I mean you can be out of touch with reality

[01:09:11,057]: You can be hallucinating

[01:09:12,077]: You can be saying all sorts of nasty things

[01:09:15,777]: 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

[01:09:24,317]: You’re not psychotic anymore

[01:09:26,317]: Hopefully you’re regretting what you did

[01:09:28,577]: Probably not remembering much of what you did

[01:09:30,417]: People will let you know

[01:09:32,397]: With amphetamine induced psychosis on the other hand classically and characteristically and what I’ve seen clinically it continues for days weeks or months after stopping the medication which means 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

[01:09:58,717]: So now we’re studying this a little more

[01:10:01,417]: But with amphetamine induced psychosis 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

[01:10:14,477]: So again it’s uncommon but it’s such a bad outcome that we really should be alerting people to it and I saw a much higher risk of this for I can get into it if we need a reasons in my population in San Francisco but I’ve had people coming from all the most prominent ADHD clinics over the years or 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

[01:10:47,547]: 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

[01:10:55,367]: And one in 500 isn’t a trivially small number

[01:10:58,027]: No it’s not trivial

[01:10:59,427]: And I mean why I got alerted to it is my rate in San Francisco is actually higher than one out of a hundred

[01:11:07,407]: And so I’ll go into I think a couple of different reasons

[01:11:11,547]: 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 in fact you know HIV induced dementia

[01:11:28,507]: So probably some of these people had brains that were compromised because of that and were vulnerable to a high incidence of methamphetamine

[01:11:37,867]: 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

[01:11:47,687]: So it’s a cousin but methamphetamine we know has higher rates of psychosis higher rates of addiction

[01:11:54,027]: This tends to be more rewarding

[01:11:56,427]: But again in that population and many of them would hide that history from me but I think that the very first person I had with amphetamine induced psychosis a guy in his 40s HIV positive for years this was back in early mid 90s was able to finish school in his mid 40s get a good paying job in two years on stimulants and then had a full blown psychotic episode where his dad had died of a heart attack 10 years earlier

[01:12:27,647]: He was threatening his mom because he believed his mom had poisoned her

[01:12:31,507]: He flew over to Rhode Island where she was living

[01:12:35,027]: He was making threats from a pay phone and because Rhode Island’s so small he was actually calling from out of state so it’s a federal crime

[01:12:41,047]: He got thrown in federal prison for this

[01:12:43,887]: And he stayed psychotic for months after he wasn’t using anything

[01:12:48,707]: But it later turned out he had had a psychotic episode 10 years earlier on street meth which he lied about when I did the evaluation

[01:12:58,187]: 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

[01:13:06,827]: So and I was comfortable with the broader range of stimulant dosages and many providers are

[01:13:15,887]: 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 of those demographics are relevant but who had histories of taking stimulants having a psychotic episode again being really paranoid

[01:13:33,687]: All and again the numbers aren’t huge but at least five people with this general profile

[01:13:40,687]: 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

[01:13:53,567]: They all liked something about the experience enough that they all wanted to get back on and all of them knew enough to lie about this past

[01:14:02,447]: So they didn’t tell me about they presented all of them also had ADHD

[01:14:07,887]: They presented with ADHD

[01:14:09,467]: They’d say I’d been on stimulants before and I’m not working with that doctor because my insurance changed or they had moved to the area

[01:14:17,447]: So they gave plausible histories and most of those within a month or two of restarting it wound up back in the psychiatric hospital

[01:14:27,287]: I had one guy computer programmer late 20s calling me from inside the psychiatric hospital to try to get me to prescribe more Adderall to him

[01:14:41,327]: And not only that he had convinced his inpatient psychiatrist that this was a good idea that this was important to treating his ADHD and helping him retain his job

[01:14:52,767]: Wow

[01:14:53,107]: So these are as you said straight white males who have psychotic episodes on their ADHD meds and continue to seek those meds because they quote unquote like the experience

[01:15:09,527]: It feels like a manic high the high dopaminergic state

[01:15:14,327]: Yeah and you put the word mania in there manic and lots of people define this as amphetamine induced mania rather than psychosis

[01:15:25,607]: I don’t because one is uniformly and maybe other people are seeing more that these people were paranoid

[01:15:33,927]: They were worried

[01:15:34,567]: They were anxious

[01:15:35,487]: They were delusional

[01:15:37,207]: But they weren’t overtly enjoying it

[01:15:40,487]: They weren’t having a great time

[01:15:42,127]: They weren’t saying I’m going to party with all you friends and I’m only worried about the people there

[01:15:48,687]: And yes they were talking more loudly

[01:15:50,847]: They were sleeping less which could be characteristic of mania

[01:15:54,487]: But there was no positive affect that I or police reports or often families give you extensive history of everything that was going on that there was nothing euphoric they were describing about it

[01:16:08,627]: I mean I think the second piece is how much of they it’s unclear how much they actually remember or recall or either through psychological suppression of it or physiologic they’re in a different enough state that didn’t register properly

[01:16:27,587]: It’s not clear

[01:16:29,227]: But they tend not to recall the paranoia and by paranoia it’s persecutory delusions

[01:16:36,247]: I have people who assaulted family members thinking that they were being spied on manipulated when they were sort of the parents trying to take care of their kids

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[01:18:03,347]: What are the options for people that think that they may have ADHD

[01:18:08,187]: Let me phrase it differently

[01:18:10,027]: Someone comes in and they have let’s say an adult they have five of the 18 criteria

[01:18:20,827]: They meet the criteria for ADHD

[01:18:23,787]: 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 and assuming they’re not on any other medications which cluster in this two sets of clusters that you described before the amphetamine type the Adderall Vyvanse et cetera versus the I realize you put Ritalin at the top of the bottom cloud Wellbutrin Ritalin Modafinil you mentioned Cymbalta

[01:19:00,367]: Which cluster do you go to first

[01:19:03,668]: I mean some of this is just individual style rather than intellectually thinking one is better or not

[01:19:09,788]: And my style is usually to listen as closely as I can to what the patient wants

[01:19:15,588]: That doesn’t mean agree with them but 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

[01:19:28,268]: For years just statistically I had many more people who are on non stimulants than stimulants compared to the general ADHD population

[01:19:37,528]: And that’s even accounting for by many variables I had I’ve always worked with a lot of people who are on disability from Medicare

[01:19:45,008]: I also worked with people who are on Medicaid and the city’s insurance before Obamacare happened

[01:19:51,768]: And so I’ve worked with not entirely but a skewed more dysfunctional more severely afflicted population which again you would think would be a better match for the more powerful drugs

[01:20:06,148]: I’ll jump back but this actually is a situation where we have more powerful drugs

[01:20:10,608]: So often when I treat people with depression they’ll try one or two or three antidepressants and say well give me something that’s more powerful

[01:20:18,408]: And with depression maybe we can put ketamine out of the picture

[01:20:22,388]: And I know this is a side issue but all of our antidepressants seem to work equally well

[01:20:27,868]: We don’t have potent antidepressants and non potent

[01:20:31,288]: If it got FDA approved it works in a certain range of likelihood

[01:20:36,568]: But with the stimulants antetamine based products really are more powerful and more So then with depression or many of our other conditions where it’s more a categorical this will help or not as long as you’re above a threshold there’s a more linear relationship

[01:20:53,648]: If a little bit of Wellbutrin helps a lot is likely to help more

[01:20:58,908]: I mean you might start getting more side effect issues and there may be good reasons to not keep going up but there’s a more linear dosage results relationship

[01:21:08,528]: Do you worry about strain on the heart with amphetamine products

[01:21:15,448]: Just even if it’s relatively low dose over time just the strain on the calcium channels and on the heart is it true that stimulant based medications for ADHD can quote unquote weaken the heart

[01:21:32,538]: When you use that term I was talking to 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

[01:21:54,468]: And you know I’ve run 100 and my heart I think is still beating so we know things we thought we know at one point

[01:22:02,548]: Common cardiovascular effects of not just the stimulants but the non stimulants that are affecting norepinephrine so wellbutrin Cymbalta modafinil it’s less clear and we can get into that when we talk about modafinil but clearly methylphenidate amphetamine on average increase at therapeutic doses increase heart rate a few points increase blood pressure a few points

[01:22:27,948]: 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

[01:22:36,408]: So we know that there’s some impact there

[01:22:40,168]: We know there’s some people with extremely rare genetic underlying conditions usually related to the neurologic wiring of the heart who are particularly vulnerable to dropping dead from a stimulant

[01:22:55,468]: Almost every year there’s you know a well trained athlete either a professional player or more than a high school or college player you know who will take cocaine take Ritalin take prescription stimulant and drop dead of a heart attack

[01:23:11,508]: The risk of that’s so uncommon this is 15 years ago when Adderall XR came out the Canadian government was worried enough about this risk that they banned Adderall XR for almost a year and because they have a comprehensive medical system that could look more extensive at the numbers and this is looking at kids the percentage of kids who dropped dead with Adderall was tiny and not just tiny it was lower than the kids who aren’t on Adderall who dropped dead of a heart attack

[01:23:47,928]: So part of it is if you’re in this rare genetic condition almost always there’s family members or you’ve had some other near death or syncopal episode where you passed out so history taking of the individual and family history and if you’re at all worried or concerned you can do EKGs which detect most of those electrical abnormalities but the cardiology and lots of my colleagues practice maybe a more conservative cover your ass medicine approach where everyone has to have an EKG before they’re on a stimulant but even the cardiology associations have said that seems to be a waste of resources

[01:24:30,108]: 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

[01:24:39,748]: But other than that these should be generally safe for most people’s hearts

[01:24:44,788]: So there was a meta analysis that came out earlier this year on so most of the studies looking at more serious other than just mild hypertension or mild elevation of heart rate haven’t found much but most of them only look you know a year out or a year of treatment do we see rates of heart attacks do we see rates of strokes do we see rates 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

[01:25:20,508]: A more recent study looked as long as 14 years out and there they found measurable statistically significant increase in risk that increased during the first three years of being on a stimulant and increased at a much lower rate for the next 10 years sort of plateaued out but still measurably higher than people with ADHD who weren’t on a stimulant but the absolute rate is still really really low

[01:25:49,228]: So for most people it’s not a risk

[01:25:52,268]: 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 know whether potentially more people are getting into more trouble

[01:26:05,388]: So if somebody presents as having ADHD as an adult and they’ve never touched stimulants and they’re would you start them on Ritalin Welbutrin or Adderall or something in the Adderall Vyvanse cloud

[01:26:19,588]: So thanks for bringing me back to your question

[01:26:23,688]: And I’m going to jump at you threw in that sort of qualifying phrase never been on any stimulant in their life or tried it or something or at least not consistently

[01:26:32,108]: Well what I would say is lots these drugs are fairly common in our society both illicitly and licitly

[01:26:41,128]: I mean we know lots of kids lots of adults with ADHD share their medication

[01:26:46,108]: Lots of people have tried these things even if it’s just once or twice

[01:26:50,508]: And that itself is valuable clinical data you know if they felt too revved up from it you know so if they have I try to find out what dose was it what did it do for you

[01:26:59,628]: What good things did it do for you

[01:27:01,528]: What bad things did it do for you

[01:27:04,008]: So my presentation is usually you know Adderall is likely to be the most strongly effective or I more often are using Vyvanse

[01:27:15,128]: These are the other options but Adderall also has again great or rare but risk for these bad problems

[01:27:22,488]: What you know does that scare you

[01:27:25,868]: Some people are petrified they’re not going to go anywhere near that

[01:27:29,408]: Some people say yeah I’m not that concerned about it

[01:27:33,528]: 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

[01:27:44,648]: And I tend to at least as a starting point listen to that

[01:27:49,428]: And now I mean there are certain reasons I absolutely would not

[01:27:54,928]: I mean my worry again I saw more of it than I think most people in a higher rate with amphetamine incurred psychosis

[01:28:03,708]: But a friend from college was just trying to refer a friend’s son who’s 27 and had a psychotic episode on marijuana and does have ADHD and is in bed depressed and not going to work and is being evaluated by two New York City doctors

[01:28:22,608]: But the psychiatrist kept him on Adderall

[01:28:25,908]: I absolutely again the likelihood of recurrence seems so high that if you have a family history of schizophrenia or psychosis or you’ve had any experience of it I would not prescribe a stimulant an amphetamine based stimulant

[01:28:43,728]: Could we go so far as to say and I suspect the answer is no but because nowadays we’re learning more about the possibility I want to highlight possibility of high THC cannabis causing psychotic episodes

[01:28:57,088]: This is something I’ve stressed on this podcast on social media

[01:28:59,788]: I took a lot of heat for this from the traditional press

[01:29:04,108]: And then ironically they’re now putting out information that essentially speaks to the same

[01:29:09,548]: I’m not saying this happens in everybody but there’s certainly a possibility there

[01:29:13,368]: But would you say that if somebody is a regular high THC cannabis user that they are at greater risk to developing psychosis if they’re taking these stimulant form ADHD meds

[01:29:28,268]: Yeah

[01:29:28,408]: I mean you could actually play that both ways

[01:29:30,988]: 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

[01:29:41,009]: Or where you were coming more from is if we’re already on one agent that’s pushing them in that direction why the heck would you ever add another that could also

[01:29:49,788]: I mean my approach clinically would be more what do you think the marijuana is doing for you

[01:29:55,728]: 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

[01:30:05,128]: So my reading of the data is very clear that there is some I mean even at low THC there’s some risk

[01:30:13,528]: Is it reefer madness that everyone who puffs a joint is freaking out

[01:30:18,188]: Clearly not

[01:30:18,968]: But again it’s much more potent than it was 10 years or that was 70 years ago I guess

[01:30:25,208]: Yeah

[01:30:25,328]: Especially as I understand we had an expert from the cannabis research community on an edible form in particular it’s harder for people to control the dosage

[01:30:33,988]: Whereas when people use inhalation as a means to deliver it seems like they kind of find the right plane without going overboard more often than with edibles in any case

[01:30:44,608]: One other big factor is that CBD actually seems in some studies to have an anti psychotic effect

[01:30:51,128]: So you know maybe strains of marijuana 50 years ago that had a whatever nature thought was a more balanced view had less of a risk but now that you can get pure THC products and I’m sure you’ve highlighted that a big problem with this whole industry is even in Colorado which three years ago was a state with the most close regulation and inspection and almost a majority of what the labels say don’t correlate with what you’re really getting

[01:31:19,889]: So this is not a well regulated industry even though states are trying to regulate their industries

[01:31:26,648]: So you may not know what you’re getting

[01:31:29,468]: CBD again may have some protective effects so getting pure and higher potency THC may be particularly undesirable

[01:31:39,408]: So in my own YouTube podcast series I’ve researched lots of subjects and most of them I wind up saying we don’t have a lot of data on it and there’s not a lot of data on marijuana

[01:31:51,569]: It’s the one subject I’ve actually changed my mind from reading what was out there

[01:31:56,608]: 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 helped them

[01:32:08,288]: And what I would tell them is the data we have and these are from everyday users is that there are measurable you know that the characteristic of the classic stoner has a grain of truth to it

[01:32:20,408]: So measurably lower motivation poor organization of thought lower energy are strongly correlated with daily marijuana use

[01:32:29,828]: Why would anyone with ADHD want any of that going on

[01:32:33,468]: That seems like a perfect misfit or accentuating what’s not working right

[01:32:39,648]: Over the years though I had a handful of people would swear it worked better for them than stimulants it worked better for them than the non stimulant alternatives

[01:32:48,808]: Clearly not everybody

[01:32:51,528]: 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

[01:33:06,428]: But there’s some research that suggests there is some subsegment and I don’t think it’s eight people with ADHD in general but some subset of that population who may actually do better and most of the time they were looking at marijuana rather than pure THC

[01:33:21,748]: And what I was going to say is there’s probably at least 70 or 80 other psychoactive components to marijuana not most of them as high a concentration as a THC or CBD but they’re out there maybe they are more important even at lower concentrations

[01:33:38,288]: I’ve heard this that for some people cannabis can help them focus and I’m certainly not one of those but it certainly is interesting

[01:33:48,908]: As long as we’re on cannabis excuse me as long as we’re discussing cannabis neither of us are on cannabis to my knowledge maybe I could just ping you for kind of the relationship between various compounds that people use that are available over the counter or with you know sort of online access to these compounds and ADHD symptoms specifically

[01:34:15,208]: And then at some point I’d like to return to the amphetamine based drugs

[01:34:20,748]: So let’s just start with nicotine

[01:34:23,569]: So these days there’s increased use of nicotine pouches gums not just smoking vaping dipping and snuffing

[01:34:32,288]: And it’s certainly a stimulant and certainly a lot of people in particular young males are using it more often

[01:34:39,968]: The traditional media is now trying to create this kind of picture of nicotine being part of the kind of wellness and fitness community

[01:34:46,368]: But in my observation many many more people outside of that category are using it

[01:34:55,608]: 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 trying to do this in ways that do not cause cancer because the smoking dipping vaping snuffing part is what causes the cancer

[01:35:13,128]: Let’s just talk about the compound nicotine

[01:35:15,428]: Yeah

[01:35:15,569]: So there’s some well done research showing nicotine is helpful for improving some of the executive functions sustained attention and I’m not sure which of the executive functions but they help people focus be sharper do better

[01:35:32,308]: There is actually a major pharmaceutical company who is 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 it was some other side effect

[01:35:50,148]: It’s worth throwing out there that although nicotine in many ways acts like a stimulant it actually is moderately unique and I hate people who say unique means one of a kind so I can’t modify it in any way

[01:36:04,988]: Unusual maybe not the only one unusual in that it both arouses people and reduces anxiety simultaneously

[01:36:14,428]: 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

[01:36:24,029]: So nicotine again seems to be both calming and helping alert or focus people and 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 it’s affordable because some of these products are pretty pricey at least the chewing gums or the Nicorette that was used for helping people with smoking cessation I have some people who feel that it’s been an important and useful part of their regimen

[01:37:00,889]: I have some people small numbers who prefer it to any other medications and almost no again other than sort of the basic neurophysiology showing that it can have beneficial effects on executive functions there’s no research at least as of a year or two ago whenever I dipped my toe not my anything else into the snuff looked into it there’s no clinical research showing does this help or not help

[01:37:32,269]: What about caffeine and in particular energy drinks

[01:37:36,688]: These days there just seems to be an explosion of drinks that include caffeine but also fairly high dosages of things like taurine alpha GPC theanine tyrosine so things that are thought to generally amplify the production or release of neuromodulators like dopamine acetylcholine and so forth

[01:38:01,128]: So epidemiologists say that the most widely used psychoactive substance on this planet and I thought it was alcohol for years but it’s actually caffeine because lots of groups outlaw alcohol who won’t outlaw caffeine

[01:38:16,368]: So lots and lots of people use it and this is a gross oversimplification but this is what I tell people even though it’s the most widely used if you used it as an equivalent dose to our stimulants I mean essentially we’re using it at a lower dose level it’s a pretty lousy stimulant I mean separate from that it’s working primarily on adenosine and indirectly working on dopamine

[01:38:39,686]: but associated with higher levels of androidy higher levels of jitteriness higher levels of cardiac toxicity if you were to use it at a equivalent dose

[01:38:49,766]: But most people are using it at a substantially lower dose

[01:38:53,906]: And the ADHD experts sort of historically have fallen into two different camps

[01:38:58,906]: Some of them have said it’s gonna interact with your stimulant or other medications it’s complicated we don’t want it messing up the picture stay off of it

[01:39:11,486]: And the other half say it’s a stimulant lots of people are using it with these other stimulants both full blown stimulants and non stimulant ADHD medications

[01:39:20,926]: And as long as you know it’s part of the picture and you’re trying to be constant with your dosage or aware of it then fine and maybe it helps you get away with the lower dose of the prescription

[01:39:32,346]: The one little piece I’d add in there is that often you don’t know what dose you’re getting

[01:39:37,726]: People have the common experience as I was saying earlier I’ve only had three cups of coffee in my whole life so this is all anecdotal or research not personal experience data

[01:39:47,706]: But lots of people have the experience go to their local Starbucks or something and say whoa that feels way stronger than usual

[01:39:55,426]: And then invariably they say oh that must just be me I’m more anxious already I’m jacked up

[01:40:01,586]: Because they think Starbucks seven billion stores around the country everything’s automated and precise they must be Starbucks isn’t they control for the aromaticity 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

[01:40:23,206]: 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 the lowest days was a three fold difference

[01:40:41,286]: And that’s Starbucks who knows what smaller so one is you may think you know what you’re and maybe the bane of coffee drinkers and maybe Sanka in a teaspoon that you’re dissolving may be the most consistent there 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

[01:41:06,316]: Very interesting

[01:41:07,366]: I mean 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 yerba mate being my preferred source of caffeine but also coffee and it certainly increases my focus

[01:41:23,006]: It’s a narrow plane though two sips too many and I can start feeling myself veer toward more lack of focus

[01:41:30,226]: It doesn’t seem to have a very pervasive effect and dosing it on an empty stomach versus after eating I mean I’m not that precise about it but I don’t see it as a very reliable stimulant

[01:41:47,646]: It’s more to get to a plane of just normalcy for me given how much I’ve been drinking it since I was a teen really

[01:41:53,266]: I think most people are similar

[01:41:54,706]: They drink it to feel normal

[01:41:56,686]: Yeah and there’s lots of well and there’s also lots of cultural and habitual if it gives you your warm fuzzies or puts you in the right mode or you’re sure you think you’re more alert or you’re listening to your favorite newscast in the morning as you’re drinking it that all is adding to its effect

[01:42:16,026]: In terms of combining it with other over the counter things there is some study looking at caffeine and L theanine together and having some at least in a tiny handful of studies some measurable beneficial effect on I think it’s mostly kids that have been looked at and nothing dangerous found across a pretty broad range of L theanine dosages but it’s I’m not aware of any good research done with adding all the other things that are currently being added to it and some logically may be doing something some may be irrelevant some may be more detrimental

[01:42:56,286]: L theanine certainly is being added to a lot of caffeine containing drinks because it seems to take the jitters off and the assumption being that people can consume more of that drink as a consequence

[01:43:07,506]: Yeah there’s a tiny bit of evidence that suggests that it may both dampen down help with anxiety but it may directly have some beneficial cognitive executive function benefits itself

[01:43:20,626]: Yeah this is in keeping with the green tea hypothesis which I believe green tea is enriched with theanine

[01:43:28,446]: You are somebody who quite refreshingly to me has talked not just about prescription drugs and behavioral tools for ADHD but also actually I think years ago you were the first person to first share with me the data about fish oil and the EPA omega 3s for depression

[01:43:50,926]: Those studies were starting to come out we were talking about those studies

[01:43:54,746]: And nowadays I think while there’s still a little bit of controversy out there about fish oils I think most everybody believes that getting high quality omega 3s from good clean sources including fish oil is mostly beneficial or beneficial

[01:44:10,786]: What about fish oil for ADHD in particular and what threshold dosages are relevant here

[01:44:20,946]: So just as with the fish oil for cardiac benefits there was a time period where the first few large and they were pretty large well done studies showed benefits for cardiovascular health

[01:44:33,166]: The more recent studies with fish oil haven’t shown an effect or benefit

[01:44:38,066]: 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

[01:44:46,306]: Well you have to reconcile all the data in the pool

[01:44:51,126]: ADHD fish oil story is a little the opposite and it’s almost everything with ADHD

[01:44:57,546]: It’s been kids that have been most strongly looked at

[01:45:00,586]: The first few studies with fish oil in kids didn’t show any benefits at all

[01:45:06,086]: And then subsequently there have been several studies that looked at benefits

[01:45:11,166]: And again and the field jumps to the second set without reconciling well how do we do a good meta analysis with everything in there

[01:45:20,686]: And I haven’t looked closely enough to know were there methodological differences dosage differences population differences that matter

[01:45:29,036]: 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 it seems

[01:45:46,966]: And I’d say that depression has been the most consistent field and that doesn’t mean every study there has been positive either but the most consistent field for a mental health benefit or a health benefit

[01:45:59,766]: And there the recommendation is usually target about 1 000 milligrams of EPA of icosapentaenoic acid a day

[01:46:10,046]: If you’re seeing some benefit but it feels like that there’s more room for improvement so this is my I tell people then you could probably double it reasonably

[01:46:20,266]: I mean some of the dramatic there were dramatic studies looking at fish oil for mania people hospitalized with it and they used dosages as high as 7 000 milligrams a day

[01:46:32,026]: To treat mania

[01:46:33,126]: Yeah and that study I think it was a Harvard area clinic that was doing it the results were so dramatic that they ethically had to stop the study before its intended completion because the benefits seemed to be so robust in the fish oil group compared to the that it was unethical to not put everyone on fish oil

[01:46:54,086]: That’s a lot of fish oil

[01:46:55,366]: That’s a lot of yeah

[01:46:56,106]: You probably need to get it in liquid form to make it so it wasn’t so expensive but I find this recency effect incredible that you which you mentioned a few moments ago that and I think this is helpful for people to hear certainly it is for me we hear 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 have not been demonstrated and there seems to be a focus on the recent studies as if the old ones don’t exist

[01:47:28,526]: That’s essentially what you described for both cardiac and ADHD

[01:47:31,966]: I think it’s really important

[01:47:33,826]: We hear this with alcohol too

[01:47:35,346]: I’ve been involved in this debate

[01:47:36,866]: I you know I don’t care if people drink one way or the other provided 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

[01:47:46,726]: I don’t have a problem with it but it’s remarkable that every time a study comes out showing a mild benefit of moderate alcohol use that seems to be the highlight and then everything else is forgotten and the inverse is also true

[01:47:59,706]: One would think that the meta analyses would include all as many good studies as possible but I think it’s important to understand that people hear that that’s not always the case

[01:48:08,146]: Just because there’s a meta analysis doesn’t mean that it included all the relevant studies so I’m just restating thank you

[01:48:15,706]: I make it a point to try and get one to two grams of EPA per day just as a general mood

[01:48:21,326]: You know I’m not clinically depressed but just to support my mood to support focus to support well being including cardiac function

[01:48:28,666]: So the other thing that I think is understudied with the fish oil issue is and it’s a Harvard guy who has a proprietary brand of purified EPA that pushes it

[01:48:41,526]: So in nature whether you’re a whale or a human or a butterfly or maybe not insects I’m not sure across the mammal bird reptile kingdom the omega 3s are found in about a two to one ratio of EPA to DHA icosapentaenoic acid to docosahexaenoic acid and what I tell people is I think Mother Nature’s probably smarter than any Harvard professor 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

[01:49:23,106]: That to me doesn’t make a lot of sense

[01:49:25,266]: So I would say we can still count or do the numbering based on about 1 000 milligrams of EPA but don’t worry that you’re getting about 300 400 milligrams of DHA and probably that’s better for you

[01:49:38,166]: I’d like to take a quick break and acknowledge one of our sponsors Matina

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[01:51:04,746]: You’re one of the first people that I ever heard discuss the gut microbiome and ADHD

[01:51:11,646]: This is me giving you credit for being way ahead of your time

[01:51:15,206]: I don’t know how you are at receiving praise especially on camera and with microphones but I just want to say that you know it was over a decade ago that I heard from you about EPA and fish oil for depression and other things about circadian rhythms an area that I’m familiar with and just the critical importance of circadian health for everything that we’re talking about today and more and on and on

[01:51:39,426]: And so you know again thank you for raising these points even if they turn out to be minor effects

[01:51:46,266]: I think nowadays we hear about the gut microbiome

[01:51:49,966]: I may have actually heard the words gut microbiome first from you

[01:51:57,786]: Gosh yeah that would be well over that would be almost 20 years ago

[01:52:04,246]: Remarkable

[01:52:05,686]: So gut microbiome what do we know about the gut microbiome and supporting it and ADHD

[01:52:11,846]: I’m going to kind of pass on that by just saying it’s complicated and probably important in so many variables that it’s hard to know what’s really valuable in a day to day real human living perspective

[01:52:27,726]: Do you do anything to support your gut microbiome

[01:52:31,006]: Just with your knowledge of the relationship between gut and mental health does it impact your behavior at all in terms of choices

[01:52:42,246]: Yeah only to the extent of trying to have a varied diet and eating at somewhat regular intervals but not more specifically

[01:52:53,446]: If that’s where we’re at well that’s where we’re at

[01:52:56,426]: Before we go back to some drugs I wanted to ask about behavioral tools for ADHD

[01:53:05,146]: I’ve seen some of the literature claiming that certain video games might actually be useful for training focus

[01:53:12,646]: I’ve managed to find a few papers that talk about focus and meditation tasks that kids in particular but adults may be able to get better at

[01:53:24,306]: I mean are any of these brain training games to get people better at focusing

[01:53:28,426]: Are any of them known to be worthwhile according to like real data or clinical observation

[01:53:34,406]: So I’ll start by stepping back a little bit and broadening it I’ll get to the video game things but one of the effective approaches that helps with symptomatic reduction with ADHD is cognitive behavioral therapy

[01:53:48,886]: So that’s a form of talking therapy

[01:53:51,206]: 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

[01:54:05,886]: And the traditional CBT was developed by Aaron Beck to treat depression probably 50 years ago maybe longer 60s I think late 60s

[01:54:18,166]: Anyway on the surface it’s a horrible match for ADHD because we know it requires lots of repetitive boring homework doing the same thing

[01:54:27,806]: It involves introspection of being aware of what you’re doing already looking at those patterns looking at what the triggers to see if you can see triggers for them and then doing lots and lots of repetitive homework which and when it’s successful for depression or PTSD or other venues we know it actually changes brain wiring and brain chemistry

[01:54:51,066]: So lots of people still think talking therapies are sort of up here doing something and chemicals and medications are really changing the brain

[01:54:59,786]: If your thoughts are changing if your behavior’s changing your brain has changed

[01:55:04,046]: That’s the only place that thoughts and behaviors come from

[01:55:07,586]: But there have been at least two groups Mary Salantos in New York and Harvard Group by I’m blanking on his first Safran and some other Ramsey at Pennsylvania developed approaches using CBT techniques specifically designed for people with ADHD to help overcome some of those hurdles and barriers

[01:55:29,846]: And both of them encourage actually the use of medications in combination with it

[01:55:36,006]: 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

[01:55:48,886]: At the core of both of those approaches is having a system of scheduling each day

[01:55:53,726]: That doesn’t mean micromanaging each minute but it’s having the essentials in place having blocks of time that you know what you’re gonna do

[01:56:03,206]: And having a task list in combination with that and ways of learning to prioritize and move things up or down

[01:56:11,906]: And again with ADHD being interest driven rather importance driven you may have a task I mean you probably have 17 task lists

[01:56:19,046]: One’s New York coffee one’s at the grocery store

[01:56:22,646]: One it’s having one consolidated list because if it’s everywhere then it’s nowhere

[01:56:28,456]: And two is the simplest triaging or organizing approach is having the things that are both urgent and important

[01:56:40,426]: So to happen today those get in the A category

[01:56:44,586]: The things that are important but aren’t as urgent are the B category

[01:56:48,366]: And all the other things are the C

[01:56:50,846]: And one of the temptations that people with ADHD have is oh I need to be productive

[01:56:58,206]: 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 and all the important things remain undone

[01:57:10,926]: So it’s a system for getting done what’s really needed to be done and eventually 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

[01:57:27,926]: And there’s much more to it so the CBT approach can work with decreasing procrastination it can help with structuring your own workspace given that you probably have much more trouble doing that than not doing it spontaneously

[01:57:43,766]: It’s how to eliminate distractions and modules on even extending your concentration time

[01:57:51,446]: 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

[01:58:14,786]: When the FDA approves devices basically they’re saying it’s not gonna kill anyone it might help

[01:58:21,699]: I mean it might help tremendously but it’s having the FDA imprimatur for that doesn’t guarantee that or mean that at all

[01:58:28,579]: Do you recall if the study of that device or the study of that video game has a conflict of interest

[01:58:34,159]: Was it run by the company

[01:58:36,099]: Yeah

[01:58:36,379]: Yeah so almost all of them have been run by the company

[01:58:39,259]: I mean it’s good people at UCSF who are at least partly involved in it

[01:58:44,539]: Oh is this Adam Gazzelli’s group

[01:58:46,399]: I think so

[01:58:47,279]: Yeah he’s I should just say that I’ve followed his work for some years

[01:58:51,699]: He’s a neuroscientist

[01:58:52,999]: I know people who have been in his lab

[01:58:55,359]: He’s known for doing very high quality and stringent work

[01:58:58,679]: 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

[01:59:08,219]: But in terms of real world how much is this really helping ADHD symptoms on a day to day basis

[01:59:15,399]: Not a lot of data at all

[01:59:17,119]: So again that doesn’t mean it doesn’t work

[01:59:19,839]: And I’m gonna go sideways in talking about neurofeedback because there’s lots and lots of neurofeedback companies across the country that are making lots and lots of money

[01:59:30,599]: And there was a article in the American Journal of Psychiatry in the last year

[01:59:36,119]: I’m not remembering which group did it

[01:59:39,379]: And it was another non a failure to find a significant impact from neurofeedback

[01:59:47,399]: 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

[01:59:57,879]: And the doctor saying oh maybe 20 more episodes will retrain your brain

[02:00:04,759]: So this gets back to a topic you brought up earlier

[02:00:08,439]: How much are we retraining our brains with immersion in social media

[02:00:13,639]: And the evidence is we are rewiring our brains

[02:00:16,699]: 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

[02:00:29,879]: I’ve made it a point to put social media on a old phone

[02:00:35,379]: So those apps are only on that phone

[02:00:37,819]: I don’t even know the number to that phone

[02:00:39,479]: If I need to post something I airdrop it onto that phone

[02:00:41,799]: And this has helped tremendously in segregating that activity and limiting it

[02:00:47,739]: 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

[02:00:55,419]: It’s helped tremendously

[02:00:56,379]: I just pass it on because it’s one of the things that’s really allowed me to restrict my social media time and yet still be you know in keeping with the fact that I think social media has its uses

[02:01:06,019]: I post there et cetera

[02:01:08,299]: Yes so getting back to the scheduling I mean what I recommend to people one of my weaknesses I don’t know the specific apps but there are apps that will help shut you out of Facebook or Discord or TikTok or whatever it is

[02:01:21,039]: If you can’t exert your own willpower which again is harder to do if you have ADHD

[02:01:26,879]: 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

[02:01:40,599]: And I think that’s a good idea for lots of people

[02:01:44,779]: I do too and I think it also helps at least in my experience to do things that are very different than social media as well but still consuming content

[02:01:53,959]: So I make it a point to read from an actual physical book a bit each day or night also because I was raised doing that and writing by hand is just sort of in keeping with the way that my brain was wired

[02:02:06,359]: So maybe that’s more specific to me and my generation

[02:02:09,339]: But I find that when I’m doing those other activities when I go on to social media it feels more like a departure from the rest of life as opposed to the other way around

[02:02:22,399]: But in any event That’s a good sign for preserving

[02:02:25,739]: I’d like to talk about some compounds that are not so typical meaning some people may have heard of these but most people probably haven’t and they are somewhat novel to me

[02:02:37,919]: The first one is guanfacine

[02:02:41,059]: What is guanfacine and why is it sometimes used for ADHD

[02:02:46,579]: So guanfacine and a related drug called clonidine which can be confused with klonopin and others

[02:02:54,559]: So clonidine and guanfacine are both alpha 2 agonists

[02:02:57,959]: So they work on a subset of the norepinephrine system

[02:03:01,639]: They’re both originally antihypertensive for lowering blood pressure

[02:03:06,199]: And it was actually studies first in clonidine that suggested this could be helpful with people with ADHD

[02:03:12,639]: And I think it was just a serendipitous initial discovery

[02:03:16,679]: It wasn’t seeking out its mode of action to see if that really worked

[02:03:20,639]: One difference between the two of them is clonidine jumps off the norepinephrine alpha 2 receptor really quickly

[02:03:28,259]: And for people who skip a dose with their blood pressure medication or stop abruptly it’s not uncommon to have rebound hypertension

[02:03:39,559]: And not just mild but way higher than what you’re being originally treated for to dangerous levels

[02:03:46,139]: Guanfacine leaves the receptors more slowly and there’ve been formal studies trying to see if this is a problem or issue there

[02:03:52,959]: And particularly given that people with ADHD forget their medication or run out and don’t fill it in time or just don’t remember to take it the rebound hypertension does not seem to be nearly as common with guanfacine

[02:04:06,559]: And that’s part of why the research has moved more towards the guanfacine

[02:04:12,739]: So there’s extensive work by I’m gonna blank on her name Amy Arden R

[02:04:19,539]: She’s at Yale

[02:04:21,539]: Oh Arnston

[02:04:22,859]: Arnston thank you

[02:04:23,679]: And her lab and related labs have shown that guanfacine’s effects seem to deal with strengthening synaptic connections in prefrontal circuitry

[02:04:34,719]: So unlike most of our drugs which are just boosting norepinephrine and or dopamine and work quickly and I’ll throw in this because we didn’t really touch this

[02:04:45,539]: Most of the ADHD experts still say stimulants amphetamine ritalin work quickly immediately because they boost dopamine right away

[02:04:55,039]: And our drugs like stratera which is adamoxetine or Cymbalta or Welbutrin work slowly for ADHD because they’re antidepressants and antidepressants work slowly

[02:05:04,739]: There’s still people saying this

[02:05:07,459]: 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

[02:05:18,259]: So neuroscience view how quickly does dopamine get the uptake get blocked by Welbutrin or by adamoxetine stratera or by Cymbalta within minutes to hours of taking it

[02:05:30,199]: So you would expect if you’re boosting norepinephrine or dopamine availability right away you should see effects right away

[02:05:36,119]: 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 it worked just like the stint

[02:05:45,819]: I could tell I took it and I walked out of your office and I mean one guy I have who loves Cymbalta said I took it in your office and I wasn’t sure it was working and I got downtown to work 15 20 maybe half hour later

[02:06:00,579]: And there was this guy coming at me on a skateboard on the sidewalk

[02:06:04,679]: 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

[02:06:13,319]: So you know it worked that quickly and dramatically

[02:06:18,019]: So that’s the aside

[02:06:19,899]: So jumping back guanfacin seems to work slowly

[02:06:22,459]: So the synaptic strengthening building and it seems to be the alpha 2 receptors that are on neurons that receive glutamate is our primary input

[02:06:37,379]: The alpha 2 receptor is modulating how glutamate is actually working and it’s actually the NMDA glutamate receptors not the more common in the brain AMPA glutamate receptors

[02:06:49,799]: No that’s an important point

[02:06:51,099]: I’ll just quickly throw in if I may that the NMDA the N methyl D aspartate glutamate receptors are the ones that typically are associated with synaptic plasticity

[02:07:03,259]: Although you know so are the AMPA receptors can do that too

[02:07:06,339]: But what Dr Cruz is referring to is the fact that guanfacin indirectly modulates those pathways

[02:07:13,499]: So the longer duration to get the effect it sounds like could be at least partially explained by a real change in neural wiring as opposed to with you use Cymbalta and Welbutrin as examples of fast changes in neurotransmitters and neuromodulators that led to this very quick effect in this patient that left your office got downtown and was already experiencing effect

[02:07:37,699]: Put differently sounds like guanfacin and clonidine not to be confused with clonopin clonidine could help ADHD but might take longer for the effects to manifest than the other drugs that we typically hear about

[02:07:52,219]: Yeah so most often it takes two three four weeks and because it I mean with the stimulants you see effects right away

[02:07:59,019]: It’s reinforcing and stimulants often in addition to having effects on concentration attention other you know do boost energy for most people do boost mood for most people

[02:08:10,719]: And can improve sleep if they’re not taken too close to sleep yeah

[02:08:13,879]: Guanfacin’s most common side effect tends to be sedating

[02:08:17,079]: So most people take it at nighttime which is like why are you taking a sedating nighttime medication for your ADHD

[02:08:23,639]: It’s because it helps it works slowly and directly

[02:08:27,219]: So Intuniv the brand name extended release guanfacin was approved in kids because again most of the research on ADHD is still on kids for treating ADHD as a solo agent

[02:08:41,679]: It clearly works in adults as well

[02:08:45,699]: And even before Intuniv was approved there were a handful of studies with either immediate release guanfacin or extended release guanfacin

[02:08:54,619]: In the studies so far the results aren’t distinguishable

[02:08:59,119]: You know they both seem to work

[02:09:00,899]: So clinically because it’s much cheaper I actually use immediately release form and all at bedtime

[02:09:10,739]: And again because my impression and I probably don’t have a N that’s big enough to do a rigorous study is the sedating effects are relegated to the nighttime and people are feeling okay during the daytime

[02:09:24,519]: 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

[02:09:33,219]: 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

[02:09:40,779]: So I’ve seen good results in some people

[02:09:43,579]: I’ve had many who either didn’t work or they didn’t perceive a result because again some part for some people of the stimulant benefit is I can feel it I know it’s working

[02:09:55,819]: So the majority at least in terms of prescription searches and what clinics tend to it looks like most people who are on guanafacin are on it in combination with either a stimulant or a norepinephrine or dopamine promoting agent

[02:10:12,579]: Let’s talk about modafinil and R modafinil by extension

[02:10:19,379]: We hear about modafinil a lot in communities like the tech community and communities where people are trying to quote unquote cognitively enhance

[02:10:29,439]: What is modafinil

[02:10:30,739]: What does it do

[02:10:31,919]: What doesn’t it do

[02:10:33,099]: How might it be useful for ADHD

[02:10:36,239]: So we’re gonna jump back to your issue with the recency in science and how to incorporate things

[02:10:42,199]: When so modafinil was a drug developed by a French company and approved there and used for decades for maybe a decade before it came to the US 25 maybe 35 years ago

[02:10:54,659]: And at the time all the research showed that it was an orexin receptor antagonist

[02:11:03,079]: Antagonist agonist works on the orexins

[02:11:06,679]: The hypocretin orexin system right

[02:11:08,719]: So boosting activity but not working like all of our stimulant alerting drugs which are working on primarily norepinephrine systems

[02:11:17,459]: So it was called the non stimulant stimulant

[02:11:21,679]: 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

[02:11:32,259]: I haven’t seen anything that to me means gives a clear consensus you know

[02:11:40,439]: So I stick with the orexin because that’s where I was taught

[02:11:44,099]: So orexin getting back to the sleep wake and the brain in arousal as I describe it there’s two ways to wake up in the morning

[02:11:51,759]: One way is the normal way that you just wake up and the other is being alarmed by an alarm clock your neighbor starting their lawnmower someone snoring an earthquake if you’re in LA or Hawaii being startled out of sleep

[02:12:08,979]: That wakefulness system is a sympathetic nervous system

[02:12:12,899]: The orexin system is a more natural normal waking system and it isn’t arousing you it’s waking you but it’s not agitating you

[02:12:22,979]: Again the claims originally was that this is how modafinil worked

[02:12:26,859]: It was waking you up but not overstimulating over revenue

[02:12:32,339]: 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 in wanting people to be alert and ready to kill 24 7 but not being hyperactive trigger happy jittery like stimulants can do

[02:12:54,859]: And this particularly in the early days this is really dating me of the Afghan war we dropped bombs on Canadian troops by accident in our friendly fire scenario things and the investigation the pilot and the crew there blamed their trigger happiness on being revved up by methylphenidate

[02:13:16,069]: So for years the military has relied on traditional stimulants to keep people able to fight around the clock and they wanted an agent that would keep you alert awake but not revved up not agitated

[02:13:31,719]: And I’d say there’s some good evidence that that’s really sort of how modafinil works or performs

[02:13:38,699]: So modafinil is called provigil for provigilance and then when they were losing their US patent like many drugs the provigil is a racemic mixture of left handed and right handed versions of the same modafinil molecule

[02:13:53,999]: They found that the R modafinil the right handed version was the one that’s doing most of the good stuff and has a longer half life than the combined version so they got a new patent for R modafinil which is NuVigil

[02:14:09,119]: So that’s the only difference between the two

[02:14:11,659]: They’re the same active ingredients as far as we can tell

[02:14:16,799]: 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

[02:14:25,579]: 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

[02:14:39,459]: But even at that time when it was approved there were dozens of studies that showed regardless of why you’re sleepy whether it was sedating medication whether you had lupus or MS whether you had some other condition it works pretty well for keeping people alert and awake

[02:14:57,199]: 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

[02:15:06,139]: My clinical experience with it it tends to be again with the amphetamine on top many fewer people describe it as being helpful or as helpful

[02:15:19,519]: 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

[02:15:35,219]: And their claim and it was a very well done study they were comparing it directly to an amphetamine product

[02:15:41,579]: Their claim was that modafinil was the one that was actually boosting cognitive functions and not just boosting motivation whereas that most of amphetamines benefit for ADHD

[02:15:53,899]: 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

[02:16:07,079]: It’s a controlled substance but not nearly not the same schedule as amphetamine and Ritalin so it’s easier for some prescribers to prescribe

[02:16:17,999]: 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

[02:16:37,979]: 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

[02:16:47,619]: So I don’t know why they came up I mean it’s just weird that people come up with the same terms

[02:16:52,779]: But it’s I mean my interpretation is that for some people this novel substance primarily may be attacking into the orexin system is serving as a signal kind of like a panic attack does that there’s something weird something different we’re being revved up and that it’s I think secondarily triggering the sympathetic system

[02:17:13,599]: Because for most of those people within a few trials within a few days they no longer had that over revved effect

[02:17:22,059]: And again the important piece for alerting people to that is if they’re expecting taking this I’m not gonna feel over roused and over agitated and they do then they’re even less prepared and more freaked out

[02:17:36,119]: Even though I’ve never tried modafinil provigil that people that I know who have and I know one who has for treatment of real narcolepsy so he’s narcoleptic but others who take it for ADHD and for work focus and cognitive enhancement people who take modafinil and are modafinil really like it

[02:18:00,699]: I don’t know if it has any reinforcing property but today’s the first day I’ve heard that it has this dopaminergic aspect

[02:18:06,759]: But they seem to really like it and rely on it

[02:18:09,919]: Have you seen a kind of a dependence form

[02:18:12,339]: I mean it is a controlled substance because some people are worried about the potential

[02:18:18,679]: And there was a woman Olympic athlete 20 15 years ago who was admodaf and said she had narcolepsy

[02:18:25,819]: I don’t know but was disqualified from the Olympics

[02:18:29,995]: But whether it has any real performance enhancing effects is not clear

[02:18:35,595]: You know it was available in France for a decade at least before it came to the U S and they didn’t see any rates of substance abuse or problems

[02:18:44,355]: I mean it clearly does not have 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

[02:19:01,975]: What about within the category of Adderall Vyvanse and the stimulant type treatments for ADHD

[02:19:10,275]: I don’t want to say what are your go to favorites because that makes it sound very non clinical but what are the general trends that you’ve observed and that others have observed clinically or in any studies about preference for long acting drugs versus shorter acting drugs

[02:19:30,575]: And maybe this is also a good opportunity for you to be able to chime in about like drug holidays you know taking weekends off and things of that sort

[02:19:41,335]: Maybe I’ll start with that

[02:19:42,955]: So for decades particularly starting with kids 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

[02:20:06,835]: So height winds up being about two centimeters not big but measurably and consistently found there for kids who are routinely on these stimulants for their growth years

[02:20:21,515]: And taking breaks that last for several months like taking it off during the summer result in overcoming that decrement in height

[02:20:31,555]: I looked and I still haven’t whether there’s any lower rate of addiction whether there’s any lower rate of developing tolerance

[02:20:39,355]: There’s nothing that shows clinically

[02:20:41,355]: I mean it may be true

[02:20:42,735]: The other recommendation when I started out was and this was before the internet before constant plugged into everything and before kids had soccer practice and violin lessons and 400 activities is that kids should take it during the workdays and not take it during the weekends and not take it during the summers

[02:21:00,635]: 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 or he’s supposed to be performing and focused and behaving

[02:21:16,615]: So the sort of excuse you could have downtime has diminished in many communities

[02:21:22,975]: And again whether there’s actual benefits to that or not other than for the height decrement which again there is evidence that taking long breaks but probably not short breaks mitigates that

[02:21:37,435]: I haven’t seen any evidence clearly showing a benefit

[02:21:41,775]: That doesn’t mean it’s not there

[02:21:43,335]: Nobody has really studied it rigorously

[02:21:46,415]: Sort of related to that you asked the question about short acting versus long acting

[02:21:54,335]: 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

[02:22:00,815]: 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

[02:22:15,435]: 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 extended release version that may actually be more of a risk but I’d say there’s more concern I think in the basic science community from the immediate realist

[02:22:37,255]: And there’s a tiny bit of data but part of it overall is that we talked earlier about global rates of addiction to any substance

[02:22:47,435]: That we have fairly good data on because the CDC tracks it but in terms of very specifically who gets addicted to Adderall who gets addicted to Ritalin

[02:22:57,275]: There’s so little data and most people just sort the same numbers that oh maybe 2 3 of kids run into trouble and it’s not common and that’s it

[02:23:08,135]: Or they study a much broader question and that’s the issue of misuse combined with abuse

[02:23:14,815]: And misuse by the research definitions means anyone who didn’t use their drug exactly as prescribed which means if you’re taking a short acting Ritalin and it says take it one every six hours apart during the day and you acknowledge taking it on one day eight hours difference you’re classified as a misuser by those studies

[02:23:37,615]: I mean I’m being maybe a little ridiculous because most of the exceptions aren’t that narrow but there’s a big blurring in the research particularly coming from the people who are worried about addiction

[02:23:50,995]: I mean we should be worried about addiction but we shouldn’t be overreacting or creating pretending it’s a problem among those where that I would say is not addiction

[02:24:03,515]: That’s not abuse

[02:24:05,535]: That’s not using it as directed

[02:24:07,875]: But people with ADHD by their very nature are not going to use things as directed either because they forgot or weren’t organized enough to get it on time or forgot what you said in the office even though you wrote it down because they lost the sheet of paper it’s written down on

[02:24:24,575]: So getting back to patients experience of it so the advantages of the immediate release is they tend to work quickly

[02:24:31,515]: You can feel it going in

[02:24:34,375]: It’s easily most people there’s a lot of individual variability but let’s say in the six to eight hour range we’ll get benefit some shorter some the immediate release lasts all day

[02:24:46,255]: But you know when it’s on you know when it’s off

[02:24:49,155]: If you forget to take your medicines in the morning but you know you have a presentation at three that afternoon you could take it at two and still be able to sleep that night

[02:24:59,035]: So it allows more flexibility it allows more pinpointing of optimizing it for points the day you want to be using it

[02:25:09,855]: 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

[02:25:19,315]: And others would say we’re trying to treat individuals who have different demands on them and have different patterns during their day

[02:25:26,055]: So there are different philosophies about what’s better or worse

[02:25:29,835]: One of the big downsides of the immediate release though is not only does it go in quickly it tends to go off quickly

[02:25:36,315]: And most people not all but most experience some withdrawal as it’s going off

[02:25:41,735]: 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

[02:25:52,535]: Many people who weren’t even aware of it increasing their energy feel my energy is crashing as I go off of it

[02:26:00,575]: Or many people who weren’t aware that it was actually elevating mood to any extent feel oh my God I’m crashing and I’m crying and cranky and miserable now

[02:26:09,655]: And with the extended release versions most of them go in more gradually so it can be harder to detect

[02:26:17,135]: They last a longer period of the day

[02:26:19,615]: And most of them go out much more gradually at the end of the day

[02:26:23,695]: The one I like the most for a long acting amphetamine product is Vyvanse

[02:26:30,515]: And Vyvanse was designed as a slow release product

[02:26:34,075]: It was designed specifically to be unattractive to drug abusers

[02:26:39,415]: So Vyvanse chemically links the dexamphetamine molecule to lysine one of the amino acids

[02:26:45,755]: It’s a basic component of proteins and 20 essential amino acids

[02:26:50,455]: And if you snort it or inject it you have an inactive prodrug

[02:26:57,295]: You have the list dexamphetamine

[02:27:01,175]: Your red blood cells actually have an enzyme that cleaves the lysine and leaves you with free active dexamphetamine

[02:27:09,255]: And that’s the slow release mechanism is how quickly your red blood cells can do it

[02:27:14,995]: And they have limited capacity to do that

[02:27:17,135]: 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

[02:27:28,175]: For some people it goes in so slowly that they say I don’t feel it

[02:27:33,195]: And also towards the end of the day one of the best in terms of not falling off abruptly

[02:27:41,155]: The potential downside is again that the capacity of the red blood cells is limited

[02:27:45,775]: 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

[02:27:56,615]: Because your red blood cells just aren’t cleaving it fast enough to make more dexamphetamine available

[02:28:03,135]: Almost invariably when I’ll ask how did this compare to your Adderall XR to Enhancy they’ll say smooth

[02:28:12,475]: They’re getting it

[02:28:13,395]: They’re not feeling too jarred too revved up

[02:28:16,575]: Yeah we don’t really have a language for these things right

[02:28:19,835]: It’s the bad speed language before cracked out bad speed smooth

[02:28:29,515]: Because what we’re talking about here is the gestalt of the subjective experience of all these neural and chemical mechanisms

[02:28:38,335]: Very interesting

[02:28:39,195]: Thank you for sharing that

[02:28:40,035]: I know that there are a lot of listeners and viewers who have tried these things or are considering or at one point used them and a lot has evolved in this realm of chemistry for ADHD but that’s very helpful

[02:28:55,475]: Before we wrap up I want to make sure that I ask you about something that’s been on my mind a lot in general but in particular as it relates to ADHD which is time perception

[02:29:06,855]: And I’m basically obsessed with time perception

[02:29:09,475]: I’ve long been fascinated by the fact that we can fine slice time when our arousal is high that’s what presumably gives people the kind of slow motion effect in very stressful environments versus when we’re relaxed our frame rate on life goes down and it’s all very dynamic

[02:29:25,075]: It’s important our brains are able to do that

[02:29:26,535]: But someone recently told me the following

[02:29:30,075]: Her partner has ADHD and she said that the big rescue to their relationship came when they together read a book about ADHD and something in there read something like this that people without ADHD keep track of time whereas people with ADHD don’t but they do know the difference between now and not now but they’re not tracking time

[02:29:56,435]: 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

[02:30:03,215]: And I think this ties back to this interest based attention system

[02:30:07,255]: What do we know about time perception in ADHD

[02:30:09,955]: And by extension do you think that these drugs are working in part to change time perception

[02:30:16,955]: Good question

[02:30:18,255]: So I’d say there’s two different angles and I think I mean the one that’s easier to objectively measure is putting people in a lab and there’s a simple test a time perception test and you interrupt them after a certain period I mean say you’re going to be estimating how long you’re left without interruption

[02:30:37,865]: And people with ADHD measurably they’re inconsistently inconsistent or consistently inconsistent

[02:30:47,435]: So it’s not that they perpetually underestimate or overestimate but they are estimating incorrectly much more often than people without ADHD

[02:30:57,205]: So there’s something at a basic time processing level that’s aberrant there but there’s also getting you know the real world aspect of not paying attention to cues or not noticing other people have left the room or not register you know being distracted which compounds a situation

[02:31:19,735]: And I mean it’s also interesting to the extent to which many people aren’t aware

[02:31:23,815]: So I often ask even though it’s not one of the 18 symptoms are you chronically late to them

[02:31:30,515]: And particularly people who show up late to my office time after time

[02:31:33,775]: So one of my favorite quotes is this person who the session before we had been talking that her boss was giving her threatening notices because she had come in two hours late one day and she had all sorts of good excuses of why she couldn’t get out the door

[02:31:50,675]: And we were talking you know are you regularly late

[02:31:54,535]: No no no

[02:31:55,355]: And I said well why was the boss so upset

[02:31:57,875]: And then I asked well when do you when is the expectation this was pre COVID pre working when is the expectation you’re there when do you usually show up

[02:32:06,135]: Oh well office starts at nine and I’m usually there by 9 15 9 20

[02:32:11,355]: That’s not late

[02:32:13,035]: In her mind it wasn’t late

[02:32:16,135]: 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

[02:32:26,015]: So the second part of the question I’m sure it’s been done and I don’t have the answer whether stimulants or other drugs measurably improve time perception in that laboratory situation of just can you estimate how much time has elapsed

[02:32:42,535]: 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 as to the content of disorganization

[02:33:00,095]: I mean there are some research groups 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

[02:33:14,235]: And there’s interesting I got to do work in the early 80s on bright light therapy for interdepression which has a measurable impact as strong as medication but there is one or two studies done on individuals with ADHD without any seasonal depression without any depression at all and just those same bright lights showing them you know a dose of bright lights early in the morning measurably improved a broad range of ADHD symptoms

[02:33:45,195]: 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 suprachiasmatic 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

[02:34:18,575]: Thank you for those reflections

[02:34:20,375]: And really I want to say thank you on behalf of myself and everyone listening and watching for doing the work you do

[02:34:26,895]: 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

[02:34:39,955]: I’m looking forward to your upcoming book however long it takes

[02:34:44,375]: I’m sure it’ll be spectacular

[02:34:47,315]: When you talk about ADHD you’re able to do it from so many different angles behavioral supplement based nutrition life and organizational life organizational aspects and of course the medication the pharmacology the neuroscience and the ways that those different nodes interact with one another because of course they do

[02:35:08,115]: So I just want to be absolutely clear how grateful we are for you for sharing all this knowledge

[02:35:14,135]: A lot of people struggle with attention issues regardless of whether or not they have a full blown ADHD or not

[02:35:19,575]: A lot of people have been treated for it

[02:35:20,955]: Some people are still wondering if they should be or not

[02:35:23,235]: And so today’s discussion was nothing short of spectacular

[02:35:27,395]: So on behalf of everybody I want to just thank you for doing what you do and for coming here to educate us

[02:35:33,955]: Thank you so much

[02:35:36,095]: I’m gobsmacked

[02:35:36,795]: Thank you for joining me for today’s discussion with Dr John Kruse

[02:35:41,875]: To learn more about his work please see the links in the show note captions

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[02:37:52,815]: Thank you once again for joining me for today’s discussion with Dr John Cruz

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