Paracetamol surprising psychoactive effects

Every day, millions of people turn to acetaminophen, also known as paracetamol – the active ingredient in Tylenol – to dull the occasional ache or pain. That’s because few side effects accompany this highly effective over-the-counter drug when taken at recommended doses. A new side effect is starting to come to light, however. Research is now revealing that acetaminophen may subtly influence your emotions.

To relieve pain, acetaminophen works its magic in the brain, but researchers still aren’t entirely sure how this trick works – a remarkable fact considering the drug has been available without prescription for sixty years! It may impact an enzyme called cyclooxygenase, or it might modulate humans’ endocannabinoid system. Some experts say one or both of these ideas tells the whole story, while others insist we’ve barely scratched the surface. Regardless, whatever acetaminophen does in the brain also seems to alter how we perceive the world.

One of the earliest and most elucidating studies on the topic was published back in 2010. A team of scientists from a variety of academic institutions in the U.S. found that subjects who took acetaminophen were not as sensitive to emotional pain compared to people given a placebo.

“In two experiments, participants took acetaminophen or placebo daily for 3 weeks,” they described. “Doses of acetaminophen reduced reports of social pain on a daily basis.”

The team also found a “smoking gun” of sorts when conducting brain scans on the participants.

“We used functional magnetic resonance imaging to measure participants’ brain activity, and found that acetaminophen reduced neural responses to social rejection in brain regions previously associated with distress caused by social pain and the affective component of physical pain.”

Five years later, a team from Ohio State recruited 167 subjects and exposed them to negative and positive images, asking the participants to evaluate the stimuli. Subjects given 1,000mg of acetaminophen described the imagery as less emotionally arousing and evaluated unpleasant stimuli less negatively and pleasant stimuli less positively, compared to subjects given a placebo.

“These findings suggest that acetaminophen has a general blunting effect on individuals’ evaluative and emotional processing,” they wrote.

Acetaminophen may also reduce one’s empathy for pain. In a double-blind, placebo-controlled study with over 200 participants, researchers at Ohio State University found that subjects given 1,000mg of acetaminophen expressed less empathy compared to those given a placebo when “reading scenarios about another’s physical or social pain, witnessing ostracism in the lab, or visualizing another study participant receiving painful noise blasts.”

How should we view these intriguing trials? Do the subtle, yet present effects of acetaminophen witnessed in the lab affect real-world decision making? Hard to say for sure, but the doses used in these studies are equivalent to just two extra strength Tylenols, so regular users of acetaminophen-based painkillers are undoubtedly being emotionally affected in some fashion. And if you think you can avoid having your emotions dulled by switching to ibuprofen, sorry, it probably has the same effects.

Of course, we could just shrug our shoulders and say “who cares?” In modern society where all sorts of stimuli exert unnoticed, mind-altering influences, what’s the problem with a bit of emotional blunting? But wait, maybe that’s the just the Tylenol talking…

A dark consensus about screens and kids

“I am convinced the devil lives in our phones.”

The people who are closest to a thing are often the most wary of it. Technologists know how phones really work, and many have decided they don’t want their own children anywhere near them.

A wariness that has been slowly brewing is turning into a region wide consensus: The benefits of screens as a learning tool are overblown, and the risks for addiction and stunting development seem high. The debate in Silicon Valley now is about how much exposure to phones is O.K.

“Doing no screen time is almost easier than doing a little,” said Kristin Stecher, a former social computing researcher married to a Facebook engineer. “If my kids do get it at all, they just want it more.”

Ms. Stecher, 37, and her husband, Rushabh Doshi, researched screen time and came to a simple conclusion: they wanted almost none of it in their house. Their daughters, ages 5 and 3, have no screen time “budget,” no regular hours they are allowed to be on screens. The only time a screen can be used is during the travel portion of a long car ride (the four-hour drive to Tahoe counts) or during a plane trip.

Recently she has softened this approach. Every Friday evening the family watches one movie.

There is a looming issue Ms. Stecher sees in the future: Her husband, who is 39, loves video games and thinks they can be educational and entertaining. She does not.

“We’ll cross that when we come to it,” said Ms. Stecher, who is due soon with a boy.

Some of the people who built video programs are now horrified by how many places a child can now watch a video.

Asked about limiting screen time for children, Hunter Walk, a venture capitalist who for years directed product for YouTube at Google, sent a photo of a potty training toilet with an iPad attached and wrote: “Hashtag ‘products we didn’t buy.'”

Athena Chavarria, who worked as an executive assistant at Facebook and is now at Mark Zuckerberg’s philanthropic arm, the Chan Zuckerberg Initiative, said: “I am convinced the devil lives in our phones and is wreaking havoc on our children.

Ms. Chavarria did not let her children have cellphones until high school, and even now bans phone use in the car and severely limits it at home.

She said she lives by the mantra that the last child in the class to get a phone wins. Her daughter did not get a phone until she started ninth grade.

“Other parents are like, ‘Aren’t you worried you don’t know where your kids are when you can’t find them?'” Ms. Chavarria said. “And I’m like, ‘No, I do not need to know where my kids are every second of the day.'”

For longtime tech leaders, watching how the tools they built affect their children has felt like a reckoning on their life and work.

Among those is Chris Anderson, the former editor of Wired and now the chief executive of a robotics and drone company. He is also the founder of GeekDad.com.

“On the scale between candy and crack cocaine, it’s closer to crack cocaine,” Mr. Anderson said of screens.

Technologists building these products and writers observing the tech revolution were naïve, he said.

“We thought we could control it,” Mr. Anderson said. “And this is beyond our power to control. This is going straight to the pleasure centers of the developing brain. This is beyond our capacity as regular parents to understand.”

He has five children and 12 tech rules. They include: no phones until the summer before high school, no screens in bedrooms, network-level content blocking, no social media until age 13, no iPads at all and screen time schedules enforced by Google Wifi that he controls from his phone. Bad behavior? The child goes offline for 24 hours.

“I didn’t know what we were doing to their brains until I started to observe the symptoms and the consequences,” Mr. Anderson said.

“This is scar tissue talking. We’ve made every mistake in the book, and I think we got it wrong with some of my kids,” Mr. Anderson said. “We glimpsed into the chasm of addiction, and there were some lost years, which we feel bad about.”

His children attended private elementary school, where he saw the administration introduce iPads and smart whiteboards, only to “descend into chaos and then pull back from it all.”

This idea that Silicon Valley parents are wary about tech is not new. The godfathers of tech expressed these concerns years ago, and concern has been loudest from the top.

Tim Cook, the C.E.O. of Apple, said earlier this year that he would not let his nephew join social networks. Bill Gates banned cellphones until his children were teenagers, and Melinda Gates wrote that she wished they had waited even longer. Steve Jobs would not let his young children near iPads.

But in the last year, a fleet of high-profile Silicon Valley defectors have been sounding alarms in increasingly dire terms about what these gadgets do to the human brain. Suddenly rank-and-file Silicon Valley workers are obsessed. No-tech homes are cropping up across the region. Nannies are being asked to sign no-phone contracts.

Those who have exposed their children to screens try to talk them out of addiction by explaining how the tech works.

John Lilly, a Silicon Valley-based venture capitalist with Greylock Partners and the former C.E.O. of Mozilla, said he tries to help his 13-year-old son understand that he is being manipulated by those who built the technology.

“I try to tell him somebody wrote code to make you feel this way – I’m trying to help him understand how things are made, the values that are going into things and what people are doing to create that feeling,” Mr. Lilly said. “And he’s like, ‘I just want to spend my 20 bucks to get my Fortnite skins.'”

And there are those in tech who disagree that screens are dangerous. Jason Toff, 32, who ran the video platform Vine and now works for Google, lets his 3-year-old play on an iPad, which he believes is no better or worse than a book. This opinion is unpopular enough with his fellow tech workers that he feels there is now “a stigma.”

“One reaction I got just yesterday was, ‘Doesn’t it worry you that all the major tech execs are limiting screen time?'” Mr. Toff said. “And I was like, ‘Maybe it should, but I guess I’ve always been skeptical of norms.’ People are just scared of the unknown.”

“It’s contrarian,” Mr. Toff said. “But I feel like I’m speaking for a lot of parents that are afraid of speaking out loud for fear of judgment.”

He said he thinks back to his own childhood growing up watching a lot of TV. “I think I turned out O.K.,” Mr. Toff said.

Other Silicon Valley parents say there are ways to make some limited screen time slightly less toxic.

Renee DiResta, a security researcher on the board of the Center for Humane Tech, won’t allow passive screen time, but will allow short amounts of time on challenging games.

She wants her 2- and 4-year-old children to learn how to code young, so she embraces their awareness of gadgets. But she distinguishes between these types of screen use. Playing a building game is allowed, but watching a YouTube video is not, unless it is as a family.

And Frank Barbieri, a San Francisco-based executive at the start-up PebblePost that tracks online activity to send direct mail advertising, tries to limit his 5-year-old daughter’s screen time to Italian language content.

“We have friends who are screen abolitionists, and we have friends who are screen liberalists,” Mr. Barbieri said.

He had read studies on how learning a second language at a young age is good for the developing mind, so his daughter watches Italian-language movies and TV shows.

“For us, honestly, me and my wife were like, ‘Where would we like to visit?'” Mr. Barbieri said.

SOTT FOCUS: MindMatters: New Show! Why Mind Really Matters, and Your Life Reflects Your Values

World Happiness Report: Americans are unhappy and the opioid epidemic may be a factor

For the third straight year, the U.S. has dropped in the rankings of the World Happiness Report.

The United States is now the 19th happiest country on Earth, its ranking falling for the third consecutive year.

This is according to the most recent World Happiness Report, released on Wednesday (March 20) or the United Nations’ International Day of Happiness.

The Washington Post reports that the seventh annual report surveyed 156 different countries and took into account six factors: GDP per capita, healthy life expectancy, the freedom to make life choices, social support, generosity and perceptions of corruption.

The top 10 countries in the report were Finland, Denmark, Norway, Iceland, Netherlands, Switzerland, Sweden, New Zealand, Canada and Austria.

“We finished 19th on the list behind Belgium,” Jimmy Kimmel said on his late night show. “The people who feel the need to put mayonnaise on their french fries are happier than we are. Cheer up, everybody.”

While the report doesn’t specify why each country ranked where it did, the authors of the report have speculated in a news release that substance use disorder and the opioid epidemic contributed to America’s ranking.

“This year’s report provides sobering evidence of how addictions are causing considerable unhappiness and depression in the U.S.,” said Jeffrey Sachs, a Columbia University professor and the author of the “Addiction and Unhappiness in America” section of the report.

“The compulsive pursuit of substance abuse and addictive behaviors is causing severe unhappiness. Government, business, and communities should use these indicators to set new policies aimed at overcoming these sources of unhappiness,” Sachs added.

Sachs also noted that the results of the report serve as building blocks for countries moving forward.

“The World Happiness Report, together with the Global Happiness and Policy Report offer the world’s governments and individuals the opportunity to rethink public policies as well as individual life choices, to raise happiness and wellbeing,” Sachs said. “We are in an era of rising tensions and negative emotions (as shown in Chapter 2) and these findings point to underlying challenges that need to be addressed.”

According to the news release, this year’s report specifically honed in on happiness and the community, taking into account how technology, social norms, conflict and government policies have played a role in shaping each country.

“The world is a rapidly changing place,” Professor John Helliwell, co-editor of the report, said in the news release. “How communities interact with each other whether in schools, workplaces, neighborhoods or on social media has profound effects on world happiness.”

Johnson & Johnson prevails in New Jersey talc cancer trial

Johnson & Johnson won a jury trial Wednesday in New Jersey in a case where a man alleged that talc in its baby powder caused his cancer.

Ricardo Rimondi, 58, said he was exposed to asbestos from Johnson & Johnson’s baby powder and that had caused his mesothelioma cancer.

But the six-person jury in Middlesex County Superior Court decided in favor of New Brunswick-based Johnson & Johnson (NYSE: JNJ).

Company officials released the following statement after the verdict: “Today’s jury unanimously ruled that Johnson’s Baby Powder does not contain asbestos and was not the cause of the plaintiff’s disease. It’s important to emphasize the track record in these cases. This is the third verdict in favor of Johnson & Johnson in recent months, and of the last 9 mesothelioma cases, three ruled in favor of J&J, and five resulted in mistrials. It remains true that of all the talc-related verdicts against Johnson & Johnson that have been through the appeals process, every one has been overturned. This trial track records underscores the decades of clinical evidence and scientific studies by medical experts around the world support the safety of Johnson’s Baby Powder.”

After the verdict Rimondi’s lawyers said in a statement that they were “obviously disappointed by the outcome, particularly in light of the overwhelming scientific and documentary evidence supporting the claims of the Rimondi family that J & J’s talcum-based baby powder is laced with asbestos.”

But Johnson & Johnson hasn’t won all of its baby powder cases. Earlier this month, The New York Times reported that a California jury ordered the company to pay $29 million to a woman who claimed that the powder caused her cancer. The company said it would appeal that verdict.

And in July, the Times reported that Johnson & Johnson was ordered to pay $4.69 billion to 22 women and their families who had claimed that asbestos in the baby powder caused their ovarian cancer. The company said it would appeal that verdict.

On its website, the company explains its thoughts on why it thinks talc is safe.

Psychosis in teens may be linked to an unlikely culprit: air pollution

An unexpected danger of urban life: Psychotic experiences are more common among teens exposed to the highest levels of nitrogen dioxide and other forms of air pollution, according to a new study. Nitrogen oxides, including nitrogen dioxide, are tailpipe pollutants, entering the air due to burning fuel.

“One of the most consistent findings over the past few decades has been a link between cities and psychosis,” Joanne Newbury, lead author of the study and a postdoctoral researcher at King’s College London, said Tuesday. “Children who are born and raised in urban versus rural settings are almost twice as likely to develop psychosis in adulthood.”

An association but not a cause-effect relationship

For the study, published Wednesday in the journal JAMA Psychiatry, Newbury and her co-authors explored whether psychotic experiences are more common among teens exposed to higher levels of air pollution. They used data from a study with more than 2,000 participants, all born in England and Wales in 1994 and 1995.

Researchers have followed up with each child repeatedly at ages 5, 7, 10, 12 and most recently at 18, Newbury explained. They were asked in a private interview, “Have you ever heard voices that other people cannot hear? Have you thought you were being followed or spied on?”

Dr. Helen Fisher, a study co-author and a reader of developmental psychopathology at King’s College London, said Tuesday that “when we talk about psychotic experiences, we are talking about people who are experiencing things like hearing or seeing things other people don’t or feeling very paranoid.”

Such symptoms — which “are actually quite common in the general population,” she said — are considered “to be a kind of milder or less extreme form of the kind of psychotic symptom like hallucinations or delusions that we see in people who experience psychotic disorders like schizophrenia.”

A total of 623 (or 30%) of the teens reported at least one psychotic experience between ages 12 and 18.

Next, the researchers gathered hourly emissions data from monitoring sites to assess pollution levels in the places where each teen spent the most time: a home address and two other places such as school.

Psychotic experiences were significantly more common among teens in the highest quartile of pollution exposure, even after the researchers accounted for factors that might also be linked to psychosis, such as cigarette smoking, cannabis dependence and neighborhood crime levels.

The teens exposed to top-quartile levels of nitrogen dioxide, nitrogen oxides and particulate matter (PM2.5, fine inhalable particles derived from chemical smoke) had 71%, 72% and 45% greater odds, respectively, of psychotic experiences compared with those exposed to the lowest-quartile levels.

“Odds gradually increase as you move from rural to suburb to urban settings,” Newbury said, with teens living in the “most urban settings” having “94% greater odds of psychotic experiences compared to those living in rural settings.”

Newbury cautioned that this is not a cause-and-effect relationship but an association between air pollution and psychosis.

Although road traffic is responsible for most of the air pollution studied, Fisher said, “it could really be noise pollution that explains what is happening here.” Noise disrupts sleep and causes stress, and both are associated with psychotic experiences, she explained.

However, if air pollution is causing psychosis, Fisher speculates that the gases and particles might be causing brain inflammation, which previous research suggests may be linked to psychosis. Pollutants could also be “stunting brain development” during sensitive periods, which might be linked to psychosis, Fisher said: “Seventy-five percent of all mental health problems are going to start during this adolescent period, so it’s a really good period to go in and prevent some of those longer-term issues.”

What to make of the findings

Dr. Jim van Os, a professor and head of the Brain Division at University Medical Center Utrecht, wrote in an email that the paper is “nice” but lacks rigor.

The finding is “highly press sensitive” and “drawn from a study with literally thousands of variables,” noted van Os, who has researched and explored psychosis but was not involved in the new research. At best, it is “a hypothesis to examine in future work. In the absence of replication it does not mean much and is most likely a false positive finding.”

Sophie Dix, a cognitive researcher and director of research at MQ, a nonprofit that funds mental health research, told the Science Media Centre that “there is more work that needs to be done with this study.”

“There is no evidence that pollution necessarily causes psychosis or whether this is one of many factors or acting in isolation,” said Dix, who was not involved in the research. “There is a bigger picture here, but that does not diminish the importance of these findings and the potential that comes from this.”Stefan Reis, who heads the Atmospheric Chemistry and Effects Unit at the NERC Centre for Ecology & Hydrology, a research organization, told Science Media Centre that “the study makes a valuable contribution to the growing body of evidence that air pollution may affect more than just cardio-vascular and respiratory health.”

Reis, who did not participate in the study, said other variables worth exploring could include “academic attainment in early life stages and cognitive decline in old age due to early-life exposure to air pollution.” It’s important, he concluded, to further our understanding of “how air pollution is related to mental health outcomes which could in future have implications for air quality policies.”

Marianthi-Anna Kioumourtzoglou, an assistant professor in the Department of Environmental Health Sciences at the Columbia University Mailman School of Public Health, wrote in an editorial published beside the study that “air pollution exposures are ubiquitous in urban environments,” yet they are “modifiable and can be reduced through rigorous regulatory action.”

“It is especially important to identify other factors that may potentially ameliorate the consequences of air pollution to protect human health,” said Kioumourtzoglou, who had no role in the new research. “These could be lifestyle, nutritional, or neighborhood-level factors.”

“As the global population is becoming increasingly urban, it is of utmost importance to incorporate public environmental health into urban planning decisions.”

In the words of the study’s authors: “Given that 70% of the world’s population will be urban by 2050, uncovering the mechanisms linking the urban environment to psychosis and developing preventive interventions constitute an urgent health priority.”

New neurons for life? Old people can still make fresh brain cells, study finds

One of the thorniest debates in neuroscience is whether people can make new neurons after their brains stop developing in adolescence – a process known as neurogenesis. Now, a new study finds that even people long past middle age can make fresh brain cells, and that past studies that failed to spot these newcomers may have used flawed methods.

The work “provides clear, definitive evidence that neurogenesis persists throughout life,” says Paul Frankland, a neuroscientist at the Hospital for Sick Children in Toronto, Canada. “For me, this puts the issue to bed.”

Researchers have long hoped that neurogenesis could help treat brain disorders like depression and Alzheimer’s disease. But last year, a study in Nature reported that the process peters out by adolescence, contradicting previous work that had found newborn neurons in older people using a variety of methods. The finding was deflating for neuroscientists like Frankland, who studies adult neurogenesis in the rodent hippocampus, a brain region involved in learning and memory. It “raised questions about the relevance of our work,” he says.

But there may have been problems with some of this earlier research. Last year’s Nature study, for example, looked for new neurons in 59 samples of human brain tissue, some of which came from brain banks where samples are often immersed in the fixative paraformaldehyde for months or even years. Over time, paraformaldehyde forms bonds between the components that make up neurons, turning the cells into a gel, says neuroscientist María Llorens-Martín of the Severo Ochoa Molecular Biology Center in Madrid. This makes it difficult for fluorescent antibodies to bind to the doublecortin (DCX) protein, which many scientists consider the “gold standard” marker of immature neurons, she says.

The number of cells that test positive for DCX in brain tissue declines sharply after just 48 hours in a paraformaldehyde bath, Llorens-Martín and her colleagues report today in Nature Medicine. After 6 months, detecting new neurons “is almost impossible,” she says.

When the researchers used a shorter fixation time – 24 hours – to preserve donated brain tissue from 13 deceased adults, ranging in age from 43 to 87, they found tens of thousands of DCX-positive cells in the dentate gyrus, a curled sliver of tissue within the hippocampus that encodes memories of events. Under a microscope, the neurons had hallmarks of youth, Llorens-Martín says: smooth and plump, with simple, undeveloped branches.

In the sample from the youngest donor, who died at 43, the team found roughly 42,000 immature neurons per square millimeter of brain tissue. From the youngest to oldest donors, the number of apparent new neurons decreased by 30% – a trend that fits with previous studies in humans showing that adult neurogenesis declines with age. The team also showed that people with Alzheimer’s disease had 30% fewer immature neurons than healthy donors of the same age, and the more advanced the dementia, the fewer such cells.

Some scientists remain skeptical, including the authors of last year’s Nature paper. “While this study contains valuable data, we did not find the evidence for ongoing production of new neurons in the adult human hippocampus convincing,” says Shawn Sorrells, a neuroscientist at the University of Pittsburgh in Pennsylvania who co-authored the 2018 paper. One critique hinges on the DCX stain, which Sorrells says isn’t an adequate measure of young neurons because the DCX protein is also expressed in mature cells. That suggests the “new” neurons the team found were actually present since childhood, he says. The new study also found no evidence of pools of stem cells that could supply fresh neurons, he notes. What’s more, Sorrells says two of the brain samples he and his colleagues looked at were only fixed for 5 hours, yet they still couldn’t find evidence of young neurons in the hippocampus.

Llorens-Martín says her team used multiple other proteins associated with neuronal development to confirm that the DCX-positive cells were actually young, and were “very strict,” in their criteria for identifying young neurons.

Heather Cameron, a neuroscientist at the National Institute of Mental Health in Bethesda, Maryland, remains persuaded by the new work. Based on the “beauty of the data” in the new study, “I think we can all move forward pretty confidently in the knowledge that what we see in animals will be applicable in humans, she says. “Will this settle the debate? I’m not sure. Should it? Yes.”

Emily Underwood is a contributing correspondent for Science, covering neuroscience.