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

30:27at this oh my god I'm where is everyone I'm still here because I was so intently working on the project. Some people strongly resist the idea that flow and I'm going to butcher the check check cheek some of them. Yeah no one can pronounce this name. Even fewer can spell it so we're okay. Yeah. My reading of when I sort of delved into this I think hyper focus is exactly a flow state because people are describing the same lack of awareness of time and it's always I mean it's a task that's somewhat champs. It's challenging and engaging and interesting it's not just that you know if it were just about enjoyment or bliss you could hyper focus looking at us.

31:13Beautiful flower people don't describe that so it needs the right amount of challenge it can't be too easy can't be too hard has to be something important and interesting to you. And involves you know oblivion not just to time but also to lots of space going around you. So I think they are pretty close if not the same phenomena flow and hyper focus. And some people with ADHD and I think some 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 at the showing up when they don't want to be hyper focused on something or or have trouble engaging it when it would be useful to.

32:02I sometimes use the absent minded professor excuse but only half jokingly there's a photograph that I love of the great Oliver sacks the neurologist turned writer man who mistook his wife or his hat awakenings and so forth people may be familiar with Oliver's work and it's a photograph of Oliver to train station lots of bodies moving around him some blurry so there's motion there and he's standing there with. I think he's got his pipe in his mouth and he's writing outside the train station his bag has fallen to the floor some items are coming out and he's and he was a known and self -professed met methamphetamine addict for a great portion of his medical and writing career and you know sort of alluded to the idea that he had these tendencies and I raised this as an example because I see that photo and I see somebody who's in the middle of the picture.

33:01He's in hyper focus in a very busy environment but he wrote and spent a lot of time with his work in his autobiography etc and talked to people who knew him and it seemed that he was constantly seeking novel environments where there was a lot of stimulation and somehow that allowed him to drop into these tunnels of focus whereas when he spent a lot of time alone there were bouts of focus but the quiet actually became a distraction it was as if somebody in here were speculating. I think about diagnoses but that there's something about external anchors and internal anchors and that the finding that sweet spot is really about knowing ourselves and where we work best at particular times and this is something I'd like to transition into here is talking about the fact that there isn't just one environment that works for somebody it seems like it's often the case that it's certain environments for morning certain environments for afternoon certain environments having returned from vacation.

34:01You can probably see where I'm going with this. What are your thoughts on people trying to with ADHD or not trying to identify sort of best conditions for them and how important is circadian time here. I know you have and of course I mentioned in the introduction that you a lot of background in circadian biology which I think brings in a really additional and unique dynamic to your understanding of ADHD. So many people come to me as a psychiatrist for ADHD are primarily focused on medications and we still know that the stimulants are the single most powerful I mean in terms of extent of symptom reduction overall and in terms of the percentage of people they help there are most potent tool.

34:46I mean the medicines not going to change everything and you need to be focusing on your life as well and I always start with scheduling and many people with ADHD find scheduling anathema that that's you know like the slaves on the galley ship being told you have to roll stroke stroke stroke and what I tell them is that the part of you that's going to help make the schedule that works for you isn't some evil task master. Trying to make you do what you don't want to do it's actually the wisest smartest nicest kind is part of you that's identified what are your lifetime what are your bigger goals how are we going to match what you're doing in the minute to line up with those bigger goals.

35:32So and this analogy isn't perfect but the best when I've come up with so rather than the guy in the Viking ship the person you the part of you that's making your schedule is a mother hand who sort of counting on you. So I'm just doing all the chicks and making things aligned in a shit nestling down and hunkering around you and taking care of you and nurturing you. And with scheduling what I tell people is before you slide in your work or your homework or your school or externally derived tasks I tell people you need to have the four basics and sleep is far away the biggest basic particularly for eight it's it's essential for all of us.

36:15So I'm trying to think about the most critical critical for ADHD and there's particular reasons why it's a particular challenge for people with ADHD but I'm trying to think if I can imagine a counter example I would say all the successful people I know with ADHD I found some way to try to regularize their sleep compared to what it would be if they were just so before essentials I say our sleep eating exercise or some amount of movement because again with the hyper activity there's there's people who consider a desk for 12 hours. Not even getting up for a bathroom break or to eat or anything that's not just bad I mean that's bad for your brain bad for your body and then the fourth thing I put in is a miscellaneous category of me time relaxation meditation I put all those in the same slot maybe they shouldn't and all those need to be in place.

37:09We can talk more about sleep but I'll just say a little bit more about the eating component one of my so we have our diagnostic criteria for ADHD but I had over the years two different real life tests. The office I had was in an old Victorian home so it was a home office the office itself is at the entrance was at the end of a short but very steep driveway so it was a separate door and I would always explain to every person new patient the exact same thing you know there's a house at 45 Hartford the office is at 45 a the entrance is at the end of the driveway and I actually did the data on it.

37:52The only people who ever showed up at the front door the home door with people with ADHD now every one it wasn't specific for ADHD it wasn't completely sensitive so some ADHD people got it right but never. Did anyone who was coming in for OCD or depression or PTSD show up at the front door and I gave the instructions at the same time and sometimes I didn't know beforehand that the person was coming in for ADHD because they didn't know but if they showed up at the front door that always made me you know I better make sure I ask specific detailed questions about the ADHD possible component so the other sort of real life diagnostic test I had if someone during the evaluation would say something like or in a subsequent session it was four o 'clock yesterday and I just realized I hadn't eaten all day.

38:47Ding ding ding ding ding that's I mean I have people who diet I have people have you know fasting regimens or others but they're not forgetting to eat and it's not that everyone at the ADHD does that but either either not getting the right interros receptive cues from your body or not paying attention to them is something that's been a measurable in people with ADHD so having a regular meal schedule so having a regular meal schedule and again getting back to the COVID in workplace if you're you know I had lots of people in tech who really lamented now I have to work for home they were giving me lunch a healthy nice lunch each day at work they're scrambling to even use the home you know meal delivery systems because getting that organized and set up is just too overwhelming for them and again these are bright people who are succeeding in most parts of their life are these people with ADHD sometimes also starting a meal taking a few bites and then going back to work and then like the meal never really never really ends it just sort of fragments into the rest of the day.

39:55That can be one variation but it's often just completely forgetting or being oblivious to I mean the other ways ADHD is can play a role is I was meaning to have breakfast before I left the house but always when it's time to leave the house you forget that you hadn't done this and the kids choose need to be tied and oh do I need a new toothbrush I better go check upstairs before I go out because I'm going to the CVS store I mean time management is a problem with ADHD and executive function problem interestingly it's not one of the 18 symptoms in our official checklist so official checklist is sort of a crude clinical attempt to map out a lot of the aspects of ADHD but it misses a lot so there's emotional regulation problems we know something like 60 % of people with ADHD acknowledge having that emotions explode or come up bigger or stronger and are harder to regulate and that's nowhere acknowledged in our official diagnostic symptomatology.

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42:16Again go to drinkag1 .com slash Huberman to claim the special offer. So we've got sleep, eating, exercise or movement and relaxation. Maybe before we start talking about some medications and some other factors that modulate ADHD if we could maybe step through each of those and you could share with us some of your favorite tools that you give your patients and that you teach online. Realizing of course that each one of those is a vast topic that we could do entire we have done entire podcasts on but I'm curious about your favorite go to tools we were talking about a few of these before we started.

42:57So sleep regular too bad and wake up times. Matthew Walker and his great book on sleep. One of my favorite things about it is he really emphasizes his point that quality sleep isn't just about eight hours. It isn't just duration. It's getting quality sleep and the timing of your sleep is every bit as important as duration. So if you're used to sleeping midnight to 8 a .m. and you're staying up dancing or partying until 4 a .m. and you say, oh it's a weekend I can sleep until noon. You may still get those eight hours but they're not restorative to the same extent as if you had slept at your regular time and it's I mean my my PhD research was on circadian rhythms we had realms of data back then so this is 40 home 30 plus years ago.

43:48We had every bit as much data then that that the timing of sleep is important as duration and yet every public service announcement just says get your eight hours this late. Why are we leaving out this other piece. We've known for decades that people with ADHD have a strong propensity to being night owls to have a different crown chronotype where they're maybe more effective or functional later in the day. We had a tendency to stay up from many years now we've actually known that there's a strongly genetically controlled so we do have you know there are genetic markers affecting sleep timing that are over represented strongly in the ADHD community so some of it is your push that way but some of it is the nature of ADHD that if you know procrastinating is part of ADHD if you procrastinate you're going to push things off till the end of the day.

44:41Some people the end of the day is a better time to work as there's fewer distractions you know if everyone else is asleep finally no one's going to come in and interrupt your work or ask what your thoughts on this project are. But again getting regular sleep and regular and sufficient doesn't mean it has to be what I'd say normal you know if it works for you if you can build your career in your social life around sleeping from 2 a .m. till 10 a .m. every day. I'd say go for it if you can be consistent with it. So what are the things that help with getting regular sleep one thing paradoxically for many people is actually being on stimulant medications so stimulants do have as a side effects some people have insomnia some people stay up later but more people with ADHD tend to either because it's the drug is wearing off at the end of the day and there's some crash and alertness or energy.

45:39Or because they're being more productively and are expanding energy and are more tired at the end of the day or it's just helping synchronize circadian clocks by getting a consistent starter in the day we don't know the mechanism by which it works there's lots of plausible and overlapping ones but again daytime alertness medications can help. Can I run something by you in that context before we jump back I don't consistently take stimulants except caffeine and I limit my caffeine intake to prior to 2 p .m. and I stack it pretty heavy in the early part of the day. But on occasion I'll take 25 to 50 milligrams of well butrin which as you know better than I is slightly dopamine orgic but certainly triggers noradrenergic release so epinephrine nor epinephrine stimulant it's a stimulant.

46:33On the days when I take that which again is very rare and I track my sleep every night I notice a significant improvement in my sleep and significant increase in my rapid eye movement sleep it's extremely consistent so from that I sort of reverse engineered the major effect being nor epinephrine epinephrine I decided well I would do something else that I know raises epinephrine which is I'll do a cold plunge first thing.

47:19So I think there's something to this epinephrine obviously going you know hand in hand with stimulants epinephrine spike early and throughout the day with better results. So I think there's a lot of better rapid eye movement sleep at night does that logically hold free it's just a story but you know I was going to say as both of some science background so I'd say I'm glad it works and what's hard to sorting out is why it's working as one is you know potential placebo effect you're doing it because you're thinking are opening it works good. And two I'd say maybe even more importantly than the placebo effect is the days that you're deciding to do this there's something different about those days to begin with because they're not doing it every day.

48:05So those potential issues aside I'll jump into insomnia and Matthew Walker talks about some of this to me maybe the biggest finding in insomnia sleep medicine in the last 20 years is that almost everyone who has a problem with insomnia doesn't have a problem with sleep. What that does sound like I'm contradicting myself what I mean is the sleep systems intact it's there it's waiting to arrive and put you to sleep each night what the problem and this is from the sleep researchers with at least 90 % of probably more of people who have insomnia problems is the failure of the daytime arousal system to shut off properly.

48:51So normally we have these two mutually inhibitory systems. Awakefulness, arousal system and a sleep sedation system and usually when one turns on the other turns off and with most people's problem with insomnia it isn't that sleep is weak or insufficient or not there it's sitting it's waiting there it's just can't land on the landing pad because you're too arous or too weak. 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.

49:42So for people with ADHD one is you know deciding on what's a reasonable bedtime you know having thinking about the side of time and two eliminating any stimulation or I mean once I exercise I'm a big fan of marathon runner I know you're heavily into exercise as well exercising too late in the evening can elevate body temperature disrupt falling asleep so physical arousal we don't want to be doing a lot of late in the day and emotional intellectual cognitive arousal so the biggest single tool in modern life is do not have your phone in your bedroom and that's hard for lots of people to do but if it's there you're going to be checking it I mean studies have been shown even if you're not checking it if it's there you're thinking about it they're looking at it just having it away out of sight is better than having it visible and turned off to is using if you have someone you're sharing a bed with their family members using them to help reinforce yes it and it's really helpful to talk about this ahead of time because the exact same words can either be sounding like a nag or someone trying to exert their power over you rather than what people with ADHD we know need reminders they know they need something to do with it.

51:11I'm a external structure and if you are on the same page and can have a partner your kid or someone else present a dead shouldn't you be turning off the computer and not into bed right now that can be helpful again it can be destructive if it's not done in a framework where both people are on board and it's not fair to make the other person responsible for your own behavior but lots of people are usually happy to help the person at the ADHD be more organized and they're like that. So we're also talking a little bit before one of my favorite tools for falling asleep is actually cyclic sign I mean there are other box breathing and other techniques to help someone relax.

51:52So we know cyclic sign engages the parasympathetic nervous system our rest and digest system. I mean one of the things that happens normally in the transition every night when you fall asleep is you're going from primarily sympathetic tone to primarily parasympathetic tone. So anything that is strengthening or putting in there already makes it easier. I know you have videos about cyclic sign and I do too I mean my own experience which I was sharing with you before we started talking was not only does cyclic sign help me fall asleep better to actually help me stay asleep throughout the night better.

52:29That's a remarkable thing because many people including myself have very little trouble falling asleep especially given how I stack caffeine in the early part of the day and then stop in the afternoon it allows me to fall sleep within seconds somewhere for me typically around 10 p .m. somewhere between 10 and 11 p .m. is my typical bedtime but then I consistently wake up at you know three in the morning usually get up use the restroom and then go back to sleep most of the time without too much trouble provided there isn't a lot of stress in my external life and provided the phone is not in the bedroom.

53:06But as we were also talking about before we turned on the microphones this idea that our bladders get smaller as we age is is complete nonsense right so that can't be the explanation why people wake up more in the middle of the night as they get older. Yeah I mean some might I mean some it may be a prostate issue with you know clearly that isn't accounting for half the population but I think it's much more the neurologic innovation of our bladder you know all our nerves start functioning not quite as well. And they're just getting the signal that I really need to urinate right now when pretty clearly most of those people don't they could wait but the signals arriving it says you have to and it's believable and you don't want to deal with it if it's you don't want to not listen to it if it is right so.

53:56How much cyclic sign are you doing before sleep and how long before sleep is the cyclic sign done 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 relax that I do I seem like a pretty mellow dude 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 sign and I tried to do it. And it was some days I was getting it in and many days I wasn't getting it until bedtime which is the then I slept really well till I was around 40 and not so well the next 20 years both the mostly with the trouble falling asleep even though I knew relaxation techniques and others so I wound up just consistently doing it to do it more for the general health and I do have slightly elevated blood pressure and relaxation and to see what effect it would be.

54:56I 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 to go back to the lowest number because again everything we're trying to do is decrease arousal if you have a timer on it and you do it for five minutes and then you're working up you're reversing or mitigating some of the benefit. So I my recommendation is do it for five minutes about but do it by counting reps and don't focus or you know if it's six minutes of it's four I mean there's so many aspects of this and we know the exhalation has to be longer I was trying to find is you know is anyone systematically you know is a four second exhalation better than 10 versus six and those studies would be so simplistic and easy to do but you know there's lots of things that I'm going to do.

55:56So we're doing the variables that we can play with to see what's optimal. I don't think we know it all it's optimal but we know what's good enough to work. Delayed to hear that it's worked so well for you I am as people know I'm a huge fan of the physiological side and I take no credit for having discovered it it was discovered by physiologists in the 1930s point that I shared with you is that prior to trying cyclics I am sighing at nighttime I was waking up virtually every single night once a night to urinate. And in the 18 months 20 months since I've been doing it I think it's been a total four times that I've hoken up during the night.

56:33Yeah fantastic. So we're talking about sleep you mentioned earlier encouraging people with ADHD or who think they might have ADHD to keep somewhat regular eating schedule or at least to make sure that they're eating. Yeah and to not let their meals get fragmented into starting a meal then finishing it later like have for some people it's breakfast lunch and dinner for some people like myself it's lunch snack dinner whatever it is keeping a regular schedule. Exercise aside from encouraging people to not exercise too late in the day. Certainly not caffeine and exercise late in the day. Are there any data about specific types of exercise being better for ADHD independent of effects on sleep I realize their hearts it's a part.

57:24Yeah there's a few studies looking at acute a aerobic exercise. Hard of it is that it's hard to study people when they're exercising during many exercise. I mean not gonna wire someone up when they're swimming for example. So there's not a lot of studies in any one approach and there's so much diversity that often it just gets lumped together. So there do seem to be some acute effects of measurably improving some of the executive functions associated with better attention from acute exercise and there seem to be some more general or longer term benefits from people who are consistently actively exercising.

58:05Having you know being able to concentrate longer being able to switch of attention more appropriately or effectively and there's a huge body of sort of clinically literature of patients reporting. You know I know I feel much more alert the day I get my workout in the gym and I feel better or the week I took off from that was a big mistake. But I would say identifying at what's the most valuable or what's the best duration I've ran through the data about a year or two ago and it's I could say that we can't make any conclusions and I would say at some level try it and see what works for you and that's what's important it doesn't what works for everyone.

58:48Is there a relationship between ADHD and addiction because of the impulsivity component? Yes and so the answer is and these are really rough statistics I actually one of my pet peeves is people who quote oh the rate of this is 27 .43%. Well it might have been in that study but that's looking at one population at one said it so I use ballpark figures the ballpark figure is Americans in the last 20 years more than that about 20 % of Americans run into some addiction substance addiction. Problem either alcohol or drugs. People with ADHD have a rate that's almost double and it's higher in men than in women double almost double almost 40 % risk and that's for substance abuse not substance behavioral addictions.

59:39Yeah 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 pet peeves there. However kids who are put on stimulant medications when they're young and I should say the stimulants themselves do have a small potential for addiction but putting kids on stimulants pretty much normalizes the rate of addiction problems. So protect half it protects them. This is a really important point that I think maybe we just hover on for a second because I think many people including myself assume that well if you were you know putting these kids on amphetamines of which you know many of the medications for ADHD are that we're creating kids that are addicted to amphetamines or to a hyper stimulation period.

1:00:32But you're telling me it's actually protective to put kids with real ADHD on medication for ADHD. Yeah I can say not absolutely every study is 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 us when I said it was a yes and it seems to be that it's not just the impulsivity traits but some of the inattentive ones too. You know if your teacher is lecturing about the risks of alcohol or this and this and you're zoning out the window and looking at the plane flying by you have less pertinent information on the topics you may be less attentive to the negative effects that other kids are seeing among the classmates who are stoneers at this age or X Y or Z.

1:01:26So it seems that both the inattentive sets of ADHD symptoms and the impulsive you know thrill seeking not weighing the consequences of heavily are all contributing to this heightened risk. 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 that's involved in executive control and directing attention and maintaining attention and avoiding distraction this kind of thing use dopamine and epinephrine and nor epinephrine at least to some extent. And we know that people with ADHD are capable of focus as you said it's a it's a failure to direct that focus maintain etc.

1:02:17So I've heard from you before this discussion that you know people that you know tend to drink lots and lots of caffeine or who can drop into an activity but have a lot of distractability that you know they might have ADHD. So what I'm imagining here is that the threshold to get dopamine epinephrine and nor epinephrine released is either much higher or more complicated for people with ADHD. And so what they're seeking is these catacolomines these three chemicals dopamine epinephrine or epinephrine 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.

1:02:59And I'm raising this now because we're talking about addiction addiction is a you know pursuit of things essentially and I guess what I'm saying is it seems to me that the model of ADHD that we hear. What I'm here about is that you know people can't focus you know their dopamine circuits are all out of whack and then you put them on this dopaminergic drug and you know basically you get them addicted to that tunnel vision or something but I have this model in mind now that what we are all seeking is to have portions of our day where we are directing our focus towards a meaningful bill the things that are you know generative in our life work school relationships etc.

1:03:38And that whether or not it's pharmacology or exercise or or what have you that it's just about getting into this plane of consciousness and I say that no woo or abstract terms is that right I mean are we really talking about here is a failure to access enough of these neuromodulators and these medications which we're about to talk about are really about putting us in the realm where those neuromodulators are just more accessible. I'll just say I can go with that. Okay well you're the expert I mean I'm putting this together based on kind of what we're talking about it like getting enough sleep to me is a way of being able to have enough arousal during the day.

1:04:17You know exercise or these medications just different ways of being able to access arousal like if you don't sleep you can't access arousal during the day so okay well that I'm going to hold that model in mind and I'm going to keep testing it to try and destroy it as we go forward. Let's talk about the medications since you raised those and you know the first one I ever heard about was riddle in. Let's start with riddle in how often is riddle in used nowadays and what is riddle in doing in neurochemically and what are your thoughts on riddle in as a useful drug for childhood and adult ADHD and I'm happy to repeat those questions.

1:04:57So riddle in is or generic methylphenidate and there's dozens now of slow release versions and there's even a patch skin patch instead of a neural version. Our definition of what a stimulant is is really squishy and vague and it's broadest sense it's any drug that has an effect in the body like the sympathetic nervous system which is a norup and ever driven fight or fight arousal system. So by the elusive criteria caffeine is a stimulant well butions of stimulant even though we classified as an antidepressant some of the decongestants are stimulants but more often when we're talking ADHD medicines we're using stimulant more specifically for amphetamine based products like Adderall and Viavance and again there's a host now of newer branded extended release forms and methylphenidate and we lumped the two together.

1:05:57Probably most ADHD experts agree with and this is where I'm going to be disagreeing with most of them. I don't consider riddle in a full stimulant so the neuro pharmacologist differ a little bit but amphetamine is a strong dopamine and norup and ever reuptake blocker so it prevents what's already been released from being taken back up so more is available longer but in addition to that amphetamine is a pretty potent to say. The vesicle manipulator so it's actually forcing a bigger release from the vesicles when they're synaptic to be released so it's not just that the signal lasts longer and is stronger because of that it's a bigger signal depending on what study you look at most of the studies suggest that methylphenidate is actually a pretty weak vesicular manipulator and some studies don't find any impact there at all which means if methylphenidate is basically a...

1:06:55norup and ever endopamin reuptake inhibitor that's what well butren is that's one or you know it's... and so it's a 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 at all products and metamine and methylphenidate products here and say you know they're here because they work better. This is you know success in reducing ADHD symptoms and all of our strutera at the auto -moxetine while butren I use symbolta lot, medaphanel, gronfocene all these other things are down here as less effective but if you actually look at any of the plots that I've looked at and separate out methylphenidate is actually closer to the pack below it's that amphetamine products are head and shoulders above everything else.

1:07:54methylphenidates usually at the top of the rest of the crowd but if you're just looking at the data objectively there's a clear decision point. So in terms of efficacy amphetamine products are stronger but in terms of some of the side that side effect that I worry most about it's not at all common but it's one of the horrible ones is amphetamine and dosycosis. Now that we're finally looking at that a little more closely because for years ADHD experts have said yeah it's really rare let's not look at it at all that's not pay attention move along you know don't look. With amphetamine et al products and that's probably dose dependent but it's close to one out of 500 people and what's going off on a tangent here but I'll keep following it because it's an important tangent.

1:08:44It's only one out of 500 people that's uncommon but this is a really bad condition because so amphetamine induced psychosis is a schizophrenic like picture usually someone is really paranoid really worried that their friends are manipulating them or the place are spying on them. I mean if you drink too much alcohol you can be batshit crazy and that's a highly technical term there you can be out of touch with reality you can be hallucinating you can be saying all sorts of nasty things. But if it's alcohol induced you fall asleep at the end of that night you wake up the next morning you may feel horrible with a hangover you're not hallucinating you're not psychotic anymore hopefully you're regretting what you did probably not remembering much about you do people will let you know with amphetamine induced psychosis on the other hand classically and characteristically and what I've seen clinically it continues for days weeks or months.

1:09:44It's after stopping the medication which means we are we've changed someone's brain and we don't have lots and lots of data and it's actually only come to us because people are concerned about marijuana causing a similar picture so now we're studying this a little more with amphetamine induced psychosis about and these again rounding from different studies about 20 % if you look 20 years out about 20 % of those people are in a permanent psychotic state still. So again it's uncommon but it's such a bad outcome that we really should be alerting people to it and I've been I saw much higher risk of this for I can get into it if we need a reasons in my population in San Francisco but I've had people coming from all the most prominent ADHD clinics over the years who just moved to the area and when I say this give this is my introduction to you know I'm happy to continue on this but are you aware of that?

1:10:43I'm not sure to a person they said no one ever told me that now maybe they've ADHD and weren't listening but it's so uniformly consistent that they didn't hear or know that that was a side effect. And one in 500 isn't a trivially small number? No it's not trivill and I mean why I got delirited to it is my rate in San Francisco is actually higher than one out of 100 and so I'll go into I think a couple different reasons. One is I worked with a lot of HIV positive men and we know HIV particularly in the days before we had effective antivirals is a virus that goes to the brain and effect and there's a HIV induced dementia so probably some of these people had brains that were compromised because of that more vulnerable to a high incidence of methamphetamine.

1:11:37So methamphetamine street speed is a chemically different molecule than amphetamine as an extra methyl group and an extra methyl group can mean a lot. So it's a cousin but methamphetamine we know has higher rates of psychosis higher rates of addiction tends to be more rewarding but again in that population and many of them would hide that history from me but I think that the very first person I had with them that amine into psychosis. The guy in his 40s HIV positive for years this is 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 at a full blown psychotic episode where he is dead a diet of a heart attack 10 years earlier.

1:12:27He was threatening his mom because he believed his mom had poisoned her he flew to Rhode Island where she was living he was making threats from a pay phone and because Rhode Island so small he was actually calling from out of state so it's a federal crime he got thrown in federal prison for this and and he stayed psychotic for months after he wasn't using any but later turned out he had had a psychotic episode 10 years earlier on street math which he lied about. So the other high risk group I had was I was known in San Francisco as someone who worked with adults with ADHD at the early stages of recognizing ADHD so and I was comfortable with the broader range of stimulant dosages and many providers are so I had people who had and they were all young white males straight males who had history and I don't know how many of those demographics are relevant.

1:13:26But who had histories of taking stimulants having a psychotic episode again being really paranoid all and again the numbers aren't huge but at least five people with this general profile. But even though they were paranoid even though they were severely impaired enough that each of them wound up in a psychiatric inpatient hospital which is pretty hard to get into in this day and age or even 20 years ago. They all liked something about the experience enough that they all wanted to get back on and all of them knew enough to lie about this past. So they didn't tell me about you know they presented all of them also had ADHD you know they presented with ADHD they'd say I'd been on stimulus before and you know I'm not working with that doctor because my insurance changed or they had moved to the area so they they gave plausible histories and most of those within a month or two of restarting it wound up back in the psychiatric hospital.

1:14:27I had one guy right computer programmer late 20s calling me from inside the psychiatric hospital to try to get me to prescribe more adderol to him. And not only that he had convinced his inpatient psychiatrist that this was a good idea that this was important to treating as ADHD and helping him retain his job. Wow. So these are as you said straight white males who have psychotic episodes on their ADHD meds and continue to seek those meds because they quote and quote like the experience it feels like a manic hot. High the dopamine or high dopamine or just state. Yeah and I'm and you put the word mania in their manic and lots of people define this is and that I mean induce mania rather than psychosis.

1:15:25I don't because one is uniformly and maybe other people are seeing more that these people were paranoid they were worried they were anxious they were delusional but they weren't overtly enjoying it. And having a great time they weren't saying I'm going to party with all you friends and I'm only worried about the people there. And yes they were talking more loudly they were sleeping less which is could be characteristic of mania but there is no positive affect that I or police reports are often families give you extensive history of everything was going on that there is nothing you for if they were describing about it.

1:16:07I 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 it didn't register properly it's not clear but they tend not to recall the paranoia and by paranoia it's persecuted to our delusions. I have people who assaulted family members thinking that they were being spied on manipulated when the parents trying to take care of their kids. I'd like to take a quick break and thank one of our sponsors element element is an electrolyte drink that has everything you need and nothing you don't that means the electrolytes sodium magnesium and potassium in the correct ratios but no sugar.

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1:18:03What are the options for people that think that they may have ADHD let me phrase it differently someone comes in and you they have you know say an adult they have five of the 18 well criteria they they meet the criteria for ADHD do you tend to well after telling them about sleep food exercise and relaxation after that squared away if the decision is to Medicaid do you just and assuming they're not on any other medications which cluster in this two sets of clusters that you described before the emphetamine type the at or all vivants etc. versus the I realize you put riddle in at the top of the bottom cloud well but you try and riddle in Modaphanil you mentioned symbol to which cluster do you go to first.

1:19:04I mean some of this is just individual style rather than intellectually thinking one is better not and my style is usually to listen as closely as I can to what the patient wants that doesn't mean agree with them but to to explain in as much detail as I can what I perceive the risks and the likelihood of those are and what I perceive the benefits to be for years just statistically I had many more people who are on non stimulants and stimulants compared to the general ADHD population and that's even accounting for by many variables I had I've always worked with a lot of people are in disability from Medicare I also work with people who are on Medicaid in the cities insurance before Obamacare happened so I worked with not entirely but a skewed more dysfunctional more severely afflicted population which again you would think would be a better way to do it.

1:20:02So I'm going to give you a better match for the more powerful drugs I'll jump back that this is actually is a situation where we have more powerful drugs so often when I treat people at depression I'll try one or two or three antidepressants and say well give me something that's more powerful and with depression maybe we can put ketamine out of the picture and I know this is a side issue but all our antidepressants seem to work equally well we don't have potent antidepressants and non -poortment the PCAD FDA approved it works in a certain range of likelihood but with the stimulants I don't think the base products really are more powerful and more so than with depression or many of our other conditions where it's more a categorical this will help or not as long as you're above a threshold there's a more linear relationship if a little bit of well -bearing helps a lot is likely to help more I mean you might start getting more side effect issues and there may be good reasons to not keep going up but there's a more linear dosage results relationship.

1:21:08Do you worry about strain on the heart with emphetamine products just even if it's relatively low dose over time just you know that's just the strain on the calcium channels and on the heart you know is it true that stimulant based medications for ADHD can quote unquote weaken the heart? When you use that term I was I was talking through a hand about running marathons and when I ran 100th anniversary of the Boston marathon they had some the medical literature from the previous decades and one of the medical warnings was you know maybe you could do one or two marathons in your life but don't do more than that because your heart will wear out and you know I've run 100 in my heart I think is still beating so we know things we thought we know at one point.

1:22:02Common cardiovascular effects of not just the stimulants but the non -stimiancid are affecting norup and so well butren, symbolta, marathonol it's less clear and we can get into that when I talk about marathonol but clearly methylphenidate emphetamine. Unaverage increase at therapeutic doses increase heart rate a few points increase blood pressure a few points but part of that obscures that probably 80 % of people don't have any change and maybe 20 % have a maybe a more slightly significant change so we know that there's some impact there. We know there's some people with extremely rare genetic underlying conditions usually related to the neurologic wiring of the heart who are particularly vulnerable to dropping dead from a stimulant and almost every year there's a well -trained athlete either professional player or marathonol high school or college player college you know who will take cocaine take riddeline take prescription stimulant and drop it.

1:23:09So we know that we're not dead of a heart attack. The risk of that so uncommon this is 15 years ago when add or all XR came out the Canadian government was worried enough about this risk that they banned add or all XR for almost a year and because they have a comprehensive medical system that could look more extensively at the numbers and this is looking at kids. The percentage of kids who drop dead with add or all was tiny and not just tiny it was lower than the kids who aren't on add or all who dropped out of a heart attack so part of it is if you're in this rare genetic condition almost always there's family members or you've had some other you know death there's syncopal episode where you passed out.

1:24:00So history taking of the individual and family history and if you're at all worried or concerned you can do EKG's 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. Absolutely do a thorough history absolutely do a thorough family history if there's anything of concern or if the patient's anxious about it get an EKG but other than that these should be generally safe for most people's hearts.

1:24:45So 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 year of treatment do we see rates of heart attacks do we see rates of strokes do we see rates of dangerous arrhythmia's 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 and year two out the more recent study looked as long as 14 years out and there they found measurable statistically significant increase in rate.

1:25:29So there's a lot of 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. So for most people it's not a risk I mean on the other hand if you start these medicines when you're 10 or 20 and maybe on them for 60 years we don't have we don't know whether potentially more people are getting into more trouble. So if somebody presents as having ADHD as an adult and they've never touched stimulants and there would you start them on riddle in well butrin or at or something in the outlaw advance for bringing me back to your question.

1:26:23And I'm going to jump it through in that sort of qualifying phrase never been on any stimulant in their life or childhood or something. And what I would say is lots these drugs are fairly common in our society both illicitly and illicitly. I mean we know lots of kids lots of adults with ADHD share their medication lots of people have tried these things even if it's just once or twice and that itself is valuable clinical data you know if they felt too revved up from it. So if they have I try to find out what dose was it what did it do for you what good things did it do for you what bad things to do for you.

1:27:03So my presentation is usually you know, adderals likely to be the most strongly effective or more often are using by -rants these are the other options but adderals also has again greater rare but risk for these bad problems. What does that scare you some people are petrified they're not going to go anywhere near that some people say yeah I'm not that concerned about it. And most people do come in with some friends at work family members X Y or Z you know they think they know what the drug is likely to have as an effect on them. And I tend to at least as a starting point listen to that and now I mean there are certain reasons I absolutely would not I mean my worry again I saw more of it than I think most people on a higher rate with the amphetamine and Cercosis but a friend from college was just trying to refer friends 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 North New York city doctors but the psychiatrist kept him on adderals I absolutely again the likelihood of recurrence seems so high that if you want to go back to the doctor.

1:28:32You have a family history of schizophrenia psychosis or you've had any experience of it. I would not prescribe the stimulant of an end of the mean based stimulant could we go so far as to say and I suspect the answer is no but because nowadays we're hearing more about the possibility I want to highlight possibility of high THC cannabis causing psychotic episodes this is something I've stressed on this podcast on social media I took a lot of heat for this from the church. I'm not saying that's a professional press and then ironically they're now putting out information that essentially speaks to the same I'm not saying this happens in everybody but there's certainly a possibility there.

1:29:14Would 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. Yeah I mean you could actually play that both ways I mean you could claim that if there have already been on an agent without developing psychosis then maybe they're more impervious to that as a potential side effect or where you're coming more from is if we're already on one agent that's pushing them that direction why the heck would you ever add another that could also. So I mean my approach clinically would be more what do you think the marijuana is doing for you and might it be more helpful to just clear that out of the picture before we add anything new onto it but depending on what they say or don't say.

1:30:05So my reading of the data is very clear that there is some I mean there's even at low THC there's some risk. Is it you know reefer madness that everyone I've said joint is freaking out clearly not but again it's much more potent than it was 10 years ago I guess. Yeah 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. Whereas when people use inhalation as as a means to deliver it seems like they they kind of find the right plane without going overboard more often than with edibles in any case.

1:30:44Well another big factor is that CBD actually seems in some studies to have an anti -psychotic effect so you know maybe strains of marijuana 50 years ago that had a whatever nature thought was a more balanced view had less of a risk but now that you can get pure. THC products and I'm sure you've highlighted that a big problem with this whole industry is even in Colorado which three years ago is 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 so. This is not a well regulated industry even though. States are trying to regulate their industries so you may not know what you're getting CBD again may have some protective effects are getting pure.

1:31:34And higher potency THC may be particularly undesirable so in my own. YouTube podcast series research lots of subjects and most of them I wind up saying we don't have a lot of data on it and there's not a lot of data on marijuana it's the one. Subject I've actually changed my mind from reading was out there and for years I would tell people. Because being in San Francisco even before the wave of legalization lots of people are using lots of people felt to help them. And what I would tell them is the data we have and these are from everyday users is that there are measurable you know that the. Characteristic of the classic stoner has a grain of truth so measurably lower motivation or organization of thought lower energy are strongly correlated with daily marijuana use.

1:32:30Why would anyone with ADHD want any of that going on that seems like a perfect misfit or accentuating what's not working right. Over the years though I had a handful of people would swear it worked better for them than stimulants it worked better than the non -stimian alternatives clearly not everybody. And when I looked at the data there is actually some tiny studies you know there's some that are funded by marijuana organizations so that. Doesn't mean they're wrong but it's harder to evaluate how objective they were but there's some research that suggests there is some sub segment and I don't think it's eight people with ADHD in general.

1:33:13But some subset of that population who may actually do better and most of the time they were looking at marijuana rather than pure k .c. And what I was going to say is there's probably at least seven or eighty other psychoactive components to marijuana not most of them is in high concentration is a THC or CBD but they're out there maybe they are more important to even lower concentrations. I've heard this that for some people cannabis can help them focus and I'm certainly not one of those but it certainly is interesting. As long as we're on cannabis excuse me as long as we're discussing cannabis neither of us are on cannabis to my knowledge maybe I could just ping you for kind of the relationship between various compounds that people use that are available over the counter or with you know sort of online access to these compounds and ADHD symptoms specifically.

1:34:15And then at some point I'd like to return to the the amphetamine based drugs so let's just start with nicotine so these days there's increased use of nicotine pouches gums not just smoking vaping dipping and snuffing. And it's certainly a stimulant and certainly a lot of people in particular young males are using it more often this the traditional media is now trying to create this kind of picture of nicotine being part of the kind of wellness and fitness community but in my observation many many more people outside of the that category are using it so what in your experience happens when somebody with ADHD.

1:35:01But to assume they're not medicating in any other way starts dabbling and nicotine use and let's assume they're going to do this in ways that do not cause cancer because the smoking dipping vaping snuffing part is what causes the cancer let's just talk about the compound nicotine.

1:35:31And so if you're doing it better there is actually a major pharmaceutical company who is developing a nicotine receptor products 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 some other side of fact it's we're throwing out there that although nicotine in many ways acts like a stimulant it actually is moderately unique. It means one of a kind so I can't say I can't modify it in any way unusual maybe not the only one unusual in that it both arouses people and reduces anxiety simultaneously not too many most of our stimulants are again banging away at the sympathetic nervous system and that's banging way I'd go to rouse and better out so anxiety so nicotine again seems to be both calming and helping alert or focus people.

1:36:32And 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 not probably definitely are and if it's affordable because some of these products are pretty pricey at least the chewing homes or the nicorette that was used for helping people with smoking cessation I have some people who feel that it's been important and useful part of their regimen. I have some people small numbers who prefer it to any other medications and almost know again other than sort of the basic neurophysiology showing that it can have beneficial effects on executive functions there's no research at least as of a year or two ago whenever I did my toe not my anything else into the snuff.

1:37:25Look into it there's no you know clinical research showing does this help or not help. What about caffeine and in particular energy drinks these days there's just seems to be an explosion of drinks that include caffeine but also fairly high dosages of things like touring alpha GPC thinning you know so it's irising. So you know things that are thought to generally amplify the production or release of neuromodulators like dopamine a state of calling and so forth. So the epidemiologist 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 outlaw caffeine so lots and lots of people use it.

1:38:18And this is a gross oversimplification but this is what I tell people even though it's most widely used if you use it as an equivalent dose to our stimulants I mean both essentially we're using it at a lower dose level it's a pretty lousy stimulant I mean separate from that it's working primarily on adenosine and indirectly working on dopamine but associated with higher levels of anxiety higher levels of jitteriness higher levels of cardiac toxicity. If you were to use it at a equivalent dose but most people are using it at substantially lower dose and the ADHD experts sort of historically have fallen into two different camps some of them have said it's going to interact with your stimulants or other medications it's complicated we don't want it messing up the picture stay off of it and the other half say it's a stimulant you know lots of people are using it with these other stimulants.

1:39:17Both the full blown stimulants and non stimulant ADHD medications and as long as you know it's part of the picture and you're trying to be constant with your dosage or aware of it then fine and maybe it helps you get away with the lower dose of the prescription. The one little piece I'd add in there is that often you don't know what dose you're getting so people have the common 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 but lots of people have the experience go to their local Starbucks or something say well that feels way stronger than usual and then invariably they say oh that must just be me I'm more anxious already I'm jacked up or I'm not going to be a doctor.

1:40:01Because they think Starbucks you know seven billion stores around the country everything is automated and precise they must be Starbucks isn't you know they control for the aroma's ticity they how many minutes each being is cooked which side it gets flipped over on they're not controlling for caffeine intake which is wild. So 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 threefold difference. Wow and that's Starbucks who knows what smaller so so one is you may think you know what you give and maybe you know the the bane of coffee drinkers and maybe sank in a teaspoon that you're dissolving maybe the most consistent there or but one of the risks with caffeine and what pretty much any over the counter drug as you may not know what dose you're getting.

1:41:05Very interesting I mean I as said several times in this podcast I think caffeine is a wonderful drug mostly because I love the things it comes in your brahmate being my you know preferred source of of caffeine but also coffee and it certainly increases my focus it's a vinauropaian though you know two sips too many and I can start feeling myself veer toward more lack of focus it just doesn't seem to have a very. The pervasive effect and and dosing it on an empty stomach versus after eating it's it I mean I'm not that precise about it but I don't see it as a very reliable stimulant 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 I think most people are similar they drink it to feel.

1:41:56Yeah I know lots of well and there's also lots of cultural and habitual you know if it makes gives you your warm fuzzies or puts you in the right mode or you're sure you think you're more alert or you're listening to your favorite. Newscast in the morning as you're drinking it that was adding to its effect in terms of combining with other over the counter things there is some study looking at caffeine and healthy a need 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 healthy and in dosages but it's.

1:42:43I'm not aware of any good research done with adding all the other things that are currently being added to and some logically maybe doing something some maybe irrelevant some maybe more detrimental. Elfianin certainly is being added to a lot of caffeine containing drinks because it seems to take the jitters of and the assumption being that people can consume more of that. That drink has a consequence a tiny bit of evidence of success it may both you know dampen down you know help with anxiety but it may directly have some beneficial cognitive executive function benefits itself. This is in keeping with the green tea hypothesis which I believe green tea is enriched with the inine.

1:43:28You 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 that EPA omega 3s for depression. You know those studies were starting to come out we were talking about those studies and nowadays I think while there's still a little bit of controversy out there about fish oils I think most everybody believes that getting high quality omega 3s from good clean sources including fish oil is mostly beneficial or beneficial. What about fish oil for ADHD in particular and what threshold dosages are relevant here.

1:44:21So just as with the fish oil for cardiac benefits you know there was a time period where the first few large and they were pretty large well done studies so benefits for cardiovascular health. The more recent studies with fish oil haven't shown an effect or benefit and strangely to me and not very scientifically. The cardiology community sort of looks at the more recent ones and say okay that's what it is well you have to reconcile all the data in the pool. The ADHD fish oil story is a little the opposite and it's been almost everything with ADHD it's been kids that have been most strongly looked at.

1:45:00The first few studies with fish oil and kids didn't show any benefits at all and then subsequently there have been several studies that looked at benefits. And again in the field jumps to the second set without reconciling well how do we you know do it good meta analysis with everything in there or so and I haven't looked closely enough to know you know where their methodological differences dosage differences population differences that matter. I'd say unless you're taking so big a dose that you're probably at risk for heavy metal poisoning which is a possible issue with big big doses of fish oil.

1:45:41I mean most of the recommendations are in the range that it seems and I'd say the depression has been the most consistent field and not that doesn't mean every study there has been positive either but the most consistent field for mental health benefit or a health benefit. And there the recommendation is usually target about a thousand milligrams of EPA of icosopentanoic acid a day. If you're seeing some benefit but it feels like that there's more room for improvement so this is my amount of people and you could probably double it reasonably. I mean some of the dramatic the dramatic studies looking at fish oil for mania people hospitalized with it but and they use dosages as high as 7 ,000 milligrams a day to treat mania.

1:46:33Yeah and I'm not study I think was a Harvard area clinic that was doing it the results were so dramatic that they ethically had to stop the study before its intended completion because the benefits seem to be so robust in the fish oil group compared to that it was unethical to not put everyone on fish oil. That's a lot of fish oil. So it's a lot of yeah you probably need to get it in liquid form to make it you know so it wasn't so expensive but I find this recency effect incredible that you meant you know which you mentioned a few moments ago that. And I think this is helpful for people to hear certainly it is for me you know we hear you know studies over the years of explored fish oil for cardiac benefits and then more recently as I understand you know these are not.

1:47:22But I think that's not been demonstrated and there seems to be a focus on the recent studies as if the old one stone exists that's essentially what you described for both cardiac and ADHD I think is really important we hear this with alcohol to have been involved in this debate I you know I don't care if people drink one way or the other provide they take care of themselves and others and if you're an alcoholic adult don't drink and if your kid don't drink but you know people want to drink a few drinks a week I don't have a problem with it but it's remarkable that every time a study comes out showing a mild benefit of.

1:47:52Modern alcohol use that seems to be the highlight and then everything else is forgotten and the inverse is also true one we think that the meta analyses would include all as many good studies as possible but I think it's important to understand that people hear that that's not always the case just because there's a meta analysis doesn't mean that it included all the relevant studies so I'm just restating thank you. I make it a point to try and get one to two grams of EPA per day just as a general mood you know I'm not clinically depressed but just to support my mood to support focus to support well being including the other thing that I think is understudied with the official issue is that and it's a Harvard guy who has a proprietary brand of purified EPA.

1:48:40The pushes it so in nature whether you're a whale or a human or a butterfly or maybe not insects I'm not sure that cost the mammal bird dropped all kingdom you may get threes are found in about a two to one ratio of EPA to DHA I cost a pentatonic acid to co -saxanoic acid and what I tell people is I think mother nature is probably smarter than any Harvard professor and the brain particularly is high in the brain. Brain and brain membranes of DHA so I don't see some people seek out EPA purified or so only EPA brands that to me doesn't make a lot of sense so I would I would say we can still counter to the numbering based on about a thousand milligrams of EPA but don't worry that you're getting about 300 400 milligrams of DHA and probably that's better for you.

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1:51:04You're one of the first people that I ever heard discuss the gut microbiome and ADHD. This is me giving you credit for being way ahead of your time. I don't know how you are receiving praise especially on camera and with microphones but I just want to say that you know it was over a decade ago that I heard from you about EPA and fish oil for depression and other things about circadian rhythms an area that I'm familiar with. And just the critical importance of circadian health for everything that we're talking about today and more and on and on and so you know again thank you for raising these points even if they turn out to be minor effects.

1:51:46I think nowadays we hear about the gut microbiome. I may have actually heard the words gut microbiome first from you. Gosh yeah that would be well over. There'll be almost 20 years ago. Remarkable so gut microbiome what do we know about the gut microbiome and supporting it an ADHD. I'm going to kind of pass on that by just saying it's complicated and probably important and so many variables that it's hard to know what's really valuable in a day to day real human living perspective. Do you do anything to support your gut microbiome just in with your knowledge of of a of the relationship between gut and mental health does it impact your behavior at all in terms of choices.

1:52:42Yeah only to the extent of trying to have a very diet and eating it somewhat regular interval intervals but not more specifically great. That's where we're at where that's where we're at before we go back to some drugs. I wanted to ask about behavioral tools for ADHD. I've seen some of the literature claiming that certain video games might actually be useful for training focus. I've managed to find a few papers that talk about focus and meditation tasks that kids in particular but adults may be able to get better at. Are any of these brain training games to get people better at focusing are any of them known to be worthwhile according to like real data or clinical observation.

1:53:34So I'll start for by stepping back a little bit and broadening it. I'll get to the video game there's but one of the effective approaches that helps with symptomatic reduction with ADHD is cognitive behavioral therapy. So that's a form of talking therapy and my quick overview of it is that it focuses on actions thoughts and feelings and the humans can have direct control of their actions and thoughts not too much over their feelings. But all three are affecting each other and the traditional CBT was developed by Aaron Beck to treat depression probably 50 years ago. Maybe longer 60s I think late six.

1:54:18Anyway, on the surface it's a horrible match for ADHD because we know it requires lots of repetitive boring homework doing the same thing 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. So lots of people still think talking therapies are sort of up here doing something and chemicals and medications are really changing the brain.

1:54:59And if your thoughts are changing, if your behavior is changing your brain has changed that's only place that thoughts and behaviors come from. But there have been at least two groups, Mary Salanto's in New York and Harvard group by I'm blanking on his first saffron and some other rams, I had Pennsylvania developed approaches using CBT techniques specifically designed for people with ADHD to help overcome some of those hurdles and barriers. And both of them encourage actually the use of medications and combination with it. So because many people with ADHD are too unfocused to unable to sit down and do it.

1:55:41But these are approaches and both approaches are amazingly similar although devised completely independently. At the core of both of those approaches is having a system of scheduling each day. That doesn't mean micromanaging each minute, but it's having the essentials in place, having blocks of time that you know what you're going to do. And having a task list in combination with that and ways of learning to prioritize and move things supper down. And again with ADHD being interested in rather important, driven you may have a task. I mean you probably have 17 has lists, one's new coffee, one's at the grocery store, one is having one consolidated list because if it's everywhere, then it's nowhere.

1:56:28And two is the simplest triaging or organizing approach is having the things that are both urgent and important. So the half to happen today, those get in the A category. The things that are important, but aren't as urgent are the B category and all the other things are the C. And one of the temptations that people with ADHD have is, I need to be productive. 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.

1:57:10So 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. So the and there's much more to it so that CBT approach can work with decreasing procrastination. It can help with structuring your own workspace given that you probably have much more trouble doing that and not doing it spontaneously. It's how to eliminate distractions and modules on even extending your concentration time. So the answer with the video games there is one product that's actually been FDA approved for use in ADHD and the really important thing to remember there is the FDA's system for addressing medications is much more rigorous, much more thorough.

1:58:10You have to demonstrate it really works and does something when the FDA approves devices basically they're saying it's not going to kill anyone it might help tremendously, but having the FDA imprimatur for that doesn't guarantee that or mean that at all. Do you recall if the study of that device or the study that video game has a conflict of interest was it run by the company? Yeah, yeah, so almost all of them have been run by the company. I mean, it's good people at UCSF who are at least partly involved in it. Oh, is this Adam Gazelle? He's I think so. Yeah, he's I should just say that I've followed his work for some years.

1:58:51He's a neuroscientist. I know people who have been in his lab. He's known for doing very, very high quality and stringent work. Their product and some of the others can clearly show you get better at their product and you get better at tests that look exactly like their product. But in terms of real world, how much is this really helping ADHD symptoms on a day to day basis? Not a lot of data at all. So again, that doesn't mean it doesn't work. And I'm going to go sideways and talking about neurofeedback because there's lots and lots of neurofeedback companies across the country that are making lots and lots of money.

1:59:30And there was an article in the American Journal of Psychiatry in the last year. I'm not remembering which group did it. And it was another non a failure to find a significant impact from neurofeedback. And again, I'm not saying it doesn't have an effect, but I had lots of people saying, writing me, should I keep spending hundreds of dollars each week as my insurance isn't covering this and the doctor is saying, oh, maybe 20 more episodes will retrain your brain. So this gets back to a topic you brought up earlier. How much are we retraining our brains with immersion in social media? And the evidence is we are rewiring our brains.

2:00:17So maybe anything pushing an opposite direction or maybe this is reinforcing some of the bad things we don't want. It's we're in a messy world without clear answers yet. I've made it a point to put social media on an old phone. So those apps are only on that phone. I don't even know the number to that phone. If I need to post something, I air drop it onto that phone. And this has helped tremendously in segregating that activity and limiting it. It also means that people send me something which would otherwise direct me to social media. It's much more difficult for me to go look it up to help tremendously.

2:00:56I just pass it on because it's one of the things that's really allowed me to restrict my social media time. And yet still be you know in keeping with the fact that I think social media has its uses I post there, etc. Yes, getting back to the scheduling. I mean what I recommend to people and one of my week I don't know the specific apps, but there are apps that will help you out of Facebook or Discord or TikTok or whatever it is. If you can't exert your own willpower, which again is harder to do if you have ADHD. And if the app approach doesn't work, the next level up is there are all sorts of companies making lock boxes and physical devices where you can lock yourself out.

2:01:38W of device for certain hours of the day. And I think that's a good idea for lots of people. I do too and I think it also helps at least in my experience to do things that are very different than social media as well, but still consuming content. So I make it a point to read from an actual physical book a bit each day or night also because I was raised doing that and writing by hand is just over and keeping with the way that my brain was was wired. So maybe that's more specific to me in my generation, but I find that when I'm doing those other activities when I go on to social media, it feels more like a departure from the rest of life as opposed to the other way around.

2:02:22That's a good sign for preserving. I'd like to talk about some compounds that are not so typical, meaning some people may have heard of these, but most people probably haven't and they are somewhat novel to me. The first one is a Guanfacine. What is Guanfacine and why is it sometimes used for ADHD? So Guanfacine and a related drug called clonidine, which can be confused with clonipin and other, it's a clonidine in Guanfacine or both alpha two agonists. So they work on a subset of the Norepinephrine system. They're both originally anti -hypertensive for lowering blood pressure. And it was actually studies first in clonidine that suggested it could be helpful with people with ADHD.

2:03:13And I think it was just a serendipitous initial discovery. It wasn't seeking out its mode of action to see if that really worked. One difference between the two of them is clonidine jumps off the Norepinephrine alpha two receptor really quickly. And for people who skip a dose for the blood pressure medication or stop abruptly, it's not uncommon to have rebound hypertension and not to smile, but way higher than what you're being originally treated for to dangerous levels. Guanfacine leaves the receptors more slowly and there have been formal studies trying to see if this is a problem or issue there.

2:03:52And particularly given that people with ADHD forget their medication or run out and don't fill it in time or just don't remember to take it, the rebound hypertension does not seem to be nearly as common with Guanfacine. And that's part of why the research has moved more towards the Guanfacine. So there's extensive work by, I'm going to blank down a little, Amy Arden. She said Yale, Armstint. And her lab and related labs have shown that Guanfacines effects seem to deal with strengthening synaptic connections in prefrontal circuitry. So unlike most of our drugs that are just boosting Norepinephrine and dopamine and work quickly, and I'll throw in this because we didn't really touch this.

2:04:45Most of the ADHD experts still say stimulants, amphetamine, riddle, and work quickly immediately because they boost dopamine right away. And our drugs like strotera, which is adamoxetine or symbolta or well -butron, work slowly for ADHD because their antidepressants and antidepressants work slowly. There's still people saying this. And for 25 years, I've been saying, this is just wrong from one of basic neuroscience point of view. And wrong from, don't you ever talk or listen to patients. So neuroscience view, how quickly does dopamine get reuptakeable blocked by well -butron or by adamoxetine strotera or by symbolta within minutes to hours of taking it.

2:05:30So you would expect, if you're boosting Norepinephrine or dopamine availability right away, you should see FX right away. And if you ask patients who these drugs work for and they don't work for anybody, all the ones I've worked with say, you know, work just like a stinger. I could tell I took it and I walked out of your office. I mean, one guy I have who loves symbolta said, I took it near office and I wasn't sure it was working and I got downtown to work 15, 20, maybe half hour later. And there was this guy coming at me on a state board on the sidewalk. And I know in my normal ADD state, I would have just been flooded and not be able to process.

2:06:10And I could just step out of the way. So, you know, it worked that quickly and dramatically. So that's the aside. So jumping back, Guantfacine seems to work slowly. So the synaptic strengthening building. And it seems to be the alpha two receptors that are on neurons that receive glutamate is a primary input. The alpha two receptor is modulating how glutamate is actually working. And it's actually an MDA glutamate receptors, not the more common in the brain ampok glutamate receptors. No, that's an important point. I'll just quickly throw in if I may, that the NMDA, the NMethodeaspartate glutamate receptors are the ones that typically are associated with synaptic plasticity.

2:07:03Although, you know, so are the ampok receptors can do that too. But what Dr. Cruz is referring to is the fact that Guantfacine indirectly modulates those pathways. So the longer duration to get the effect, it sounds like could be at least partially explained by a real change in neural wiring as opposed to with you use Symbalta and well buterin 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. But put differently sounds like Guantfacine and clonidine, not to be confused with clonapin, clonidine could help ADHD but might take longer for the effects to manifest than the other drugs that we typically hear about.

2:07:52Yeah, so most often it takes two, three, four weeks and because it, I mean with the stimulants, you see effects right away. It's reinforcing and stimulants often in addition to having effects on concentration attention, another you know, do boost energy for most people, do boost mood for most people and can improve sleep if they're not taken too close to sleep. Yeah, Guantfacine's most common side effect tends to be sedating so most people take it at night time, which is why are you taking a sedating night time medication for your ADHD, it's because it helps it works slowly and directly. So in tune of the the brand name extended release, Guantfacine was approved in kids, because again most of the research on ADHD is still on kids.

2:08:37For treating ADHD as a solo agent, it clearly works in adults as well and even before intuniv was approved, there were a handful of studies with either immediate release, Guantfacine or extended release, Guantfacine. In the study so far, the results aren't distinguishable, you know, they both seem to work. So clinically, because it's much cheaper, I actually use immediately release form and all of bedtime. And again, because it's my impression and it probably don't have an end that's big enough to do a rigorous study, is the sedating effects are relegated to the night time and people are feeling okay during the daytime.

2:09:24I mean, some of the rationale with the extended release is you're sort of smearing it over a longer time, so it should be less sedating. But depending on the time curve and how it works, you could actually wind up with being more uniformly sedated day and night with the extended release. So I've seen good results in some people. I've had many who either didn't work or they didn't perceive result because again some part for some people of the stimulant benefit is I can feel it, I know it's working. So the majority, at least in terms of prescription searches and what clinics tend to do, it looks like most people who are on Guantfacine are on in combination with either a stimulant or an epinephrine or dopamine promoting agent.

2:10:13Let's talk about Modaphanil and our Modaphanil by extension. We hear about Modaphanil a lot in communities like the tech community and communities where people are trying to quote unquote cognitively enhance. What is Modaphanil? What does it do? What doesn't it do? How might it be useful for ADHD? So we're going to jump back to your issue with the recent C in science and how to incorporate things when some Modaphanil 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 or maybe 35 years ago. And at the time all the research showed that it was an O -Rexan receptor antagonist, right antagonist, agonist.

2:11:05Works on the O -Rexan, the hypercrete in the O -Rexan system. So boosting activity but not working like all of our stimulant, the learning drugs which are working on primarily nor epinephrine systems. So it was called the non stimulant stimulant. Now most of the pharmacology literature refers to it as a dopamine acting drug and there's some people are debating whether it's O -Rexan that it's working via dopamine. I haven't seen anything that to me means it gives a clear consensus. So I stick with the O -Rexan because that's where I was taught. So O -Rexan getting back to the sleep wake in the brain in a rousal as I describe it, there's two ways to wake up in the morning.

2:11:52One way is the normal way that you just wake up and the other is being alarmed by an alarm clock, your neighbor starting the earth lawnmower, someone snoring, earthquake, if you're an L .A. or Hawaii. Being startled out of sleep. That wakefulness system is a sympathetic nervous system. The O -Rexan system is a more natural normal waking system and it isn't arousing you, it's waking you but it's not agitating you. Again, the claims originally was that this is how the definal worked, it was waking you up but not overstimulating over revenue. So that the other than being developed by this French company, the entity that spent most research funds looking into what this does or doesn't do was the US military.

2:12:43Because they have a big investment in wanting people to be alert and ready to kill 24 -7 but not being hyperactive trigger happy jittery like stimulants can do. And particularly in the early days, this is really dating me of the Afghan war. We drop bombs on Canadian troops by accident, friendly fire, scenario things, and the investigation, the pilots and the crew there, waned their trigger happiness on being revved up by a metal fanatite. 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 give you alert awake but not revved up, not agitated.

2:13:32And I'd say there's some good evidence that that's really sort of how a Modephanol works or performs. So Modephanol was called Provigil for Provigilants and then when they were losing their US patent, like many drugs, the Provigil is a receemic mixture of left -handed and right -handed versions of the same Modephanol molecule. They found that the Armadaffinol, 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 Armadaffinol which is new vigil. So that's the only difference between the two.

2:14:12They're the same active ingredients as far as we can tell. So when it got approval in the US, it was approved for narcolepsy where people were falling a drop of sleep during the day so it keeps them alert and awake there. It also got approval for circadian sleep shift work disorder where because you're on a shift schedule, you're sleeping weirdly. And it got approval for daytime sleepiness from sleep apnea. But even at that time when it was approved, there were dozens of studies that showed regardless of why you're sleepy, whether it was sedating medication, whether you had bloopers or MS, whether you had some other condition, it works pretty well for keeping people alert and awake.

2:14:57So more than keeping alert and awake, there does seem to be evidence that it helps with some of the executive functions of attention, concentration. My clinical experience with it tends to be, again, with the amphetamine on top. Many fewer people describe it as being helpful or as as helpful. On the other hand, there's one study and I'm forgetting the principal investigators, it was a Brown University where they used some very clever, sophisticated approach to try to sort out motivation versus pure cognitive functioning and their claim. And it was a very well done study. They were comparing it directly to an amphetamine product.

2:15:42Their claim was that Modephanol was the one that was actually boosting cognitive functions and not just boosting motivation, whereas that most of amphetamines benefit for ADHD when we say it helps me concentrate, helps me sustain focus, it makes me less distracted. Their feeling, their analysis was that stimulant was mostly working on motivation. It's a controlled substance, but not nearly not the same schedule as amphetamine and riddled. And so it's easier for some prescribers to prescribe. Even though it's the non -stimulant stimulant, and I'd say most people do experience, you know, I feel more alert or awake or better, but I don't feel rubbed up.

2:16:27And 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 rubbed up when they take it the first few times. And invariably, the people I've worked with have said, this feels like bad speed, including people who haven't too, who never even took speed. So I don't know why they came up, I mean, it's just weird that people come up with the same terms. But it's, I mean, my interpretation is that for some people, this novel substance primarily may be tacking into the OREXAN system is serving as a signal kind of like a panic attack does that there's something weird, something different or being revved up.

2:17:09And it's, I think, secondarily triggering the sympathetic system. Because for most of those people within a few trials, within a few days, they no longer had that over revved effect. And again, the important piece for alerting people to that is if they're expecting taking this, I'm not going to feel overroused and over agitated, and they do, then they're even less prepared and more freaked out. Even though I've never tried Modaphanil Providial, 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 have taken it for ADHD and for work focus and cognitive enhancement.

2:17:56People who take Modaphanil and Armodaphanil really like it. They, I don't know if it has any reinforcing property, but today is the first that I've heard that has this dopaminergic aspect. But they seem to really like it and rely on it. Have you seen a kind of a dependence form? I mean, it is a controlled substance because some people are worried about the potential. And there was a woman in the half late 2015 years ago who was Admardaphanil and said she had narcolepsy. I don't know the word, but was disqualified from the Olympics because of it. Whether it has any real performance enhancing effects is not clear.

2:18:35You know, it was available in France for a decade, at least before it came to the US, and they didn't see any rates of substance abuse or problems. I mean, it clearly does not have there on any tests or animal studies. The propensity that the amphetamines do, and I'd say it's to me not to conclude its subject, whether there's any potential for addiction or that. What about within the category of Adderall, ViVance and the stimulant type treatments for ADHD? I don't want to say what do you go to favorites because that makes it sound very non -clinical. But, you know, what are the general trends that you've observed and that others have observed clinically or in any studies about preference for long -acting drugs versus shorter -acting drugs?

2:19:30And maybe this is also a good opportunity for you to be able to chime in about drug holidays, you know, taking weekends off or things of that sort. Maybe I'll start with that. So, for decades, particularly starting with the kids, the dogma has been taking breaks from stimulants as a good idea because it will decrease the likelihood of developing addictions, it will decrease tolerance. And not a lot of rigorous research, but one of the known side effects of stimulants for kids is growth suppression. So, height winds up being about two centimeters, not big, but measurably and consistently found there for kids who are routinely on these stimulants for their growths years.

2:20:21And taking breaks that last for several months, like taking it off during the summer, result in overcoming that decrement and height. I looked and I still have whether there's any lower rate of addiction, whether there's any lower rate of developing tolerance. There's nothing that shows clinically. I mean, it may be true. The other recommendation when I started out was, and this is before the internet, before constant plugged into everything, and before kids had soccer practice and violin lessons and 400 activities, is that kids should take it during the work days and not take it during the weekends and not take it during the summers.

2:21:01And now, and for many years, we've lived in a world where little Johnny has soccer practice and ballet and piano and has 42 things to get to where he's supposed to be performing and focused and behaving. So, the sort of excuse you could have downtime has diminished in many communities. And again, whether there's actual benefits to that or not, other than for the height decrement, which again, there is evidence that taking long breaks, but probably not short breaks, mitigates that. I haven't seen any evidence clearly showing a benefit. That doesn't mean it's not there. Nobody has really studied it rigorously.

2:21:46Sort of related to that, you asked the question about short acting versus long acting. And there's differences in the realm of what's clinically helpful or useful, and then there's the issue of risks or side effects. So again, one of the claims is that part of what makes a drug more addictive is not just the level it reaches, but how quickly it's going in and out, and that the short acting drugs may predispose someone to higher rates of addiction. There are at least occasionally some people arguing on the other side that saturating the receptors for longer periods of time, but tie doses with a long extended release version.

2:22:27That 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 relisk. And there's a tiny bit of data, but part of it overall is that we talked early about global rates of addiction to any substance. That we have fairly good data on because the CDC tracks it, but in terms of very specifically, who gets addicted to Adderall, who gets addicted to a riddle, and there's so little data and most people just sort the same numbers that, oh, maybe two to three percent of kids run into trouble, and it's not common, and that's it. Or they study a much broader question, and that's the issue of misuse combined with abuse, and misuse by the research definitions means anyone who didn't use their drug exactly as prescribed, which means if you're taking a short acting riddle in and it says, take it one and every six or six hours a part during the day, and you acknowledge taking it on one day, eight hours difference.

2:23:35Your classified as a misuser by those studies. I mean, it's a, I'm being maybe a little ridiculous because most of the exceptions aren't that narrow, but there's a big blurring in the research, particularly coming from the people who are worried about addiction. I mean, we should be worried about addiction, but we shouldn't be overreacting or creating pretending it's a problem among those where that I would say is not addiction. That's not abuse. That's not using as directed, but people with ADHD by their very nature are not going to use things as directed either because they forgot or weren't organized enough to get it on time, or forgot what you said in the office.

2:24:20So it's not that we're going to use this even though you wrote it down because they lost a sheet of paper, it's written down on. So getting back to patients experience of it. So the advantages of the immediate release is they tend to work quickly, you can feel it going in. It's easily most people, there's a lot of individual variability, but let's say in the six to eight hour range will get benefit some shorter some immediate release last all day, but you know when it's on, you know when it's off. If you forget to take your medicines in the morning, but you know you have a presentation at three that afternoon, you could take it at two and still be able to sleep that night.

2:24:58So it allows more flexibility, it allows more pinpointing of optimizing it for points the day you want to be using it. Some people philosophically say that in itself is wrong or bad that you should be absolutely steady and constant because what we're trying to do is be consistent and reproducible and others would say we're trying to treat individuals who have different demands on them and have different patterns during the day. So there are different philosophies about what's better worse. One of the big downsides of the immediate release though is not only does it go in quickly, it tends to go off quickly and most people not all but most experience some withdrawal as it's going off.

2:25:41And although when we're using us for ADHD, we focus on the cognitive executive function benefits the focus, the attention, the concentration and people can experience that many people who weren't even aware of it increasing their energy feel my energies crashing as I go off of it or many people who weren't aware that it was actually elevating mood to any extent feel oh my god, I'm crashing and I'm crying and cranking and miserable now. And with the extended release versions, most of them go in more gradually so it can be harder to detect the last longer period of the day and most of them go out much more gradually at the end of the day.

2:26:24The one I like the most or for a long acting amphetamine product is vivants and vivants was designed as a slow release product. It was designed specifically to be unattractive to drug abusers. So vivants chemically links the dexer and phatamine molecule to lysine one of the amino acids. It's a basic component of proteins and 20 essential amino acids. And if you snored it or injected it, you have an inactive pro drug. You have the list of x amphetamine. You have a red blood cell that actually needs to have an enzyme that cleaves the lysine and leaves you with free active dexer and phatamine. And that's the slow release mechanism is how quickly your red blood cells can do it and they have limited capacity to do that.

2:27:17So although they designed it to be an anti drug abuse drug, it actually turns out to be one of the sort of most consistently evenly entering the body. For some people it goes in so slowly that they say I don't feel it. And also towards the end of the day one of the best in terms of not falling off abruptly. The potential downside is again that the capacity the red blood cells is limited. So at some point for most people because that's a rate limiting step when you're adding more and more, you're actually extending the duration of time more than you're getting a bigger peak because your your red blood cells just aren't cleaving it fast enough to make more dexer and phatamine.

2:28:03Almost invariably when I ask you know how did this compared to your adorol axiom or to enhance your to they'll say smooth smooth. They're getting it. They're not feeling too jarred too wrapped up. Yeah, we don't really have a language for these things right. Hence the bad speed language before cracked out bad speed smooth. Because what we're talking about here is the gist of all of the subjective experience of all these neural and chemical mechanisms. Very interesting. Thank you for sharing that. I know that there are a lot of listeners and viewers who have tried these things or are considering or you know one point use them and a lot is evolved in this realm of chemistry for ADHD, but that's very helpful.

2:28:55Before we wrap up I want to make sure that I ask you about something that's been on my mind a lot in general, but in particular as it relates to ADHD which is time perception. And I'm basically obsessed with time perception. I've long been fascinated by the fact that we can find slice time when our rousal is high. That's what presumably gives people the kind of slow motion effect and you know high very stressful environments versus when we relaxed our frame rate on life goes down. And it's all very dynamic. It's important our brains are able to do that. But someone recently told me the following her partner has ADHD and she said that the big rescue to their relationship came when they together read read a book about ADHD and something in their red something like this that people without ADHD keep track of time.

2:29:47Whereas people with ADHD don't but they do know the difference between now and not now. But they're not tracking time. They know that what they're doing in the moment is not what they're going to be doing later or what they did in the past, but they're not tracking time the same way. And I think this ties back to this interest based attention system. What do we know about time perception in ADHD and by extension do you think that these drugs are working in part to change time perception. Good question. 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 time perception test and you interrupt them after certain period.

2:30:32I mean say you're going to be estimating how long your your left without interruption and people with ADHD measurably are they're inconsistently inconsistent. Consistently inconsistent. So it's not that they perpetually underestimate or over estimate, but they are estimating incorrectly much more often than people with ADHD. So there's something at a basic time processing level that's apparent there, but there's also getting you know that the real world aspect of not paying attention to cues or not noticing other people left the room or not register being distracted, which compounds the situation and I mean it's also interesting to the extent to which many people aren't so often asked even though it's not.

2:31:26Not one of the 18 symptoms are you conically late to and particularly people who show up late to my office time after time. So one of my favorite quotes is this person who the session before we had been talking that her boss was giving her threatening notices because she had come in two hours late one day and she had all sorts of good excuses of why she couldn't get out the door. And I were talking you know are you regularly late no no no and I said well why was the boss so upset that's it and then I asked well when do you when is the expectation this is pre -COVID pre -working when it's the expectation you're there when do you usually show up.

2:32:06Oh, well, the office starts at nine and I'm usually there by 915 920 that's not late. In her mind it wasn't late so you know and so when you ask a question are you retrainably late you're going to get meaningless information on your little checklist unless you know what that means to the individual. So the second part of the question I'm sure it's been done and I don't have the answer whether stimulants or other drugs measurably improved time perception in that you know laboratory situation of just can you estimate how much time is elapsed. I I should know that but I don't have that on top of my and the more global question of how central that's sort of the time aspect of organization of thoughts and attention is to the content of disorganization.

2:32:59I'm there are some research groups because I'm in a Danish group who's feeling that ADHD is primarily a circadian rhythm disruption that that's the central neurologic issue at play and there's interesting I got to do work in the early 80s on bright light therapy for winter depression which as a measurable impact as strong as medication but there is one or two studies. So I'm just on on individuals with ADHD without any seasonal depression with an any depression at all and just the same bright lights showing them you know a dose of bright lights early in the morning measurably improved a broad range of ADHD symptoms and the claim is that that was working because it was helping.

2:33:57So I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and I'm just on the other side of the screen and mario thor will always settle considering me than your ADHD, you're able to do it from so many different angles, behavioral, supplement -based, nutrition, life, an 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.

2:35:08So I just want to be absolutely clear how grateful we are for you for sharing all this knowledge. A lot of people struggle with attention issues, regardless of whether or not they have a full -blown ADHD or not, a lot of people would not treat it for it, some people are still wondering if they should be or not. And so today's discussion was nothing short of a spectacular. So on behalf of everybody, I want to just thank you for doing what you do and for coming here to educate us. Thank you so much. Thanks, I'm God -smacked. Thank you for joining me for today's discussion with Dr. John Cruz. To learn more about his work, please see the links in the show -note captions.

2:35:45If you're learning from Ender and enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero -cost way to support us. In addition, please click follow for the podcast on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five -star review. If you have questions for me or comments about the podcast or guess for topics you'd like me to consider for the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. Please also check out the sponsors mentioned at the beginning and throughout today's episode.

2:36:14That's the best way to support this podcast. For those of you that haven't heard, I have a new book coming out. It's my very first book. It's entitled Protocols, an operating manual for the human body. This is a book that I've been working on for more than five years and that's based on more than 30 years of research and experience. And it covers protocols for everything from sleep to exercise to stress control protocols related to focus and motivation. And of course, I provide the scientific substantiation for the protocols that are included. The book is now available by pre -sale at protocolsbook .com.

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2:37:49And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. John Cruz. And last, but certainly not least, thank you for your interest in science.