Podcasts about nmda

This week, host Sam Ko goes upstream from our usual clinical and business topics to sit down with Dr. Roberto Malinow, emeritus professor at UC San Diego, member of both the National Academy of Sciences and the National Academy of Medicine, and one of the world's leading researchers on synaptic plasticity and NMDA receptor biology. His work has been cited more than 30,000 times, and his recent perspective piece takes a very different view of what's actually happening during a ketamine infusion.The core of this conversation is his hypothesis that ketamine works by selectively weakening hyperactive brain circuits, but only the ones actively firing while the drug is on board. It's a finding that raises some genuinely uncomfortable questions about the standard set and setting approach, and points to chronic pain treatment as a practical place to start testing these ideas clinically.You'll also hear about the brain's "disappointment center," the lateral habenula, and why it may be hyperactive in depression, the Stanford anesthesia study and what it suggests about brain activity during treatment, and a wide ranging look at consciousness, optogenetics, the gut-brain connection, and what basic science still doesn't fully understand about how psychiatric drugs work.What You'll Learn in This Episode· Revolutionary ketamine mechanism - How Dr. Malinow's hypothesis suggests ketamine works by weakening hyperactive brain circuits, but only when those specific circuits are actively firing during treatment· The disappointment center concept - Understanding the lateral habenula as the brain's disappointment center that inhibits dopamine and may be hyperactive in depression, serving an evolutionary purpose in reinforcement learning· Challenge to set and setting orthodoxy - How activating negative thoughts or painful experiences could possibly enhance therapeutic outcomes· Neuroplasticity fundamentals - How synapses can be rapidly modified and why NMDA receptors are crucial for both strengthening and weakening neural pathways, forming the basis for learning and memory· Rapid vs. delayed therapeutic effects - Why ketamine can work almost immediately while traditional antidepressants take weeks, and what this reveals about different mechanisms of action· Chronic pain treatment implications - How activating pain circuits during ketamine infusions might be more effective than current protocols, and why chronic pain could be the ideal testing ground for this hypothesis· Basic science translation - How laboratory findings about synaptic plasticity and NMDA receptors connect to real-world therapeutic applications in depression, PTSD, and pain management· Optogenetics technology - How scientists can now deliver light-sensitive proteins to specific neurons, allowing precise activation or inactivation of brain circuits to study behavior and memory· Memory manipulation research - Fascinating studies showing how specific memories can be turned on and off using targeted brain stimulation, with implications for trauma and addiction treatment· Consciousness and synaptic function - Exploring the complex relationship between individual neurons and higher-order brain functions, and why bridging these levels remains challengingEpisode 59 show notes:00:00:00 Teaser: Those hyperactive circuits…00:00:24 Episode Introduction and Guest Overview00:01:12 Sam Introduces and Welcomes Dr. Roberto Malinow00:02:41 Background: From Reed College to The MD/PhD Path00:05:17 Why Basic Science Won Out Over Clinical Medicine00:06:06 The Lecture That Started It All: Professor Rodolfo Llinás and Synapses00:06:51 How Ketamine Interacts with the NMDA Receptor00:07:47 The "Disappointment Center": What the Lateral Habenula Does and Why It Matters in Depression00:09:16 The Standard Set and Setting Approach in Outpatient Ketamine Clinics00:10:12 The Three-Part Hypothesis: Neuroplasticity, Hyperactive Circuits, and Negative Thoughts00:11:49 Written Exposure Therapy and PTSD: Priming Circuits Before the Infusion00:12:53 Chronic Pain as the Easier Testing Ground for the Hypothesis00:14:20 Activating the Pain Pathways During a Ketamine Infusion00:17:23 The Anesthesia Study (Heifets/Stanford): Why the Brain Needs to Be Active00:18:48 What Would a Human Study Design Actually Look Like?00:20:41 Animal Study Evidence Supporting the Active-Stimulus Hypothesis00:21:33 Zooming Out: Synapses, Consciousness, and the Shakespeare Analogy00:23:18 Optogenetics Explained: Using Light to Control Specific Neurons00:27:31 What Don't We Understand About Depression?00:28:29 Lateral Habenula in Animal Depression Models and Dr. Malinow's Own Experiments00:29:13 The Dystopian Scenario: Using Ketamine-Like Drugs to Wipe Out Ideas00:31:31 Common Misconceptions Clinicians Have About Synapses00:32:47 What Surprised Dr. Malinow Most About Studying Synapses00:35:15 Why Ketamine Works Rapidly While SSRIs Take Weeks00:37:30 The "Party Trick": Learning Is Neuroplasticity in Real Time00:39:13 NMDA Receptors and Their Role in Learning and Memory00:39:47 Optogenetics Research: Turning Fear Memories On and Off in Animals00:42:08 Glutamate: 90% of Synaptic Transmission Explained00:43:55 Synapses in the Gut: The Enteric Nervous System00:45:58 The Gut-Brain Connection and Future Research00:46:23 Papers Worth Reading in the Ketamine Space00:47:50 The Psychedelic Renaissance: Psilocybin, the Disappointment Center, and What's Next00:50:20 Could the Activation Hypothesis Apply to Psilocybin and MDMA as Well?00:52:57 Rapid-Fire Questions Begin00:53:19 Time Travel00:54:19 Hidden Talent00:54:48 Alternate Career00:55:42 Advice to 18-Year-Old Roberto00:56:29 Final Thoughts and Call to Action for Clinicians00:57:00 Where to Find Dr. Malinow's Research (UCSD Website)00:57:40 Sam's Closing Remarks00:58:32 Episode EndingThanks for listeningConnect with Dr. Malinow:Website: https://biology.ucsd.edu/research/faculty/rmalinowEmail: rmalinow@ucsd.edu

Today on The Boat Princess Podcast, we're joined by one of the most respected and influential voices in the marine industry, Nancy Cueroni, Senior Vice President of the National Marine Distributors Association (NMDA). With an impressive 27-year career dedicated to supporting and advancing the recreational boating industry, Nancy has witnessed remarkable transformation across every facet of the business—from evolving consumer trends and technological innovation to changing distribution models and workforce challenges. Throughout her career, she has worked closely with manufacturers, distributors, dealers, and industry leaders, helping shape the conversations and strategies that drive the marine sector forward. In this episode, Nancy shares her professional journey, reflects on the biggest changes she has seen over nearly three decades in the industry, and discusses the opportunities and challenges that lie ahead. We also explore her concerns for the future of boating, including workforce development, industry sustainability, market fluctuations, and how the next generation of boating enthusiasts will shape the industry's direction. Whether you're a marine professional, boat owner, or simply passionate about the future of boating, Nancy offers valuable insights, practical perspectives, and a wealth of experience gained from nearly three decades at the heart of the industry. As she hands the helm to her Protege Emily Saving we listen to what Emily looks forward to bringing to the table for the future of the National Marine Distributors Association.  Please welcome Nancy Cueroni and Emily Saving to The Boat Princess Podcast. This podcast was recorded at IBEX in 2025 To find out more about IBEX:  https://www.ibexshow.com/   To find out more about the NMDA:  https://www.nmdaonline.com/   To sign up for our Newsletter or find out about more of what we do at The Boat Princess or to enquire about sponsorship go to: https://www.theboatprincess.com/  

Sleeping in a covered wagon on a lavender farm sounds like a movie scene, but we're doing it for real in Tularosa, New Mexico. We're recording on-site at Floren Family Farms, where the stars are bright, the cottonwoods are tall, and the vibe is intentionally low-noise. Tom Floren explains why their Conestoga wagon glamping stay is built for rest, complete with modern comforts but without the usual distractions, so you can actually look up, breathe deep, and feel the place.Rent your stay in a covered wagon in Tularosa, NM!: https://www.airbnb.com/rooms/1183640343138023493?unique_share_id=a80b354f-78e3-45bd-aeda-1320fd24b8d2&viralityEntryPoint=1&s=76Visit Floren Family Farms -FlorenFamilyFarms.comThank you to NMDA for supporting this episode! Big Bend Episodes: OP and SequimAlexa's Tea's that utilize Lavender: VegabondTeas.com/SequimVegabondTeas.com/Provence https://www.123farm.com/Leavenfoods.com @leavenfoodsFrom there, we zoom out into what makes this farm a true agritourism destination in New Mexico. We talk you-pick lavender season, fall flowers like zinnias and sunflowers, and why people drive out for weddings, baby showers, and open-air gatherings in the middle of an arid landscape that somehow feels like a green oasis. Tom also shares the behind-the-scenes ecology that keeps the farm thriving, including a partnership for bees and a powerful story about rescuing a great-horned owl and planning a public release event that teaches just how important raptors are.If you love practical takeaways, this conversation delivers: we break down lavender varieties, culinary vs high-camphor types, essential oil distillation, and the biggest reason lavender dies in home gardens. Tom's advice on soil mix, drainage, watering, and sunlight is simple enough to remember and specific enough to change your results. We also share our From ROAM to Home moment, connecting lavender farm travel to everyday rituals like sourdough and the small tools that make it easier to keep traditions going while you're on the road.Subscribe, share the episode with a friend who needs a nature reset, and leave us a review. What would you bring home from a lavender farm: a plant, a recipe, or a new daily ritual?#Florenfamilyfarms,,,#Remedies4relief.Wanna hit the road? Get 10% OFF your own roadsurfer adventure!https://link.roadsurfer.com/roamiesCODE: ROAMIES10And it means the world to us when you subscribe, rate and share our podcast.Alexa and RoryThe ROAMiesFollow us at:http://www.TheROAMies.com@The ROAMies: Facebook and Instagram YouTube and X.

🧭 REBEL Rundown Click here for Direct Download of the Podcast. 💨 What Is Nitrous Oxide? Nitrous Oxide (N2O) is a colorless, odorless inhaled anesthetic that has been used for centuries, particularly in the surgical world. Mechanistically, it can induce euphoria, anxiolysis, and intoxication via NMDA receptor antagonism.During the late twentieth century, nitrous oxide was increasingly used recreationally due its accessibility and perceived benign nature.The modern day slang term for nitrous oxide is “whippets” – which tends to refer to the canisters that contain this agent and are frequently used as whipped cream foaming agents.Despite the legal nature and benign perception of nitrous, frequent use can lead to lasting and permanent neurologic effects. 🧠 How Nitrous Oxide Causes Toxicity Nitrous oxide toxicity results from its ability to oxidize the cobalt moiety in Vitamin-B12, thus leading to a functional B12 deficiency, despite adequate consumption and absorption.1Functioning B12 is needed as a cofactor for methionine synthase.2 This enzyme has two critical roles:The conversion of 5-methyl tetrahydrofolate to tetrahydrofolate; tetrahydrofolate is essential for the synthesis of our DNA.And the conversion of homocysteine to methionine; methionine is needed to maintain the integrity of the myelin sheath of our axons.As a result, nitrous toxicity leads to: a megaloblastic anemia and demyelination of both the dorsal columns and the lateral corticospinal tracts (also known as subacute combined degeneration). 🚶‍️ Clinical Manifestations of Nitrous Oxide Toxicity These patients will have a combination of both upper and lower motor neuron symptoms due to demyelination of the dorsal columns, lateral corticospinal tracts, and peripheral nerves. As a result, the following may manifest:Dorsal Columns: diminished sense of proprioception, vibration, and fine touch.Lateral Corticospinal Tracts: upgoing plantars, hyperreflexia, weakness of voluntary distal muscle controlPeripheral Nerves: numbness/tingling and weakness in a glove and stocking pattern (symptoms that start initially in the feet and hands that progressively spread proximally to the ankles and wrists)Taking all of this into account, patients may present with difficulty ambulating, positive Romberg sign, dysmetria (difficulty with finger to nose or heel to shin), upgoing Babinski reflex, and decreased strength and sensation in a glove and stocking pattern. 🔍 How to Diagnose Nitrous Oxide Neurotoxicity History is key! As with a lot of pathologies in toxicology, identifying the exposure will expedite management.A thorough neurologic exam will narrow the differential – with a particular focus to fine, peripheral motor and sensory deficits, dysmetria, proprioception, and ability to ambulate.Magnetic resonance imaging of the spine may identify enhancement and/or edema of the dorsal columns, specifically on T2 weight axial imaging – sometimes referred to as the “inverted V” or “inverted rabbit ears appearance.”3Serum B12 concentrations may be normal as the issue is with a functional deficiency as opposed to a vitamin absence. However, patients have elevated concentrations of both homocysteine and methylmalonic acid, both of which are metabolized in the presence of functional B12. 💉 Management of Nitrous Oxide Toxicity First and foremost, cessation of nitrous oxide abuse is crucial to limit/prevent toxicity.While there is no universally agreed upon treatment regimen, supplementation with intramuscular B12 is recommended.Approaches vary from daily or every other day injections until symptoms improve at which point injections can be spaced out to weekly and then monthly.Physical and occupational therapy may be needed depending on the degree of functional debility.It is important to note, that depending of the severity and chronicity of toxicity, some proportion of patients may not fully return to their baseline. 📌 Take-Home Points Though legal and seemingly benign, nitrous oxide abuse can lead to permanent neurologic dysfunction.Nitrous oxide toxicity can affect the dorsal columns, lateral corticospinal tracts, and peripheral nerves.Thus leading to a constellation of both upper and lower motor neuron deficits, particular in a glove and stocking pattern: deficits in proprioception and fine motor skills, positive Romberg, upgoing Babinski, peripheral numbness, tingling, and weakness.Magnetic resonance imaging may identify symmetric high signal intensity in the dorsal columns.Treatment includes B12 supplementation and physical/occupational therapy as needed. 📚 References Long H. Chapter 81. Inhalants. In: Nelson LS, et al. Goldfrank’s Toxicologic Emergencies. 11th ed. New York: McGraw-Hill; 2019Shah K, Murphy C. Nitrous Oxide Toxicity: Case Files of the Carolinas Medical Center Medical Toxicology Fellowship. J Med Toxicol. 2019 Oct;15(4):299-303. doi: 10.1007/s13181-019-00726-x. Epub 2019 Aug 6. PMID: 31388940; PMCID: PMC6825085.Schmitz ZP, Hoffman RS. Magnetic resonance imaging in a patient with nitrous oxide-induced subacute combined degeneration of the spinal cord. Clin Toxicol (Phila). 2023 Nov;61(11):1006-1008. doi: 10.1080/15563650.2023.2286205. Epub 2023 Dec 19. PMID: 38060330. Post Peer Reviewed By: Marco Propersi, DO (Twitter/X: @Marco_propersi), and Mark Ramzy, DO (X: @MRamzyDO) 👤 Associate Editor Anand Swaminathan MD, MPH All Things REBEL EM Meet The Team 🔎 Your Deep-Dive Starts Here REBEL Core Cast – Pediatric Respiratory Emergencies: Beyond Viral Season Welcome to the Rebel Core Content Blog, where we delve ... Pediatrics Read More REBEL Core Cast 143.0–Ventilators Part 3: Oxygenation & Ventilation — Mastering the Balance on the Ventilator When you take the airway, you take the wheel and ... Thoracic and Respiratory Read More REBEL Core Cast 142.0–Ventilators Part 2: Simplifying Mechanical Ventilation – Most Common Ventilator Modes Mechanical ventilation can feel overwhelming, especially when faced with a ... Thoracic and Respiratory Read More REBEL Core Cast 141.0–Ventilators Part 1: Simplifying Mechanical Ventilation — Types of Breathes For many medical residents, the ICU can feel like stepping ... Thoracic and Respiratory Read More REBEL Core Cast 140.0: The Power and Limitations of Intraosseous Lines in Emergency Medicine The sicker the patient, the more likely an IO line ... Procedures and Skills Read More REBEL Core Cast 139.0: Pneumothorax Decompression On this episode of the Rebel Core Cast, Swami takes ... Procedures and Skills Read More Showing Slide 1 of 7 The post REBEL Core Cast—Nitrous Oxide Toxicity: Whippets and Neurologic Injury appeared first on REBEL EM - Emergency Medicine Blog.

Dr. Deb Muth 00:00:09 Hi there, how are you? Bob Miller 00:00:10 Excellent! Pedaling as fast as humanly possible, but doing okay. Dr. Deb Muth 00:00:14 Good, good. Well, I’m looking forward to our conversation today. This should be amazing. Bob Miller 00:00:20 Yeah, it should be a lot of fun. Dr. Deb Muth 00:00:22 Yeah, anything that’s off-limits for you in, our conversation? Bob Miller 00:00:28 No. Dr. Deb Muth 00:00:29 Okay, anything you want me to make sure we cover for you? Bob Miller 00:00:33 Well, I mean, is it okay if we put a little plug-in for our software? Dr. Deb Muth 00:00:35 Absolutely. Bob Miller 00:00:36 Yeah. Dr. Deb Muth 00:00:37 Absolutely. Bob Miller 00:00:36 Yeah. Dr. Deb Muth 00:00:37 Absolutely. Bob Miller 00:00:38 Hey, can we… can we do a screen share? Yes, we can. Yeah, because I want to show you some maps, and… Dr. Deb Muth 00:00:43 Okay. Things like that, yeah, so… Perfect. So just let me know when you want to do screen share. Bob Miller 00:00:48 Okay. Dr. Deb Muth 00:00:49 And yeah, feel free to plug your software wherever you want to. Bob Miller 00:00:53 Okay, well, good. Let me pull up a, a slide for that, and give me one second, I just want to shut the door to my office to get the noise down. Dr. Deb Muth 00:01:01 No worries. Bob Miller 00:01:16 And, how should I refer to you? Dr. Debb? Dr. Muth, what do you like? Dr. Deb Muth 00:01:18 Dr. Deb is great, or Deb, either way, I’m pretty informal, so… Bob Miller 00:01:22 Yeah, and… Bob is fine for me. Okay. Yeah. Yeah, there you go. Why people feel like they need this, son. Special name, it’s like, seriously. Dr. Deb Muth 00:01:33 Right? I agree. Bob Miller 00:01:35 When I work with my clients, it’s like, Dr. Millison, just, just bop, just, just bop. Dr. Deb Muth 00:01:41 Yep, that’s how I am, too. Just call me Deb, it’s good. Dr. Deb Muth 00:01:44 They feel a little awkward with that, you know? They’re not used to that, but… Bob Miller 00:01:48 Alright. And you’re a naturopath, medical doctor. Dr. Deb Muth 00:01:52 A nastropathic doctor and a nurse practitioner. Oh, nice. Yeah, so I got the best of both worlds, right? Bob Miller 00:01:58 Yeah, damn. Okay. Alright, so here we go… There we go. Alright, so I got that ready, and then I will do a, I will do a screen share. I think you’re gonna really, appreciate what we’ve come up with. We’ve come up with the concept of, Cellular CPR. Dr. Deb Muth 00:02:23 Oh, nice! Bob Miller 00:02:24 And that is, construct the cell membrane, Protect the cell membrane. And restore it if it’s damaged. Dr. Deb Muth 00:02:32 Love that. Bob Miller 00:02:34 I love that. Yeah, so that’s what we’re focusing on, and then how, You know, we want to get to the point that, you know, most people think of genetics, they think of, like, 23andMe or Ancestry. Dr. Deb Muth 00:02:44 Yeah. Bob Miller 00:02:45 And then you have the professional geneticists who are looking at, you know, odd things that could create a disease. We’re looking at functional genomics. Dr. Deb Muth 00:02:54 Which is so much better. Bob Miller 00:02:56 Yeah. Are you familiar with what we do here, or… Dr. Deb Muth 00:02:58 A little bit, a little bit. So, it’ll be new to me, too, so I’m excited. Bob Miller 00:03:03 And how much time do we have? Dr. Deb Muth 00:03:04 We have an hour, give or take a little bit on either side. Do you have a hard stop anywhere? Bob Miller 00:03:10 No, no, I put a, I moved my clients around, and I don’t have anybody till, 3.30, so we’re good. Okay. Dr. Deb Muth 00:03:16 Perfect. Alright. Bob Miller 00:03:18 It’s like we’re getting started early as well, so… Dr. Deb Muth 00:03:19 Yeah, we’re getting started a little bit early, so that’s good. Bob Miller 00:03:22 Yeah, I just got my office cleaned up, so… Dr. Deb Muth 00:03:23 Okay, good. All right, are you all set to get started? Bob Miller 00:03:28 I’m good to go, my friend. Dr. Deb Muth 00:03:29 I’m gonna just record a little intro and a little bit of a, hook for people, and then we’ll get started. I’ll ask you to kind of tell us a little bit about yourself, and then we’ll just take this conversation wherever it’s supposed to go. Bob Miller 00:03:39 Okay, you got it. Dr. Deb Muth 00:03:40 Alright, sounds good. So what if the reason you’re not healing isn’t your diet, your supplements, or your labs, but it’s actually your genes? Dr. Bob Miller is uncovering how genetic variants, when combined with modern toxins, explain why some of us stay sick no matter what we try. Today, we’re talking genetic pathways, detox blocks, and the new science every wellness warrior needs to know. Welcome back to Let’s Talk Wellness Now, the show where we uncover the root causes of chronic illness, exploring cutting-edge regenerative medicine, and empower you to heal from the inside out. I’m Dr. Deb, your medical detective, and today, our guest, Dr. Bob Miller, is a true pioneer in functional genomics. He’s a board-certified traditional naturopath and the founder of Neutrogenetic Research Institute. And he’s the leading groundbreaking research on how genetic variants influence chronic illness, inflammation, and detoxification. His work has been recognized on international stages, uncovering links between genetic expression and conditions like Lyme disease, mast cell activation, or MCAS, and mitochondrial dysfunction. I’m so excited to talk to Dr. Bob today. He is gonna reveal some things that even I don’t know about, so I’m excited to learn alongside of you guys. So… Dr. Bob, let’s get started. Tell us a little bit about yourself, and kind of how you got on this journey. Bob Miller 00:05:04 Well, that’s, that’s interesting. I was sort of like a mid-career coming to the natural health field, because in my early 30s, I found myself with a severe case of ulcerative colitis. Bob Miller 00:05:15 And I was in the hospital for 21 days. probably within hours of death, pleading to death. And they told me I’ve got one option, and that is cut out the colon and wear a bag. Didn’t sound like a lot of fun. Dr. Deb Muth 00:05:27 Not an option I would want. Bob Miller 00:05:29 So, you know, the medical folks wasn’t real happy with me, but I said, yeah, I’d like to explore some alternative things.Never thinking that I’d get into this field, and then I just, you know, worked with some herbalists and things that I found absolutely fascinating. So, that’s how I got into this around 30 years ago. And, haven’t looked back since, and just having a… having a blast as we now move into how our genetics impacts things. So, that’s what we’re gonna… that’s what we’re gonna talk about today. Dr. Deb Muth 00:05:58 I’m excited to talk about this genetic thing. When you started over 30 years ago, what kind of patience and problems first inspired you to dig deeper into that root cause healing and kind of get into the genetic piece of it? Bob Miller 00:06:10 Sure. Well, you know, as a… now, I’m in a part of the country called Lancaster County, Pennsylvania, where there’s a lot of Amish and Mennonite, and they gravitate towards these things.So, this is their first thing to do, and that doesn’t work, then they’ll go other routes. So, you know, back then, we just saw typical, you know, a little tired, constipation. You know, a little bit of fatigue, arthritis, those kind of things. But things have changed dramatically over the years, as people are now getting more chronically sick. You know, it’s worse than it’s ever been. And what we’re finding is the, the culprits Primarily is mold exposure and Lyme disease. When people get those two together, they’re just… it’s an inflammatory cascade that nobody can seem to unravel. So that’s where we spend a lot of our time. And we’re also spending a lot of time looking at mental health, like ADD, ADHD. And, we give… this year I’ll be speaking at three autism conferences. And we can dig into that a little bit as to why we think we’re seeing such a dramatic increase. And aside from autism, that used to be 1 out of 1,000, now it’s 1 out of 33, or 23. You know, we’re also seeing dramatic increases in ADD, ADHD. People are stressed out. And today, I think we’ll have the time to actually go through and show how environmental factors combine with genetics to cause that to happen. So we’ll… we should have a fun visit here today. And today, I think we’ll have the time to actually go through and show how environmental factors combine with genetics to cause that to happen. So we’ll… we should have a fun visit here today. Dr. Deb Muth 00:07:37 This should be a fun visit. We can cover lots of topics. I am so excited. So, you founded Nutri Genetic Research Institute in 2015. What did you hope to accomplish, and what kind of surprised you in your findings so far about that? Bob Miller 00:07:51 Well, you know, let’s back up at what, you know, genetics is used for. Everybody’s familiar with 23andMe and Ancestry that, you know, tells you where your ancestors came from. Then you have your professional geneticists. I mean, these are people with a degree in genetics. And they’ll look for, you know, very odd sort of things that are prone to relate to a disease. So there are disease-related genetics. Well, in functional, we don’t look at either of those. We look at For example, how you’re breaking down your fats and utilizing them. How you’re recycling your glutathione. How you might be handling your iron. And none of those are disease-causing on their own.And none of those are disease-causing on their own. But when they pile up on you, and then combine that with environmental factors, that’s when things start to go south on us. So, that’s what we’re doing, we’re looking at patterns. And our first foray into this was, we did studies on Lyme disease. And our first foray into this was, we did studies on Lyme disease. So, we looked at, like, I think 50 people with Lyme disease. We looked at their genome. So, we looked at, like, I think 50 people with Lyme disease. We looked at their genome. And we found patterns that were more evident in those with Lyme. Now, this doesn’t… these genetics don’t mean you get Lyme, it just means if you get Lyme, you react worse to it. And we found patterns that were more evident in those with Lyme. Now, this doesn’t… these genetics don’t mean you get Lyme, it just means if you get Lyme, you react worse to it. So, as you know, some people get Lyme, they go on a round of antibiotics, and they’re done. So, as you know, some people get Lyme, they go on a round of antibiotics, and they’re done. Others have a little more struggle, and then others are struggling terribly for years. So there’s an old adage of genetics loads the gun, environment pulls the trigger. Dr. Deb Muth 00:09:14 Yeah, that is so true, and I think when we’re talking about Lyme and mold and things like that, we forget sometimes that our genetics can predispose us to be more sensitive to those things, and if we have genetic pathways where we don’t clear things properly, it’s harder for us to get them out of the body. And then you add on that whole rain barrel effect that we’ve always used as a functional medicine term, right? If the barrel’s half full, you’re okay. If it’s full, and now it’s spilling over, it’s a bigger problem. Have you guys found, too, that some of these environmental things actually are changing the genetics of people, or how they’re processing their own genetics? Bob Miller 00:09:53 Well, let’s go back to, Genetics 101. But we’ll go back a little bit further. So, what an interesting mechanism, what a miracle the body is. Bob Miller 00:10:03 Fats, carbohydrates, proteins, drink water, breathe air, expose the sunlight, and somehow everything gets made. I mean, when you just step back and think about that, it’s like, It’s pretty darn amazing. Dr. Deb Muth 00:10:15 I always tell women, you know, the fact that we get pregnant and we have healthy pregnancies and births is a miracle, because if we had to try to control that, that wouldn’t work so well. Bob Miller 00:10:25 Right. Well, that’s another miracle. These microscopic sperm and egg, human being, 9 months later, it’s like. But even inside of us. We are making our hair, our skin, our nails, our blood vessels, our ATP, our energy, it’s all being created. Well, that gets created by enzymes. So, enzymes take one substance, combine it with something else, and make something new. Then another enzyme comes along and does the same thing. Your DNA is the instructions on how to make the enzymes. So, when we are conceived. If it’s a, if it’s a female, of course, it’s the XX, the two chromosomes. You know, we’ve… everybody’s seen those… the genetics that… Listed pair. So, if it’s a female, the father donated the X enzyme. And the mother has no choice but to give the eggs, so that’s female. If the father donates the Y, you have a male that’s in chromosome number 1. Then 2 through 23 is the rest of the instructions on how to make enzymes. So, what can happen? We can get what are called SNPs, single nucleotide polymorphisms. And SNPs just mean that the instructions to make the enzyme’s not quite as good. So, if one parent gives a SNP on the making of an enzyme, The enzyme’s fine. It works. But, general rule of thumb, It may only work at 70-80% of efficiency. Now, a good analogy is think of an 8-cylinder and a 6-cylinder car. If parents give you good information, that’s like having an 8-cylinder car. If one parent gives you that snip, it’s like having a 6-cylinder car. Now, is a 6-cylinder car a fine car? Sure. It’ll get you from point A to point B, but it’s just going to have the power of an 8-cylinder. Then if both parents give you a SNP on the same enzyme, it may be 30-40%, and that’s like having a 4-cylinder car. Sits in the driveway, looks the same, puts gas in it, everything. But if you’ve got a 4-cylinder car. Probably not a good idea to go cross-country pulling a trailer behind you up and down mountains. Dr. Deb Muth 00:12:29 This is true. Bob Miller 00:12:32 So… We can get an 8-cylinder, 6-cylinder, or 4-cylinder enzyme. Now, if it’s not under a lot of stress, if that 4-cylinder car is just taking you to the bank and the grocery store. It’s just as good as an 8-cylinder car. But if you gotta pull that trailer, and there’s a lot of stress on it, being mountains, it’s gonna struggle. Now, there’s one other little caveat to this, and that is some genetic mutations are gain-of-function. They actually work faster. Now, we have enzymes that do all kinds of things. We have enzymes that make and recycle our antioxidants, but we also have enzymes that make inflammation. No, that’s a good thing, because if we get a virus or bacteria, if you didn’t make inflammation to kill it, well, we’d all die of infection. So, you know, we tend to think of free radicals as bad, antioxidants as good. They both play an important role. But interestingly, some of the major enzymes that make inflammation, they can be overactive. They can be turbocharged. And when they’re stimulated by environmental toxins, they overreact. Bob Miller 00:13:40 And therein lies the problem. When they overreact, we have a problem. Bob Miller 00:13:46 So, if we have genes that overreact when stimulated. And then the enzymes that take care of inflammation are underactive. Then you’re gonna be more inflamed. You know, the majority of people that, you know, come for functional medicine Or naturopathic help, or… Inflammation that they can’t seem to get under control. Dr. Deb Muth 00:14:06 Right. Bob Miller 00:14:07 And we will be, you know, during this hour, we’re going to look at some of the pathways that make that happen. So, what we can do then, we can’t change our genetics. When you’re conceived, that’s the hand you’re dealt. When your life would be over, if someone would take some tissue and measure, it’d be exactly the same as conception. Does it change. Bob Miller 00:14:28 The enzyme’s ability to do its job may be compromised. Because remember I said there’s a, the enzyme takes a cofactor. So an enzyme takes substance A, cofactor, make substance B. Well, if that cofactor’s not there, the enzyme’s not going to work either. So, you could have an 8-cylinder car, and if there’s no gas in it, it’s not going anywhere. So… It’s the strength of the enzyme, it’s the cofactor to do the A to B conversion. And that’s what we’re going to get into. So, many people say, well, where did these SNPs come from? Nobody knows for sure. Sometimes they’re what’s just called de novo, when the sperm and egg go together, the instructions get mixed up a little bit. We do believe a lot of it came from a long time ago, when we were almost wiped out by sexually transmitted diseases. And those STDs were altering the genes when the conception, in other words, when the sperm went into the egg, the STDs were interfering. And causing the problem, so… I often joke, if you want to blame somebody. Blame your great-great-great-great-great-great-great-grandparents for, being a bit promiscuous, so… Dr. Deb Muth 00:15:31 Yeah, for being… having a little too much fun, right? Bob Miller 00:15:35 So, we don’t know for sure, but, you know, there are some that, But most of the SNPs that we get inherit from our parents. So, if you look at a child. And you look at the SNPs. 99.9% of the time, it came from one of the parents. Dr. Deb Muth 00:15:50 In identical twins, do they have the exact same identical makeup? Bob Miller 00:15:54 Yep, Dr. Deb Muth 00:15:56 But not in fraternal twins, correct? Bob Miller 00:15:59 No, no, those could be different, Jeff. Dr. Deb Muth 00:16:00 It could be different because they have different sacs, they’re not sharing that same genetic makeup. Bob Miller 00:16:04 Yeah, so keep in mind, both your mother and your father have, you know, the two And so you get one from one parent, one from another. Dr. Deb Muth 00:16:13 So… Bob Miller 00:16:14 Interesting situation. I had, 3, 3 boys. And, we were looking at an enzyme related to breaking down oxalates. Now, the mother and father each had one SNP, and that’s called heterozygous. Three boys, and they all come together, they’re Amish boys, they’re a lot of fun. And I looked at their genomes, and the one boy didn’t have any SNPs at all. And one had won. And the other one had two. Dr. Deb Muth 00:16:41 Interesting. Bob Miller 00:16:42 So, we don’t quite know how these things get handed off, but with the parents each having one, you could have a child with none, one, or two. So, the one, his ability to break down oxalates, which is fine. The other one was slightly impaired, and the other one was dramatically impaired. So, you can have 3 children, and it all depends what the parents have. Now, if a parent has a homozygous, or 2 copies. And the other parent has nothing. Every child will have one. Okay. If both parents are homozygous, that they both have two, Every child will have two. Dr. Deb Muth 00:17:19 too. Bob Miller 00:17:20 Yes, so that’s the way it works, but, you know, but it’s somewhat rare that both parents are homozygous on an enzyme, but it can happen. Dr. Deb Muth 00:17:27 Do we think that infections today, like Lyme disease or mold exposure, things like that, if the parent, the woman, primarily, I’m thinking, is pregnant, and she actively has these infections. Can those infections affect the genetics, kind of like a past sexual transmission did where we thought back in the day? Bob Miller 00:17:47 Yeah, I… I mean, I’m not that much of a geneticist to answer that for sure, but my thought would be no, that at conception, the pattern’s made. Dr. Deb Muth 00:17:55 Okay. And then that’s… that’s the hand you’re dealt. Bob Miller 00:17:58 Yeah. So, I tell people we have good news and bad news. The good news is we can compensate for the weakness. The bad news is we can compensate for the weakness. Dr. Deb Muth 00:18:09 That is so very true. Bob Miller 00:18:11 Yeah, we can’t, because I often get asked, so we’ll do some things now, and we’ll check my genes again, and they’ll be better. It’s like, nope. Dr. Deb Muth 00:18:18 Oh, – – Bob Miller 00:18:19 You gotta play the hands you’re dealt, so… Dr. Deb Muth 00:18:21 That’s right. Bob Miller 00:18:22 You can test your genetics… if you’re looking at the same enzyme, you can test it every year. It’s not gonna change. It’s like the blueprint. Dr. Deb Muth 00:18:30 It’s good and bad, right? It’s the one test you only have to do once in your lifetime. Bob Miller 00:18:34 No, unless, you know, like, our. Dr. Deb Muth 00:18:36 All the time. Bob Miller 00:18:37 Yeah, now our test looks at, called the Functional Genomic Analysis Test of your genomic Resource. We look at 220,000 steps. Dr. Deb Muth 00:18:46 Wow, that’s a lot. Bob Miller 00:18:47 That’s not all of them. Dr. Deb Muth 00:18:49 Right. Bob Miller 00:18:50 So, maybe in the next year, we’re gonna come out with our third version of the chip. And then, if someone wants to get those new things that weren’t on it, they’d have to repeat. But whatever we measured is gonna stay the same. Dr. Deb Muth 00:19:03 That’s a lot of SNPs to look at. Bob Miller 00:19:05 Keeps us busy. Dr. Deb Muth 00:19:06 But there’s still, but there’s still SNPs that we. Bob Miller 00:19:09 That we’d like to have that we don’t have, so… Bob Miller 00:19:11 We started out with version 1 on our genetic test, then we worked with version 2, and we’re already compiling a list of what version 3 would look like. So if somebody has our version 2, And we’re saying, you know what, it’d be nice if we could see these, well, then you’d repeat, but it won’t change what you already know, so… Dr. Deb Muth 00:19:29 Got it, got it. So, when you started out, and you started looking at the research of Lyme disease and chronic infections, which detox pathways are most important for people who struggle with those conditions? Bob Miller 00:19:43 Okay. You know what might make sense as we do a screen share, and I’ll actually show you the pathway. Does that make sense? Bob Miller 00:19:48 Alright, so… let’s see if I… let me just press the share… Dr. Deb Muth 00:19:52 Yep, you should just be able to press share. Bob Miller 00:19:54 And… number 2. Okay. Are we seeing the screen there? Bob Miller 00:20:01 Okay. Dr. Deb Muth 00:20:02 So, this is a map that we made. Bob Miller 00:20:05 And by the way, this is not… All-inclusive of all the things we look at, but we believe this is a core issue. So, where we’re going to start here, there’s something called the microglia. And the microglia are glial cells. They’re in the brain and the central nervous system. And they’re very interesting little creatures, because most of the time, and this is just a drawing of what they sort of look like. Most of the time, they’re in what’s called the M2 anti-inflammatory mood. What that means, these little guys pick up dirt, debris, Recycle them. Turns on an enzyme called interleukin-10 that’s anti-inflammatory. And just kind of does general housekeeping. And just kind of does general housekeeping. However, when a trigger comes along. However, when a trigger comes along. They… it’s the same glial cell, but it moves over to a very pro-inflammatory enzyme. A pro-inflammatory glial cell. And it triggers these 3 enzymes, Actually, these four. That are pro-inflammatory. Tumor necrosis vector alpha, Interleukin-6. NF Kappa B, Inos. Now, these create inflammation. So you might think, well, why is that good? Well, if you have some foreign invader, virus, bacteria coming in, parasite. If you didn’t have these guys coming to the rescue, you would just die of infection. So, these guys are your friend unless they’re your worst enemy. Because TNFA, and we’ll show you when we actually do a demo account, TNFA can be overactive. So, in other words, it over-responds. Interleukin-6 can be overactive. And if Kappa-B can be overactive. The INOS, and I’ll explain each of these as we go through a demo, can be overactive. Now, what that means is, you’re very good at killing virus and bacteria. But this is where autoimmune disease comes in, and just inflammatory conditions. Now, this is just speculation, but we think what happened is, as you know. Thousands of years ago, we didn’t have refrigeration, we didn’t have sewer, we didn’t have pure water, and we didn’t have antibiotics. So, if you made it to 40, you were an old-timer, because everybody was dying of infection. So, what we believe happened is, by what’s called natural selection, Having these overactive. A thousand years ago was to your advantage. Dr. Deb Muth 00:22:31 Hmm. Bob Miller 00:22:32 But now… We have pure water, we have refrigeration, we have sewers, we have antibiotics. But now we have environmental factors that are stimulating them. Now it’s to our disadvantage. And we’ll talk about that a little bit as it relates to the hemochromatosis genes and maybe the G6PD. Dr. Deb Muth 00:22:48 Yep. Bob Miller 00:22:49 Now, why are we becoming so inflamed? Let’s look at the triggers. Now, one of my, favorite expressions is. I was born all the way back in 1954. Dr. Deb Muth 00:23:01 And it was a different world back then. Bob Miller 00:23:05 These are some of the triggers. And we’ll get into these, but right now, high fructose corn syrup, And the high-fat diet. High fructose corn syrup only came about in 1968. So now we’re being exposed to high fructose corn syrup. Then… we didn’t have these, these viruses like COVID. Dr. Deb Muth 00:23:26 Yeah. Bob Miller 00:23:27 Now, there’s now pretty strong evidence that COVID Was actually, you know, made as a gain of function. It’s debated, and I’m not taking an opinion on it, but there’s some people who believe Lyme disease was also a part of experimentation. Dr. Deb Muth 00:23:40 Go. Bob Miller 00:23:41 Then we have molds, and it appears as though mold is getting stronger. you know, 20 years ago, when I was seeing folks, mold wasn’t on the radar. I would say 7 out of the 10 folks we speak to today have mold problems. Yeah, 20 years ago, we talked more about mold allergy being an issue versus mold toxicity being an issue. Right. So… I know some folks are, you know, speculating what’s happening, but one of the theories out there is that EMF is strengthening mold. I don’t know if you ever heard that theory, and I don’t… Dr. Deb Muth 00:24:13 I have. Bob Miller 00:24:14 I’m not claiming it’s true, but it’s an interesting theory. Then even, you know, your black mold from water-damaged buildings. Then our air pollution is getting worse. We’re getting more toxic metals. Dr. Deb Muth 00:24:26 You know, if we have a… Bob Miller 00:24:27 You know, we’re gonna look back someday and say, what were we thinking, smearing aluminum into our armpits? The, what were we doing putting mercury in our teeth? Then, you know, glyphosate. When I was a kid, there was no glyphosate. So, all of these herbicides and pesticides. Polychlorinated biphenols, And then EMF. So, we love our cell phones, you know, and I think unless you, or in the middle of the desert, or down in a cave, you’re being exposed to EMF somewhere. So, you know, we have our cell phones with us, we have, We have Wi-Fi, the towers are everywhere. And we don’t know long-term, but we may find that this can… this creates some inflammation. And I don’t know if you get any folks, but do you have any folks that have… are they EMF sensitive? Dr. Deb Muth 00:25:16 Oh yeah, we have a whole bunch of them. Bob Miller 00:25:18 Yeah, and then if you have any TBIs, So, plenty of things here. that will stimulate into the microglia, M1. Now, you could say, well. We’re all pretty much exposed to the same thing. Why do some people get hit harder than others? So here’s where we’re gonna start. There’s an enzyme called Nrf2 and RF2. And Nrf2 is the enzyme that senses when there’s inflammation. And turns on hundreds of anti-inflammatory enzymes. We’ll show when we do the demo, you can have genetic weakness on NERF2. And NERF2 inhibits and slows down microglia M1. supports M2. Now, if it’s not complicated enough, there’s an enzyme called KEEP1. And KEEP1 inhibits NRF2. And you can actually have gain of function on keep 1, that makes Keap 1 stronger. So… A lot of the people who land on my doorstep So… A lot of the people who land on my doorstep Both parents gave a mutation on KEEP1, making it overactive. Both parents gave a mutation on KEEP1, making it overactive. Dr. Deb Muth 00:26:31 Hmm. Dr. Deb Muth 00:26:31 Hmm. Bob Miller 00:26:32 Suppressing Nrf2, nerve 2 might be weak. So, nobody’s putting the brakes on, M1. And by the same token, Nerve 2 supports M2. Then there’s a process called mTOR and autophagy. mTOR stands for mammalian tard of rapamycin, the growth of new cells. And then autophagy, taking our dead cells and recycling them. We need a balance between the two of them. If we didn’t have mTOR, the sperm and the egg would never become the baby, the baby would never become the adult, we wouldn’t make new cells. But our cells are constantly, you know, the old cells dying off. Autophagy is where we take that debris from the cell and recycle it, just like a farmer Plows the crop under at the end of the year. The dead plant then becomes the fuel for the spring, your dead cell becomes the fuel for the spring, and that’s autophagy. So we’re gonna look back someday and say, what were we thinking? We give our animals growth hormones so they get fatter faster. Oh my. So, we consume those animals, and inventory runs faster. Now, for anybody who’s, You know, maybe above 40, 45 years old. Think back when you were 12, and what did girls look like? They were primarily flat-chested little girls. Now they look like 16-year-olds. Because environmentally, we’re jacking up mTOR. So, mTOR stimulates microglia M1, suppresses microglia M2. Probably 80% of the folks we visit with. This is the part of the problem. NRF2 is weak. mTOR is strong. Environmental factors come along. And this guy gets carried away. He doesn’t do that burst and move back. Stays here. We’re calling that How environmental factors create a locked-in, pro-inflammatory. and neurotoxic phenotype. In other words, once it starts, it just keeps… Feeding upon itself. Alright, so what happens now when microglia is overactive. it triggers these 3 enzymes, TNFA, N of kappa B, And interleukin-6. Each one of these can have genetics that make them run stronger. Then it stimulates an enzyme called NLRP3, Which makes what are called inflammasomes. Now, guess what inflammasomes can be? Your best friend or your worst enemy? Because they will, if you’ve got, again, a virus or bacteria, or possibly even some bad cells in the body. They will zap them. Well, that’s good. Unless it’s overactive. Unless it’s overactive. And then what it does, through interleukin-1 beta, makes excess glutamate. And then what it does, through interleukin-1 beta, makes excess glutamate. Anxiety, gut inflammation, OCD, ADD, autism. And, you know, glutamate, we’ll talk about that a little bit, but glutamate makes you intelligent, highly motivated go-getter. but can also be excitatory. And then, look what it does. Let’s see, do I have the drawing tool here? Yes, I do. Okay. So, it comes down through here, Makes the glutamate. Comes back up through here. through the ADORA 2A enzyme, Then we’ve got a feedback loop that feeds upon itself. Then, through interleukin-18, we make histamine. and mast cells. And then through histamine receptor site number 1, we come back and spin it. And now you’ve just got this spinning feedback loop. So, the glutamate will make you anxious, the histamine will give you allergies and make you anxious. And you’re allergic to everything, and you’re feeling horrible. Now, it doesn’t end there, Dr. Dad. It then goes on to make something called gast dermins that creates pyroptosis, where it actually starts punching a hole in the cell membrane. And you’re only going to be as healthy as your cells are. Just a little background. You know, we’re made up of trillions of cells, and each one of them has what’s called a lipid bilayer, made from lipids, which comes from fats. And you’re only going to be as healthy as those membranes are. So that’s why we coined an interesting phrase. Cellular CPR. Construct the cell. Protect the cell. And restore the cell membrane. And we believe that’s going to be revolutionary in the functional medicine world. So… It’s not hard to figure out that if you start punching holes in the cell membrane, that’s not a good thing, okay? Bob Miller 00:31:22 Now… There’s an interesting molecule called NAD. Thicotide adenoside dinucleotide. And anybody who’s in the, you know, listening to the health podcasts and things, they’re… They’re, they’re learning about NAD. And I’m going to show you a chart later, all the good things that NAD does, but For the most part, it helps what’s called sirtuins. And sirtuins are quite interesting. If anybody’s looking at longevity. The sirtuins is where they’re looking at.Because sirtuins turn on good things. Turn off bad things. And I’ll show some charts on that later. So for right here, this sirtuin uses NAD, to slow down NF-kappa-B. CERT 2 uses NAD to slow down an ORP3. So, if we’ve got genetic weakness on these, or we don’t have enough NAD, We don’t hold this pathway back. Make sense? Dr. Deb Muth 00:32:24 Yeah, makes perfect sense. Bob Miller 00:32:25 Now, I’ll show this a little bit later. So, people are like, oh, well, I’m gonna start taking some NAD. Dr. Deb Muth 00:32:31 Right. Bob Miller 00:32:32 And there’s functional doctors who give NAD intravenous. It was just this morning, I was talking to a woman who said, Oh my gosh. I went and got intravenous NAD, and it took me a month to recover from that. Dr. Deb Muth 00:32:45 Hmm. Bob Miller 00:32:46 what happens is, and I’ll show this in a little more detail, there’s an enzyme called CD38, that’s stimulated by NF-kappa-B. And it takes NAD, To make intracellular calcium. that stimulates NLRP3 and actually makes things worse. So, if we have this guy upregulated, and I’ll show a chart what does that. taking NAD will make you worse. Again, when I go into the software, I’ll show you that whole pathway, so… I would encourage people, you know, just don’t go out and start taking massive amounts of NAD, you know, stick your toe in the water, see how you do. Because everything you’ve heard about, how good it is, is true, unless this guy says, oh, thank you very much, let me make more inflammation. Now, this might be part of our innate immune system, that if we have some pathogen that’s gonna kill us. By golly, we want that to happen. But if this is happening by environmental factors, Then it’s detrimental. So the immune system that protected us a thousand years ago now might be turning on us because of the environmental factors that we showed earlier. All right. Then there’s an enzyme called PARP that’s NAD-dependent, and that actually repairs strain breaks in your DNA. Now, the next thing that happens… is there’s an enzyme called NADPH oxidase that gets stimulated. and something called INOS. Now, I’m sure most people know about nitric oxide. It’s a gas that dilates your blood vessels. That’s why sometimes they’ll even give people drugs, nitroglycerin, to boost their nitric oxide. That’s why people are doing beetroots and other things to boost their nitric oxide. But there’s an OS3 enzyme that makes the nitric oxide that’s good for blood flow. But there’s an INOS That makes nitric oxide to kill pathogens. probably might be the third or fourth time I’ve said this. That’s a good thing, unless it isn’t. So, if it’s killing some pathogen, great. It was just misfiring. it combines… With superoxide that’s made by this enzyme, and makes something called peroxynitrite, which is one nasty free radical that chews you up and spits you out. So, the NOx enzyme, NADPH oxidase, uses NADPH, To make this free radical called superoxide. If we have time, we’ll get into it. NADPH is what your body needs to recycle your antioxidants.So, I coined the phrase, the NADPH steel. Where the NOX enzyme takes this very important NADPH, And rather than being useful, makes superoxide. Now, again, is that fine if you’ve got some bacteria to kill? Of course. But if it’s just chronically running, it’s just making all this chronic inflammation. Then it makes something called hydrogen peroxide. And we need to clear hydrogen peroxide by 3 enzymes, catalase, thyroid reduction. And glutathione peroxidase. If we have genetic issues on here, or we don’t have the cofactors. There’s something called the Fenton reaction, discovered in 1895 by Dr. Fenton. Where hydrogen peroxide combines with iron to make what are called hydroxyl radicals. And guess what they do? They create lipid peroxides, That damages your cell membranes. Now, again, the body’s pretty darn amazing. We have glutathione, And here’s where your body’s taking glutathione and recycling it. But look who’s needed to recycle it. NADPH. So, if this guy up here is chewing it up, We don’t recycle our glutathione. And then an enzyme called glufon peroxidase 4, Takes this damaged lipid and repairs it. So, here we’ve got this protecting, we want to protect it by not having this happen. But then we also need this guy to do the restoration. So, there’s a lot that can go wrong in here, Dr. Deb. Dr. Deb Muth 00:37:07 There’s a lot that could go wrong. And I can imagine some of my listeners are thinking that lipid peroxidase, is that the same thing as what they’re thinking of when we talk about lipids and cholesterol? Is that the same process that’s happening there? Bob Miller 00:37:22 Well, no, no, the lipids can be used to make cholesterol, but here we’re talking about where they’re going to build the cell membrane. And they’re being… and they’re being, destroyed. If anybody would like to see a visual representation of this, just go on YouTube. And type in, ferrooptosis Animation. cool little video, it’s about 3 minutes long, and it shows the lipids coming over, being oxidized, and now GPX4 fixes them, so… YouTube, Pharaoptosis Animation, cute little video. It’s just that really… Shows vividly what we’re… what we’re talking about here. Now, this is… Dr. Deb Muth 00:37:59 And so this is very common, too. Like, a lot of people do hydrogen peroxide IVs. Dr. Deb Muth 00:38:04 And so, if somebody doesn’t know their genetics, they could have a problem with doing those, just like they could doing the NADHIVs, correct? Bob Miller 00:38:13 Sure, yeah, yeah, yeah. So, I’ve talked to so many, you know, of course, the hydrogen peroxide kills pathogens. I mean, that’s what it does. So… but I’ve spoken to so many people that said. I had one client that said they’ve never been the same after having one hydrogen peroxide infusion. Dr. Deb Muth 00:38:30 Interesting. Bob Miller 00:38:31 Yeah. So… it can be… I see why people use it, because it. Bob Miller 00:38:36 pathogens, But on the other hand. And now’s a good time to speak about… I don’t have it on here, but there’s a, there’s an enzyme called the HFE gene. And that is what causes you to absorb iron. And there’s mutations in it that cause something called hemochromatosis. Were you overabsorb iron? Now, true hemochromatosis is when both parents give you a mutation. But there’s now growing evidence even a heterozygous can cause a little bit more iron absorption, not to the human chromatosis point, but overabsorption. So, if you overabsorb iron, And you have too much hydrogen peroxide that’s not cleared, All kinds of inflammation. Now, what’s happened is sometimes this inflammation Will damage the red blood cells. And some well-meaning doctor says, oh, you need some iron. And they take iron and it makes it worse. So, can’t tell you how many people I’ve said, you’ve got the overabsorption of iron, and they say, well, that can’t be right, because I’m low in iron. Well, that could be because it’s being chewed up here. Dr. Deb Muth 00:39:40 Sure. GPX1 and TXN turn it into, to water. The, catalase turns it into water and oxygen. Dr. Deb Muth 00:39:58 Now, I see a lot of my clients who have mutations or SNPs on that GPX gene, on that glutathione gene. And they really struggle to clear a lot of their toxins. Bob Miller 00:40:12 Sure. Dr. Deb Muth 00:40:14 Yeah, absolutely. Well, GPX4. Bob Miller 00:40:18 is what, repairs, but you can see GPX1 Is what uses glutathione. To turn hydrogen peroxide. So, but it all depends upon having enough glutathione. Dr. Deb Muth 00:40:30 Yeah. Bob Miller 00:40:31 Well, guess who controls making a glutathione? Dr. Deb Muth 00:40:34 Nerf 2. Bob Miller 00:40:37 So, if you have a keep one weakness, or strength to two… I’m sorry, keep one is too strong. Nrf2 is too weak. You don’t make glutathione. So, when a lot of people do that, it’s like, well, I’m gonna take glutathione. Dr. Deb Muth 00:40:51 Right. Bob Miller 00:40:52 And some do great, and some do poorly. You know, because… and I’ll show this on one of the other charts. You can see here that the, The glutathione has to be recycled. And if we don’t recycle it, it actually turns into superoxide free radical. So… NADPH are the cofactors, For taking the oxidi… here’s oxidized glutathione, here’s reduced. So, this is a good glutathione. After it does its job, you can see it becomes oxidized.We need to recycle it. Well, if we have weakness on the enzyme that does that, or a weakness in Nrf2, or not enough NADPH. The oxidized glutathione never gets recycled. So, I’ve talked to a lot of people who said, oh, glutathione made me so sick, and say, well. Dr. Deb Muth 00:41:43 Yeah. Bob Miller 00:41:44 You need it, but you need to recycle it. Dr. Deb Muth 00:41:46 Can you speak for just a brief moment, too, about MTHFR? That is a very popular gene, it’s all over social media as the major gene, but can you speak to a little bit about that, and how that fits into this whole process of things? Because it is just such a small piece. Dr. Deb Muth 00:42:04 understanding genetics. Bob Miller 00:42:06 Yeah, to be honest, it drives me nuts. Dr. Deb Muth 00:42:08 Me too. Bob Miller 00:42:11 Alright, so… You know, there are people on social media I won’t say what I think, I’ll be kind. But… But the, And, you know, they might mean well. But they talk about, if you have MTHFR and COMT and PEMT, that’s… oh my goodness, that’s horrible, and we’ll fix that for you, and you’ll be fine. Bob Miller 00:42:36 it just irritates me to no end. And it really could get anybody who’s doing this legitimately in trouble. I mean, I’m afraid someday, you know, there might be some cracking down on this kind of nonsense. Now, to answer your question about MTHFR. Dr. Deb Muth 00:42:51 I mean, it really is, but I’ll tell you what, why don’t we hold that thought until I go to another map and I can actually… Okay. Bob Miller 00:42:56 But the real… the cliff notes is the MTHFR puts a methyl group on your folate, which is needed, but it has gotten way, way, way too much attention. And people learn they have MTHFR, and they start taking a multivitamin with methylfolate, then they take a B vitamin with methylfolate. Dr. Deb Muth 00:43:13 And they’re pushing it too hard. Bob Miller 00:43:15 Yeah. So I can’t tell you how many people I’ve helped by saying, stop it. Dr. Deb Muth 00:43:20 Yeah, take less of it. Bob Miller 00:43:21 Take less of it, yeah. So, yeah. Yeah, there’s a… If somebody, say, ranked the enzymes at their level of importance, MTHFR might be 40 or 50 on a scale of 100, you know. Keep one Nerf two. big deals. Dr. Deb Muth 00:43:40 deals. Bob Miller 00:43:41 NQO1 that I didn’t even talk about yet, NQO1, takes your, NA… your NAD goes into NADH, To make electrons for the electron transport chain. you need NQ01 to bring that back. If that’s not working, and I’ll show you on the NAD map how disastrous that can be. Now, the next piece is here, and I think You know, if you talk to any school teachers and say, if you’ve taught for more than 10 years, how are the kids today? Every one of them says, more ADD, ADHD, more autism. Just look at human beings, we’ve never been so agitated. You know, everybody, and it might be a social media thing, but people take a position on something, and if anybody doesn’t share that position, they view them as the enemy. Dr. Deb Muth 00:44:29 And it’s kind of scary what’s happening to us. Bob Miller 00:44:33 So, we can’t agree to disagree anymore. We see anybody who has a differing opinion as the enemy. And, you know, there was… there’s people that didn’t have Christmas dinners together, because they had political differences, like… Dr. Deb Muth 00:44:44 Excuse me. Bob Miller 00:44:45 can’t you put your political differences aside to have Christmas together, you know? Dr. Deb Muth 00:44:49 Right? Bob Miller 00:44:50 become that, you know, no matter what your position is, and I’m not saying anyone’s right or wrong, I’m just saying. You know, in the old days, they used to say that the Republicans and Democrats in Congress would argue policy and then go have dinner together. And now everybody’s all up in arms, angry. Dr. Deb Muth 00:45:05 Yeah. Bob Miller 00:45:06 So… There’s likely multiple reasons for that. But let me show you one of them. That, you know, to what degree this is… very important, we don’t know, but I think We’re beginning to believe this is very important. So, there’s something… there’s a neurotransmitter called GABA. And God buys the don’t worry, relax, be happy. Chill. Okay. Dr. Deb Muth 00:45:31 Nobody has enough of that anymore. Bob Miller 00:45:33 Well, yeah, you’ll be surprised what I’m gonna show you. So, let me see if I can find a, Let me see if I can find the right slide here. Let me look for it here. So, there’s something called a GABA receptor site. And here you can see… This is a neuron, and this is where you, The neuron normally is excitatory. However, there’s normally low chloride in the neuron. Dr. Deb Muth 00:46:09 Hmm. Bob Miller 00:46:10 So, GABA itself is neither relaxing. For excitatory, all GABA does, it opens up what’s called a chloride channel. And then chloride, which has a negative charge, will flow into the neuron. Follow me there? Dr. Deb Muth 00:46:26 Yep. Bob Miller 00:46:27 And as it does, it changes this from a positive charge to a negative charge, And it’s relaxing. and inhibitory. Dr. Deb Muth 00:46:34 Hmm. Bob Miller 00:46:36 Now, on the other hand, there’s enzymes called NKCC1, That will push chloride in. and KCC2 that will bring chlor… oops and bring chloride out. And then there’s a sodium channel. And, sodium has a positive charge. And glutamate will push that in. So, as long as this is happening. And GABA says, receptor sites, open, chloride goes in, Chill. However, If NKCC1 Pushes extra chloride in. KCC2 doesn’t pull it out. and GABA hits the receptor site, the GABA comes flowing out, Sodium comes in, And now it’s excitatory. So Gabba didn’t change. GABA just opened the receptor site, that’s all it does. Dr. Deb Muth 00:47:33 Yeah. Bob Miller 00:47:34 But it’s the chloride balance that’s going to determine whether this is relaxing or not. Now, these are the things that go along with when they lose that KCC2 or gain NKCC1. Pain and sensitivity, burning electrical, neuropathic pain. Normal touch hurts. Sound and light sensitivity. Tinnitus can flare. Headaches and migraines. Seizure tendency. Body jolts. Spasticity, cramps, stiffness, startle reflex. Trouble falling asleep, non-restorative sleep. Anxiety, stress, reactivity, that’s what we have now. Hyperarousal, panic-like surges, irritability, racing thoughts. Brain fog, slowed processing, working memory slip-ups. Mental fatigue. Episodes of racing hearts, sweaty palms, guts on edge. Those are all the things that happen when this GABA switch occurs. Now, here’s what happens, and this is what I’m going to be presenting at an autism conference. When you have a newborn, they need that NKCC dominant to develop. By early childhood, it should… or, sorry, early adulthood. we should move over to the KCC dominant, that’s the taking the chloride out. Nice-looking 25-year-old boys, functioning very well. However, when we get microglia M1 upregulated. Because of environmental toxins, processed foods, Tylenol, aluminum. they stay in NKCC1 dominant, and there’s ADD, ADHD, Autism, the whole spectrum. because… They’ve not moved over to the… They’ve not moved over to the KCC2. And again, this is caused by… Environmental factors. Stimulating the microglia. And then, interleukin-1, interleukin-18 weakens KCC2, interleukin-1 beta, Strengthens NKCC1. high chloride. We open up the chloride channel, In Rebell Excitatory. So, I think when, When the pediatricians get ahold of this, they’re going to be very excited to know that This could be why we’re seeing such a rise, and not just autism, but ADD, ADHD, anxiety, the whole shit mess. Dr. Deb Muth 00:49:58 thing. Bob Miller 00:49:59 Yeah, so… and you can see NF-kappa-B stimulates that. These stimulate it, and I think that’s why everyone’s getting so anxious. Now, there’s a little bit more to it, and we’ll get into this when we look at some of the maps, but… The, the glutamate, Which is excitatory. will stimulate the NMDA receptor, make more glutamate, And glutamate will inhibit KCC2. And then we also need an astrocyte To, take both ammonia And glutamate, and… Turn them back into glutamine. And I’m going to talk to you a little bit about arachidenic acid, and if we have too much arachidenic acid. or TNFA is upregulated, that doesn’t happen. Ammonia goes up, and there may be multiple reasons for this, but this is a reason why some of the autistic kids do flapping. Dr. Deb Muth 00:50:49 Hmm. Bob Miller 00:50:50 Because they’re not clearing their ammonia. And you can tell if somebody has high ammonia by… they get that old person smell, you know. Dr. Deb Muth 00:51:00 Yup. Bob Miller 00:51:01 your vehicle cycle’s not taking out the, the ammonia. Now, last pathway here. There’s growing interest in mast cell activation. So, back here, we talked about peroxynitride. And that will stimulate mast cells, and those are white blood cells that are your best friend, unless they’re your worst enemy. Then it’ll make histamine. And there’s enzymes called histidine decarboxylase that’ll make more. Dr. Deb Muth 00:51:28 I’m sure everybody’s heard of DAO, the enzyme that degrades histamine. Yep. Bob Miller 00:51:31 We can have genetic weakness, we don’t make that. There’s an enzyme called histamine and methyltransferase, That, That breaks down the histamine. Then if we don’t do that, it’ll get stuck in the histamine receptor site. And then it’ll make something called, renin. Which will cause angiotensinogen to turn into angiotensin. One, that turns into angiotensin II,And that’s where people make aldosterone, where they’ll get the, The swollen ankles and high blood pressure. But interestingly, there’s an enzyme called ACE2, that takes this guy and turns it into angiotensin 1-7, Which is anti-inflammatory and also inhibits… TNFA. Now, you can have weakness on ACE2, But… and anybody’s saying, that sounds familiar? Dr. Deb Muth 00:52:25 That’s where COVID comes in, using ACE2. Bob Miller 00:52:28 And now we just found there’s literature that if you get COVID long enough, it can actually make ACE2 not be able to work as well. So look what it does. It comes down here, stimulates the NADPH oxidase, More superoxide. More peroxynitrite. And we’re on a cycle here. We’ve actually named this the Home Cycle Hypothesis, the proposed feed-forward loop. That just keeps feeding on itself. All being caused by… Primarily, The environmental factors. But hitting those who have genetic weakness the hardest. That’s why. Dr. Deb Muth 00:53:08 To the people. Bob Miller 00:53:09 Don’t live in a moldy house. One person is sick as can be, and the other person says, well, you must be imagining things, because I don’t feel anything. Dr. Deb Muth Yeah. Same thing with long haul, right? Two people can both get sick, one gets sick and never seems to recover, and somebody else gets sick, and they have absolutely no problems with it at all. Bob Miller 00:53:30 Sure. Well, think about it, if you get COVID, and ACE2 is weak, and some of this other stuff is going on. This thing just starts feeding upon itself. Dr. Deb Muth 00:53:38 Keep creating more inflammation, more complications, nothing’s calming down. Bob Miller 00:53:43 Yeah. Now, you, you ask about, MTHFR. So, this is the, this is the, the software called Functional Genomic Analysis. There’s a demo report we have. So, let’s talk a little bit about, MTHFR. So, we actually have a map called a methylation map. Now, what happens is, when you do your saliva test, you, you know, you spit, you put some saliva. in a collection kit, goes to a lab, takes out the DNA data, sends it to the computer, and now you can actually see it visually. Okay. So, it’s gonna take a second for this, data to load up, it’s, and each of these Circles, each of these ovals, is an enzyme. And the data gets loaded up to see where it is. So, until it gets loaded up here, I didn’t preload this. There it goes. So… The primary thing about methylation is There’s a nasty substance called homocysteine that, if it’s too high, can really be detrimental. The body takes methylfolate, and combines with methyl B12, To bring this back up to methionine. And then through the MAT genes, we make SAMI, S-adml methionine. Which is involved in so many processes. Then after it does its thing, it turns back into homocysteine. And this thing needs to keep spinning around. That’s why, you know, it’s a good idea to keep homocysteine at, do you have a number that you’d like? 7, 8? What do you like for a number? Dr. Deb Muth 00:55:24 Yeah, I like mine below 7. Bob Miller 00:55:26 Yeah. So if the homocysteine goes too high. It, caused all kinds of problems. So, here’s where you ask about the MTHFR. So, here you can see on this individual. I click on MTHFR, and you can see it comes up here, here’s the C677. And you can see here where it says, variants. I’ll… I’ll draw in case somebody’s having a hard time seeing that. So, you can see there’s nothing in there. That means there’s no genetic mutations. If one parent would have given a mutation, there’d be a 1. If both parents did, there’d be a 2. Now, here’s why Yes, methylation is important, I’m not saying it isn’t important, but look at this MTHFRC677. In my software. Only 42.5% of the population does not have a mutation. 44.7% have won. 12.9 have 2. So, this isn’t some rare, oh my god, I’m gonna die… Kind of thing, yeah. Dr. Deb Muth 00:56:27 Right. Bob Miller 00:56:28 So, And then what happens is that, and again, I’m not dismissing methylation, I… we could do a whole show on methylation. Bob Miller 00:56:36 get it. But I think that what people are doing is they’re, they’re learning about MTHFR, they get it measured, they panic. They start taking massive amounts of methylfolate, which many times is to their detriment. Dr. Deb Muth 00:56:50 Well, it’s… and isn’t it true, too, with MTHFR, like, you have to also look at MTR, MTRR, and the more we stack up of those, the more complicated than MTHFR can be. It’s not… it’s not as simple as just saying MTHFR 677 versus 1298. It’s more complex than that, kind of like what you’ve already shown with some of the other things. There’s more to it than just that one little sliver. Bob Miller 00:57:17 Oh, sure, well, let’s take a look. So, remember I said there’s a cofactor? One of the cofactors is called FAD. Just a Bob Miller observation, that’s all. But when people have trouble with their riboflavin and they don’t have enough FAD, They’re doing much worse than people who have just a C677. So, right here, you could have perfect C677th. And if you don’t have the cofactor, it’s not gonna work, okay? Dr. Deb Muth 00:57:48 And as you said, there’s an MTR enzyme. Bob Miller 00:57:51 that takes methylfolate and methyl B12, to spin it around. So, here on this individual. here’s your… here’s your B vitamins, or I’m sorry, your B12s. There’s an enzyme called TCN1 that takes it from the stomach into the blood. Then there’s other enzymes that take it from the blood into the tissue. And if you’re having trouble here. Well, then you’re not going to have this working, so… Even if you don’t have MTHFR, And you have MTR, like this, no, I’m sorry, this person doesn’t. But they have the MTRR, and then they don’t have enough B12, this isn’t gonna work, aside from that. And then there’s a middle pathway. And then there’s enzymes called the MAT1. they take the methionine to the salmon. If that’s not working, we stick… we get stuck in methionine. So, it’s, it’s not just an MTHFR. And then, one of the things that people forget about. is through these CBS enzymes and CTH, We make cysteine, which is needed to make glutathione. The master antioxidant. So, it really is that… I call it the, The 3D chess game played underwater. Dr. Deb Muth 00:59:07 It really is. I mean, I see people who have CVS, COMT, glutathione, MGHFR genes. And some of them function just fine. Like, they have Like, I look at this person and I’m like, oh my gosh, I don’t know how they’re functioning because they’re double mutated on so many pathways, but yet they don’t have a lot of symptoms, they don’t have a lot of complications. Somehow their body has figured out a way to adapt to what it has so it can stay alive and it can function at a high functioning level. Bob Miller 00:59:36 Yeah, and they may be, you know, eating right? Yeah. Staying out of a moldy house. reducing stress. So, it’s diet, it’s stress, it’s genetics, environmental factors. So, yeah, we can’t just say somebody’s gonna be good or somebody’s gonna be bad. You know, some people get scared, oh, I got all these, it’s like, well… Bob Miller 00:59:56 Are you living in a moldy house? You know, and if you live in a moldy house and your glucuronidation pathway doesn’t do well, or if you’re, you know, a smoker, or you’re constantly eating junk food, I mean, all. Bob Miller 01:00:07 things come together. Although, you know, when we focus on genetics, we’re well aware that this is just a piece of it. You know, you could have identical twins, Genetically, and if one… Is exposed to mold and smokes and drinks and stressed out. They’re gonna be a whole lot sicker than their sibling. Bob Miller 01:00:28 Yep. Dr. Deb Muth 01:00:29 Yeah, it’s that concept of taking twins, and one gets raced with one family, and one gets raced with another family, and they don’t have the same… problems that… that each other have, you know? It’s a very unique situation, we don’t think about that enough. Bob Miller 01:00:44 Alright, so again, genetics loads the gun, environment pulls the trigger. So, if you’ve got a loaded gun, but you don’t have the triggers, you’re okay. Dr. Deb Muth 01:00:53 Yeah. Bob Miller 01:00:54 Yeah. So, remember I said I was going to talk about NAD? So, here’s NAD, and what it does, it turns into NADH. And what NADH does, it, Comes down this pathway, what’s called the electron transport chain. And that makes your ATP, that’s your energy. So, if this wasn’t working, we wouldn’t be alive, because we wouldn’t have energy. So it donates an electron, that’s why it’s called electron transport chain. So, we need NAD, To make this, to make the energy. But remember I said that NQ01, this would probably be, like, on my top 10 list of… Bob Miller 01:01:36 Much more important than MTHFR. This one takes NADH back to NAD. If we’re stuck over here, We’re low in this NAD+, But what happens is, NQO1 also provides CoQ10. And CoQ10 Is what’s needed for the electron transport chain to flow. So if we get too many electrons up here. And they don’t turn them into energy. They make a nasty free radical called superoxide. Okay. Now, NAD plus also makes NADPH, And that is needed. Remember I said we need to recycle our antioxidants. So, if we have a problem with FAD from riboflavin. Yeah, we don’t have enough NADPH, Glutathione’s not getting recycled, and you’re gonna be inflamed. And you take glutathione, you’ll feel worse. There’s another enzyme called thimoredoxin. Same thing, needs NADPH and FAD. And same way with your nitric oxide, there’s an enzyme called NOS3, That makes the nitric oxide that dilates your blood vessels. And if we don’t have enough NADPH or fat, You’re gonna make superoxide. Rather than nitric oxide. Now, remember

In this conversation, Dr. Marc Smith shares his journey from hedge fund trading in New York's financial district to building an integrated ketamine psychiatry practice in California. After three years in finance doing trading and sales, Dr. Smith made the bold decision to completely pivot his career toward medicine, driven by a desire for purpose and meaning that his financial career couldn't provide.Dr. Smith's path took him through Columbia University for medical school, followed by psychiatry residency at USC, where he discovered his passion for interventional treatments like TMS and ketamine therapy. His unique perspective, having worked in both profit-maximizing finance and purpose-driven healthcare, provides valuable insights into the challenges of maintaining ethical medical practice in an increasingly commercialized healthcare environment.Dr. Smith's practice, Clear Ketamine + Psychiatry, represents an integrated model where he personally handles psychiatric evaluation, preparation therapy, ketamine treatment administration, and post-treatment integration sessions.What You'll Learn in This Episode· Career transition insights - How Dr. Smith navigated the complete pivot from finance to medicine, including the challenges and rewards of choosing purpose over profit in healthcare· Mental health crisis analysis - Dr. Smith's perspective on factors contributing to rising depression, anxiety, and suicide rates, including social isolation, technology impacts, and healthcare access barriers· Treatment-resistant depression understanding - Why 30% of patients don't respond to traditional antidepressants and how ketamine offers a different mechanism through NMDA receptor antagonism and neuroplasticity induction· Integrated practice model - Dr. Smith's unique approach combining psychiatric evaluation, preparation therapy, ketamine administration, and integration sessions all under one provider rather than outsourcing components· Intentions versus goals framework - How to help patients set internal emotional states they're striving for (intentions) alongside specific, measurable functional outcomes (SMART goals) for comprehensive treatment planning· Ketamine as catalyst concept - Understanding how ketamine works like "jumpstarting a car" to improve mood and motivation, while ongoing therapy and lifestyle changes provide the maintenance needed for sustained improvement· Ethical practice building - Dr. Smith's mission to combat ketamine stigma through evidence-based protocols while addressing concerns about recreational associations and inappropriate use in the field· Private practice autonomy benefits - How owning your own practice allows values-driven decisions that may conflict with profit maximization, contrasting with private equity-driven healthcare models· Business building practical advice - The importance of talking to other practice owners, understanding it's a marathon not a sprint, and knowing your limitations to outsource effectively· Biopsychosocial treatment approach - Addressing biological, psychological, and social elements of mental health through medications, therapy, exercise, sleep, nutrition, social connection, and nature exposureEpisode 58 show notes:00:00:00 - Teaser: Profit vs. Purpose in Healthcare 00:00:35 - Episode Introduction00:02:03 - Dr. Smith's Background: From East Coast to Medicine 00:02:30 - Career Transition: Three Years in Financial Industry 00:04:12 - Discovering Psychiatry Through Clinical Rotations 00:05:32 - Why Psychiatry: Deep Relationships and Human Connection00:08:50 - Tools in the Toolbox: TMS, Ketamine, and Treatment Options 00:09:30 - The Leap: Stepping Away from Finance Success 00:11:17 - The Marble Metaphor: Chiseling Away What We Aren't 00:12:46 - Self-Actualization and Gratitude in Medicine 00:14:01 - USC Residency and Academic Reception of Ketamine 00:16:54 - Evidence-Based Medicine and the Slow Pace of Change 00:19:17 - Mental Health Crisis: Social Isolation and Technology 00:22:50 - The Invisible Nature of Mental Health Challenges 00:25:28 - Private Equity vs. Patient Care: The Business Tension 00:30:18 - Private Practice Autonomy and Values-Based Decisions 00:32:15 - Clear Ketamine + Psychiatry: The Integrated Model 00:36:11 - Treatment Protocol: Six Sessions with Therapy Integration 00:37:56 - Ketamine as Jumpstart: The Car Analogy 00:42:00 - Intentions vs. Goals: Internal States and SMART Outcomes 00:46:30 - Ethical Standards and Combating Ketamine Stigma 00:50:15 - Practice Building Advice: Talk to Other Providers 00:52:55 - Rapid Fire Questions: Book Recommendation 00:54:52 - Last Meal 00:55:52 - Pickleball Obsession and the Philosophy of the Game 00:56:50 - Time Travel00:58:46 - Alternative Career01:00:04 - Advice to 20-Year-Old Self01:01:53 - Contact Information and Practice Details 01:03:03 - Final Thoughts: Gratitude and Evidence-Based Care 01:04:20 - Ending and ResourcesThanks for listeningConnect with Dr. Marc Smith at:Website: https://www.clearketapsych.comInstagram: @clearketapsych, @marcsmithmdLinkedIn: www.linkedin.com/in/marcsmithmdGoogle Maps: https://maps.app.goo.gl/GCHVy8q183c7WvfLA

This is a recap of the top 10 posts on Hacker News on June 03, 2026. This podcast was generated by wondercraft.ai (00:30): Gemma 4 12B: A unified, encoder-free multimodal modelOriginal post: https://news.ycombinator.com/item?id=48385906&utm_source=wondercraft_ai(01:55): Meta workers can opt out of being tracked at work up to 30 minOriginal post: https://news.ycombinator.com/item?id=48383220&utm_source=wondercraft_ai(03:21): Pwnd Blaster: Hacking your PC using your speaker without ever touching itOriginal post: https://news.ycombinator.com/item?id=48382310&utm_source=wondercraft_ai(04:46): Elixir v1.20: Now a gradually typed languageOriginal post: https://news.ycombinator.com/item?id=48388324&utm_source=wondercraft_ai(06:12): I was recently diagnosed with anti-NMDA receptor encephalitisOriginal post: https://news.ycombinator.com/item?id=48384355&utm_source=wondercraft_ai(07:38): DaVinci Resolve 21Original post: https://news.ycombinator.com/item?id=48384482&utm_source=wondercraft_ai(09:03): Uber's $1,500/month AI limit is a useful signal for AI tool pricingOriginal post: https://news.ycombinator.com/item?id=48383056&utm_source=wondercraft_ai(10:29): 32GB of DDR5 now costs $375 – AI shortage continues to squeeze PC buildingOriginal post: https://news.ycombinator.com/item?id=48383241&utm_source=wondercraft_ai(11:54): U.S. to dismantle system tracking Atlantic currents that are at risk of collapseOriginal post: https://news.ycombinator.com/item?id=48392232&utm_source=wondercraft_ai(13:20): MacBook Neo is so popular that Apple doubled productionOriginal post: https://news.ycombinator.com/item?id=48386238&utm_source=wondercraft_aiThis is a third-party project, independent from HN and YC. Text and audio generated using AI, by wondercraft.ai. Create your own studio quality podcast with text as the only input in seconds at app.wondercraft.ai. Issues or feedback? We'd love to hear from you: team@wondercraft.ai

In this episode of Mind the Meds, Erica Marini, PharmD, highlights information from the European Stroke Organization Conference include encouraging data on asundexian(Bayer), a factor XIa inhibitor showing reduced recurrent ischemic stroke risk without increased bleeding, as well as positive results from three trials of tirofiban in acute ischemic stroke settings. On the multiple sclerosis (MS) front, Marini covers the FDA approval of ocrelizumab (Ocrevus; Genentech) for pediatric relapsing-remitting MS in children 10 and older, a new study supporting early use of high-efficacy agents in pediatric MS, and 2 Lancet publications on ocrelizumab — one examining higher weight-adjusted dosing (which did not improve disability progression) and one confirming benefit in a broader primary progressive MS population. She also briefly discusses PADOVA (NCT04777331), a phase 2b trial of prasinezumab in early Parkinson's disease, which failed to meet its primary end point.The bulk of the episode is a discussion with guest Millad Sobhanian, PharmD, BCPS, clinical pharmacy specialist in neurology at the University of Maryland, focused on Alzheimer disease. They cover dextromethorphan/bupropion (Auvelity; Axsome Therapeutics), newly approved in April 2026 for agitation associated with Alzheimer dementia. Sobhanian walks through key safety considerations—including additive NMDA antagonism if combined with memantine, cardiovascular risks from the bupropion component, and the ever-present black box warning on antipsychotics in dementia patients—while both note that the efficacy data, though statistically significant, shows modest clinical effect sizes compared to the threshold for meaningful within-patient change.The conversation then turns to lecanemab's subcutaneous initiation formulation (Leqembi Iqlik; Eisai, Biogen), whose FDA decision has been delayed to about August 2026 as regulators seek more data on bioavailability and ARIA monitoring in the at-home setting. Sobhanian shares his real-world perspective on anti-amyloid therapy, describing a patient population that is typically early-stage, high-functioning, and has a mean age of about 60 to 70 years, and emphasizing the pharmacist's role in expectation-setting around the modest but potentially cumulative slowing of cognitive decline. The episode closes with a thorough discussion of the April 2026 Cochrane review on amyloid-targeting monoclonal antibodies, which both Marini and Sobhanian find overly broad in its conclusions. They note limitations such as the inclusion of withdrawn agents like aducanumab (Aduhelm; Biogen), heterogeneous inclusion criteria across trials, and an 18-month study horizon that may be too short to capture the full benefit suggested by longer-term open-label extension data.Key Takeaways:1. New options for Alzheimer's agitation exist, but fit carefully into the treatment algorithm. Dextromethorphan/bupropion offers a novel NMDA-based mechanism for treating agitation in Alzheimer dementia, but its clinical effect size is modest, and it carries meaningful safety considerations—particularly around the bupropion component in elderly patients. Like all pharmacologic options in this space, it remains a later-line choice after nonpharmacologic interventions have been exhausted, and medication reconciliation is critical given its interaction potential with memantine and CYP2D6 inhibitors.2. Anti-amyloid therapies are imperfect but not ready to be written off. The April 2026 Cochrane review drew significant attention with its conclusion that anti-amyloid monoclonal antibodies produce only trivial cognitive benefits, but its findings are limited by the inclusion of older, withdrawn agents, heterogeneous trial populations, and an 18-month time horizon that may be too short to capture the full trajectory of benefit.3. The pharmacist's role in anti-amyloid therapy goes well beyond dispensing. As illustrated by Sobhanian's practice at the University of Maryland, clinical pharmacists embedded in neurology clinics play a critical role in patient selection, expectation-setting, ARIA counseling, and informed decision-making for patients considering anti-amyloid therapy—a complex, high-stakes treatment decision that these patients and their caregivers should never be navigating alone.

Send us Fan MailPregnenolone, a neurosteroid derived from cholesterol, affects brain activity and shows promise for treating mood and substance abuse disorders.TOPICS DISCUSSED:Steroid Biosynthesis: Cholesterol converted to pregnenolone, the precursor for all steroid hormones including cortisol, aldosterone, and sex hormones.Corticosteroids: Synthetic versions like prednisone primarily target glucocorticoid receptors for anti-inflammatory uses but can impact mood and cognition.Pregnenolone Mechanisms: Positive allosteric modulator of NMDA receptors for cognition and negative allosteric modulator of CB1 cannabinoid receptors.Allopregnanolone: GABAergic derivative of pregnenolone; its IV form Brexanolone is FDA-approved for postpartum depression.Clinical Trials: Pregnenolone at 100-500 mg improved depressive symptoms in placebo-controlled studies of bipolar disorder patients.Cannabis Interaction: THC robustly induces brain pregnenolone production; supplementation may reduce cannabis and alcohol use.Corticosteroid Brain Impact: Prednisone use associated with smaller hippocampal volumes and memory deficits.ABOUT THE GUEST: Sherwood Brown, MD, PhD is Vice Chair for Clinical Research in the Department of Psychiatry at the University of Texas Southwestern Medical Center in Dallas. With a background in chemistry, his research focuses on steroids and comorbidities in people with mood disorders.RELATED EPISODE:M&M 124: Hormonal Contraception, Sex Hormones, Menstruation, Pregnancy, Puberty, Estrogens, Androgens, Effects of Birth Control on Cognition | Adriene BeltzSupport the showHealth Products by M&M Partners:AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models.OmegaQuant: At-home blood testing to see fatty acid profiles, including omega-3 fatty acids. Use link to see options and support M&M.SiPhox Health: Comprehensive, cost-effective bloodwork from the comfort of home. Use code TRIKOMES for 20% off.KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime)Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they're hiding, with this easy-to-use mobile app.SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.For all the ways you can support my efforts

Advances in immunotherapies for multiple sclerosis and related disorders have increased the risk of infections and raised important questions about vaccination efficacy. This episode reviews infection risks across treatment classes, emphasizes the importance of monitoring and patient education, and discusses optimal vaccine timing to preserve protective immune responses. In this episode, Aaron L. Berkowitz, MD, PhD, FAAN, speaks with Avindra Nath, MBBS, FAAN, coauthor of the article "Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders" in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue. Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology in the Department of Neurology at the University of California, San Francisco, in San Francisco, California. Dr. Nath is the chief of the Section of Infections of the Nervous System at the National Institute of Neurological Disorders and Stroke, National Institutes of Health, in Bethesda, Maryland Additional Resources Read the article: Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Full episode transcript available here Dr Berkowitz: Over the last decades, there has been a revolution in the treatment of multiple sclerosis, neuromyelitis optica spectrum disorder, and other immune-mediated neurologic conditions with countless new, highly effective medications. However, with every new treatment comes new risks; and in the case of immunomodulatory therapy, many of those risks relate to infection. Today, I have the privilege of talking with an expert on this topic, Dr Avindra Nath, about the infectious risks of treatments for multiple sclerosis and other immune-mediated neurologic disorders.  Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.  Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Avi Nath about his article on vaccine considerations and infection risk in multiple sclerosis and related disorders, which he coauthored with Dr Amit Bar-Or. This article appears in the April 2026 Continuum issue on multiple sclerosis. Welcome to the podcast, Dr Nath, and could you please introduce yourself to our audience?  Dr Nath: Thanks very much for inviting me to this podcast. I'm absolutely delighted to have the opportunity to discuss our areas of interest and expertise related to infections and vaccinations for MS patients. My area has been studying the infections of the nervous system since the beginning of the AIDS pandemic, and over the years and decades, we've developed expertise related to various types of CNS infections. That includes ones that are developing in individuals who have immune compromise due to a variety of different reasons. Dr Berkowitz: Fantastic. Well, glad to have the opportunity to speak with you today. When I was in medical school---and you were my attending, actually, we were just reminiscing, which we probably think was not that long ago, but is now over twenty years ago---there were just two medications for MS, right? Beta interferon and glatiramer acetate. And now we have over a dozen, and it's amazing to think of all the progress in these last two decades, as well as for related diseases like NMO. I don't think we even had the aquaporin-four biomarker, right, when I was working with you as a med student in the early 2000s. Dr Nath: And that certainly dates me a lot.  Dr Berkowitz: Both of us.  Dr Nath: Yeah.  Dr Berkowitz: Of course, with all these new treatments, these have been amazing advances for our patients, right? But these come with new treatment-related risks to monitor for with the immunomodulatory medications for MS and related disorders. And one of those most important risks is that of infection. So, your article reviews the potential infectious complications of medications used to treat MS, NMO, etc, and also covers considerations related to thinking about vaccines in this patient population. So, as the MS treatment landscape grows, I can say as a general neurologist, keeping up with all these medications and what to screen for and what to worry about and when to vaccinate just becomes more challenging every year. And your article has so many helpful tables, some organized by medicine, some organized by- sorry, medication, some organized by infection, some by vaccines. So, this is gonna be a great resource for our providers to print out and tape up in their clinic rooms. We won't be able to get into all the depth and detail that you have in this article today, but I do want to focus on some of the key points here related to the common medications we use for MS and which infections to think about and which vaccine considerations we might need to keep in mind for these medications. But before we delve into the drugs, I just wanna ask you more broadly, you talk in the article about the challenge of patients with immune-mediated diseases who are on immunomodulatory therapy being at risk for both flares of their disease and for infections; and these infections can present somewhat atypically, right, in immunomodulated hosts, to maybe coin a term you can correct me on, because they can't mount the full inflammatory response. So how do you approach new symptoms in patients on these immunomodulatory medicines as far as distinguishing disease flare from a treatment-related infection?  Dr Nath: So, I have to say that although a lot of new treatments have come along for MS, and they've really, you know, improved the outcome tremendously and there are so many different options, it has also kept people like me relevant because they cause a lot of various types of infections, and so keeps me in business all the same. But just as you mentioned, there's so many of them, even I have difficulty keeping track of what does what. So, you do need to be able to refer back to published literature, and the tables, I hope, will be quite useful in that regard. You're absolutely right, and you can get new infections, you can get reactivation of existing infections, and you can get atypical presentations of various types of infections that you may not normally think of. So that presents multiple challenges to the treating physician. The other interesting thing about MS is, just as you mentioned, that you already have CNS lesions to begin with. Now, on top of it, you have an infection, so now how to sort out what is the existing disease and what is the infection, it can again become challenging. But one thing is for sure: all these infections are caused by an organism. So, what you really need to do is, the underlying diagnostic is to demonstrate the presence of the organism. Whether you demonstrate it depending on the infection in the spinal fluid or in the brain or, you know, some peripheral organ system, that is going to be key to making the diagnosis. So, all your clinical acumen is good, but that alone may not be sufficient. Dr Berkowitz: Very good. So, when you see a, a patient now who has a new neurologic symptom in the context of an immune-mediated disease who's on immunomodulatory therapy, what goes through your mind? Are you thinking this disease and this drug, and sort of what are the infections, and does the syndrome match? Or are you thinking, you know, you can't always rely on the imaging to distinguish between, say, a flare of an MS and PML because white matter lesions could look similar? How do you sort of approach this scenario when it comes up?  Dr Nath: So, you're right. You have to keep an open mind so that even though you know some infections are more likely to occur with certain types of medications, that doesn't mean that others cannot occur. So, I think when you first see the patient, you should not jump to conclusions, but rather have an open mind. But yes, for example, your patient is on natalizumab, the chances of PML are going to be high. It's a very interesting drug. It does not cause immune compromise in the periphery, but what it's doing is preventing these cells from getting into the brain. So, because then it's acting at the blood-brain barrier. So that means that organisms that are already present in the brain have an opportunity to get reactivated. Turns out you don't have a lot of organisms in the brain, except JC virus seems to be one of them that does somehow, in some individuals, manage to reside out there. And so that can get reactivated. It can get reactivated in the periphery and then enter the brain, too. So, where the very specific mutations have to occur in that virus in order to take residence in the brain. That would be a suspicion that you might have, and MRI can be useful in, again, helping you think about that possibility. If you have typical lesions involving the U fibers, they're demyelinating, usually you do not have much edema around them because patient is immune compromised, but certainly within the brain in these individuals. And so, then you need to demonstrate the organism. The demonstration of the organism should be in the spinal fluid and not in the blood because in the virus, it can-- is reservoir in the kidneys and in the lymph nodes, and periodically it'll shed into the blood. Detection of the organism in the blood can be a false positive, but in the spinal fluid, it shouldn't be there unless you have an infection. Or if you cause a traumatic tap, I guess, if a patient is viremic, that's a possibility, but those are extremely rare. So at least for PML, that's the way that you would diagnose it. Now, you can develop, for example, if an individual is on fingolimod, you can get a wide variety of infections. Here it's a totally different type of mechanism of action. Here the cells are trapped within the lymph nodes, so that means now your entire periphery is immune compromised, right?  So here you can get viral infections, bacterial infections, fungal infections. So here, if a patient presents with new neurological symptoms, you have to have a really open mind for all these possibilities. Now, let's say a patient was on dimethyl fumarate, and dimethyl fumarate causes neutropenia early on. So here you have to worry about an individual developing bacterial infections, so latent tuberculosis or bacterial meningitis can occur in these individuals. That's something to keep in mind. It's not that other infections cannot occur with dimethyl fumarate, you can see PML and other things too, but the chances of bacterial infections are greater. So, you got to make sure that you draw all the cultures for that purpose. Similarly, if you're on a complement inhibitor, like a C5 inhibitor or the thing that I could use in NMO, there are the chances of meningococcal meningitis. So, these patients, you need to prevaccinate them before you start these kinds of treatments and look for that possibility. When you suspect bacterial infections, particularly acute bacterial meningitis, there time is of essence. Also, in some of the acute viral infections, for example---herpes encephalitis is another one---you have to be so careful, and if you suspect any of them, even if they're with possibly atypical manifestations, you treat first and then diagnose later, and draw all your cultures, whatever you need to, and just treat them. And these infections can also cause cerebral edema, so one has to be careful about doing spinal taps in these individuals. You want some kind of neuroimaging before you do them. In the days when we didn't have neuroimaging, we used to say, "Okay, if your patient has focal neurological signs or is comatose, you don't do it." But these days, you can get imaging very quickly and very easily. All the-- Because of our stroke management, we've learned how to do them so quickly. So, I think there's little excuse not to do imaging and prevent herniation from occurring.  Dr Berkowitz: That's very helpful. So, using the information we know about the drug, and we're going to rapid-fire review some of that in a bit to know what infections the patient is susceptible to, but acknowledging that any patient can get any infection, right? Whether they're on particular medications or not. And then if you're not sure, based on the neuroimaging, which as you said, is helpful, but not always helpful in distinguishing between infections and flares or, as you said, in the case of meningitis, encephalitis, early on at least, especially in immunocompromised or immunomodulated, quote unquote, patient might not see the typical imaging. So really, when safe, getting CSF or cultures, PCRs, and other infectious studies too is really gonna be the definitive diagnostic maneuver here. Is that fair summary across the board?  Dr Nath: I think you said that absolutely right. And you summarized that correctly. And, you know, thing about infection, a lot of neurological diseases are, you know, diagnosed by clinical acumen, like your Parkinson's and Alzheimer's and others. Think about infections is caused by an organism, demonstrate the organism, right? That should be your goal. It doesn't mean that clinical acumen is not important, but here you have an opportunity to demonstrate the organism, so you should depend upon that.  Dr Berkowitz: Okay. Well, you gave us a nice segue by talking about some of the infections to worry about with some of the medications. So what I'd like to do now for the sort of second half of our interview here is to go through some of the more common medications used for MS, and if we have time, for NMO, and just sort of go kind of rapid fire here, and for each medication, if you can tell us the kind of top infectious concerns and whether when to consider them or what screening needs to take place before or during administration of the medication, and then any vaccine considerations we should be aware of. Some of these will obviously be quite short depending on the medicine. So, going back to the two medications I alluded to earlier that were the only ones in play when you and I last saw each other on the wards when I was a medical student, beta interferon, glatiramer acetate, any infections or vaccine considerations with these medications?  Dr Nath: No, I think they're probably your safest medications now as far as immunomodulatory therapies are concerned. These two, and IVIG, if you ever use them, are probably the safest, do not require any vaccine considerations, per se. Dr Berkowitz: Perfect. Okay. So, moving on to fingolimod and others in the sphingosine-one phosphate receptor modulator family, what are the infectious considerations? Any prescreening or vaccination considerations?  Dr Nath: I think all your patients should be prescreened for antibodies to JC virus, because there is a risk for PML, and those who are positive should be closely monitored. So, it's not an absolute contraindication for using these medications, but they just require closer monitoring. With this class of drugs, PML is of consideration. Also, these varicella-zoster virus infection, yeah, with that you can develop zoster encephalitis or myelitis. It can present with motor symptoms as well, which can be atypical. You don't usually see them otherwise in immune-competent individuals. So, varicella-zoster, sometimes you can develop encephalitis, also vasculitis with varicella-zoster, so one has to be careful. So, getting the shingles vaccine can be actually very helpful to prevent these things. And then some patients can even develop herpes simplex encephalitis also, and that can be extremely atypical. So, they don't- they can involve the basal ganglia, can involve the brain stem and cerebellum. So again, your index of suspicion should be very high. Interestingly, although HSV encephalitis has been associated with NMDA receptor encephalitis, those reports of NMDA receptor encephalitis have not been published yet with NMS patients. Not sure why, maybe they just have been missed. But that doesn't seem to be a major concern. And then there are a whole host of other infections that can occur with this class of drugs, and that can include toxo; fungal infections, particularly crypto. There's a case report of histoplasmosis; hepatitis virus, particularly hepatitis C; and then the poxvirus is a good example. You can get molluscum contagiosum; warts with papillomavirus; you can get atypical mycobacteria; and even Kaposi sarcoma, which is HHV8. So, there's a huge variety of infections with the sphingosine one phosphate receptor modulators.  Dr Berkowitz: And any- aside from screening for JC virus before initiating these, any- and then continuing to monitor for JC antibody index, any other considerations as far as labs to send, monitoring before or on the drug or vaccine considerations for patients on fingolimod and the others in this category, siponimod, etcetera?  Dr Nath: Yeah, there are a lot of things to consider. All the details are really available in the chapter if you look at them. But briefly, all the things that one could potentially vaccinate patients for, all these infections I mentioned, one should do so. The timing is critical so that if you can do it before treatment, I think, before starting treatment, that is absolutely important. And you got to give them at least, you know, two to three weeks for these vaccines to take effect before starting your medication. If your patient already arrives on a medication, then you got to play this game of you know, before the next dose, give them again two to three weeks before the next dose and start vaccinating them and get all the vaccines in. Broadly, about the things to worry about the vaccines are you have live vaccines, and you've got the inactivated vaccines or the subunit vaccines. You have to be careful with live vaccines, because if your patient is immunocompromised, that virus can sometimes itself cause harm. For example, you know, yellow fever is one, and there you can develop encephalitis from it. Measles, mumps, rubella, these are all live vaccines. Now, the good thing is that a lot of us have been immunized very early in childhood, but that may not be the case any longer. And so, these things, one has to be very careful with when you're giving live vaccines, that we want to avoid them as much as possible, and individuals are gonna be immune-compromised. But all the others, meningococcus, for example, you should- the HPV vaccines, the varicella zoster vaccines, all these things, you've got to pre-vaccinate and make sure that they have an antibody response to them before starting immunocompromising therapy. Dr Berkowitz: Perfect. Okay, moving on to some of the other orals. What infectious and/or vaccine considerations do we have with teriflunomide?  Dr Nath: Okay, yeah. Teriflunomide is a very interesting drug. It's relatively safe. There is concern about the possibility of varicella zoster infection, people have reported that, and also tuberculosis. But PML is extremely rare, if not at all, and we haven't seen herpes encephalitis quite yet.  Dr Berkowitz: Got it. How about dimethyl fumarate? Dr Nath: Yeah. So dimethyl fumarate is... as I mentioned earlier, it's interesting because it causes this neutropenia. It's transient, but it occurs early on, and these patients can be at risk of PML, although small. They can develop varicella zoster virus infection, herpes encephalitis, and also fungal infections. For example, cryptococcal infection has been reported with dimethyl fumarate. Dr Berkowitz: Okay. We've spoken a bit about natalizumab and PML, and you have extensive information on this in your article, and I'll defer the reader to that. But for natalizumab, what are the key points every neurologist should know about natalizumab and PML as far as from the practical perspective, screening, frequency of screening, when to worry, when to not use natalizumab at all in the first place based on what you find in your screening for JC virus? What are the key points every neurologist should know?  Dr Nath: Uh, yes. You bring up an important point, and that is all patients should be monitored for JC virus. If they're JC virus-negative, so that's your most ideal patient to go on natalizumab, but that doesn't mean they cannot get infected with the virus. In fact, there's an interesting study claiming that, you know, patients, when they get these infusions, they're all sitting in the same room getting infused. Some have JC virus, some don't have JC virus, and so there's the potential that we may be aiding the transmission here in some way or another. The virus is an interesting one. It comes out in urine, and then it's spread through oral contamination, gets into the tonsils, and then spreads from there to your marrow and resides in the kidney and the marrow, as well as the lymph nodes, forever. So, you, you have to monitor these patients to see that during the course, even if they're negative, they could turn out positive. So, every six months or a year, an antibody test should be done on all patients irrespective. If a patient already has antibodies, that's not an absolute contraindication. It just means you've got to monitor them closely for development of new symptoms, and if, whenever there are new symptoms, don't just assume this is due to MS, but just make sure the MRI is done with and without contrast. The- and if there's still a suspicion, that you do a CSF evaluation for JC virus. Just detecting, looking for JC virus in the blood, a rising titer is another thing that can help you. And so, the titer is also important. And the reason you have rising titers is it means that there's an infection that's already occurred in the brain, and the immune system is reacting to that infection by increasing titers. But that alone is not sufficient to make the diagnosis. You still- that gives you an index of suspicion. You've got to then do the MRI and the spinal tap to, you know, be absolutely certain. So, each patient is a little bit different, so the way you monitor them is going to depend on where they are. You know, if they've had prior immunomodulatory therapy before starting natalizumab, or if they're on natalizumab for more than two years, then the chances of PML are much greater, so you may want to monitor them more closely. Uh, they never had any prior immunomodulatory therapy, you're just starting natalizumab, maybe once a year is sufficient. So, I think you've got to tailor it depending on what your risks are for each patient. Dr Berkowitz: Perfect. That's very helpful. And again, you write extensively about PML and natalizumab and PML considerations in your article. So, for a more detailed and in-depth discussion of what we just discussed, definitely hope readers will take a look at your article. Okay. Last but not least---certainly not least, 'cause we're using these probably, it seems, the most commonly in many places I've worked---rituximab, ocrelizumab are B-cell therapies for MS. What are some of the infectious and vaccine considerations related to these infusion medications?  Dr Nath: So, there's concern for PML with anti-B-cell therapies also, maybe not to the same degree as natalizumab, but the same principles should be applied. A lot of people think that these are relatively safe. I don't think so. I think we see enough number of patients on B-cell therapies with PML. So, I would use the same caution because these infections are... you know, can be fatal. So, one should be very careful, even with anti-B-cell therapies. And just with natalizumab, you also have the risk of VZV infection causing shingles. HSV1 has been reported, but there's another interesting complication that has been reported with anti-B-cell therapies, and that is severe West Nile encephalitis. And as mosquitoes-borne diseases are getting more and more prevalent, and we're seeing West Nile cases erupting every summer, I think one's got to be, you know, very cognizant of the fact that this can occur. These patients should take precautions to prevent mosquito bites from occurring and not expose themselves to areas where they could be at risk for it. Unfortunately, there is no vaccine for it and no specific treatment for West Nile. So, all one can do is use prevention strategies for mosquito bites.  Dr Berkowitz: Yeah, I'm glad you mentioned that. I think the only really truly severe neuroinvasive cases I've seen of West Nile virus have indeed been in patients who were being treated with B-cell therapy. Not, if I'm remembering correctly, for immune-mediated disease, but for a lymphoma, so probably other confounding factors there. But yeah, it's a disease we learn about and think about, but I've only seen the most severe cases in patients who had abnormal immune systems, so I'm glad you flagged that. This has been a very helpful discussion, and I've learned a lot from you. I learned a lot from your article, just as I did when you were my attending some 20-something years ago on the wards when I was a medical student. So, it's good to continue learning from you through your writing and research, and today from getting to talk to you again. I encourage our readers to read your article and to bookmark those tables for when these considerations come up for your patients on these immunomodulatory therapies and you're wondering which infections to worry about and how to manage vaccines in this patient population. So again, today I've been interviewing Dr. Avi Nath about his article on vaccine considerations and infection risk in multiple sclerosis and related disorders, which he wrote with Dr. Amit Bar-Or. This article appears in the April 2026 Continuum issue on multiple sclerosis. Be sure to check out Continuum Audio episodes from this and other issues, and thank you again to our listeners for joining today.  Dr Nath: Thank you so much, Aaron, for that wonderful interview, and I'm extremely proud of all your accomplishments over the last 20 years. You've done an amazing job, and it was such a pleasure to see you and to be able to do this interview with you. Thank you again.  Dr Berkowitz: Thanks. That means a lot. I never would have imagined- we won't say 20, how many, but 20-something years ago as the medical student looking up to you and all your expertise on these infections and all of your research that led to so much of our understanding on these, that I would find myself interviewing you two decades later. So, for all the students listening, you never know where you'll end up, but I appreciate your very kind words.  Dr Nath: That's what we hope for all our students. Thank you so much.  Dr Berkowitz: Thanks again.  Dr Monteith: This is Dr. Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

In this must-listen episode, Dennis sits down with Dr. Jon Andrews—former 5th and 20th Group Special Forces medic turned Duke-trained anesthesiologist (pediatric & cardiac fellowships)—to tackle one of the biggest headaches in austere medicine: you have a tiny box of opioids and ketamine, a long mission, and a patient who needs to stay alive AND comfortable.They break down exactly how to stretch every milligram using real OR strategies adapted for prolonged field care: patient-specific planning, smart titration, multimodal synergy, regional blocks, ketamine myths, and when (and how) to layer non-narcotics without crashing your patient or your supply.Why this episode matters: Acute pain becomes chronic pain. Chronic pain leads to opioid dependence, PTSD, and worse outcomes. In the field, your choices today shape your patient's tomorrow—and whether you still have meds left when the next casualty shows up.Key TakeawaysStart low, titrate smart. Cut your first dose in half on sick or unstable patients. You can always give more—never the other way around.Multimodal is mission-critical. Hit pain from every angle (blocks + ketamine + acetaminophen + judicious NSAIDs) to dramatically reduce opioid requirements and prevent chronic pain pathways.Ketamine IS an analgesic. It's not just dissociation—it's an NMDA antagonist that blunts central sensitization and has proven opioid-sparing effects.Schedule your non-opioids. Acetaminophen (1 g IV/PO/PR q6h) and longer-acting adjuncts form your baseline; use fentanyl or morphine only for breakthrough.Blocks beat everything—if you can do them. Pre-emptive regional anesthesia (when feasible) is the single highest-yield move before surgical stimulus hits.Monitor like your life depends on it. Heart rate, blood pressure, and respiratory rate are your best pain score when the patient can't talk.Plan for worst-case evacuation. Bring more than you think you'll need and dose for the opioid-naïve or opioid-tolerant reality in front of you.Why treating hypertension in the OR (or field) almost always starts with fixing pain firstThe “start low, see response, add more” mantra every austere provider needsWhy Tylenol often performs as well as morphine in blinded ED studies (and why your patients still doubt it)Real talk on ultrasound-guided blocks in 2011 vs. today—and why proficiency still mattersThe dangerous synergy of opioids + benzos + ketamine on respiratory driveWhy you must get comfortable decreasing doses, not just ramping them upChapters01:55 – The austere reality: limited narcotics and why your favorite med won't last forever03:37 – OR planning vs. field reality: opioid-naïve vs. chronic users05:57 – Multimodal analgesia explained (blocks, ketamine, Tylenol, NSAIDs, dexmedetomidine)08:28 – Patient & mission factors that should drive your loadout12:23 – Golden rule: start low, titrate to effect, monitor vitals15:05 – Sick-patient hack: cut your mental dose in half16:01 – Is ketamine actually an analgesic? (NMDA, opioid-sparing, PTSD data)19:12 – Extending your supply: bolus vs. infusion, redosing strategy24:27 – First-line multimodal choices in the field27:43 – Juggling multiple agents: timing, scheduling, and longer-acting blocks30:15 – Regional anesthesia timing—pre-emptive is king (post-injury limitations)32:48 – Ultrasound & blocks in the current PFC world35:08 – Safety considerations for adjuncts (liver, kidneys, bleeding, alcohol)36:59 – Bang-for-buck data on Tylenol vs. morphine38:55 – Practical integration: layering Tylenol/ketamine with fentanyl titration41:54 – Getting comfortable titrating down (and why pain scores can lie)42:53 – Final wisdom: use everything you're comfortable with.For more content go to ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.prolongedfieldcare.org⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Consider supporting us: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠patreon.com/ProlongedFieldCareCollective⁠⁠⁠⁠⁠⁠ or ⁠⁠⁠⁠⁠⁠www.lobocoffeeco.com/product-page/prolonged-field-care

A “happy place” isn't always a pin on a map. Sometimes it's a flash of memory that hits while you're doing dishes, and suddenly you're back in Switzerland or on a quiet stretch of the Oregon coast. We unpack what's really happening in those moments and how to recreate the feeling without needing a plane ticket every time.Thank you to the NMDA's New Mexico— Grown with Tradition®/Taste the Tradition® Logo Program along with  Hatch Chile Store https://www.hatch-green-chile.com/ for sponsoring this episode! YUMM! We share our own travel happy places, then get practical with an “H is for habits” reset you can use on any trip: health first, move your body, hydrate, bring herbs and healthy fuel, build in hush and quiet, protect your sleep, add small home touches, set up your temporary habitat, find hidden gems, and make space for human connection. Then we take it home, literally, with ideas like making collages or a “happy place journal” so you can spot your patterns and translate them into real-life choices like home design, routines, and the way you set up your workspace.Guest Robin Chuby (Life of Glow, PrairieGlowAcres.com) joins us from Manitoba to talk about turning her garden into a full-on haven: tea gardens, sensory joy, simple syrup drinks, DIY confidence with power tools, and the reality of keeping a home livable while you're juggling projects. We also lean into “H is for hometown” with a New Mexico tradition that never leaves our kitchen: Hatch green chile. Pam Rowell from The Hatch Chile Store shares how the company started, what to order, and how to bring real Hatch flavor to your meals wherever you live.If this sparks your own happy place memories, subscribe, share the show, and leave a review.  Also mentioned on this episode:SwitzerlandEpsidoe 2; 192, 193: 249 Sirenian bay251: 252: 253: 254: 255: Sadies of Albuquerque : Episode 5:Victor and MJ: Episode 272: San Diego, 18: https://www.buzzsprout.com/263670/episodes/2540800Hawaii 136: https://www.buzzsprout.com/263670/episodes/8832467232: https://www.buzzsprout.com/263670/episodes/16268878Kauai: 197: https://www.buzzsprout.com/263670/episodes/11483207198: https://www.buzzsprout.com/263670/episodes/11483186Oceanside Trip  152; : https://www.buzzsprout.com/263670/episodes/9456320153: https://www.buzzsprout.com/263670/episodes/9462208155: https://www.buzzsprout.com/263670/episoPlease support our show by shopping through Eagle Creek: https://alnk.to/gVNDI6N  and/or feel free to donate to:http://paypal.me/TheROAMies And it means the world to us when you subscribe, rate and share our podcast.Alexa and RoryThe ROAMiesFollow us at:http://www.TheROAMies.com@The ROAMies: Facebook and Instagram YouTube and X.

It is increasingly understood that our brain health is dependent on our having healthy nutrient levels. But how do nutrients actually impact our neurotransmitters.We might assume that certain nutrient levels would cause certain symptoms or conditions. Instead, what we find are biotypes - one condition is often associated with a small handful of imbalances. For example, the biotypes of depression from the Walsh Research Institute, included undermethylation, overmethylation, pyrrole disorder, copper overload and metal toxicity. And reversely, one nutrient imbalance can contribute to a range of brain symptoms. Copper overload, for example, can be a factor in ADHD for one person, but for another contribute to panic or insomnia and still another rage or tantrums. There are some conditions, however, that have a very strong associations with specific nutrient imbalances. In this newsletter, I will address:* 5 Ways Nutrients Impact Neurotransmitter Functioning* Psychiatric Conditions That Can Almost Predict a Specific Nutrient ImbalanceThe data comes from the Walsh Research Institute. Nutrient Imbalances Can Be Due to Too Much or Too LittleI use the term nutrient imbalances, because it's not just about deficiencies of certain nutrients. Specific nutrient overloads can impact brain health as well. This biochemical diversity means we don't all have the same needs when it comes to diet and supplementation. Some of us, for example, can benefit from folate, but for others with excess folate, supplementation could worsen depression and anxiety. Those with copper overload can similarly have worsening of symptoms with copper supplementation, while others will have a need for copper.What Causes Nutrient ImbalancesWhile it might seem that this is all about our intake of nutrients, we can come by these imbalances genetically. We can also acquire deficiencies and even overloads through high oxidative stress. This is when our body (including our brain) is dealing with too many insults, resulting in a depletion of our inherent antioxidants leaving us vulnerable to DNA and thus cell damage, inflammation and their consequences). Copper zinc imbalances and elevated pyrroles, which results in relatively low zinc and B6, are signs of oxidative stress. Often an imbalance appears to have multiple causes. For example a woman with high copper causing high anxiety, could have a family history of high copper conditions (post partum depression, ADHD, angry outbursts) and thus have a likely genetic vulnerability. She may also, be taking a multivitamin with copper, eating a lot of chocolate (high in copper) dealing with high oxidative stress and not the least, be on an oral contraceptive (added estrogen can make copper go up).5 Ways Nutrients Can Impact Neurotransmitter FunctioningNutrients often function as co-factors, helping certain enzymes do their job. Specific nutrients are needed: * For production of neurotransmitters. Vitamin B6, for example is needed to make serotonin, dopamine and GABA. B6 can be low in pyrrole disorder and thus contribute to a range of symptoms.* To convert one neurotransmitter to another. Copper is needed to turn dopamine into norepinephrine (think adrenaline). If we are high in copper, we could have relatively low dopamine and high adrenaline states, which is what is seen in ADHD.* To support enzymes involved in the breakdown of neurotransmitters. For example MAOA is an enzyme that needs Vitamin B2 to do its job breaking down serotonin, dopamine and norepinephrine. If these aren't broken down, there could be problems with activation and anxiety.* To help receptors do their job. Receptors are what neurotransmitters bind to, resulting in a impulse being sent down the nerve cell. Zinc and magnesium help regulate the NMDA receptor. If not well regulated, there can be high activity, which can look like thoughts getting stuck - ruminations, obsessions in OCD, cravings in addiction, and even delusions in psychosis.* Regulate the expression of genes for serotonin reuptake receptors. Folate causes an increase in the expression of these genes (and thus production of these receptors). This results in more serotonin being picked up and less available between nerve cells. This could be a problem for someone who already has low serotonin symptoms. SAMe, on the other hand, does the opposite and it can function like an SSRI.Why One Diagnosis Isn't Always Associated With One Imbalance* Psychiatric conditions appear to have various causes. If someone comes to me with a diagnosis of depression, for example, that only tells me what type of symptoms they likely have. It doesn't tell me if those symptoms are related to high copper, a methylation imbalance, elevated pyrroles, candida, a misaligned upper cervical spine , mast cell activation, mold toxicity, metal toxicity, hormone imbalances or a combination of any of these…….or something else.* More often multiple factors appear to be aligning. It is not uncommon, for example, to have candida or mold causing high pyrroles causing low zinc, leading to high copper, and as an aside also be undermethylated.* One “root cause” can contribute to a range of conditions and symptoms. Some people with high copper are diagnosed with depression or anxiety and others with ADHD. Some people who are undermethylated have OCD, others depression and still other schizophrenia. Very often, people will be have multiple diagnoses fitting with an imbalance. “Comorbidities” in psychiatry are the norm, rather than the exception.Despite all of this, there are certain nutrient imbalances that occur so commonly in certain psychiatric conditions that they can almost be predicted . Data From Walsh Research InstituteSimply knowing someone has a mental health condition makes it more likely that they will have a methylation imbalance - more often undermethylation.The Walsh Research Institute has looked at the methylation status of 30,000 over 40 year and found that 70% of those with mental illness exhibit a methylation imbalance (undermethylation and overmethylation). This is relative to the general population, in which 30% had a methylation imbalance.Other Data From the Walsh Research Institute:* History of Postpartum Depression - 95% have copper overload* ADHD - 68% have a copper zinc imbalance* Autism Spectrum Disorder - 98% undermethylation, 98% low zinc* Antisocial Personality Disorder - 95% undermethylation, 95% pyrrole disorder, 95% low zinc* Oppositional Defiant Disorder - 85% undermethylation* Schizoaffective Disorder - 90% undermethylation* Anorexia - 82% undermethylation* Schizophrenia - 70% undermethylation* Violent behavior - 78% high copperEvaluation & Labs Are Still ImportantNone of these are 100%. And, again, there is rarely one contributing factor, so a comprehensive evaluation and lab testing are still important. Even if I am fairly confident that someone is low in zinc, I don't recommend starting zinc without checking zinc and copper levels. Starting zinc too rapidly can mobilize high copper and worsen symptoms. If copper is low, zinc can cause a further decrease.Also, there are occasions when it can be difficult to address an imbalance, without addressing another contributing issue first. For example, I see some patients who are unable to tolerate treatment of undermethylation until they begin treatment for candida or mold.There is always so much more data to share, when it comes to the Walsh Research Institute. I look forward to discussing biotypes of depression, ADHD and schizophrenia in a future episode.As always, I welcome your comments and questions.Until next time,CourtneyTo learn more about my discovery calls, non-patient consultations, and treatment practice, visit:CourtneySnyderMD.comMedical Disclaimer:This newsletter is for educational purposes and not intended or implied to be a substitute for professional medical advice, diagnosis, or treatment for either yourself or others, including but not limited to patients that you are treating (if you are a practitioner). Consult your physician for any medical issues that you may be having. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit courtneysnydermd.substack.com/subscribe

Focus Supplements | How Neurotransmitters Keep Us Locked InFocus is not just willpower—it is brain chemistry in action. In this full episode of In Search of Insight, Emiel and Erika break down how key neurotransmitters like dopamine, norepinephrine, acetylcholine, and serotonin work together to support focus, motivation, and that elusive flow state where everything seems to click. You will learn: - What focus actually is from a neuroscience perspective and why it feels so different from distraction or simple alertness. - How neurotransmitters influence attention, mood, drive, and mental stamina throughout your day. - Practical habits that support healthy neurotransmitter balance, including sleep, light exposure, movement, and nutrition. - How specific supplements can help you stay locked in on your goals—whether you are training, studying, working creatively, or managing a busy life. Featured supplements in this episode: Agmatine – Supports healthy NMDA receptor activity, mood, and cognitive function, making it a useful tool for dialed-in mental performance. Sabroxy – An extract of Oroxylum indicum that helps promote motivation, alertness, and a “get-things-done” mindset. Cognance – Standardized for ebelin lactone to support memory, learning, and clear, sustained concentration. Mushroom Magic Coffee – A delicious functional coffee blend with lion's mane, cordyceps, tiger milk, and poria mushrooms to support energy, cognition, and immune health alongside your daily caffeine ritual. If you have ever wondered why some days you can lock in for hours and other days you cannot string two focused minutes together, this episode will give you a clear, science-backed framework—and actionable tools—to understand and improve your focus. ⏱ Timestamps will be added after the premiere so you can easily jump to neurotransmitter deep dives, lifestyle strategies, and specific supplement discussions.

A 2022 LessWrong post on orexin and the quest for more waking hours argues that orexin agonists could safely reduce human sleep needs, pointing to short-sleeper gene mutations that increase orexin production and to cavefish that evolved heightened orexin sensitivity alongside an 80% reduction in sleep. Several commenters discussed clinical trials, embryo selection, and the evolutionary puzzle of why short-sleeper genes haven't spread. I thought the whole approach was backwards, and left a comment: Orexin is a signal about energy metabolism. Unless the signaling system itself is broken (e.g. narcolepsy type 1, caused by autoimmune destruction of orexin-producing neurons), it's better to fix the underlying reality the signals point to than to falsify the signals. My sleep got noticeably more efficient when I started supplementing glycine. Most people on modern diets don't get enough; we can make ~3g/day but can use 10g+, because in the ancestral environment we ate much more connective tissue or broth therefrom. Glycine is both important for repair processes and triggers NMDA receptors to drop core temperature, which smooths the path to sleep. While drafting that, I went back to Chris Masterjohn's page on glycine requirements. His estimate for total need [...] ---Outline:(01:49) Glycine helps us sleep by cooling the body(02:26) Glycine cleans our mitochondria as we sleep(04:12) Most people could use more glycine(05:28) Fever is plan B for fighting infection; glycine supports plan A(09:28) Glycines cooling effect via the SCN is unrelated to its immune benefits(10:35) Glycine turns out to be a legitimate antipyretic after all(11:51) Practical considerations --- First published: March 22nd, 2026 Source: https://www.lesswrong.com/posts/87XoatpFkdmCZpvQK/is-fever-a-symptom-of-glycine-deficiency --- Narrated by TYPE III AUDIO.

In this first part of what became a two-part conversation, we sat down with anesthesia provider Charles Miller from Scenic City Neurotherapy for a discussion that challenged so many assumptions about ketamine therapy.Charles presents what he calls the "collective lie" in ketamine therapy - the argument that the obsession with psychedelic experiences and mystical insights for a growing segment of providers in our industry is not just misguided, but actually making our patients worse. He walks through the neurobiological evidence showing that the real therapeutic action happens days after treatment during the neuroplasticity window, not during those profound moments when patients feel like they're talking to God or having life-changing realizations.You'll hear Charles critique the research methodologies that seem to support ketamine-assisted psychotherapy, explaining why group averages can mask poor individual outcomes and why the frequently cited KAP studies may actually show lower success rates than standard ketamine protocols. He also shares refreshingly honest advice about starting a clinic - including his decision to open with folding chairs rather than go into debt for impressive furniture.We're also trying something new with this episode: audio sidebars. As we talk, we'll pause to provide additional context about complex concepts like psychoplastogens, research study limitations, and the cutting-edge science behind separating therapeutic effects from psychedelic experiences. Think of these as educational moments designed to help you fully understand and enjoy the episode.This conversation will make you question whether the approaches many of us have been using actually serve our patients - or if we've been chasing the wrong mechanisms entirely.What You'll Learn in This Episode· Charles's entrepreneurial journey - How he started Scenic City Neurotherapy with minimal capital and his advice for keeping overhead low during startup· The "collective lie" concept - Why Charles believes the field's emphasis on ketamine experiences actually reduces treatment success rates· Neuroplasticity mechanisms - Detailed explanation of the NMDA-glutamate-BDNF pathway and why the therapeutic window occurs after, not during, ketamine administration· Psychoplastogens vs psychedelics - Understanding David E. Olson's groundbreaking research on compounds that promote neuroplasticity without hallucinogenic effects· Research methodology critique - Analysis of popular KAP studies and why methodological flaws may be masking poor individual patient outcomes· Evidence-based positioning - How to counter the "ketamine is just anesthesia" criticism with solid neurobiological science· Experience vs neuroplasticity - Why Charles argues that focusing on insights and visions during treatment may be counterproductiveKey Takeaways· Ketamine may function primarily as a psychoplastogen rather than a classic psychedelic, blocking NMDA receptors to trigger neuroplasticity cascades instead of flooding serotonin receptors like traditional psychedelics· The therapeutic neuroplasticity window occur days to weeks after ketamine administration, when BDNF-driven synaptic remodeling takes place, not necessarily during the acute dissociative experience· Research comparing ketamine-assisted psychotherapy to standard protocols could show mixed results, with some studies reporting lower individual response rates despite promising group averages· Providers who overfocus on experiential components during treatment may inadvertently create performance pressure that could reduce patient outcomes and increase perceived treatment failure rates· Startup ketamine clinics might benefit from beginning embarrassingly small with minimal overhead, focusing resources on essential clinical equipment rather than impressive lobbies or furniture· David E. Olson's psychoplastogen research suggests that neuroplastic benefits might be separable from psychedelic experiences, supporting approaches that prioritize physiological mechanisms over experiential componentsEpisode 52 show notes:00:00:00 - Teaser: When Patients Feel They Failed00:00:17 - Introduction and Episode Setup00:02:06 - Charles's Journey into Ketamine Therapy00:04:30 - The Entrepreneurial Leap00:06:00 - Startup Advice: Think Embarrassingly Small00:08:30 - Evolution of the Ketamine Field00:10:00 - The "Collective Lie" Concept Introduction00:12:30 - Neurobiological Mechanisms00:16:30 - Psychoplastogens vs. Psychedelics00:24:00 - David E. Olson's Revolutionary Research00:27:27 - Audio Sidebar: Psychoplastogens & David E. Olson00:30:00 - Research Critique: KAP Study vs Real-World IV Ketamine Data00:34:27 - Episode Wrap-upThanks for listening

Dans ce témoignage, Vanina raconte le jour où sa vie a basculé.Tout commence par des symptômes difficiles à comprendre : tristesse intense, insomnies, hallucinations… Très vite, elle est hospitalisée en psychiatrie avant qu'un diagnostic neurologique rare ne soit finalement posé : une encéphalite auto-immune à anticorps anti-récepteurs NMDA, une maladie qui attaque le cerveau et peut provoquer de graves troubles cognitifs et psychiatriques. Depuis 2021, Vanina traverse un parcours médical extrêmement lourd : hospitalisations, coma, traitements immunologiques, rechutes… mais aussi l'apparition de nouvelles pathologies neurologiques et chroniques. Dans cet épisode, elle partage sans filtre :la violence de la maladie et de l'errance médicaleles séjours à l'hôpital et le sentiment de solitudele regard des autres face au handicap invisiblela fatigue extrême qui bouleverse le quotidienle rôle essentiel des proches et des aidantset la manière dont on apprend, malgré tout, à reconstruire sa vieUn témoignage profondément humain sur la résilience, la vulnérabilité et la force de continuer à vivre autrement.

In this final episode of the Progesterone Promise series, Dr. Brendan McCarthy, Chief Medical Officer of Protea Medical Center, breaks down one of the most misunderstood hormones in women's health: progesterone. Progesterone is not “good” or “bad.” It's contextual. In today's world of quick sound bites and social media medicine, hormones are often reduced to oversimplified claims like “progesterone fixes anxiety” or “progesterone causes breast cancer.” The truth? It depends on your body, your stress levels, your liver health, your inflammation, your delivery method, and whether you're using bioidentical progesterone or synthetic progestins.   Citations: 1. Oral Progesterone → First-Pass Metabolism & Allopregnanolone Claim: Oral micronized progesterone undergoes significant hepatic first-pass metabolism, increasing neuroactive metabolites (especially allopregnanolone), which positively modulate GABA-A receptors and produce sedative/anxiolytic effects. Core Evidence: Simon et al., 1993; de Lignières et al., 1995; Freeman et al., 1990 — Oral progesterone produces measurable neuroactive metabolites. Paul & Purdy, 1992; Rupprecht et al., 2001 — Allopregnanolone enhances GABA-A receptor activity. Supports: Sedation variability by route • Neurosteroid generation • GABA-A modulation 2. Sulfation vs 5α-Reduction → Opposing Neurologic Effects Claim: Progesterone metabolites can produce calming (5α-reduced) or excitatory (sulfated) neurologic effects depending on enzyme routing. Core Evidence: Majewska et al., 1990 — Pregnenolone sulfate negatively modulates GABA-A. Wu et al., 1991 — Sulfated neurosteroids enhance NMDA signaling. Schumacher et al., 2007; Reddy, 2010 — Pathway reviews of sulfation vs 5α-reduction. Supports: Reverse responding hypothesis • Divergent neurologic experiences • Enzyme-dependent effects 3. Stress & Enzyme Modulation Claim: Chronic stress alters HPA axis tone and hepatic enzyme expression, influencing steroid metabolism balance. Core Evidence: McEwen, 1998 — Allostatic load model. Charmandari et al., 2005 — Cortisol's systemic regulatory effects. Zanger & Schwab, 2013; Gibson & Skett, 2001 — Stress alters cytochrome P450 expression. Supports: Stress-biased metabolism • Context-dependent hormone response 4. Breast Tissue Signaling & Context Claim: Progesterone influences mammary differentiation and interacts with estrogen signaling in context-dependent ways. Core Evidence: Brisken & O'Malley, 2010 — Progesterone receptor biology in breast tissue. Beleut et al., 2010 — RANKL mediates progesterone-driven proliferation. Hofseth et al., 1999 — PR-ER signaling interaction. Stanczyk & Bhavnani, 2014 — Natural vs synthetic differences in breast effects. Supports: Lobuloalveolar differentiation • RANKL pathway • Context-dependent proliferation 5. Synthetic Progestins vs Bioidentical Progesterone Claim: Synthetic progestins differ structurally and bind off-target receptors, producing distinct tissue effects. Core Evidence: Stanczyk et al., 2013 — Receptor binding differences. Sitruk-Ware, 2004 — Biologic comparisons. Chlebowski et al., 2003 (WHI) — Breast cancer signal with CEE + MPA. Supports: Structural divergence • Receptor-level differences • WHI clarification 6. Route of Delivery Differences Claim: Oral, vaginal, transdermal, and sublingual progesterone produce distinct pharmacokinetic profiles and tissue targeting. Core Evidence: Simon, 1995 — Oral vs vaginal PK comparison. Cicinelli et al., 2000 — “First uterine pass effect.” Wren et al., 2003 — Route-dependent systemic levels. Supports: Uterine targeting • Neurosteroid variability • Sedation differences 7. Progesterone, PMS & Migraine Claim: Neurosteroid fluctuations influence GABAergic tone and may contribute to PMS and migraine susceptibility. Core Evidence: Backstrom et al., 2011 — Allopregnanolone fluctuations in PMS. Reddy & Rogawski, 2002 — Neurosteroids and seizure threshold. Martin & Behbehani, 2001 — Hormonal fluctuations and migraine. Supports: Luteal neurosteroid shifts • GABA instability • Migraine association   Dr. Brendan McCarthy is the founder and Chief Medical Officer of Protea Medical Center in Arizona. With over two decades of experience, he's helped thousands of patients navigate hormonal imbalances using bioidentical HRT, nutrition, and root-cause medicine. He's also taught and mentored other physicians on integrative approaches to hormone therapy, weight loss, fertility, and more. If you're ready to take your health seriously, this podcast is a great place to start.  

Join us for this episode which is a fast, honest tour through what ketamine can actually do for mental health—without the hype. We sit down with addiction psychiatrist Dr. Mark Hrymoc to unpack where the evidence is strongest, who qualifies, and why IV ketamine often produces quicker relief than nasal esketamine when depression won't budge. From treatment-resistant depression and acute suicidality to anxiety and PTSD, we dig into the protocols that matter: six-session inductions, customized maintenance, and practical strategies for measuring progress with tools like the PHQ-9.We pull back the curtain on how ketamine works at the receptor level—NMDA antagonism, downstream dopamine effects, and BDNF-driven neuroplasticity—and explain why dissociation may help some patients but isn't required for benefit. You'll hear how we screen candidates, manage blood pressure, reduce nausea, and set up sessions with eye masks, ambient music, and a nurse at the bedside so the experience is safe, focused, and grounded. We also get real about addiction risk, clarifying the difference between recreational use and a carefully monitored medical protocol, and how stable recovery timelines factor into clinical decision-making.For PTSD and anxiety, we explore pairing ketamine with psychotherapy and post-session integration to turn insights into change. We compare IV ketamine's dosing flexibility with Spravato's structured pathway, talk costs and coverage, and outline how to taper other meds only after sustained stability. Looking ahead, we spotlight promising research directions—from extending response with adjuncts to early signals for substance use disorders—and why interventional psychiatry is opening a much-needed chapter beyond traditional antidepressants. If you've wondered whether ketamine is a bridge or a destination, this conversation gives you a clear, practical map. Subscribe, share with a clinician friend, and leave a review to help others find evidence-based mental health care.To contact Dr. Grover - ammadeasy@fastmail.com

In this episode of the Headliner Mindset Podcast, I sit down with one of my coaching clients NIMDA for a raw, honest conversation about the realities of building a career in heavy music.We talk about touring burnout, creative pressure, comparison, and what it actually takes to stay mentally healthy while flying nonstop, staying up all night making music, and performing at a high level.NMDA opens up about:Burnout from touring and constant travelThe pressure of making new music for every setStaying disciplined without burning outLetting go of comparison and worst-case thinkingWhy great music and a strong brand matter more than going viralThis episode is for artists who love what they do — but are feeling the weight of it.If you're chasing the dream and trying not to lose yourself in the process, this conversation will hit home.Follow NIMDA here:www.instagram.com/nimda_ukAnd follow Nik Cherwink here:www.instagram.com/nikcherwink

To get live links to the music we play and resources we offer, visit www.WOSPodcast.comThis show includes the following songs:Lustbar - No Turning Back søftbleach - Neverland FOLLOW ON SPOTIFYTracy Jane Comer - The Best Things in Life FOLLOW ON SPOTIFYSherry Hodge feat. Rachael Anderson - Still Don't Belong FOLLOW ON SPOTIFYSunlending Sky - The Other Land FOLLOW ON YOUTUBEAlissa Feudo - Frequency FOLLOW ON SPOTIFYNMDA - I Got You Too FOLLOW ON SPOTIFYGRACE PERIOD - Empty Again FOLLOW ON SPOTIFYLinda Mizzi - Let Him Go FOLLOW ON SPOTIFYWayward Vine - Imperfect Beings FOLLOW ON SPOTIFYLaLa Land - Brand New FOLLOW ON SPOTIFYAva Scott & Paul Petrucelli - Then I Found You FOLLOW ON YOUTUBEwriter Howard Delnick - The Sun Will Still Shine Over (feat. Katie Shorey) FOLLOW ON SPOTIFYCheryl Hardy (writers Rick Beneteau & Larry Thompson) - The More The Bluebillies - Run Daddy Run FOLLOW ON SPOTIFYFor Music Biz Resources Visit www.FEMusician.com and www.ProfitableMusician.comVisit www.wosradio.com for more details and to submit music to our review board for consideration.Visit our resources for Indie Artists: https://www.wosradio.com/resourcesBecome more Profitable in just 3 minutes per day. http://profitablemusician.com/join

Ketamine is a dissociative anesthetic that provides powerful analgesia while preserving spontaneous ventilation, airway reflexes, and sympathetic tone, which makes it especially valuable in trauma, bronchospasm, difficult airways, and in patients with high opioid tolerance. As a phencyclidine derivative with a chiral center, it exists as two enantiomers, with S-ketamine roughly twice as potent as R-ketamine and associated with fewer unpleasant emergence reactions, while its pKa and balanced water–lipid solubility allow rapid CNS penetration and redistribution-limited offset. Its multimodal mechanism centers on noncompetitive NMDA antagonism but also includes opioid receptor modulation, catecholamine reuptake inhibition, AMPA receptor effects, ion channel blockade, muscarinic antagonism, and anti-inflammatory actions, all of which underpin clinical dosing strategies for induction, maintenance, procedural sedation, and analgesic infusions as well as key considerations around emergence delirium, secretions, cardiovascular status, and ICP.Want to learn more? Grab our Cardiac Pharm Course --> [HERE]⚛️ CONNECT:

Le protoxyde d'azote, plus connu sous le nom de « gaz hilarant », est souvent perçu comme une substance légère, presque anodine. Utilisé à l'origine en médecine pour ses propriétés analgésiques et anxiolytiques, il s'est diffusé ces dernières années dans les usages récréatifs. Mais ses effets sur le cerveau sont loin d'être bénins. Derrière les rires et la sensation d'euphorie se cache une action neurologique puissante, complexe… et potentiellement dangereuse.Dès l'inhalation, le protoxyde d'azote agit comme un antagoniste des récepteurs NMDA, des récepteurs essentiels à la communication entre neurones. En les bloquant, il provoque une déconnexion temporaire dans certaines zones cérébrales, d'où la sensation de flottement, d'irréalité, de dissociation. Cette altération du traitement sensoriel explique également les perceptions modifiées : sons étouffés, vision déformée, impressions d'éloignement du corps.Le gaz stimule également le système dopaminergique, ce qui renforce la sensation d'euphorie. La dopamine, neurotransmetteur de la récompense, crée un pic bref mais intense, donnant à l'utilisateur la sensation que tout devient soudain amusant, léger, dédramatisé. Ce mécanisme explique la recherche de répétition : plus on consomme, plus on souhaite reproduire ce “flash” plaisant.Mais derrière ces effets immédiats se cachent des risques importants. Le protoxyde d'azote perturbe l'absorption de la vitamine B12, un élément indispensable à la fabrication de la myéline, cette gaine protectrice qui permet aux neurones de transmettre les signaux électriques. Une carence prolongée peut entraîner des atteintes de la moelle épinière, des fourmillements, des pertes d'équilibre, voire des paralysies partielles. Et ces dommages peuvent parfois être irréversibles.Le gaz réduit également la quantité d'oxygène disponible pour le cerveau. Une inhalation répétée ou mal contrôlée peut conduire à une hypoxie, c'est-à-dire un manque d'oxygène dans les tissus cérébraux. À court terme, cela provoque des pertes de connaissance ; à long terme, cela peut léser les zones impliquées dans la mémoire, l'attention ou la coordination.Enfin, l'usage fréquent modifie la connectivité neuronale, à la manière d'autres substances dissociatives. Certains utilisateurs témoignent d'un sentiment de brouillard mental, d'une fatigue cognitive durable, voire de troubles anxieux ou dépressifs après consommation répétée.En résumé, si le protoxyde d'azote procure une euphorie rapide, il agit profondément sur le cerveau : il altère la communication neuronale, perturbe la myéline, prive temporairement l'organisme d'oxygène et peut laisser des séquelles durables. Un plaisir fugace, mais un risque réel. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

This episode dives deep into excitatory neurons—the brain's primary “go” signal—and their outsized role in the autistic phenotype. We explore how pyramidal neurons, powered by glutamate through AMPA and NMDA receptors, drive lightning-fast information transmission, synaptic hyperplasticity via BDNF, and elevated gamma oscillations (30–80 Hz) in V1, S1, and A1. This overactive excitatory push, paired with reduced parvalbumin and somatostatin inhibition, creates the well-documented E:I imbalance that fuels sensory hypersensitivity, one-trial learning, rigid memory encoding, repetitive behaviors, and the classic distal-connection timing mismatch from early sensory cortices to prefrontal regions.The autistic brain gets to the first two stops blazingly fast yet struggles to reach the final destination typical brains arrive at effortlessly.Inhibition Episodes: https://youtu.be/cjwbog7Rk4c?si=uSaLLNmS5EJLa_iHhttps://youtu.be/Oee4L7Vsj4E?si=Y5F2eVudCLhkxNw1 https://youtu.be/PBHVssvoQkM?si=A6SPedQi-Dt-DVO_E/I https://youtu.be/ETChjRQ0SzQ?si=yIFNovzldwSZRMeThttps://youtu.be/jl0xwjnyXII?si=dmk49CMQo3Uf17axDaylight Computer Company, use "autism" for $50 off at https://buy.daylightcomputer.com/autismChroma Light Devices, use "autism" for 10% discount at https://getchroma.co/?ref=autismFig Tree Christian Golf Apparel & Accessories, use "autism" for 10% discount at https://figtreegolf.com/?ref=autismCognity AI for Autistic Social Skills, use "autism" for 10% discount at https://thecognity.com00:00 Excitatory Neurons, Push-Pull System, Parvalbumin Deficiency03:30 E:I Imbalance, Sensory Hypersensitivity, Repetitive Behaviors07:00 Pyramidal Neurons, Glutamate, AMPA/NMDA Receptors10:30 Brain Regions: DLPFC, Anterior Insula, V1 S1 A114:00 Amygdala Misnomer, Low Road vs High Road, Emotional Hub18:30 Receptors: AMPA 1-5ms, NMDA 10-200ms, mGluR Modulatory22:00 Gamma Oscillations, BDNF Hyperplasticity, Sensory Overload25:30 Distal Connections, Point-A-to-Point-B Timing Mismatch29:00 BDNF Critical Period, One-Trial Learning, Rigid Memory32:30 TRN Dysfunction, Repetitive Behaviors, Corticostriatal Circuit34:30 Go-Signal vs Stop-Signal, Push-Pull Bowling Bumpers36:00 Rubenstein & Merzenich 2003, E:I Imbalance Foundation37:08 Daylight Computer Company, use "autism" for $50 discount39:32 Chroma Light Devices, use "autism" for 10% discount42:35 Reviews/Ratings & Contact InfoX: https://x.com/rps47586YT: https://www.youtube.com/channel/UCGxEzLKXkjppo3nqmpXpzuAemail: info.fromthespectrum@gmail.com

Broadcast from KSQD, Santa Cruz on 11-06-2025:>/p> Dr. Dawn interviews Cindy Jackonette and Dr. Michael Alexander about a fundraiser for pancreatic cancer awareness on November 15th at Bargetto Winery from 2-5pm, supporting the Santa Cruz Cancer Benefit Group. Dr. Alexander explains pancreatic cancer has only 10-15% five-year survival rates and is difficult to screen for. Screening involves complex endoscopy procedures examining pancreatic ducts, CT scans and biomarker scans. The disease represents 3% of cancer cases but 8% of deaths. Immune checkpoint inhibitors show limited success except in Lynch syndrome patients with DNA repair defects. The Santa Cruz Cancer Benefit Group donates annually to local cancer organizations and is all volunteer-run with minimal overhead. An emailer asks when her 56-year-old half-African American son should get colon cancer screening given his father and uncle both had the disease. Dr. Dawn explains African Americans have increased risk and recommends immediate colonoscopy despite the ideal screening window being 10 years ago. She emphasizes identifying whether he produces polyps, which would require surveillance every 3-5 years. Unlike pancreatic cancer, colon cancer is highly curable when detected early, with death rates dropping 30-40% since colonoscopies became standard in the mid-1990s. She recommends preventive measures including daily 200mg ibuprofen (if no ulcer history) and a high-fiber diet rich in colorful vegetables containing antioxidants that reduce oxidative stress and DNA damage from free radicals. An emailer from Israel asks about supporting his 38-year-old son's rectal adenocarcinoma treatment. Dr. Dawn recommends nutritional strategies including juicing 10 different fruits and vegetables daily, 20mg melatonin for synergy with chemotherapy, vitamin D supplementation, and L-glutamine as primary food for bowel healing and lymphocyte function. She suggests DHA fish oil to enhance chemotherapy effectiveness, green tea for oncogene inhibition, astragalus herb to increase phagocytic activity and natural killer cells, and rotating water-extracted mushroom formulas with beta-glucans, particularly maitake and shitake. Glutamine also protects mucous membranes from radiation burns. Dr. Dawn discusses alarming cancer rate increases among young adults in Corn Belt states including Iowa, Nebraska, Illinois, Minnesota, Indiana, and Kansas. Since 2015, these states show 5% higher cancer rates for ages 15-49 compared to national averages, with particularly elevated kidney and skin cancer rates. Young women face 66% higher skin cancer risk than peers in other states. . Governor Kim Reynolds invested $1 million for research while Bayer's attempt to shield Roundup from lawsuits failed. Dr. Dawn notes Roundup now contains diquat after removing glyphosate. It has taken decades to accumulate evidence of glyphosates harms, She warns that absence of evidence of Diquats being harmful isn't evidence of safety and that Ames testing suggests high mutation potential. An emailer shares a JAMA article on lithium for Alzheimer's disease. Dr. Dawn explains that calcium dysregulation through NMDA receptors plays an upstream role in Alzheimer's pathology. Lithium, a bipolar disorder treatment, can reset deranged calcium gates, inhibiting mitochondrial damage and tau protein production. She emphasizes tau protein as the true culprit in Alzheimer's while amyloid beta is more symptomatic. Correcting calcium homeostasis allows neuronal autophagy systems to clear waste more efficiently rather than being overwhelmed. She reports dramatic peanut allergy declines following 2017 pediatric recommendations for introducing peanuts at 4-6 months based on the LEAP study showing 81% reduction. Between 2017-2020, peanut allergies dropped from 0.79% to 0.45% of all children under 3, with overall food allergies declining 36%. Studies also show pregnant mothers eating peanuts reduces offspring allergy risk by promoting immune tolerance. We conclude with breakthrough wireless retinal implants for macular degeneration, where cameras on glasses convert images to near-infrared signals to retinal implants which stimulate surviving retinal neurons. The prototype allowed patients to improve by two lines on eye charts and perceive facial expressions and read smaller print.

In this episode of the PFC Podcast, Dennis and Kevin dive deep into the complexities of ketamine, exploring its pharmacodynamics, pharmacokinetics, and practical applications in emergency medicine. They discuss the drug's disassociative properties, its analgesic effects, and the importance of individualized dosing based on patient physiology. The conversation also touches on the risks of catecholamine depletion and the management of side effects, particularly in trauma patients. Throughout the discussion, Kevin shares valuable insights and practical advice for medics and healthcare professionals using ketamine in real-life scenarios.TakeawaysKetamine is an NMDA receptor antagonist with various effects on the body.It can cause profound analgesia and disassociation at different doses.S-ketamine is preferred for its more intense analgesic effects and quicker recovery.Dosing should be individualized based on patient condition and physiology.Ketamine can lead to catecholamine depletion, especially in trauma patients.Smaller doses are safer for patients with compromised vital signs.Analgesic effects can be achieved without full disassociation at lower doses.Managing side effects is crucial, especially in the 'party zone' of ketamine use.Always have a plan for potential complications when using ketamine.Refer to clinical practice guidelines (CPGs) for best practices.Chapters00:00 Understanding Ketamine: Basics and Mechanisms09:17 Pharmacokinetics of Ketamine: How It Works15:58 Dosing Ketamine: Individualized Approaches25:23 Analgesic Properties of Ketamine: Beyond Disassociation31:39 Managing Side Effects: The Party Zone and Hallucinations39:19 Catecholamine Depletion: Risks and Considerations43:05 Practical Advice for Medics: Using Ketamine SafelyFor more content, go to ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.prolongedfieldcare.org⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Consider supporting us: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠patreon.com/ProlongedFieldCareCollective⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ or ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.lobocoffeeco.com/product-page/prolonged-field-care

We dive into the latest research on ketamine's therapeutic potential, including its role in treating ischemic stroke, postoperative cognitive dysfunction (POCD), and PTSD. You'll hear how scientists are studying its effects on brain regions like the hippocampus and amygdala, as well as its impact on neuroinflammation, fear memory, and neurogenesis.   We'll also explore ketamine's use in anesthesia, its interactions with drugs like oral morphine, and how it's monitored using tools like EEG. From molecular techniques like RT-qPCR and Western blotting to real-world applications—this episode breaks down the science driving ketamine's future in medicine.   Here's some of what you'll hear in this episode:

Contributor: Aaron Lessen, MD Educational Pearls: Prehospital seizures are typically managed with intramuscular midazolam (Versed) Seizures theoretically involve the NMDA pathway, and ketamine is a potent NMDA antagonist A recent retrospective cohort study analyzed a Florida EMS protocol that uses ketamine in seizures refractory to midazolam One group received two doses of midazolam for seizure control The other group received a dose of midazolam followed by a dose of ketamine After matching, 82% of the midazolam-only group patients had resolution of convulsions prior to ED arrival 94.4% of patients in the midazolam + ketamine group experienced resolution Absolute difference between groups was 12.4% (95% CI 3.1% to 21.7%) Limitations to the study include its prehospital setting and limited long-term follow-up References Zitek T, Scheppke KA, Antevy P, et al. Midazolam and Ketamine for Convulsive Status Epilepticus in the Out-of-Hospital Setting. Ann Emerg Med. 2025;85(4):305-312. doi:10.1016/j.annemergmed.2024.11.002 Summarized & Edited by Jorge Chalit, OMS4 Donate: https://emergencymedicalminute.org/donate/  

Summary In this episode of the Pain Exam Podcast, Dr. David Rosenblum provides a comprehensive review of herpes zoster and postherpetic neuralgia (PHN), focusing on pathophysiology, diagnosis, and treatment options. Dr. Rosenblum explains that postherpetic neuralgia affects approximately 25% of patients with acute herpes zoster, causing debilitating unilateral chronic pain in one or more dermatomes. He discusses the three phases of herpes zoster: acute (up to 30 days), subacute (up to 3 months), and postherpetic neuralgia (pain continuing beyond 3 months). Dr. Rosenblum identifies risk factors for developing PHN, including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. He details the pathophysiology involving peripheral and central sensitization, and explains different phenotypes of PHN that can guide treatment approaches. For treatment, Dr. Rosenblum reviews various options including antiviral medications (which should be started within 72 hours of onset), corticosteroids, opioids, antidepressants (particularly tricyclics and SNRIs), antiepileptics (gabapentin and pregabalin), topical agents (lidocaine and capsaicin), and interventional procedures such as epidural injections and pulsed radiofrequency. He emphasizes that prevention through vaccination with Shingrix is highly effective, with 97% effectiveness in preventing herpes zoster in patients 50-69 years old and 89% effectiveness in those over 70. Dr. Rosenblum mentions that he's currently treating a patient with trigeminal postherpetic neuralgia and is considering a topical sphenopalatine ganglion block as a minimally invasive intervention before attempting more invasive procedures. Chapters Introduction to the Pain Exam Podcast and Topic Overview Dr. David Rosenblum introduces the Pain Exam Podcast, mentioning that it covers painful disorders, alternative treatments, and practice management. He explains that this episode focuses on herpes zoster and postherpetic neuralgia as board preparation for fellows starting their programs, with ABA boards coming up in September. Dr. Rosenblum notes that he's not only preparing listeners for boards but also seeking the latest information to help treat his own patients with this notoriously difficult disease. Upcoming Conferences and Educational Opportunities Dr. Rosenblum announces several upcoming conferences including Aspen in July, Pain Week in September, and events with NYSIP and the Latin American Pain Society. He mentions he'll be teaching ultrasound and regenerative medicine at these events. Dr. Rosenblum invites listeners to sign up at nrappain.org to access a community discussing regenerative medicine, ultrasound-guided pain medicine, regional anesthesia, and board preparation. He also offers ultrasound training in New York and elsewhere, with upcoming sessions in Manhattan on July 12th and October 4th, plus private shadowing opportunities. Overview of Postherpetic Neuralgia Dr. Rosenblum defines postherpetic neuralgia as typically a unilateral chronic pain in one or more dermatomes after acute herpes zoster infection. He states that the incidence of acute herpes zoster ranges between 3-5 patients per thousand person-years, and one in four patients with acute herpes zoster-related pain will transition into postherpetic neuralgia. Dr. Rosenblum emphasizes that while this condition won't kill patients, it can be extremely debilitating and significantly reduce quality of life. Treatment Options Overview Dr. Rosenblum reviews treatment options according to the WHO pain ladder, including tricyclics like nortriptyline and antiepileptic drugs such as gabapentin. He explains that if pain is not significantly reduced, interventional treatments like epidural injections with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion are options. For postherpetic neuralgia specifically, Dr. Rosenblum notes that preferred treatments include transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. Phases of Herpes Zoster and Definitions Dr. Rosenblum outlines the three phases during herpes zoster reactivation: acute herpes zoster-related pain (lasting maximum 30 days), subacute herpes zoster-related pain (pain after healing of vesicles but disappearing within 3 months), and postherpetic neuralgia (typically defined as pain continuing after 3 months). He mentions that acute herpes zoster pain often begins with prodromal pain starting a few days before the appearance of the rash. Incidence and Risk Factors Dr. Rosenblum states that the incidence of herpes zoster ranges between 3-5 patients per 1,000 person-years, with approximately 5-30% of cases leading to postherpetic neuralgia. He identifies risk factors including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. Dr. Rosenblum describes the clinical manifestations as a mosaic of somatosensory symptoms including burning, deep aching pain, tingling, itching, stabbing, often associated with tactile and cold allodynia. Impact on Quality of Life Dr. Rosenblum emphasizes that postherpetic neuralgia can be debilitating, impacting both physical and emotional functioning and causing decreased quality of life. He notes that it leads to fatigue, insomnia, depression, anorexia, anxiety, and emotional distress. Dr. Rosenblum stresses the importance of exploring methods for prevention of postherpetic neuralgia and optimizing pain treatment for both subacute herpes zoster-related pain and postherpetic neuralgia. Literature Review and Pathophysiology Dr. Rosenblum mentions that he's discussing a literature review from 2024 that updates previous practical guidelines published in 2011. He explains the pathophysiology of postherpetic neuralgia, which involves sensitization of peripheral and sensory nerves from damage. Dr. Rosenblum describes how inflammatory mediators reduce the stimulus threshold of nociceptors and increase responsiveness, resulting in pathological spontaneous discharges, lower thresholds for thermal and mechanical stimuli, and hyperalgesia. Central Sensitization and Nerve Damage Dr. Rosenblum explains that central sensitization results from peripheral nociceptor hyperactivity leading to plastic changes in the central nervous system, involving amplification of pain signals and reduced inhibition. He describes how nerve damage in postherpetic neuralgia patients results from neuronal death due to severe inflammatory stimuli or secondary to neuronal swelling. Dr. Rosenblum notes that motor defects occur in 0.05% of patients with herpes zoster, observed as abdominal pseudohernias or motor weakness of limbs limited to the affected myotome. Different Phenotypes and Classification Dr. Rosenblum discusses different phenotypes of postherpetic neuralgia and how phenotyping can determine treatment. He explains that there are several ways to classify the phenotypes, with one categorizing patients into three subtypes: sensory loss (most common), thermal gain, and thermal loss with mechanical gain. Dr. Rosenblum describes the mechanistic categorization, including the irritable nociceptive phenotype characterized by preserved sensation, profound dynamic mechanical allodynia, reduced pressure pain threshold, and relief with local anesthetic infiltration. Deafferentation Phenotype Dr. Rosenblum explains that a deafferentation phenotype may arise from destruction of neurons by the virus in the dorsal root ganglion. This phenotype is characterized by sensory loss, including thermal and vibratory sensation without prominent thermal allodynia. He notes that mechanical allodynia can occur secondary to A-beta fibers activating spinothalamic pathways (known as phenotypic switches), along with pressure hyperalgesia and temporal summation suggesting central sensitization. Dr. Rosenblum mentions that in one study, this phenotype was present in 10.8% of individuals, and for those with deafferentation pain, gabapentinoids, antidepressants, and neuromodulatory therapies like repetitive transcranial magnetic stimulation may be beneficial. Diagnosis and Physical Examination Dr. Rosenblum discusses the diagnosis of herpes zoster and postherpetic neuralgia, emphasizing the importance of physical examination. He explains that diagnosis is based on the rash, redness, papules, and vesicles in the painful dermatomes, with healing vesicles showing crust formation. Dr. Rosenblum notes that the rash is generally unilateral and does not cross the midline of the body. In postherpetic neuralgia patients, he mentions that scarring, hyper or hypopigmentation is often visible, with allodynia present in 45-75% of affected patients. Sensory Testing and Assessment Dr. Rosenblum explains that in patients with postherpetic neuralgia, a mosaic of somatosensory alterations can occur, manifesting as hyperalgesia, allodynia, and sensory loss. These can be quantified by quantitative sensory testing, which assesses somatosensory functions, dermal detection thresholds for perception of cold, warmth, and paradoxical heat sensations. He notes that testing can provide clues regarding underlying mechanisms of pain, impaired conditioned pain modulation, temporal summation suggesting central sensitization, and information about the type of nerve damage and surviving afferent neurons. Prevention Through Vaccination Dr. Rosenblum discusses prevention of acute herpes zoster through vaccination, noting that the risk increases with reduced immunity. He highlights studies evaluating Shingrix, a vaccine for herpes zoster, which showed 97% effectiveness in preventing herpes zoster in patients 50-69 years old with healthy immune systems and 89% effectiveness in patients over 70. Dr. Rosenblum states that Shingrix is 89-91% effective in preventing postherpetic neuralgia development in patients with healthy immune systems and 68-91% effective in those with weakened or underlying conditions. Treatment Objectives Dr. Rosenblum outlines the treatment objectives for herpes zoster and postherpetic neuralgia. For acute herpes zoster, objectives include relieving pain, reducing severity and duration of pain, accelerating recovery of epidermal defects, and preventing secondary infections. For postherpetic neuralgia, the objectives are pain alleviation and improved quality of life. Dr. Rosenblum lists available treatments including psychotherapy, opiates, antidepressants, antiepileptics, NMDA antagonists, topical agents, and interventional treatments such as epidurals, pulsed radiofrequency, nerve blocks, and spinal cord stimulation. Antiviral Medications Dr. Rosenblum emphasizes that antiviral drugs should be started within 72 hours of clinical onset, mentioning famciclovir, valacyclovir, and acyclovir. He notes there is no evidence for effectiveness after 72 hours in patients with uncomplicated herpes zoster. Dr. Rosenblum provides dosing information: for immunocompetent patients, famciclovir 500mg and valacyclovir 1000mg three times daily for seven days; for immunocompromised patients, famciclovir 1000mg three times daily for 10 days, while acyclovir should be given IV in the immunocompromised. Benefits of Antiviral Therapy Dr. Rosenblum explains that antiviral medication accelerates the disappearance of vesicles and crusts, promotes healing of skin lesions, and prevents new lesions from forming. By inhibiting viral replication, he notes that antiviral therapy likely reduces nerve damage, resulting in reduced incidence of postherpetic neuralgia, and should be started as soon as possible. Corticosteroids and Opioids Dr. Rosenblum discusses the use of corticosteroids, noting that when added to antiviral medications, they may reduce the severity of acute herpes zoster-related pain, though increased healing of skin lesions was not observed in one study. He mentions that a Cochrane review found oral corticosteroids ineffective in preventing postherpetic neuralgia. Regarding opioids, Dr. Rosenblum states they are commonly used alongside antivirals for controlling acute herpes zoster pain, with tramadol having a number needed to treat (NNT) of 4.7 and strong opioids having an NNT of 4.3 for 50% pain reduction. Methadone and Antidepressants Dr. Rosenblum discusses methadone as an NMDA receptor antagonist used in acute and chronic pain management, though he notes there are no randomized controlled trials determining its efficacy in acute herpes zoster pain or postherpetic neuralgia. He explains that methadone can modulate pain stimuli by inhibiting the uptake of norepinephrine and serotonin, resulting in decreased development of hyperalgesia and opioid tolerance, but has side effects including constipation, nausea, sedation, and QT prolongation that can trigger torsades de pointes. Dr. Rosenblum identifies antidepressants as first-line therapy for postherpetic neuralgia, including tricyclics and SNRIs, with tricyclics having an NNT of 3 and SNRIs an NNT of 6.4 for 50% pain reduction. Antiepileptics and Pharmacological Treatment Summary Dr. Rosenblum discusses antiepileptics like gabapentin and pregabalin for postherpetic neuralgia. He cites two trials measuring gabapentin's effect, concluding it was effective compared to placebo with a pooled NNT of 4.4, while pregabalin had an NNT of 4.9. Dr. Rosenblum summarizes that pharmacological treatment is well established for subacute herpes zoster pain, though new high-quality evidence has been lacking since the last update in 2011. Topical Agents Dr. Rosenblum discusses local anesthetic topical agents including lidocaine and capsaicin creams and patches. He notes that 8% capsaicin provided significant pain reduction during 2-8 weeks, while 5% lidocaine patches provided moderate pain relief after eight weeks of treatment. Dr. Rosenblum also mentions acute herpes zoster intracutaneous injections, citing a study where single intracutaneous injection with methylprednisolone combined with ropivacaine versus saline alone showed significant difference in VAS score at 1 and 4 weeks post-intervention favoring the intervention group. Intracutaneous Injections Dr. Rosenblum discusses the effect of repetitive intracutaneous injections with ropivacaine and methylprednisolone every 48 hours for one week. He cites a randomized control trial comparing antivirals plus analgesics to antivirals plus analgesics and repeat injections, finding the intervention group had significantly shorter duration of pain, lower VAS scores, and lower incidence of postherpetic neuralgia (6.4% vs 28% at 3 months). Dr. Rosenblum notes that a potential side effect of cutaneous methylprednisolone injection is fat atrophy, though this wasn't reported in the study. Summary of Local Anesthetics Dr. Rosenblum summarizes that there are no new studies reporting the efficacy of capsaicin 8% for postherpetic neuralgia, but it remains widely used in clinical practice and is approved in several countries. He notes that lidocaine patches can reduce pain intensity in patients with postherpetic neuralgia but may be more beneficial in patients with allodynia. Dr. Rosenblum adds that intracutaneous injections may be helpful for short periods, while repetitive injections with local anesthetics may reduce VAS scores for up to six months but can cause subcutaneous fat atrophy. Interventional Treatments: Epidural and Paravertebral Injections Dr. Rosenblum discusses interventional treatments, noting that previous guidelines found epidural injection with corticosteroids and local anesthetic as add-on therapy superior to standard care alone for up to one month in managing acute herpes zoster pain. He mentions a randomized controlled trial showing no difference between interlaminar and transforaminal epidural steroid injections for up to three months after the procedure. Dr. Rosenblum adds that previous guidelines reported high-quality evidence that paravertebral injections of corticosteroids or local anesthetic reduces pain in the active phase of herpes zoster. Comparative Studies on Injection Approaches Dr. Rosenblum discusses a trial comparing efficacy of repetitive paravertebral blocks with ropivacaine versus dexmedetomidine to prevent postherpetic neuralgia, which showed significantly lower incidence of zoster-related pain one month after therapy in the dexmedetomidine group, with effects still significant at three months. He also mentions a study comparing steroid injections administered via interlaminar versus transforaminal approaches, finding both groups had significantly lower VAS scores at 1 and 3 months follow-up compared to baseline, though this could align with the natural course of herpes zoster. Timing of Interventions and Continuous Epidural Blockade Dr. Rosenblum cites a retrospective study showing that transforaminal epidural injections administered for acute herpes zoster-related pain were associated with significantly shorter time to pain relief compared to those performed in the subacute phase. He also mentions a randomized controlled trial finding that continuous epidural blockade combined with opioids and gabapentin reduced NRS pain scores more than analgesic drug treatments alone during three-day follow-up, though both studies were low-quality. Interventions for Postherpetic Neuralgia Dr. Rosenblum discusses interventions specifically for postherpetic neuralgia, citing a small randomized controlled trial that demonstrated decreased NRS pain scores six months post-treatment for repeat versus single epidural steroid injections (15mg vs 5mg dexamethasone) administered over 24 days. The trial also found increased likelihood of complete remission during 6-month follow-up in the group receiving repeat epidural dexamethasone, though this was low-quality evidence. Summary of Epidural and Paravertebral Injections Dr. Rosenblum summarizes that epidural or paravertebral injections of local anesthetic and/or glucocorticoids could be considered in treating acute herpes zoster-related pain. For subacute postherpetic neuralgia pain, he notes low-quality evidence supporting epidural injections, while for postherpetic neuralgia, evidence supports continuous epidural infusion, though also of low quality. Dr. Rosenblum emphasizes that none of the included studies for postherpetic neuralgia investigating epidural or paravertebral injections resulted in decreased pain compared to standard therapy. Pulsed Radiofrequency (PRF) Evidence Dr. Rosenblum discusses pulsed radiofrequency (PRF), noting that previous guidelines indicated moderate quality evidence that PRF of the intercostal nerve reduces pain for 6 months in patients with postherpetic neuralgia, and very low-quality evidence that PRF to the dorsal root ganglion (DRG) reduces pain for 6 months. He mentions that multiple studies have been published since then assessing PRF efficacy. PRF Studies for Acute Herpes Zoster Dr. Rosenblum discusses a randomized controlled trial with 60 patients comparing high-voltage bipolar PRF of the cervical sympathetic chain versus sham, with treatment repeated after three days in both groups. He reports that VAS scores in the PRF group at each post-interventional point (1 day, 2 days, 1 month, 2 months, 3 months) were significantly lower than in the sham group, and at 3 months, the incidence of postherpetic neuralgia was 16.7% in the PRF group compared to 40% in the sham group. PRF for Trigeminal Neuralgia Dr. Rosenblum cites another randomized controlled trial evaluating high-voltage long-duration PRF of the Gasserian ganglion in 96 patients with subacute herpes-related trigeminal neuralgia, which found decreased VAS pain scores at all post-interventional time points (3, 7, 14 days and 1, 3, and 6 months) compared to the sham group. He also mentions a randomized comparative effectiveness study in 120 patients with subacute trigeminal herpes zoster, comparing a single application of high-voltage PRF to the Gasserian ganglion versus three cycles of conventional PRF treatment, finding significantly lower mean VAS pain scores for up to six months in the high-voltage PRF group. PRF Compared to Other Interventions Dr. Rosenblum discusses a randomized controlled trial comparing PRF to short-term spinal cord stimulation, which found decreased pain and improved 36-item short-form health survey scores in both groups at six months. He also mentions a randomized controlled trial in 72 patients where PRF of spinal nerves or peripheral branches of cranial nerves combined with five-day infusion of IV lidocaine resulted in greater pain reduction, less rescue analgesia, and reduced inflammatory cytokines at two months compared to PRF with saline infusions. Dr. Rosenblum notes a major limitation of this study was not accounting for the high natural recovery rate. Summary of PRF and Final Recommendations Dr. Rosenblum summarizes that PRF provides significant pain relief lasting over three months in patients with subacute herpes zoster and postherpetic neuralgia. He notes that since few studies have compared PRF versus sham, it's not possible to calculate an accurate number needed to treat. Dr. Rosenblum mentions there are no comparative studies comparing PRF to the intercostal nerves versus PRF of the DRG, but both preclinical and clinical studies suggest superiority of the DRG approach. He adds that evidence for spinal cord stimulation for postherpetic neuralgia is of low quality, and more research is needed given its invasive nature. Sympathetic Blocks and Conclusion Dr. Rosenblum notes there is low-quality evidence for using sympathetic blocks to treat acute herpes zoster-related pain, but no evidence for their use in postherpetic neuralgia. He mentions that risks of treatment with intrathecal methylprednisolone are unclear and therefore not recommended. Dr. Rosenblum concludes by praising the comprehensive article he's been discussing and mentions it provides insight for treating his patients, including a recent case of trigeminal postherpetic neuralgia. Personal Clinical Approach and Closing Dr. Rosenblum shares that he doesn't currently perform PRF in his practice, partly because it's not standard of care and not well reimbursed, creating barriers to implementation. However, he notes that PRF is a very safe procedure as it doesn't involve burning tissue. For his patient with trigeminal neuralgia pain, Dr. Rosenblum plans to try a topical sphenopalatine ganglion block as the least invasive intervention before considering injecting the trigeminal nerves at the foramen, in addition to pharmacotherapy. He concludes by thanking listeners, encouraging them to check the show notes and links, mentioning institutional memberships and shadowing opportunities, and asking listeners to rate and share the podcast. Q&A No Q&A session in this lecture Pain Management Board Prep   Ultrasound Training REGISTER TODAY!   Create an Account and get Free Access to the PainExam- NRAP Academy Community Highlights     David Rosenblum, MD, currently serves as the Director of Pain Management at Maimonides Medical Center and AABP Integrative Pain Care.  As a member of the Department of Anesthesiology, he is involved in teaching, research, CME activities, and was key faculty in developing the anesthesiology residency's regional anesthesia block rotation, as well as institutional wide acute and chronic pain management protocols to ensure safe and effective pain management. He currently is a managing partner in a multi-physician private pain practice, AABP Integrative Pain Care, located in Brooklyn, NY. He is one of the earliest interventional pain physicians to integrate ultrasound guidance to improve the safety and accuracy of interventional pain procedures.   Awards New York Magazine: Top Doctors: 2016, 2017, 2018, 2021, 2022, 2023, 2024, 2025 Schneps Media: 2015, 2016, 2017, 2019, 2020 Top Doctors New York Metro Area (digital guide): 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023 2025 Schneps Media - Brooklyn Courier Life: 2021, 2022, 2023   Dr. Rosenblum written several book chapters on Peripheral Neuromodulation, Radiofrequency Ablation, and Pharmacology.  He has published numerous noteworthy articles and most recently is developing the ASIPP Guidelines for Peripheral Neuromodulation in the treatment of chronic pain. He has been named several times in NY Magazine's Best Pain Management Doctor List, Nassau County's Best Pain Physician, has appeared on NY1 News, and has made several appearances on XM Radio's Doctor Talk. He currently is lecturing on a national and international level and has partnered with the American Society of Interventional Pain Physicians (ASIPP), American Society of Pain and Neuroscience (ASPN), IASP Mexican Chapter, Eastern Pain Association (EPA), the North American Neuromodulation Society (NANS), World Academy of Pain Medicine United, as well as various other organizations, to support educational events and develop new courses. Since 2008, he has helped over 3000 physicians pass the Pain Management Boards, and has been at the forefront of utilizing ultrasound guidance to perform pain procedures.  He now hosts the PainExam podcast, AnesthesiaExam Podcast, PMRExam Podcasts and uses this platform to promote the safe and effective use of ultrasound in the performance of various procedures such as Peripheral Nerve Stimulation, Caudal Epidurals, Selective Nerve Root Blocks, Cluneal Nerve Blocks, Ganglion impar Blocks, Stellate Ganglion Blocks, Brachial Plexus Blocks, Joint Injections and much more!   Doctor Rosenblum created the NRAP (Neuromodulation Regional Anesthesia and Pain) Academy  and travels to teach various courses focused on Pain Medicine, Regenerative Medicine, Ultrasound Guided Pain Procedures and Regional Anesthesia Techniques.  Dr. Rosenblum is persistent when it comes to eliminating pain and has gained a reputation among his patients for thinking "outside the box" and implements ultrasound guidance to deposit medications, biologics (PRP, Bone Marrow Aspirate, etc.) and Peripheral Nerve Stimulators near pain generators. He is currently treating patients in his great neck and Brooklyn office.  For an appointment go to AABPpain.com or call Brooklyn     718 436 7246 Reference Adriaansen, E. J., Jacobs, J. G., Vernooij, L. M., van Wijck, A. J., Cohen, S. P., Huygen, F. J., & Rijsdijk, M. (2025). 8. Herpes zoster and post herpetic neuralgia. Pain Practice, 25(1), e13423.

Summary In this episode of the Pain Exam Podcast, Dr. David Rosenblum provides a comprehensive review of herpes zoster and postherpetic neuralgia (PHN), focusing on pathophysiology, diagnosis, and treatment options. Dr. Rosenblum explains that postherpetic neuralgia affects approximately 25% of patients with acute herpes zoster, causing debilitating unilateral chronic pain in one or more dermatomes. He discusses the three phases of herpes zoster: acute (up to 30 days), subacute (up to 3 months), and postherpetic neuralgia (pain continuing beyond 3 months). Dr. Rosenblum identifies risk factors for developing PHN, including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. He details the pathophysiology involving peripheral and central sensitization, and explains different phenotypes of PHN that can guide treatment approaches. For treatment, Dr. Rosenblum reviews various options including antiviral medications (which should be started within 72 hours of onset), corticosteroids, opioids, antidepressants (particularly tricyclics and SNRIs), antiepileptics (gabapentin and pregabalin), topical agents (lidocaine and capsaicin), and interventional procedures such as epidural injections and pulsed radiofrequency. He emphasizes that prevention through vaccination with Shingrix is highly effective, with 97% effectiveness in preventing herpes zoster in patients 50-69 years old and 89% effectiveness in those over 70. Dr. Rosenblum mentions that he's currently treating a patient with trigeminal postherpetic neuralgia and is considering a topical sphenopalatine ganglion block as a minimally invasive intervention before attempting more invasive procedures. Chapters Introduction to the Pain Exam Podcast and Topic Overview Dr. David Rosenblum introduces the Pain Exam Podcast, mentioning that it covers painful disorders, alternative treatments, and practice management. He explains that this episode focuses on herpes zoster and postherpetic neuralgia as board preparation for fellows starting their programs, with ABA boards coming up in September. Dr. Rosenblum notes that he's not only preparing listeners for boards but also seeking the latest information to help treat his own patients with this notoriously difficult disease. Upcoming Conferences and Educational Opportunities Dr. Rosenblum announces several upcoming conferences including Aspen in July, Pain Week in September, and events with NYSIP and the Latin American Pain Society. He mentions he'll be teaching ultrasound and regenerative medicine at these events. Dr. Rosenblum invites listeners to sign up at nrappain.org to access a community discussing regenerative medicine, ultrasound-guided pain medicine, regional anesthesia, and board preparation. He also offers ultrasound training in New York and elsewhere, with upcoming sessions in Manhattan on July 12th and October 4th, plus private shadowing opportunities. Overview of Postherpetic Neuralgia Dr. Rosenblum defines postherpetic neuralgia as typically a unilateral chronic pain in one or more dermatomes after acute herpes zoster infection. He states that the incidence of acute herpes zoster ranges between 3-5 patients per thousand person-years, and one in four patients with acute herpes zoster-related pain will transition into postherpetic neuralgia. Dr. Rosenblum emphasizes that while this condition won't kill patients, it can be extremely debilitating and significantly reduce quality of life. Treatment Options Overview Dr. Rosenblum reviews treatment options according to the WHO pain ladder, including tricyclics like nortriptyline and antiepileptic drugs such as gabapentin. He explains that if pain is not significantly reduced, interventional treatments like epidural injections with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion are options. For postherpetic neuralgia specifically, Dr. Rosenblum notes that preferred treatments include transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. Phases of Herpes Zoster and Definitions Dr. Rosenblum outlines the three phases during herpes zoster reactivation: acute herpes zoster-related pain (lasting maximum 30 days), subacute herpes zoster-related pain (pain after healing of vesicles but disappearing within 3 months), and postherpetic neuralgia (typically defined as pain continuing after 3 months). He mentions that acute herpes zoster pain often begins with prodromal pain starting a few days before the appearance of the rash. Incidence and Risk Factors Dr. Rosenblum states that the incidence of herpes zoster ranges between 3-5 patients per 1,000 person-years, with approximately 5-30% of cases leading to postherpetic neuralgia. He identifies risk factors including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. Dr. Rosenblum describes the clinical manifestations as a mosaic of somatosensory symptoms including burning, deep aching pain, tingling, itching, stabbing, often associated with tactile and cold allodynia. Impact on Quality of Life Dr. Rosenblum emphasizes that postherpetic neuralgia can be debilitating, impacting both physical and emotional functioning and causing decreased quality of life. He notes that it leads to fatigue, insomnia, depression, anorexia, anxiety, and emotional distress. Dr. Rosenblum stresses the importance of exploring methods for prevention of postherpetic neuralgia and optimizing pain treatment for both subacute herpes zoster-related pain and postherpetic neuralgia. Literature Review and Pathophysiology Dr. Rosenblum mentions that he's discussing a literature review from 2024 that updates previous practical guidelines published in 2011. He explains the pathophysiology of postherpetic neuralgia, which involves sensitization of peripheral and sensory nerves from damage. Dr. Rosenblum describes how inflammatory mediators reduce the stimulus threshold of nociceptors and increase responsiveness, resulting in pathological spontaneous discharges, lower thresholds for thermal and mechanical stimuli, and hyperalgesia. Central Sensitization and Nerve Damage Dr. Rosenblum explains that central sensitization results from peripheral nociceptor hyperactivity leading to plastic changes in the central nervous system, involving amplification of pain signals and reduced inhibition. He describes how nerve damage in postherpetic neuralgia patients results from neuronal death due to severe inflammatory stimuli or secondary to neuronal swelling. Dr. Rosenblum notes that motor defects occur in 0.05% of patients with herpes zoster, observed as abdominal pseudohernias or motor weakness of limbs limited to the affected myotome. Different Phenotypes and Classification Dr. Rosenblum discusses different phenotypes of postherpetic neuralgia and how phenotyping can determine treatment. He explains that there are several ways to classify the phenotypes, with one categorizing patients into three subtypes: sensory loss (most common), thermal gain, and thermal loss with mechanical gain. Dr. Rosenblum describes the mechanistic categorization, including the irritable nociceptive phenotype characterized by preserved sensation, profound dynamic mechanical allodynia, reduced pressure pain threshold, and relief with local anesthetic infiltration. Deafferentation Phenotype Dr. Rosenblum explains that a deafferentation phenotype may arise from destruction of neurons by the virus in the dorsal root ganglion. This phenotype is characterized by sensory loss, including thermal and vibratory sensation without prominent thermal allodynia. He notes that mechanical allodynia can occur secondary to A-beta fibers activating spinothalamic pathways (known as phenotypic switches), along with pressure hyperalgesia and temporal summation suggesting central sensitization. Dr. Rosenblum mentions that in one study, this phenotype was present in 10.8% of individuals, and for those with deafferentation pain, gabapentinoids, antidepressants, and neuromodulatory therapies like repetitive transcranial magnetic stimulation may be beneficial. Diagnosis and Physical Examination Dr. Rosenblum discusses the diagnosis of herpes zoster and postherpetic neuralgia, emphasizing the importance of physical examination. He explains that diagnosis is based on the rash, redness, papules, and vesicles in the painful dermatomes, with healing vesicles showing crust formation. Dr. Rosenblum notes that the rash is generally unilateral and does not cross the midline of the body. In postherpetic neuralgia patients, he mentions that scarring, hyper or hypopigmentation is often visible, with allodynia present in 45-75% of affected patients. Sensory Testing and Assessment Dr. Rosenblum explains that in patients with postherpetic neuralgia, a mosaic of somatosensory alterations can occur, manifesting as hyperalgesia, allodynia, and sensory loss. These can be quantified by quantitative sensory testing, which assesses somatosensory functions, dermal detection thresholds for perception of cold, warmth, and paradoxical heat sensations. He notes that testing can provide clues regarding underlying mechanisms of pain, impaired conditioned pain modulation, temporal summation suggesting central sensitization, and information about the type of nerve damage and surviving afferent neurons. Prevention Through Vaccination Dr. Rosenblum discusses prevention of acute herpes zoster through vaccination, noting that the risk increases with reduced immunity. He highlights studies evaluating Shingrix, a vaccine for herpes zoster, which showed 97% effectiveness in preventing herpes zoster in patients 50-69 years old with healthy immune systems and 89% effectiveness in patients over 70. Dr. Rosenblum states that Shingrix is 89-91% effective in preventing postherpetic neuralgia development in patients with healthy immune systems and 68-91% effective in those with weakened or underlying conditions. Treatment Objectives Dr. Rosenblum outlines the treatment objectives for herpes zoster and postherpetic neuralgia. For acute herpes zoster, objectives include relieving pain, reducing severity and duration of pain, accelerating recovery of epidermal defects, and preventing secondary infections. For postherpetic neuralgia, the objectives are pain alleviation and improved quality of life. Dr. Rosenblum lists available treatments including psychotherapy, opiates, antidepressants, antiepileptics, NMDA antagonists, topical agents, and interventional treatments such as epidurals, pulsed radiofrequency, nerve blocks, and spinal cord stimulation. Antiviral Medications Dr. Rosenblum emphasizes that antiviral drugs should be started within 72 hours of clinical onset, mentioning famciclovir, valacyclovir, and acyclovir. He notes there is no evidence for effectiveness after 72 hours in patients with uncomplicated herpes zoster. Dr. Rosenblum provides dosing information: for immunocompetent patients, famciclovir 500mg and valacyclovir 1000mg three times daily for seven days; for immunocompromised patients, famciclovir 1000mg three times daily for 10 days, while acyclovir should be given IV in the immunocompromised. Benefits of Antiviral Therapy Dr. Rosenblum explains that antiviral medication accelerates the disappearance of vesicles and crusts, promotes healing of skin lesions, and prevents new lesions from forming. By inhibiting viral replication, he notes that antiviral therapy likely reduces nerve damage, resulting in reduced incidence of postherpetic neuralgia, and should be started as soon as possible. Corticosteroids and Opioids Dr. Rosenblum discusses the use of corticosteroids, noting that when added to antiviral medications, they may reduce the severity of acute herpes zoster-related pain, though increased healing of skin lesions was not observed in one study. He mentions that a Cochrane review found oral corticosteroids ineffective in preventing postherpetic neuralgia. Regarding opioids, Dr. Rosenblum states they are commonly used alongside antivirals for controlling acute herpes zoster pain, with tramadol having a number needed to treat (NNT) of 4.7 and strong opioids having an NNT of 4.3 for 50% pain reduction. Methadone and Antidepressants Dr. Rosenblum discusses methadone as an NMDA receptor antagonist used in acute and chronic pain management, though he notes there are no randomized controlled trials determining its efficacy in acute herpes zoster pain or postherpetic neuralgia. He explains that methadone can modulate pain stimuli by inhibiting the uptake of norepinephrine and serotonin, resulting in decreased development of hyperalgesia and opioid tolerance, but has side effects including constipation, nausea, sedation, and QT prolongation that can trigger torsades de pointes. Dr. Rosenblum identifies antidepressants as first-line therapy for postherpetic neuralgia, including tricyclics and SNRIs, with tricyclics having an NNT of 3 and SNRIs an NNT of 6.4 for 50% pain reduction. Antiepileptics and Pharmacological Treatment Summary Dr. Rosenblum discusses antiepileptics like gabapentin and pregabalin for postherpetic neuralgia. He cites two trials measuring gabapentin's effect, concluding it was effective compared to placebo with a pooled NNT of 4.4, while pregabalin had an NNT of 4.9. Dr. Rosenblum summarizes that pharmacological treatment is well established for subacute herpes zoster pain, though new high-quality evidence has been lacking since the last update in 2011. Topical Agents Dr. Rosenblum discusses local anesthetic topical agents including lidocaine and capsaicin creams and patches. He notes that 8% capsaicin provided significant pain reduction during 2-8 weeks, while 5% lidocaine patches provided moderate pain relief after eight weeks of treatment. Dr. Rosenblum also mentions acute herpes zoster intracutaneous injections, citing a study where single intracutaneous injection with methylprednisolone combined with ropivacaine versus saline alone showed significant difference in VAS score at 1 and 4 weeks post-intervention favoring the intervention group. Intracutaneous Injections Dr. Rosenblum discusses the effect of repetitive intracutaneous injections with ropivacaine and methylprednisolone every 48 hours for one week. He cites a randomized control trial comparing antivirals plus analgesics to antivirals plus analgesics and repeat injections, finding the intervention group had significantly shorter duration of pain, lower VAS scores, and lower incidence of postherpetic neuralgia (6.4% vs 28% at 3 months). Dr. Rosenblum notes that a potential side effect of cutaneous methylprednisolone injection is fat atrophy, though this wasn't reported in the study. Summary of Local Anesthetics Dr. Rosenblum summarizes that there are no new studies reporting the efficacy of capsaicin 8% for postherpetic neuralgia, but it remains widely used in clinical practice and is approved in several countries. He notes that lidocaine patches can reduce pain intensity in patients with postherpetic neuralgia but may be more beneficial in patients with allodynia. Dr. Rosenblum adds that intracutaneous injections may be helpful for short periods, while repetitive injections with local anesthetics may reduce VAS scores for up to six months but can cause subcutaneous fat atrophy. Interventional Treatments: Epidural and Paravertebral Injections Dr. Rosenblum discusses interventional treatments, noting that previous guidelines found epidural injection with corticosteroids and local anesthetic as add-on therapy superior to standard care alone for up to one month in managing acute herpes zoster pain. He mentions a randomized controlled trial showing no difference between interlaminar and transforaminal epidural steroid injections for up to three months after the procedure. Dr. Rosenblum adds that previous guidelines reported high-quality evidence that paravertebral injections of corticosteroids or local anesthetic reduces pain in the active phase of herpes zoster. Comparative Studies on Injection Approaches Dr. Rosenblum discusses a trial comparing efficacy of repetitive paravertebral blocks with ropivacaine versus dexmedetomidine to prevent postherpetic neuralgia, which showed significantly lower incidence of zoster-related pain one month after therapy in the dexmedetomidine group, with effects still significant at three months. He also mentions a study comparing steroid injections administered via interlaminar versus transforaminal approaches, finding both groups had significantly lower VAS scores at 1 and 3 months follow-up compared to baseline, though this could align with the natural course of herpes zoster. Timing of Interventions and Continuous Epidural Blockade Dr. Rosenblum cites a retrospective study showing that transforaminal epidural injections administered for acute herpes zoster-related pain were associated with significantly shorter time to pain relief compared to those performed in the subacute phase. He also mentions a randomized controlled trial finding that continuous epidural blockade combined with opioids and gabapentin reduced NRS pain scores more than analgesic drug treatments alone during three-day follow-up, though both studies were low-quality. Interventions for Postherpetic Neuralgia Dr. Rosenblum discusses interventions specifically for postherpetic neuralgia, citing a small randomized controlled trial that demonstrated decreased NRS pain scores six months post-treatment for repeat versus single epidural steroid injections (15mg vs 5mg dexamethasone) administered over 24 days. The trial also found increased likelihood of complete remission during 6-month follow-up in the group receiving repeat epidural dexamethasone, though this was low-quality evidence. Summary of Epidural and Paravertebral Injections Dr. Rosenblum summarizes that epidural or paravertebral injections of local anesthetic and/or glucocorticoids could be considered in treating acute herpes zoster-related pain. For subacute postherpetic neuralgia pain, he notes low-quality evidence supporting epidural injections, while for postherpetic neuralgia, evidence supports continuous epidural infusion, though also of low quality. Dr. Rosenblum emphasizes that none of the included studies for postherpetic neuralgia investigating epidural or paravertebral injections resulted in decreased pain compared to standard therapy. Pulsed Radiofrequency (PRF) Evidence Dr. Rosenblum discusses pulsed radiofrequency (PRF), noting that previous guidelines indicated moderate quality evidence that PRF of the intercostal nerve reduces pain for 6 months in patients with postherpetic neuralgia, and very low-quality evidence that PRF to the dorsal root ganglion (DRG) reduces pain for 6 months. He mentions that multiple studies have been published since then assessing PRF efficacy. PRF Studies for Acute Herpes Zoster Dr. Rosenblum discusses a randomized controlled trial with 60 patients comparing high-voltage bipolar PRF of the cervical sympathetic chain versus sham, with treatment repeated after three days in both groups. He reports that VAS scores in the PRF group at each post-interventional point (1 day, 2 days, 1 month, 2 months, 3 months) were significantly lower than in the sham group, and at 3 months, the incidence of postherpetic neuralgia was 16.7% in the PRF group compared to 40% in the sham group. PRF for Trigeminal Neuralgia Dr. Rosenblum cites another randomized controlled trial evaluating high-voltage long-duration PRF of the Gasserian ganglion in 96 patients with subacute herpes-related trigeminal neuralgia, which found decreased VAS pain scores at all post-interventional time points (3, 7, 14 days and 1, 3, and 6 months) compared to the sham group. He also mentions a randomized comparative effectiveness study in 120 patients with subacute trigeminal herpes zoster, comparing a single application of high-voltage PRF to the Gasserian ganglion versus three cycles of conventional PRF treatment, finding significantly lower mean VAS pain scores for up to six months in the high-voltage PRF group. PRF Compared to Other Interventions Dr. Rosenblum discusses a randomized controlled trial comparing PRF to short-term spinal cord stimulation, which found decreased pain and improved 36-item short-form health survey scores in both groups at six months. He also mentions a randomized controlled trial in 72 patients where PRF of spinal nerves or peripheral branches of cranial nerves combined with five-day infusion of IV lidocaine resulted in greater pain reduction, less rescue analgesia, and reduced inflammatory cytokines at two months compared to PRF with saline infusions. Dr. Rosenblum notes a major limitation of this study was not accounting for the high natural recovery rate. Summary of PRF and Final Recommendations Dr. Rosenblum summarizes that PRF provides significant pain relief lasting over three months in patients with subacute herpes zoster and postherpetic neuralgia. He notes that since few studies have compared PRF versus sham, it's not possible to calculate an accurate number needed to treat. Dr. Rosenblum mentions there are no comparative studies comparing PRF to the intercostal nerves versus PRF of the DRG, but both preclinical and clinical studies suggest superiority of the DRG approach. He adds that evidence for spinal cord stimulation for postherpetic neuralgia is of low quality, and more research is needed given its invasive nature. Sympathetic Blocks and Conclusion Dr. Rosenblum notes there is low-quality evidence for using sympathetic blocks to treat acute herpes zoster-related pain, but no evidence for their use in postherpetic neuralgia. He mentions that risks of treatment with intrathecal methylprednisolone are unclear and therefore not recommended. Dr. Rosenblum concludes by praising the comprehensive article he's been discussing and mentions it provides insight for treating his patients, including a recent case of trigeminal postherpetic neuralgia. Personal Clinical Approach and Closing Dr. Rosenblum shares that he doesn't currently perform PRF in his practice, partly because it's not standard of care and not well reimbursed, creating barriers to implementation. However, he notes that PRF is a very safe procedure as it doesn't involve burning tissue. For his patient with trigeminal neuralgia pain, Dr. Rosenblum plans to try a topical sphenopalatine ganglion block as the least invasive intervention before considering injecting the trigeminal nerves at the foramen, in addition to pharmacotherapy. He concludes by thanking listeners, encouraging them to check the show notes and links, mentioning institutional memberships and shadowing opportunities, and asking listeners to rate and share the podcast. Q&A No Q&A session in this lecture Pain Management Board Prep   Ultrasound Training REGISTER TODAY!   Create an Account and get Free Access to the PainExam- NRAP Academy Community Highlights     David Rosenblum, MD, currently serves as the Director of Pain Management at Maimonides Medical Center and AABP Integrative Pain Care.  As a member of the Department of Anesthesiology, he is involved in teaching, research, CME activities, and was key faculty in developing the anesthesiology residency's regional anesthesia block rotation, as well as institutional wide acute and chronic pain management protocols to ensure safe and effective pain management. He currently is a managing partner in a multi-physician private pain practice, AABP Integrative Pain Care, located in Brooklyn, NY. He is one of the earliest interventional pain physicians to integrate ultrasound guidance to improve the safety and accuracy of interventional pain procedures.   Awards New York Magazine: Top Doctors: 2016, 2017, 2018, 2021, 2022, 2023, 2024, 2025 Schneps Media: 2015, 2016, 2017, 2019, 2020 Top Doctors New York Metro Area (digital guide): 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023 2025 Schneps Media - Brooklyn Courier Life: 2021, 2022, 2023   Dr. Rosenblum written several book chapters on Peripheral Neuromodulation, Radiofrequency Ablation, and Pharmacology.  He has published numerous noteworthy articles and most recently is developing the ASIPP Guidelines for Peripheral Neuromodulation in the treatment of chronic pain. He has been named several times in NY Magazine's Best Pain Management Doctor List, Nassau County's Best Pain Physician, has appeared on NY1 News, and has made several appearances on XM Radio's Doctor Talk. He currently is lecturing on a national and international level and has partnered with the American Society of Interventional Pain Physicians (ASIPP), American Society of Pain and Neuroscience (ASPN), IASP Mexican Chapter, Eastern Pain Association (EPA), the North American Neuromodulation Society (NANS), World Academy of Pain Medicine United, as well as various other organizations, to support educational events and develop new courses. Since 2008, he has helped over 3000 physicians pass the Pain Management Boards, and has been at the forefront of utilizing ultrasound guidance to perform pain procedures.  He now hosts the PainExam podcast, AnesthesiaExam Podcast, PMRExam Podcasts and uses this platform to promote the safe and effective use of ultrasound in the performance of various procedures such as Peripheral Nerve Stimulation, Caudal Epidurals, Selective Nerve Root Blocks, Cluneal Nerve Blocks, Ganglion impar Blocks, Stellate Ganglion Blocks, Brachial Plexus Blocks, Joint Injections and much more!   Doctor Rosenblum created the NRAP (Neuromodulation Regional Anesthesia and Pain) Academy  and travels to teach various courses focused on Pain Medicine, Regenerative Medicine, Ultrasound Guided Pain Procedures and Regional Anesthesia Techniques.  Dr. Rosenblum is persistent when it comes to eliminating pain and has gained a reputation among his patients for thinking "outside the box" and implements ultrasound guidance to deposit medications, biologics (PRP, Bone Marrow Aspirate, etc.) and Peripheral Nerve Stimulators near pain generators. He is currently treating patients in his great neck and Brooklyn office.  For an appointment go to AABPpain.com or call Brooklyn     718 436 7246 Reference Adriaansen, E. J., Jacobs, J. G., Vernooij, L. M., van Wijck, A. J., Cohen, S. P., Huygen, F. J., & Rijsdijk, M. (2025). 8. Herpes zoster and post herpetic neuralgia. Pain Practice, 25(1), e13423.

Summary In this episode of the Pain Exam Podcast, Dr. David Rosenblum provides a comprehensive review of herpes zoster and postherpetic neuralgia (PHN), focusing on pathophysiology, diagnosis, and treatment options. Dr. Rosenblum explains that postherpetic neuralgia affects approximately 25% of patients with acute herpes zoster, causing debilitating unilateral chronic pain in one or more dermatomes. He discusses the three phases of herpes zoster: acute (up to 30 days), subacute (up to 3 months), and postherpetic neuralgia (pain continuing beyond 3 months). Dr. Rosenblum identifies risk factors for developing PHN, including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. He details the pathophysiology involving peripheral and central sensitization, and explains different phenotypes of PHN that can guide treatment approaches. For treatment, Dr. Rosenblum reviews various options including antiviral medications (which should be started within 72 hours of onset), corticosteroids, opioids, antidepressants (particularly tricyclics and SNRIs), antiepileptics (gabapentin and pregabalin), topical agents (lidocaine and capsaicin), and interventional procedures such as epidural injections and pulsed radiofrequency. He emphasizes that prevention through vaccination with Shingrix is highly effective, with 97% effectiveness in preventing herpes zoster in patients 50-69 years old and 89% effectiveness in those over 70. Dr. Rosenblum mentions that he's currently treating a patient with trigeminal postherpetic neuralgia and is considering a topical sphenopalatine ganglion block as a minimally invasive intervention before attempting more invasive procedures. Chapters Introduction to the Pain Exam Podcast and Topic Overview Dr. David Rosenblum introduces the Pain Exam Podcast, mentioning that it covers painful disorders, alternative treatments, and practice management. He explains that this episode focuses on herpes zoster and postherpetic neuralgia as board preparation for fellows starting their programs, with ABA boards coming up in September. Dr. Rosenblum notes that he's not only preparing listeners for boards but also seeking the latest information to help treat his own patients with this notoriously difficult disease. Upcoming Conferences and Educational Opportunities Dr. Rosenblum announces several upcoming conferences including Aspen in July, Pain Week in September, and events with NYSIP and the Latin American Pain Society. He mentions he'll be teaching ultrasound and regenerative medicine at these events. Dr. Rosenblum invites listeners to sign up at nrappain.org to access a community discussing regenerative medicine, ultrasound-guided pain medicine, regional anesthesia, and board preparation. He also offers ultrasound training in New York and elsewhere, with upcoming sessions in Manhattan on July 12th and October 4th, plus private shadowing opportunities. Overview of Postherpetic Neuralgia Dr. Rosenblum defines postherpetic neuralgia as typically a unilateral chronic pain in one or more dermatomes after acute herpes zoster infection. He states that the incidence of acute herpes zoster ranges between 3-5 patients per thousand person-years, and one in four patients with acute herpes zoster-related pain will transition into postherpetic neuralgia. Dr. Rosenblum emphasizes that while this condition won't kill patients, it can be extremely debilitating and significantly reduce quality of life. Treatment Options Overview Dr. Rosenblum reviews treatment options according to the WHO pain ladder, including tricyclics like nortriptyline and antiepileptic drugs such as gabapentin. He explains that if pain is not significantly reduced, interventional treatments like epidural injections with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion are options. For postherpetic neuralgia specifically, Dr. Rosenblum notes that preferred treatments include transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. Phases of Herpes Zoster and Definitions Dr. Rosenblum outlines the three phases during herpes zoster reactivation: acute herpes zoster-related pain (lasting maximum 30 days), subacute herpes zoster-related pain (pain after healing of vesicles but disappearing within 3 months), and postherpetic neuralgia (typically defined as pain continuing after 3 months). He mentions that acute herpes zoster pain often begins with prodromal pain starting a few days before the appearance of the rash. Incidence and Risk Factors Dr. Rosenblum states that the incidence of herpes zoster ranges between 3-5 patients per 1,000 person-years, with approximately 5-30% of cases leading to postherpetic neuralgia. He identifies risk factors including older age, female sex, immunosuppression, prodromal pain, severe rash, and greater acute pain severity. Dr. Rosenblum describes the clinical manifestations as a mosaic of somatosensory symptoms including burning, deep aching pain, tingling, itching, stabbing, often associated with tactile and cold allodynia. Impact on Quality of Life Dr. Rosenblum emphasizes that postherpetic neuralgia can be debilitating, impacting both physical and emotional functioning and causing decreased quality of life. He notes that it leads to fatigue, insomnia, depression, anorexia, anxiety, and emotional distress. Dr. Rosenblum stresses the importance of exploring methods for prevention of postherpetic neuralgia and optimizing pain treatment for both subacute herpes zoster-related pain and postherpetic neuralgia. Literature Review and Pathophysiology Dr. Rosenblum mentions that he's discussing a literature review from 2024 that updates previous practical guidelines published in 2011. He explains the pathophysiology of postherpetic neuralgia, which involves sensitization of peripheral and sensory nerves from damage. Dr. Rosenblum describes how inflammatory mediators reduce the stimulus threshold of nociceptors and increase responsiveness, resulting in pathological spontaneous discharges, lower thresholds for thermal and mechanical stimuli, and hyperalgesia. Central Sensitization and Nerve Damage Dr. Rosenblum explains that central sensitization results from peripheral nociceptor hyperactivity leading to plastic changes in the central nervous system, involving amplification of pain signals and reduced inhibition. He describes how nerve damage in postherpetic neuralgia patients results from neuronal death due to severe inflammatory stimuli or secondary to neuronal swelling. Dr. Rosenblum notes that motor defects occur in 0.05% of patients with herpes zoster, observed as abdominal pseudohernias or motor weakness of limbs limited to the affected myotome. Different Phenotypes and Classification Dr. Rosenblum discusses different phenotypes of postherpetic neuralgia and how phenotyping can determine treatment. He explains that there are several ways to classify the phenotypes, with one categorizing patients into three subtypes: sensory loss (most common), thermal gain, and thermal loss with mechanical gain. Dr. Rosenblum describes the mechanistic categorization, including the irritable nociceptive phenotype characterized by preserved sensation, profound dynamic mechanical allodynia, reduced pressure pain threshold, and relief with local anesthetic infiltration. Deafferentation Phenotype Dr. Rosenblum explains that a deafferentation phenotype may arise from destruction of neurons by the virus in the dorsal root ganglion. This phenotype is characterized by sensory loss, including thermal and vibratory sensation without prominent thermal allodynia. He notes that mechanical allodynia can occur secondary to A-beta fibers activating spinothalamic pathways (known as phenotypic switches), along with pressure hyperalgesia and temporal summation suggesting central sensitization. Dr. Rosenblum mentions that in one study, this phenotype was present in 10.8% of individuals, and for those with deafferentation pain, gabapentinoids, antidepressants, and neuromodulatory therapies like repetitive transcranial magnetic stimulation may be beneficial. Diagnosis and Physical Examination Dr. Rosenblum discusses the diagnosis of herpes zoster and postherpetic neuralgia, emphasizing the importance of physical examination. He explains that diagnosis is based on the rash, redness, papules, and vesicles in the painful dermatomes, with healing vesicles showing crust formation. Dr. Rosenblum notes that the rash is generally unilateral and does not cross the midline of the body. In postherpetic neuralgia patients, he mentions that scarring, hyper or hypopigmentation is often visible, with allodynia present in 45-75% of affected patients. Sensory Testing and Assessment Dr. Rosenblum explains that in patients with postherpetic neuralgia, a mosaic of somatosensory alterations can occur, manifesting as hyperalgesia, allodynia, and sensory loss. These can be quantified by quantitative sensory testing, which assesses somatosensory functions, dermal detection thresholds for perception of cold, warmth, and paradoxical heat sensations. He notes that testing can provide clues regarding underlying mechanisms of pain, impaired conditioned pain modulation, temporal summation suggesting central sensitization, and information about the type of nerve damage and surviving afferent neurons. Prevention Through Vaccination Dr. Rosenblum discusses prevention of acute herpes zoster through vaccination, noting that the risk increases with reduced immunity. He highlights studies evaluating Shingrix, a vaccine for herpes zoster, which showed 97% effectiveness in preventing herpes zoster in patients 50-69 years old with healthy immune systems and 89% effectiveness in patients over 70. Dr. Rosenblum states that Shingrix is 89-91% effective in preventing postherpetic neuralgia development in patients with healthy immune systems and 68-91% effective in those with weakened or underlying conditions. Treatment Objectives Dr. Rosenblum outlines the treatment objectives for herpes zoster and postherpetic neuralgia. For acute herpes zoster, objectives include relieving pain, reducing severity and duration of pain, accelerating recovery of epidermal defects, and preventing secondary infections. For postherpetic neuralgia, the objectives are pain alleviation and improved quality of life. Dr. Rosenblum lists available treatments including psychotherapy, opiates, antidepressants, antiepileptics, NMDA antagonists, topical agents, and interventional treatments such as epidurals, pulsed radiofrequency, nerve blocks, and spinal cord stimulation. Antiviral Medications Dr. Rosenblum emphasizes that antiviral drugs should be started within 72 hours of clinical onset, mentioning famciclovir, valacyclovir, and acyclovir. He notes there is no evidence for effectiveness after 72 hours in patients with uncomplicated herpes zoster. Dr. Rosenblum provides dosing information: for immunocompetent patients, famciclovir 500mg and valacyclovir 1000mg three times daily for seven days; for immunocompromised patients, famciclovir 1000mg three times daily for 10 days, while acyclovir should be given IV in the immunocompromised. Benefits of Antiviral Therapy Dr. Rosenblum explains that antiviral medication accelerates the disappearance of vesicles and crusts, promotes healing of skin lesions, and prevents new lesions from forming. By inhibiting viral replication, he notes that antiviral therapy likely reduces nerve damage, resulting in reduced incidence of postherpetic neuralgia, and should be started as soon as possible. Corticosteroids and Opioids Dr. Rosenblum discusses the use of corticosteroids, noting that when added to antiviral medications, they may reduce the severity of acute herpes zoster-related pain, though increased healing of skin lesions was not observed in one study. He mentions that a Cochrane review found oral corticosteroids ineffective in preventing postherpetic neuralgia. Regarding opioids, Dr. Rosenblum states they are commonly used alongside antivirals for controlling acute herpes zoster pain, with tramadol having a number needed to treat (NNT) of 4.7 and strong opioids having an NNT of 4.3 for 50% pain reduction. Methadone and Antidepressants Dr. Rosenblum discusses methadone as an NMDA receptor antagonist used in acute and chronic pain management, though he notes there are no randomized controlled trials determining its efficacy in acute herpes zoster pain or postherpetic neuralgia. He explains that methadone can modulate pain stimuli by inhibiting the uptake of norepinephrine and serotonin, resulting in decreased development of hyperalgesia and opioid tolerance, but has side effects including constipation, nausea, sedation, and QT prolongation that can trigger torsades de pointes. Dr. Rosenblum identifies antidepressants as first-line therapy for postherpetic neuralgia, including tricyclics and SNRIs, with tricyclics having an NNT of 3 and SNRIs an NNT of 6.4 for 50% pain reduction. Antiepileptics and Pharmacological Treatment Summary Dr. Rosenblum discusses antiepileptics like gabapentin and pregabalin for postherpetic neuralgia. He cites two trials measuring gabapentin's effect, concluding it was effective compared to placebo with a pooled NNT of 4.4, while pregabalin had an NNT of 4.9. Dr. Rosenblum summarizes that pharmacological treatment is well established for subacute herpes zoster pain, though new high-quality evidence has been lacking since the last update in 2011. Topical Agents Dr. Rosenblum discusses local anesthetic topical agents including lidocaine and capsaicin creams and patches. He notes that 8% capsaicin provided significant pain reduction during 2-8 weeks, while 5% lidocaine patches provided moderate pain relief after eight weeks of treatment. Dr. Rosenblum also mentions acute herpes zoster intracutaneous injections, citing a study where single intracutaneous injection with methylprednisolone combined with ropivacaine versus saline alone showed significant difference in VAS score at 1 and 4 weeks post-intervention favoring the intervention group. Intracutaneous Injections Dr. Rosenblum discusses the effect of repetitive intracutaneous injections with ropivacaine and methylprednisolone every 48 hours for one week. He cites a randomized control trial comparing antivirals plus analgesics to antivirals plus analgesics and repeat injections, finding the intervention group had significantly shorter duration of pain, lower VAS scores, and lower incidence of postherpetic neuralgia (6.4% vs 28% at 3 months). Dr. Rosenblum notes that a potential side effect of cutaneous methylprednisolone injection is fat atrophy, though this wasn't reported in the study. Summary of Local Anesthetics Dr. Rosenblum summarizes that there are no new studies reporting the efficacy of capsaicin 8% for postherpetic neuralgia, but it remains widely used in clinical practice and is approved in several countries. He notes that lidocaine patches can reduce pain intensity in patients with postherpetic neuralgia but may be more beneficial in patients with allodynia. Dr. Rosenblum adds that intracutaneous injections may be helpful for short periods, while repetitive injections with local anesthetics may reduce VAS scores for up to six months but can cause subcutaneous fat atrophy. Interventional Treatments: Epidural and Paravertebral Injections Dr. Rosenblum discusses interventional treatments, noting that previous guidelines found epidural injection with corticosteroids and local anesthetic as add-on therapy superior to standard care alone for up to one month in managing acute herpes zoster pain. He mentions a randomized controlled trial showing no difference between interlaminar and transforaminal epidural steroid injections for up to three months after the procedure. Dr. Rosenblum adds that previous guidelines reported high-quality evidence that paravertebral injections of corticosteroids or local anesthetic reduces pain in the active phase of herpes zoster. Comparative Studies on Injection Approaches Dr. Rosenblum discusses a trial comparing efficacy of repetitive paravertebral blocks with ropivacaine versus dexmedetomidine to prevent postherpetic neuralgia, which showed significantly lower incidence of zoster-related pain one month after therapy in the dexmedetomidine group, with effects still significant at three months. He also mentions a study comparing steroid injections administered via interlaminar versus transforaminal approaches, finding both groups had significantly lower VAS scores at 1 and 3 months follow-up compared to baseline, though this could align with the natural course of herpes zoster. Timing of Interventions and Continuous Epidural Blockade Dr. Rosenblum cites a retrospective study showing that transforaminal epidural injections administered for acute herpes zoster-related pain were associated with significantly shorter time to pain relief compared to those performed in the subacute phase. He also mentions a randomized controlled trial finding that continuous epidural blockade combined with opioids and gabapentin reduced NRS pain scores more than analgesic drug treatments alone during three-day follow-up, though both studies were low-quality. Interventions for Postherpetic Neuralgia Dr. Rosenblum discusses interventions specifically for postherpetic neuralgia, citing a small randomized controlled trial that demonstrated decreased NRS pain scores six months post-treatment for repeat versus single epidural steroid injections (15mg vs 5mg dexamethasone) administered over 24 days. The trial also found increased likelihood of complete remission during 6-month follow-up in the group receiving repeat epidural dexamethasone, though this was low-quality evidence. Summary of Epidural and Paravertebral Injections Dr. Rosenblum summarizes that epidural or paravertebral injections of local anesthetic and/or glucocorticoids could be considered in treating acute herpes zoster-related pain. For subacute postherpetic neuralgia pain, he notes low-quality evidence supporting epidural injections, while for postherpetic neuralgia, evidence supports continuous epidural infusion, though also of low quality. Dr. Rosenblum emphasizes that none of the included studies for postherpetic neuralgia investigating epidural or paravertebral injections resulted in decreased pain compared to standard therapy. Pulsed Radiofrequency (PRF) Evidence Dr. Rosenblum discusses pulsed radiofrequency (PRF), noting that previous guidelines indicated moderate quality evidence that PRF of the intercostal nerve reduces pain for 6 months in patients with postherpetic neuralgia, and very low-quality evidence that PRF to the dorsal root ganglion (DRG) reduces pain for 6 months. He mentions that multiple studies have been published since then assessing PRF efficacy. PRF Studies for Acute Herpes Zoster Dr. Rosenblum discusses a randomized controlled trial with 60 patients comparing high-voltage bipolar PRF of the cervical sympathetic chain versus sham, with treatment repeated after three days in both groups. He reports that VAS scores in the PRF group at each post-interventional point (1 day, 2 days, 1 month, 2 months, 3 months) were significantly lower than in the sham group, and at 3 months, the incidence of postherpetic neuralgia was 16.7% in the PRF group compared to 40% in the sham group. PRF for Trigeminal Neuralgia Dr. Rosenblum cites another randomized controlled trial evaluating high-voltage long-duration PRF of the Gasserian ganglion in 96 patients with subacute herpes-related trigeminal neuralgia, which found decreased VAS pain scores at all post-interventional time points (3, 7, 14 days and 1, 3, and 6 months) compared to the sham group. He also mentions a randomized comparative effectiveness study in 120 patients with subacute trigeminal herpes zoster, comparing a single application of high-voltage PRF to the Gasserian ganglion versus three cycles of conventional PRF treatment, finding significantly lower mean VAS pain scores for up to six months in the high-voltage PRF group. PRF Compared to Other Interventions Dr. Rosenblum discusses a randomized controlled trial comparing PRF to short-term spinal cord stimulation, which found decreased pain and improved 36-item short-form health survey scores in both groups at six months. He also mentions a randomized controlled trial in 72 patients where PRF of spinal nerves or peripheral branches of cranial nerves combined with five-day infusion of IV lidocaine resulted in greater pain reduction, less rescue analgesia, and reduced inflammatory cytokines at two months compared to PRF with saline infusions. Dr. Rosenblum notes a major limitation of this study was not accounting for the high natural recovery rate. Summary of PRF and Final Recommendations Dr. Rosenblum summarizes that PRF provides significant pain relief lasting over three months in patients with subacute herpes zoster and postherpetic neuralgia. He notes that since few studies have compared PRF versus sham, it's not possible to calculate an accurate number needed to treat. Dr. Rosenblum mentions there are no comparative studies comparing PRF to the intercostal nerves versus PRF of the DRG, but both preclinical and clinical studies suggest superiority of the DRG approach. He adds that evidence for spinal cord stimulation for postherpetic neuralgia is of low quality, and more research is needed given its invasive nature. Sympathetic Blocks and Conclusion Dr. Rosenblum notes there is low-quality evidence for using sympathetic blocks to treat acute herpes zoster-related pain, but no evidence for their use in postherpetic neuralgia. He mentions that risks of treatment with intrathecal methylprednisolone are unclear and therefore not recommended. Dr. Rosenblum concludes by praising the comprehensive article he's been discussing and mentions it provides insight for treating his patients, including a recent case of trigeminal postherpetic neuralgia. Personal Clinical Approach and Closing Dr. Rosenblum shares that he doesn't currently perform PRF in his practice, partly because it's not standard of care and not well reimbursed, creating barriers to implementation. However, he notes that PRF is a very safe procedure as it doesn't involve burning tissue. For his patient with trigeminal neuralgia pain, Dr. Rosenblum plans to try a topical sphenopalatine ganglion block as the least invasive intervention before considering injecting the trigeminal nerves at the foramen, in addition to pharmacotherapy. He concludes by thanking listeners, encouraging them to check the show notes and links, mentioning institutional memberships and shadowing opportunities, and asking listeners to rate and share the podcast. Q&A No Q&A session in this lecture Pain Management Board Prep   Ultrasound Training REGISTER TODAY!   Create an Account and get Free Access to the PainExam- NRAP Academy Community Highlights     David Rosenblum, MD, currently serves as the Director of Pain Management at Maimonides Medical Center and AABP Integrative Pain Care.  As a member of the Department of Anesthesiology, he is involved in teaching, research, CME activities, and was key faculty in developing the anesthesiology residency's regional anesthesia block rotation, as well as institutional wide acute and chronic pain management protocols to ensure safe and effective pain management. He currently is a managing partner in a multi-physician private pain practice, AABP Integrative Pain Care, located in Brooklyn, NY. He is one of the earliest interventional pain physicians to integrate ultrasound guidance to improve the safety and accuracy of interventional pain procedures.   Awards New York Magazine: Top Doctors: 2016, 2017, 2018, 2021, 2022, 2023, 2024, 2025 Schneps Media: 2015, 2016, 2017, 2019, 2020 Top Doctors New York Metro Area (digital guide): 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023 2025 Schneps Media - Brooklyn Courier Life: 2021, 2022, 2023   Dr. Rosenblum written several book chapters on Peripheral Neuromodulation, Radiofrequency Ablation, and Pharmacology.  He has published numerous noteworthy articles and most recently is developing the ASIPP Guidelines for Peripheral Neuromodulation in the treatment of chronic pain. He has been named several times in NY Magazine's Best Pain Management Doctor List, Nassau County's Best Pain Physician, has appeared on NY1 News, and has made several appearances on XM Radio's Doctor Talk. He currently is lecturing on a national and international level and has partnered with the American Society of Interventional Pain Physicians (ASIPP), American Society of Pain and Neuroscience (ASPN), IASP Mexican Chapter, Eastern Pain Association (EPA), the North American Neuromodulation Society (NANS), World Academy of Pain Medicine United, as well as various other organizations, to support educational events and develop new courses. Since 2008, he has helped over 3000 physicians pass the Pain Management Boards, and has been at the forefront of utilizing ultrasound guidance to perform pain procedures.  He now hosts the PainExam podcast, AnesthesiaExam Podcast, PMRExam Podcasts and uses this platform to promote the safe and effective use of ultrasound in the performance of various procedures such as Peripheral Nerve Stimulation, Caudal Epidurals, Selective Nerve Root Blocks, Cluneal Nerve Blocks, Ganglion impar Blocks, Stellate Ganglion Blocks, Brachial Plexus Blocks, Joint Injections and much more!   Doctor Rosenblum created the NRAP (Neuromodulation Regional Anesthesia and Pain) Academy  and travels to teach various courses focused on Pain Medicine, Regenerative Medicine, Ultrasound Guided Pain Procedures and Regional Anesthesia Techniques.  Dr. Rosenblum is persistent when it comes to eliminating pain and has gained a reputation among his patients for thinking "outside the box" and implements ultrasound guidance to deposit medications, biologics (PRP, Bone Marrow Aspirate, etc.) and Peripheral Nerve Stimulators near pain generators. He is currently treating patients in his great neck and Brooklyn office.  For an appointment go to AABPpain.com or call Brooklyn     718 436 7246 Reference Adriaansen, E. J., Jacobs, J. G., Vernooij, L. M., van Wijck, A. J., Cohen, S. P., Huygen, F. J., & Rijsdijk, M. (2025). 8. Herpes zoster and post herpetic neuralgia. Pain Practice, 25(1), e13423.

In this episode, I sit down with Susannah Cahalan—American journalist and bestselling author of Brain on Fire, The Great Pretender, and most recently, The Acid Queen. We discuss her harrowing experience with anti-NMDA receptor encephalitis, a rare brain inflammation that led to seizures, vivid hallucinations and hospitalization during a month long psychotic episode. This ordeal that ultimately sparked her deep interest in psychology and neuroscience. Susannah also shares insights from her latest work, offering a compelling look into the life of Rosemary Woodruff Leary, a central figure in the 1960s psychedelic movement and the wife of Timothy Leary from 1967 to 1976. Check out our Merch⁠⁠⁠⁠⁠⁠⁠⁠ Follow us on:⁠⁠⁠⁠⁠⁠⁠⁠ Instagram⁠⁠⁠⁠⁠⁠⁠⁠,⁠⁠⁠⁠⁠⁠⁠⁠ TikTok⁠⁠⁠⁠⁠⁠⁠⁠,⁠⁠⁠⁠⁠⁠⁠⁠ Twitter⁠⁠⁠⁠⁠⁠⁠⁠ For business inquiries contact: OtherworldTeam@unitedtalent.com If you have experienced something paranormal or unexplained, email us your story at ⁠⁠⁠⁠⁠⁠⁠⁠stories@otherworldpod.com To learn more about listener data and our privacy practices visit: https://www.audacyinc.com/privacy-policy Learn more about your ad choices. Visit https://podcastchoices.com/adchoices

Aujourd'hui, je vous emmène dans un voyage fascinant à l'intérieur du cerveau...Un moment mystérieux que beaucoup ont vécu, mais que peu comprennent vraiment : l'anesthésie générale.Remontons un instant dans le passé.Le 16 octobre 1846, à Boston, au Massachusetts General Hospital, un dentiste du nom de William Morton réalise la première démonstration publique réussie d'une anesthésie générale à l'éther.Ce jour-là, un patient subit l'ablation d'une tumeur au cou... sans douleur, ni cri.Une révolution est née.Avant cela, la chirurgie relevait de l'épreuve de force : on opérait à vif, rapidement, et dans la souffrance.Depuis cette date, l'anesthésie générale a sauvé des millions de vies en rendant possibles des interventions longues, complexes… et indolores.Lorsque vous êtes allongé sur la table, une équipe vous entoure. Une seringue est connectée à votre bras, une substance s'écoule. Et, très vite... plus rien.Pas de rêve, pas de sensation, pas de douleur. Comme si l'on avait appuyé sur un bouton "off".Mais ce n'est pas un simple sommeil.Des études en imagerie cérébrale montrent que l'anesthésie ne mime pas le sommeil, mais provoque une déconnexion brutale entre les différentes zones du cerveau, notamment entre le thalamus – une sorte de centre de tri sensoriel – et le cortex, responsable de la conscience.Les signaux sensoriels n'arrivent plus à destination. Résultat : le cerveau ne perçoit plus le monde extérieur.Ce phénomène est orchestré par des molécules puissantes : propofol, kétamine, halogénés comme le sévoflurane… Ces agents anesthésiques modifient en profondeur la chimie cérébrale.Leur cible principale ? Les neurotransmetteurs, ces messagers chimiques entre les neurones.Parmi eux, le plus important ici s'appelle GABA, le grand régulateur de l'activité neuronale.Les molécules anesthésiques agissent comme des "amplificateurs" de ce neurotransmetteur.En se liant à ses récepteurs, elles renforcent son effet inhibiteur, ralentissant ou stoppant carrément la transmission des signaux nerveux.Résultat ?Le cerveau devient moins excitable, les réseaux de neurones cessent de communiquer efficacement entre eux, et l'activité cérébrale s'effondre progressivement, un peu comme si on plongeait un ordinateur en mode veille.Mais ce n'est pas tout.D'autres molécules anesthésiques comme la kétamine bloquent un autre récepteur fondamental : le NMDA, impliqué dans la transmission de la douleur et de la conscience.D'autres encore agissent sur des canaux ioniques, modifiant la façon dont les neurones échangent les signaux électriques.En clair : c'est tout un orchestre neurochimique qui est désorganisé volontairement, pour plonger le cerveau dans un état de silence contrôlé.Et pourtant, le cerveau n'est pas mort. Il continue de réguler la respiration, le rythme cardiaque, la température... comme s'il restait en mode automatique.Puis vient le réveil. Là encore, c'est mystérieux : certains patients mettent quelques secondes, d'autres plusieurs minutes.Le cerveau se reconnecte progressivement. Il n'est pas rare de se sentir confus, désorienté, voire agité dans les premières minutes.Et dans de très rares cas – un pour 15 000 environ – une conscience résiduelle peut persister pendant l'opération : on parle alors de conscience peropératoire.Le patient est paralysé, incapable de parler, mais entend ou ressent partiellement. Cela reste rare, mais suffisamment sérieux pour que les anesthésistes utilisent aujourd'hui des moniteurs de profondeur d'anesthésie. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

In this episode, we dive deep into the basics of anesthesia pharmacology—perfect for ICU nurses starting CRNA school or senior residents needing a solid refresher. We break down foundational topics like pharmacodynamics, pharmacokinetics, and pharmacogenomics, and explain why understanding physiology is key to mastering pharmacology. You'll learn about drug targets like GABA and NMDA receptors, and the real mechanisms behind anesthetics, opioids, local anesthetics, and muscle relaxants. We also walk through “top drawer drugs” in the OR, including quick quizzes to reinforce your understanding of real-time drug decisions—like when to choose ephedrine over phenylephrine. This is a science-heavy episode, but one that sets the groundwork for more advanced content.

Nerinetide is a neuroprotective eicosapeptide designed to reduce ischemic brain injury by disrupting the interaction between N-methyl-D-aspartate (NMDA) receptors and downstream excitotoxic signaling. It was tested in two major clinical trials for acute ischemic stroke: • ESCAPE-NEXT Trial: Assessed Nerinetide in patients undergoing endovascular thrombectomy (EVT) without prior thrombolysis, finding no significant improvement in functional independence at 90 days. • FRONTIER Trial: Evaluated prehospital Nerinetide administration within 3 hours of stroke onset, showing no overall benefit but potential efficacy in ischemic stroke patients receiving reperfusion therapy.   Although Nerinetide was safe, its clinical benefit remains uncertain, with timing and patient selection emerging as key factors for its potential role in stroke treatment. Further studies are needed to refine its use in combination with reperfusion therapies.

In this episode of the Addict to Athlete podcast, Coach Blu Robinson welcomes Dr. Faried Banimahd to discuss the complexities of ketamine therapy in the context of mental health and addiction recovery. They explore the history of ketamine, its medical uses, particularly in pain management and mental health treatment, and the implications of its recent popularity as a therapeutic option. Dr. B provides insights into the mechanisms of ketamine, its FDA approval for treatment-resistant depression, and the importance of caution in its use, especially for individuals with a history of substance abuse. The conversation emphasizes the need for a comprehensive approach to mental health treatment, integrating therapy with any pharmacological interventions. In this conversation, Blu Robinson and Dr. Faried Banimahd delve into the complexities of psychedelics, particularly ketamine, and their potential therapeutic benefits for mental health. They discuss the risks associated with psychedelics, personal experiences, and the importance of controlled environments for treatment. The conversation also highlights the stigma surrounding these substances, the necessity of ongoing treatment, and the role of medical professionals in guiding patients through their mental health journeys. Ultimately, they emphasize the need for a multidimensional approach to treatment and the importance of understanding individual experiences within the broader healthcare system. Takeaways Ketamine is chemically related to PCP and has a history of abuse. It is used as a disassociative anesthetic in medical settings. Ketamine's role in pain management is significant, especially for chronic pain patients. The FDA has approved ketamine for treatment-resistant depression under specific protocols. Ketamine works by blocking NMDA receptors, affecting pain perception and mood. Long-term efficacy of ketamine therapy is still under research and not well established. Caution is advised for individuals with a history of substance abuse when considering ketamine therapy. Matthew Perry's case highlights the risks associated with unsupervised ketamine use. Therapy should be the first line of treatment for depression, even when using ketamine. Meaningful existence and self-development take time and should not be rushed. People with a history of severe bipolar and schizophrenia should be cautious with psychedelics. Psychedelics can awaken dormant psychological issues. Personal experiences with psychedelics can lead to significant insights and awareness. The perception of psychedelics as dangerous hinders their therapeutic potential. Therapeutic environments are crucial for the safe use of psychedelics.   Dr. B YouTube · Dr.B36087.1K+ followersDr.B360 insta Instagram · getdrb2.4K+ followersAddiction Medicine (@getdrb) • Instagram photos and videos     Please join Addict to Athlete's Patreon support page and help us turn the mess of addiction into the message of sobriety! https://www.patreon.com/addicttoathlete Please visit our website for more information on Team Addict to Athlete and Addiction Recovery Podcasts. https://www.AddictToAthlete.org Join the Team! Circle, our new social support event, along with the team and athlete communication platform, is designed to help us break free from doom scrolling and shadow banning and foster stronger connections among us. Follow the link, download the app, and start this new chapter of Team AIIA! Join Circle https://a2a.circle.so/join?invitation_token=16daaa0d9ecd7421d384dd05a461464ce149cc9e-63d4aa30-1a67-4120-ae12-124791dfb519

OCD, or Obsessive Compulsive Disorder, is a debilitating condition that involves intrusive thoughts and time-consuming, repetitive behaviors. It impacts 80 million worldwide, 2-4% of the US population or 1 in 100 people here in the US.It can be difficult to overstate the suffering caused by OCD, not only for those with this condition but also for their family members. In addition to the distress caused by the obsessional thoughts and compulsions, there can be shame and loss - loss of more meaningful, purposeful, or pleasant thoughts and behaviors. and loss of time connecting with others or engaging in purposeful or enjoyable activities.Other conditions associated with obsessive-compulsive disorder include:* Body dysmorphic disorder* Skin picking* Trichotillomania (hair pulling)* Hoarding* Hypochondria* Olfactory reference syndrome (an irrational feeling or belief that one emits a foul smell and often attempts to remove the odor).It´s not unusual for someone with OCD to have other conditions, such as:* Other forms of anxiety* Depression* ADHD* Autism spectrum disorder* Eating disorders* TourettesResearch suggests that having OCD raises one´s vulnerability to developing dementia. Many other brain conditions, however, also appear to increase this vulnerability similarly.Treatment ChallengesOCD is particularly challenging to treat. Of those with OCD, 60% do not respond to typical therapies (often medication in combination with psychotherapy involving gradual exposure to that which is being avoided). Typical medications include:* SSRI´s (Selective Serotonin Reuptake Inhibitors) -e.g., sertraline, fluoxetine, fluvoxamine, citalopram, paroxetine* Tricyclic antidepressant - clomipramine* SNRI - (Serotonin and Norepinephrine Reuptake Inhibitor) - venlafaxine* Atypical antipsychotic medications are sometimes addedMedication is combined with CBT (Cognitive Behavioral Therapy), which involves exposure and response prevention, or CBT is used alone.As you can see, most medication approaches aim to increase serotonin activity. Serotonin, however, is just one of the neurotransmitters involved. What has become increasingly clear from the research is that OCD involves abnormal activity at the NMDA receptor - a glutamate receptor.NMDA & GlutamateThe NMDA receptor is found throughout the brain. Glutamate, the primary excitatory neurotransmitter in the central nervous system, binds to the NMDA receptor. NMDA and glutamate are involved in synaptic plasticity (creating neuronal connections), learning, memory, and motor function.The synapse is the space between communicating neurons. Presynaptic neurons release glutamate, which binds to the NMDA receptor on postsynaptic neurons. This results in a cascade of signaling events that lead to “neuronal excitation.” The problem arises when this receptor has too much (or too little) activity. In the case of OCD, there is too much activity.Implications* Dysregulation at the NMDA receptor appears to play a role in OCD, depression, PTSD, schizophrenia, bipolar disorder, and substance use disorders.* Weak memory extinction can result from high activity at the NMDA receptor. While memory is a good thing, we can have problems with too much memory - or rather, problems putting our memories aside. This can look like thoughts getting stuck, for example:* Intrusive thoughts in OCD* Flashbacks in PTSD* Delusions in psychotic disorders* Cravings in addiction.* Neurodegenerative disorders, such as Alzheimer's, Parkinson's, and ALS, have also been linked to NMDA receptor malfunction.Methylation & NMDAThose who are undermethylated, especially those with OCD or addictions, have high activity at the NMDA receptor. To remind you, undermethylation is a biochemical process with many functions, including the breakdown of histamine, support of detoxification, and support of serotonin activity. When someone is undermethylated, they can tend to have allergies (from high histamine), be perfectionistic, competitive, strong-willed, have obsessive-compulsive tendencies, be ritualistic, have dietary inflexibility, and have high accomplishment or have family members with high accomplishment. Undermethylation can contribute to the low serotonin activity seen in OCD. Simply addressing undermethylation, like merely addressing serotonin, will only bring partial benefit. To address undermethylation, those of us trained by the Walsh Research Institute, use SAMe and/or methionine, B12, B6, magnesium, and antioxidants. We address this before starting methylation treatment for those with high homocysteine. But how can we also decrease activity at the NMDA receptor?Blocking NMDA & Normalizing Glutamate ActivityEsketamine or Ketamine, which has been getting much attention in recent years, can impact the brain in various ways; however, its primary mechanism is as an NMDA blocker or antagonist. For some, it can serve as a rapid-acting and highly effective antidepressant. It can also decrease OCD symptoms. Other NMDA-blocking drugs include memantine and dextromethorphan (combined with bupropion). Lamotrigine can decrease glutamate release and has been used as an adjunct medication for OCD.Nutrients, however, play an important role in the NMDA receptor. NAC or N-acetyl cysteine is a precursor to glutathione and, thus, an antioxidant. It is also anti-inflammatory and a binder for a particular toxin made by candida and mold. But, it is also a potent NMDA antagonist (decreases activity at NMDA) and has been shown to reduce obsessions and compulsions of OCD. It has also been studied in alcoholism, opiate addiction, cocaine abuse, gambling disorder, shopping disorder, cigarette addiction, and trichotillomania. It has been used by itself and as an adjunct to medication therapy. NAC has become part of the Walsh undermethylation nutrient protocols for those with OCD and/or addiction.Zinc also plays an important role in regulating functioning at the NMDA receptor. The Walsh Research Institute found that 90% of those with brain symptoms had relatively low zinc. Dosing of zinc is determined after testing plasma zinc levels using a narrow range (the Walsh/Pheiffer range differs from typical lab ranges). Zinc is checked in conjunction with copper. Zinc has been found to improve treatment response in those with OCD treated with SSRIs. Zinc can be depleted because of very high oxidative stress and/or high pyrroles, which also cause low B6. Because B6 is needed to make serotonin, pyrroles are also important to address if elevated.Inositol is a nutrient involved in the serotonin and glutamate signaling systems. It, too, is beneficial for OCD symptoms; however, it can require very high doses.The challenge of research, as you can see, is that these approaches are all looked at in isolation, as opposed to, for example, addressing undermethylation, optimizing zinc, decreasing activity at the NMDA and addressing sources of oxidative stress.Candida & MoldAside from undermethylation, low serotonin activity, and high activity at the NMDA receptor, those with OCD appear to have high oxidative stress, as is the case with most brain-related conditions. One of the more common sources of oxidative stress I see in my practice is candida overgrowth in the GI tract, which often follows antibiotic exposure and /or mold toxicity due to water damage causing seen or unseen toxic mold. Because mold and candida (yeast) thrive on sugar and a high-carb diet, symptoms can fluctuate with sugar or carb intake. How might candida and mold intersect with the NMDA receptor? Mold and yeast can contribute to high histamine states. Histamine can increase activity at the NMDA receptor. EstrogenFor women and teen girls that I see with OCD, there is often a fluctuation in their OCD symptoms with their cycle. Typically, their symptoms worsen during the times of the month when estrogen is the highest. This may be because estrogen can increase activity at the NMDA receptor.PANDAS & PANSWhen a child has an abrupt onset of OCD symptoms, PANDAS and PANS should be considered.* PANDAS = Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections* PANS = Pediatric Acute-Onset Neuropsychiatric SyndromePANDAS and PANS are autoimmune conditions, meaning the immune system is acting on the body, in this case, a part of the brain called the basal ganglia, that involves an acute onset of OCD symptoms. Other symptoms can include restricted eating, mood symptoms, regression in academic or social skills, and motor tics. While triggers are often viral, bacterial (strep in the case of PANDAS), candida,or other microbial source, what is underlying the dysregulated immune response to such microbes, in my experience, is mold toxicity. SummaryBecause OCD can be difficult to treat, my hope in sharing this information is to raise awareness that effective OCD treatments can require a multifaceted approach that includes:* addressing methylation (and high pyrroles if present) to improve serotonin activity* decreasing activity at the NMDA receptor* by optimizing zinc* using supplements or medication* addressing sources of inflammation and high histamine* address sources of oxidative stress - trauma, stress, toxins, inflammation If you find this information helpful and would like to help me get this out into the world, please consider sharing:As always, I welcome your comments, questions, and experience.Until next time,CourtneyP.S. To learn more about non-patient consultations, treatment, and monthly mentorship groups, please visit my website at:CourtneySnyderMD.comMedical Disclaimer:This newsletter and podcast episode is for educational purposes and not intended or implied to be a substitute for professional medical advice, diagnosis, or treatment for yourself or others, including but not limited to patients you are treating (if you are a practitioner). Consult your physician for any medical issues that you may be having. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit courtneysnydermd.substack.com/subscribe

Welcome to the SHE MD podcast! Today hosts Dr. Thais Aliabadi and Mary Alice Haney dive into a groundbreaking topic with Dr. Peyman Tashkandi and Anabel González: the transformative potential of ketamine therapy for mental health. From treatment-resistant depression and severe anxiety to postpartum depression, this episode explores how ketamine is reshaping the landscape of mental health treatment.Dr. Tashkandi breaks down the science behind ketamine's unique mechanism, which boosts neuroplasticity, reduces inflammation, and balances neurotransmitters to offer life-changing relief for those who haven't found success with traditional treatments. Anabel shares her deeply personal story of overcoming postpartum depression and lifelong mental health struggles through a structured ketamine infusion program paired with therapy.You'll also hear about the importance of integration therapy, how to identify who is—and isn't—a good candidate for ketamine, and the need to advocate for innovative mental health solutions. Whether you're a medical professional, a patient seeking new options, or simply curious about cutting-edge treatments, this episode is packed with insights to transform how we approach mental health. Let's get started!Access more information about the podcast and additional expert health tips by visiting our website at shemdpodcast.com and Ovii.com/shemd. Sponsors: Cymbiotika: Go to Cymbiotikia.com/SHEMD for 20% off your order + free shipping today.Lume: Control Body Order ANYWHERE with @lumedeodorant and get 15% off with promo code SHEMD at Lumepodcast.com/SHEMD! #lumepodDR. PEYMAN TASHKANDI & ANABEL GONZALEZ TAKEAWAYS:Explore Ketamine as a Transformative Option: Ketamine therapy offers rapid relief for individuals suffering from treatment-resistant depression, severe anxiety, and postpartum depression. Its unique mechanism of action—boosting neuroplasticity, reducing inflammation, and balancing neurotransmitters like glutamate—makes it life-changing for patients where traditional medications have failed.Understand the Science Behind Ketamine's Impact: Ketamine works differently from standard antidepressants by targeting NMDA receptors, increasing glutamate activity and enhancing neuroplasticity. This helps patients break free from patterns of chronic depression or anxiety, offering not just temporary relief but lasting mental health improvements with proper infusion protocols.Recognize the Spectrum of Mental Health Needs: Ketamine therapy is not a one-size-fits-all solution. It is most effective for those with clinical depression, severe anxiety, or debilitating conditions like postpartum depression. Understanding the distinction between everyday stress and clinical symptoms is essential for determining who can benefit from this cutting-edge treatment.Pair treatment with integration therapy for maximum impact: Therapy within 72 hours of ketamine infusions enhances the benefits by helping process and integrate experiences. While infusions alone can be effective, combining them with tools like EMDR can lead to profound and lasting emotional breakthroughs. Advocate for awareness and education: Despite its potential, ketamine therapy remains underutilized due to slow guideline changes and resistance from some mental health professionals. Push for greater understanding and open discussions with providers about innovative treatments, especially when conventional methods aren't meeting your needs.THIS EPISODE: [4:27] Ketamine for depression and how it works scientifically[13:53] Clinical depression and anxiety and Anabel shares her story of depression and her first ketamine infusion[22:31] Therapy, the infusion experience and who is not a good candidate[31:24] Long-term effects of ketamine treatments and finding the right clinic[38:45] Treating a child or adolescent with ketamine and the difference between women's and men's symptomsRESOURCES:Dr. Tashkandi's InstagramKetamine Clinics of Los Angeles WebsiteDr. Tashkandi's Private Psychiatry Practice WebsiteAnabel's Company, Good BacteriaGood Bacteria's Instagram GUEST BIOGRAPHY:Dr Peyman TashkandiDr. Tashkandi is a Double Board Certified Psychiatrist in Child and Adolescent and General Adult psychiatry. He is a former Associate professor of psychiatry at University of Southern California School of Medicine and is currently in Private practice in Beverly Hills, California. For the past two years he was the Director of psychiatry at Ketamine Clinics Los Angeles. Dr. Tashkandi has spent his career exploring the inner workings of the mind and is especially interested in the relationship between psychiatry, medicine, and the human experience.Anabel GonzálezAnabel's postpartum journey led her to seek transformative healing through ketamine therapy and a focus on gut health. The profound impact of these approaches not only helped her recover from severe postpartum challenges but also ended a lifelong battle with depression. This personal transformation inspired her to start developing Good Bacteria, now in its pre-launch phase, dedicated to creating science-backed solutions that bridge the gap between real food and microbiome support. As a mom on a mission, Anabel is committed to helping other women heal and thrive, sharing her story to remind us all that our bodies, minds, and spirits are powerful and capable of profound recovery.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Anti-amyloid therapies provide the first FDA-approved option to alter AD pathology, but an understanding of overall utility and value to patients remains in its infancy. In this episode, Teshamae Monteith, MD, FAAN, speaks with David S. Geldmacher, MD, FACP, FANA, author of the article “Treatment of Alzheimer Disease” in the Continuum® December 2024 Dementia issue. Dr. Monteith is the associate editor of Continuum® Audio and an associate professor of clinical neurology at the University of Miami Miller School of Medicine in Miami, Florida. Dr. Geldmacher is a professor and Warren Family Endowed Chair in Neurology and the director of the Division of Cognitive and Behavioral Neurology, Department of Neurology, Marnix E. Heersink School of Medicine at the University of Alabama at Birmingham in Birmingham, Alabama. Additional Resources Read the article: Treatment of Alzheimer Disease Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @headacheMD Transcript Full interview transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME. Dr Monteith: This is Dr Teshamae Monteith. Today, I'm interviewing Dr David Geldmacher about his article on treatment of Alzheimer's disease, which appears in the December 2024 Continuum issue on dementia. Welcome to our podcast, Dr Geldmacher. How are you?  Dr Geldmacher: I'm very well, thank you. It's a pleasure to be here.  Dr Monteith: Yeah. So, why don't you introduce yourself to our audience? Dr Geldmacher: Sure. I'm David Geldmacher. I'm a professor of neurology at the University of Alabama in Birmingham and I lead the division of Cognitive and Behavioral Neurology.  Dr Monteith: So, I'm really excited about this, to personally learn, and I know that or neurology community is also really excited about this interview. So, why don't we start off with your main objective.  Dr Geldmacher: So, my main goal in the article was to review the FDA-approved pharmacologic treatments for dementia. There's lots of ways of thinking about treatment of dementia; psychosocial, caregiver support, and so forth. But I really wanted to focus on the issues of drug treatment because that's what has been our backbone for a long time and now has recently expanded.  Dr Monteith: Why don't we talk a little bit about, first of all, the boom in the field? What's that been like?  Dr Geldmacher: So, the big change in the field is over the last several years, we've had treatments become available that actually attack the underlying Alzheimer pathology, and that's new and different. For decades, we've been able to treat the symptoms of the disease, but this is the first time we've really been able to get to the root of the pathology and look toward removing amyloid plaques from the brain.  Dr Monteith: Let's step back a little bit and talk about the framework of diagnosis and how that leads into the therapeutic potential. I know you're going to dive into some of the biologics, but we should probably talk about the kind of holistic approach to considering the diagnosis. Dr Geldmacher: Sure. So, you know, when someone comes to the clinic with memory complaints, our question we have to ask is, is this neurologic origin, a structural origin like Alzheimer's disease or vascular dementia? Are there complicating factors, the software issues of mood disorders and sleep disorders and pain that can all magnify those symptoms? The clinical reasoning is a critical part of that, but in Alzheimer's disease, typically the problems revolve around difficulty forming new memories of events and activities, the episodic memory. And then it's often accompanied by changes in word finding and semantic knowledge. And those are the things that we look for in the clinic to really point toward an AD diagnosis. And then we support it with exclusion of other causes through blood work and identification of patterns of brain atrophy on MRI. And then most recently in the last couple of years, we've been able to add to that molecular imaging for amyloid with PET scans as well as, most recently, blood-based biomarkers for Alzheimer's pathology. So, it's really been a revolution in the diagnosis over these last several years.  Dr Monteith: And when approaching patients or populations of individuals, there seems to be a real full spectrum with looking at the societal burden, the biological impact, of course, risk factors of primary prevention, and now this whole area of brain health and secondary prevention. How do you kind of tie all of this together when talking to patients and family members?  Dr Geldmacher: Sure. So, the approaches for brain health apply to everyone. In basically every clinic visited, our brain aging and memory clinic, we reviewed lifestyle approaches to brain health like regular physical exercise, healthy diet, cognitive and social stimulation. And those are fundamental to the approach to everyone, whether they have cognitive impairments that are measurable or not. These are all things that are good for our brain health. And then, you know, focusing on the vascular risk factors in particular and working with the patient and their primary care team to ensure that lipids and blood sugar and blood pressure are all in good healthy ranges and being appropriately treated.  Dr Monteith: You know, there's this kind of whole considerations of clinically meaningful endpoints and clinical trials, and even when we're talking to our patients. What would you say the field has kind of identified has the best endpoints in helping patients? Would you call it impaired daily function? Is that like the best hard endpoint? Obviously, there are other things such as caregiver burden, but you know, how do you approach assessing patients? Dr Geldmacher: Defining the endpoints is very difficult. Typically, if we talk to patients and their families, they would like to have better memory or improve memory. How that applies in everyday life actually is daily function. And so, we focus very much on daily function. And when I talk about our therapies, whether they're symptomatic therapies or the new disease-modifying therapies, I really talk about maintenance of function and delays and decline or slowing of decline, helping to foster the person's independence in the activities that they have and be able to sustain that over the longer term.  Dr Monteith: And when thinking about diagnosis- and we're going to get into treatments, but when thinking about the diagnosis, and of course, it's full-spectrum from mild cognitive impairment to moderate and severe forms of dementia, but who should have CSF testing and PET imaging? Obviously, these are invasive, somewhat invasive and expensive tests. Should all people that walk in the door that have memory complaints? How do you stratify who should have tests? Dr Geldmacher: I think about this in a big funnel, basically, and the starting point of the funnel, of course, is the person with memory complaints. Then there's that neurologic reasoning. Are these memory complaints consistent with what we expect from the anatomy of Alzheimer's disease, with atrophy in in the hippocampus and temporal lobe? Do they have episodic memory loss or not? That first step is really trying to characterize, do the clinical patterns act like those of Alzheimer's disease or not? And then we follow the Academy of Neurology guidelines, looking for reversible sources of cognitive decline, things like B12 deficiency and depression, sleep disorders and the like, and try to exclude those. We start with structural imaging with everyone, and MRI, typically, that will help us understand vascular burden and patterns of atrophy, looking for things like mesial temporal atrophy or precuneus atrophy that are characteristic of Alzheimer's disease. If those things are all pointing in the direction of AD as opposed to something else, then typically before moving on to CSF or PET scan, we will use blood-based biomarkers, which are one of the big changes in the field in the last year or so, and there are now multiple panels of these available. The downside is they are typically not covered by insurance. On the other hand, they can really help us identify who is likely to have a positive PET scan or positive findings on CSF. We start to provide that counseling and information to the patient before they get to those more definitive tests. We can push people in the other direction. We can say, your blood-based biomarkers are negative or do not indicate AD as the most likely source of your condition now, so let's treat other things. Let's see what else we can focus on. The blood-based biomarkers are now, in our clinic at least, the critical choke point between the routine workout that we've always done on everyone and then the more advanced workup of proving amyloid pathology with CSF or a PET scan. Dr Monteith: How sensitive are those blood biomarkers and how early are they positive?  Dr Geldmacher: The sensitivity is generally pretty good, in the ninety plus percent range on average and it depends on which panel. And as you point out, when in the course of symptoms that they're done, we know that they become positive and presymptomatic or asymptomatic people. We're using these kinds of markers to screen people for prevention trials. So, I think when someone is symptomatic, they're a good indicator of the presence or absence of AD pathology. Now that doesn't mean the AD pathology is the sole cause of their symptoms. And so, we still need to think about those other things like sleep and mood and so forth. But they do point us in the in the direction of Alzheimer's change.  Dr Monteith: So why don't we talk about some of the more standard older treatments, and it's also important to leave with kind of some rational approach to when we start and what should we be counseling our patients on. So why don't we start with the older, you know, choline esterase inhibitors and then some of the MDA- I guess there's only one modulator, SEPTA modulator. Dr Geldmacher: So, I've been really fortunate in my career span, the time from the first of those symptomatic agents reaching the market in 1993 to seeing the disease modifying drugs enter the market now. I think most neurologists actually have entered practice after those clinical trials of the colon esterase inhibitors were published. So, one of my goals in this article was to review that primary data and what can we expect from those symptomatic drugs. We know that they are inconsistently effective in mild cognitive impairment, and the Academy of Neurology guidelines says there is not strong evidence to use them in mild cognitive impairment. But in mild AD and beyond, the cholinesterase inhibitors provide meaningful benefits. They delay decline, they can delay nursing home placement. They reduce overall costs of care. So, I think they provide real value. So, in the article I have reviewed what the data looked like on those. My approach is to start with oral Donepezil at five milligrams and increase it to ten in everyone who tolerates the five. If for whatever reason the oral Donepezil is not well tolerated, I'll switch to transdermal rivastigmine to help improve tolerability. There are very few head to head comparisons, but nothing suggests that one of the cholinesterase inhibitors is superior to the other for clinical outcomes, and there's no evidence to support conjoint use of more than one at a time. Should someone be showing decline then on typical cholinesterase inhibitor therapy - and people will, it's often delayed, but the decline will reemerge - then I will add the NMDA receptor, a modulator memantine and titrate that up to full dosing, either 10 mg twice a day for the conventional release or 22 mg extended release. And at that point we're sort of on maximal pharmacologic therapy for Alzheimer's disease. These agents can provide some benefit in other conditions, they're off-label except for Lewy body disease where rivastigmine is labeled. But they can provide benefit across different conditions. And there's some preliminary data, for instance, of acetylcholinesterase inhibitors being helpful in vascular cognitive impairment. So, I will use them, but I expect the greatest response when someone really does follow the patterns of Alzheimer's disease.  Dr Monteith: And you have a great chart, by the way, and nice figures looking at some of the meta-analyses on cognitive outcomes as well as functional outcomes. So, thank you for that.  Dr Geldmacher: In general, all of those tables favor treatment over placebo in the domains of cognition, daily function, neuropsychiatric symptoms. And it's that consistency of result that lets me know that we really are seeing a drug effect, that it's not a class effect with those, that we really are helping our patients. It's not like some studies are positive and some are negative. They are very consistently positive. Small magnitude, but consistently positive.  Dr Monteith: And I know we have a lot of patients coming in where, at least, their caregivers are complaining about agitation, and sleep is also a problem for others. And so how do you help that patient? I know you have a good algorithm that also you included in your article, but why don't you summarize how we should approach these symptoms? Dr Geldmacher: Sure. So, for nonpsychotic agitation, you know, just restlessness, wandering, pacing and so forth, my first choice is an off-label use of citalopram. And there is good clinical trials evidence to support that. if someone has psychotic agitation that is with delusions or hallucinations and so forth, I think we do need to move to the antipsychotic drugs. And the one drug that is now approved for treatment of agitation and Alzheimer's disease does fall into that antipsychotic category, along with its various black box warnings - and that's brexpiprazole. For many of our patients, getting coverage for that agent is difficult. It's not on many formularies. So, it is something I progress toward rather than start with. Similarly, for sleep, there is one approved agent for sleep, that's a dual orexin agonist. And it shows effectiveness, but can have some negative cognitive effects, and so I tend not to start with that either. My first choice when sleep is the primary issue for our patients with dementia is trazodone, and there are some small, limited studies for it's off-label used to enhance sleep. It's safe, inexpensive, often effective, and therefore it's my first choice. Dr Monteith: So, now let's get into the big conversations that everyone is having. Let's talk about the newer disease modifying anti amyloid therapies. Give us a summary dating back 2021 probably, although we can hold the preclinical work, but let's talk about what is available to our patients. Dr Geldmacher: Sure. And the development of anti-amyloid therapies goes all the way back to 1999. So, it's a pretty long course to get us to where we are today.  Dr Monteith: Yeah, that's why we limited that.  Dr Geldmacher: With that first approved agent with aducanumab in 2021, it received a limited or accelerated approval in FDA parlance. These agents, the aducanumab, lecanemab and donanemab, all approved, are known to remove amyloid pathology from the brain as measured by CSF and/or BIPET. They are amyloid lowering therapies, often called disease-modifying therapies. And across the agents there's some variable results. But if we look at the two with full approval, lecanemab and donanemab, they slow clinical progression by 25% to 35% on average. And that's measured by either cognitive measures or global measures or composite measures, but it's pretty consistent in that range of about one-third slowing. That makes it really difficult to discern in an individual patient, though, because there's so much variability in the progression of the disease already that it can be difficult to tell in one person that these drugs are working. They're also complex to use, so there's a qualification process that involves MRI to exclude things like a high tendency toward hemorrhage. It includes genetic testing for papal E4 status to help us understand the risk for complication, and then once-monthly or twice-monthly infusions with standardized schedule for MRI scanning. So, there's a lot that goes into managing these agents. And they are expensive, and we don't yet know their cost effectiveness. The cost effectiveness of the cholinesterase inhibitors was questioned when they first came out back in the 1990s, and it took five or ten years to really understand that they provided benefit to society and to individuals in those domains of quality of life and return on investment. And we're still learning about that with the disease modifying therapies.  Dr Monteith: So, two questions. One, the case that you presented was an individual having symptoms and kind of voiced their desire to be on these therapies. So, people are going to be asking, coming to clinic asking and then of course, they're going to be people that you select out. So, how do you make that decision to recommend this treatment for patients given the potential risk? Dr Geldmacher: We've got some really good guidance from appropriate use recommendation papers for aducanumab and lecanemab, and I'm expecting one from donanemab fairly soon. But the key is to identify individualized risks, and that involves knowing their APOE4 status, knowing their- whether they've had microhemorrhages in the brain previously, and then documenting that they really do have amyloid pathology with something like PET scan to establish those baselines. I talk to people about the burden of twice-monthly infusions or, now with donanemab, once-monthly infusions. And for instance, for someone who's got a working caregiver, getting to an infusion center twice a month can be a significant burden. And then if there are complications, frequent MRI scans and so forth. So, we talk about the burden of entering into this therapeutic pathway. The reality is that people who are qualified generally want it. I have relatively few folks who have said, no, these risks are more than I'm willing to accept. For decades my patients have said, anything you can do to slow this down, I'm willing to try. And now we're seeing that translated to reality with people willing to accept high-risk, high-cost treatments with the chance of slowing their individual progression.  Dr Monteith: And how do you select between the two treatments? Dr Geldmacher: So far that's been easy because donanemab's not readily available.  Dr Monteith: Outside of clinical trials, right?  Dr Geldmacher: Exactly. For prescription use, it's coming in - the first cases have now been infused - but it's not generally available. Nonetheless, what I will do for patients in this is look at the risk tables. So donanemab appears to have in general some higher rates of the Aria complications, amyloid-related imaging anomalies, and some people are going to be more risk tolerant of that for the payoff of potentially faster response. The donanemab trials restructured that. They did their first assessment of effectiveness. I had amyloid removal at six months and a significant proportion of people were eligible to discontinue treatment at six months because their amyloid was below treatable thresholds. So higher risk, perhaps faster action and fewer infusions for donanemab. Lecanemab we have more direct experience with, and between the two of them, the eighteen month outcomes are pretty much the same and indistinguishable. So are we in it for a quick hit, or are we in it for the long race? And different patients and different families will have differing opinions on where they want to accept that risk and burden and so forth. But so far, the data don't indicate a lot of difference in their longer-term outcomes. We still have plenty to learn.  Dr Monteith: And so, it sounds like, as you mentioned, we're looking at eighteen months out for kind of a hard outcome, and that there is a lot of variability in response rate. How are you tracking patients- you know about the imaging, so just in terms of clinical outcomes and efficacy?  Dr Geldmacher: Sure. So, for Medicare to reimburse on these treatments, people need to be enrolled in a registry program - and there are several of these, CMS runs one of their own. But the requirement for that is, every six months, to do cognitive and functional outcomes through the first two years. Cognitive outcomes are up to the clinician, but things like the mini mental state exam, the MoCA, are appropriate. In our own program, we use something we developed locally called the Alabama Brief Cognitive Screener. As for the cognitive outcomes and then for functional, we use an instrument called the General Activities of Daily Living Scale, but there are many other ADL scales that could be used as well. CMS does not mandate specific tests. Since the progression of the disease is variable to begin with, we don't really know how to interpret these results in reference to whether the drug is working, but I can tell a patient or a family member, your scores are stable, or, you have a decline of three points in this test. That's typical for this duration of illness. But there isn't a good way to know whether the drug is working in this person at this time, at least with our current levels of data.  Dr Monteith: So, I think we have to talk about health equity, and it sounds like Medicare is reimbursing for some of us. We look at different socioeconomic backgrounds, educational backgrounds, race, ethnicity. Not everyone is aware of these treatments. So, how do we get more patients to become aware of these treatments? And how do we get them to more people to help people? Dr Geldmacher: Yeah, I mean, that's- it's a major, major issue of inequity in our population. We've done some work at UAB looking at the flow of members of minority communities into memory clinics. So, we know that the overall population of, and I'll choose, for an example, blacks and African Americans, that they are represented a much higher rate in our overall UAB treatment population than they are in our memory clinic population. So, they're not even getting to us in the specialty clinic at the same rates as other segments of our population. We also know that blacks and African Americans in our population are not receiving PET scans as often as the overall treatment population. So yes, there are real, real problems with access. There are cultural issues behind this as well. And in many communities, a change in cognition, a loss of memory is an expected part of the aging process rather than recognized as a disease. So, people who come to us from minority communities are often further along in the course of cognitive and functional decline and beyond the point where they might qualify for the disease-modifying therapies, where early AD is the sort of defining boundary. So, I think more awareness and more screening in primary care settings, perhaps more community outreach to let people know that changes in memory that affect daily function are not normal as part of the aging process and should be evaluated for intervention. So, there's lots of places in our healthcare community where we could foster better outreach, better knowledge to get more folks access to the medicines. And this is before we even get to cost. Dr Monteith: Yeah, yeah. And obviously, there's some stigma as well.  Dr Geldmacher: That's right.  Dr Monteith: Really recognizing what the issues are and diving and asking those questions and funding research that asks those questions, as you mentioned, is really important. And then you have also a nice area where, you know, looking on the impact of treatments on caregiver-related outcomes, and of course ultimately want to keep patients out of nursing homes and prevent death. And so, can you talk a little bit about that? And, you know, mainly the caregiver burden.  Dr Geldmacher: So, my research in that area goes back a long way now. But I learned early in the course of therapy that many times the outcome that the family is noticing for symptomatic therapies is not a change in the patient's memory per se, but that there is less work involved in the caregiving. Less time is spent in direct caregiving roles. The patient may shadow less and because they have better independent cognition. I remember one family member once told me, the medicine you started is a godsend because now I can go to the bathroom by myself and he's not pounding on the door saying where are you, where are you. He's able to recall long enough that I'm in the bathroom that I have that moment of privacy. That was very meaningful to me to hear that. So. Dr Monteith: Cool. So why don't you just help us wrap this up and just give us, like, three main takeaway points that we should be getting out of your article? Dr Geldmacher: The three points that I would emphasize from my article is that the symptomatic therapies provide meaningful benefits and measurable, consistent, meaningful benefits. The second is that those benefits extend beyond things like cognitive test scores and into things like caregiver well-being and maintenance of independence in the home environment. And the third is that the disease-modifying therapies are an exciting opportunity to modify the pathology, but we still are learning about their cost effectiveness and their long-term benefit both to individuals and to society. But the only way we're going to learn that is by using them. And that was the experience that we gained from the symptomatic therapies that took use in the community for years before we really began to understand their true value. Dr Monteith: Thank you. That was excellent. And I put you on the spot, too.  Dr Geldmacher: No problem.  Dr Monteith: Again, today I've been interviewing Dr David Geldmacher, whose article on treatment of Alzheimer's disease appears in the most recent issue of Continuum on Dementia. Be sure to check out Continuum audio episodes from this and other issues. And thank you to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, associate editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at contentpub.com/AudioCME. Thank you for listening to Continuum Audio.

Recently, an interview by Christiane Amanpour caught my attention. It was with Coralie Fargiat, the director of “The Substance.” Though I haven't seen this 2024 body horror movie (nor do I intend to), the story brings up several teaching points about the left brain, undermethylation, neuroplasticity, and our collective obsession with beauty.The movie is about an actress, Elizabeth, who loses her job hosting a fitness television show when she turns fifty. She has “aged out.” While in the hospital after a car accident, someone directs her to a product - the substance - a neon green liquid that will allow her to bud off a younger version of herself - Sue. The rule is that Sue can only go out into the world for one week at a time, alternating each week with Elizabeth while the other lies dormant. Not surprisingly, Sue has more advantages in the world (that Elizabeth inhabits), including replacing Elizabeth on her former TV show. Increasingly, when it's time to switch, Sue breaks the one-week rule. This results in part of Elizabeth's body becoming increasingly deformed. The culmination is a grotesque battle of gore between the two, who initially were instructed to remember, “You are one.”In the interview, the director, Coralie Fargeat, discusses her personal experience:“I turned 40 and was more impacted than ever about what it's like to be a woman, the feeling that if I wasn't young and pretty and sexy, I would be totally erased from the surface of the earth. So there was this kind of emergency, this vitality to the things I speak about in my film.”Research supports this thinking that beautiful people are treated better and thus have more advantages. With the use of photoshopping, social media filters, and even plastic surgery, many teens and young adults are experiencing neuroplastic changes that are making real people, including themselves, appear increasingly off or even grotesque. Left Brain“The Substance” is a left-brain nightmare. It shows us the self-destructive path the left brain can take us on, especially in a world that tells it exactly how things should look. Elizabeth, the main character in the movie, is rigid in her thinking, addicted to an image of herself, perfectionistic, and highly competitive. In some ways, these left-brain attributes have served her, but unchecked, they destroy her. If the left brain were a person, it would have the following traits and perspective on appearance: (These traits are oversimplified and pulled from Dr. Iain McGilchrist's work) - * Detail-oriented, narrow focus of attention - “That doesn't look right.”* Prefers what it knows and prioritizes what it expects - “I should look this way.”* Has difficulties disengaging - “I can't stop thinking about this and how to fix it.”* Sees parts (as opposed to the whole) * Sees the body as a sum of parts * Doesn't have a whole image of the body (as found in those who have damage to the right hemisphere)* Is competitive - “I need to look better than they do”* Fears of uncertainty and lack of control (As you can imagine, this is a problem for anyone human and thus who will age)The left brain will set its sights on beauty, success, titles, money, objects, or anything else that feeds the “I.” Because the left brain can't see the “big picture,” it has a hard time pulling back far enough to see how its way of thinking may be getting in the way. The Right BrainOur ability to feel embodied is a job for our brain's right hemisphere. When the voice in the movie reminds Elizabeth, “You are one,” it may as well be speaking on behalf of the right hemisphere.Our right brain allows us to have compassion, including self-compassion. It honors diversity and differences. It can see the bigger picture of our lives that involve multiple developmental stages. It can sit with uncertainty. It knows that our imperfections and differences promote connection with actual humans.UndermethylationLeft brain tendencies strongly overlap with undermethylation traits. Methylation is a biochemical and cellular phenomenon that serves many important functions. If we “undermethylate,” we can have more difficulties breaking down histamine, more difficulties detoxifying, and lower serotonin activity. Methylation is impacted by a number of genes, the most well-known being MTHFR.Undermethylated traits include perfectionism, obsessive-compulsive tendencies, being highly competitive, having ruminations, and addictive tendencies. The NDMA ReceptorThose of us who are undermethylated can have high activity at the NMDA receptor, resulting in a problem with “memory extinction” or letting go of a thought. This could look like obsessive-compulsive tendencies (including those seen in body dysmorphia) and addictive tendencies. High histamine (again due to undermethylation) can increase activity at this receptor. Low zinc, high estrogen, and low magnesium can also be at play.I suspect Elizabeth is undermethylated and has high activity at the NMDA receptor. Both could be assessed for and treated (in part) using targeted nutrients. I say, in part, because the brain training / neural training that occurs through social media is difficult to override if someone is still “using.” Interestingly, EMF exposure (from phones and wireless technology) can increase histamine, further driving these issues.Neuroplasticity and Images of PerfectionThe more images of beautiful images of people we see, the more those images become the norm in our mind, and the more any deviation from that norm will stand out as problematic. This was already a problem with the photoshopping of celebrities and models. But now, with social media filters, teens and young women aren't just comparing themselves to celebrities and models; they're comparing themselves to a filtered image of themself.Filters can create larger eyes, bigger lips, more angular jawlines, whiter teeth, slimmer faces, and smooth and even skin tones. Research into the use of filters:* Millennials are predicted to take 25,000 selfies on average over their lifetimes* About 90% of women aged 18-30 report using beauty filters before posting selfies on social media. * Repeated interactions with filtered images and associated beliefs and worries are increasing the risk of mental health issues such as:* depression* social anxiety* reduced self-esteem* appearance anxiety* body dysmorphia* increase of plastic surgery* 62% of plastic surgeons report that their patients wanted cosmetic procedures because of dissatisfaction with their social media profiles* Snapchat dysmorphia” is what plastic surgeons are calling the act of taking a picture of one's self and using a filter.* Selfies are the leading cause of plastic surgery among young people* Girls who routinely shared self-images on social media had considerably higher body dissatisfaction relative to those who share selfies less frequently. * Body Dysmorphic Disorder among young women has been linked to social media use.In short, the research shows that investing in one's self-presentation on social media is often a harmful practice. The more one does it, the more damaging it tends to be. It encourages hyperattention to unrealistic beauty standards and a desire to change one's physical appearance. This problem of hyperattention to unrealistic beauty standards isn't just a phenomenon of teenage girls and younger women. I´m 57 and understand these things, and still, I´ve had to be intentional about how much attention and neuronal wiring I put into what increasingly feels like defying the very full and lovely reality of my current age. A SequelIf I could write a sequel to “The Substance,” it would be about how Elizabeth (the main character) gets off screens and finds a group of real women (her age and older) that she comes to trust, finds refuge, and who she is inspired by. Instead of looking through a lens of culturally defined beauty, she is struck by the strength, courage, and peace they never could have embodied at a younger age. These women who inspire and shape her would like Helen Mirin (79), who corrected a podcast interviewer after they said to her, “But you are young at heart.” She tells him that no, she is not….”My spirit is the age that I am. When you say 'youthful', I'm not full of youth. I'm full of the life that I've lived up to this point.As girls and women, we need these women in our lives. We can do our part to become these women - the desperately needed embodiments of the right brain. Wishing you peace and wholeness,CourtneyCourtneySnyderMD.comP.S. This Saturday begins the mentoring group for MDś, NDś, DOś, NP and PAś. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit courtneysnydermd.substack.com

In this episode of The Vet Dental Show, Dr. Brett Beckman, a board-certified veterinary dentist, shares valuable insights into pain management, anesthesia protocols, and best practices in veterinary dentistry. The episode discusses the cautious use of lidocaine in cats, the role of bupivacaine for effective local blocks, and the potential applications of Renia for managing chronic pain in refractory stomatitis cases. Packed with actionable advice, this episode is a must-listen for veterinarians and technicians looking to elevate patient care in their practice.     Podcast Details Host: Dr. Brett Beckman, DVM, FAVD, DAVDC, DAAPM     Key Highlights Topic 1: Lidocaine Use in Cats Question: Should lidocaine be used with caution in cats? Answer: Yes, lidocaine can potentially cause seizures in cats, especially when used as a continuous rate infusion (CRI). Recommendation: Replace lidocaine with bupivacaine for local nerve blocks to ensure longer-lasting analgesia (6-10 hours). Use lidocaine sparingly and with proper discretion. Topic 2: Lidocaine for Intubation Discussion: Historically, lidocaine was applied to the larynx for intubation in cats. Dr. Beckman and his team now prefer using a blunt cannula for safer intubation without the risks associated with lidocaine.     Topic 3: Pain Management for Chronic Cases Case Example: Use of Renia (NK1 antagonist) in refractory stomatitis Mechanism: Blocks Substance P at the postsynaptic membrane to prevent ascending pain signals. Clinical Context: Effective for managing chronic pain when combined with ketamine (NMDA receptor antagonist). Outcome: While Dr. Beckman's team hasn't used it extensively, anecdotal feedback from the veterinary community is positive.     Topic 4: Local Blocks with Bupivacaine Best Practice: Use 0.5% bupivacaine for local nerve blocks in cats and small animals. Dosage: 0.2 mL per foramen ensures safety and efficacy. Rationale: Provides prolonged analgesia compared to lidocaine, minimizing the risk of complications.     Actionable Takeaways Transition to bupivacaine for local nerve blocks to enhance patient comfort and safety. Consider using Renia for managing chronic pain in severe stomatitis cases. Adopt safer intubation techniques, such as using blunt cannulas, to mitigate risks in feline patients. Leverage evidence-based pain management protocols to improve patient outcomes.     Sponsor Mention: This episode is brought to you by the Veterinary Dental Practitioners Program. Learn more and request an invitation at ivdi.org/inv. Closing Note: "I hope you enjoyed this episode filled with actionable items to elevate your dentistry practice. Implement these tips today and see the long-term benefits for your patients and practice!"     If you're ready to take your dentistry skills to the next level, visit ivdi.org/inv to join the Veterinary Dental Practitioners Program!  

In this episode of the In Vivo podcast, Peter Flynn, CEO of Arialys Therapeutics, discusses the exciting field of autoimmune neuropsychiatry and the company's monoclonal antibody, which it is investigating for the treatment of a rare condition called anti-NMDA receptor encephalitis and potentially other indications.

On this episode of the Real Life Pharmacology Podcast, I cover 5 more medications of the top 200. Fenofibrate is a medication used primarily to reduce triglycerides. This medication differs from statins which tend to focus on LDL management. Doxazosin is an alpha-blocker. The primary indications of doxazosin are hypertension and BPH. Naproxen is an NSAID. Of all the NSAIDs, naproxen is one of the lower-risk agents with regard to cardiovascular risk. Spironolactone is an aldosterone antagonist and also classified as a potassium sparing diuretic. Memantine is an NMDA antagonist that is indicated for the management of Alzheimer's dementia. If you are looking for study materials and our list of popular Amazon books, check out meded101.com/store!

FREE! CRNA School Interview Prep Guide: https://www.cspaedu.com/uc9a5ih4Ketamine: A Unique Anesthetic with Diverse ApplicationsDive deep into the world of ketamine, exploring its history, pharmacology, mechanism of action, clinical uses, and side effects. Dr. Kelly Elmore, Assistant Program Director at Mary Baldwin University's Nurse Anesthesiology Program, guides listeners through this fascinating drug, highlighting its potential for anesthesia, pain management, and even mental health treatment.Targeting NMDA Receptors for Dissociative AnesthesiaKetamine is classified as a dissociative anesthetic, distinct from depressant anesthetics like propofol. It primarily works by blocking NMDA receptors in the central nervous system, thereby reducing excitatory signals and producing profound analgesia and amnesia. This mechanism also contributes to the characteristic dissociative state, where patients may appear detached from their environment and experience hallucinations.Beyond Anesthesia: Exploring Ketamine's Diverse UsesBeyond its role in anesthesia, ketamine offers a range of benefits in various clinical settings:Pain Management: Ketamine's analgesic properties make it valuable for treating acute and chronic pain conditions, including neuropathic pain, complex regional pain syndrome, and post-surgical pain.Mental Health: Emerging research suggests ketamine's potential in treating treatment-resistant depression, PTSD, and suicidal ideation. Low-dose ketamine infusions combined with psychotherapy have shown promise in these areas in the form of ketamine-assisted therapy.Emergency Medicine: Due to its bronchodilatory effects and ability to maintain airway patency, ketamine is a valuable tool in emergency departments for managing patients with respiratory distress.Important Considerations for Ketamine UseWhile ketamine offers numerous advantages, it's crucial to be aware of its potential drawbacks:Side Effects: Nausea, vomiting, and hallucinations are common side effects, particularly at higher doses.Abuse Potential: Ketamine's popularity as a street drug necessitates caution, especially in outpatient mental health settings.Cardiac Effects: In critically ill patients with depleted catecholamines, ketamine can worsen cardiovascular depression.Mental Health Risks: Ketamine may exacerbate symptoms in some mental health disorders.S-Ketamine: A Promising Option for Treatment-Resistant DepressionThe FDA-approved S-ketamine nasal spray offers a new avenue for treating treatment-resistant depression. This medication is typically used alongside other oral antidepressants.Conclusion: A Multifaceted Drug with Ongoing ResearchKetamine's unique properties make it a valuable tool for CRNAs across various healthcare settings. Ongoing research continues to explore its potential benefits and refine its use for optimal patient care.Join the Free CSPA Community! Connect with a network of Aspiring CRNAs, Nurse Anesthesia Residents, practicing CRNAs and CRNA Program Faculty Mentors here: https://www.cspaedu.com/communityNeed Interview Prep Help In A Hurry?Fast-Track Your CRNA School Interview Prep with our CRNA Interview Crash Course! https://www.cspaedu.com/4wotmldsGet access to application & interview preparation resources plus ICU Educational Workshops that have helped 1,000s of nurses accelerate their CRNA success.Become a member of CRNA School Prep Academy:https://cspaedu.com/joinGet CRNA School insights sent straight to your inbox! Sign up for the CSPA email newsletter: https://www.cspaedu.com/podcast-emailBook a mock interview, resume or personal statement critique, transcript review and more: www.teachrn.comAttend an upcoming Virtual Information Session with Mary Baldwin University Nurse Anethesiology Program: https://marybaldwin.edu/programs/nurse-anesthesiology-dnp/Special Note- Application Deadline for their next cohort is 12/15/2024!

Over the past 20 years, more than 50 antibodies have been identified and associated with autoimmune neurologic disorders. Although advances in diagnostic testing have allowed for more rapid diagnosis, the therapeutic approach to these disorders has largely continued to rely on expert opinion, case series, and case reports. In this episode, Allison Weathers, MD, FAAN, speaks with Tammy L. Smith, MD, PhD, an author of the article “Therapeutic Approach to Autoimmune Neurologic Disorders,” in the Continuum® August 2024 Autoimmune Neurology issue. Dr. Weathers is a Continuum® Audio interviewer and associate chief medical information officer at the Cleveland Clinic in Cleveland, Ohio. Dr. Smith is a GRECC investigator and staff neurologist at George E. Wahlen Veteran Affairs Medical Center and an assistant professor of neurology, at the University of Utah in Salt Lake City, Utah. Additional Resources Read the article: Therapeutic Approach to Autoimmune Neurologic Disorders Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Transcript Full episode transcript available here   Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology.  Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Weathers: This is Dr Allison Weathers. Today, I'm interviewing Dr Tammy Smith about her article on therapeutic approach to autoimmune neurologic disorders, which she wrote with Dr Stacey Clardy. This article is a part of the August 2024 Continuum issue on autoimmune neurology. Although, one of the things I love most about being an interviewer for Continuum is getting the opportunity to meet new neurologists and learn all about their areas of expertise, there's something really special when I get the chance to interview and catch up with old colleagues - and today, I'm fortunate to do just that. I had the privilege of working with Dr Smith when she was a resident at Rush, and I'm so excited to be able to speak to her today about her fantastic and really comprehensive article on this very timely topic. Welcome to the podcast, Dr Smith, and please introduce yourself to our audience.   Dr Smith: Hi. Yeah, thank you for inviting me to participate in the podcast and to write this article. So, I'm Tammy Smith. I am a neurologist who practices in Salt Lake City. I primarily work at the Salt Lake City VA Medical Center where I get to treat veterans with all sorts of neurologic diseases. I'm also an assistant professor of neurology at the University of Utah in the division of Neuroimmunology and Autoimmune Neurology, and I serve as a Clinical Consultant for ARUP Laboratories to help improve diagnostic testing for immune-mediated neurologic diseases.   Dr Weathers: Wow. That is a lot of different roles and things that you have on your plate. I want to start, actually, by talking about the article. Again, you cover so much ground (you and Dr Clardy) in this really comprehensive article, but if you had to choose the one most important message - if you wanted our listeners to walk away remembering one key point, what would it be?   Dr Smith: I think the key point I want our listeners to think about is just to use the resources that are available to you. Nobody can have all of these drugs (as we're talking about treatment of autoimmune neurologic diseases in this article) - no one can have all of those drugs memorized, all of the mechanisms of action, all of the approved treatments and off-label treatments, and all of the symptomatic therapies. But that's why resources like the Continuum exist - so that we can provide those resources to clinicians who are busy at that touch of, er, hopefully - or when they open their issue - to get the information they need to make decisions to take good care of their patients.   Dr Weathers: I think that is so reassuring. As I was reading this article, that was, like, one of the things that really struck me is that, you know, thinking about even being a resident and studying for something like the rate exam, you know, how much easier it used to be when there was such a limited number of drugs thinking about the autoimmune diseases or epilepsy, where just the number of drugs has just, kind of, multiplied so manyfold since I was in training, that it's really overwhelming. And I think you make a great (and as I said, a very reassuring) point that we don't have to memorize these, that there are these incredible resources (like Continuum) where it's not any longer about kind of memorization and keeping it in our heads, that it's more about knowing where to look and thinking about what's the right thing for the patient - knowing how to go and get the information is the more important knowledge there. And, actually, thinking about that and moving on, given your expertise, how do you personally approach the management of a patient with an autoimmune neurologic disorder? Again, in the article, you speak about all the different things to keep in mind, both from a therapeutic (really, treatment) standpoint, as well as a symptomatic standpoint - but what is your personal approach?   Dr Smith: My personal approach really involves considering whether the diagnosis of an autoimmune neurologic disorder is correct, first and foremost, and gathering the information to help support that diagnosis - and I think that's something that often gets overlooked in the excitement of a patient coming in with a rare-looking syndrome. Someone sends off diagnostic testing, rules out a few things, decides it's autoimmune, and starts down a pathway and keeps pushing forward. And I understand that inclination on a busy neurology service or in a busy clinic to just decide on one path and move forward, but I'm always questioning the diagnosis, even in the presence of positive antibody results sometimes. If my patient doesn't respond to the treatment that I'm giving them based on their presentation and the antibody results, I reassess and wonder if there's something else going on, are there two syndromes going on, or was that antibody result really not the right answer for some reason. So, I think my approach, really, is to always have a healthy amount of skepticism around the diagnosis, and even when I'm fairly confident in the diagnosis, to continually reassess that patient and their unique response to treatment. And then, also, their unique circumstances - so, everyone will need different symptomatic management, as well as different rehabilitation resources and other resources mobilized to help them maximize their recovery. And so, there's just not a “one size fits all” approach, but always keep talking to the patient, keep re-evaluating, stay curious, and don't be afraid to change paths when things aren't making sense.   Dr Weathers: I think that is incredibly sound, really thoughtful advice. So, I can imagine how incredibly challenging those cases must be when you think you have the right answer, it looks like it's lining up, the antibodies are pointing you in the right direction, and then, they're not responding. What else do you feel is the most challenging aspect of the management of these conditions? Is there some other kind of aspect that you also feel is really challenging in the treatment of these patients?   Dr Smith: Yeah, I think other challenges are really access to state-of-the-art therapies due to financial barriers - I think that's a pretty significant challenge for a lot of these patients, and I think we need to continue to work on advocacy efforts to make sure all patients have access to the medications they need to treat the disorders they are diagnosed with. And it's a real challenge, even when there's FDA-approved therapeutics - a lot of them are quite expensive, and then we end up playing the insurance game, and we learned that AI is automatically denying people's insurance claims, and so, we're battling computers as well as insurance companies. And I think that's a really significant challenge for a lot of these patients. And then, really, just the fact that a lot of immune-mediated neurologic disorders have a long tale. So, we don't treat a patient the same way we do for an infection and expect a dramatic and rapid recovery - a lot of the recovery for these patients happens over months to years. It's a process, and I think it's really important to be counseling patients and caregivers and other providers and educating them about this that we continue to mobilize resources to help our patients long past their inpatient hospitalization and the most dramatic part of their recovery.   Dr Weathers: Again, you raised some really insightful points there. No, I think they're really key. And I think, to your point, that even for some of these patients, that even if we can get over the economic barriers of the medications themselves and get them authorized, get them covered, you're left with, for a lot of patients, all of the other limitations of some of their social determinants of health challenges, right? So, the transportation challenges to even kind of get them to the appointments, and some of the other challenges they face, which makes some of these treatments very, very hard for them to be able to accomplish. So, it is very challenging - I think that's a very important call-out. What do you think is the easiest mistake to make when treating patients with autoimmune neurologic disorders, and how should our listeners avoid it?   Dr Smith: Yeah, that's an excellent question. One of the most common mistakes I see is either overvaluing diagnostic testing or not ordering the appropriate diagnostic testing for the clinical syndrome in any given patient. And where this comes into play, really, is the fact that when we order diagnostic testing in the United States for immune-mediated neurologic disorders, these autoantibody panels are available to us that test for a multitude of autoantibodies all at the same time, and if we don't choose the appropriate test for the clinical syndrome that the patient is there with, we run the risk of getting a positive result for an antibody that's unrelated to the syndrome we're seeing in the patient – and no test is 100% specific (or 100% sensitive, for that matter), but these low-specificity issues when you indiscriminately test really can cloud the clinical picture and delay getting the appropriate diagnosis. And so, I really think that one of the biggest mistakes is seeing maybe a low-positive result for an antibody that does not match the clinical syndrome if you go back to the books and use your resources to figure out if that result is meaningful - overvaluing that antibody result and maybe plowing forward with a treatment plan that involves a long course of immunomodulatory therapy is a pretty significant mistake. And then, on the flip side is that because these panel tests, you order them as a block, and you think that you ordered the right thing - or you think that whoever you asked to order the order for you ordered the right thing – and so often, people say the panel was negative, and they don't look at the individual results of the antibodies that were tested in the panel, and because different antibody panels are designed to test for different clinical phenotypes. I see the error where a clinician thinks that all of the antibodies necessary to test for were tested for and negative, and now they feel like their hands are tied. And so, it's both this overvaluing the diagnostic testing and forgetting to question the testing results if they're not what you expect once you get more clinical data - I think both of those are pretty big mistakes. And continuing, again, always be curious, always recheck results, and don't take laboratory values in an EMR that are in black and white as the stone-cold truth that tells you your answer - you have to stay curious about the patient, their history, their neurologic presentation, their response to treatment over time, and really keep assessing. My other soap box here about diagnostic testing is that, historically, a lot of the antibodies that we test for were called paraneoplastic (and that's because they were some of the first antibodies discovered, so, they were some of the earliest ones that we developed tests for), and clinical reference laboratories continue to offer paraneoplastic panels for historical reasons and because a lot of people think that that's what they want. But, paraneoplastic panels, in and of themselves, are not representative of a specific clinical phenotype - they just diagnose patients who have a high risk of malignancy associated with an antineural antibody. And so, most of the clinical reference labs I know of - certainly at ARUP, we have a notice on our testing page, I know Mayo Clinical Laboratories also has a notice that says, “Paraneoplastic panels are not generally the recommended panel to test for antineural antibodies. Consider ordering the phenotype-specific panel that fits the patient's clinical syndrome”. And I think that's super important – we still have paraneoplastic stuck in our head for historical reasons, and it is almost never the right answer.   Dr Weathers: It's really interesting. At my organization, you know, we actually have had some really thoughtful conversations about, do we really restrict it (you know, as part of lab stewardship efforts) - and, you know, these are expensive, and to your point, they can be frankly, really dangerous, you know, to really send somebody down this wrong path with a lot of surveillance, committing them to immunomodulatory therapies, and take you in completely the wrong direction when, actually, your low test probability was very low. So, I think that is an excellent one to really call out and for people to be very thoughtful of - and the way, again, to avoid it is to be very thoughtful about the panels. And for people, certainly, they are very convenient, but people need to be really aware of what's in them and what they are ordering and how to interpret them. And I love that advice about not just thinking about the wholesale as negative - really, you know, for many of us, they are still coming in as scan documents, you know, click into them, read every line, really understand what those results mean.   Dr Smith: And I would also say that I think people don't realize, but clinical reference laboratories would love for you to reach out when there are questions. So, if you don't understand the diagnostic testing that was performed or result, you pretty much all have hotlines. You can call and reach out to an expert in the testing and ask them some questions, and don't be afraid to reach out to your colleagues who might have more experience. We love hearing from people with questions and helping to direct them to the right testing and help them get the answers that they really want to for their patients.   Dr Weathers: I think that is a great plug. Before you order, preferably, before you send in.   Dr Smith: I do like when I hear from people before mistakes were made. Yes. That's nice.   Dr Weathers: It's a great point.   Dr Smith: When you order these panels, you do run the risk of having these low positive results that may or may not be clinically meaningful. And we do recommend that most of the diagnostic testing be ordered in both serum and CSF. And so, a good example of a mistake that can be made is a very low-positive NMDA-receptor antibody in serum - maybe it was ordered for a patient with cognitive decline or confusion (maybe not under the ideal clinical scenario for ordering), and then it's negative in the CSF. So, an NMDA-receptor positive, negative in the CSF, not the right clinical picture, people can get really jazzed and want to treat an NMDA-receptor encephalitis, that in that case, really isn't meeting diagnostic criteria, and there are excellent diagnostic criteria that have been developed and published for that disorder and for several other autoimmune neurologic disorders, and I think going back to those criteria and really questioning yourself before you start blindly down a path based on a lab result is really important.   Dr Weathers: I think that's excellent advice, too, always keeping that in mind that just because you have gone down this path and gotten that result doesn't mean that you are stuck and committed to it. Always keeping that criteria in mind, always going back, always checking it is really important as well. Moving on from mistakes to kind of an adjacent question, what do you think is the biggest controversy right now when it comes to the treatment of patients with autoimmune neurologic disorders?   Dr Smith: You know, one of the big controversies that I see and I'm concerned about is that we've gotten into a habit of treating the way we've always treated based on expert opinion, and while experts have their opinions based on a lot of experience, they don't take the place of well-designed randomized controlled clinical trials - and in rare diseases (like autoimmune neurologic diseases), it can be really challenging to conduct those trials, especially in the face of people who have a pathway that they always do with their patients. If they have a NMDA-receptor encephalitis patient, they feel very comfortable doing their standard of care with IV steroids and then either plasma exchange or IVIG, and then possibly (and very often), I see following with a B-cell inhibitor, like rituximab, as sort of just a “kitchen-sink” approach to treatment. And while I understand the passion and the desire to make a really sick patient sitting in front of us better as fast as possible, I don't think we have adequate evidence to support that being the “one-size-fits-all kitchen-sick” approach for treatment. And I really am passionate about all clinicians all over the world, supporting randomized controlled clinical trials that are well-designed with the backing of experts in the community, so that when we look at a patient and tell them that we recommend a course of treatment, we're recommending it based on the best quality evidence available, not just what everyone's always done before. I think we can do better than that. And I think there's some controversy in this. Some people think that it doesn't make sense, we already know the answer, but I would say we haven't asked the right question and thoroughly investigated enough. And this is especially important with children, right? We know pediatric patients often don't have well-designed clinical trials to guide their treatments - but in NMDA-receptor encephalitis, many of the patients are children, and I think that they deserve to be involved in well-designed clinical trials in order to support the recommendations that we make for treatment.   Dr Weathers: And in addition to children, think about all of the other patient populations that have traditionally not been well represented in trials, right - pregnant patients, patients of color (historically very underrepresented in trials) - many, many other patient populations that have not been adequately represented.   Dr Smith: Absolutely. Yeah. I think we need to really care about that and face that problem head on and speak to it. We can't just say this is the way we've always done things, so we're going to keep doing it that way. I think we owe it to our patients and ourselves, when we look our patients in the eye, to say that we have good evidence to support the recommendations we're making.   Dr Weathers: I think we have already answered this question in many ways with each of the questions we've already talked about, but is there any other strong arguments that you can make for why it's important for neurology clinicians to read your article?   Dr Smith: Dr Clardy and I spent a lot of time working on this article, trying to put together a piece that will be a resource that people could turn to again and again. I don't think that this article is something that you should read from top to bottom and think that you've absorbed and digested everything, right? So, what we work to do was to really provide a structure and a framework to think about the treatment of immune-mediated neurologic diseases. So, rather than memorizing specific drugs for specific conditions, we developed sort of a space where you could talk about B-cell targeting therapies and the different ways we can target B-cells, we talked about complement inhibitors, neonatal FC receptors, and, really, just at a high level, how these drugs work and how they're targeted, so that going forward in three, four, five years, what I believe we'll know more about each of the individual diseases mediated by antineural antibodies. When we understand what causes that disease, we'll be able to go to a resource like this and choose rationally based on mechanism of action, a drug to treat our patient - even if it's in a patient with such a rare disease that we don't have the luxury of a clinical trial to guide our choices.   Dr Weathers: That's a really excellent point - and I know I've said it a few times, but I think you guys did such a really excellent job at really laying it out in a way that makes it this really comprehensive, really easy-to-use resource at that point of care for providers to be able to do exactly that. Well, I always like to end on a hopeful note, so, this is always my favorite last question – but, what do you think is the next breakthrough coming in the treatment of patients with autoimmune neurologic diseases?   Dr Smith: Yeah, I think in the near future (I certainly hope, at least) that the next breakthrough is going to be in really being able to deliver personalized care based on what we understand about the mechanisms of a patient's rare disease. So, again, right now, I find we're kind of left with the “kitchen-sink” approach because we know so little about the mechanisms that drive each of these unique neurologic diseases and we don't have enough information from clinical trials to inform rational treatment decisions, so we go with these broad approaches - and I really think that in the near future, with work being done by a lot of people (dedicated people over the world) on biomarkers and things that predict either onset of disease or relapse or disease severity or really looking at basic fundamental mechanisms that drive disease, we're going to be able to make more rational choices in the treatment of these patients and mobilize the resources that are expensive, but valuable for the right patient at the right time.   Dr Weathers: That is a very exciting and hopeful future to look towards. Thank you, Dr Smith, for joining me on Continuum Audio. It was wonderful to get to spend this time with you again. Again, today, I've been interviewing Dr Tammy Smith, whose article on therapeutic approach to autoimmune neurologic disorders, written with Dr Stacey Clardy, appears in the most recent issue of Continuum on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners for joining today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/AudioCME. Thank you for listening to Continuum Audio.

“Addicted” - “exhibiting a compulsive, chronic, physiological or psychological need for a habit-forming substance, behavior, or activity.” Like other health conditions, addiction is multifactorial. It is the result of an alignment of root causes. In this newsletter, I'll discuss:* Substance addiction and behavioral addictions* Why addiction is not simply about dopamine and why there are multiple addictive personalities* How & why we differ in our physiologic response to substances* Our culture's shaming and punishment of addiction while fueling addiction* The role of attachment disruption, trauma, emotional dysregulation, and social isolationSubstance AddictionWhen it comes to addiction, you might expect me to talk a lot about dopamine.  Not all substance addictions are the same, however. Opioids act very differently on the body than alcohol, which acts differently than cocaine.  Some substances are more addictive than others, and even more so in certain people.  For most people, marijuana is less addictive, while alcohol, cocaine, and opioids are more addictive. Addictive Substances:* Alcohol* Caffeine* Cannabis* Hallucinogens* Sedatives and Hypnotics/Anxiolytics* Inhalants* Opioids* Stimulants* TobaccoSeemingly, 10-20 % of people who try substances will have problems with addiction. Our genetic makeup and the expression of our genes will impact how we react to substances, just as they will affect how we metabolize specific medications or environmental toxins.  We could, for example, have a weak enzyme that slows our metabolism of alcohol and results in our becoming more intoxicated more quickly.  We may have high neurotransmitter activity that we're trying to calm down with substances, or we may have low neurotransmitter activity and are taking substances or even carrying out certain behaviors that increase our neurotransmitter activity.   Behavioral AddictionWhile we can become severely addicted to substances, we can also become addicted to behaviors or the feelings brought on by the behavior or anticipation of the behavior. Examples of Behavioral Addiction:* Food addiction* Sex addiction* Love and relationship addiction* Codependence is considered a relationship addiction in that relationships are often one-sided, emotionally destructive, or even abusive.* Exercise addiction* Body dysmorphic disorder* Health addiction* Shopping addiction* Gambling addiction* Work addiction* Video game addiction* Internet addiction* Smartphone addiction* Social media addiction* Porn addiction* News addiction* Information addiction* Self-harm addiction* Extremism is also felt to overlap with addictionWe can become addicted to anything that spikes the reward chemicals in our brains.  If we're not sure if we're addicted, we can ask ourselves, “Is the compulsive behavior having negative consequences?”The severity of our addictions falls on a spectrum.  I may not have a gambling addiction where I am putting myself at financial risk; however, I could be addicted to sugar, which I know negatively impacts my health, gives me brain fog and fatigue, and causes me to check out of my relationships, including my relationship with myself. Culture: Shame & Punishment The last thing that we need if we are addicted to a substance or behavior is shame and punishment. Our culture still tends to see addiction as a moral failing or even a sin that can be removed with punishment.  This thinking leads to simplistic consequences such as rejection by family and friends and even imprisonment.  The same happens with other forms of mental illness, but in this case, there is even less understanding, less compassion, more anger, and more disdain.Culture: Fueling AddictionMeanwhile, most of us are becoming more addicted - addicted to our cell phones, social media, divisive stimulating news and information.  We have more information coming at us than we can process.  Our brains are flooded with catecholamines as we stay in highly stimulated states. One of those catecholamines is dopamine, which will drive motivation and have us in pursuit of “more.”  While there may be a type of pleasure in that pursuit, it's not a joyful or even content type of pleasure. When we are in pursuit, we are not present in our lives.   Many of us can barely process our moments, days, and lives in these modern times. For many, what was a life of memorable moments (positive and painful) has become a blur of days quickly passing by. Before we've had time to process what has happened, what we've experienced, or what we've felt, our minds are in pursuit of the next thing we need to know or have.With addictive technology comes the marketing and its messages - “more food, more sex, more youth and beauty, more health, more money, more success, and even more love - the elusive movie kind.  We are forgetting how to be satisfied and tolerate uncomfortable feelings.Attachment & TraumaWe haven't all had the same early attachment experiences. Some of us have experienced childhood trauma. We don't know what safety feels like. Two-thirds of those with opioid addiction have childhood trauma. This doesn't account for the trauma that can occur before verbal memory, which is usually not reported.Childhood trauma impacts our autonomic nervous system, our limbic system, and our hormonal stress response. Before we even experience a stressor, our baseline neurotransmitters may already be too high. Our trauma, in combination with our genetic variants, may result in high neurotransmitters that we may try to calm down with our addiction, or our trauma, in combination with our genetic variants, may have us seeking out stimulation so we can feel more alive and connected.Social IsolationPart of our understanding of addiction comes from the work of American psychologist Dr. Bruce Alexander, who did the “Rat Park” study.  Previous research had already shown that when rats were put in solitary confinement and given a choice between water and heroin or cocaine, the rats repetitively consumed the drug-laced water until they overdosed and died.Alexander realized that the problem may not be the rats but the environment.  Rats are social animals, just as we are.  So, he created “rat parks,” where the rats could roam, play, socialize, and have sex.  Despite being given the same access to the two types of drug-laced water, these rats preferred the plain water.  Even if they did drink the drug-laced water occasionally, they never did obsessively, nor did they overdose.  The social environment was protective against addiction. If we want to help those with addiction, we need to think about connection. If we want to help ourselves with an addiction, we need to think about connection.Emotional RegulationOur ability to regulate our emotions (increase calm and decrease fear and anger) comes through interactions with other humans - safe humans. Ideally, we learn to regulate our emotions during our first three years. When we were distressed as infants and toddlers, we communicated that distress through our cries and facial expressions, our caregivers responded, and our physiology returned to a sense of calm and safety. This repeated process - not necessarily perfect, but “good enough” - resulted in our internalizing that early relationship and, with that, an ability to recognize our feelings, trust others, feel worthy, respond to uncomfortable feelings with coping skills, and return to our baseline emotional state.  Without this skill we acquire through attachment, we can become overwhelmed by our feelings or detached from our feelings. Our experiences, genetics, and temperament will impact which direction we go.There is not one “addictive personality” but many addictive personalities. Some of us will be highly sensitive, and others will have a low level of sensitivity. Some of us will become overwhelmed by stress or stimulation and use addictions as a way to try to calm our emotional and high neurotransmitter states.  Others will seek sensory stimulation or risk-taking to bump those neurotransmitters and increase the feeling state. Of course, our biochemical differences impact this as well:* For those of us who are undermethylated, we may find that we are sensory seeking, have high activity at the NMDA receptor, and find ourselves craving whatever has come to have meaning or has left a mark on our neurophysiology.  * For those of us who are overmethylated, we may have the desire to calm things down, slow our racing thoughts, and lower our high neurotransmitter activity.* For those of us with high pyrroles (and or CAPs profile), we may feel socially anxious or overstimulated and desire to feel calm and comfortable, but at other times, we may feel brave and invincible.“Being bold and adventurous and being sad and cautious seem like opposite personality types. However, these two paths to addiction are actually not mutually exclusive. The third way involves having both kinds of traits, where people alternatively fear and desire novelty and behavior swings from being impulsive and rash to being compulsive, fear driven, and stuck in rigid patterns. ……My own story spirals around this paradoxical situation: I was driven enough to excel academically and fundamentally scared of change and of other people—yet I was also reckless enough to sell cocaine and shoot heroin.” - Maia Szalavitz We need to think more broadly about addiction, just as we would any other health condition.  We need to address the underlying physiological root causes, meet our human need for connection, and learn ways to experience, tolerate, and cope with our very human and necessary feeling states.  In this week's paid newsletter, I look forward to discussing cases to illustrate how various neurotransmitters can be at play with different substance addictions and how targeted nutrients can be used in the treatment of addictions - both substance and behavioral. Until next time,CourtneyIf you'd like to dive deeper into the root causes of brain symptoms, consider becoming a paid subscriber. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit courtneysnydermd.substack.com/subscribe

We are BACK for SEASON FIVE of the pod! In this episode, Dr. Jessica Steier and Dr. Sarah Scheinman discuss Alzheimer's disease and cognitive decline. They cover essential topics including the definition and symptoms of Alzheimer's, the genetic and epigenetic basis of the disease, brain changes associated with Alzheimer's, risk factors such as age, genetics, and lifestyle, modifiable risk factors and prevention strategies, and current treatments and their controversies.The scientists emphasize that maintaining overall health is crucial for brain health. They recommend a combination of lifestyle choices that promote general well-being, which in turn support cognitive health.They explore various treatment options, including cholinesterase inhibitors, NMDA receptor antagonists, and monoclonal antibodies targeting amyloid beta. The conversation highlights the ongoing debates about treatment efficacy and the need for further research.The episode aims to provide valuable insights and alleviate fears surrounding Alzheimer's disease. It concludes with a rapid-fire Q&A segment addressing listeners' questions.All our sources from this episode are available at: https://www.unbiasedscipod.com/episodes/dont-you-forget-about-me-unraveling-alzheimers(00:01) Music and Season Five Welcome(04:30) Introducing Dr. Sarah Scheinman and the Topic of Alzheimer's(07:49) Understanding Alzheimer's Disease and Its Symptoms(10:50) The Genetic and Epigenetic Basis of Alzheimer's(18:23) Risk Factors for Alzheimer's: Age, Genetics, and Lifestyle(26:02) The Role of Amyloid Plaques and Tau Tangles in Alzheimer's(30:37) Promoting Early Diagnosis and Intervention for Alzheimer's(35:21) Breaking Down the Stigma and Building Scientific Literacy(41:51) Treatments for Alzheimer's Disease(46:27) Monoclonal Antibodies and Controversy(53:50) Diagnosing Alzheimer's Disease(55:32) Final Thoughts: Q&A: Common Questions About Alzheimer's DiseaseInterested in advertising with us? Please reach out to advertising@airwavemedia.com, with “Unbiased Science” in the subject line.PLEASE NOTE: The discussion and information provided in this podcast are for general educational, scientific, and informational purposes only and are not intended as, and should not be treated as, medical or other professional advice for any particular individual or individuals. Every person and medical issue is different, and diagnosis and treatment requires consideration of specific facts often unique to the individual. As such, the information contained in this podcast should not be used as a substitute for consultation with and/or treatment by a doctor or other medical professional. If you are experiencing any medical issue or have any medical concern, you should consult with a doctor or other medical professional.Further, due to the inherent limitations of a podcast such as this as well as ongoing scientific developments, we do not guarantee the completeness or accuracy of the information or analysis provided in this podcast, although, of course we always endeavor to provide comprehensive information and analysis. In no event may Unbiased Science or any of the participants in this podcast be held liable to the listener or anyone else for any decision allegedly made or action allegedly taken or not taken allegedly in reliance on the discussion or information in this podcast or for any damages allegedly resulting from such reliance. The information provided herein do not represent the views of our employers. Hosted by Simplecast, an AdsWizz company. See pcm.adswizz.com for information about our collection and use of personal data for advertising.

We are BACK for SEASON FIVE of the pod! In this episode, Dr. Jessica Steier and Dr. Sarah Scheinman discuss Alzheimer's disease and cognitive decline. They cover essential topics including the definition and symptoms of Alzheimer's, the genetic and epigenetic basis of the disease, brain changes associated with Alzheimer's, risk factors such as age, genetics, and lifestyle, modifiable risk factors and prevention strategies, and current treatments and their controversies. The scientists emphasize that maintaining overall health is crucial for brain health. They recommend a combination of lifestyle choices that promote general well-being, which in turn support cognitive health. They explore various treatment options, including cholinesterase inhibitors, NMDA receptor antagonists, and monoclonal antibodies targeting amyloid beta. The conversation highlights the ongoing debates about treatment efficacy and the need for further research. The episode aims to provide valuable insights and alleviate fears surrounding Alzheimer's disease. It concludes with a rapid-fire Q&A segment addressing listeners' questions. All our sources from this episode are available at: https://www.unbiasedscipod.com/episodes/dont-you-forget-about-me-unraveling-alzheimers (00:01) Music and Season Five Welcome (04:30) Introducing Dr. Sarah Scheinman and the Topic of Alzheimer's (07:49) Understanding Alzheimer's Disease and Its Symptoms (10:50) The Genetic and Epigenetic Basis of Alzheimer's (18:23) Risk Factors for Alzheimer's: Age, Genetics, and Lifestyle (26:02) The Role of Amyloid Plaques and Tau Tangles in Alzheimer's (30:37) Promoting Early Diagnosis and Intervention for Alzheimer's (35:21) Breaking Down the Stigma and Building Scientific Literacy (41:51) Treatments for Alzheimer's Disease (46:27) Monoclonal Antibodies and Controversy (53:50) Diagnosing Alzheimer's Disease (55:32) Final Thoughts: Q&A: Common Questions About Alzheimer's Disease Interested in advertising with us? Please reach out to advertising@airwavemedia.com, with “Unbiased Science” in the subject line. PLEASE NOTE: The discussion and information provided in this podcast are for general educational, scientific, and informational purposes only and are not intended as, and should not be treated as, medical or other professional advice for any particular individual or individuals. Every person and medical issue is different, and diagnosis and treatment requires consideration of specific facts often unique to the individual. As such, the information contained in this podcast should not be used as a substitute for consultation with and/or treatment by a doctor or other medical professional. If you are experiencing any medical issue or have any medical concern, you should consult with a doctor or other medical professional. Further, due to the inherent limitations of a podcast such as this as well as ongoing scientific developments, we do not guarantee the completeness or accuracy of the information or analysis provided in this podcast, although, of course we always endeavor to provide comprehensive information and analysis. In no event may Unbiased Science or any of the participants in this podcast be held liable to the listener or anyone else for any decision allegedly made or action allegedly taken or not taken allegedly in reliance on the discussion or information in this podcast or for any damages allegedly resulting from such reliance. The information provided herein do not represent the views of our employers. Learn more about your ad choices. Visit megaphone.fm/adchoices

Dr. Will Van Derveer, joins Dr. Jill Carnahan to discuss the promising advancements and therapeutic benefits of psychedelic substances in treating mental health conditions like **PTSD**. Dr. Van Derveer is a renowned expert in integrative psychiatry and brings invaluable insights into how these unconventional therapies are reshaping the future of mental health care. Key Points ✅ Could psychedelics may become legal and appropriate treatment for depression and PTSD this year? ✅ What are the different potential indications of NMDA, psilocybin (magic mushrooms) or ketamine therapy in the treatment of psychiatric disorders and PTSD ✅ Why is it important to have trained medical staff and therapists for these types of therapies  and their success in treating patients with depression, anxiety or PTSD Will Van Derveer, MD Will Van Derveer, MD is co-founder of Integrative Psychiatry Institute, which offers comprehensive training for mental health professionals in psychedelic-assisted psychotherapy and other continuing education programs.   He is medical director of Integrative Psychiatry Center of Boulder, CO, providing integrative psychiatry for a broad range of conditions and ketamine-assisted psychotherapy for treatment-resistant depression and PTSD.   In addition to his clinical practice and teaching, he has been involved with several studies sponsored by MAPS, investigating MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD, a breakthrough treatment which could be approved in late 2024 by FDA.