Adderall, Stimulants & Modafinil for ADHD: Short- & Long-Term Effects
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Welcome to the huberman lab podcast, where we discuss science and science space tools for everyday life. I'm ander huberman and i'm a professor of neurobiology and optimal gy at stanford school of medicine. Today, we are discussing stimulants, in particular stimulus for the treatment of A D H, D or attention deficit hyperactivity disorder.

As many of you know, there is tremendous interest in drugs like adorable riddling, vivants and other stimulants, as well as non stimulant prescription drugs that have been shown to improve the symptoms of A D H D such as modane r model. And gone for scene. Today, i'm going to discuss all of these compounds in the context of how they work to improve the symptoms of adhd.

I'm going to address common questions about these compounds, such as, are they just speed? Are they similar to math or method? Fine, i'll talk about their addictive potential as well as their potential to cause psychotics symptoms, both in the short and long term.

And of course, I will talk about the scientific literature surrounding the most frequently asked question about these compounds, which is, what are the long term consequences of taking any of them in childhood or in adult hood? Now, today's discussion centers around the use of these compounds, both for childhood in for adult A D H D. But of course, i'd be remissions identikit ledge that there are a tremendous number of people that use these prescription drugs without a prescription in order to improve their ability to focus and indeed also use them recreationally.

In fact, some surveys reveal that is highly eighty percent of college age Young adults have used one or several of prescription drugs such as ador al riddle in vivants or similar at some point and are doing so without a prescription. So they are either obtaining those drugs from those that do have prescriptions for them for add or they are obtaining them through black market sources, which of course, Carries in additional and very serious risk related to the social sentiment crisis that is as high as seventy five percent of black market drugs nowaday of various kinds, but certainly including the sorts of drugs we're going to talk about today, are contaminated with fenton's m, and therefore are very deadly. So today i'm going to describe what these various drugs really are, how they work at the level of neurons and brain networks, and how they change those brain networks in ways that really can allow people with add to be able to focus Better.

I will answer the common question, which is, why is IT that giving children in speed? Because indeed, several, not all, but several of the compounds are going to discuss our speed. They are and fedex en.

Why would that cause a reduction in hyperactivity if speed as a stimulant? Or answer that question for you. And I will also answer questions that are commonly asked, such as how these drugs impact things like sleep, hormone health, reproductive health, as well as what is their impact on height.

Indeed, IT was one prominent hypothesis that these A D H D meds could actually restrict the height of children. All tell you whether not that's actually true or not. And then i'll discuss the data.

Surroundings, whether not these drugs pretty expose people to becoming addicts to other substances, even if people seize or continue taking the stimulus that can help them in the clinical sense for adhd. Before we begin, i'd like emphasized that this podcast is separate from my teaching and researchers at stanford. IT is, however, part of my desire and effort bring zero cost to consumer information about science and science related tools to the general public.

In keeping with that theme, i'd like to thank the sponsors of today's podcast. Our first sponsor is element. Element is an electoral light drink with everything you need and nothing you don't.

That means plenty of salt magnesium in peason, the so called electronic and no sugar. Now, salt, magnesium and patashie are critical to the function of all the cells in your body, in particular to the function of your nerve cells, also called neurons. In fact, in order for your neurons to functions properly, all three electroliers ts need to be present in the proper ratio.

And we now know that even slight reductions in lateral light concentrations or dehydration of the body can lead to deficits. And cognitive and physical performance element contains a science back electronic light ratio of one thousand milligrams that one gram of sodium, two hundred milligrams of plastic um and sixty milligrams of magnesium. I typically drink element first thing in the morning when I wake up in order to hydrates my body and make sure I have enough electrical. And while I do any kind of physical training, and after physical training as well, especially if i've been sweating a lot, if you would like to try element, you can go to drink element that's element t dot com slash huberman to claim a free element sample pack with your purchase again, that drink element element dot com slash huberman. Today's episode is also brought to us by waking up, waking up as a meditation APP that includes hundreds of meditation programs, mindfulness trainings, yoga eja sessions and nsd r non sleep depressed protocols.

I started using the waking up up a few years ago because even though i've been doing regular meditation since my teens and I start doing yoga eja about a decade ago, my dad mentioned to me that he had found an APP turned out to be the waking up APP, which could teach you meditations of different durations, and that had allowed of different types of meditations to place the bringing body into different states, and that he liked IT very much. So I gave the waking up up a try. And I too founded to be extremely useful, because sometimes I only have a few minutes to meditate, other times I have longer to meditate.

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Let's talk about treatments for A D, H, D, and why stimulant treatments in particular can be so effective. First of all, it's long been known that there are specific brain networks involved in what we call attention. Now, attention is not one thing actually.

IT involves several different cognitive Operations, including the suppression of noise, that is, turning down the background chatter in our heads and turning down our attending to things outside us, like noises or visual queues that are not relevant to what we want to do. And IT also involves ramping up or attending or focusing on particular things that are happening either in our immediate environment or in our head or both. So if that all sounds rather complex, indeed, IT is that involves several different networks Operating in parallel.

But what we know for sure, based on a lot of clinical and scientific laboratory data, is that the social prefrontal cortex, the region of neural real state in your brain just behind your forehead, is critically important for orchestrating which neural circuits are going to be more or less active at a given moment in order to bring about what we call focus or attention or tasks switching, or our ability indeed to multitask, because we can actually multi task to some extent. In fact, if you were to look at somebody and a focus on perhaps the expression on their face, you could do that while also attending to a conversation that's happening nearby. It's energetically demanding.

It's hard to do, but we can do that. That's actually referred to as covert attention. You're covert leap ying attention to something else, and then you can switch that attention back to just one thing or one small collection of things.

The point being that attention is a powerful resource, is what allows us to navigate through life with efficiency and to be adaptive in our behaviors is what allows us to learn to build relationships and to have successful school careers and professional careers and so on. But IT is indeed expensive. IT takes meta lic resources just at rest.

If you were to think about essentially nothing or whatever just pops in your mind with no dedicated effort or paying attention to anything, your brain would consume about twenty five percent of your daily Clark needs. And then when you lump on top of that, your need or your attempts to focus on things, to pay attention, specific things, IT should come as no surprise as to why that often can make us feel tired, as if we've been working really hard. We've been running a quote of mental marathon when trying to learn and attended things.

It's hard work for the brain. And yet we can pay attention because of that very precious real state just behind our foreheads, the preference to cortex. Now, in people, both children and adults, that have adhd, their prefrontal cortex is not necessarily deficient in any specific way, except that IT is not as good at orchestrating the activity of other brain networks Operating in parallel with IT.

What do I mean by that? Well, if we take a step back and say, what is the prefrontal cortex really doing? The prefrontal cortex has this amazing ability through what's called top down inhibition, to quite other brain area. So for instance, if you are feeling agitated, but you need to sit still, your ability to sit still, even if IT takes a bit of work, is coordinated by your preferable cortex, sending inhibitory ory suppressive electrical signals to the networks of your brain that are to generate physical action.

In addition to that, if you are in a conversation that either a difficult one or a boring one, or you are tempted to interrupt and you are actively holding back your desire to walk away or to yn, or to blurt something out, it's your prefrontal cortex that is controlling that active suppression. So in many ways, you can just think of the prefrontal cortex as an orchestra conductor that is essentially saying or not right now, be quiet. This is not the time to many different brain networks all IT wants.

Now, in addition to that, your prefrontal cortex is coordinating with other brain networks that are involved in generating what's called silence or attention to particular signals. So the preventive cortex, in many ways, is like a teacher or an orchestra conductor. IT can point you in the new chemical sense, that is, point to a given brain structure and say you, i'd like to hear more from you right now.

Yes, you, the student in the back speak up and a moment later, point to a collection of small students chattering in the back again. i'm. Presenting all this by by analogy and say, hey, hey, hey, you guys quite IT down right now. So and so is going to come up to the front of the room and help us work through this particular math problem.

So when we hear that the prefrontal cortex exerts what's called executive function, what that refers to is the provenal cortex is ability to quit IT the activity of particular neural circuits and to enhance or increase the silence of other neural circuits that are involved in creating our spotlight of attention. And what we know for sure, based on many, many brain imaging studies, is that adhd is not necessarily a deficit in prefrontal cortical function, but rather the prefrontal cortex is ability to communicate with other brain areas in the proper ways. And so what results in the brain of a person either Younger, old with adhd, is that a lot of the background chatter becomes very, very loud.

So for instance, ince, we have a brain network called the default mode network. This is a fascinating brain network. This is the brain network that is active when you just sort of sit in place and don't think about much, and then you start having ideas about what you might do next week.

IT tends to be very autobiographical. So you might remember an experience from the past. You might think about some of your desire, some of your dislikes. This defauts mode network, as it's called, is also involved in our imagination, our in our schooling together of different experience that we've had. IT doesn't tend to be the thing that's really focused on anything external.

In particular, all IT wants the default on network is always active, but it's when we start to attend to something, especially things external to us, like know something written a page or conversation or something that we really need to learn, something we need to pay attention to, that the activity, the default mode network, is suppressed somewhat. And that suppression occurs not just by accident, but because the profile cortex is actively suppressing IT in kids and adults with A D H D. The default mode network is often still active at a very robust level even while we're trying to attend to things.

And that's why someone who want the hd will sit down and trying to do some focused work. And i'll start thinking about something they want or something they dislike. Their internal state will start to distract them.

And of course, there are other networks in the brain. There's actually what's called the true silence network. There is the dorsal attention network. There are a bunch of different networks in brain areas. But again, when thinking about add, and especially when thinking about how the drugs that we're going to talk about today work to alleviate the symptoms of A D H D.

And in thinking about why so many people use or even abuse these drugs for sake of learning or recreationally, we might say you start to realize that everything centers back to the prefrontal, to cortex. And the preference to cortex is ability to actively suppress and actively enhancer activity of these multiple brain 点 networks， including default mode network, salience network, dorsal attention network at settle. So rather than overwell you with a bunch of names of brain areas and brain networks today, i'd really like our discussion to focus on, first, what the various drugs that are used to treat A D H D R, that is, how do they work at the level of neurons. Second, how they create a certain set of conditions that allow the prefrontal cortex to be a Better conductor. Third, how that can be leveraged during development to actually teach the prefrontal cortex of a Young child to learn to be a Better conductor, because that's really the hallmark of the use of these drugs, is to try and enhance the activity of particular circuits to create a sort of learning so that the prefrontal cortex is much more efficient at doing its job of conducting and then forth.

We're going to talk about the various things that I think most people out there ask about when they hear about drugs like adora vivants and riddle at sea, which is, you know, are they addictive? Why are they addictive? Can one use them briefly, or even from time to time and still be OK? What if I use them as a child and I don't want to be on them anymore? Should I put my child on these drugs at set up? IT is, I believe, only by understanding the biology of how these drugs work and they are potential both to improve brain function, but also some of the dangers associated with these drugs, that one can really answer those questions for themselves or for their children.

okay. So let's start with a very basic but critical question, which is, why in the world would epidemic speed or other stimulants improve the symptoms of A D. H.

D. That's so critical to answer? Because if you think about IT, the prefrontal cortex needs to coordinate the actions of these other circuits. And so just increasingly, amount of activity in prefrontal cortex, you can imagine, would create a state of hyper focus, perhaps, but actually that's not the case.

If you just were to ramp up the activity of prefrontal cortex, what you would find is that somebody would become even less efficient at paying attention to what they wanted to. Rather, they would pay attention to whatever was presented in front of them. With laser focus, they would lock on to essentially anything.

And that's not good. One of the key things about preference cortex is that IT needs to be flexible. IT needs to be able to pay attention to this.

Then they need to be able to pay attention to that. Then he needs to go back to pay attention to the thing that was paying attention to previously, and so on and so forth. Life, that is an effective adaptive life. A good life, consists of self directing one's attention most all of the time.

So why would stimulants do that? Well, almost all, not all, but almost all of the drugs used to treat A D H D fall under the category of stimulus, or what are called sipah o minmetals sympathic myneer c refers to the fact that we naturally have a component of our nervous system called the automobile nerve system. The automatic nervous system has two major components. One is called the sympathetic ARM of the autonomic nervous system. Has nothing to a sympathy, has everything to do with ramp ing up our level of attention and arousal.

IT is this so called fight or flight aspect of our nervous system, or rather, immediately fight or flight, but immediately a bunch of other things too, including sexual areas, or including excitement and focus about something that we want to learn, or somebody that we want to learn more about, or remembering a phone number or anything that puts us into a state of alertness and focus. The other ARM of the autonomic nervous system is the so called paris sympathetic ARM of the autonomic nervous system, and that's often referred to as the so called arrest in digest component of a nervous system. And yes, IT controls rest.

Indeed, IT puts us into sleep. And yes, it's involved in digestion, but it's involved in a unch of other things as well, including sexual ously, including rates of digestion, including a, including all sorts of things that don't just have to do with resting and digesting. The way to think about the automation ic over system is is a sort of sea saw.

So it's always at a baLance, some place between either predominantly sympathetic or predominantly parasympathetic. But both the parasympathetic and the sympathetic arms of the authority ervy system are always active all the time. It's not as if one is completely act when the others shut off. Even in sleep, your sympathetic nervous system is not completely turned off, and even during a panic attack, your paris sympathetic nervous system is not completely turned off.

Drugs to treat A D, H, D, which fall under the category of stimulants, are sympathy in medics, because they trigger the release of neurochemicals and the activation of components of our nervous system that very much resemble the activation of the so called sympathetic nervous system, the one that makes us more alert and more aroused. So that's why they are called sympathy memetics. And the word stimulant refers to a general category of drugs that are sympathic tics.

Now, the most commonly discuss sympathy in medic is one that fortunately is not prescribed for add. And that's meh. ef.

To me, these days we hear a lot about math. Math, which is method, ted and theme, is an extremely potent sympathy memetic. And IT has tremendous abuse potential.

Believe IT or not, math or meth npt mine is actually available as a prescription drug. But IT is used very rarely because of its high abuse potential and all the terrible things that I can do in terms of cardiff asked lar health. In terms of oral health, right? There's a steroid pe that math users have very degraded teeth and did they do? There's a reason for that related to how math impacts the brain body.

I'm going to talk a little bit about math and fedex in a little bit later, but let's just place method for demand high on the shelf as the most potent sympathy memetics that's out there because even though it's not often prescribed for adhd, there are a classic compounds very similar to IT that have a very similar pattern of action that is not quite important, but that leverages the same underlying mechanisms, and they are very commonly prescribed for add, namely atrial and vivants. So first, let's talk about atra. And what atra is at erl is a combination of what called and fedex in salt.

And fedex, I insults, refers to the fact that there are two major forms of infect mine. There is A D M. Fetish, or dex femme and evo and fine, or L M fedex ine.

So i'll refer to these as d and L M fetish. And for you chemistry minded folks out there, the D, N, the l also referred to the fact that there is A L left handed version of the molecule. And there's a idea right handed version of the molecule.

This is only important understand, in so far as you know, that the d and the l forms of the molecule look very similar, but the mirror images of one another, and yet they can have very different actions in the brain and body. So atom is a three to one ratio of dm fetching to lm fet mine. You should know that L M.

Fatma tends to be less potent in increasing certainty, chemicals in the brain. Og, talk about which narrow chemicals that are in a moment then is D M. headmen. So dm, headmen is potent stuff, not as potent methamphetamines, potent stuff. L ehem me a little bit less pot.

L ept mine tends to be the effects me that increases blood pressure and heart rate when we call peripheral effects, because IT happens in the perfect outside the central nervous system. Peripheral effects like increased hearts rate, increased blood pressure, sweating and seta are mostly activated by lm fetish. Whether dm fedex, en tends to work mainly on receptors in the brain, and therefore have effects mainly restricted to the brain.

Now, what are these effects that i've been referring to? The major effect of atall. And other sympathize atic stimulus is to increase the activity of two neurochemicals. The first of those neurochemicals doping and the other of those neurochemicals is nor ef ran.

First off, I want to be clear that when I say nor epinephrine, I could just as easily say nor a drennen, because those are the exact same thing. And forgive me, even though I wasn't the one to name the same thing, two different things i'll try and stay with, nor appeared. But I may say nor journal, they are the same thing.

There's whole stories to how they got named, two different things. But it's the same thing. The major effect of atter, all in other sympathy memetic stimulus, is to increase the transmission of dopamine and european afra.

So what is dopamine and what is europe? And ephron, well, both doping and north and american are what are called neuromodulators. That is, they have the ability to increase or decrease the firing patterns, the electrical activity of particular brain circuits. But dupine and north and africa separate rules in creating certain states with an our brain body. But they like to collaborate, meaning they tend to be released at similar locations in the brain in order to deliver us to a particular state of mind and our body. So if we were to take a look at just dopamine, we would find that dopamine is released at sights within the brain and increases the activity of brain networks that, for the most part, lead to increases in motivation, pursuit and to some extent, mood. If we were to look .

at north .

and offer and where it's released in the brain, IT tends to be released that many, not all, but many of the same sites where dominis released and the main function of neuroanatomy to increase the activity of neural networks that are involved in attention and focus to particular things in our environment.

And so think of dopamine and north and american as collaborators, because indeed they are, and actually they are very neuroma ally, similar as well. IT actually just takes one chemical conversion to turn dopamine, internet and everyone. So they are very similar, but like close cousins that work together to help us achieve a common goal that involves increased motivation, focus and alertness.

So when we talk about attention in adhd, or we talk about quiting, the hyperactivity or impulse sivy of adhd, one of the reasons why drugs that are effective in treating A D H D are so effective is because they increase motivation, focus and alertness. And they tend to do that at very vocal locations in the brain. It's we're taking a couple of minutes to think about how some athon metics such at all actually increased dopamine and north and american.

They do so by affecting a couple of specific Operations that the so called synapses, what are synapses? Synapses are the communication points between neurons that actually the spaces between neurons. But that's where a lot of the action is when neurons, as we say, are stimulating the next neuron, are activating the next neuron or inhibiting the next neuron.

The word neuron just simply refers to nerve cell. And so what nerve cells have is they have a cell body that contains their DNA and a bunch of other stuff. They have a long wireless process, which is refer to as an x on.

And at the end of that acts on, there are a bunch of proteins in there that do really interesting things. So for instance, there are proteins down at the end of the x on that package neurotransmitter, or into little spiral things that we call vesicles. Those vesicles confuse with the end of the x on and vomit the contents. Those neurotransmitters ors into the synaptic craft, into that little space between neurons. And then if enough of those neurotransmitters ors buying to receptors on what's called the post nap tic side, which simply means the neuron on the other side.

well, then the next .

neuron will become active, and then the signal will propagate from one neuron to the next. Now, I just described that whole process pretty quickly, and i'd like to think pretty simply, but IT actually involves a lot of different protein bits and some pretty complex machinery in order to make that happen.

I don't want to over complate our conversation, but what I will tell you is that down in the synapse, in the prison APP to terminal the neuron that is going to releasing our transmitter. There are what I called transporters, which sit there and suck up or suck back up. Some of them are transmitter that's been released.

There are dopamine e transporters, and there are nor up and afra or nor aderke c transporters down in the synapse. What at all does and what other same athletics do is to inhibit or disrupt the action of those transporters. And the net consequence of that is that when dopamine and or epomeo released into the synapse, some of IT is allowed to stick around to bind the receptors on the post and optic cell, then would be the case if atrial or the other stimulant were not present in the system.

So one way that atrial increases dopamine, and or an f an, is by disrupting the activity of these person apc transporters for dopamine e and orpen afan. The other way that atter all increases dopamine and aruba phone, is that IT disrupts the activity of a different piece of machinery in the personal tic neuron, which is called A V mat, the vesical monolithic transporter, too. If you really want to get specific, you don't have to remember these names. But what these remains do is actually really cool. What they do is they actually take whatever transmittance has been brought back up into the cell by transporters, and they package IT into those vehicles that are then going to .

be released by disrupting .

the transporters that vacuum back up some of the dopamine or europe afra that's been released, and by also disrupting the packaging of dopamine and north an american into vehicles themselves. What ends up happening is that there is a build up of a lot more dopamine in north, an ean in the personates terminal, so that when electrical signals travels down the neuron now, the total amount of doped and or an effort that's released is increased.

okay. So what's happening when you take at all is that you're getting more out of the dopamine and or an effort that you're releasing and you're releasing more dopamine and your penetrant altogether. And there's a third mechanism by which atrial increases the amount of dopamine in r.

And every present in synapse is and therefore connections on other neurons. And that has to do with disruption of the entire network between these different proteins. Not going to go into that in any detail because I get somewhat complicated in terms of the cell biology and some of the biochemistry down at the tips of these actions. But so to say that atrial is such an effective sympathy matic, that is, IT can increase dopamine to such a great extent, especially compared to other treatment for rad hd because of its ability to increase dopamine release and transmission and therefore action as well as naderi c release and transmission and action down there in the synapse. And it's worth pointing out that most of the effect of atoll is an increasing dopamine, as opposed to north an america.

IT does increase nor up an, but its major effects, we should say, the major effects that have made IT such an attractive drug to so many people, both for the treatment of A D H D, and for people to take recreationally or off prescription, or for sake of studying or work, simply because they want to focus more and longer, is because of its ability to increase the open mine to such a great extent. I'd like to take a quick break and acknowledge one of our sponsors, athletic Greens. Athletic Greens, now called ag one, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs.

I've been taking athletic Greens s since two thousand and twelve, so i'm delighted that they're sponsoring the podcast. The reason I started taking athletic Greens and the reason I still take athletic Greens once or usually twice a day, is that IT gets to be the probiotics that I need for good health. Our god is very important, is populated by got microbiome that communicate with the brain, the immune system and basically all the biological systems of our body to strongly impact our immediate and long term health.

And those probiotic ics and athletic Greens are optimal and vital for microbiota health. In addition, athletic Greens contains a number of adaptations, vitamin minerals, that make sure that all of my foundational nutritional needs are met. And IT tastes great.

If you'd like to try athletic Greens, you can go to athletic Greens dot com slash huberman, and they'll give you five free travel packs that make IT really easy to mix up athletic Greens while you're on the road, in the car, on the plane, at sea and theyll give you a year supply of vitamin d 3k two。 Again, that's athletic Greens dot comm slash huberman to get the five free travel packs in the year supply of vitamin three k two. Now a bit earlier, I mentioned that l enfevered leval is present in at all.

But at one quarter, the amount of dm fedex OK, there's a little bit of M, F, M and a lot of dm fedex in atall. Many of you are probably familiar with vive. Vive is a commercial name for what many people think is extended release at or all.

But actually, violence is not extended release at all. Violence is a drug in which the pharmaceutical industry has taken one component of at all, just the D. M.

Feminine component, and attach to IT in the mino acid called license. The mino acid licence is a bigger mino acid. And the attaching of licence to dm fet mine. What we call vivants makes IT.

What's call the pro drug IT actually can't have any effect on its own, but when one takes vivants and its broken down in the gut, but to a Green extent actually in the bloodstream, the licensees are cleaved off slowly over time. And as a consequence, vision is basically time to release. D.

M. fine. This is important because I think a lot of people think that at all, which again is dm fetching and L M femme.

And those two things is Operate quite a bit differently at the level of north of in and epanchin and cardiac s as brain effects. A lot of people think violence is just slow release at all, but IT is not what violence is. Is is D M.

Fetish only. But in time released form and violence was actually developed as a way to try and get around, or rather prevent some of the abuse potential of at all and other drugs that contain dm. Femme, D M, fedex, ine stands for dexter and fedex in and in the seventies and eighties, there were fair amount of movies, and there was a lot of trafficking, and there was a lot of criminal activity related to what was called dextran.

Dextran is pure dm federman. So if we are going to be very direct, if I were going to just frame these things in the context of their neurochemistry. But I can tell you is that vivants is time released dexterity. It's not time released at all now just because they're movies and reports of criminal activity related to dexterity IT doesn't necessary mean that dexedrine is not an effective and useful pharmacology. In fact, vian, which is time release dexedrine, has proved to be very effective in the treatment of ag for a lot of people.

And the reason for that is this time release dos indeed prevent abuse in the sunset, despite people's many attempts from what I hear to increase the rate of entry of the dm pto amine into their system by either snorting italy, you got forbid, even injecting, and things at that sort. The attaching of that license to DNF deming really does slow the absorption. So when somebody takes vivants, and hopefully people are taking IT responsibly when they take violence, what they're really getting is a slow trickle of the effect mine into their system, and therefore a slow, long lasting increase in dopamine, eua and african.

Indeed, that's what happens. The effects of vivants can extend over anywhere from twelve to sixteen, sometimes even eighteen hours, depending on how quickly somebody metabolises IT. And I should say that there is no way to predict how quickly one will metabolite any of these drugs, except by trying.

And that's one of the are downsides of the state of things these days. There is no blood test or animated test that will tell you whether or not you're going to be a fast metabolize or a slow metabolize. And that's why people just have to sort through different dosages, which will talk about a little bit.

They have to sort through different types of sympathy memetics. You know, people try out at all, and they find that, you know, the quick time course of, out of all, at least quick for them of about sixty eight hours, is just too fast. And then IT wears off, and they get into a slump in the afternoon.

Other people find that one ador all taking IT six A M will have them going all day long and into the night, and it's just too much stimulation. And they need to come way, way down in those. Or they need to think about other tomato memetics for D H.

D. We will talk about what some of those other options are a little bit as well. So the important thing understand is the atta l is really two drugs dnl, fetid viands dm, fedex ine, which is also called dexedrine.

But with this time released aspect created by lumping a licence on there, and you may notice that I haven't mentioned one of the major drugs used to treat A D H D. And that's riddle in, or what sometimes also called concerta, depending on, again, the time released forms. That said, a riddle lin was very commonly proscribed for the treatment of hd early in the days of using sympathy and medics in order to treat hd.

So for instance, I went to college in the early nineties, so I started college in ninety three and I graduate ninety eight. IT was one year in there as what's called a transition year. I can recall hearing that reddin was being prescribed for add in kids.

And I, like many other people, were wondering, what are the long term consequences of this going to be? I also, like many other people, was very perplexed to why a stimulant sya theme medic like riddle in was being prescribed for hyperactive kids. That will become clear in a moment, but we don't hear so much about brilliant nowadays.

And I think that's because atrial and violence and things like them have become so popular for the treatment of hd. It's worth noting that riddle in is not actually ephedrine riddle lin is what's called metal fitted. And metal finite works in a lot of ways that are similar to the way that atrial and violence work, but there are certain ways in which is different.

Now riddles in metal fa date does increase dopamine in transmission at synapses si, s, and IT does so also by inhibiting the function of that person optic dopamine transporter that would otherwise suck more dopamine e back up into the personae tic cell method. Date riddler also disrupts the activity of the norwegian gic transporter, leading to net increases in the amount of europe africa synapse, but IT is not as much a pot inhibitor of the north generic transporter, and therefore most of the effect of method date is to increase dopamine at synapse sis lot people don't realize this. A lot of people think that riddler is just a very short acting atole, and that's not the case.

IT is true. That riddle, at least in its standard form, tends to have a pretty short half life, and therefore its effects basically kick in about twenty to forty minutes after taking IT, sometimes a little bit sooner, sometimes a little later. And they last about four to six hours, as supposed to the six to eight hours.

Typical of adorable. But ridley is not short acting. Adorable riddle in is mainly increasing doping, and to some extent, nor of an effort at synapses, is whether adorable and vivants are increasing both dopamine n orpen F N to a much greater extent. And for those of you that are interested in the underlying cell, biological reason for that IT has something to do with riddle's relatively lower affinity for the new energy transporter.

But it's also because, remember, I listed off three mechanisms by which adorable and by extension, vivants increased dopamine and eur, an election transmission right disruption, the transporter disruption of the v mat to, as well as the disruption of the whole kind of complex of communication between those proteins well ridden in is really only tapping into the drug's the ability to disrupt the domine and or adeno gic transport. So it's three mechanisms of increasing dopamine in and uh and american for adorable and vivants and by extension, dexia ine and it's only one mechanism for riddling to increase doping and ora an offer and they're in mostly doping. So we take a step back for a moment from all these drugs and all this cell ology of neurons and so forth.

And we go back to the brain networks involved in attention. Remember the orchestra model or the teacher model, where the preference to cortex really sits in top seat in terms of ordinating the actions, both push required and the, yes, please speak, actions of the brain, really bringing about what we think of as focus, attention and test switching, all the stuff that goes on with learning and focus on cognition. Well, what we know is that dopamine and north and afan, which are differentially incase by these different drugs that we've been talking about, also differentially impact the various aspects of executive function of the prefrontal cortex, increasing our attention for specific things.

And while there is a lot of nuance in the literature about this, we can safely say a couple of things. First of all, increasing dopamine in a particular synapses and networks in the brain can serve as what's called noise reduction. IT can help further enhances the quieting of all that background stuff.

That background stuff can be attention to things in your environment, like noises or visual cues. IT could be some internal narrative that had about yesterday, or something that somebody said about you, or something that somebody you like. Would you like to say about you, or whatever that might be that's happening in your head that's distracting you as well as your representation of your internal bodily state?

What we call into reception, this is a really important aspect of attention that we don't often hear about, which is that we have the ability to attend the things outside of us, which is called exterior tion, as well as an ability to attend things inside of us, which includes things like thoughts, but also includes, you know, for insinuation, empty or full, our gut feels when then not. We're comfortable in our chair. You know, when we think about the practice of focus and learning or focusing as a verb, IT involves often forcing ourselves to sit still.

IT often involves us suppressing the fact that our food is a little bit cramped or that we might need to use the restaurant room for, know, we might want to delay that for ten and fifteen minutes, even though you might be fairly urgent. All these sorts of things are central to our ability to attend and focus. And so dope mean, while IT does many different things in the brain, many, many different things.

One of its main functions in the context of all this prefrontal cortex and attention stuff is to quit the amount of noise, that is, IT helps the prefrontal cortex suppress the signals that would otherwise distract us into thinking about, i'm kind of thirsty right now. I need to use the restaurant. I really want to make this color, really want to pick up my phone.

All of that stuff, all of that suppression, that that quiet down of all the background chatter related to things external and internal to us in our head and our body is greatly facilitated by having more dopamine present in the synapses that allow for what we call noise reduction. Now, in parallel to that is north and emit an afra is released from multiple sites in the brain, in body. But within the brain, there's one major site of neons that manufacturer nor up an afra.

And the name of that site is lost. Seul us sits in the back of the brain. It's actually a relatively small collection of neurons, but they are very, very powerful. They extend their little axons, their wires to multiple locations in the brain. And they released the north and after at those locations.

So think of them sort of as a sprinkle system that originates from one of very vocal location, but that can sprinkle north and offer at multiple locations in the brain. And the amazing thing about los ulia and that sprinkler system is that indeed, the sprinkler system can be pretty widespread, where everywhere there's a sprinkle head, somebody's getting no up and effort. But I also can fairly vocally release nor up an effort at particular sites.

So while in the context of today's discussion, dopamine is acting largely to impart noise reduction, nura an f an has the ability to boost signals at synapses, is to increase the implicit and frequency of communication between neons. And in that way, in the context of day's discussion, nor up an effort when released at the particular synapses in the particular brain, networks that are related to attention and learning is largely serving to increase signal. So what we have in the context of a drug like at all, or which, to some extent, method date redland does this as well, is an increase in dopamine in europe.

And afin that is leading to two things, both the reduction in noise acquired of the circuitry that we don't want to hear so much from, and an increase in the signal of the networks that we do want to pay attention to. And the net effect of that noise reduction and signal amplification is what the engineers refer to as increased signal to noise. And the consequence of that is a heightened subjective sense or ability to decide what we want to focus on, sit down or stand there and just focus on IT.

So the way that we've been discussing drugs to treat A D H D and their ability to increase demmin in europe and if an, and thereby to reduce the amount of noise, so to speak, in the brain, and to increase the amount of signal related to things that we want to attend to, all presumes that the amount of dopamine and the amount of no upe and afra that's being increased is perfect for what we want to accomplish, which is increased focus and reduced hyperactivity and impulse sivy. But of course, in the real world, that's not always the case. Depending on the dosage of the drug, on sensitivity to the drug, even what stage of development across the life span a person is that things can really go haywire pretty fast.

And when i'm referring to when I say, hey, wire, is you think about doping and its ability to reduce noise, well, dopamine does a bunch of other things as well. And in fact, we know that if dolph in is increased too much in the brain of somebody that has A D H D, or somebody that doesn't have A D H D, people can become euphoric, people can become manic, people can even become psychotic. Likewise, if not un american is increased too much, people won't just become alert.

They will become very anxious, have panic attacks, and depending on the drug they're taking, they may even experience very serious purfoy symptoms, meaning elevated heart rate and sweating that is super uncomfortable and on and on. So everything i've been discussing up until now is true, but I want to make IT clear that it's true in the context of appropriately dose prescribed drug for a given condition, which leads us to the next question, which is, why would I be that giving these drugs, which are in fact stimulate? Why would that calm a kid down? Why would that common adult with hd down? And the answer to that is not completely straight forward.

And IT is worth pointing out that not everyone with adhd has impulsivity and hyperactivity and therefore an inability to focus. Some kids and adults with hd do have chAllenges with impulsivity and hyperactivity. Some do not.

Some just have chAllenges with focus. And I didn't entire episode about adhd, and we are going to have an expert guest on this podcast who specializes in the treatment of A D H. D to talk about some of these issues further.

But I just want to remind everybody that, as in the general population, children and adults with add are capable of very concentrated periods of focus. The pattern, however, tends to be that children and adults with A D A SHE have a harder time getting into that state of focus. And perhaps most importantly, they have a very hard time getting into a forced state of focus for things that they don't enjoy doing.

I'm sure many of you are also thinking, wait, I don't like to do certain things. And that is harder to focus on those things than on the things I like. Of course, does that mean I have the hd? And the answer is not necessarily so.

Kids and adults with A D H D exhibit in extreme variation in their ability to focus such that if there's something they really, really like doing, they can indeed focus, however, for many, many other activities that are required in order to develop. I guess we'll just call a Normal life advancement. So sitting still listen to conversations that we may may not be particularly interested in.

That's where the chAllenge has come about. So the point is that these brain networks and these modulators like doped in europe effort that we've been talking about and fairly straightforward terms as IT relates to a drug ability to increase their transmission and therefore ign improved ability to focus, presumes two things that presumes that the dosing is right. That is, that the levels of increases in these new modulators is just right.

And I also just want to acknowledge that A D H D is, first of all, not an inability to focus at all. IT is immense chAllenges in focusing on lots of different things as required for Normal life progression. And it's also the case that there is no one specific pattern of add that applies to everyone with a some people, both kids and adults, will exhibit the hyperactivity, but not the impulsivity.

Although those two things tend to go hand in hand, some people have a chAllenge in focus without hyperactivity, impulsivity and so forth. And all this just really speaks to the complexity of ad. And yet, and yet, we can confidently say that there are more drugs to treat A D H D than any other psychiatric condition.

We talked about a few now, but among those at oral vive ritalin, also called method candidate, there are time released versions. There are different variations on those time released versions. There's been straight dexterity, which is prescribed for radiation in some cases, and on and on. And you might also find IT interesting to know that that very large kit of drugs, all of which least the ones we talk about so far, sympathy and addix are stimulants, are more effective at treating add than are any other collection of drugs for treating other psychiatric disorders.

So what all of that diversity of symptom ology and adhd, as well as differences in sensitivity to drugs and individual variation, what all of that speaks to is that the large kit of drugs that out there is designed to be assessed with the careful console of a very qualified psychiatrists in order to allow the child or adult to arrive at a specific drug and the specific dosage that's ideal for their particular pattern of add. And that issue actually gives rise to the answer to that now somewhat Angels question as to why giving stimulants to a kid that is hyperactive would calm them down. And the answer is that the hyperactivity, impulsivity and focus issues present in A D H, D in children and adult are the consequence, not necessarily of deficient activity of neural circuits in the profondo cortex or deficient activity of the default mode network or deficient activity of the silence network at seta.

What appears to be the case based on a lot of high quality, newer imaging data is that the brains of children and adults with add have all of these networks functioning. But those networks are actually hyper connected, that is, they tend to be coache at times when ordinary, meaning in kids and adults without a they would not be. So that's an important point because it's easy to get the impression that A H deep is just a deficiency in the in the phone, and that simply not the case.

If you recall, dopamine e an effort are neural modulators. They modulate the activity of other neural circuits, and they can both increase and decrease activity within those circuits. So you don't necessarily wanted think about dopamine and aran afra just as molecules that increased neural activity. And you certainly don't want to think about ada. He is just a deficiency in dopamine or deficiency in north p and american.

The way these drugs work when they are used effectively to treat hd is to tune the amount of dopamine, europe and ever that are present, in particular brain networks, in order to allow the person to arrive at just the right baLance between the activation of these different neural circuits, causing them largely to be less synchronous in their firing. So this takes us back to this question, why giving stimulus to a kid would calm them down? It's not so much that you're giving a stimulant to a kid to place them into a state of calm.

I think that's a common misconception, rather by increasing dopamine and orpen efron these drugs, yes, increased levels of overall automation ic ousel. They are, after all, sympathy metics, but more importantly, to the treatment of add symptoms, you are activating the prefrontal cortex in a way that allows you to be more of a coordinator of that orchestra conductor. Or, if you prefer, the analogy to a teacher in the classroom to cramp up the activity of certain neural circuits in the given moment and quiet IT down the activity of other neural circuits such that the defauts mode network can still performance incredible actions.

After all, the default mode network is involved not just in self referencing and kind of daydreaming, but also creativity and imagination has been well described in the literature, as well as the silence network and these other networks that are designed to drop us into very narrow trenches of attention. These drugs for the treatment of A D H D are are indeed stimulants, but the goal are, prescribing these drugs to a child or adult with A D H D is to adjust dosage, timing and the duration over which somebody takes IT in their lifespan in order to allow those neural circuits to work in the proper way. Meaning for the conductor to activate the instruments in that little symphony or band in the appropriate order, in order to arrive at the right music, as opposed to all the instruments playing at once, which would just be complete noise.

Or if, again, if you prefer the classroom teaching an analogy for the teacher to call on one student while the others are quiet, and then to call on a different student, have one student returned to their seats to have the students work in small groups. Again, all of this by analogy, the point being that dopamine, ora and afford are all allowing these networks to be activated to the precisely correct levels and in the precisely correct sequence. Now the other key aspect of drugs like ador of events, riddle and similar to treat hd, has everything to do with these neuromodulators dopa and orpen efron.

But IT has to do with their other incredible feature, besides just their ability to reduce noise and increase signal within these brain networks. And that incredibly important feature is what we call neuroplasticity, or the brain nerve systems, ability to change in response to experience. I've done entire episode of the human land podcast on neural plastic, what IT is and how to access IT at different stages of development and in adulthood, by the way, you can find those episodes huberman lab, dcom, by simply searching plasticity in the search function.

But the important thing to understand about plasticity in the context of today's discussion is that while there are many different ways to induce neuroplasticity, almost all of them, almost all of them involve strongly activating certain brain networks, and in that case, also strong or elevated release of certain neuromodulators. Now we talk about dopamine in north and american. They are but two of many neuromodulators.

Others include sarti in to Colin. And each of the neuromodulators does different things that different synapse is in the brain. And there are some global statements that can be made about each of them.

We made some of those earlier like dopamine is broadly involved in motivation, craving and pursuit and european in signal detection and drawing of focus or silence. Do something in our environment or in our body or inner experience. Tony, does other things see to do other things.

But what's really important understand is that any time there is a dramatic elevation in doped in eupeptic, an relative to baseline, relative to what was happening with dopamine, european africa prior to that, that has a tendency to promote neuroplasticity at particular synapse is. So here is where it's appropriate to remind everybody that neuromodulators are different than neurotransmitters. Ors neurotransmitters ors are chemicals that, just like dopamine, european f are released between neons.

And they are what actually contribute to the electrical signals going upper down between different neurons. And again, dopa minor, euan evan modulate, that activity causing a given amount of neurotransmitter or to have an even greater effect, for instance. So when we hear about dopamine and nurp and afan and we hear about motivation or focus at that's all fine and good, but it's also important to remember that when doping and norumbia american are increased, there is a higher probability of strengthening connections where dopamine and north and ever or increased.

And what that means is that later, even if levels of dopamine and north and american are not increased, if they go back to baseline, it's often the case that if in our prior history or the history of a given set of neurons in our brain, there was more doping or north and afan around, it's very likely that the connect tions where that took place are strengthened and therefore more easily activated. And this takes us back to the really original purpose of prescribed ing, the synthes atic stimulus to children with add during development. IT was, yes, designed to try to help them focus to reduce their hybrid activity and help them focus.

But IT was also designed to help the brain networks that are responsible for focus to undergo neuroplasticity, that is, for the synapse is involved to strengthen so that those networks could function more efficiently later on, even after station of the drug. This is an absolutely crucial point that I think is not often discussed when people, for instance, say, should I put my kid on A D H D mads, or should I take my kid off of A D H D mad as they transition from add a lessons to their later ten years and into college. Mean, after all, no child or parent or adult, for that matter, wants to achieve a bunch of benefits with a drug and then lose those benefits later.

Nor does any parent or child want to take a drug that they don't need to take when they could access other routes to improving the neural circuitry or the function of some health system in the body. Because I don't think anyone really wants to medicate their kids unless they have to, I would hope not. And I don't think any kid wants to be medicated unless they absolutely need to be medicated.

So increasing dopamine in europe, american with these drugs like at all vivants ridley and is causing several things and some of those things actually provide some general answers as to whether not parents should put their kids on these compounds in the first place. Obviously you're gona do that in the uh under the careful console of a qualified psychiatrist, I would hope, and only under those circumstances, but also whether not the child should stay on those drugs over time. And here's what we do know for sure.

I did a vast search within the literature in order to arrive at what is very clear, which is that children with A D H D, true A D H D, who are diagnosed with A D H D and are treated with appropriate doses of drugs like adorable, riddle in or vivants, far, far Better, both in childhood and later in life. When IT comes to performance in school, performance in terms of focusing on anything and in terms of general outcomes. So for instance, a lot of people have wondered and worried about whether or not treatment with these drugs early in life will set up a predisposition for illicit drug abuse or craving addicted potential later.

And IT is very clear from the studies that have emerged over the last really fifteen years, but mainly within the last five years. That's when most of the data have arrived, that children with A D H D who are not treated correctly, both with drugs and behavioral treatments, because really the combination of drugs and behavioral treatments is the optimal situation. So kids with add who are not treated with drugs and behavioral treatments to deal with their hd have a much higher tendency towards illicit drug use and addictive drug potential in their adult d okay.

So there is a real danger to not treating adhd during childhood. And the reverse is also true, which is that children with add who take prescription drugs that are sympathy medics. So yes, as you've heard, they are speed effet min speed.

Although I should say if they take method fdic riddling or concerned something and that sort that's not emphatic omy, none. There's it's a stimulant. It's a synthetic matic. Also, these are kids that are taking these drugs in development. And therefore, levels of dopamine levels of north panama are being increased in their brain and body.

And you might say, well, when that lead to a craving for the things later in life, and that does not appear to be the case, in fact, there are some very nice, no imaging studies, mainly positive on emission torode phy studies, that all provide a link to in the showed captions that show the early treatment with these drugs actually leads to combinations of increased dopamine e transmission in the forebrain later in life at a lower level or a lower threshold. I should say, in a way that essentially says there's Normalization of the circuits across time by the application of these drugs early in life. Again, in the case of children that have diagnosed A D, H, D, I in no way, shape, perform, want to imply that all children should be treated with these drugs.

This quite clearly not going to be a good idea. So all of this really speaks to the critical importance of getting an accurate diagnosis of hd. Diagnostic criteria include many things in children.

They're multiple. They're more than nine diagnostic criteria for each of the categories relating to impulsivity, hyperactivity and so on. So a well qualified psychiatrists will do several things. They will, first of all, do IT careful diagnostic evaluation of a child.

And in addition, one would hope that they would think about prescribing both appropriate for mac logic treatments for adg, but also be aware of and prescribed the various other types of prescriptions, meaning behavioral prescriptions. So there are clearly certain learning tools and things that kids can do in order to improve their ability to focus and to be less impulsive. That combined especially well with drug treatments, as well as new advancements in the realm of nutrition and supplementation that are constantly coming online.

And the best psychiatrist s are going to be tuned into all of those aspects of treatment for add, not just prescription drugs, but also behavior treatments, also nutritional guidelines, also supplementation, and also updating each and all of those things as a child matures from each stage of development to the next. Now the other common question is, if a child has been treated with these adhd image during development, do they need to continue on these drugs indefinitely? And the short answer to this is IT depends.

And that can be a somewhat frustrating answer, I realized. But the good news is it's something that can be assessed in a fairly straight forward way. Let's recall that the use of these drugs to treat d is designed to accomplish two things, is designed to improve the function of those neural circuits that allow a child to focus.

And it's also designed to increase the strength of those circuits to effectively teach the circuits how to learn what focus is. In other words, these drugs are designed, in some cases, to be used and then withdrawn later because the circuits that they helped to build up are functioning well. In some cases, however, the circuits that under life focus are not going to be able to function at the level required for Normal healthy life progression unless there's continued application of the drug.

So how would this work in the real world context? Well, think any child or adolescent or person Younger than twenty five that taken these drugs has no doubt achieved some level of neural plasticity of the neural circuits related to all the things we call focus on. And I want to be very clear, there is no single brain area or set of brain circuits for what i'm referred to.

His focus because, after all, focus involves test switching. Focus involves all sorts of different cognitive Operations, depending on what we're focusing on. The focusing on a sport is have basically a practice of directing one's attention in different locations, at different moments. Focusing on studying is an entirely different pattern to focus all together.

But the point being, if a person twenty five years or Younger takes a drug that increases dopamine and uh and f and assuming that things are working, meaning to do this right, they're achieving Better ability to focus at at a those circuits are going to get stronger. And IT seems entirely reasonable. In fact, IT was supported by the psychiatrist that I poke to prior to the episode that people have been on add meds for any point of time prior to twenty five.

Talk to their psychiatrists about what tapering off those drugs in order to examine whether or not they still need those drugs would look like. Now I mentioned the word taper because there is a withdraw potential of simply stopping these drugs very quickly because they do ramp up dopamine and north and earphone, even though they increase plasticity of the neural circuits for focus and mood and motivation. If one very abruptly ceases taking any of these drugs, IT does not feel good.

That drop in doping, that one inevitably and experiences, is almost always associated with leverage, with mood, with feeling not good in a number ways, and of course, chAllenges and focus. So any time one is going to go off, one of these drugs are sample. What IT is to even reduce dosage that has to be done in close communication with a board certified psychiatrist.

At the same time, IT was made very clear to me from A D. H. D.

Experts catrice, that reductions in dosage over time often are optimal for a patient. Kay, and this gets to the whole issue of dosage. generally. I spent a good amount of time talking to somebody who prescribe bes these drugs, both to children in adults, about dosage ranges. And I don't want to spend too much time on this from the perspective of how much one should take.

In fact, I don't want anyone to think that what am about to say should dictate what they should take, specifically because that something that really has to be worked out on an individual basis. But IT is worth noting that you look at the studies on atter all and method finites, you'll see this is a pretty broad range in those studies. And that's because some of the studies used people that we're already taking these drugs and ask them to participate in their imaging studies.

Other studies actually put people on these drugs for the very first time or adJusting their dosage. And so you'll see A A tremendous range of drug doses explored. For instance, you will see anywhere from ten to forty milligrams of atter all per day.

You'll see anywhere from tend to sixty milligrams of riddling per day. And here we could easily be talking about studies on children or adults. With respective vivants, you'll see that the dosages tend to be much higher.

In part that's because vivants has, if you recalled, is that license, which is a big molecule stuck on D M. Fedex, in which is a smaller molecule. And so the dosages of violence tend to be in the hundreds of milligram ranges, but most of that hundreds milligrams of vivant is not going to be the dm federman.

It's going to be the license, which doesn't do anything in the context of treating the brain, is just there to control the slow release. So it's thought that one hundred milligrams of vivans translates to roughly nine milligrams about all and on and on. And actually, it's pretty hard to translate between dosages of different drugs in any direct way.

And in speaking with a psychiatrist expert in hd in preparation for this episode, he made very clear that he is extremely, extremely difficult to predict how a child or adult will react to a given dosage of any of these drugs. So much so, in fact, IT he, an idol, reported to me that one of his patience is a male, three hundred pound, diagnosed with add, and who achieves tremendous relief from just two point five milligrams of at all per day. And at the same time, he has two patients, both of whom are sisters, so are genetically related, who are in the hundred and twenty two hundred and forty pound range, who did not respond well at all for the treatment of the d hd.

Until their dosages were very, very high. And if I tell you these dosages, I just want to warn you in advance. I'm not suggesting anyone explore these dosages without, of course, the approval of their psychiatrists. Turns out that neither of these two Young women responded at all to A D. H.

Medication until they achieve dosages in the range of one hundred and eighty in the case of one sister, and two hundred and forty milligrams in the case of the other sister per day, which is an astronomically hypos on the face of IT. But this physician and board certified physician expert in verified for me that indeed, neither of them experience any discomfort, side effects that let them to not want to take the drug. But of course, that amount of adorable could send somebody else into an absolute psychotic fit, could potentially even cause cardiac arrest.

I mean, it's remarkable the ranges of atole that are used effectively in children and adults. And this is true for a lot of the other sympathy tics used to treat adhd. And of course, a good psychiatrists will always assess dosage as IT relates to positive benefits, relief of symptoms, so relief of impulsivity, relief of hyperactivity, improvements and ability to focus. And of course, they are going to consider side effects and an uncomfortable adverse effects that come from taking the drug at a given dosage or taking the drug at all. Now, of course, this all begs the question of why such tremendous variation.

Is this due to genetic differences in the amount of dopy? Or euan, if that people make IT appears that the major underlying factor for why people require such vastly different dosages of these synthetic metics for the relief of add has to do with the different enzymes or levels of enzyme s that people make, which metabolite these drugs, both in the brain and body. And unfortunately, there is no simple blood test or saliva test or test of any kind that can predict how someone respond to these drugs.

So the most logical and safe way to assess dosage is to start with the lowest possible effective dose and to increase only as necessary in order to achieve the positive benefits. Well, of course, paying attention to any side effects that might arise. A question that comes up from time to time when discussing the long term effects of drugs like atrial riddle and vivants is whether or not they can negatively impact height or growth or development in some other way.

This is a logical question to ask because after all, these drugs are effectively mimicking stress in the body. And most everyone has heard by now that while stress can help us in the short term, IT helps us deploy immunity, lead les to protect us against infection. IT sharpens our visual focus on our ability to respond things for survival, chronically elevating our stress over long periods of time, we know reduces the effectiveness of arming system and can actually cause certain forms of brain degeneration.

And while there aren't a lot of launch to no studies on the heights of kids with A D H D, and of course, we never can tell how told someone would have grown to be if they were treated with the drug, because we don't have a perfect control experiment, even in the case of identical twin experiments. And there and there rented that many of those examples where one twin was treated for d hd in the other wasn't, IT said. But here's what we know.

IT does not appear that treatment with synthetic metics during development, provided the dosages are kept in the appropriate ranges, is going to limit overall height. In fact, if you look at the data, IT appears that children with adhd who are treated with A D H D mads actually arrive at slightly higher bm s body mass indexes compared to age matched peers. Now, of course, body max index doesn't necessarily correlated with height, right?

Someone could not achieve a full height, but could be heavier either through bone or fat or muscle or combination of all three. But what we know is that the appropriate use of hd mads during development is not stunting development in any kind of overall way. It's not preventing maturation of the body in ways that are leading to reduced weight or somehow impaired growth overall.

With that said, long term elevations of sympathetic nervous system activity does Carry some risk, and one of the primary risks that people have wondered about is cardiovascular risk. And this makes perfect sense, right? When you increase the activity, the sympathetic system, you increase, blood pressure will increase heart rate.

You increase, in some cases poor for sweating. You are all the things that we associate with stress. So you can imagine that a child or adult with ad that takes these sympathetic metics every day, even if the dosage is kept in a range that doesn't allow them to experience any immediate untoward side effects.

So they're not feeling miserable, they're just feeling like they can focus Better. But one always wonder what's going on under the hood, so to speak. There is, as far as I know, one major study that addressed this, and the conclusions of that study were a little bit hard to put into a single category.

IT did point to a subtle increase in cardiovascular risk, but the results did not point to anything so dramatic that the authors of the study warned against taking these drugs are encouraging people to seize taking these drugs again, provided are being prescribed by abort certified ysp an 4 add and at the appropriate dosage for that person。 That said, I think this all again speaks to the importance of arriving at minimal effective dosage. And IT stands to reason that if you're somebody who's taking hd mads, or if your child is taking adhd mads, that one would want to do all the other things that they could do in order to try and to improve cardiovascular health, or at least not put IT at additional risk.

So those are going to be the obvious things like avoiding smoking or walking. nicki. Um regular exercise is going to be encouraged and things of that sort and that dub tails into a bunch of other questions that are often asked any time the topic of ador all riddle comes up, which is what about alcohol you know is drinking alcohol at the same time or at different times even going to be problematic if one is taking these drugs is taking bench and I ask a peans going to be a problem at set up, set up.

There's a very straight forward answer to this, which is it's very clear that alcohol, certainly in children, but also an adult, is best not consumed. I did entire episode about alcohol got into this and the data for this. If you've heard that having some alcohol and particularly red wine is Better for you, that no alcohol, that is simply not true.

Sorry, it's not true. Most adults who are not alcoholics can probably have up to two, that's right, two drinks per week and still beyon the safe side of health, although zero is Better than two. And once you get past two, you start seeing effects on various systems, including increased cancer risk, especially brain neuron loss and the generation risk.

I covered all of those data in the episode on alcohol. You can find a huberman lab dot com combining alcohol with sympathy metics, even though they reside in very different pathways within the brain. In fact, the sympathy metics are driving up sympathetic nerve system activity. Where has alcoa is actually doing the opposite, depressing IT. And yet, all the data point to the fact that combining alcohol with sympathy metics, such as by vance atrial redlining or any kind of amphetamine, is going to be more detrimental to the brain and body than simply taking those drugs on their own.

Put differently and more directly, if you are taking any of the drugs that we've been talking about to treat A D H D, or if you just happened to be taking them for whatever reason, you are going to want to avoid drinking alcohol at any time, and you're going to want to avoid benzo diasaster and similar unless they've been prescribed you by your physician. In the advance of this episode, I put a call out on social media for questions about at all at sea, and I got a lot of questions about whether not their impacts of these drugs on the hormones systems of the body, and if they impact the reproductive system in particular. I also got questions about whether not these drugs impact sexual behavior or labels, or anything of that sort.

In reviewing the literature, what I can tell you is that there are very few studies, unfortunately, of the long term effects of these drugs on the indecent or hormonal systems of the body. But we do know a few things for sure. First of all, when you increase the activity of the sympathetic nerve system for long periods of time, you are very likely increasing levels of cortisol corzo a cording stress hormones.

But cortisol also play some really important positive roles in your body. In fact, do you want court is all released especially early in the day? You don't want court is all released so much late in the day? This actually relates back to timing and schedules of taking drugs.

This is something, again, that needs to be worked out with your psychiatrist or your children's psychiatrist. But one of the reasons why there are so many different drugs for the treatment of hd is that each and all of them has a different time course of action. So riddling is very short lived, which might sound bad because then you have to take a multiple times throughout the day.

But if you think about from the perspective of sleep, in the importance of having low cortez all at night and these drugs increase court is all, and the importance of getting sleep, because, after all, sleep is. The foundation of mental health, physical health and performance in kids and adults is responsible for growth is when neuroplasticity happens is just so vitally important. A lot of the drugs that we've been talking about can severely limit ones ability to fall and stay a sleep.

And so a short acting drug like riddle is actually attractive from the perspective of being able to take IT in the morning and still get to a sleep at night, or taking IT in the morning and in the afternoon and maybe even again in the evening, depending on the person, and then still being able to fall a sleep at night. We're as londres ation release of D M. Fet in which is what you get when you take vivants, for some people, is going to inhibit their sleep.

We'll get a nice steady rise and improvement in focus in reduction in hyperactivity, but they might have a lot of trouble falling and sleep at night and add all having a somewhat intermediate time course of action between real in which is short lived in vivans, which is very long lived, perhaps is going to be the best solution for somebody else, where they can take IT early in the day, perhaps. So low dose may be again later in the day, low dose, and then still fall asleep at night. But i've spoken to people, and I spoke to this clinic expert in A D.

H, G, who told me that some people take as little as two point five milligrams of adorable at six am and have a hard time falling asleep later that night at eleven pm. So again, vastly different sensitivities to these drugs, leading to vastly different requirements of dosage and timing of intake in which particular drug somebody might choose to or choose not to take. So how does that relate to hormones and sex and reproduction? Well, court is all itself is a hormones can act as a bit of a horn and a neal transmitter in the brain.

But for the most part, it's acting as a hormone in the brain and body. And IT does is a number of things. First, all IT can enhance your levels of focus and alertness.

IT can activate your immune system. I know the immunologists out there. Just clinch when I say activate the new system, immo system is a doing various things, so it's always active, just as your nervous system is always active.

But I can to be specific, IT can amplify or mobilize the release of anti inflaming molecules in your brain and body to combat different types of bacteria, viral and fungal infections, doing an enormous number of positive things. It's also involved in setting mood. IT has interactions with virod hormonal pathways.

I've done entire episodes about cortisol and cortisol regulation to paint all of that with a very broad brush. And briefly, now its advantages to have your court is all released high in the early part of the day and to taper off toward the end of the day. In fact, late day elevations in court is all are a strong correct of depressive symptoms.

This was demonstrated by my colleagues David speel, and I would supose cate stanford school of medicine, but does not to say that course l is bad. It's to say that the timing of cortisol release is key. So do these sympathy matic drugs disrupt the indecent system? Well, they can. If you are very awake and very alert, regardless of whether not you're taking your sympathy, edc treatment for hd early in the day or late in the day, you are very likely experiencing elevations in court is all late in the day.

So IT is important even for those of you that like to study and need to focus in the evening and nigh time hours that you're try to limit your levels of overall alertness and certainly stress late in the day, because doing that day after day after day for several weeks or months or years can indeed disrupt other hormones in the underground system. And again, that's because court is all is interacting with firewood hormones and testosterone and estrogen. In fact, court is all in many ways compete swith or can out compete for the production of testosterone and other so called steroid hormones.

Remember, court is all itself is a cortical steroid hormones. So when we hear there with stereos, often ized people just think about athletes and steroid abuse in sports. But skid hormones includes a lot of different types of hormones, which are good for us.

Our doggy ous stereo hormones are vital for all sorts of things. Fatality, reproduction is set up. And the way this works in general terms, is that the cholesterol molecule is used to create test.

Astro in court is all. And as rogen, if we make too much cortisol, we in many ways are reducing the total amount of testosterone that we make or that is active. It's not exactly that straight forward, but we can make that statement with with confidence.

For instance, if you Spike your court is all just briefly during the decays, some sort of stressful event that's not going to inhibit your test ostrom. In fact, IT probably is going to boost your test oster R N levels somewhat. However, if your cordial levels are chronically elevated, yes, indeed, it's likely that you're going to suppress your total and or free unbound forms of this and downstream to that.

You will experience effects such as reductions in the beto, reductions in muscle and bone mass, reductions in all sorts of aspects of testosterone related psychology and bodily biology. This is true for both males and females. And the same thing could be said for estrogen.

Now, what's impossible for us to say is whether or not taking a given treatment for D H D is going to, for instance, prevent a woman from emulating that could happen through chronic elevations in courter. But there's no direct link, meaning there are no studies, at least that i'm aware of showing that people that take out of all have irregular observatory cycles or that they see me strating entirely. I don't think there's any evidence for that whatsoever, nor is there any evidence that people that take at all or other same athon medics for the treatment of have lower overall test strong.

In fact, you can imagine all sorts of instances in which the opposite was true, that a child or Young adult or adult, who has A D, H, D, but then goes on these means to improve their symptoms, is now focusing in achieving more in life. We know that happiness can impact depine and vice's sa and testosterone levels and productivity itself and reaching our goals can feed back on the hormones system. So anytime there's a discussion about hormones, where a study that shows that doing x or not doing why impacts hormonal levels of a given type, we have to be very careful to make sure that we're talking about causality, because all of these hormones are in a very intricate cross talk with one another.

We can, however, make a very general statement, which is that when you are in states of stress for long periods of time, that is not a favorable condition for your immune system, your hormone d system, or Frankly, any other system in the brain and body. So the trees of a city with these drugs should never be done at the expense of these other critical biological systems. Another common question in concern is whether not kids, and I suppose for that matter, adults that take medication for adhd are basically being predisposed to psychosis and or other forms of addiction.

And earlier we talked a bit about the risk for addiction and the take home message. There is very clear that kids and adults that are treated for d hd, appropriately so, with the appropriate dosage of the appropriate drugs under the supervision of a board certified qualified psychiatrists, are at less risk for forming addictions to other substances in adult or other substances generally. I think a lot of people also wonder whether or not those kids and those adults that take the D H, D.

Mads become addicted to the medications themselves. It's a bit of a tRicky issue to resolve any time one stops taking a drug or even tapers off a drug that's used to treat something where they feel Better on the drug, they're going to experience two sets of effects. And these two sets of effects are often confounded with one another.

One is the withdraw effects. So the effects of removing the drug that makes somebody feel less good than baseline. So for instance, a kid that takes A D H D meds until there are like teens are only twenty years, decides are going to taper off.

They do that and they're elling loudly during the taper or when they reduce their dosage to zero their foggy brain. They can't focus that. If you a little bit depressed mood, it's unclear whether not those are withdrawal symptoms or whether not those are the consequence of not having the systems in their brain activated the way that those systems were activated.

Before I realized that for some of you, that my team like the same thing, but that's not necessarily the same thing. And probably the best analogy would be something along the lines of a hangover, right? If somebody drinks too much on a given night, the next morning they've hangover, the hanger makes them feel louse IT is actually withdraw from alcohol effect.

But then when they recovered from the hangover, they realized that their sober state and feels pretty good. IT doesn't obviously feel the same as being on alcohol, but that sober state is not a state of with your all OK. We were to look at removal or tapering off of adhd meds.

There's going to be a period of withdrawal symptoms. But then the real question is, how does somebody feel after they get through those withdrawal symptoms? So important issue to highlight.

Now in terms of psychosis, this is a very interesting and very important literature. First of all, any m fet me where the D M femme L M fetching, and also metal finites for that matter, riddler can induce psychosis. Now there are number different factors that are going to predispose somebody to psychosis.

Having a first relative whose had psychotic episodes, either schizophrenic episodes or bipolar episodes, is certainly a strong previous position, of course, of an individual themselves have had psychotic episode that the strongest to predisposition that one can imagine. So having a first relative with chizen hernia or with bipolar depression, or sometimes called bipolar disorder, sometimes it's also just called bipolar these days, is going to be a strong previous position for psychotic episodes, made much greater. Anytime one takes a synthetic metic drug such as effet mine, but also method finny riddling, going to increase the likelihood of psychotic episodes.

Then comes the question of, if somebody has a psychotic episode, as is the consequence of taking any of these drugs, whether not it's been proscribed for adhd or not, will those psychotic symptoms go away after the person stops taking the drug? There appears to be a divide in the literary, or rather, or divide according to drug, such that people that take riddle in method date and have a psychotic episode, often, not always, but most often if they stop taking metal final date, the psychotic c episode will cease, not always the case, but most often times IT will seize. Whereas in individuals who have a previous position to psychosis.

Or even if they're not aware of a previous position of psychosis and they take ad of all, which is, you recall his accommodation of d and l fedex ine. They can have psychotic episodes that sometimes are very long lasting even after the sensation of the drug. And while that might sound kind of shocking and really scary, and indeed IT is scary, IT perhaps shouldn't shock us that much.

Because if you recall, D. M, fine, which there is a lot of in adorable, it's a very potent way of increasing dopamine. And any time you potentially increased dopamine in a person who has a pretty position of psychotic episodes, you are shifting the whole system toward, uh, greater propensity for psychosis.

This would also be the appropriate time to talk about mess. mess. M femme and method to me is considered an illicit drug, a drug of abuse.

IT is responsible for a lot of the misfortune and tragedy that you see on the streets of major cities and even outside of major cities in rural areas. IT has all sorts of negative effects on health, including oral health. Cardiff asked lar health um IT is neurotoxic to serotonin. Gic neurons kills serotonin neurons that is absolutely clear. IT kills dopamine, a gic neurons that is absolutely clear.

One of the ways that metheny demi creates so many the problems that IT does, inning effects on the body abuse potential, addictive potential, the fact that method fet me can Spark kosis in those that have a pretty disposition of psychosis, but also that I can create psychosis in individuals who have no pretty position to psychosis. All of this points to meth epidemic just being a terrible drug all around. And yet, if you recall back to the begin of the episode, there is one form of prescription method timing, but its uses are extremely narrow.

And it's probably best left out of this conversation because its uses are so, so narrow in the clinical sense. I managed to talk to one expert. This is a board certified psychiatrist who is expert in he who is also a very familiar with the psychosis symptoms induced by metem headmen and by various adhd drugs and people who have the predisposition.

They made IT very clear that any of the sympathy matic hd drugs that are of the effect mine variety, so that would be at all. And extended release ador, all I will be peer dexedrine, or any variants that include ampt mine are going to have higher likelihood of inducing psychosis and people that have a previous position of psychosis. And yet they did assure me that that appropriately prescribed and safe dosages, that the total instances of psychosis in people that take those drugs is still fairly low and not that much greater than in the general population.

Although there is an increased risk, it's not that severe. And they also highlighted fact that methods ini riddle in Carries a lower potential for inducing psychosis, not zero, but the lower level of inducing psychosis then for the infected me types impair me medics. Now, one exception is via vance, that long release. The effects me that we talked about earlier, there does seem to be something protective about that long duration release of dm fedex in that occurs with violence, which is not to say that there's zero abuse or addictive potential with vivants. Um I was told by the same individual that indeed um .

they've had knowledge of patients trying to increase the rate of absorption .

of violence and release of vision or technically of the dmf deming in order to get more of a high from violence as supposed just the extended release but they did assure me, however, that vivants seems to be associated with fewer psychotic episodes and less abuse and addictive potential overall which again is not to say that it's a perfectly safe drug but really this just highlights the fact that the connect ics of the time course of dopamine and or reef n release that caused by a given drug is going to correct very strongly with its abuse potential and addictive potential and its potential to induce psychotics episodes.

And this is where the discussion about math becomes especially relevant. One of the reasons why math is so dangerous in terms of it's addictive potential and its potential to induce psychotics episodes is, first of all, how much dopamine IT releases, again, five times more than any of the other drugs that we've been talking about, but also how fast that peak comes on. It's a very fast onset.

That's true. Whether or not people are snorting IT up, they're taking IT orally or especially if they inject IT intravenous eusden. But math, because IT increases, demeans so fast into such A A great degree.

And then the the peak and dooming comes down very fast as well and drops below the baseline levels of doping that were at present initially. That's one of the reasons why meant fet mine is so dangerous in terms of addiction and in terms of psychotic episodes. This gets back to a bunch of issues we've talked about before on the human mind lab podcast about dopamine connector s.

And i've done two episodes on doping that will refer you. One is called dopamine motivation and drive, which is all about doping and regulating doine. And the other one is about optimizing dopa minutes more but tool kit focused epsom, both those who can find a huberman and lab dog calm.

But the general take away that's relevant for what we're talking about now is that with dopamine, it's not just about the absolute levels of dopamine in that are reach, but how long lasting those increases in doping are. So with vivant, even though vivant is D M. fatma.

Fairly and not as potent and as math, but fairly potent at increasing doping in north and american. It's a long extended release in dopamine, the north and effort, which reduces its overall abuse potential because IT doesn't tend to create that immediate euphoria and high and then crash below baseline. Lot of you will hear that IT increases dopamine a lot and then stays up as translating to okay, well, then you're just you fork for sixteen hours, but that's not the case when IT comes to dopamine.

It's an issue of how high that peak is and whether or not that peak is stable or whether or not that comes down again. And when IT comes to psychotic episodes or addictive potential, IT seems that any drug or behavior that increases dopamine very quickly and then brings dopamine down very quickly is what sets the high potential for addiction and abuse and for inducing psychotics episodes. So that's why talking about these two things in parallel.

And now IT should be very clear why vivants doesn't have so much addictive and abuse potential and has at least lower potential for reducing psychotics episodes. And IT should also be cleared to you that for people who do not have A D H, D as a child, or for people that do not have adhd in adult, if they were to take any truly any of the compounds that we're talking about thus far, method date riddling, atrial vivants dexedrine and certainly matthee amine. What we observe from neuroimaging studies is that these people get enormous increases in doping.

They're not familiar with these drugs. So the increases in dopamine e are just cosmic for them. They experience a lot of euphoria, even if the dosages are low. The euphoria associated with this a very heightened degree of focus they never really felt before here with talking about, is a lot of the recreational and off prescription use of adorable and things like IT. And what we know is that that sets in motion both a potential for abuse and addiction to that feeling and substance as well as a higher potential for psychotic episodes down the road. okay.

So put differently, children who have adhd and are prescribed any of these drugs, or adults who have adhd and are prescribed any of these drugs who take them for some period of time, are actually at lesser risk to all of the issues related to having chronically elevated and greatly elevated dopamine as a kind of first time event or as a rare event. Whether anyone who takes these drugs without a prescription and decide OK, I want na focus more. I'm onna.

Use this to stay up for a couple of days or using IT recreationally. We're using IT for gona performance enhancement. Is that far greater risk for addiction to the substance? Ces, because of the amplitude and the time course of dopamine that results when one takes these drugs just out of the blue. And so for that reason, I really want to caution everybody against using any of the compounds that i've discussed as far, unless it's been described to you by a physician for the specific purpose of add.

Now i'm sure someone else there is screaming ing from the back, wait, if a kid takes these drugs because they are prescribed them for add the very first time they take them, they are going to have a huge amplico dopamine response or if an adult goes in and talk to their psychiatrists, sts and said, you know, i'm having issues with focusing in their prescribed one of these meds for hd and they take IT, they're going to have a huge ample to top amine response isn't that going to set in motion all the same things that somebody who is using these drugs recreationally would have? And indeed, that's one of the reasons why a lot of psychiatrists will start with a very low dosage or the lowest possible dosage to see how somebody responds that low dosage and then over time, might or might not increase that dosage. In fact, they might didn't bring IT down further depending on how sensitive somebody is to the drug.

But equally important is the fact that IT is the repeated taking of that drug by the child with A D. H, D, or by the adult with A D H. That actually leads to lesser and lesser peaks and dopamine each time, which is not to say that the person becomes entirely desensitized to the effects of the drug, but rather that the system calibrates through what's called homeostatic plasticity, sometimes referred to broadly as habituation to a drug.

But there are systems in the brain and body that regulate the connections between neurons so that if dopamine erp, an american, are elevated above baseline levels for a while, the system Normalizes so that instead the connections between neurons to become stronger. And there isn't a critical requirement for all that increase in dopamine. And north.

And evan, I realized that might sound a bit technical, but basically what i'm saying is the response that somebody has to taking a drug for the first time is far and away different. Then the response to a drug that somebody has, if they are taking the same drug day after day after day, this gets to another issue, which is not discussed that often in these days, but that is really important. If you go back to the original clinical literature on the symptom mics, what you will find is that the original use of these sympathy medics to treat childhood hd suggested that children not take these drugs every single day.

Now i'm not recommending that kids take drug holidays. Because i'm not a clinical i'm not promoting any specific dose or dosing regime. But in speaking again to a psychist st expert in hd, who by the way, is going to be a gust on this podcast in the not too distant future, what he told me was that many of these drugs were designed to be taken during the school week for children with weekends off, or during the school year with weekends off, but then also with vacations during the summer holidays.

And that these days, rarely, if ever, is that the pattern of intake that these kids are following, and why that is, has interesting sociological and financial explanations. Not alluding to any kind of conspiracy here, but this is an aspect of the dosing with these drugs that is falling away in recent years, but I think is really interesting. And it's something that actually was supported for the treatment of adult adhd as well.

Again, there is a very different biological and neural plastic response to taking a drug once versus taking a drug for, say, five days and then taking weekends off to taking a drug over and over again every single day for a pattern of years. And when expLoring the literature in preparation for this episode, I confessing was a bit disease to find answers to what are the long term effects of taking at all, or what are the long term effects of taking violence at set up? In fact, most of the literature on the long term effects of taking drugs to treat adhd has focused on method findon riddling.

There are studies on violence in atom and actually those were the studies ah that I will link in the showed te captions primarily because that's we're most of the interests these days. The reason why so many of the studies have focused on method Fanny on the riddle is largely because that was one of the first drugs used to treat hd. So in terms of addressing sing long term effects of kids treated with hd mads, those kids are now adults and therefore can be narrow image and assessed whether a lot of kids that have been prescribed out of all or vive answer similar have not yet made IT to stages of life in which we can answer that question directly.

There are a few studies, and i've made IT clear to include those studies in my description of results today, in particular the result I talked about earlier, where there's an improvement in executive function in kids that have taken hd mads or adults that have taken A H emds for a longer period of time, anywhere from months to years. Those studies did include both atrial and vivants and method end date, and again, link to those studies. But by in large, most of what we know about the long term effects of any of these drugs has to do primarily with studies of method date.

I'd like to spend a little bit of time talking about some compounds that are not considered in fet mines at all, but that are now being used to treat adhd, both in children and adults more frequently. The major drug in this category of non infect mine treatments for add is modiano, which is also called by its commercial name provoque. There's a variant on this, which is our modano, which goes by the brand name nuvigil.

The major difference between and armored final, aside from having a slight chemical difference, is that modano was released first, armored ol the second, in the generation of these drugs. And modano tends to be very expensive. That's one of the reasons why it's prohibitive for some people to take.

IT can be as expensive as twenty five dollars a pill, more and more than a thousand dollars per month, and armored fi tends to be far for less expensive. I talk to a couple experts about whether not there any genuine differences between these two drugs, and they report no consumers of these drugs for whatever reason, whether not placement or not, report. Yes, there is a different when I say placement, I in no way mean that these drugs are just acting as placable.

I just mean that you people tend to get very attached to certain drugs. And whether or not the brand name or the generic version works Better for them, there's all sorts of lower about this. In fact, there are a lot of people out there who strongly feel that brand name add all works Better than generic ata all for them.

There are a lot of people out there who say the same thing about vivants. There are a lot of people there say the same thing about brilliant and all sorts of drugs. Whether not that's true or not is unclear.

IT is clear that generic versions of drugs can use binder and other things that are in the pillow or capsule that are different than what the brand name pillar capsule uses as binder to hold the drug together, and that can impact rates of release and metabolic. Ta, but a lot of this is just law red. In fact, I went into the litter church to try and find any real concrete support for the idea that scene atoll is less potent or less effective than brand name at at all.

And despite the tens of thousands of people who will say to the contrary, I could not find any peer reviewed publish data about that. So who knows? Maybe it's a belief of factors. It's called maybe there's a real difference there nowaday more different and are more definer prescribe bed for a huge range of daytime sleeping, this issues. And we were talking about narcolepsy, but there are also people who suffer from daytime sleepiness related to dementia, daytime sleeping, this related to post surgery anesthesia.

So there's this thing where people have surgery, and then they come out of surgery and they feel Better for a few days, but then they find that they aren't recovering their Normal levels of wakeful ness. So it's prescribe bed sometimes to try and get people back into a Normal state of wakeful ness. So prescribed for a traumatic head injury after stroke.

Again, all of these prescribe users have to be Carried out by a certified physician. You really don't want to start carboy um the use of final or modano or any other prescription drug for that matter must say that in discussing all these different drugs during today's episode, I have zero knowledge of any of these drugs from a first time experience except for armored fi. Back in twenty seventeen I was prescribed a very, very low dose of armored affinity for jet lag, for daytime sleeping ess issues, really, when I was travelling overseas to give a talk.

So armored afi o was given to me in a twenty five milligram tablet. IT was advised to me that I take a half, even a quarter of that. So I started with a quarter.

I am a believer in minimal effective dose, and also somebody who's fairly hypersensitive to most medication. So I took what I measured out to be five to seven milligrams of r modal. And what I experience was pretty profound.

Certainly, IT relieved any daytime sleepiness. In fact, IT made me feel extremely alert for a period of about four to six hours. I can't say IT was the most comfortable state. Although I did not feel if I had a racing hard to anything at that sort, I basically felt as if I was in a narrow tunnel of attention for that entire period. Um one thing I did not like about the experience is that there was a very hard experience to come down from.

There was no crash, but I found that that high arsenal state didn't taper off for many hours later even though I was most tightened for four hours, I would say anywhere from eight to twelve hours later, I still felt like I was blinking once every four minutes or so. And i've certainly been accused on this podcast, and at other times of blinking to seldom, to my knowledge, C, I don't have a hd. I've never been prescribed mads.

I've never been tested for adhd. I don't think I have A D. H. D. And yet, taking armored official certainly increased my levels of attention. But least by that, one experience is not something that I would want to repeat again. I certainly wouldn't not want to be in that state for learning new material.

When I sit down to research a podcast or research papers in my labor ford for information, or learn from people are books or lectures or podcast, I want to be in a state of alertness, but calm, where I can really consider the ideas, where I can script things out by hand. Am a big believer in writing things out by hand to remember them later, drawing little diagrams. I would not want to be in the state that even that very low dose of armored final put me in in order to learn.

And I should mention that both model and our model are associated with a good number of side effects. If they don't agree with you, if the dosage is too high, things like decrease appetite, people get a running, no headache. There is this um instance of skin rashes.

In fact, on one of the reasons why model or model aren't more broadly prescribed is that there's a very rare skin condition in which people who have taken certain drugs, not just mode afo or moda, have developed these very severe burn type blisters. And in some cases this can be fatal. This is, again, very rare.

And IT was observed in at least one patient who took mod final as part of a trial for model al as a treatment for adhd. It's called Stevens Johnson syndrome. Please, if you are screams to images of skin ibrahim and legions and things that sort, please don't look IT up on the internet unless you're able to handle that.

And maybe not at all. But the point here is that one of the reasons that modano and our movie are not more widely prescribed ed for D H. D, and that is still only prescribed off label, is that Stephen Johnson syndrome was flag as kind of a potential risk.

Although the adhd specialist that I spoke to are somewhat frustrated with that, because they insist that the frequency of this syndrome that causes the skin rash that sometimes fatal is no more frequent in those that took more definite in this trial than with other drugs that have been approved. So this gets into all sorts of issues around what drugs make IT to approval, in which ones don't. And so no model or our model or are already being prescribed in the general population for other things.

Now this was dealing specifically with the question of whether not should be prescribed in kids with add. And certainly I am a proponent of exerting extreme caution when thinking about which drug should be approved for the treatment of anybody, but especially kids. And to round out our discussion of drugs used for the treatment of hd that fall into, let's call, the a typical category, right? The typical category being at all a date and things of that variety, the less typical would be model or model al preparation and so forth.

The last in this category of a typical is gone. Fosco gone for scent is an interesting compound, is a compound that was developed to lower blood pressure. And indeed, IT does lower blood pressure.

And IT is an alpha to a agonist alpha to a being a reception for nor ef in. So gala fa cine is a non stimulant medication to treat A D H D. And it's also used to treat some other conditions as well. That is only working on the northern c system.

IT is not tapping into the dopamine system, but all the other self that we talked about is really ramping up doping and north and afra gamel cen is only increasing north penetrant and is doing so by what we say, agonizing or stimulating one particular aspect of the garage and merging system. And as the alpha to a system. What's interesting about gala sen is that IT has a bunch of pathways that IT activites that feed onto the autonomic nervous system to damped and down the activation of the sympathetic nervous system.

So well, as most of what we talk about today are some pathan medics they can to make us more ramped up, more aroused alert 光。 Fosse is doing the opposite. And as a consequence, it's not prescribed that often. Because a lot of times when people take one fosco, IT either has no effect on add symptoms or IT tends to make people feel very sleepy.

However, there is a small subset of individuals, about five to ten percent of people, that try IT, including kids, that do get some significant revenue from their add symptoms, and they seem to tolerate one of have seen Better than they're tolerating some of the other drugs that we've talked about up until now. The way gone for scene works is also really interesting. You're now familiar with the lost rule, as this will pack IT, or we call IT, a nucleus of neurons in the back of the brain that released more than never to other sites in the brain.

And they're going to be those alpha 2a receptors that galpy a scene， works on and stimulates lots of different places in the brain related to increasing sillies and relevance of particular stimuli that we see and that we need to attend to. IT appears that galvin can activate the prefrontal cortical networks in ways that are above their Normal based lines. So that's good.

So improvements and executive function that orchestra teacher like function we talked about before, and can increase the efficacy of that output from local rui us. And what that seems to do is increase the coordinated firing of locust released neurons with prefrontal cortex. So in many ways, it's acting like a fine tuning of that orchestra conductor Operation that is so valuable in teaching these brain circuits s during childhood of how to attend to one thing and ignore everything else.

So this is one reason why one fossey is now approved, not just for adults with adhd, but is primarily used in kids age six to seventeen years old for the treatment of A D H D. Again, with the hope that these kids can take the drug and these circuits can learn how to focus on how to attend to certain things and limit impulsivity and hyperrational tivy, and then perhaps come off the drugs, although sometimes, again, people have to stay on them indefinitely. Thing about gama sen is that because IT lowered blood pressure and IT has this effective kind of dampening down overall sympathetic arsa, sometimes IT is prescribed ed in conjunction with other adhd meds.

So yes, there are kids out there and adults out there who are taking atter al N G fosco e, where they're taking five vans and gone for scene, and this where IT starts to get into drug cocktails and a bunch of other things that gets everybody a little bit uncomfortable, I think, because the idea of taking one drug to dampen down the side effects of another drug into offset things and compensate, you know, is getting toward to what's called Polly pharma logy. And, you know, I think it's understandable that people be concerned about that. And yet again, in reviewing this with some of the experts on a, there do seem to be a certain category of children there, an adults who really struggle with the standard adhd meds.

And in that case, quantity en has provided a certain number of these individuals tremendous relief. One note about confessing in no way, shape, perform. And I encouraging anyone who's not prescribed granfer en to take IT, but should you know someone who's taking them for seen off label in order to improve their focus or enhance h any aspect of their biology or psychology? A please let them know, know that IT has a profound effect on lowering the tolerance alcohol, such that even small amounts of alcohol can lead to really serious problems and even potentially death.

So that's a very serious warning with confessing. So today we discuss a lot of different compounds for the treatment of adhd and and now should become clear what the general themes of those compounds is. The general theme is that they tend to increase overall levels of arousal and wakefulness, which leads to decrease levels of hyperactivity, impulsivity and focus.

And on the face of IT that might seem counter intuit, raise article to reduce hyperactivity and impulsivity. Indeed, that's the case because these compounds, because they act on neuromodulator systems like doping and neuroanatomy effective in creating neuroplasticity, they change the strength of the connections in the neural circuits of the brain that lead to states of heightened focus and reduced impulsivity and reduced hyperactivity. So we talked about the different mechanisms by which the different medications for radio to accomplish this, both the typical sort, like metal 4 date and adorable and vivants， and some of the eight typical compounds that are now being used in addition, such as modified or modified gon fosco and well button. And we're possible.

I tried to highlight both the short and long term effects of these various compounds, and I try to address some of the major concerns about these compounds, most notably the question of why we putting so many kids on and feet me, and what is the long term consequence of that? And throughout today's episode, I tried to highlight with the immediate and long term benefits, but also the immediate and long term risks that can exist with these compounds. Certainly, when taken without a prescription recreationally, there is a real risk for abuse and addiction, as well as even the risk for psychotic episodes, but also the risk that a company long term use of these drugs in people with adhd.

And yet IT is also clear that not treating the symptoms of add Carry significant risk as well. And what's very clear from the scientific and clinical literature, and is covered in a significant amount of detail in the episode that I did about A D H D, which you can find a human lab dot com, is that combination of drug treatments and behavioral protocols seem to surpass either drug treatments or behavioral protocols alone. Speaking to the tremendous importance of combining multiple methodologies when treating A D H D and working with the board certified psychiatrist who really understands hd and is really up to date on all the latest scientific and clinical nature, if you're learning from and or enjoy this podcast, please subscribe our youtube channel.

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