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  • Midnight Drop: How a $16M Alzheimer's Miracle Vanished

    Midnight Drop: How a $16M Alzheimer's Miracle Vanished
    2026/07/24
    Midnight Drop: How a $16M Alzheimer's Miracle Vanished

    Hope turned to doubt overnight: a $16 million NIH grant, hundreds of patients in trials, and a drug called simufilam that rested on a disputed protein called filamin A - then every criminal charge was dropped at midnight. What happened to the biomarker data, the images that triggered retractions, and the independent verification that never arrived?

    In this episode, we lay out the timeline from the 2012 Journal of Neuroscience paper that introduced PTI-125 to the 2025 courtroom where charges were dismissed, tracing the grant, the clinical trials, the failed and later conflicting biomarker results, and the unresolved scientific record. How did foundational research, public funding, and patient trials converge - and vanish - without a clear resolution?

    Person: Hoau-Yan Wang
    Person: Lindsay Burns
    Event: Retraction of foundational opioid-related FLNA papers in 2022
    Date: Phase IIb failed biomarker analysis in May 2020
    Amount: $16,000,000 federal grant from NIH

    - 2012: PTI-125 (later renamed simufilam) first described in the Journal of Neuroscience.
    - 2017: Mouse data supporting the mechanism published in Neurobiology of Aging.
    - 2018: National Institutes of Health awarded Cassava Sciences $16,000,000 to support early clinical trials.
    - May 2020: Cassava's Phase IIb cerebrospinal fluid biomarker analysis initially failed to show the expected biological signal.
    - 2022: Foundational FLNA opioid-related papers by Wang and Maya Frankfurt were retracted due to similarities in background pixels in western blot images.

    To listen to this podcast ad-free and access premium episodes, try our subscription with a 14-day free trial at obomedia.com.

    © 2026 OBOMEDIA. All rights reserved.
    This episode and its content (audio, text, and related materials) are the exclusive property of OBOMEDIA and are protected by applicable copyright laws. Reproduction, distribution, editing, or commercial use, in whole or in part, without prior written permission from OBOMEDIA is prohibited. For permissions, licensing, and business inquiries: business@obomedia.com.
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    22 分
  • The Protein That Promised a Cure - and Vanished from the Data

    The Protein That Promised a Cure - and Vanished from the Data
    2026/07/24
    The Protein That Promised a Cure - and Vanished from the Data

    Hope turned to doubt when pixel-for-pixel repeats in lab images and a single lab's dominance over the evidence underpinned a drug that enrolled over 400 people with Alzheimer's - so what happened to the missing verification that should have stopped human trials? Who knew about the data shifts, and why did a failed biomarker readout get reversed months later?

    In this episode, we follow the path from a scaffolding protein called filamin A to a compound taken into human trials, tracing publications, funding, and the contested biomarker results to ask whether the scientific basis for simufilam was ever independently confirmed.

    Person: Hoau-Yan Wang
    Person: Lindsay Burns
    Company: Cassava Sciences (formerly Pain Therapeutics)
    Drug: simufilam (PTI-125)
    Enrollment: more than 400 people by August 2022

    - In 2012 Wang and Burns published a key paper linking filamin A to Alzheimer's in the Journal of Neuroscience.
    - In 2017 a follow-up study in Neurobiology of Aging reported that PTI-125 improved pathology in transgenic Alzheimer's-model mice.
    - In 2018 the NIH awarded funding to Cassava Sciences for early human trials of simufilam.
    - By March 2020 open-label human studies had begun with blood biomarker measurements taken from enrolled patients.
    - In May 2020 a Phase IIb biomarker analysis failed to support the hypothesized effects, but in September 2020 Cassava announced that an outside lab had produced improved biomarker results.

    To listen to this podcast ad-free and access premium episodes, try our subscription with a 14-day free trial at obomedia.com.

    © 2026 OBOMEDIA. All rights reserved.
    This episode and its content (audio, text, and related materials) are the exclusive property of OBOMEDIA and are protected by applicable copyright laws. Reproduction, distribution, editing, or commercial use, in whole or in part, without prior written permission from OBOMEDIA is prohibited. For permissions, licensing, and business inquiries: business@obomedia.com.
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    23 分
  • The Case of the Vanishing Blots: How Simufilam's Evidence Disappeared

    The Case of the Vanishing Blots: How Simufilam's Evidence Disappeared
    2026/07/24
    The Case of the Vanishing Blots: How Simufilam's Evidence Disappeared

    A single set of laboratory photographs - western blots - became the fulcrum of a dispute that touched federal grand juries, NIH funding, and hundreds of Alzheimer’s patients. Pixels matching across images from supposedly separate experiments, an outside lab that turned out to be the same academic group behind the drug, and a night-before-trial DOJ decision leave one central question: how did the visual evidence underpinning simufilam vanish into ambiguity?

    In this episode, we trace the chronology of simufilam’s rise and the contested data that sustained it, laying out the key players, the published papers, and the discovery that blurred the line between independent confirmation and internal reanalysis. What does the record show about the provenance of the western blots, and why did four federal investigations still not resolve that question?

    Person: Hoau-Yan Wang
    Person: Lindsay Burns
    Person: Thomas Südhof
    Date: September 2020
    Event: Re-analysis of biomarker data presented as from an outside laboratory

    - Cassava Sciences announced an outside laboratory confirmed simufilam’s biomarker improvements in September 2020.
    - The “outside laboratory” that re-analyzed the failed May 2020 cerebrospinal fluid biomarkers was Wang’s CUNY lab.
    - Simufilam (PTI-125) was built on findings about filamin A (FLNA) reported in PLOS One papers co-authored by Wang, Burns, and Maya Frankfurt.
    - NIH funding was awarded in 2018 and open-label studies began in March 2020 for simufilam.
    - Four simultaneous federal investigations occurred and the original laboratory data was never produced, leaving no court-established guilt or institutional proof of misconduct.

    To listen to this podcast ad-free and access premium episodes, try our subscription with a 14-day free trial at obomedia.com.

    © 2026 OBOMEDIA. All rights reserved.
    This episode and its content (audio, text, and related materials) are the exclusive property of OBOMEDIA and are protected by applicable copyright laws. Reproduction, distribution, editing, or commercial use, in whole or in part, without prior written permission from OBOMEDIA is prohibited. For permissions, licensing, and business inquiries: business@obomedia.com.
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    23 分
  • The Drug That Nausea Kept From Becoming a Psychedelic Mystery

    The Drug That Nausea Kept From Becoming a Psychedelic Mystery
    2026/07/24
    The Drug That Nausea Kept From Becoming a Psychedelic Mystery

    Nausea ended nearly every human trial before quipazine could show whether it was psychedelic - at 25 mg oral doses subjects had severe gastrointestinal distress, while rodents and monkeys showed clear LSD-like effects. How did a compound that substituted fully for LSD in animals fail so completely in people?

    In this episode, we trace quipazine’s discovery in 1966, its pharmacological profile across serotonin receptors, and the contrasting human and animal data that left researchers baffled. Can the same molecule trigger vomiting and mimic psychedelics at once, and what does that tell us about translating animal models to human consciousness?

    Person: quipazine
    Date: 1966 (first appearance in literature)
    Dose (human): 25 mg oral produced nausea and gastrointestinal distress
    Receptor affinity: strongest for 5-HT3; also binds 5-HT2A, 5-HT2B, 5-HT2C, 5-HT1B, 5-HT1A
    Animal finding: substituted fully for LSD in rodents and monkeys; produced head-twitch response in rodents

    - The literature records a single footnoted human report listing a 0.5 mg dose with an effect noted (printed with "sic").
    - At 25 mg oral in human subjects quipazine caused nausea, flatulence, cramps, and diarrhea with no LSD-like effects observed.
    - Quipazine’s strongest receptor affinity is for 5-HT3, a receptor whose activation provokes nausea and vomiting in humans.
    - In 1977 rodents given quipazine showed the head-twitch response, blocked by the 5-HT2A antagonist ketanserin.
    - Drug discrimination studies found quipazine substituted fully for LSD, DOM, and in reverse tests LSD, mescaline, and psilocybin substituted fully for quipazine in animals.

    To listen to this podcast ad-free and access premium episodes, try our subscription with a 14-day free trial at obomedia.com.

    © 2026 OBOMEDIA. All rights reserved.
    This episode and its content (audio, text, and related materials) are the exclusive property of OBOMEDIA and are protected by applicable copyright laws. Reproduction, distribution, editing, or commercial use, in whole or in part, without prior written permission from OBOMEDIA is prohibited. For permissions, licensing, and business inquiries: business@obomedia.com.
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    15 分
  • The Sic That Screamed: Half a Milligram, Full Psychedelic Mystery

    The Sic That Screamed: Half a Milligram, Full Psychedelic Mystery
    2026/07/24
    The Sic That Screamed: Half a Milligram, Full Psychedelic Mystery

    Half a milligram of quipazine is printed in the scientific record with a sic-an editor’s signal that the number looks wrong but was left as written-and that same tiny dose is reported to have produced a full psychedelic response. How could a compound that caused reliable nausea and blocked human testing also show unmistakable psychedelic markers in animals at doses supposedly far below prior thresholds?

    In this episode, we trace the paper trail from a 1966 research optimism to animal head-twitch responses in 1977, primate vomiting reports, and stalled human trials halted by dose-limiting nausea, and we ask whether the anomalous half-milligram report is a clerical fluke, a hint of hidden pharmacology, or evidence that quipazine’s effects were never fully testable.

    Person: James Winter
    Date: 1966
    Date: 1977
    Compound: quipazine
    Drug class: serotonin agonist

    - The published report records a dose of 0.5 milligram with the editorial insertion "sic".
    - In 1977, rodents exposed to quipazine produced the head-twitch response associated with psychedelics.
    - Monkeys given quipazine showed agitation, disrupted motor patterns, altered social interaction, and projectile vomiting.
    - Early human trials were limited by nausea, with a maximum tolerated dose recorded at 25 milligrams and no confirmed LSD-like effects below that ceiling.
    - James Winter proposed in 1994 using ondansetron to block nausea and reveal quipazine’s potential psychoactive effects.

    To listen to this podcast ad-free and access premium episodes, try our subscription with a 14-day free trial at obomedia.com.

    © 2026 OBOMEDIA. All rights reserved.
    This episode and its content (audio, text, and related materials) are the exclusive property of OBOMEDIA and are protected by applicable copyright laws. Reproduction, distribution, editing, or commercial use, in whole or in part, without prior written permission from OBOMEDIA is prohibited. For permissions, licensing, and business inquiries: business@obomedia.com.
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    22 分
  • A molecule proving psychedelic in animals for decades - blocked entirely by nausea

    A molecule proving psychedelic in animals for decades - blocked entirely by nausea
    2026/07/24
    A molecule proving psychedelic in animals for decades - blocked entirely by nausea

    A single compound produced the classic head‑twitch and substituted for LSD across decades of rodent studies, yet it never advanced in humans - because the same molecule caused projectile vomiting in primates that rodents cannot report. How did a reproducible psychedelic signal in animals get concealed by a basic anatomical difference, and what does that mean for interpreting decades of serotonin research?

    In this episode, we lay out the experimental trail from the compound’s 1966 synthesis through repeated rodent assays and primate trials, and follow how an ordinary physiological effect altered the course of scientific and clinical judgment. What happens when a reliable animal marker misses the one symptom that would make all the difference?

    Person: quipazine (one-(2-quinolinyl)piperazine)
    Date: 1966 (synthesis), 2007 (recording mentioned)
    Topic: serotonergic psychedelic activity and head-twitch response
    Event: projectile vomiting observed in primate trials
    Period: 1960s-2000s (decades of animal studies)

    - The compound quipazine was synthesized in 1966 and later used as a serotonin receptor probe.
    - In the 1970s, quipazine reliably produced the mouse head-twitch response, a standard marker of psychedelic-like serotonergic activity.
    - Drug-discrimination studies showed animals trained on LSD pressed the same lever when given quipazine, indicating subjective equivalence in nonverbal assays.
    - Rodents cannot vomit anatomically, so rodent studies could not reveal nausea or emesis caused by quipazine.
    - Primate trials showed LSD-like behaviors accompanied by projectile vomiting, halting further meaningful human trials.

    To listen to this podcast ad-free and access premium episodes, try our subscription with a 14-day free trial at obomedia.com.

    © 2026 OBOMEDIA. All rights reserved.
    This episode and its content (audio, text, and related materials) are the exclusive property of OBOMEDIA and are protected by applicable copyright laws. Reproduction, distribution, editing, or commercial use, in whole or in part, without prior written permission from OBOMEDIA is prohibited. For permissions, licensing, and business inquiries: business@obomedia.com.
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    23 分
  • The Molecule That Mimicked LSD - But Made Humans Vomit First

    The Molecule That Mimicked LSD - But Made Humans Vomit First
    2026/07/24
    The Molecule That Mimicked LSD - But Made Humans Vomit First

    A molecule that behaved like LSD in every animal test still failed humans because the body rejected it first: quipazine produced full animal substitution and head-twitch responses, yet in primates and humans it provoked pronounced, persistent vomiting that made psychedelic effects irrelevant. How did a compound pass rigorous behavioral signatures for half a century and still never arrive in human consciousness?

    In this episode, we trace quipazine’s unusual history through animal discrimination studies, primate trials, and the lone human reports, and ask whether the architectural clash between receptors explains the long puzzle. Could blocking one receptor have revealed the psychedelic effects that animals repeatedly signaled?

    Person: James Winter
    Date: 2007 (anonymous human report recorded; published 2011)
    Date: 1994 (Winter’s proposal)
    Topic: quipazine pharmacology
    Event: doctoral thesis at Columbia University sealed until 2030

    - Quipazine produced full substitution in drug discrimination studies trained on LSD, not partial or approximate.
    - Quipazine reliably evoked the head-twitch response in mice, a key 5-HT2A activation marker.
    - In primates, quipazine caused pronounced, persistent projectile vomiting linked to 5-HT3 activation.
    - A human trial at 25 mg produced no LSD-like subjective effects and intolerable gastrointestinal side effects.
    - A published document lists a 0.5 mg dose flagged with "sic," unexplained and anomalously low.

    To listen to this podcast ad-free and access premium episodes, try our subscription with a 14-day free trial at obomedia.com.

    © 2026 OBOMEDIA. All rights reserved.
    This episode and its content (audio, text, and related materials) are the exclusive property of OBOMEDIA and are protected by applicable copyright laws. Reproduction, distribution, editing, or commercial use, in whole or in part, without prior written permission from OBOMEDIA is prohibited. For permissions, licensing, and business inquiries: business@obomedia.com.
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    21 分
  • The Antidepressant That Vomited Its Way Toward Being a Psychedelic

    The Antidepressant That Vomited Its Way Toward Being a Psychedelic
    2026/07/24
    The Antidepressant That Vomited Its Way Toward Being a Psychedelic

    A forgotten drug from 1966 behaved like a true psychedelic in animals yet produced projectile vomiting in monkeys and severe gastrointestinal distress in humans at 25 mg - so how could the same molecule show LSD-like head-twitches and still fail to produce visions in people? What if a single receptor blockade could have unlocked its psychedelic effects?

    In this episode, we trace the published record from the first syntheses through animal conditioning studies, receptor pharmacology, and halted human exposure to ask whether quipazine’s paradox could ever have been resolved and what remained unpublished in later work.

    Person: Jerrold C. Winter
    Date: 1966
    Compound: quipazine (one-(two-quinolinyl)piperazine; 2-QP)
    Dose reported in humans: 25 mg
    Behavioral marker: head-twitch response in rodents and monkeys

    - Quipazine was first described in the scientific literature in 1966.
    - By 1971 researchers characterized quipazine as antidepressant-like in laboratory animals.
    - In 1977 animal studies documented quipazine produced a head-twitch response similar to LSD, psilocybin, and mescaline.
    - Human subjects given 25 mg reported nausea, flatulence, and severe gastrointestinal distress with no visions.
    - Quipazine is a potent agonist at 5-HT3 (causing vomiting) but its psychedelic-like animal effects were mediated through 5-HT2A, blocked by ketanserin.

    To listen to this podcast ad-free and access premium episodes, try our subscription with a 14-day free trial at obomedia.com.

    © 2026 OBOMEDIA. All rights reserved.
    This episode and its content (audio, text, and related materials) are the exclusive property of OBOMEDIA and are protected by applicable copyright laws. Reproduction, distribution, editing, or commercial use, in whole or in part, without prior written permission from OBOMEDIA is prohibited. For permissions, licensing, and business inquiries: business@obomedia.com.
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    24 分