Predicting long-term psychedelic side-effects

Schizotypal traits may not be caused by taking LSD or magic mushrooms

PNAS Nexus

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Psychedelic drugs are seeing a surge of interest from mainstream medicine, and initial results suggest that psychedelic-therapy can be a safe and effective treatment for some mental health conditions. However, the side-effect profile is still incompletely understood. In particular, the use of psychedelics has been posited to carry a risk of triggering latent psychotic disorders or persistent visual hallucination, known as Hallucinogen Persisting Perception Disorder (HPPD). In order to better understand the prevalence and risk factors of such side-effects, Katie Zhou and colleagues surveyed 654 people online who were planning to take psychedelics through their own initiative. Of those, 315 people were resurveyed two weeks after their experience and 212 people were resurveyed again four weeks after their experience. The sample was 74% male, and 77% university educated. About one third had been diagnosed with at least one psychiatric condition. The authors found a weak correlation between lifetime psychedelic use and both delusional ideation and magical thinking. However, on average, delusional ideation was slightly reduced one month after psychedelic use. These results suggest that schizotypal traits may not be caused by taking LSD or magic mushrooms, in keeping with the principle that correlation does not imply causation. About a third of individuals surveyed at the four-week mark did have some lingering hallucinatory sensory experiences, such as intensified colors and afterimages. However, the majority of those who experienced this did not report being distressed by it. The strongest predictors of persistent visual aftereffects were the personality trait absorption—the tendency to be easily immersed in sensory or imaginative experiences—and younger age. This corroborates previous findings showing that young people and adolescents may be at a particular risk of HPPD. According to the authors, empirical scrutiny of the potential risks of psychedelics should accompany changes in policy and access to psychedelic drugs.

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Journal

PNAS Nexus

Article Title

Prediction of hallucinogen persisting perception disorder and thought disturbance symptoms following psychedelic use

Article Publication Date

22-Apr-2025

Single-dose psychedelic boosts brain flexibility for weeks, peer-reviewed study finds

Groundbreaking research reveals potential for psychedelic compounds to enhance cognitive agility in neuropsychiatric treatment

Genomic Press

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image: 

Figure 1. Experimental timeline and overview. (A) Experimental timeline. (B) Schematic of the SEQFR2-forward protocol. Mice have to sequentially poke left and then right within 30 s to earn a reward pellet. (C) Schematic of the SEQFR2-reversal protocol. Mice now are required to poke right and then left within 30 s to get a reward pellet.

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Credit: Dr. Omar J Ahmed

ANN ARBOR, Michigan, USA, 22 April 2025 – In a groundbreaking research study, University of Michigan researchers have discovered that a single dose of a psychedelic compound can enhance cognitive flexibility—the brain's ability to adapt to changing circumstances—for weeks after administration, potentially revolutionizing treatments for depression, PTSD, and neurodegenerative diseases.

The study, published today in the journal Psychedelics, demonstrates that mice treated with a single dose of 25CN-NBOH, a selective serotonin 2A receptor agonist, showed markedly improved performance in reversal learning tasks compared to control groups when tested 2-3 weeks after treatment.

Key Findings

"What makes this discovery particularly significant is the sustained duration of cognitive benefits following just one psychedelic dose," explains Professor Omar J. Ahmed, the study's senior, corresponding author from the University of Michigan's Department of Psychology. "We observed enhanced learning adaptability that persisted for weeks, suggesting these compounds may induce lasting and behaviorally meaningful neuroplasticity changes in the prefrontal cortex."

Using an innovative automated sequential learning paradigm, researchers measured how effectively mice could adapt to rule reversals—a standard test for cognitive flexibility. The psychedelic-treated mice demonstrated superior adaptability compared to saline controls, with enhanced task efficiency, higher percentages of correct trials, and increased reward acquisition during the reversal phase.

Implications for Brain Science

The results complement existing cellular research showing psychedelic-induced structural remodeling in the prefrontal cortex but uniquely demonstrate sustained cognitive benefits persisting long after the immediate effects of the drug have dissipated.

As interest in psychedelic medicine continues to grow, this research raises intriguing questions about how psychedelics might reshape neural pathways governing flexible thinking. Could these compounds potentially reopen critical periods of brain plasticity? What molecular mechanisms underlie these long-lasting cognitive improvements? How might the timing and frequency of administration affect long-term neuroplasticity?

“The current study focused on the long-term effects of a single psychedelic dose. A key question is what happens with two, three, or even twenty doses taken over several months. Is every additional dose increasingly beneficial for flexible learning or is there a plateau effect or even a negative effect of too many doses? These are important questions to answer next in the quest to make psychedelic medicine more rational and mechanistic,” according to Dr. Ahmed.

Sex Differences and Clinical Potential

Importantly, the study found that both male and female mice showed significant improvements in cognitive flexibility, suggesting the potential broad applicability of psychedelic therapy across biological sexes.

"The most striking aspect of our findings is that these cognitive benefits were measured 15-20 days after a single psychedelic administration," notes Elizabeth J. Brouns, first author of the study. "This suggests that a single dose of a psychedelic isn't just temporarily altering perception, but potentially inducing lasting beneficial changes in brain function."

Methodological Advances

The study's automated behavioral task represents a significant methodological advance for evaluating flexible learning, enabling researchers to efficiently evaluate cognitive flexibility in future investigations of psychedelic compounds. This high-throughput approach could accelerate the development of targeted psychedelic therapies for specific cognitive deficits.

The full Psychedelics peer-reviewed research article, titled “Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks after administration” is available on 22 April 2025 in Psychedelics. The research includes Dr. Tyler Ekins as a co-author and was supported by the National Institutes of Health and the University of Michigan Eisenberg Family Depression Center. The article is freely available online at https://doi.org/10.61373/pp025r.0002.

About the Journal

Psychedelics: The Journal of Psychedelic and Psychoactive Drug Research (ISSN: 2997-2671) is a peer-reviewed medical research journal published by Genomic Press, New York. Psychedelics is dedicated to advancing knowledge across the full spectrum of consciousness altering substances, from classical psychedelics to stimulants, cannabinoids, entactogens, dissociatives, plant derived compounds, and novel compounds including drug discovery approaches. Our multidisciplinary approach encompasses molecular mechanisms, therapeutic applications, neuroscientific discoveries, and sociocultural analyses. We welcome diverse methodologies and perspectives from fundamental pharmacology and clinical studies to psychological investigations and societal-historical contexts that enhance our understanding of how these substances interact with human biology, psychology, and society.

Caption

Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks after administration

Credit

Dr. Omar J Ahmed

Journal

Psychedelics

DOI

10.61373/pp025r.0002 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks after administration

Article Publication Date

22-Apr-2025

COI Statement

The authors declare no competing financial interest.

LA REVUE GAUCHE - Left Comment: Search results for psychedelics

 

A multimodal 3D imaging atlas of a brain-computer interface based on mixed reality

Using a multimodal 3D imaging atlas of a rat brain-computer interface (BCI) and mixed reality to create a 3D interactive anatomical model

Compuscript Ltd

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A Exposure of the cranial region and local drilling of the skull; B completion of skull fxation pin implantation; C implantation of microelectrode needles into the left visual cortex; D fxation of the BCI device using dental cement

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Credit: Current Medical Science

Brain-computer interface (BCI) technology enables the direct interaction between brain signals and external devices, helping people with neurologic injury communicate with or control real or virtual objects by bypassing damaged neurologic regions. Intracortical BCIs, a subset of invasive BCIs, are valuable tools for finely interpreting brain activity and controlling external devices.

Previous studies on BCIs have extensively focused on scientific exploration and fundamental studies, while research into their application in public scientific cognition and education is limited. In this study, published in the Current Medical Science journal, researchers at Huazhong University of Science and Technology, Hospital for Special Surgery, University of Chicago, Fuzhou University, Fujian Provincial Hospital, Ningxia Medical University, Hubei University of Chinese Medicine, and Wuhan Neuracom Technology Development Co., Ltd, employed, “a novel approach for developing a multimodal 3D atlas of invasive BCIs in rats through multimodal fusion based on high-resolution T2 and TOF sequence MRI scans and micro-CT imaging”, which comprises the cranium, functional brain regions, vasculature and BCI devices, and uses mixed reality (MR) for creative visualization. This study successfully constructed the world's first micrometer-level 3D multimodal atlas integrating cranium, functional brain regions, cerebral vasculature, and invasive brain-computer interface devices, establishing a high-dimensional, high-precision visualization bridge for in-depth BCI research.

An invasive BCI was implanted in the left visual cortex of 4-week-old Sprague–Dawley rats and multimodal imaging techniques, like micro-CT and 9.4 T MRI, were used to acquire images of the rat cranial bone structure, vascular distribution, brain tissue functional zones, and BCI device before and after implantation. These images were then fused through spatial transformations using the 3D-slicer software, followed by image segmentation and 3D model reconstruction.

MRI T2 and TOF image sequence data were integrated to successfully establish a 3D atlas of brain functional parcellation and arterial vasculature, displaying the precise spatial and anatomical relationships among the 37 functional brain regions, including 19 cortical functional areas from frontal, lateral, and superior views. Similarly, the micro-CT scanning and 3D modeling data of BCI devices and cranial tissues were integrated to generate a comprehensive 3D atlas that incorporates the functional regions of brain tissue, cerebral arteries, BCI devices, and cranial structures, providing a detailed visualization of spatial relationships and anatomical organization of various components in the rat brain across the frontal, lateral and superior perspectives. The micrometer-level presentation of spatial relationships between BCI devices and brain tissues lays a solid foundation for precise and safe three-dimensional preoperative planning, intraoperative navigation, and postoperative evaluation of brain-computer interface surgeries.

Finally, using the HoloLens platform for MR visualization, the authors developed an interactive visualization atlas system incorporating BCI devices to enable the intuitive visualization and interaction of functional brain regions, arterial vasculature, cranial structures, and BCI devices. By magnifying the brain-computer interface and brain tissues hundreds of times in three-dimensional space, users can engage in three-dimensional interactive visualization between the real world of brain-computer interfaces and digital imaging, creating a novel paradigm for subsequent in-depth BCI research and medical education.

In conclusion, the authors of this study integrated multimodal imaging techniques and mixed reality to generate a comprehensive 3D atlas that “delineates the precise anatomical structures and spatial interrelationships among brain tissue, arterial vessels, BCI devices, and cranial tissues". 

A Frontal view of the integrated 3D atlas, including brain tissue functional regions, cerebral arteries, the BCI device, and cranial tissue; B lateral view of the integrated 3D atlas; C top view of the integrated 3D atlas; D posterior view of the integrated 3D atlas

A–C Constructed 3D interactive atlas including brain tissue functional regions and the BCI device (frontal view, lateral view, and top view); D–F constructed 3D interactive atlas including brain tissue, cerebral arteries, and a BCI device (frontal view, lateral view, and top view); G–I constructed 3D interactive atlas including brain tissue functional regions, cerebral arteries, the BCI device, and cranial tissue

Credit

Current Medical Science

Reference

Title of the original paper: Construction of a Multimodal 3D Atlas for a Micrometer Scale Brain–Computer Interface Based on Mixed Reality

Journal: Current Medical Science

DOI: https://doi.org/10.1007/s11596-025-00033-3

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Journal

Current Medical Science

DOI

10.1007/s11596-025-00033-3 

 

Oil cleanup agents do not impede natural biodegradation

American Society for Microbiology

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Highlights:

• Biodegradation is an important natural process during oil spill cleanup.
• A new study revealed that using spill treating agents does not negatively impact naturally occurring biodegradation.

Washington, D.C.—Using spill treating agents to clean up oil spills does not significantly hinder naturally occurring oil biodegradation, according to a new study. The study, published in Applied and Environmental Microbiology, a journal of the American Society for Microbiology, provides information that will be useful in future oil spills.

Biodegradation is an incredibly important natural process when it comes to oil spill cleanup. A significant portion of the oil can be permanently removed from the contaminated area through microbial activity. On-scene coordinators and other first responders must weigh the benefits against potential risks of any response action, such as using spill treating agents. Emergency response actions to oil spills vary widely depending on the scale of an oil spill, location and environmental conditions.

Different treating agents serve different functions. Oil dispersants break the oil into smaller droplets. Surface washing agents lift stranded oil from solid substrates. Chemical herders corral oil into a thicker slick to ease mechanical removal and can also enhance burning efficiency. Oil dispersants are the most well-known category of spill treating agent due to their unprecedented use during the high-profile Deepwater Horizon oil spill. Their effect on oil biodegradation has been extensively scrutinized by the scientific community. Some of the lesser-known spill treating agents are used far more frequently than chemical dispersants, and their impacts on oil biodegradation remain unknown.

“With the support of both the United States and Canadian governments, we were able to address some of those knowledge gaps with our laboratory-based study investigating the impacts of a surface washing agent and a chemical herder on oil biodegradation,” said lead study author Kiara Lech, Ph.D., a research biologist at the Center for Environmental Solutions and Emergency Response at the U.S. Environmental Protection Agency’s Office of Research and Development.

In their study, Lech and colleagues exposed a community of bacteria to crude oil that was treated with 2 types of spill treating agents (surface washing agent or chemical herder); they also had sets of single-agent control treatments where the microbial community was only exposed to crude oil alone or the spill treating agents alone. They then monitored how the microbial community responded to the addition of crude oil and spill treating agent. 
 
The researchers observed an initial delay in oil biodegradation with the addition of the treating agents, but that inhibition was later overcome by the diverse microbial community that actively degraded the treating agents simultaneously with the crude oil. A subset of oil compounds did not degrade as extensively when treated with surface washing agent compared to the oil-alone treatment. The researchers concluded that in the natural environment, this impact would likely be negligible but should be evaluated.

“One of the most interesting findings was how quickly and effectively the oil-degrading bacteria were able to pivot to the treating agents as a food source,” Lech said. “We found striking and significant differences in the composition of the microbial communities, with certain groups of bacteria becoming more prominent depending on treatment.”

Lech said that at the EPA Office of Research and Development, one of the core responsibilities is to provide regional and programmatic partners with the research that supports their decision-making during an environmental emergency. “The nagging question during an oil or other hazardous substance spill response is ‘how clean is clean?’ Thankfully, microbial communities are well-adapted to degrade oil, and we rely on biodegradation and other processes to whittle away at residual contamination,” Lech said. “The findings presented in this study provide confidence that using these spill treating agents will not significantly hinder naturally occurring oil biodegradation.”
 

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The American Society for Microbiology is one of the largest professional societies dedicated to the life sciences and is composed of over 37,000 scientists and health practitioners. ASM's mission is to promote and advance the microbial sciences. 

ASM advances the microbial sciences through conferences, publications, certifications, educational opportunities and advocacy efforts. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to all audiences. 

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Journal

Applied and Environmental Microbiology

 

Telemedicine had an impact on carbon emissions equivalent to reducing up to 130,000 car trips each month in 2023

University of California - Los Angeles Health Sciences

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Telemedicine use in 2023 reduced monthly carbon dioxide emissions by the equivalent of up to 130,000 gas operated vehicles, suggesting it could have a positive effect on climate change, new UCLA-led research finds.

The findings, to be published April 22 in the peer-reviewed American Journal of Managed Care, suggest that telemedicine could have a modest but noticeable impact on the environment by decreasing the number of vehicles traveling to and from medical appointments. They could also have policy implications, said co-senior author Dr. John N. Mafi, associate professor-in-residence of medicine in the division of general internal medicine and health services research at the David Geffen School of Medicine at UCLA.

“As Congress debates whether to extend or modify pandemic-era telehealth flexibilities, our results provide important evidence for policymakers to consider, namely that telemedicine has the potential to reduce the carbon footprint of US health care delivery,” Mafi said.

The U.S. health system now contributes about 9%, and transportation comprises about 29%, of greenhouse emissions in the country, the researchers write in the paper.

The researchers used de-identified data from the Milliman MedInsight Emerging Experience database to quantify nearly 1.5 million telemedicine visits, including about 66,000 in rural areas, during the April 1 through June 30, 2023 study period. They estimated that between 741,000 and 1.35 million of those were substitutes for in-person visits.

Extrapolating from these calculations, the researchers estimate that CO2 emissions were reduced by between 21.4 million and 47.6 million kg each month in the U.S. due to telemedicine use, which translates to the amount produced by 61,000 to 130,000 gas powered vehicles or recycling 1.8 million to 4 million trash bags.

"The health care sector contributes significantly to the global carbon footprint,” said Dr. A. Mark Fendrick, professor of medicine and director of Center for Value-Based Insurance Design at the University of Michigan and the study’s co-senior author. “Our findings suggest that the environmental impact of medical care delivery can be reduced when lower-carbon options, such as telemedicine, are substituted for other services that produce more emissions."

The researchers note some limitations to their findings. Their sampling method was based on data that was from a single, easy to access source rather than a random selection, so the findings may not represent the broader population or account for regional variations. Also, driving distances and vehicle market share were based on data sources from before 2023, though driving distances to in-person care were not likely to differ much from what they were prior to that year. Finally, telemedicine use has fallen since the end of the COVID pandemic, which may have led the researchers to overestimate the amount of emissions averted due to variations in telemedicine use rates.

Study co-authors also include Dr. Benjo Delarmente, Artem Romanov, Manying Cui, Chi-Hong Tseng, and Dr. Catherine Sarkisian of UCLA; Melody Craff, Dale Skinner, and Michael Hadfield of Milliman MedInsight, and Cheryl Damberg of RAND.

The study was funded by the National Institutes of Health/National Institute on Aging.

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Journal

The American Journal of Managed Care

Method of Research

Data/statistical analysis

Subject of Research

Not applicable

Article Title

Impact of Telemedicine Use on Outpatient-Related CO2 Emissions: Estimate From a National Cohort

Article Publication Date

22-Apr-2025

Journalist David Zweig analyzes American schools, the virus, and a story of bad decisions

"An Abundance of Caution" publishes from The MIT Press this week

The MIT Press

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Cover art to "An Abundance of Caution."

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Credit: The MIT Press, 2025.

A searing indictment of the American public health, media, and political establishments’ decision-making process behind pandemic school closures.

9780262549158| $39.95 US | hardcover | April 22nd, 2025 | 464 pp. |

Cambridge, MA, April, 2025

For immediate release

This spring marks the 5th anniversary of the initial Covid lockdowns. While we all experienced the pandemic differently, for 50 million American children the unprecedented––and for many of them, years-long––disruption to their education may be the most consequential collective event in more than a generation. Yet, until now, we've lacked a comprehensive investigation behind it.

In An Abundance of Caution: American Schools, the Virus, and a Story of Bad Decisions (on sale 4/22/2025 from The MIT Press), journalist David Zweig details a devastating account of the decision-making process behind one of the worst American policy failures in a century—the extended closures of public schools during the pandemic. Researched with scholarly rigor yet told with a craftsman's flair, An Abundance of Caution is poised to become not only the definitive record of that extraordinary episode in our recent history but a modern classic of science reportage and social and political critique.

In fascinating and meticulously reported detail, David Zweig shows how some of the most trusted members of society—from Pulitzer Prize-winning journalists to eminent health officials—repeatedly made fundamental errors in their assessment and presentation of evidence. As a result, for the first time in modern American history, healthy children were barred from school. Millions of them did not set foot in a classroom for more than a year. All along, millions of kids in Europe had been learning in person. Even many peers at home—in private schools, and public schools in mostly “red” states and districts—were in class full time from fall 2020 onward.

Whatever inequities that existed among American children before the pandemic, the selective school closures exacerbated them, disproportionately affecting the underprivileged. Deep mental, physical, and academic harms—among them, depression, anxiety, abuse, obesity, plummeting test scores, and rising drop-out rates—were endured for no discernible benefit. As the Europeans had shown very early, after they had sent kids back to class, there was never any evidence that long-term school closures, nor a host of interventions imposed on students when they were in classrooms, would reduce overall cases or deaths in any meaningful way.

The story of American schools during the pandemic serves as a prism through which to approach fundamental questions about why and how individuals, bureaucracies, governments, and societies act as they do in times of crisis and uncertainty. Ultimately, this book is not about Covid; it's about a country ill-equipped to act sensibly under duress.

David Zweig's pandemic reporting was unparalleled:

• Zweig wrote the first piece in a major American publication, in early May 2020, which argued, backed by a compendium of evidence, that schools should reopen.
• He was present at the formation and signing of the Great Barrington Declaration, and interviewed its three authors.
• He was one of the Twitter Files journalists, in which he reported on censorship of true information about Covid on social media platforms.
• Zweig penned two highly influential investigative features critical of mask mandates, for New York magazine and the Atlantic.
• He broke a story on Covid pediatric hospital statistics for New York magazine, and broke a follow-up for the Atlantic on adult hospital statistics.
• He wrote the first major feature on "pod" schools, for the New York Times.
• He was the first journalist in a major outlet to interview the Israeli doctor who found the safety signal of myocarditis for the COVID-19 vaccine, later recognized by the CDC.
• His reporting on the CDC's draconian camp guidelines was directly followed by the agency rescinding its requirement for kids to be masked outdoors.

EARLY PRAISE FOR DAVID ZWEIG’s

AN ABUNDANCE OF CAUTION

“An Abundance of Caution is a book the world badly needed. David Zweig writes crisply, with a rare combination of journalistic rigor and empathy. But his book is unsparing in revealing how frustratingly predictable many of the mistakes made during the pandemic were—and how partisanship was used to suppress the pursuit of science and undermine the public interest. As much as some might hope to forget the pandemic, An Abundance of Caution is indispensable reading for preventing the next catastrophe.”
—Nate Silver, founder of FiveThirtyEight and author of Silver Bulletin

“This book is important. It tells a disturbing story. Faced with the erosion of its legitimacy and authority, the scientific community needs to engage seriously with Zweig’s analysis.”
—Paul Romer, winner of the Nobel Prize in Economics, former Chief Economist of the World Bank, and Director of the Center for the Economics of Ideas at Boston College

“For those interested in the failure of evidence-based medicine and public health to protect our children during prolonged COVID school closures, An Abundance of Caution is a uniquely rigorous, incisive, and must-read account.”
—Jeffrey S. Flier, MD, Harvard University Distinguished Service Professor and Former Dean, Harvard Medical School

“A powerful analysis of the largest public health intervention in modern history. Using a clear, scientific approach, Zweig asks piercing questions that shed light on medical dogma propagated by groupthink.”
—Marty Makary, MD, Commissioner of the FDA, Johns Hopkins surgeon, and bestselling author of Blind Spots 

“Through both his reporting and his congressional testimony, David Zweig was one of the only journalists brave enough to tell the truth about the ill-fated school closure policies during the pandemic. His book is a meticulously researched history of unpopular, scientifically unsupported, socially catastrophic policy decisions.”
—Matt Taibbi, investigative journalist, bestselling author, and publisher of Racket News

Author Photo of David Zweig.

Credit

David Zweig, 2025.

ABOUT THE AUTHOR:

David Zweig is the author of the novel Swimming Inside the Sun and the nonfiction book Invisibles. He has testified twice before Congress as an expert witness on American schools during the pandemic, and his investigative reporting on the pandemic has been cited in numerous Congressional letters and a brief to the Supreme Court. Zweig's journalism has appeared in the New York Times, the Wall Street Journal, the New Yorker, the Atlantic, New York, Wired, the Free Press, the Boston Globe, and, most often, his newsletter, Silent Lunch. He lives with his family in New York State.