TRANSCRIPT[00:00:00] Welcome back to the Better Brain Fitness podcast. My name is Tommy Wood, and I am joined by my sedate, but not sedated, co host, Dr. Josh Turknett. Say hello, Josh.
Hello. Hello, Tommy. How are you?
I’m very good. I’m working on my cup of coffee so that maybe I’ll be a little less sedate.
We have another question today that Josh is going to tackle.
This one comes from Nancy in Washington, D. C. She says, I’m a dedicated Brain Joe follower and appreciate your really helpful and interesting podcast. Thank you, Nancy. What does research indicate about the effects on the brain with long term use of drugs commonly prescribed for anxiety? Josh, what can you tell us?
All right. Good question, Nancy. So to try to make this answer kind of generally applicable, I’m going to first start by talking about a framework that I use for thinking about pharmaceutical interventions in general and health interventions in general. And then I’ll address the specifics of anxiety medications after that.
So a few years ago, I tried to kind of formalize my own decision making process of how I thought about the various things that we might do to improve health, including things that I might prescribe or advise, and so developed a framework where you can kind of place any action you might take. , in one of four quadrants with each quadrant representing a different priority level.
So things in the first quadrant would be top priority and then move into other quadrants as needed in order. So again, categorize any intervention in the name of health into one of those four quadrants. And I typically refer to this, , Framework by the ingenious title of the four quadrant model. So I’ll talk [00:02:00] about the model first and then kind of give an example of how to illustrate how it works.
So again, we have four quadrants. We can categorize any intervention along two different dimensions that will then give us which quadrant it goes in. The first dimension is whether the intervention is a game level or a source code intervention. And that terminology comes from a talk that I’ve given about the parable of Angry Birds.
Angry Birds referring, referring to the video game. And I can link to that in the, that talk in the podcast description. But the gist is, if we want to learn how to get really good at playing Angry Birds or any video game, Then the best way to do so is to play the game a bunch of times and get really good at playing the game.
Even though we know that the game runs on a programming language of some kind, and that runs on machine language, we’re still far more likely to win the game by playing [00:03:00] the game rather than trying to monkey with the source code while the game is running. And furthermore. The most likely outcome if we do monkey with the code is that we’ll just crash the game.
So, bringing it back into the world of biological systems and health, we can categorize an intervention by whether or not it’s acting at the level of the game. And in this case, this would kind of be all the moves, so to speak, that we’ve been able to make in our time as a species on this planet. Or if it’s an attempt to monkey with our source code.
So a, an intervention that is game level is acting at the level of the evolutionary forces we’ve been adapting to throughout the history of our species. So things like lifestyle and diet that we would think of because they are. They’re acting at the level of those forces. They’re tapping into millions of years of evolved wisdom [00:04:00] that our body has for maintaining health and that is deeply woven into our physiology.
This is why lifestyle interventions are our most powerful tools for promoting health. So they have both the widest level of influence and are far and away the safest because they are self regulating. And so it’s why things like nutrition, sleep, exercise, social connections are by far our biggest tools, because those are the inputs that our physiology has been shaped by for all of human evolution.
And they are safest because we have evolved self regulating mechanisms, right? It’s really hard to sleep more than you need, or it’s really hard to exercise beyond a certain point because your body has all these feedback systems that tell you when to stop. Or when you’ve had enough. It’s also why our modern, most of our modern health issues are from mismatches between our present environment and our natural one.
So by us [00:05:00] not getting some critical game level input we need or getting ones that we don’t need. And then source code interventions, on the other hand, are an attempt to monkey with our own source code. So typically here we’re talking about ingesting a compound or molecule of some kind that’s impacting our physiology at the cellular and molecular level or the quote source code level.
And these things are evolutionarily novel, meaning they weren’t part of our natural habitat are, but are a product product of modern technology that has allowed us to make these things. So source code interventions in general are less potent in terms of their benefits. And have much more potential for harm because our regulatory mechanisms didn’t evolve with those in the mix.
, so this includes kind of most pharmaceuticals, especially, , synthetic ones, and. Of course, because they are [00:06:00] inherently more dangerous, we require lots of safety testing before they can be released on the market. That’s why we do that sort of thing. Whereas we don’t do that for, you know, exercise. So that’s the first dimension, game level or source code.
And the other one is whether that intervention or action that we’re taking is supportive or disruptive, meaning is it supporting something or some process that our body is already trying to do, or is it disrupting our physiology in some way in an attempt to steer it in a different direction than the status quo.
So in the realm of source code interventions, taking a supplement because of a nutrient deficiency like magnesium or omega 3 would be an example of a supportive source code intervention. So even though we don’t have evolutionary experience with magnesium or omega 3 supplements, these are still an attempt to support the body’s efforts to do what it’s already trying to do.
Right. We’re just trying to make sure it has what it needs to [00:07:00] thrive and to solve its own problems. It’s like making sure a chef has all the ingredients he or she needs to make the dish that they’re trying to make. And then an example of a disruptive intervention um, would be a psychotropic or a drug that we’re taking that will fundamentally alter the status quo of the neurochemical status quo and steer things in a different direction.
And so again, when we’re taking a drug, that is our intention. So now, instead of, you know, ensuring the chef has all the ingredients he or she needs, or instead throwing a bunch of new ingredients and saying, here, make something different, right? So to give a concrete example, let’s say we’re trying to think about things we might do to Improve attention and focus in someone who’s struggling to pay attention and having trouble getting things done.
So a supportive and game level intervention would be, things we would do to promote better sleep. And again, these things in this category would be our top priority. , so [00:08:00] it’s going to be the most powerful sorts of intervention, right? You think about, you know, what are the effects of sleep deprivation?
Nobody is able to pay attention when they are sleep deprived. And it’s going to be. safe, right? Again, it’s very hard to do too much of a game level intervention because you have natural regulatory mechanisms. You can’t force yourself to sleep so much that it’d be, that’d be dangerous. Your brain just won’t let you.
And this is why, you know, I think both of us think that the concept of environmental mismatch is so useful. Right. Because identifying those mismatches and correcting them is by far and away, the most powerful strategy we have for improving our health and wellbeing. The next quadrant would be things that are game level, but disruptive so disrupting the status quo, an example here for attention might be listening to something that isn’t, that is intended to entrain a particular brain state or particular kinds of brain activity.
So I love using the app brain. fm. for that [00:09:00] purpose. So we’re using something that’s evolutionarily familiar in sound coming in through our ears, but sort of applying our understanding of the neuroscience of attention and EEG to shape that sound in ways that promotes a particular brain state.
And then the next category would, would be things that are source code, but are supportive. So an example here might be taking a choline supplement if someone is deficient in choline, right? So choline is one of the materials needed to make acetylcholine, which is a neurotransmitter that’s widely used.
In networks that mediate attention. So here, you know, again, ensuring the body or the brain has what it needs, even though it’s in a form that’s evolutionarily novel, right? There weren’t Choline supplements in our natural ancestral habitat. Now, our preferable approach would always be to get that through food, which is a game level, intervention. But, you know, supplementing, it would be the next best thing for someone if you can’t get it for [00:10:00] some reason, whether or not it’s a, you know, insufficient of the diet or some issues with absorption or whatever.
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And then the final category would be quadrant four things that are source code, intervention, and disruptive. So in the things that we might do to promote attention, you’d have drugs like methyl phenidate or Ritalin, amphetamine or Adderall, modafinil or Provigil. So here we’re acting at the level of neurochemicals or our source code and doing so in a way that’s disruptive, right?
We’re vetoing our natural [00:11:00] neurophysiology, doing so presumably in a way with a belief that that altered state. is preferable to the status quo. Now, one thing that happens when you do this sort of thing, , is that the brain will make adjustments to bring, to try to bring things back to the status quo, to restore the balance that it had before the drug was taken.
So, for example, if you suddenly flood all of your synapses with dopamine from an outside source, your brain’s gonna do things like reduce its own production of dopamine, increase the clearance of dopamine from the Synapses in an effort to restore balance and the longer the disruption, meaning the longer and more regularly a drug like that it would be taken, the more resources it’s going to deploy to maintain balance, including kind of more long term efforts like changing the transcription of genes that are involved in these regulatory processes.
So because of that ongoing effort to restore [00:12:00] balance with chronic use, you reach a point typically where you’re not better off than when you, where you started. And furthermore, if you stop taking the drug, you feel worse than you did before you started. Because your body has down or your brain is down the regulated all those systems.
So then you have to go through some degree of unpleasantness to kind of get back to that original state without the drug to the where you were begin with. And this is exactly why the common scenario for any drug that impacts the nervous system is that it can help in the short term with whatever issue you’re trying to help, but with chronic usage ends up making that issue worse.
And the rates of mental illness have grown exponentially in the era of psychotropics, which, of course, you know, if they’re an effective long term treatment, that effect should be to push those rates down. And. [00:13:00] likely that this particular phenomenon of adaptation and sort of the long term worsening of these issues with chronic usage is a factor there.
There’s a great book on this topic If anybody’s interested called anatomy of an epidemic, and it’s kind of the story of of mental health in the pharmaceutical era. So. needless to say, it’s probably evident that I have a very high threshold for using anything in quadrant four especially things that are interacting with the central nervous system, including psychotropics, and which under that umbrella is our anti anxiety medications.
And that’s because, you know, I see my ultimate job as a physician and neurologist to reduce suffering. And again, it’s so easy with these drugs to trade short term relief of suffering for a very significant long term increase in suffering and that’s what we’re trying to avoid. I think the other big problem with the quadrant four interventions is that we’ve come to see these as our primary tool or our best tool when hopefully as this model illustrates, they are both are least effective in our most likely to cause harm.
And so we would want to ensure that we’re not neglecting all the other things in the other quadrants that can provide that have a much more likely chance of providing long term relief of suffering. So kind of with that as the background, my approach has always been to use drugs in this category, including ones for anxiety as a bridge while we’re trying to address the other factors.
And to use them for the minimum amount of time at the lowest dose and frequency possible, and then furthermore, within that, to try to choose the drugs that have the best benefit to risk ratio. Within the category of the Anti-anxiety meds or anxiolytics, the two big ones are the benzodiazepines and then the serotonin reuptake inhibitors, either the SSRIs or SNRIs.
So the benzodiazepines are things like alprazolam, , known as Xanax, , diazepam, Valium lorazepam Ativan, and Clonazepam or Klonopin. These drugs are very good at promoting tolerance and dependence, and so I am not fond of them at all for use with anxiety. They also disrupt sleep architecture, and so are, are not good for brain health from that standpoint.
Unfortunately, they’re often used to help people sleep, but they’re in a lot of ways similar to alcohol in that they may help you fall asleep, but the sleep you get is going to be poor quality. The least bad in this category, I would say, is Clonazepam because it has a slower onset of action. The faster acting and more potent a drug like this is the worst the issues are with tolerance and dependence. Xanax, probably being the worst. And I despise that drug. I’ve seen it ruin too many lives.
There are specific clinical situations where these drugs can be used and used effectively and are very helpful, particularly in certain forms of epilepsy. But I don’t like using them for anxiety. I’ve seen them cause much more harm than good. So, the other category I mentioned are the SSRIs like Fluoxetine, Prozac, Sertraline, Zoloft, and then the SNRIs which prevent the reuptake of norepinephrine and probably serotonin as well.
Things like venlafaxine or Effexor and duloxetine or Cymbalta. My preference has been, and if I’m gonna use something, this is the kind of the category I would choose. My preference has been the SSRIs, typically just because they’re a little bit cleaner only impact one main neurotransmitter system. There aren’t any known issues with impacting sleep architecture. And there’s less of an issue with tolerance and dependence. I don’t see them as a long term solution and still consider them to be disruptive. So they are sort of interfering with natural processing in the brain in ways that I don’t think were anywhere near understanding.
So I still always want to use them for the shortest period of time. And while we’re trying to address the other big therapeutic levers in the other quadrants that can really make a difference over the long term. So, I think I’ve blathered enough. Tommy, any additional thoughts on that topic?
I thought that was a really great overview. Thank you. As well as you know, acknowledging that for some people, these may be helpful, particularly in the short term as a bridge. And just to kind of… I guess hone in a little bit more on the evolutionary aspect um, sort of support your, your quadrant model and your thoughts is that anxiety is a It’s a dangerous signal, right, it’s an evolved hypervigilance, that is [00:18:00] probably grounded in some aspect of truth, that there is some previous trauma or other exposure that is causing this, this hypervigilance, and that signal should not be ignored through sedation, particularly with benzodiazepines.
And so I think it’s worth just bearing in mind that, you know, it’s not all in your head. There is some physical or psychological thing that’s driving this, for good reason, because when you’re anxious, you upregulate certain aspects of your physiology that may help with wound healing or other things, right?
This is, this is part as an evolved mechanism. And, you know, Alert you to danger if, if some is present so that you can avoid it. These things are, are helpful and it’s trying to tell you something. It might be difficult to figure out exactly what that is. But it’s just worth bearing in mind that [00:19:00] this just doesn’t just happen.
This is an evolved mechanism that’s telling you something, right?
Right. It’s a signal.
Yeah. So, so that’s why I think the game level interventions are identifying potential either parts of your psychological or physical environmental history and exposures that may help you understand where the signal is coming from.
You know, those are the things that are going to be most impactful, but, you know, in the interim, um, if you’re able, you may be able to better engage in that process. With with some some short term, you know, targeted medication.
Yeah, that’s a great point. And another way to kind of that you can think about it as well as is it, is it adaptive or maladaptive right there?
Like, like you said that, you know, there are many instances where it may be having some kind of adaptive function. Your brain, you know, is generating that feeling, um, for a reason. [00:20:00] And then you may have maladaptive reasons like, You’re, you know, not getting enough sleep. So you don’t have those systems aren’t supported well enough, right?
So it’s sort of malfunction giving you an anxiety signal when maybe it shouldn’t. There could be many different reasons why that could be occurring. A lot of them mismatch related. And I think they’re the tendency is for us to overlook the fact that these mental symptoms are still originating in a biological organ, right?
And so even things like nutrient deficiencies could very well be a major player in anxiety, right? Because, like I mentioned, we want the brain to have all the resources it needs to do what it, you know, what it does best. And, this can be a manifestation of it not getting what it’s what it’s needing.
And those sort of systems malfunctioning as a result.
Where does caffeine fit in your quadrant model? We talked about coffee. I was wondering whether that was going [00:21:00] to come in.
I wondered if that would come up. So, I think that it’s a good illustration of the fact that, like, we want some… So, I drink coffee.
Right? And it is quadrant four. Now we’ve probably been exposed to it for quite a long period of time. But I still think of it in terms of that, that usage as a, as a quadrant four, however, and, and so you want a very high burden of proof and I think it has a very, you know, it has a lots of evidence that it’s not only not harmful, but there may be potential advantages to it.
And those may become from sort of the, you know, plant compounds and so forth that are, that are in it. Maybe, you know, you might consider more game level, right? But, and talking about coffee in particular. So I think the weight of the evidence at this point sways me enough to not to think that there are, you know, not only potentially safe levels of consumption, but potentially even beneficial.
Right. And there’s some evidence that it may reduce the risk of certain conditions. All[00:22:00] the major, all the major sources, coffee, tea, chocolate or, you know, particularly the polyphenols and other. Compounds that come along with, um, with, with the caffeine or, or the, the multiple related compounds to caffeine that have similar effects that come, come from those various things all seem to have potential health benefits.
So I, so I say this framework would, would be a reason why you’d say, get your caffeine from coffee, not from a caffeine pill, right? I think that also this framework you know, you can make an argument about things like psychedelics being. Inherently safer because we may have a lot longer evolutionary experience with them, then we do with more modern synthetic drugs.
Yeah. Well, I wasn’t going to throw you that one without.
Yeah. All right. Well, anything else to add, Tommy? No,
I think this was really helpful Nancy, hopefully that helps to address your [00:23:00] question. If anybody has any follow ups or any thoughts please do send them to us and we would love to dig back into this. Yes.
And we’ll maybe reference this particular model with answers to future questions as well.
Okay. Well thanks so much for listening. If you have a question for us, you can go to brainjo.academy/questions and ask it there. Thanks so much for listening and we’ll see you guys next time.