This episode, I explain what major depression is at the biological and psychological level and the various treatments that peer-reviewed studies have revealed can help prevent and treat depression. I explain the three major chemical systems that are altered in depression: norepinephrine, serotonin and dopamine. I discuss genetic predispositions to depression and how stress, thyroid hormone and cortisol play a role in many forms of depression. I also discuss inflammation as a common feature of many depression symptoms. I review 8 specific science-supported protocols for treating and avoiding depression, including EPA fatty acids (which have been shown to rival certain prescription treatments), how exercise protects against depression, studies of creatine, adjusting dopamine balance and more. I also discuss the results of ongoing clinical trials for ketamine and psilocybin for depression, how these compounds work and finally, I review how ketogenic diets can help in certain cases of depression, especially treatment-resistant major depression.
For the full show notes, visit hubermanlab.com.
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<h2>Timestamps</h2>
(00:00:00) Mood Disorders & Maintaining Mental Health (Protocol 1)
(00:07:25) Sponsors: AG1, LMNT
(00:11:15) Major Depression
(00:18:40) “Anti-Self” Confabulation
(00:21:42) Autonomic (Vegetative) Symptoms of Depression
(00:26:58) Norepinephrine, Dopamine & Serotonin
(00:31:50) SSRIs (Prozac, Zoloft, etc.): Selective Serotonin Reuptake Inhibitors
(00:37:00) Epinephrine/Motor Functions, Dopamine/Motivation & Craving, Serotonin/Emotions
(00:39:33) Physical & Emotional Pain are Linked: Substance P
(00:41:50) Hormones & Depression: Thyroid & Cortisol
(00:46:50) Genetic Susceptibility to Depression: Impact of Stress
(00:50:50) Understanding Biological Mechanism Is Key: Recipes versus Skills
(00:52:50) Tools for Dealing with Depression: Logic & Implementation (Protocol 2)
(00:56:25) Brain Inflammation & Mental State: Cytokines, Prostaglandins, etc.
(00:59:20) Protocol 3: Essential Fatty Acids (Omega-3, EPAs: Eicosapentaenoic Acid)*
(01:02:50) How EPAs Help Offset Depression: Serotonin Synthesis, Kynurenine, Quinolinic Acid
(01:05:25) Protocol 4: How Exercise Offsets Depression
(01:11:44) Protocol 5: Creatine Monohydrate, Forebrain Function & NMDA receptors*
(01:20:30) Protocol 6*: Ketamine, PCP (*Prescription-Only), & NMDA-Receptor Function
(01:33:08) Protocol 7*: Psychedelics (*In Clinical Trials) for Major Depression: Psilocybin*
(01:47:00) Protocol 8: Ketogenic Diet, GABA (Gamma-Aminobutyric Acid)
(01:54:50) Summary of Protocols Covered
(02:00:10) Support & Additional Resources
Title Card Photo Credit: Mike Blabac
Disclaimer
This is an unofficial transcript meant for reference. Accuracy is not guaranteed.
- 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
What this 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.
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...
This 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
The major 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.
This 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,
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, and 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,
or 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
And that in an ongoing way won't lead to this over tipping or this increase in the amount of pain or addiction.
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