Understanding & Conquering Depression

**Andrew D. Huberman** (0:00)
Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. This month, we're talking all about disorders of the mind, things like depression, attention deficit disorders, eating disorders, schizophrenia, and bipolar disorder. During the course of this month, we are going to discuss the psychological and biological underpinnings of mood disorders of all kinds. You'll learn a lot of science. You'll also learn a lot about the various treatments that exist and that are in development for these various mood disorders. We will talk about behavioral tools, things like exercise, meditation, breath work, but also prescription drugs, supplements, and novel compounds that are now being tested in various clinical trials. Across the month, I think you'll start to realize that there are common pathways underlying many mood disorders. In fact, mood disorders that look quite different from one another often depend on the action of the same neurochemicals or neural circuits in the brain and body. That actually should be a point of great relief because what it means is that by understanding the biology of one mood disorder or understanding how one treatment or behavioral intervention can impact a mood disorder, we gain insight into other mood disorders as well. As always, we will discuss science and science related tools that people could implement should they choose. Before we dive into today's topic, I'd like to discuss a very particular set of scientific findings that relate to today's topic and that are important for understanding all mood disorders and all states of motivation, happiness, and sadness, as well as depression. Basically, I'm going to paraphrase a brief segment of my discussion with Dr. Anna Lemke, who I sat down with to discuss addiction and the biological basis of addiction and addiction treatment. A very important aspect of that discussion was when Dr. Lemke described the pleasure pain balance, literally the circuits in our brains that control our sense of pleasure and pain, and ultimately whether or not we remain happy in our pursuit of pleasure or not.
This is an absolutely crucial aspect to the way that we function in everyday life, and especially under conditions of mood disorders. The pathway that she was describing is the so-called pleasure system. However, what most people don't realize is that the pleasure system is also directly associated with, and in fact is the very same system that modulates mental or psychological anguish and pain. Essentially, what she described is that whenever we pursue something that we think will bring us pleasure, and that could be anything that we think will bring us pleasure, from food to video games to sex to a particular job or goal, short-term or long-term, that we experience release of the neuromodulator dopamine. Now, dopamine is associated with increased levels of motivation and drive. It is not the molecule of reward. It is the molecule of craving, motivation and drive. However, as Dr. Lemke pointed out, when we are in pursuit of something, there is a release of dopamine in our brain. That makes us feel motivated, and in general, it makes us feel good. But very shortly thereafter, and beneath our conscious awareness, there is a tilt of the pleasure pain balance in the brain, literally a shift in the neural circuits that underlie pleasure and pain, such that every bit of pleasure or pleasure-seeking that causes release of dopamine will be balanced out by a little bit of pain. And we don't experience this as physical pain, at least not at first. We experience it as craving for more of the thing that brought us pleasure. Now that sounds pretty good. You get pleasure, and then you get a little bit of pain to balance it out. It's subconscious, and you experience it as the desire to seek out more pleasure. However, it's actually more diabolical than that. And we really need to keep an eye on this if we are to remain happy, if we are to remain in pursuit of our goals. The crucial thing to understand is that if we remain in constant pursuit of pleasure, the pain side of the balance tips so that each time we are in pursuit of that pleasureful thing, activity or substance, we are going to experience, we literally achieve less dopamine release each subsequent time. So we get less pleasure and the amount of craving increases. Now, after a certain point or threshold, we call that addiction. And the way to reset the balance, this is very important, the way to reset the balance is actually to enter into states in which we are not in pursuit of pleasure. To literally enter states in which we are bored, maybe even a little bored and anxious, and that resets the pleasure pain balance so that we can return to our pursuit of pleasure in a way that's healthy and that in an ongoing way won't lead to this over tipping or this increase in the amount of pain or addiction. So this is very important. And if this seemed vague, what this means is we should always be cautious of any state of mind or body or any pursuit that leads to very large increases in dopamine. And if it does, we should be very careful to not pursue that repeatedly over time. During today's episode, I'm going to give an example, a real life example of a discussion that I've been in with a young man who's 21 years old, who's dealing with a disruption in this pleasure-pain balance. He is essentially depressed. And he's depressed because of his ongoing pursuit of a particular activity that initially led to a lot of dopamine, but over time has led to less and less dopamine and more and more of this pain side of the balance. We could call him addicted to that particular activity, whether or not he's addicted by clinical standards or not really isn't important. What is important is that he experiences this as depression, as low affect as it's called or anhedonia, an inability to experience pleasure from that thing or from anything else. And he's currently undergoing treatment through a rebalancing of this pleasure-pain pathway. So while I can't reveal his identity to you, that wouldn't be appropriate. He did give me permission to reveal the general architecture of what he's coping with. And I spent some hours with him on the phone this week talking to him as well as to the various people that he's working with to really understand what's going on here, because I think it can illustrate the relationship between dopamine, pleasure, and pain for sake of addiction, but also for understanding how to avoid depressive states, how to remove ourselves from depressive states. And as you'll see today, as we discuss depression, many of the molecules and neural pathways and biological mechanisms that we know can be used to counter depression, feed back onto this pleasure pain balance. Before we begin, I'd like to say that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Athletic Greens. Athletic Greens is an all-in-one vitamin mineral probiotic drink. I've been taking Athletic Greens since 2012, 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 twice a day is that it helps me cover all of my basic nutritional needs. It makes up for any deficiencies that I might have. In addition, it has probiotics, which are vital for microbiome health. I've done a couple of episodes now on the so-called gut microbiome and the ways in which the microbiome interacts with your immune system, with your brain to regulate mood, and essentially with every biological system relevant to health throughout your brain and body. With Athletic Greens, I get the vitamins I need, the minerals I need, and the probiotics to support my microbiome. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman and claim a special offer. They'll give you five free travel packs plus a year's supply of vitamin D3K2. There are a ton of data now showing that vitamin D3 is essential for various aspects of our brain and body health. Even if we're getting a lot of sunshine, many of us are still deficient in vitamin D3. And K2 is also important because it regulates things like cardiovascular function, calcium in the body, and so on. Again, go to athleticgreens.com/huberman to claim the special offer of the five free travel packs and the year's supply of vitamin D3K2. Today's episode is also brought to us by Element. Element is an electrolyte drink that has everything you need and nothing you don't. That means the exact ratios of electrolytes are an element, and those are sodium, magnesium, and potassium, but it has no sugar. I've talked many times before on this podcast about the key role of hydration and electrolytes for nerve cell function, neuron function, as well as the function of all the cells and all the tissues and organ systems of the body. If we have sodium, magnesium, and potassium present in the proper ratios, all of those cells function properly, and all our bodily systems can be optimized. If the electrolytes are not present, and if hydration is low, we simply can't think as well as we would otherwise. Our mood is off, hormone systems go off, our ability to get into physical action, to engage in endurance and strength, and all sorts of other things is diminished. So with Element, you can make sure that you're staying on top of your hydration, and that you're getting the proper ratios of electrolytes. If you'd like to try Element, you can go to drinkelement, that's lmnt.com/huberman, and you'll get a free Element sample pack with your purchase. They're all delicious. So again, if you want to try Element, you can go to elementlmnt.com/huberman.