Chapter 4. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology

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Rhitu Chatterjee For the first time in a decade, overdose deaths among teens in the United States rose dramatically in 2020 and kept rising through 2021 as well. That's according to the results of a new study published Tuesday in JAMA. "This is very alarming because what we've seen in other parts of the population is that when overdose death rates start to rise, they tend to continue to do so for quite some time," says Joe Friedman, a public health researcher at the University of California, Los Angeles, and the lead author of the new study. "We're still really in the early days in terms of teen overdose. And that makes this an especially important time to intervene," he adds. Friedman and his colleagues found that fatal overdoses among adolescents nearly doubled from 492 in 2019 to 954 in 2020, an increase of 94%. There was an additional 20% rise in 2021 compared to the previous year. The highest rates were among Native American and Alaskan Native teens, followed by Latino teens. "For decades, we've seen overdose rates rising among adults, and teens have been insulated from that," says Friedman. "And now, for the first time, the overdose crisis is reaching teens as well." It appears that the rise in deaths was fueled not by greater numbers of teens using drugs – substance use in this age group actually went down during the pandemic – but by use of dangerous and highly potent forms of fentanyl. The study found that fentanyl-related deaths increased from 253 in 2019 to 680 the following year. And in 2021, 77% of all teen overdose deaths involved fentanyl. © 2022 npr

Keyword: Drug Abuse
Link ID: 28281 - Posted: 04.13.2022

By Gina Kolata Last week, two patients asked Dr. Stanley L. Hazen, a cardiologist at the Cleveland Clinic, how much daily alcohol consumption would be good for their cardiac health. He gave them both well-accepted medical advice — an average of about one drink a day helps the heart. “I didn’t give it a second thought,” he said. Then he saw a paper published in JAMA Network Open whose findings upended his thinking about what to tell patients. The paper, he said, “totally changes my life.” Its conclusion: There is no level of drinking that does not confer heart disease risk. The risk is small if people have an average of seven drinks a week when compared with none. But it increases quickly as the level of alcohol consumption rises. “Dose matters a lot,” said Dr. Krishna G. Aragam, a preventive cardiologist at Massachusetts General Hospital and an author of the study. “Just realize that, as you go up beyond modest ranges, the risk goes up quite a bit.” The study, which may help resolve medical disputes over the effects of alcohol on the heart, involved sophisticated analyses of the genes and medical data of nearly 400,000 people who participate in the U.K. Biobank, a British repository that investigators use to study genes and their relation to health. The average age of subjects selected for the alcohol study was 57, and they reported consuming an average of 9.2 drinks a week. Some researchers have reported that drinking modestly protects the heart because moderate drinkers as a group have less heart disease than those who drink heavily or those who abstain. Dr. Aragam and his colleagues also saw that effect. But the reason, they report, is not that alcohol protects the heart. It is that light to moderate drinkers — those who consume up to 14 drinks a week — tend to have other characteristics that decrease their risk, like smoking less, exercising more and weighing less than those who drink more heavily and those who do not drink. © 2022 The New York Times Company

Keyword: Drug Abuse
Link ID: 28260 - Posted: 03.30.2022

By Roni Caryn Rabin Almost a million people in the United States have died of Covid-19 in the past two years, but the full impact of the pandemic’s collateral damage is still being tallied. Now a new study reports that the number of Americans who died of alcohol-related causes increased precipitously during the first year of the pandemic, as routines were disrupted, support networks frayed and treatment was delayed. The startling report comes amid a growing realization that Covid’s toll extends beyond the number of lives claimed directly by the disease to the excess deaths caused by illnesses left untreated and a surge in drug overdoses, as well as to social costs like educational setbacks and the loss of parents and caregivers. Numerous reports have suggested that Americans drank more to cope with the stress of the pandemic. Binge drinking increased, as did emergency room visits for alcohol withdrawal. But the new report found that the number of alcohol-related deaths, including from liver disease and accidents, soared, rising to 99,017 in 2020, up from 78,927 the previous year — an increase of 25 percent in the number of deaths in one year. That compares with an average annual increase of 3.6 percent in alcohol-related deaths between 1999 and 2019. Deaths started inching up in recent years, but increased only 5 percent between 2018 and 2019. The study, done by researchers with the National Institute on Alcohol Abuse and Alcoholism, a division of the National Institutes of Health, was published in The Journal of the American Medical Association on Friday. Using information from death certificates, the researchers included all deaths in which alcohol was listed as an underlying or contributing cause. (Only a very small number also involved Covid-19.) “The assumption is that there were lots of people who were in recovery and had reduced access to support that spring and relapsed,” said Aaron White, the report’s first author and a senior scientific adviser at the alcohol abuse institute. © 2022 The New York Times Company

Keyword: Drug Abuse; Stress
Link ID: 28253 - Posted: 03.26.2022

Allison Whitten Every time you reach for your coffee mug, a neuroscientific mystery takes shape. Moments before you voluntarily extend your arm, thousands of neurons in the motor regions of your brain erupt in a pattern of electrical activity that travels to the spinal cord and then to the muscles that power the reach. But just prior to this massively synchronized activity, the motor regions in your brain are relatively quiet. For self-driven movements like reaching for your coffee, the “go” signal that tells the neurons precisely when to act — instead of the moment just before or after — has yet to be found. In a recent paper in eLife, a group of neuroscientists led by John Assad at Harvard Medical School finally reveals a key piece of the signal. It comes in the form of the brain chemical known as dopamine, whose slow ramping up in a region lodged deep below the cortex closely predicted the moment that mice would begin a movement — seconds into the future. Dopamine is commonly known as one of the brain’s neurotransmitters, the fast-acting chemical messengers that are shuttled between neurons. But in the new work, dopamine is acting as a neuromodulator. It’s a term for chemical messengers that slightly alter neurons to cause longer-lasting effects, including making a neuron more or less likely to electrically communicate with other neurons. This neuromodulatory tuning mechanism is perfect for helping to coordinate the activity of large populations of neurons, as dopamine is likely doing to help the motor system decide precisely when to make a movement. The new paper is one of the latest results to expand our knowledge of the crucial and varied roles that neuromodulators play in the brain. With recent advances in technology, neuroscientists can now view neuromodulators at work in networks that traverse the entire brain. The new findings are overturning some long-held views about these modulators adrift in the brain, and they’re revealing exactly how these molecules allow the brain to flexibly change its internal state amid ever-changing environments. All Rights Reserved © 2022

Keyword: Movement Disorders; Drug Abuse
Link ID: 28251 - Posted: 03.23.2022

Brian Mann Nine state attorneys general have agreed to drop their objection to a deal granting immunity from opioid lawsuits to members of the Sackler family who own Purdue Pharma, the maker of OxyContin. In exchange, the family has agreed to increase the amount it pays from personal holdings from roughly $4.5 billion under a previous settlement to $6 billion. Washington state Attorney General Robert Ferguson described the terms of the new settlement as a victory. "Rather than join the majority of states in settlement, Washington chose to lead the fight against the Sacklers and Purdue," Ferguson said in a statement. "As a result, we won more than $100 million for Washington state to address the opioid epidemic, and more than $1 billion for states, cities and tribes across the country." The prior deal was overturned by a federal judge in Manhattan last December after some states and the Justice Department filed an appeal. States demanding more money from the Sacklers — California, Connecticut, Delaware, Maryland, New Hampshire, Oregon, Vermont and Washington — have among the highest overdose death rates in the country. In a statement, members of various branches of the Sackler family again denied any wrongdoing and described the settlement as one that will "allow very substantial additional resources to reach people and communities in need." "While the families have acted lawfully in all respects, they sincerely regret that OxyContin, a prescription medicine that continues to help people suffering from chronic pain, unexpectedly became part of an opioid crisis that has brought grief and loss to far too many families and communities." Critics, including many of the state attorneys general who approved this deal, have long accused members of the Sackler family of aggressively marketing opioids in ways that contributed to soaring rates of addiction and overdoses. © 2022 npr

Keyword: Drug Abuse
Link ID: 28230 - Posted: 03.05.2022

By Jan Hoffman For years, Dr. Xiulu Ruan was one of the nation’s top prescribers of quick-release fentanyl drugs. The medicines were approved only for severe breakthrough pain in cancer patients, but Dr. Ruan dispensed them almost exclusively for more common ailments: neck aches, back and joint pain. According to the Department of Justice, he and his partner wrote almost 300,000 prescriptions for controlled substances from 2011 to 2015, filled through the doctors’ own pharmacy in Mobile, Ala. Dr. Ruan often signed prescriptions without seeing patients, prosecutors said. Dr. Ruan has been serving a 21-year sentence in federal prison, convicted in 2017 for illegally prescribing opioids and related financial crimes. To collect millions of dollars in fines, the government seized houses, beach condos and bank accounts belonging to him and his business partner, as well as 23 luxury cars, such as Bentleys, Lamborghinis and Ferraris. On Tuesday, lawyers both for Dr. Ruan and for Dr. Shakeel Kahn, who is serving 25 years on charges related to pill mill clinics in Arizona and Wyoming will argue before the Supreme Court of the United States that the criminal standard the physicians faced is applied inconsistently among the federal circuits. In asking that the doctors’ convictions be overturned, they want the court to establish a uniform standard that permits doctors to raise a “good faith” defense. Juries could then consider whether doctors subjectively believed they were using their best medical judgment. The likelihood of these two doctors being set free is small, legal experts believe, but the court’s decision on the broader legal questions could have significant implications for the latitude doctors can take in prescribing potentially addictive painkillers and other restricted medications. The cases confront an uneasy relationship between law and medicine. In an era when overdose deaths are soaring, how should the law balance letting physicians exercise their best judgment with stopping egregious outliers? © 2022 The New York Times Company

Keyword: Drug Abuse; Pain & Touch
Link ID: 28226 - Posted: 03.02.2022

Brian Mann Over the next two weeks, some of the biggest U.S. corporations accused of "turbocharging" the opioid epidemic could finalize payouts to victims and governments worth roughly $32 billion. "We've lost more than a million Americans to this epidemic, and sadly, it's at an all-time high as overdose deaths continue to rise," said Texas Attorney General Ken Paxton last week, in a statement announcing his state is now in line to receive roughly $1.1 billion. Paxton said pharmaceutical companies that made, distributed and sold opioids were "at the root of the problem." Their payments will help fund "treatment for those currently still struggling with opioid addiction," he added. This comes as communities across the U.S. are scrambling for resources to combat an opioid crisis that keeps getting worse. Drug overdoses killed more than 104,000 Americans in the most recent 12-month period for which data is available, according to the Centers for Disease Control and Prevention. That's a tragic new record for the U.S. There are two major negotiations nearing completion. The largest involves major drug distributors and wholesalers AmerisourceBergen, Cardinal Health and McKesson, along with health products giant Johnson & Johnson. Article continues after sponsor message The four firms, which maintain they did nothing wrong, have tentatively agreed to payouts totaling $26 billion. The Texas money would come from that deal, as would roughly $590 million that would go to Native American tribes. © 2022 npr

Keyword: Drug Abuse
Link ID: 28216 - Posted: 02.23.2022

By Jan Hoffman The federal government on Thursday proposed new guidelines for prescribing opioid painkillers that remove its previous recommended ceilings on doses for chronic pain patients and instead encourage doctors to use their best judgment. But the overall thrust of the recommendations was that doctors should first turn to “nonopioid therapies” for both chronic and acute pain, including prescription medications like gabapentin and over-the-counter ones like ibuprofen, as well as physical therapy, massage and acupuncture. Though still in draft form, the 12 recommendations, issued by the Centers for Disease Control and Prevention, are the first comprehensive revisions of the agency’s opioid prescribing guidelines since 2016. They walk a fine line between embracing the need for doctors to prescribe opioids to alleviate some cases of severe pain while guarding against exposing patients to the well-documented perils of opioids. Dr. Samer Narouze, president of the American Society of Regional Anesthesia and Pain Medicine, an association of clinicians, praised the tone, level of detail and focus of the project. “It’s a total change in the culture from the 2016 guidelines,” he said, characterizing the earlier edition as ordering doctors to “just cut down on opioids — period.” By contrast, the new proposal “has a much more caring voice than a policing one, and it’s left room to preserve the physician-patient relationship,” added Dr. Narouze, chairman of the Center for Pain Medicine at Western Reserve Hospital in Cuyahoga Falls, OH. The 229-page document warns of addiction, depressed breathing, altered mental status and other dangers associated with opioids, but it also notes that the drugs serve an important medical purpose, especially for easing the immediate agony from traumatic injuries such as burns and crushed bones. In those instances when opioids seem the way to go, the recommendations said, doctors should start with the lowest effective dose and prescribe immediate-release pills rather than long-acting ones. © 2022 The New York Times Company

Keyword: Drug Abuse; Pain & Touch
Link ID: 28207 - Posted: 02.16.2022

By Emma Yasinski By the time kids diagnosed with attention deficit hyperactivity disorder meet with clinical psychologist Mary O’Connor, they have often been taking multiple medications or unusually high doses of stimulants like Ritalin. “They may have had a trial of stimulants that worked initially,” she says, but when the effect waned, their physicians prescribed higher doses, sometimes to the point of toxicity. O’Connor researches fetal alcohol spectrum disorders at the University of California, Los Angeles, where she has provided both diagnosis and treatment to children exposed to alcohol in the womb. At one end of the spectrum sits fetal alcohol syndrome, characterized by facial abnormalities, growth problems, and intellectual disabilities. The other end of the spectrum is characterized by subtler symptoms, including poor judgement and impulsivity — in other words, what looks to many like ADHD. But experts say standard ADHD treatments often don’t work as well for children exposed to alcohol in-utero. And lack of awareness, a shortage of specialists, and social stigma have combined to limit families’ ability to receive an accurate diagnosis and support for FASD, a condition that is underdiagnosed in the United States and could affect between 1 and 5 percent of this country’s children. The lack of diagnoses, scientists say, stifles research on treatments and may even cloud data on therapies for other disorders.

Keyword: ADHD; Drug Abuse
Link ID: 28206 - Posted: 02.16.2022

By Elizabeth Landau My grandmother was in the advanced stages of Alzheimer’s disease when she died in 2007, not long after I graduated from journalism school. As a budding health reporter, I tried to learn everything I could about Alzheimer’s and wrote about new research on preventions and treatments that everyone wanted to believe had potential. It is demoralizing and infuriating to think about how, nearly 15 years later, no breakthrough cure or proven prevention strategy has panned out. But neurologist Sara Manning Peskin argues in “A Molecule Away from Madness: Tales of the Hijacked Brain” that we could be on the brink of a revolution in confronting diseases like this because scientists have a better handle on how molecules work in the brain. Molecular research has transformed our understanding and treatment of cancer in recent years, and now it is beginning to do the same for brain diseases. In fact, it has already been key to solving several mysteries of why seemingly healthy people appear to suddenly fall into a mental inferno. While the shadow of Alzheimer’s looms over the book, representing an intractable condition that Peskin routinely confronts in her clinical practice, “A Molecule Away from Madness” is a fascinating tour of different kinds of ways that the brain can lead to the breakdown of mental life. The book is organized according to how different molecules interact with our brains to wreak havoc — Peskin calls them “mutants, rebels, invaders, and evaders.” Some have helped scientists solve longstanding puzzles, while others, like the molecules associated with Alzheimer’s, continue to leave millions of people waiting for a cure.

Keyword: Alzheimers
Link ID: 28196 - Posted: 02.12.2022

By Lenny Bernstein The federal government on Thursday proposed new guidelines for prescribing opioids that would eliminate numerical dosage recommendations for treatment of chronic pain in favor of a more flexible approach by caregivers. FAQ: What to know about the omicron variant of the coronavirus The recommendations call for doctors and other prescribers to weigh the risks and benefits of starting, increasing and halting treatment with opioids. They leave out previous advice on the amount and duration of painkiller treatments that patients and doctors have contended was sometimes misinterpreted, causing serious harm to people suffering unrelenting pain. For some with chronic pain, the problem is not in their backs or knees but their brains Some states and caregivers adopted tight rules based on the recommendations, first issued in 2016, resulting in patients having difficulty obtaining pain drugs or having them cut off abruptly. “There’s not a one size fits all,” said Christopher Jones, acting director of the National Center for Injury Prevention and Control, part of the Centers for Disease Control and Prevention. “We’ve heard that quite clearly. When you have hard thresholds like 90 [morphine milligram equivalents] or a specific duration, it makes it too easy for policymakers or others to take that out of context and apply that as a rigid cap.” Bobby Mukkamala, chairman of the American Medical Association Board of Trustees, issued a statement saying that “for nearly six years, the AMA has urged the CDC to reconsider its problematic guideline on opioid prescriptions that proved devastating for patients with pain. The CDC’s new draft guideline — if followed by policymakers, health insurance companies and pharmacy chains — provides a path to remove arbitrary prescribing thresholds, restore balance and support comprehensive, compassionate care.” Andrew Kolodny, one of the fiercest critics of opioid manufacturers, said he believes some of the opposition was orchestrated by drug companies that saw the attempt to curb opioid prescribing — especially of high-dose pills — as a threat to their profit margins. © 1996-2022 The Washington Post

Keyword: Drug Abuse
Link ID: 28195 - Posted: 02.12.2022

By Christina Caron After 10 years of marriage, Ree, 42, and her husband were ready to call it quits. Even their therapist had given up, she said, in part because her husband “was so closed off, just unable to open up.” “We loved each other a lot and we were very compatible, however, we didn’t know how to deal with conflict,” Ree said. She was often anxious about their relationship and could be “a little neurotic at times,” but the more she pushed her husband to connect, the more withdrawn he became. Their sex life suffered. Then a friend suggested that they try the illegal drug MDMA, popularly known as Ecstasy or Molly. For Ree — who, along with her husband, requested anonymity to speak about drug use, and is referred to by a nickname — the answer was an “immediate no.” MDMA, long associated with rave culture, is currently categorized as a Schedule I drug — meaning it has a high potential for abuse and no accepted medical use in the United States. “We are about as strait-laced as you can come,” she said. “We’re not people who break laws or do drugs.” Six months later, after reading “How to Change Your Mind,” the best-selling book by Michael Pollan that details his transformative experience with psychedelics, Ree reconsidered. And that’s how they found themselves in a secluded area of Utah at a large, rented house with a beautiful view of the mountains to trip on MDMA with five other couples. In recent years, clinical trials have shown that MDMA, when combined with talk therapy, can bring relief to those suffering from post-traumatic stress disorder, a finding that has elevated MDMA’s reputation from party drug to potential therapeutic. Some couples, drawn to the drug’s ability to produce feelings of empathy, trust and compassion, have started using unregulated MDMA on their own in an effort to help them reconnect, improve communication and have better sex. © 2022 The New York Times Company

Keyword: Drug Abuse; Depression
Link ID: 28192 - Posted: 02.09.2022

By Amelia Nierenberg A couple of glasses of wine or a few drinks in the evening will probably make you fall asleep faster than normal. Who among us hasn’t left the dishes for the next morning or neglected a skin-care routine after a dinner party or festive night out? But even if you thud into dreamland, there’s a good chance that too much alcohol will mean a fitful night of sleep. That’s because alcohol disrupts what’s known as your sleep architecture, the normal phases of deeper and lighter sleep we go through every night. A night of drinking can “fragment,” or interrupt, these patterns, experts say, and you may wake up several times as you ricochet through the usual stages of sleep. “You pay for it in the second half of the night,” said Dr. Jennifer Martin, a psychologist and professor of medicine at the University of California, Los Angeles. Alcohol is “initially sedating, but as it’s metabolized, it’s very activating.” Here’s how it breaks down. In the first half of the night, when fairly high levels of alcohol are still coursing through your bloodstream, you’ll probably sleep deeply and dreamlessly. One reason: In the brain, alcohol acts on gamma-aminobutyric acid, or GABA, a neurotransmitter that inhibits impulses between nerve cells and has a calming effect. Alcohol can also suppress rapid eye movement, or REM sleep, which is when most dreaming occurs. Later in the night, as alcohol levels drop, your brain kicks into overdrive. You may toss and turn as your body undergoes a rebound arousal. “As the levels decline, you’re going to get more issues with the fragmentation,” said Dr. R. Nisha Aurora, a member of the board of directors of the American Academy of Sleep Medicine. You’ll also probably have more vivid or stressful dreams and — because fitful sleep means that you’re waking up more regularly — you are more likely to remember them.

Keyword: Sleep; Drug Abuse
Link ID: 28183 - Posted: 02.02.2022

ByRobert F. Service More than 50 years after the Summer of Love, psychedelics are again the rage. This time the love comes from doctors beginning to embrace psychedelics such as LSD and psilocybin to treat depression, substance abuse, and other serious mental health conditions. But because the drugs cause hallucinations, their medical use requires intensive monitoring by clinicians. That drives up treatment costs, making psychedelics impractical for widespread therapeutic use. In recent years, researchers have begun to tweak psychedelics’ chemical structures, aiming to make analogs that retain medical usefulness but don’t cause hallucinations. Now, researchers report in Science they’ve teased apart the molecular interactions responsible for psychedelics’ antidepressive effects from those that cause hallucinations. They used that knowledge to make new compounds that appear to activate brain cellular circuits that help relieve depression without triggering a closely related pathway involved in hallucinations. So far, the compounds have only been studied in mice. But if such psychedelic analogs work in humans, they could spawn new families of pharmaceuticals. “This work is going to generate a lot of interest,” says Bryan Roth, a pharmacologist at the University of North Carolina School of Medicine, whose lab is also seeking nonhallucinogenic psychedelic analogs. The need is profound. Mental or neurological disorders are estimated to affect roughly one-quarter of U.S. adults every year, and therapies often don’t work. LSD, psilocybin (the main ingredient in magic mushrooms), and other psychedelics might do better. Studies have shown a single dose of psilocybin can offer relief from depression for months at a time, and last year, a clinical trial of 3,4-methylenedioxymethamphetamine, or ecstasy, showed it can alleviate posttraumatic stress disorder. © 2022 American Association for the Advancement of Science.

Keyword: Depression; Drug Abuse
Link ID: 28177 - Posted: 01.29.2022

Sung Han & Shijia Liu You’re startled by a threatening sound, and your breath quickens. You smash your elbow and pant in pain. Why does your breathing rate increase dramatically when you’re hurting or anxious? As neurobiologists studying how the brain responds to environmental threats and the neural circuitry of emotion, we were curious about the answer to this question ourselves. In our recently published study, we discovered that one particular circuit of the brain in mice underlies this tight connection between pain, anxiety and breathing. And this discovery may eventually help us develop safer pain killers for humans. One of the most common symptoms of both pain and anxiety disorders is shortness of breath, or hyperventilation. On the other hand, slow, deep breathing can reduce pain and distress. The simplest way to explain this, we reasoned, is the existence of a common pathway in the brain that regulates breathing, pain and anxiety simultaneously. So we searched for brain regions previously reported to regulate breathing, pain and emotion. A small area in the brainstem called the lateral parabrachial nucleus caught our attention. Not only is it part of the breathing regulation center of the brain, it also mediates pain and negative emotions like fear and anxiety. Searching through a public database of gene expression patterns, or how genetic material is translated into proteins that let cells function, in the mouse brain, we serendipitously found that one type of opioid receptor called the µ-opioid receptor is highly expressed in parabrachial neurons. © 2010–2022, The Conversation US, Inc.

Keyword: Emotions; Drug Abuse
Link ID: 28167 - Posted: 01.22.2022

By Lisa Sanders, M.D. The mother stood in the baggage-claim area of the Buffalo Niagara International Airport, waiting for her 37-year-old son, who had just flown in from North Carolina. The carousel was nearly empty by the time she caught sight of him. She was shocked by how sick he looked. His face was pale and thin, his hair and clothes rumpled as if he felt too awful to care. Most surprising of all: He was being rolled toward her in a wheelchair. “I had some trouble with the stairs,” he explained. He thanked the attendant and then struggled to get to his feet. He didn’t make it. Before he got more than a few inches off the seat, his arms and then his legs began to shake and wobble, and he fell heavily back into the chair. His mother collected his bag and pushed him out to where her husband was waiting in the car. On the drive home, the young man struggled to explain what was going on. He had always considered himself to be pretty strong and healthy, but these past few weeks had been rough. It started in his legs. He felt wobbly. When he walked, his hips, legs and especially his feet felt as if they might not be able to hold him up. He saw his physician assistant about it — he worried that it was caused by the cholesterol-lowering medication he had started taking — but the P.A. assured him it wasn’t. He was running a few times a week, but he had to stop because his legs were done well before the run was. And he didn’t feel as sharp as he used to be. His brain seemed foggy and slow. Then this morning he had trouble climbing the stairs to the plane. That was scary. The guy behind him helped by holding up his backpack, but his feet felt like dead weights. He had to use his arms to help get his body up high enough to take each step. Once on the plane, he supported himself on the headrests to get to his assigned seat. They offered the wheelchair when he arrived in Buffalo, and he gratefully accepted. His mother tentatively asked if he thought he should see a doctor. She knew he hated it when she tried to tell him what to do. He had flown up to see a football game with her ex-husband, his father, and a hockey game with his stepbrother. If he didn’t feel any better after that, he conceded, it would be time to see a doctor. © 2022 The New York Times Company

Keyword: Movement Disorders; Drug Abuse
Link ID: 28150 - Posted: 01.12.2022

By Charles F. Zorumski One minute you’re enjoying a nice buzz, the next your brain stops recording events that are taking place. The result can mean having vague or no memory of a time period ranging anywhere from a few minutes up to several hours. Scary—isn’t it? Unfortunately, alcohol-induced blackouts aren’t a rarity, either. A 2015 survey of English teenagers who drank showed 30 percent of 15-year-olds and 75 percent of 19-year-olds suffered alcohol-induced blackouts. In medical terms this memory loss is a form of temporary anterograde amnesia, a condition where the ability to form new memories is, for a limited time, impaired. That means you can’t remember a stretch of time because your brain was unable to record and store memories in the first place. Neuroscientists do not fully understand how blackouts occur. Researchers long assumed alcohol impairs memory because it kills brain cells. Indeed, long-standing alcohol abuse can damage nerve cells and permanently impact memory and learning. It is unlikely, however, that brain damage is behind acute blackouts. It is clear that processes in the hippocampus—the area of brain involved in the formation, storage and retrieval of new memories—are disturbed. Specifically, it appears alcohol impairs the so-called long-term potentiation of synapses at the pyramidal cells in the hippocampus. Alcohol alters the activity of certain glutamate receptors, thereby boosting the production of specific steroid hormones. This in turn slows the long-term potentiation of hippocampal synapses. Normally this mechanism, responsible for strengthening the synaptic transfer of information between neurons, is the basis of memory formation. © 2022 Scientific American,

Keyword: Drug Abuse; Learning & Memory
Link ID: 28142 - Posted: 01.08.2022

By Emily Witt In the fall of 1972, a psychiatrist named Salvador Roquet travelled from his home in Mexico City to the Maryland Psychiatric Research Center, an institution largely funded by the United States government, to give a presentation on an ongoing experiment. For several years, Roquet had been running a series of group-therapy sessions: over the course of eight or nine hours, his staff would administer psilocybin mushrooms, morning-glory seeds, peyote cacti, and the herb datura to small groups of patients. He would then orchestrate what he called a “sensory overload show,” with lights, sounds, and images from violent or erotic movies. The idea was to push the patients through an extreme experience to a psycho-spiritual rebirth. One of the participants, an American psychology professor, described the session as a “descent into hell.” But Roquet wanted to give his patients smooth landings, and so, eventually, he added a common hospital anesthetic called ketamine hydrochloride. He found that, given as the other drugs were wearing off, it alleviated the anxiety brought on by these punishing ordeals. Clinicians at the Maryland Psychiatric Research Center had been studying LSD and other psychedelics since the early nineteen-fifties, beginning at a related institution, the Spring Grove Hospital Center. But ketamine was new: it was first synthesized in 1962, by a researcher named Calvin Stevens, who did consulting work for the pharmaceutical company Parke-Davis. (Stevens had been looking for a less volatile alternative to phencyclidine, better known as PCP.) Two years later, a doctor named Edward Domino conducted the first human trials of ketamine, with men incarcerated at Jackson State Prison, in Michigan, serving as his subjects. At higher doses, Domino noticed, ketamine knocked people out, but at lower ones it produced odd psychoactive effects on otherwise lucid patients. Parke-Davis wanted to avoid characterizing the drug as psychedelic, and Domino’s wife suggested the term “dissociative anesthetic” to describe the way it seemed to separate the mind from the body even as the mind retained consciousness. The F.D.A. approved ketamine as an anesthetic in 1970, and Parke-Davis began marketing it under the brand name Ketalar. It was widely used by the U.S. military during the Vietnam War, and remains a standard anesthetic in emergency rooms around the world. © 2021 Condé Nast.

Keyword: Depression; Drug Abuse
Link ID: 28132 - Posted: 12.31.2021

By Vanessa Barbara JUIZ DE FORA, Brazil — My first encounter with ketamine did not go well. A lifelong depressive — I picked up the habit of despairing sadness in early adulthood, and it remained faithfully with me — I’d turned to a more experimental form of treatment: ketamine infusions, in which a kindly anesthesiologist funnels the drug into a sad person’s veins for around 50 minutes and hopes it perks her up. Forty-five minutes into my first session, I rather anxiously asked my partner, who was in the room with me, if our 3-year-old daughter was fine. He decided it was the perfect time for a joke. Our daughter, he answered, was safe at home — and as a matter of fact, he added, she was already a very independent 15-year-old. I panicked. While under the strong, dissociative effect of the drug, patients sometimes enter what’s called a k-hole, in which their sense of time and space is distorted or eliminated. In that state of oblivion, I found it entirely plausible that my daughter was not a toddler anymore, but a strong-willed teenager. I became very distressed. My heartbeat accelerated. The anesthesiologist hurriedly ended the session as my partner said: “I’m kidding! Sorry! She’s still 3!” It was an inauspicious start, but I was determined to make the best of it. Ketamine, long used as an anesthetic but better known as an illegal party drug and, of course, a horse tranquilizer, has in recent years been gaining traction as an antidepressant. People have written enthusiastic accounts of their experiences, and researchers and psychiatrists, in a cascade of studies, have pointed to its possible benefits, not least the speed with which it can alleviate symptoms. Today, hundreds of clinics around the world provide infusions to people who have found little, if any, improvement with other treatments. That’s where I come in. Over the years, apart from the good old psychotropic medications, I have tried several types of talk therapy, meditation, acupuncture, singing lessons, bungee jumping and transcranial magnetic stimulation. (I still have sweet memories of the woodpecker sounds tapped into my brain.) © 2021 The New York Times Company

Keyword: Depression; Drug Abuse
Link ID: 28130 - Posted: 12.29.2021

By Gretchen Reynolds People who work out regularly and are aerobically fit tend to guzzle a surprising amount of alcohol, according to a new study, well timed for the holidays, of the interplay between fitness, exercise and imbibing. The study, which involved more than 40,000 American adults, finds that active, physically fit men and women are more than twice as likely to be moderate or heavy drinkers as people who are out of shape. The results add to mounting evidence from previous studies — and many of our bar tabs — that exercise and alcohol frequently go hand in hand, with implications for the health effects of each. Many people, and some researchers, might be surprised to learn how much physically active people tend to drink. In general, people who take up one healthy habit, such as working out, tend to practice other salubrious habits, a phenomenon known as habit clustering. Fit, active people seldom smoke, for instance, and tend to eat healthful diets. So, it might seem logical that people who often exercise would drink alcohol sparingly. But multiple studies in recent years have found close ties between working out and tippling. In one of the earliest, from 2001, researchers used survey answers from American men and women to conclude that moderate drinkers, defined in that study as people who finished off about a drink a day, were twice as likely as those who didn’t drink at all to exercise regularly. Later studies found similar patterns among college athletes, who drank substantially more than other collegians, a population not famous for its temperance. © 2021 The New York Times Company

Keyword: Drug Abuse; Obesity
Link ID: 28121 - Posted: 12.22.2021