Joe Rogan | Why Xanax Doesn't Stop Anxiety w/Joseph Ledoux

Now how do things like Xanax work? What's the mechanical process? Okay, so that's part of the class of drugs called benzodiazepine. They bind to receptors in the brain. The brain has receptors for all kinds of chemicals, and many of these things are things that exist in nature. And what they bind to is a receptor called the GABA receptor, which is the major inhibitory transmitter in the brain. So when you have a benzodiazepine binding to a GABA receptor, what it's going to do is increase inhibition. So the kind of simple reason why those things can help is they kind of inhibit. So they tone down the brain a bit, and so things that would normally trigger a response no longer trigger it. So it's like increasing the threshold for something to bother you in a sense. And a lot of people enjoy that with alcohol. And you're not supposed to? Well, alcohol also attacks those receptors, so it's like you get double the effect. Right. Is that why they tell people don't have Xanax? Yeah, because you can, you know, if you take a lot of Xanax and drink a lot of booze, you can OD. Or you could just say crazy things, not totally be aware. Do you remember that story about a woman? She was, I believe she was a publicist, and she got on a plane. She's flying to Africa. And she said, I'm going to Africa. Hope I don't get AIDS. Just kidding. I'm white. LOL. She thought she was just being funny. And you laughed. And she landed in Africa. That must have been a surprise. Do you know the story? No, but there are other stories like that. This was one of the original stories of someone ruining their entire life with just putting, you know, one little tweet online. She thought she was being funny. She would say a bunch of snarky things like that, a bunch of funny, trying to be funny. But she was on Xanax and drinking and woke up completely oblivious, and her life had been destroyed. She was fired. She was a social pariah. I'm pretty sure that was Xanax and alcohol that she was blaming it on. Yeah, well, you know, these are powerful drugs. So back to how they work and they work. So a drug like that, all of the drugs that we take go to the entire body. They're not able to just find their way to one little spot in the brain and do their trick. You know, talk about magic bullet drugs that might be able to be targeted for specific circuits, but that's fantasy at this point. So if you reduce inhibition in the entire brain, yes, you might reduce anxiety, but you're also going to change a lot of other things. So you're going to make, for example, forethought and ability to rein in things like the stuff the woman was saying more difficult because they're attacking the prefrontal cortex where you have some inhibitory control over behavior. They're going to alter your ability to retrieve and store memories and to attend to things. And to the extent that these drugs have a positive effect on some people, it's been said that part of the reason is that it's kind of a general blunting of emotion. It's not an anti-anxiety drug. It's just kind of an adulting of everything. And you get anxiety, anti-anxiety as a part of that. But if we want to understand how to do better, we have to figure out what the brain circuit that's really making us anxious is and not just what's making us not toning down everything. It's kind of like you go to a restaurant, the music's too loud. Somebody says, please turn it down. So they turn it down a little bit. The music stays the same. It's the same song. But it's not as annoying because you've turned the volume down. And I think that's a lot of what these medications can do is turn the volume down a bit or turn it up depending on what you do. Correct me if I'm wrong, but isn't there some sort of a slingshot effect? Like after you take these things and your anxiety is ramped up afterwards? Well, it can be a rebound effect. There can also be kind of a lot of people next day feel depressed because the stuff is out of your system and just kind of ugh. It's kind of like taking sleeping pills. Things like Ambien are of the same general category of drug, benzodiazepines. And so you get this hangover the next day. Okay. So it's just a physiological response to the medication. It's not that if you alleviate some anxiety, then the anxiety wants to come back even stronger. I've proposed in my previous book that we each have an anxiety set point that let's say you're worried about something and all of a sudden that gets resolved. I just make room for the next thing to work with. So we each kind of fill that void because our brain is, we've developed a brain that has a certain kind of set point for everything it's doing. And that just makes room for, you know, to fill that up. If you're an anxious person, you probably will always be somewhat anxious. So there's no magic bullet that's going to take that out. What you have to do is attack the process from knowledge of how it all works. And that requires that we have a more sophisticated understanding than is possible from simply observing behavior. Because behavior does not tell you necessarily what's on the mind. Behavior tells you how the brain has responded. But just to go back to the fear threat example, when let's say I bring you into the laboratory, show you a picture of something like a blue square. My colleague Liz Phelps, who used to be at NYU, who is now at Harvard, did experiments like this. And every time the blue square would come on, the person would get a mild shock to their finger. And so then she would present the blue square subliminally. That means, you know, really quickly with something that follows it, that kind of masks it. And that prevents the information from getting into the conscious mind and so the person, so that I didn't see anything. But if you put the person in an imaging machine, fMRI, and image what's happening, that stimulus, that threat, the blue square gets to the amygdala, turns it on, the heart begins to race, palms are sweating, but the person has no fear. The person doesn't know it's there and doesn't experience fear. The amygdala is not about fear. It's about detecting and responding to danger. In order to be afraid, that has to reach your conscious mind so that you can experience it as a state of this autonomic consciousness that we're talking about, a self-involved consciousness. That's hard for people to separate. Yeah. The idea that there's a physical response, but that your mind's unaware of it. Right. But when you understand that, that's why you become to understand that's why the medications are not working. They're targeted to work on these underlying systems in rats or mice, but that's not where we are experiencing our anxiety. These medications are very profitable, right? People enjoy it. Millions of prescriptions get written. Are they just going to phase those out? They're probably all going off patent and because the company can't find anything new, they're not going to keep pursuing it because it's not going to be a profit anymore. But don't people still want them? I mean, it seems like that's a really popular medication. Yes, it would be like they'll go to, you know, they'll become generics and people will be able to get them for less money. And they'll just do with whatever they want. Yeah. Off label, whatever. Yeah. I mean, it's, you know, I do think that, for example, the drugs that are available do help people because it's important to reduce the behavioral timidity and the physiological arousal that goes with that. Because if you don't treat that, then the conscious mind will be reactivated by those responses. If you only treat the conscious mind, then the physiological stuff will bring the conscious stuff back. You know, everything will bring back to everything else unless you treat the whole system and you have to do that, you have to understand the system. And we've just misunderstood it, I think, for so long. I have a friend who, he takes it every day, takes Xanax every day and he says he needs it. He says without it, he's just a mess. Well, you know, whatever gets you through the day, I guess, you know, I'm not a therapist. I'm not like advocating that. I know, I understand. But from your perspective, from an understanding of the human mind and all the systems that are at work, it seems like that's really not the way to do it. Yeah, I mean, it's, you know, I'm sure that that's, you know, in a sense, maybe that's his crutches way to get through the day. 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