Drug Story

You may not think of fluoride as a drug, but it fits the bill: The FDA classifies fluoride as a drug, an essential nutrient to human health, and regulates its use. So yeah. It’s a drug.Fluoride used to be boring. 75% of US water is fluoridated, and it has greatly reduced the rate of tooth decay in this country and worldwide. Fluoridation has been among the biggest success stories in medical history.But like a lot of medicine these days, fluoride is suddenly controversial. Again. Here and there, governments - the whole state of Utah, towns all over Florida - have removed fluoride from water. And predictably, the rate of tooth decay in children soars afterwards.Still fluoride is also a riddle. Because while the US has had a lot of success with fluoride, most countries do NOT add it to their water - and many non-fluoridated countries have much the same rate of tooth decay as the US. Is fluoride toothpaste enough?What is going on with fluoride?!4 out of 5 dentists recommend you listen to this episode!Sources for this episode [1] Dentition of a Mesolithic Population (1967) American Journal of Physical Anthropology: Pre-industrial populations experienced significantly lower rates of dental caries, demonstrating the impact of modern diet and environment on oral disease.[2] Toothache (1994) Poetry Foundation: William Greenway: William Greenway’s visceral portrayal of dental pain.[3] A Colorado Story (2015) Colorado Dental Association: Naturally fluoridated water was definitively linked to reduced tooth decay, establishing the scientific basis for fluoridation policy.[4] The Story of Fluoridation (2024) National Institute of Dental and Craniofacial Research: Fluoridation emerged from observed natural fluoride exposure and was adopted as a nationwide preventive health strategy.[5] Pipe Dreams: America’s Fluoride Controversy (2011) Science History Institute Museum & Library: Water fluoridation sparked decades of political and scientific conflict, becoming one of the most contested public health interventions in U.S. history.[6] Big Hopes for Little Teeth (2024) National Institute of Dental and Craniofacial Research: Fluoridation significantly reduced childhood tooth decay and became a foundational population-level prevention strategy.[7] Community Water Fluoridation in Focus: A Comprehensive Look at Fluoridation Levels across America (2023) International Journal of Environmental Research and Public Health: Access to fluoridated water varies widely across the U.S., reinforcing geographic and socioeconomic disparities in preventive oral health.[8] Water fluoridation less effective now than in past (2024) Cochrane: Fluoridation still reduces cavities, but the magnitude of benefit is smaller than in the mid-20th century.[9] Water fluoridation for the prevention of dental caries (2024) Cochrane Library: Fluoridation consistently lowers rates of tooth decay across populations, though evidence quality and modern applicability vary.[10] Research review contends fluoride in water is less effective than in 1970s (2024) American Dental Association: The marginal benefit of water fluoridation has decreased due to widespread fluoride exposure from toothpaste and other sources.[11] Out of Pocket: A Snapshot of Adults’ Dental and Medical Care Coverage (n.d.) CareQuest Institute: Lack of dental coverage forces many adults to delay or forgo care, increasing reliance on low-cost public health interventions like fluoridation.[12] Health Disparities in Oral Health (2024) CDC: Oral health outcomes are consistently worse for low-income and minority populations due to structural barriers and uneven access to prevention.[13] Two Cities Fluoride Removal Evidence (2025) Science News: Discontinuing fluoridation results in measurable declines in dental health outcomes.[14] What happened when Juneau took fluoride out of the drinking water? (2019) University of Alaska Anchorage: Removing fluoridation leads to increased tooth decay and higher rates of dental procedures, especially in children.[15] The Fluoride Wars Rage On (2021) nature: Fluoridation remains politically and culturally polarizing despite decades of scientific support. Get full access to Drug Story at www.drugstory.co/subscribe

This episode is all about ivermectin - which truly is a wonder drug! A veritable miracle cure.For, ahem, river blindness. And for some other parasitic diseases, like hookworm. Mostly in animals.But in the US, you have likely heard of ivermectin not as a treatment for parasites but for different purposes altogether. There are thousands of videos on YouTube and Instagram extolling ivermectin for viral diseases like Covid, various cancers, and for something called a “parasitic detox,” or a “parasitic cleanse.”Really? This one drug does all that?No. It does not.In this episode of Drug Story, we tell the tale of ivermectin, and what gets all those people on TikTok raving about this drug - what they hope it could be, what they believe it works on.And then, with an open mind, we go to the science – to tease apart the true miracles from the mere fantasies.Source for this episode:[1] Dirt Eaters (2006) NCpedia: Hookworm spreads through skin contact with contaminated soil, with infection linked to poor sanitation and barefoot exposure.[2] What Would It Take to Describe the Global Diversity of Parasites? (2020) Proceedings B (Royal Society): Discussion of parasite diversity and implications for global health.[3] Charles Wardell Stiles (n.d.) The Online Collection and Catalog of Rockefeller Archive Center: Stiles identified hookworm as a widespread cause of disease in the American South and helped initiate national eradication efforts.[4] The Great Hookworm Crusade (1978) Facing South: Exploration of early 20th-century public health campaigns targeting hookworm.[5] The Germ of Laziness: Rockefeller Philanthropy and Public Health in the New South (2007): Analysis of the Rockefeller Sanitary Commission’s hookworm eradication campaign and its role in shaping public health systems.[6] How a Worm Gave the South a Bad Name (2016) NOVA (PBS): Hookworm caused anemia, fatigue, and cognitive impairment, contributing to stereotypes of laziness in the American South[7] Lessons Learned (2016) Vanderbilt University: Hookworm campaigns demonstrated the importance of sanitation, education, and coordinated public health infrastructure.[8] Public Health: How the Fight Against Hookworm Helped Build a System (2020) REsource: Early hookworm eradication efforts contributed to the formation of organized public health systems in the U.S.[8] Dr. Abbott Assails “Freedom” League (1910) The New York Times: Physicians publicly criticized groups opposing national health initiatives during early 20th-century reforms.[10] America’s Deadly Flirtation with Antiscience and the Medical Freedom Movement (2021) Journal of Clinical Investigation: Historical medical freedom movements mirror modern resistance to public health guidance.[11] The Hookworm Blues: We Still Got ’Em (2017) American Journal of Tropical Medicine and Hygiene: Hookworm infection remains present in parts of the U.S., particularly in areas with inadequate sanitation and persistent poverty.[12] The American Murderer (2023) Bunk History: Hookworm campaigns in the U.S. South prioritized poor white populations to address labor productivity and regional stigma, while excluding Black communities from interventions.[13] The Debate Is On: To Deworm Or Not To Deworm? (2015) NPR Goats and Soda: Mass deworming programs reduce worm infections and may improve school attendance, though evidence on long-term health and economic benefits remains debated.[14] Hookworm Persists in U.S. Despite Belief That It Was Wiped Out (2017) NPR: Ongoing hookworm cases in Alabama are linked to failing wastewater systems and persistent poverty.[15] Nobel laureate William Campbell describes developing a new drug to Cornell audience (2016) Cornell University College of Veterinary Medicine: Overview of the discovery of ivermectin and its development as a breakthrough antiparasitic drug.[16] Progress and Impact of 13 Years of the Global Programme to Eliminate Lymphatic Filariasis (2014) PLOS Neglected Tropical Diseases: Mass drug administration programs using ivermectin significantly reduced transmission of filarial diseases worldwide.[17] The Discovery of Ivermectin: A Crapshoot or Not (2007) Cambridge University Press: Ivermectin originated from screening soil microbes, with discovery driven by trial-and-error experimentation.[18] The Life and Times of Ivermectin — A Success Story (2004) Nature Reviews Microbiology: Ivermectin disrupts parasite nerve and muscle function, supporting mass drug administration campaigns that significantly reduced global parasitic disease burden.[19] Two Elite Medical Journals Retract Coronavirus Papers (2020) Science: Retractions of major COVID-19 studies exposed weaknesses in peer review and data verification.[20] Medical Liberty and Drugless Healers Confront Allopathic Doctors (1910–1931) (2008) Journal of Medical Humanities: Early 20th-century conflicts between alternative practitioners and mainstream medicine centered on regulation and authority.[21] Ivermectin and COVID-19: How a Flawed

Today we’re sharing an episode of Cautionary Tales, by Tim Harford.This show concerns Lydia Pinkham’s Vegetable Compound - one of the most popular patent medicines of the late 19th century. Mrs. Pinkham’s compound was sold as a “women’s tonic,” ideal for menopause or menstrual pain. The package promised big: "It cures bloating, headaches, nervous prostration, general debility, sleeplessness, depression, and indigestion.”But did it, really? No, it did not. Lydia Pinkham’s compound was the epitome of a cure-all that cured nothing, a secret concoction of herbs and roots and other ambiguous ingredients that promised tremendous benefits without any evidence whatsoever. Eventually, it was outrage over patent medicines like Mrs. Pinkham’s that turned into the creation of the FDA, and the evidence-based medicine we have today. Back next week with a new episode of DRUG STORY! Get full access to Drug Story at www.drugstory.co/subscribe

20 years ago, pharmacogenomics was all the buzz: matching specific drugs to our personal DNA was supposed to transform medicine and human health.But here we are 20 years later, and much of that excitement has fizzled. Very few doctors are actually tailoring their treatments to individual patient DNA in the clinic.In this special episode, I talk with Dr. Eric Topol, author of the new book Super Agers, about the promise of pharmacogenomics and the new frontiers of medicine. We talk about how he has always put science first - he shares the story of Vioxx, a pain reliever that he was early to see carried massive risks. Eric put his career on the line to let the world know about the problems. Get full access to Drug Story at www.drugstory.co/subscribe

Ever heard of neurasthenia, aka Americanitis? It was the first epidemic of the 20th century - and it's number one symptom was insomnia.It may have just been the electricity.In this episode of Drug Story, we step into that sweet oblivion called sleep, and that infernal torment called insomnia. We visit hustle culture, where sleep is just an obstacle to crushing it.And we learn about Ambien: the most popular sleeping pill ever invented. Until women started showing up in emergency rooms with amnesia...Sources for this episode[1] NEURASTHENIA, DEGENERACY, AND MOBILE ORGANS (1906) The British Medical Journal: Neurasthenia is defined by a state of "nervous exhaustion" and can include physical symptoms like head or spinal pain, insomnia, and constipation, along with mental depression.[2] Neurasthenia and a Modernizing America (2003) JAMA: Introduces neurasthenia after the Civil War as a nervous-energy disorder; the term declined in use after the 1930s.[3] ‘Americanitis’: The Disease of Living Too Fast (2016) The Atlantic: Frames neurasthenia as a disease of living too fast in industrializing America.[4] Insomnia and the late nineteenth-century insomniac: the case of Albert Kimball (2020) Interface Focus:The identity of the “insomniac” emerged alongside industrial-era stress and the concept of neurasthenia.[5] A short history of insomnia and how we became obsessed with sleep (2023) The Conversation: Industrialization increased insomnia rates through artificial lighting, work shifts, and societal change.[6] The Pathophysiology of Insomnia (2015) Contemporary Reviews In Sleep Medicine: Insomnia can be influenced by genetics, cellular and physiological mechanisms, and sleep behaviors.[7] Insomnia: a cultural history (2018) The Lancet: Contrasts pre-industrial ritualized sleep with modern increases in chronic insomnia.[8] Phenome-wide Analysis of Diseases in Relation to Objectively Measured Sleep Traits and Comparison with Subjective Sleep Traits in 88,461 Adults (2025) Health Data Science: In a research study, poor sleep quality was associated with increased risk for 172 different diseases including Parkinson's disease and type 2 diabetes.[9] A Short History of Sleeping Pills (2018) Sleep Review: The history of treatments for insomnia covering alcohol, opiates, barbiturates, benzodiazepines, and “Z drugs” like Ambien.[10] The Evolution and Development of Insomnia Pharmacotherapies (2007) Journal of Clinical Sleep Medicine: History of pharmacological treatment for insomnia: from older, less safe options like barbiturates to the current generation of medications with improved safety profile.[11] The Big Sleep (2013) The New Yorker: In 1973, Jean-Pierre Kaplan began work on a new class of sleeping pills at Synthélabo, leading to zolpidem’s development.[12] Critics say drug ads should be a wake-up call (2006) Star News: Critics link increased use of Ambien and Lunesta to aggressive advertising campaigns.[13] Evaluation of the long term efficacy and safety of zolpidem-MR 12.5 mg compared to placebo, when both are administered over a long term period “as needed”, in patients with chronic primary insomnia (2008) Sanofi-Aventis: Summary of Phase III clinical trial investigating the long-term efficacy and safety of the extended-release sleep medication, zolpidem.[14] Emergency Department Visits for Adverse Reactions Involving the Insomnia Medication Zolpidem (2013) SAMHSA: There was a 220% increase in emergency department visits related to adverse reactions from the sleep medication zolpidem between 2005 and 2010[15] FDA Drug Safety Communication: FDA approves new label changes and dosing for zolpidem products and a recommendation to avoid driving the day after using Ambien CR (2013) The U.S. Food and Drug Administration: FDA recommended lower doses and advised avoiding driving the day after using Ambien CR.[16] FDA adds Boxed Warning for risk of serious injuries caused by sleepwalking with certain prescription insomnia medicines (2019) The U.S. Food and Drug Administration: The official safety communication from the FDA announcing a Boxed Warning for specific prescription insomnia medications, including eszopiclone, zaleplon, and zolpidem, due to reports of dangerous side effects.[17] Zolpidem-Induced Sleepwalking, Sleep Related Eating Disorder, and Sleep-Driving: Fluorine-18-Flourodeoxyglucose Positron Emission Tomography Analysis, and a Literature Review of Other Unexpected Clinical Effects of Zolpidem (2009) Journal of Clinical Sleep Medicine: PET scans and literature review on zolpidem’s association with abnormal sleep behaviors.[18] Zolpidem and Driving Impairment — Identifying Persons at Risk (2013) New England Journal of Medicine: Examines risks of zolpidem, including sleepwalking, sleep-related eating disorder, and sleep-driving. Get full access to Drug Story at www.drugstory.co/subscribe

Pain is probably the oldest problem in medicine. It’s the way our bodies tell us that something is wrong here.But pain has long been considered a symptom. So when medicine can’t find what’s wrong, or when medicine can’t fix the pain, well, that’s usually the end of the story. And that’s left a lot of people with chronic pain suffering in silence.In this episode, we learn why pain is one of the great mysteries of medicine - one of the most challenging conditions to diagnose, to measure, and to treat successfully.We explore why the worthy effort to bring pain into the light inadvertently created what may be the most devastating social crisis (ahem, opioid epidemic) of the last century.And we look at a new pain medicine - Journavx - which is not approved for chronic pain (yet) but has a lot of people hoping for a path to peace without addiction.Sources for this episode[1] "Wrestling With Pain:" John J. Bonica, MD. Autobiography (1987) The International Symposium on Pain Analgesia: Dr. John J. Bonica recounts his life as a "wrestling match" against medical indifference to establish the multidisciplinary approach to pain therapy. [2] Oral History Interview with John J. Bonica (1993) John C. Liebeskind History of Pain Collection: John Bonica is widely regarded as the founding father of pain management.[3] International Symposium on Pain (1974) Raven Press: Proceedings from the first major international meeting on pain research and management.[4] Individual Differences in Pain: Understanding the Mosaic that Makes Pain Personal (2017) PAIN: Explains how biological, psychological, and social factors shape personal pain experiences.[5] Chronic Pain: What Does It Mean? A Review on the Use of the Term Chronic Pain in Clinical Practice (2021) Journal of Pain Research: "Chronic pain" is a semantically inaccurate and potentially misleading clinical label because it overemphasizes duration while failing to account for biopsychosocial factors.[6] Prevalence of Depression and Anxiety in Chronic Pain (2025) JAMA: Systematic review and meta-analysis showing high rates of depression and anxiety among adults with chronic pain.[7] Improving Outcomes of Analgesic Treatment: Is Education Enough? (1990) Annals of Internal Medicine: The persistent undertreatment of pain is rooted in a historical medical focus on physical lesions over subjective symptoms. [8] Pain as the 5th Vital Sign Toolkit (2000) The Veterans Health Administration: A comprehensive guide developed by the Veterans Health Administration (VHA) to institutionalize a standardized, system-wide approach to managing patient discomfort.[9] A Capsule History of Pain Management (2003) JAMA: Historical overview of approaches to managing pain, from ancient remedies to modern treatments.[10] Bridging Old and New in Pain Medicine: An Historical Review (2023) Cureus: Historical review linking traditional pain remedies with modern medical practices.[11] The Opioid Epidemic: It’s Time to Place Blame Where It Belongs (2017) The Journal of the Missouri State Medical Association: Dr. Ronald Hirsch argues that the opioid crisis was driven by a network of "co-conspirators" including pharmaceutical companies, medical oversight organizations, and government agencies.[12] The 5th Vital Sign and America’s Painkiller Epidemic (2016) The University of Arizona Health Sciences: The institutionalization of pain management led to a surge in prescription drug abuse and overdose deaths. [13] The Promotion and Marketing of OxyContin: Commercial Triumph, Public Health Tragedy (2008) The American Journal of Public Health: Oxycotin’s commercial success was driven by predatory marketing tactics, such as targeting high-volume prescribers and systematically understating the risk of addiction.[14] The fifth vital sign: A complex story of politics and patient care (2016) Cleveland Clinic Journal of Medicine: Aggressive marketing and institutional mandates minimized the perceived risks of addiction, leading to the current opioid epidemic.[15] The Pain and Opioid Epidemics: Policy and Vital Signs (2016) JAMA Health Forum: The historical movement to treat pain as a fifth vital sign inadvertently fueled a massive increase in narcotic prescriptions.[16] Addiction Rare in Patients Treated with Narcotics (1980) The New England Journal of Medicine: a 1980 letter to the editor of the New England Journal of Medicine covers the low incidence of narcotic addiction in medical settings. [17] Remove Pain as 5th Vital Sign, AMA Urged (2016) Medpage Today: Medical professionals at an American Medical Association met to advocate for the removal of pain as a "fifth vital sign".[18] FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain (2025) US Food & Drug Administration: FDA announcement of approval for a new, non-opioid treatment for moderate to severe acute pain.[19] F.D.A. Approves Drug to Treat Pain Without Opioid Effects (2025) The New York Times: The FDA approved a non-opioid painkiller developed by

The idea of drug patents makes a lot of sense: The company that put the effort and resources into developing the medicine is the first to reap the benefits. That company gets a limited monopoly for 20 years, when it is the only company allowed to manufacture and sell that drug.The deal is that after that patent expires, other companies can manufacture and sell the drug, too. The drug goes “generic.” Typically that means lower prices for patients - more people benefit. That’s how the system is supposed to work. But that system relies a lot on good faith - and many pharma companies have gotten very good at finding ways to extend that 20 years, making small tweaks to a drug to extend their monopoly for years.Today, I hand Drug Story over to the excellent journalist Dan Weissmann, host of the NPR podcast An Arm and A Leg. In this episode of An Arm and a Leg, Dan talks with John Green - author of the new book, Everything is Tuberculosis. Green explains a very effective drug for TB was kept under patent protection for years, making it too expensive to treat millions of people with tuberculosis, leading to thousands of unnecessary deaths worldwide. Get full access to Drug Story at www.drugstory.co/subscribe

It used to be that getting older meant slowing down. A little less pep, a little less zip, a little less zest. So it goes.For men, this was partly about testosterone. After 40 or so, our bodies produce less and less testosterone, the hormone that helps give men energy and vigor and sex drive. Lower testosterone was just part of growing older.But that was then! Nowadays, “Low T” is a bonafide medical condition - easily treated with a shot at your local neighborhood men’s health clinic.Today, what used to be a secret sauce of bodybuilders or cheating athletes is now downright normal. Millions of men worldwide take testosterone therapy - and not just those over 40. Check out Reddit or TikTok...It is a WHOLE THING.In this episode of Drug Story, we look at how TRT went mainstream, and how part of ordinary aging somehow became a disease.Sources for this episode[1] Male Hypogonadism (2024) STAT Pearls:Male hypogonadism is defined as inadequate testosterone production or impaired spermatogenesis, diagnosed via symptoms and low morning testosterone levels.[2] Brown-Séquard: An improbable genius who transformed medicine (2011) The Journal of Clinical Investigation: Charles-Edouard Brown-Séquard, a pioneering 19th-century scientist who rose from a difficult childhood in Mauritius is said to be the founder of modern endocrinology and neurology.[3] The life and legacy of Brown-Séquard (2017) Brain: Charles-Edouard Brown-Séquard’s insights helped show how nerves control blood vessels and laid the foundation for modern endocrinology by identifying internal secretions and early hormone therapy.[4] The “Elixir of Life” (1889) J.G. Cupples Co: In a self-report, Charles-Édouard Brown-Séquard covers his controversial self-experiments where he injected animal testicle extracts in pursuit of rejuvenation.[5] The effect produced on man by subcutaneous injections of a liquid obtained from the testicles of animal (1889) Lancet: In a 1889 Lancet article, Brown-Séquard describes his pioneering experiments with subcutaneous injections of animal testicular extracts to combat the physical and mental decline associated with aging.[6] A Brief History of Testosterone (2001) Journal of Urology: Hormone therapy became widely used to treat age and disease-related hormone decline, before risks were fully understood.[7] History of Testosterone and Therapeutic Potential (2020) Sexual Medicine Reviews: Testosterone was isolated in 1935 by the Organon group, with independent synthesis by Adolf Butenandt and Leopold Ruzicka.[8] Adolf Butenandt—Nobel Prize for Chemistry (2012) Mayo Clinic Proceedings: Adolf Butenandt isolated key sex hormones, contributing to foundational methods for steroid chemistry and earning the 1939 Nobel Prize in Chemistry.[9] Monkey business: reflections on testosterone (2012) BMJ: Testosterone is widely believed to drive masculinity, aggression, and performance, but strong evidence in humans is limited and inconsistent.[10] The male hormone (1945) Harcourt, Brace and Company: The Male Hormone was an influential book that shaped public and medical perceptions of testosterone as central to masculinity and male health.[11] Endocrines: The Use of Testosterone (1940) The New England Journal of Medicine: Dr. Joseph C. Aub’s NEJM article discusses testosterone as proven therapy for hypogonadism, with experimental applications for women and other conditions.[12] History of Doping in Sport (2001) International Sports Studies: Testosterone and anabolic steroids became central substances in performance enhancement, prompting regulatory responses and anti-doping frameworks in international sport.[13] New 'Breakfast of Champions': A Recipe for Victory or Disaster? (1988) The New York Times: Anabolic steroid use, including testosterone derivatives, was widespread in elite athletics despite known health risks and weak enforcement.[14] FTC Sues Drug Companies for Unlawfully Conspiring to Delay the Sale of Generic AndroGel Until 2015 (2009) Federal Trade Commission: Pharmaceutical companies used patent litigation and settlement agreements to delay generic testosterone gel competition and maintain market exclusivity.[15] Androgen deficiency in males (2010) Expert Review of Endocrinology & Metabolism: Clinical definitions of androgen deficiency rely on serum testosterone thresholds combined with symptoms, with variability across populations.[16] The male menopause—does it exist? (2000) BMJ: Age-related testosterone decline occurs gradually and inconsistently and does not parallel the hormonal cessation observed in female menopause.[17] Evolution of Guidelines for Testosterone Replacement Therapy (2019) Journal of Clinical Medicine: Article examines how definitions, diagnoses, treatments, and follow-up recommendations for testosterone replacement therapy have evolved across major societies (ISSAM, Endocrine Society, ISSM, AUA).[18] The Hazards of Male Menopause (1997) Science: Medicalization of age-related testosterone decline outpaced clinica

Do you feel that?That doubt and dread and worry?That’s anxiety - and lucky for you, there’s a pill for that.It’s called Xanax. And it works. Really well. And really fast.Prescribed for panic attacks and anxiety, one dose of Xanax usually kicks in within 15 or 30 minutes. Just like that, a sense of calm sets in, and your concerns fall away. It’s not a high, more like the opposite. You feel relaxed, your brain stops racing. It does the trick.Which is why Xanax is also super dangerous. Because of how well it works, and the way it works, Xanax is highly addictive. It brings such relief that one pill every once in a while turns into a little nibble every night. It tricks people into thinking that their concerns and worries can disappear with just one dose. Which is why Xanax is among the most counterfeited and abused drugs in the world right now.Writing this episode, I started thinking that Xanax was a perfectly fine drug that is sometimes a problem. But as I dug in, I realized that Xanax, like all benzodiazepines, is a trickster. It promises to be an easy, even fun way to push our anxiety aside. But as much as it brings relief, it also brings consequences - which can turn deadly.In this episode of Drug Story, we look at the idea of anxiety as a disease - a common human problem that can become, for some, a treatable condition. And we consider what “treatment” means, for good and for bad.Sources for this episode[1] Quitting Xanax: One Writer's Story (2024) Vogue Magazine: Martha McPhee details her seventeen-year dependence on Xanax, originally prescribed for panic attacks.[2] Fear and fitness: An evolutionary analysis of anxiety disorders (1994) Ethology and Sociobiology: Anxiety evolved as a defense mechanism with subtypes adapted to specific threats; anxiety disorders arise from dysregulated defenses.[3] A history of anxiety: from Hippocrates to DSM (2022) Dialogues in Clinical Neuroscience: Traces the understanding and classification of anxiety from ancient Greek and Roman philosophy to the DSM, noting Greco-Roman recognition of anxiety as a medical condition and early cognitive-behavioral approaches.[4] Should You Be Upset? Cicero on the Desirability of Emotion (2022) Antigone Journal: Examines Cicero’s views on whether suppressing or embracing emotions is desirable.[5] Cicero and the state-trait theory of anxiety: Another case of delayed recognition (1983) American Psychologist: H.J. Eysenck argues Cicero anticipated the modern distinction between anxious temperament and temporary anxious states.[6] The Effects of Stoic Training and Adaptive Working Memory Training on Emotional Vulnerability in High Worriers (2021) Cognitive Therapy and Research: Results from a study show that practicing Stoicism significantly reduces rumination and boosts self-efficacy.[7] Seneca (2024) Stanford Encyclopedia of Philosophy: Lucius Annaeus Seneca was a Roman philosopher who shaped stoicism and contributed to the concept of mindfulness and use of the present to manage emotions. [8] The developmental origins of anxiety (2004) Nature: Early developmental mechanisms establish a predisposition to anxiety through the interplay of genetic and environmental factors. While anxiety is a biological adaptive response to danger it becomes pathological when interfering with normal life. [9] DSM-III and the transformation of American psychiatry: a history (1993) The American Journal of Psychiatry: American psychiatry transitioned from a biopsychosocial model to a research-based medical model following the publication of the Diagnostic and Statistical Model.[10] The Feminine Mystique (1963) National Humanities Center: In her 1963 seminal writings, Betty Friedan wrote about a pervasive dissatisfaction and feeling of emptiness among American housewives.[11] Barbiturates: A Blessing and a Menace (1947) Journal of the American Pharmaceutical Association: A 1947 journal article aptly describes the nature of barbiturates as both a blessing and menace describing their medical importance as sedatives and their ability to be misused. [12] Listening to the Past: History, Psychiatry, and Anxiety (2005) The Canadian Journal of Psychiatry: 19th–early 20th century treatments for anxiety included the use of bromides, alcohol, opiates, and later barbiturates for relief.[13] How Was Anxiety Treated in the 1900s? (2023) Connect by ManagedMinds: Historically, anxiety has been treated by asylums, rest cures, early psychotherapy, and modern psychiatric medications like SSRIs.[14] The history of benzodiazepines (2013) The Consultant Pharmacist: Leo Sternbach discovered one of the first benzodiazepines, Valium, in 1955.[15] The Launch of Xanax (1989) Drug Information Journal: Upjohn Company ran a successful marketing strategy using targeted psychiatrist outreach and consistent messaging to establish Xanax’s market position.[16] Listening to Xanax (2012) New York Magazine: This article explores “functional anxiety” in high-achieving urban professionals and Xanax’s

For decades, obesity was treated as a matter of self-control and free will: If you were fat, it was your own fault.You could try a diet - but the diet companies were also in on the fix: For years, Weight Watchers was owned by Heinz food … and Jenny Craig was owned by Nestle. But it was still up to you. You made your choices, and you had to live with them. And so the obesity rate in the US soared from around 15% of the population in 1970 to more than 40% today. Clearly something is going on other than free will and personal choices.In this episode of Drug Story, we explore the origins of the obesity epidemic: the Green Revolution in agriculture, which saved a billion lives, but also made grain cheap cheap cheap. And we look at what happened when the tobacco companies decided to diversify into the food business (surprise: food became a lot more addictive, and a lot less healthy). And we re-consider the whole idea of personal freedom and free will.This episode's drug is Ozempic, and the whole class of GLP-1s that have up-ended our presumptions around obesity. These drugs have transformed millions of lives - they are surely one of the most impactful medical discoveries of the century. Unfortunately, these drugs have not dispelled the stigma around obesity. They’ve just shifted it a bit. If you think taking a GLP-1 is “cheating,” you’re still stuck in the old blame game.Sources for this episode[1] KFF Health Tracking Poll May 2024: The Public’s Use and Views of GLP-1 Drugs (2024) KFF: KFF poll showing awareness, perceptions, and use of Ozempic, Wegovy, and similar medications in the U.S.[2] Norman Borlaug Man Of The Year 1969 (2011) The International Maize and Wheat Improvement Center: Norman Borlaug introducing himself as a man who grew up during the Great Depression and was raised on a farm in Iowa. [3] Norman Borlaug and the Green Revolution (2017) 20th Century Time Machine: Norman Borlaug created a high-yield wheat strain that transformed the agricultural industry and saved an estimated one billion lives. Considered the father of the Green Revolution, he was awarded the Nobel Peace Prize in 1970.[4] Chapter 1 | The Man Who Tried to Feed the World (2020) American Experience PBS: Norman Borlaug, inspired by his own upbringing in struggling Iowa, helped the world avoid famine and hunger through revolutionizing wheat production.[5] Food Timeline FAQs: historic food prices (2024) Food Timeline: In addition to increasing the supply of food globally, the Green Revolution also made food much more affordable.[6] What Is the Evidence for “Food Addiction?” A Systematic Review (2018) Nutrients: A systematic review of 52 studies concludes that food addiction is a valid diagnostic construct that is more similar to substance use disorder than behavioral addiction, especially among processed foods with added sweeteners and fats.[7] The Origins of the Obesity Epidemic in the USA–Lessons for Today (2022) Nutrients: The origins of obesity can be traced back to the introduction of ultra-processed food in the American diet. [8] US obesity rates have tripled over the last 60 years (2025) USA Facts: American rates of obesity have tripled since the 1960s, with over 40% of Americans having obesity.[9] Daily supply of calories per person (2025) Our World in Data: From 1970 to 2020, Americans increased their daily calorie intake from about 3,000 to over 3,800 calories.[10] US tobacco companies selectively disseminated hyper-palatable foods into the US food system: Empirical evidence and current implications (2024) Addiction: In a study reviewing industry documents and U.S. Department of Agriculture data from 1988 to 2002, food produced U.S. Tobacco companies that owned food companies were 80% more likely to be high in carbs and sodium than other foods.[11] Many of today’s unhealthy foods were brought to you by Big Tobacco (2023) University of Michigan Department of Psychology: Research shows how major tobacco companies exerted their influence on the American diet by applying their expertise in chemical dependency to the food industry.[12] Ultra-processed Food Consumption in Youth and Adults: United States, August 2021–August 2023 (2025) CDC: According to the CDC, ultra-processed foods are hyperpalatable, high in sodium, and low in fiber, like sandwiches, sweet bakery products, and sweetened beverages.[13] Highly processed foods can be considered addictive substances based on established scientific criteria (2022) Addiction: Using the same scientific criteria the U.S. Surgeon General employed in 1988 to identify tobacco as addictive, this analysis suggests that highly processed foods, rich in refined carbs and added fats, should be considered addictive.[14] Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake (2019) Cell Metabolism: In a randomized control trial, researchers discovered that participants on an ultra-processed diet voluntarily consumed about

There’s no blood test for depression, no MRI or CT scan that can detect it. Because depression, like a lot of things involved with mental health, is invisible. Still, depression is the most common mental health issue in the US and worldwide. Nearly 30% of Americans will be diagnosed with depression in their lifetimes. Many people wind up taking an antidepressant. You’ve probably heard of these drugs by their brand names: Prozac Lexapro, Paxil and - the drug in this episode - Zoloft.These drugs do help, but finding the right drug that works for the right person can take a lot of time, and a lot of trial and error. This can be a messy and frustrating process. In this episode of Drug Story, we jump into that mess. We explore the mystery of how these drugs actually work - and why depression seems so much more common today than in the past. Sources for this episode:[1] History of depression through the ages (2020) Archives of Depression and Anxiety: From Hippocrates’ humoral theory to Freud, key historical figures shaped the understanding and treatment of depression.[2] History of Depression (2015) The Oxford Handbook of Mood Disorders: Symptom-focused diagnosis and treatment have contributed to the medicalization of normal human sadness.[3] Minnesota Multiphasic Personality Inventory (2023) StatPearls: Developed in the 1930s and published in 1942, the Minnesota Multiphasic Personality Inventory (MMPI) is the most common psychometric test for assessing personality traits and psychopathology including depression.[4] The development of Minnesota Multiphasic Personality Inventory (1994) Journal of the History of the Behavioral Sciences: Two scientists at the University of Minnesota, Starke Hathaway and J. C. McKinley, developed the MMPI in the 1930s, a widely adopted survey measuring mental illness.[5] Depression as a disease of modernity: Explanations for increasing prevalence (2012) Journal of Affective Disorders: Modern lifestyle factors like poor diet, inactivity, and social isolation may contribute to rising depression rates.[6] The creation of the concept of an antidepressant: An historical analysis (2008) Social Science & Medicine: The term antidepressant gained traction in the 1950s-1960s, framing drugs as disease-specific treatments for depression.[7] A RATING SCALE FOR DEPRESSION (1960) Journal of Neurology, Neurosurgery & Psychiatry: Max Hamilton published the Hamilton Rating Scale for Depression (HAM-D) questionnaire to measure severity of depression symptoms.[8] The PHQ-9 (2001) Journal of General Internal Medicine: The Patient Health Questionnaire (PHQ-9) is a nine-item depression symptom questionnaire used to screen adults for depression. Kurt Kroenke developed the PHQ in the mid-1990s with funding from Pfizer. [9] The Origin Story of the Zoloft Sad Blob, a Clinically Depressed Icon (2021) Mel Magazine: Early 2000s ads used a blob character to represent depression, which drew both praise and criticism.[10] Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature (2005) PLoS Medicine: SSRIs are marketed as correcting a serotonin deficiency, despite a lack of conclusive scientific evidence.[11] Antidepressants Don’t Work the Way Many People Think (2022) The New York Times: Experts note that the chemical imbalance theory of depression is outdated.[12] Development of the commercial process for Zoloft®/sertraline (2005) Chirality: Continuous chromatography enabled efficient large-scale production of sertraline.[13] The Architect of Zoloft (2015) Reed Magazine: Kenneth Koe modified tametraline compounds to block serotonin reuptake, leading to sertraline hydrochloride’s release as Zoloft in 1992.[14] ACS Award for Team Innovation (2006) Chemical & Engineering News: Zoloft’s discovery was led by Pfizer scientists Reinhard Sarges, B. Kenneth Koe, Willard M. Welch, Albert Weissman, and Charles A. Harbert.[15] Sertraline versus other antidepressive agents for depression (2010) Cochrane Database of Systematic Reviews: Sertraline is a selective serotonin reuptake inhibitor (SSRI) used as a first-line treatment for major depression, with evidence demonstrating superior efficacy over other antidepressants.[16] Do Antidepressants Work? (2018) The New York Times: In multiple meta-analyses of antidepressant trials, researchers confirm that while antidepressants are more effective than placebos for treating acute major depression, the actual clinical benefits are mostly modest. Study design, participant selection, and publication bias may result in more favorable evidence supporting the use of antidepressants.[17] What Obesity Drugs and Antidepressants Have in Common (2023) The New York Times: Aaron Carroll writes that because science cannot fully explain the biological mechanisms of mental health and obesity drugs, these treatments are stigmatized and incorrectly viewed as a lack of willpower rather than medically necessary.[18] The STAR*D study: treating depression in the real w

Once you turn 40, it seems like half the people you know are taking a statin drug. You know, because their cholesterol is high, and to prevent heart disease down the line. It makes sense: better safe than sorry.This is a huge triumph for preventive medicine. Statin drugs have saved (or improved) the lives of millions of people because they acted early. This is how medicine (and public health) is supposed to work.But the devil is in the details. Like all drugs, statins have side effects. And when they are prescribed for many millions of people, the math means that millions of people will not, in fact, get any benefit from the drug. It turns out that atorvastatin (and other statin drugs) may be the most over-prescribed drugs in the history of medicine. And therein lies a Drug Story.Sources for this episode:[1] Akira Endo- Gairdner Gala Acceptance Speech (2017) Canada Gairdner Awards: Akira Endo, the Japanese biochemist who discovered the first statin, reflects on American dietary and lifestyle habits that inspired him to develop a solution to prevent heart disease.[2] Influence of nicotinic acid on serum cholesterol in man (1955) Archives of Biochemistry and Biophysics: Since 1955, the B-vitamin niacin (nicotinic acid) has been used in the treatment of high cholesterol.[3] Atherosclerotic Cardiovascular Disease Risk Estimates Using the Predicting Risk of Cardiovascular Disease Events Equations (2024) JAMA Internal Medicine: The Predicting Risk of Cardiovascular Disease Events (PREVENT) cardiovascular risk equation excludes race, adds kidney function and statin use, and suggests fewer adults may be eligible for statins compared to pooled cohort equations.[4] It Took A Brilliant Marketing Campaign To Create The Best-Selling Drug Of All Time (2011) Business Insider: Lipitor became the best-selling drug of all time through aggressive marketing to doctors and coinciding with the FDA’s allowance of direct-to-consumer drug advertising in 1997.[5] Learning From Our Parents’ Heart Health Mistakes (2017) The New York Times: Indigenous South Americans, the Tsimane, have low rates of coronary artery disease and healthier lifestyles compared to Americans, offering a model for prevention.[6] CHOLESTEROL: DRUG HAILED AS TREATMENT BREAKTHROUGH (1987) The New York Times: The New York Times introduces lovastatin, a novel drug predicted to revolutionize the treatment of high cholesterol.[7] Millions fewer people may need statins, a new study suggests. But guidelines have yet to agree (2024) STAT: The number of adults recommended for statins could drop from 45.4 million to 28.3 million based on new risk calculations.[8] A historical perspective on the discovery of statins (2010) Proceedings of the Japan Academy: Akira Endo’s discovery of compactin from fungal cultures led to lovastatin, the first commercial statin.[9] The Role of Lipids and Lipoproteins in Atherosclerosis (1950) Science: John Gofman discovered LDL cholesterol and its correlation with atherosclerosis through ultracentrifugation of plasma lipoproteins.[10] Statins for Primary Cardiovascular Disease Prevention: Time to Curb Our Enthusiasm (2022) JAMA Internal Medicine: Cardiologists question the benefit of statins for individuals with low cardiovascular disease risk, citing limited evidence.[11] History of the Framingham Heart Study (1957) Framingham Heart Study: The Framingham Heart Study identified key cardiovascular risk factors, including high cholesterol, blood pressure, smoking, obesity, diabetes, and inactivity.[12] “For Me There Is No Substitute”: Authenticity, Uniqueness, and the Lessons of Lipitor (2010) American Medical Association Journal of Ethics: Lipitor backlash followed when it was revealed that Dr. Robert Jarvik, spokesperson in Lipitor ads, was not licensed to practice medicine and misrepresented his credentials.[13] Lipitor a story of rags to riches (2011) Arkansas Democrat-Gazette: Lipitor achieved success by lowering LDL cholesterol more effectively than competitors, aided by expanded statin eligibility guidelines.[14] History in medicine: the story of cholesterol, lipids and cardiology (2021) e-Journal of Cardiology Practice: Cardiology research has an extensive history: from its identification in gallstones in 1769 to Nobel Prize-winning discoveries on lipids and atherosclerosis.[15] Discovery of Lipitor (2009) Triumph of the Heart: The Story of Statins: Despite being the fifth statin introduced, Lipitor dominated the market due to superior LDL-lowering efficacy.[16] Counting Cholesterol (1987) The MacNeil/Lehrer NewsHour: Merck’s Mevacor became the first FDA-approved statin and cholesterol-lowering drug.[17] Cardiovascular Disease Resulting From a Diet and Lifestyle at Odds With Our Paleolithic Genome: How to Become a 21st-Century Hunter-Gatherer (2004) Mayo Clinic Proceedings: High cholesterol may stem from a mismatch between modern diets and Paleolithic human biology.[18] What Will the New Cardiovascular Risk Calculator Mean for Patients?

Epipen is an exquisitely engineered, expertly marketed, totally modern drug. And it’s an amazing success story, especially if you count success through dollars - Epipen sales rose from $200 million in 2007 to $1 billion a year in 2015 to more than $2 billion in 2023. Epipen is what they call in the pharma business, a blockbuster.The story of Epipen is also a story of unintended consequences and unexpected discoveries, one that goes from the Azores, some islands in the middle of the Atlantic Ocean, to Sweden, the home of the Nobel Prize, to Vietnam, during the Vietnam War.This story also lands very close to home. Today, Epipens are in schools, they’re in malls, they’re on airplanes, they may even be in your backpack or purse or glove compartment - just in case. So in this episode, we’ll learn all about that.And there’s also the biggest unintended consequence of all. It turns out that for many of the millions of people like Alex who live with food allergies - and the risk of anaphylaxis - their condition may in fact be the result of one of the biggest blunders of the past century of medicine and public health.Sources for this episode[1] A Mighty Pen (2013) Science History Institute Museum and Library: In the 1970s, inventor Sheldon Kaplan developed an epinephrine autoinjector in response to the need for rapid, self-administered injections to treat anaphylactic shock.[2] Auvi-Q Versus EpiPen: Preferences of Adults, Caregivers, and Children (2013) The Journal of Allergy and Clinical Immunology: This study evaluates preference for the Auvi-Q epinephrine autoinjector over the EpiPen among adults, caregivers, and children.[3] Epinephrine Administered in Anaphylaxis: The Evolution of 0.3 mg Dosage (2023) Therapeutic Advances in Allergy and Rhinology: Anaphylaxis was first formally discovered by French scientists Charles Richet and Paul Portier in experiments with dogs. They found that dogs became more sensitive, rather than less sensitive, to a toxin after an initial small dose.[4] Northeastern alumnus the genius behind life-saving EpiPen (2016) Northeastern Global News: Sheldon Kaplan reengineered a Cold War-era device, the ComboPen, that delivered a nerve agent antidote, into a device that delivered epinephrine. The new device, EpiPen, was patented under Kaplan’s name in 1977.[5] Body and Mind; Backward Protection (1989) New York Magazine: Anaphylaxis is a biological mechanism where the immune system provides misguided “backwards protection” by overreacting to allergens such as nuts, penicillin, or insect stings.[6] The Use of Adrenal Substance In the Treatment of Asthma (1900) Journal of the American Medical Association: Early research by Dr. Solomon Solis-Cohen showed that using extracts from animal adrenal glands could significantly relieve asthma symptoms by strengthening blood vessels and reducing swelling in the airways.[7] The Allergy Epidemics: 1870–2010 (2015) The Journal of Allergy and Clinical Immunology: The rise in allergies over the past 150 years can be attributed to advances in hygiene and lifestyle changes, such as increased sedentary indoor lifestyles.[8] History of food allergy and where we are today (2024) World Allergy Organization Journal: Once poorly understood, food allergies are now managed through strategies beyond avoidance, including immunotherapy, biologic treatments, and early allergen introduction for prevention.[9] How Marketing Turned the EpiPen Into a 20 Billion-Dollar Business (2015) Bloomberg Businessweek: Mylan Pharmaceuticals, the manufacturer of EpiPen, ran marketing campaigns emphasizing the dangers of food allergies and lobbied lawmakers to place EpiPens in schools and public venues. As a result, the EpiPen became a $1 billion-per-year product, and its price increased by 400% after Mylan acquired it in 2007.[10] Epinephrine: a short history (2015) The Lancet Respiratory Medicine: In 1894, the English physician George Oliver and the English physiologist Edward Schafer discovered the physiological effects of adrenal medulla extract. In 1899, American biochemist John Jacob Abel successfully purified the extract’s active ingredient and named it epinephrine. It was then synthesized in ampules by Parke-Davis & Company in 1909.[11] The ancestry of allergy: Being an account of the original experimental induction of hypersensitivity recognizing the contribution of Paul Portier (1985) The Journal of Allergy and Clinical Immunology: In 1902, Paul Portier and Charles Richet discovered anaphylaxis after observing that a second, weak injection of sea anemone toxin caused fatal hypersensitivity in dogs rather than the expected immunity.[12] Feed Your Kids Peanuts, Early and Often, New Guidelines Urge (2017) The New York Times: The National Institute of Allergy and Infectious Diseases shifted its approach to child nutrition in 2017 by recommending that parents introduce peanut-based foods to infants as early as four to six months of age.[13] Portier, Richet, and the discovery of anaphylax

Diabetes and anxiety and insomnia and depression and food allergies. For every modern malady, there are drugs promising to fix it. SO MANY DRUGS.But they never really fix the problem, do they? Yes, drugs can help people manage their disease. They treat the symptoms. But they rarely remedy what caused the disease in the first place. And therein lies a story. Launching Jan. 6, 2026. Get full access to Drug Story at www.drugstory.co/subscribe