Scott Alexander examines the surprisingly broad effects of GLP-1 drugs like Ozempic, exploring their mechanisms and speculating on why they seem to impact so many different conditions. Longer summary

Scott Alexander explores the wide-ranging effects of GLP-1 receptor agonist medications like Ozempic, which are approved for diabetes and obesity but show promise for many other conditions. He delves into the mechanisms behind their effects on diabetes, weight loss, and addiction, speculating on why these drugs seem to have such broad impacts. The post discusses how GLP-1 drugs work in the brain to reduce hunger and dampen reward systems, potentially explaining their effects on addiction. Scott also touches on their anti-inflammatory properties and potential benefits for neurodegenerative diseases, while cautioning that some reported effects may not replicate. Shorter summary

Scott Alexander challenges Robin Hanson's claim that medicine doesn't work by analyzing health insurance studies and presenting evidence of medicine's effectiveness. Longer summary

Scott Alexander critiques Robin Hanson's claim that medicine doesn't work, analyzing three major health insurance experiments (RAND, Oregon, and Karnataka) and other studies. He argues that these studies are underpowered to detect medication effects and don't support Hanson's conclusion, citing evidence of medicine's effectiveness in improving survival rates for various diseases. Shorter summary

Scott Alexander updates on Lumina probiotic, discussing FDA trials, effectiveness, potential risks, and his nuanced stance on the product. Longer summary

Scott Alexander provides updates on Lumina, a genetically modified anti-tooth-decay bacterium. He clarifies information about FDA testing, discusses rat trial results, reports on recent colonization studies, addresses potential side effects, and shares some anecdotal results. Scott also explains his stance on Lumina, emphasizing that while he sees potential benefits, he doesn't fully endorse it and acknowledges the uncertainties and risks involved. Shorter summary

Scott Alexander announces the winners of ACX Grants 2024, covering a diverse range of projects from medical research to policy advocacy. Longer summary

Scott Alexander announces the results of the ACX Grants 2024, detailing the winners and their projects. The grants cover a wide range of areas including medical research, technology development, policy advocacy, and scientific studies. Scott explains the selection process, acknowledges contributors, and mentions future plans for the grants program. He also discusses how Manifund will handle payments and create an impact market for unfunded projects. Shorter summary

Scott Alexander examines a study challenging ketamine's effectiveness as an antidepressant, discussing potential confounding factors and maintaining his belief in ketamine's utility despite the study's results. Longer summary

Scott Alexander discusses a recent study on ketamine's effectiveness as an antidepressant when administered during anesthesia. The study found no significant difference between ketamine and placebo groups, challenging previous beliefs about ketamine's antidepressant properties. Scott analyzes the study's methodology and results, pointing out several factors that might have influenced the outcomes, such as the strong placebo effect, the antidepressant properties of anesthetics, and the potential impact of surgery on depression symptoms. He concludes that while the study raises questions, it doesn't completely invalidate previous research showing ketamine's effectiveness, and he maintains his belief in ketamine's potential as an antidepressant for some patients. Shorter summary

The post challenges the notion that effect sizes below 0.50 for medications are clinically insignificant, using antidepressants as a case study and comparing them to other common drugs. Longer summary

This post discusses the interpretation of effect sizes in medical studies, particularly for antidepressants. It challenges the common notion that effect sizes below 0.50 are clinically insignificant. The author presents a Danish study that simulates various hypothetical medications, showing that even drugs that cure or significantly improve depression in a large percentage of patients might not meet traditional effect size thresholds. The post explains why these thresholds might be unrealistic due to factors like the placebo effect, high standard deviations in placebo groups, and patient dropouts. It also compares antidepressant effect sizes to those of other widely accepted medications, concluding that many common drugs would be considered 'clinically insignificant' by strict effect size standards. The author suggests that claims about 'meaningless effect sizes' should be given less weight compared to other evidence, such as clinical experience. Shorter summary

Scott Alexander reviews a book critiquing Institutional Review Boards, arguing they now harm medical research more than they help. Longer summary

Scott Alexander reviews Simon Whitney's book 'From Oversight To Overkill', which critiques the current state of Institutional Review Boards (IRBs) in medical research. The book traces the history of IRBs from their noble beginnings to their current state of over-regulation and obstruction. Whitney argues that while IRBs were intended to protect research subjects, they now cause more harm than good by delaying or preventing potentially life-saving research. The review discusses several case studies that illustrate the problems with IRBs, and concludes by considering Whitney's proposed reforms and the broader societal trends that have led to this situation. Shorter summary

Scott Alexander critiques Ben Hoffman's arguments about Vitamin D dosing, maintaining that it is primarily a bone-related chemical with limited evidence for other benefits. Longer summary

Scott Alexander responds to Ben Hoffman's critique of his views on Vitamin D dosing. He argues that ancestral populations likely received much less Vitamin D from sunlight than Hoffman suggests, and that the doses used in most studies are appropriate. Scott reviews the literature on Vitamin D dosing, discusses various recommendations and debates within the medical community, and explains why he remains skeptical of claims about Vitamin D's non-skeletal benefits, including for COVID-19 treatment. Shorter summary

Scott Alexander proposes using high-dose oral progesterone as a potential low-cost alternative to Zulresso for treating postpartum depression, based on pharmacological research. Longer summary

Scott Alexander explores the possibility of using high-dose progesterone as a cheaper alternative to Zulresso for treating postpartum depression. He explains that Zulresso is a metabolite of progesterone and presents research suggesting that a specific regimen of oral progesterone could potentially mimic the effects of Zulresso. The post discusses the pharmacokinetics, dosing schedule, and potential cost savings, with progesterone treatment costing only about $11 compared to Zulresso's $35,000. Scott acknowledges potential obstacles in implementation but hopes researchers will investigate this approach further. Shorter summary

Scott Alexander shares the second half of ACX Grants, presenting 59 diverse project proposals seeking funding or support. Longer summary

Scott Alexander presents the second half of ACX Grants, a list of projects seeking funding or support that he couldn't fully fund himself. The post includes 59 diverse project proposals (numbered 67-125) covering topics such as medical research, technology development, social initiatives, and scientific studies. Each proposal includes a brief description of the project, its goals, and contact information for those interested in supporting or collaborating. Shorter summary

Scott Alexander responds to comments on his ivermectin article, discussing criticisms, the worms hypothesis, vaccine skepticism, and journalism quality. Longer summary

This post highlights comments on Scott Alexander's previous article about ivermectin as a potential COVID-19 treatment. Scott responds to criticisms from ivmmeta.com, discusses the worms hypothesis with various commenters, addresses concerns about the TOGETHER trial, and shares perspectives on vaccine skepticism and journalism quality. He also reflects on his own writing process compared to traditional journalism. Shorter summary

Scott Alexander analyzes ivermectin studies for COVID-19, finding most positive results likely due to methodological flaws, fraud, or confounding by parasitic infections. Longer summary

Scott Alexander provides an in-depth analysis of ivermectin studies for COVID-19 treatment, examining methodological issues, potential fraud, and confounding factors. He concludes that ivermectin likely doesn't significantly reduce COVID mortality except potentially in areas with high parasitic worm infections. The post explores broader issues around scientific credibility, fraud detection, and public trust in science. Shorter summary

Scott Alexander examines the current research on Long COVID, analyzing its prevalence, symptoms, and potential impacts to assess personal risk and societal implications. Longer summary

Scott Alexander reviews the current research on Long COVID, examining its prevalence, symptoms, duration, and impact on different groups. He explores various studies, discusses potential mechanisms, and evaluates the psychosomatic argument. The post concludes with an assessment of personal risk and comparisons to other post-viral syndromes, emphasizing the uncertainties still surrounding Long COVID. Shorter summary

Scott Alexander reviews comments on his posts about aducanumab and the FDA, acknowledging some mistakes while defending his overall critique of FDA conservatism. Longer summary

Scott Alexander reviews comments on his recent posts about aducanumab and the FDA. He acknowledges some mistakes in his original post, but defends his overall critique of the FDA as overly conservative. The comments cover various aspects of drug approval, including the aducanumab controversy, surrogate endpoints, the FDA's impact on small biotech companies, and comparisons to other regulatory systems. Scott reflects on how to improve his fact-checking process while still writing passionate pieces. Shorter summary

Scott Alexander corrects and expands on the story of Omegaven, a life-saving infant nutritional fluid, using it to illustrate systemic issues with medical regulation and drug approval. Longer summary

Scott Alexander revisits a story about Omegaven, a fish-oil-based nutritional fluid for infants, correcting some details from his previous post. He explains how the fluid was discovered to prevent liver disease in infants requiring IV nutrition, and the challenges faced in getting it approved by the FDA. While the FDA comes off relatively well in the story, Scott argues that the real problem is the systemic hurdle of drug approval that makes everything in medicine illegal by default. He discusses how this hurdle makes scientific discoveries harder and potentially costs lives, even when many individuals involved are trying their best. Shorter summary

Scott Alexander explains how the vastly higher doses taken by recreational drug users compared to psychiatric patients lead to misconceptions about drug safety in clinical settings. Longer summary

Scott Alexander discusses how recreational drug users consume substantially higher doses of drugs compared to psychiatric patients, which leads to misconceptions about drug safety in clinical settings. He provides examples of ketamine and amphetamines to illustrate this point. For ketamine, psychiatric doses are around 280 mg/month, while recreational users consume about 90,000 mg/month. Similarly, for amphetamines, Adderall patients typically take 20 mg daily, whereas methamphetamine addicts use the equivalent of 1000 mg oral amphetamine daily. Scott argues that many concerns about drug side effects in clinical settings are based on studies of recreational users, and that these concerns may not apply to patients taking much lower doses under medical supervision. Shorter summary

Scott Alexander examines the treatment for progeria and its potential implications for understanding and treating normal aging processes. Longer summary

This post discusses the implications of progeria treatments for understanding normal aging. Scott Alexander explores the recent FDA approval of lornafarnib for Hutchinson-Gilford Progeria Syndrome and its potential relevance to normal aging processes. He explains the cellular mechanisms behind progeria, involving defective lamin A protein production, and how this leads to accelerated aging through DNA damage accumulation. While initially concluding that lornafarnib might not help prevent normal aging, Scott then presents research suggesting that similar protein defects might play a role in normal aging processes. The post ends with uncertainty about the extent to which these mechanisms contribute to regular aging. Shorter summary

Scott Alexander investigates the optimal dosage of Lexapro, comparing it to other antidepressants and exploring the reasons behind its effectiveness at lower doses. Longer summary

Scott Alexander explores the question of the right dose for Lexapro (escitalopram), an antidepressant. He examines official recommendations, compares Lexapro to other SSRIs, and investigates why Lexapro might be effective at lower doses. The post delves into studies on antidepressant dosing, the unique properties of Lexapro, and the potential benefits and risks of higher doses. Scott concludes that while there's no strong evidence for high doses of any antidepressant being more effective, prescribing higher doses of Lexapro might be as safe as other SSRIs and potentially more beneficial in some cases. Shorter summary

Scott Alexander explores the history and mechanism of DNP, a dangerous but effective weight-loss drug, and discusses recent developments in safer mitochondrial uncoupling agents. Longer summary

Scott Alexander discusses 2,4-dinitrophenol (DNP), a controversial and dangerous weight-loss drug that works by uncoupling mitochondria. He traces its history from the 1930s to modern times, explaining its effectiveness and severe side effects. The post then explores recent developments in mitochondrial uncoupling research, including potential safer alternatives and therapeutic applications beyond weight loss. Shorter summary

Scott Alexander critically examines a new theory on antidepressant mechanisms, expressing skepticism while acknowledging its potential significance if proven true. Longer summary

Scott Alexander reviews a recent study proposing a new theory for how antidepressants work, which suggests they bind directly to TrkB receptors rather than acting through serotonin. He explains the study's findings and their potential implications, but expresses skepticism about the theory. Scott outlines several reasons why he finds the new theory unconvincing, including existing evidence supporting the serotonin hypothesis, issues with the study's claims about drug accumulation, and expert opinions on the difficulties of TrkB research. He concludes by stating he will stick with the conventional theory for now, while remaining open to future developments. Shorter summary

Scott Alexander critically evaluates the evidence for Vitamin D's role in COVID-19 prevention and treatment, ultimately leaning towards skepticism while acknowledging the low risk of supplementation. Longer summary

Scott Alexander examines the evidence for and against Vitamin D's effectiveness in preventing or treating COVID-19. He reviews various studies, including observational data, randomized controlled trials, and Mendelian randomization studies. While some evidence suggests a potential link between Vitamin D levels and COVID-19 outcomes, Scott ultimately leans towards skepticism. He discusses possible confounding factors and methodological issues in some of the positive studies. Despite his skepticism, Scott acknowledges the low risk of Vitamin D supplementation and suggests it may still be beneficial for other reasons. Shorter summary

Scott Alexander examines whether psychiatric conditions result from evolutionary failures or tradeoffs, proposing that most disorders involve a combination of both. Longer summary

Scott Alexander explores the nature of psychiatric conditions, discussing whether they result from evolutionary failures or tradeoffs. He presents evidence for both hypotheses, noting that recent research favors the failure hypothesis. However, he argues that some conditions likely involve both failures and tradeoffs. He uses analogies from justice systems and nuclear war scenarios to illustrate how failures and tradeoffs can interact. The post concludes by suggesting that most psychiatric disorders exist on a spectrum from mostly-tradeoff to mostly-failure, and critiques the neurodiversity movement's blanket statements about conditions like autism. Shorter summary

Scott Alexander warns about the potential misinterpretation of odds ratios in studies, explaining how to convert them to effect sizes for more accurate understanding. Longer summary

Scott Alexander discusses the potential for misinterpreting odds ratios in statistical studies, using a personal anecdote from a journal club. He explains how odds ratios can seem more significant than they actually are, and provides a method for converting them to effect sizes for better interpretation. The post includes a reference to Chen's study on interpreting odds ratios in epidemiological studies and gives an example of how a seemingly impressive odds ratio can translate to a more modest effect size. Scott emphasizes the importance of careful comparison between studies that report results using different metrics. Shorter summary

Scott Alexander analyzes the PANDA Study, a large real-world antidepressant trial, discussing its methodology, results, and implications for understanding antidepressant efficacy. Longer summary

This post discusses the PANDA (Prescribing ANtiDepressants Appropriately) Study, the largest non-pharma antidepressant trial ever conducted. The study aimed to measure the real-world efficacy of antidepressants, specifically sertraline, in a naturalistic setting. Scott Alexander analyzes the results, which show small to low-medium effect sizes for various depression and anxiety measures. He notes that while the effects are modest, they are not clinically insignificant. The study found that patient-reported improvement had a higher effect size than researcher-measured tests, potentially indicating a disconnect between clinical measures and patient experiences. Scott discusses the implications of these findings for antidepressant efficacy and suggests that targeted treatment approaches might yield better results. Shorter summary

Scott Alexander argues that psychiatric diagnoses, while imperfect, are useful tools despite potentially combining multiple conditions with different causes. Longer summary

Scott Alexander discusses the criticism that psychiatric conditions like autism or depression are not unitary categories but rather collections of different conditions with different causes. He argues that this view, while correct, is not as revolutionary as some think and doesn't invalidate the usefulness of these diagnoses. Scott compares psychiatric conditions to medical conditions like pulmonary edema or stroke, which can have multiple causes but are still useful diagnostic categories. He suggests that psychiatric disorders might ultimately be understood as computational conditions, with various biological, psychological, and environmental factors affecting the brain's computational parameters. The post emphasizes that while research into subtypes of conditions like depression hasn't been very productive, current psychiatric diagnoses remain the most useful tool available, despite their limitations. Shorter summary