Chapter 4. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology

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7 Things Everyone Should Know About Antidepressants By Christina Caron Even if you’ve never taken an antidepressant, you’re probably familiar with the criticism and controversy that surrounds these drugs. It’s not uncommon to hear things like: “Those pills are just a placebo.” “You’ll definitely gain weight.” “Once you start, you’ll become dependent on them.” Is any of this true? Some of these statements have “a kernel of truth,” said Dr. Gerard Sanacora, a professor of psychiatry at the Yale School of Medicine. And it’s important to set the record straight because the expectations people have about their treatment — whether good or bad — “really do play a large role in how the treatment actually unfolds,” he added. Dr. Sanacora and other experts addressed some common questions and misconceptions about antidepressants. Will antidepressants change who I am? When an antidepressant starts to work, you may feel like a different person in some ways, said Naomi Torres-Mackie, a clinical psychologist in New York City. “Picture this giant, dark cloud weighing you down — as that lifts, the world is going to look different,” she said, adding: “But as you get used to it, you may see that it actually allows you to have more joy in your life.” On the other hand, up to half of people who take antidepressants may experience some degree of emotional blunting or numbed emotions, and research suggests that the blunting is more likely to happen with a higher medication dosage. When antidepressants are working correctly, patients should still feel a range of emotions, even if the sadness they used to feel every day is gone, said Dr. Laine Young-Walker, chair of the department of psychiatry at the University of Missouri School of Medicine. © 2024 The New York Times Compan

Keyword: Depression
Link ID: 29593 - Posted: 12.11.2024

By Shane O’Neill In 2018, Matt Christensen kicked heroin by replacing drugs with drinking. When he stopped drinking in 2022, he turned to food. He put on 95 pounds. His doctor recommended he try Wegovy, part of a class of drugs known as GLP-1 receptor agonists, to help him lose weight. Eventually he switched to a different drug called Zepbound, which targets both GLP-1 and GIP agonists. The drugs worked. Get concise answers to your questions. Try Ask The Post AI. But a funny thing happened on his weight-loss journey: His cravings for food had diminished but so had his cravings for drugs and alcohol. Christensen, 42, started drinking at age 9 and using heroin at 17. For decades, catching a cold meant reaching for a hot toddy. Work stress meant numbing out with Xanax. Even passing through certain neighborhoods in Chicago where he used to buy drugs would lead to cravings. But after he started taking GLP-1 agonists, those triggers became, well, less triggering. “It was the weirdest thing,” he said. “It was just quiet. I just found it really easy all of a sudden.” More than that, Christensen noticed that an unease he had always felt in his body — a discomfort he perpetually tried to quell with fidgeting, food or drugs — was diminishing. “That’s a feeling that I’ve had my entire life,” he said. “Taking these drugs has toned that down. “There’s no silver bullet for addiction or mental illness, but for me, in concert with the other treatments, it has been an absolute game changer,” he said. Matt Christensen says weight-loss drugs like Ozempic and Zepbound have been “an absolute game changer” when it comes to his addiction struggles.

Keyword: Drug Abuse; Obesity
Link ID: 29589 - Posted: 12.07.2024

By Christina Caron The holidays offer an excuse to gather with loved ones, let loose and indulge: Plates loaded with comfort foods. Unapologetic napping. All the pie. And, for some, plenty of alcohol. But heavy drinking is not limited to the holiday season. Nor is it mainly the pastime of college students. Overall binge drinking rates are now equivalent among young adults and those in midlife. That’s because young people, especially young men, are bingeing less — while middle-aged adults are throwing back more alcohol in a single session than they previously did. We’ve long been warned about the risks of binge drinking, usually defined as having four or five drinks in a two-hour span. And now researchers are increasingly focused on a more dangerous pattern of alcohol use that they call high-intensity drinking: consuming eight or more drinks in a row for women and 10 or more drinks in a row for men. High-intensity drinking is even riskier than binge drinking, and it’s on the rise among certain segments of the population. How does high-intensity drinking differ from binge drinking? The definition of binge drinking stems from the work of Henry Wechsler, a social psychologist at Harvard University who in 1993 tracked alcohol use among college students across the country. He found that young women who reported consuming at least four drinks in a night and men who consumed at least five experienced the most drinking-related problems. But other researchers noticed that some of the worst consequences associated with binge drinking, such as blackouts and alcohol poisoning, tended to happen when people had much more than four or five drinks. Over the years, experts have referred to heavier levels of binge drinking in different ways, including “extreme drinking” and the far less catchy “extreme ritualistic alcohol consumption.” In recent years they settled on “high-intensity drinking.” © 2024 The New York Times Company

Keyword: Drug Abuse
Link ID: 29582 - Posted: 11.30.2024

By Roni Caryn Rabin The number of deaths caused by alcohol-related diseases more than doubled among Americans between 1999 and 2020, according to new research. Alcohol was involved in nearly 50,000 deaths among adults ages 25 to 85 in 2020, up from just under 20,000 in 1999. The increases were in all age groups. The biggest spike was observed among adults ages 25 to 34, whose fatality rate increased nearly fourfold between 1999 and 2020. Women are still far less likely than men to die of an illness caused by alcohol, but they also experienced a steep surge, with rates rising 2.5-fold over 20 years. The new study, published in The American Journal of Medicine, drew on data from the Centers for Disease Control and Prevention. Deaths related to alcohol included those caused by certain forms of heart disease, liver disease, nerve damage, muscle damage, pancreatitis and alcohol poisoning, as well as related mental and behavioral disorders. The study did not include other deaths influenced by alcohol, such as accidents. “The totality of the evidence indicates that people who consume moderate to large amounts of alcohol have a markedly increased incidence of premature deaths and disability,” said Dr. Charles Hennekens, a professor of medicine at Charles E. Schmidt College of Medicine at Florida Atlantic University and one of the study’s authors. The increase at the onset of the pandemic appears to have persisted. Adults reported more heavy drinking and binge drinking in 2022, another recent study found. Some 48,870 alcohol-related deaths were reported in 2020, up from 19,356 in 1999, the new study found. The mortality rate rose to 21.6 deaths per 100,000 in 2020, an increase from 10.7 deaths per 100,000 in 1999. © 2024 The New York Times Company

Keyword: Drug Abuse
Link ID: 29570 - Posted: 11.23.2024

By Kim Tingley There are two opposite paths to achievement in science. The first is straightforward: Identify a problem and set about solving it. The second is rather unscientific-sounding and perhaps more faith-based: Study in obscurity and hope serendipity strikes. In 1980, a young gastroenterologist named Jean-Pierre Raufman wound up taking the latter road through the digestive-diseases branch of the National Institutes of Health. His goal there was to gain research experience. While doing so, he chanced to meet the lead chemist of another laboratory, John Pisano, who had a passion for seeking out new and interesting examples of a specific kind of hormone, called a peptide, in animal venoms. Pisano regularly appealed to local insect and reptile enthusiasts in the classified pages of The Washington Post; in response, they would show up at his office door carrying plastic bags wriggling with possibility. Pisano offered some venom samples to Raufman for his meandering analyses. Over the following month, Raufman experimented with them to see if they stimulated pancreatic cells harvested from guinea pigs. The venom with the biggest effect by far came from a desert reptile that Raufman had never heard of: the Gila monster. Gila monsters — sluggish, thick-tailed ground dwellers — are native to southern Arizona and northern Mexico. They have blunt noses and bumpy black skin with tan, pink or orange squiggles. They spend 95 percent of their lives underground. Like their cousins to the south, Mexican beaded lizards, they are one of the very few lizard species that produces venom, which they excrete from mouth glands into grooves in their serrated teeth. The strength of their jaws is typically enough to subdue their prey (chicks, frogs, worms and the like). But if threatened and unable to escape or hide, they may bite a predator. Whenever they clamp down, piercing the skin, venom enters the victim’s bloodstream. This causes intense pain and can initiate a cascade of other symptoms that, in people, includes vomiting, dizziness, rapid heart rate, low blood pressure and, in rare circumstances, death. © 2024 The New York Times Company

Keyword: Neurotoxins; Obesity
Link ID: 29555 - Posted: 11.13.2024

Denis Campbell Health policy editor Hundreds of thousands of smokers will be given a pill that increases people’s chances of quitting, in a move that NHS bosses believe will save thousands of lives. About 85,000 people a year in England will be offered the chance to use varenicline, a once-a-day tablet that experts say is as effective as vapes at helping people to kick the habit. Amanda Pritchard, the chief executive of NHS England, hailed the pill as a potential “gamechanger” in the fight to tackle smoking and the huge harm to health it causes. The drug helps people to quit by reducing their cravings for nicotine and ensuring that it cannot affect the brain in its usual way. It has also been found to reduce the side-effects smokers can experience when they stop using tobacco, such as trouble sleeping and irritability. The NHS in England will give varenicline as part of its efforts to keep driving down the number of people who smoke. A decline in smoking rates over the past 20 years means that only 11.6% of adults in England still have the habit – about 6 million people. Health service bosses hope its use will lead to 9,500 fewer smoking-related deaths over the next five years. The drug – known at the time as Champix – began being used in 2006 and was taken by about 85,800 people a year until July 2021. It then became unavailable after the Medicines and Healthcare products Regulatory Agency (MHRA), which regulates drugs, found impurities in it. That problem has now been addressed to the MHRA’s satisfaction and it has recently approved a generic version of the drug, which NHS England will use. It cited research by University College London that found it would save £1.65 in healthcare costs for every £1 it spent on the pill. © 2024 Guardian News & Media Limited

Keyword: Drug Abuse
Link ID: 29554 - Posted: 11.13.2024

By Elle Hunt The first time Nick (not his real name) tried ketamine, he felt as if he’d entered another dimension. Though he smoked marijuana regularly and had experimented with other drugs, Nick had never even heard of ketamine. But when his friend pulled out a bag of white powder, “I did what anybody else would do at 20 years old. I tried it,” he says. “And I found it really fun, to be honest.” The floaty feeling, like he’d been lifted out of his own body, was “euphoric”, he says. “Like you’re in a fairy world.” Sixteen years later, reality is biting hard. Nick, now 36, has spent the past three months in recovery for ketamine addiction after more than a decade of heavy use. His bladder is a fifth of the size it should be, he says. It’s “more than likely” that it will have to be removed and replaced with a urostomy bag. That’s setting aside all the other “brutal things” he’s gone through as a consequence of ketamine addiction – from being bed-bound by pain to embarrassing bladder failures. Now six months clean, Nick still cannot last half an hour without needing to use the toilet. “I am now a disabled person, having been such a fit lad,” he says. Nick is sharing his story to warn others of the dangers of ketamine, which is rapidly emerging as gen Z’s recreational drug of choice. Widely used in human and veterinary medicine as an anaesthetic, in illicit use the class B substance is typically snorted for its dissociative effects. According to the most recent government figures, use in England and Wales has more than doubled since 2016; among 16- to 24-year-olds, it has more than tripled, and there are stories of addicts as young as 12 or 13. The story is similar elsewhere. In Australia, recreational use of ketamine was reported to have reached a record high last year. In the US, seizures of illicit ketamine grew by 349% between 2017 and 2022. The death of Friends actor Matthew Perry at the age of 54 from “acute effects” of ketamine raised awareness of the risks of addiction. © 2024 Guardian News & Media Limited o

Keyword: Drug Abuse
Link ID: 29543 - Posted: 11.06.2024

Ian Sample Science editor Humans may have turned drinking into something of an art form but when it comes to animals putting alcohol away, Homo sapiens are not such an outlier, researchers say. A review of published evidence shows that alcohol occurs naturally in nearly every ecosystem on Earth, making it likely that most animals that feast on sugary fruits and nectar regularly imbibe the intoxicating substance. Although many creatures have evolved to tolerate a tipple and gain little more than calories from their consumption, some species have learned to protect themselves with alcohol. Others, however, seem less able to handle its effects. “We’re moving away from this anthropocentric view that alcohol is used by just humans and that actually ethanol is quite abundant in the natural world,” said Anna Bowland, a researcher in the team at the University of Exeter. After trawling research papers on animals and alcohol, the scientists arrived at a “diverse coterie” of species that have embraced and adapted to ethanol in their diets, normally arising through fermented fruits, sap and nectar. Ethanol became plentiful on Earth about 100m years ago when flowering plants began to produce sugary fruits and nectar that yeast could ferment. The alcohol content is typically low, at around 1% to 2% alcohol by volume (ABV), but in over-ripe palm fruit the concentration can reach 10% ABV. In one study, wild chimpanzees in south eastern Guinea were caught on camera bingeing on the alcoholic sap of raffia palms. Meanwhile, spider monkeys on Barro Colorado Island, Panama, are partial to ethanol-laden yellow mombin fruit, revealed to contain between 1% and 2.5% alcohol. “Evidence is growing that humans are not drinking alone,” the authors write in Trends in Ecology and Evolution. © 2024 Guardian News & Media Limited

Keyword: Drug Abuse; Evolution
Link ID: 29537 - Posted: 11.02.2024

By Megan TwoheyDanielle Ivory and Carson Kessler As marijuana legalization spreads across the country, people are consuming more of the drug, more often and at ever-higher potencies. Most of the tens of millions of people using marijuana, for health benefits or for fun, don’t experience problems. But a growing number, mainly heavy users, have experienced addiction, psychosis and other harmful effects, The New York Times found. “Cannabis is a lot of things at once,” said Dr. Kevin Gray, a psychiatrist and specialist in bio-behavioral medicine at Medical University of South Carolina Health. “It can be medically therapeutic. It also can be highly problematic.” In interviews and surveys, hundreds of people told The Times about serious — sometimes frightening — symptoms that they were stunned to learn could be caused by cannabis. Here are some of their stories. David Krumholtz, an actor known for films like “10 Things I Hate About You” and TV shows like “Numb3rs,” resumed smoking marijuana in 2016, after a decade-long break. Within months, he started to experience cycles of intense nausea and vomiting — a sometimes debilitating condition called cannabinoid hyperemesis syndrome. It can lead to dehydration, seizures, kidney failure, cardiac arrest and even death in rare instances. He lost 100 pounds and was in and out of emergency departments. At home in New Jersey, he would spend 10 hours at a time in hot baths, which for unknown reasons can temporarily relieve symptoms. “I had numbness in my extremities, pain in my chest and my blood pressure skyrocketed,” he said. Mr. Krumholtz, 46, believes he would have eventually died had he not suffered an episode that almost derailed his dream job, a role in the blockbuster 2023 film “Oppenheimer,” and inspired him to quit marijuana for good. © 2024 The New York Times Company

Keyword: Drug Abuse
Link ID: 29511 - Posted: 10.09.2024

Pien Huang More than half of all U.S. states have legalized cannabis, be it for medical purposes, recreational use, or both. The shelves of cannabis dispensaries offer an ever-widening array of gummies, drinks and joints. Meanwhile, the federal government still considers most types of cannabis illegal. A new report from the National Academies of Sciences, Engineering and Medicine, released this week, finds this disconnect between the states and the federal government is leading to fragmented policies, and risks to the public. As states built new commercial markets for cannabis, they initially focused on regulating sales and revenue. “The consequence of that is the public health aspects were often given a backseat and we're now playing catch up for that,” says Dr. Steven Teutsch, chair of the National Academies committee that wrote the report on how cannabis impacts public health. The report calls for federal leadership and national standards on cannabis quality and potency, to safeguard public health. Here are five takeaways: 1. People consume cannabis more regularly than alcohol in the U.S. In 2022, more U.S. adults reported using cannabis than alcohol on a near-daily basis, according to the National Survey on Drug Use and Health. It was the first time that regular marijuana use surpassed regular alcohol use. © 2024 npr

Keyword: Drug Abuse
Link ID: 29499 - Posted: 10.02.2024

By Elie Dolgin The first schizophrenia medication in decades with a new mechanism of action won US regulatory approval today. The approval offers the hope of an antipsychotic that would be more effective and better tolerated than current therapies. The drug, known as KarXT, targets proteins in the brain known as muscarinic receptors, which relay neurotransmitter signals between neurons and other cells. Activating these receptors dampens the release of the chemical dopamine, a nervous-system messenger that is central to the hallmark symptoms of schizophrenia, such as hallucinations and delusions. But muscarinic signalling also modulates other brain circuits involved in cognition and emotional processing. This mode of action provides KarXT with a more comprehensive therapeutic effect than other schizophrenia treatments, which mainly blunt dopamine activity alone. In clinical trials, KarXT not only alleviated core symptoms of schizophrenia, but also showed signs of improving cognitive function, all while avoiding many of the burdensome side effects commonly associated with older antipsychotics. “This will be a revolution of the treatment of psychosis, and I’m not saying this lightly,” says Christoph Correll, a psychiatrist at the Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York, who helped to analyse data from the trials. “Now we will now be able to treat people who haven’t been helped with traditional antipsychotics. That’s highly exciting.” KarXT is just the first of many next-generation drug candidates designed to engage muscarinic receptors in the brain. Several follow-on schizophrenia therapies are already in or nearing clinical trials, showing promise for improved tolerability and more convenient dosing schedules. This progress is leading clinicians and drug developers to imagine a future in which schizophrenia treatment becomes more tailored to individual needs — providing an alternative for the many people who don’t benefit from current therapies or abandon them owing to intolerable side effects. © 2024 Springer Nature Limited

Keyword: Schizophrenia
Link ID: 29498 - Posted: 09.28.2024

By Maia Szalavitz Last year over 70,000 Americans died from taking drug mixtures that contained fentanyl or other synthetic opioids. The good news is that recent data suggests a decline in overdose deaths, the first significant drop in decades. But this is not a uniform trend across the nation. To understand this disparity, it’s important to examine how we got here. Today’s crisis is often described as a series of waves. But if you look at the data, it was more like a couple of breakers followed by a tsunami. First, prescription opioid fatalities rose. Then heroin deaths surged. And finally, illicitly manufactured fentanyl overtook all that preceded it. Once fentanyl and other synthetic opioids dominate a market, whether a state is red or blue doesn't matter. Skyrocketing overdose deaths are nearly unavoidable, regardless of whether a state enforces tough penalties for drug possession or decriminalizes it. Understanding how fentanyl saturated the drug supply, moving from the East Coast of the United States to the West, is critical to ending the worst drug crisis in American history. In 2000, America was in its first wave of the opioid crisis. This was dominated by deaths from prescription painkillers like OxyContin. As you can see in the first map, though not entirely new to the country, illicitly manufactured fentanyl made up a tiny percentage of total drug seizures nationwide. Because escalations in opioid prescribing to treat pain were seen as the cause of the overdose problem, doctors began cutting off patients and law enforcement shuttered so-called pill mills. The number of opioid prescriptions began plummeting. © 2024 The New York Times Company

Keyword: Drug Abuse
Link ID: 29496 - Posted: 09.28.2024

Brian Mann For the first time in decades, public health data shows a sudden and hopeful drop in drug overdose deaths across the U.S. "This is exciting," said Dr. Nora Volkow, head of the National Institute On Drug Abuse [NIDA], the federal laboratory charged with studying addiction. "This looks real. This looks very, very real." National surveys compiled by the Centers for Disease Control and Prevention already show an unprecedented decline in drug deaths of roughly 10.6 percent. That's a huge reversal from recent years when fatal overdoses regularly increased by double-digit percentages. Some researchers believe the data will show an even larger decline in drug deaths when federal surveys are updated to reflect improvements being seen at the state level, especially in the eastern U.S. "In the states that have the most rapid data collection systems, we’re seeing declines of twenty percent, thirty percent," said Dr. Nabarun Dasgupta, an expert on street drugs at the University of North Carolina. According to Dasgupta's analysis, which has sparked discussion among addiction and drug policy experts, the drop in state-level mortality numbers corresponds with similar steep declines in emergency room visits linked to overdoses. Dr. Nabarun Dasgupta, a researcher at the University of North Carolina, is an expert on the U.S. street drug supply. He believes data shows a sudden drop in drug overdose deaths nationwide that could already by saving Dr. Nabarun Dasgupta, a researcher at the University of North Carolina, is an expert on the U.S. street drug supply. He believes data shows a sudden drop in drug overdose deaths nationwide that could already by saving "roughly 20,000 lives" per year. © 2024 npr

Keyword: Drug Abuse
Link ID: 29486 - Posted: 09.21.2024

By Roni Caryn Rabin Adults under age 50 have been developing breast cancer and colorectal cancer at increasingly higher rates over the last six decades, and alcohol use may be one factor driving the trend, according to a scientific report published on Wednesday. The report, by the American Association for Cancer Research, highlights scientific breakthroughs that have led to new anticancer drugs and improved overall survival. But the authors also described a troubling pattern: Even as cancer death rates have declined, the overall incidence of several cancers has been rising inexplicably, with an especially alarming increase among younger adults in cancers of the gastrointestinal system, like colorectal cancer. The report estimates that 40 percent of all cancer cases are associated with modifiable risk factors. It recommends reducing alcohol consumption, along with making lifestyle changes such as avoiding tobacco, maintaining a healthy diet and weight, exercising, avoiding ultraviolet radiation and minimizing exposure to pollutants. The authors called for raising awareness through public messaging campaigns and adding cancer-specific warning labels to alcoholic beverages. The recommendations come amid a radical rethinking of the putative health benefits of moderate alcohol consumption, which for years was considered to be protective against heart disease. Just last month, a large study that followed more than 135,000 older British adults for over a decade found that moderate and light drinkers did not benefit from a reduction in heart disease when compared with occasional drinkers. And both moderate and light drinkers experienced more cancer deaths than occasional drinkers, a finding accentuated among low-income seniors and those with existing health problems. © 2024 The New York Times Company

Keyword: Drug Abuse
Link ID: 29483 - Posted: 09.18.2024

By Angie Voyles Askham Nathaniel Daw has never touched a mouse. As professor of computational and theoretical neuroscience at Princeton University, he mainly works with other people’s data to construct models of the brain’s decision-making process. So when a collaborator came to him a few years ago with confusing data from mice that had performed a complex decision-making task in the lab, Daw says his best advice was just to fit the findings to the tried-and-true model of reward prediction error (RPE). That model relies on the idea that dopaminergic activity in the midbrain reflects discrepancies between expected and received rewards. Daw’s collaborator, Ben Engelhard, had measured the activity of dopamine neurons in the ventral tegmental area (VTA) of mice as they were deciding how to navigate a virtual environment. And although the virtual environment was more complex than what a mouse usually experiences in the real world, an RPE-based model should have held, Daw assumed. “It was obvious to me that there was this very simple story that was going to explain his data,” Daw says. But it didn’t. The neurons exhibited a wide range of responses, with some activated by visual cues and others by movement or cognitive tasks. The classic RPE model, it turned out, could not explain such heterogeneity. Daw, Engelhard and their colleagues published the findings in 2019. That was a wake-up call, Daw says, particularly after he watched videos of what the mice actually experienced in the maze. “It’s just so much more complicated, and high dimensional, and richer” than expected, he says. The idea that this richness could be reduced to such a simple model seems ludicrous now, he adds. “I was just so blinded.” © 2024 Simons Foundation

Keyword: Attention; Drug Abuse
Link ID: 29479 - Posted: 09.14.2024

By Christina Caron Patients and caregivers have struggled for two years to find stimulant medications like Adderall, Vyvanse and Concerta to treat attention deficit hyperactivity disorder. Some spend hours each month going from pharmacy to pharmacy to find a drug, while others are forced to switch to a different brand or formulation, or go without medication for weeks. This week the Drug Enforcement Administration announced a potential solution: It is raising the amount of lisdexamfetamine (Vyvanse) that can be produced by U.S. manufacturers this year by nearly 24 percent to meet demand in the United States and abroad. Vyvanse is an amphetamine that has been approved for use in children and adults with A.D.H.D. and has become commonly prescribed after the generic version was introduced last year. According to the D.E.A., the latest data shows that demand for the drug has been rising globally. But right now every manufacturer of generic Vyvanse listed on the Food and Drug Administration website is experiencing a shortage. Many health care providers who specialize in treating patients with A.D.H.D. said that the D.E.A.’s decision was a positive development but that it was unclear just how much of an effect it might have on the shortage. “Obviously it’s not going to solve the problem completely,” said Ami Norris-Brilliant, clinical director of the Division of A.D.H.D., Learning Disorders, and Related Disorders at the Icahn School of Medicine at Mount Sinai in New York City. “But I think anything that helps increase drug availability is a good thing.” It is not the first time that the D.E.A. has increased production quotas for A.D.H.D. drugs. Last year it announced a new 2023 limit for methylphenidate, which is used to make drugs like Ritalin and Concerta, raising the allotted amount by 27 percent for 2023. The drug remains in shortage, however, in the extended release formulation. © 2024 The New York Times Company

Keyword: ADHD
Link ID: 29473 - Posted: 09.11.2024

By Olivia Gieger Unlike traditional antidepressants, ketamine acts quickly to relieve depression symptoms, and its effects last long after the drug has cleared the system. Researchers have puzzled over what ketamine is doing in the brain to achieve these results. For one thing, the drug acts on N-methyl-D-aspartate (NMDA) glutamate receptors, which appear on neurons all over the brain. “Then the question is: Does the drug hit on all these brain regions simultaneously?” says Hailan Hu, professor of brain science at Zhejiang University. Or does it affect one region first, which sets off a series of downstream antidepressant effects? The answer is the latter, Hu and her colleagues report in a new study. Ketamine acts first on neurons in the lateral habenula, they found, in mice with depression-like symptoms. The structure—known as the “anti-reward” center—is hyperactive in people with depression and in mice modeling the condition, previous work has shown. That activity makes it highly susceptible to the drug’s effects, Hu and her colleagues discovered. Ketamine binds the NMDA receptors of cells in the lateral habenula and renders them inactive, which in turn interrupts downstream mechanisms of depression. The findings, published in Science in August, help explain how the known targets of ketamine are involved in such a rapid antidepressant response, explains Christophe Proulx, associate professor of psychiatry and neuroscience at Laval University. Proulx was not involved in the work but co-authored a Perspective article on it. Spotlighting the lateral habenula’s role also represents a new way of thinking about ketamine’s effects on depression—involving a shift away from a focus on weakened circuits and impaired plasticity, says Todd Gould, professor of psychiatry and neurobiology at the University of Maryland School of Medicine, who was not affiliated with the study. “[The work provides] additional strong evidence supporting a different view about how ketamine may be working.” Although ketamine inactivated NMDA receptors in the lateral habenula of the depressive-like mice, it had less impact in the CA1 region of the hippocampus, Hu and her colleagues observed using in-vitro slice electrophysiology and electrode recordings in awake animals. © 2024 Simons Foundation

Keyword: Depression
Link ID: 29472 - Posted: 09.11.2024

By Cassandra Willyard Megan Hodge’s first bout of intense pain arrived when she was in her mid-20s. Hodge and her husband were getting ready to visit family for Thanksgiving. Though Hodge had been dealing with a variety of chronic health issues, her workout had gone well that morning and she finally felt like she was getting a handle on her health. Hodge began packing. As she reached into her closet to grab a sweater, her back gave out. The pain was excruciating, so intense that she felt light-headed and thought she might vomit. As the years passed, Hodge had more frequent and more severe bouts of back pain. Any small movement could be a trigger — grabbing a towel from the linen closet, picking up a toy off the floor, sneezing. In 2021, Hodge experienced a particularly bad flare-up. None of the strategies she had previously used to help her manage seemed to be working. She was afraid to make any movement. She felt hopeless. “I just could not regain footing, metaphorically and physically,” she says. “I truly felt frozen in my chronic pain and chronic health journey.” Hodge is far from alone. In the United States, chronic pain affects tens of millions of people — about 1 in 5 adults and nearly 1 in 3 people ages 65 and older. “The amount of suffering from arthritis and aging that I’ve seen in my pain clinic, it’s overwhelming to me as a pain doctor,” says Antje Barreveld, an anesthesiologist at Mass General Brigham’s Newton-Wellesley Hospital in Massachusetts. What’s more, the mainstay therapy for severe acute and chronic pain — prescription opioids — has helped fuel an epidemic that kills tens of thousands of people each year. “We have to have some better alternatives,” she says. So researchers have doubled down in their quest to find new pain treatments that aren’t as addictive as opioids. “The pain field has really made very rapid and tremendous progress in the last decade,” says D.P. Mohapatra, a former pain scientist who now oversees research at the National Institute of Neurological Disorders and Stroke in Bethesda, Md. © Society for Science & the Public 2000–2024.

Keyword: Pain & Touch; Drug Abuse
Link ID: 29470 - Posted: 09.07.2024

By Christina Jewett The number of teenagers who reported using e-cigarettes in 2024 has tumbled from a worrisome peak reached five years ago, raising hopes among public health officials for a sustained reversal in vaping trends among adolescents. In an annual survey conducted from January through May in schools across the nation, fewer than 8 percent of high school students reported using e-cigarettes in the past month, the lowest level in a decade. That’s far lower than the apex, in 2019, when more than 27 percent of high school students who took the survey reported that they vaped — and an estimated 500,000 fewer adolescents than last year. The data is from the National Youth Tobacco Survey, a questionnaire filled out by thousands of middle and high school students that is administered each year by the Food and Drug Administration and the Centers for Disease Control and Prevention. Overall, it found that just under 6 percent of middle and high school students reported vaping in the last month, down from nearly 8 percent among those surveyed last year. Use among high school students largely accounted for this year’s decline; middle school use stayed fairly steady with 3.5 percent reporting they had vaped compared to 4.6 percent the year before. “I want to be unequivocally clear that this continued decline in e-cigarette use among our nation’s youth is a monumental public health win,” Brian King, the director of the F.D.A.’s tobacco division, said during a news briefing on Wednesday. Public health experts said several factors may have contributed to the decline in teenage vaping, including city and state flavored tobacco bans, a blitz of enforcement against sellers of flavored vapes and three public messaging campaigns aimed at young people about the dangers of vaping. © 2024 The New York Times Company

Keyword: Drug Abuse
Link ID: 29467 - Posted: 09.07.2024

By Jan Hoffman The message emblazoned on a walkway window at the airport in Burlington, Vt., is a startling departure from the usual tourism posters and welcome banners: “Addiction is not a choice. It’s a disease that can happen to anyone.” The statement is part of a public service campaign in yet another community assailed by drug use, intended to reduce stigma and encourage treatment. For decades, medical science has classified addiction as a chronic brain disease, but the concept has always been something of a hard sell to a skeptical public. That is because, unlike diseases such as Alzheimer’s or bone cancer or Covid, personal choice does play a role, both in starting and ending drug use. The idea that those who use drugs are themselves at fault has recently been gaining fresh traction, driving efforts to toughen criminal penalties for drug possession and to cut funding for syringe-exchange programs. But now, even some in the treatment and scientific communities have been rethinking the label of chronic brain disease. In July, behavior researchers published a critique of the classification, which they said could be counterproductive for patients and families. “I don’t think it helps to tell people they are chronically diseased and therefore incapable of change. Then what hope do we have?” said Kirsten E. Smith, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine and a co-author of the paper, published in the journal Psychopharmacology. “The brain is highly dynamic, as is our environment.” The recent scientific criticisms are driven by an ominous urgency: Despite addiction’s longstanding classification as a disease, the deadly public health disaster has only worsened. © 2024 The New York Times Company

Keyword: Drug Abuse
Link ID: 29461 - Posted: 09.04.2024