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. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman LMNT: https://drinklmnt.com/huberman Thesis: https://takethesis.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Timestamps (00:00:00) Mood Disorders & Maintaining Mental Health (Protocol 1) (00:07:25) Sponsors: AG1, LMNT, Thesis, Momentous (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