Chapter 4. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology

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Lilly Tozer By analysing more than one million people’s genomes, researchers have identified stretches of DNA that could be linked to cannabis addiction. They also found that some of the same regions in the genome are associated with other health conditions, such as lung cancer and schizophrenia. The findings are evidence that cannabis addiction “could have substantial public-health risks if the usage increases”, says Daniel Levey, a medical neuroscientist at Yale University in New Haven, Connecticut, and a co-author of the study, published today in Nature Genetics1. Taking cannabis recreationally is legal in at least 8 countries, and 48 countries have legalized medicinal use of the drug for conditions including chronic pain, cancer and epilepsy. But one-third of people who take cannabis end up becoming addicted, or using the drug in a way that is damaging to their health. Previous studies have suggested that there is a genetic component, and have shown links between problematic cannabis use and some cancers and psychiatric disorders. Weighing the dangers of cannabis Drug taking and addiction can be influenced both by people’s genes and by their environment, which makes them extremely difficult to study, says Levey. But the team was able to build on data from previous work2 by including genetic information from additional sources, predominantly the Million Veteran Program — a US-based biobank with a large genetic database that aims to improve health care for former military service members. The analysis encompassed multiple ethnic groups, a first for a genetic study looking at cannabis misuse. As well as identifying regions of the genome that might be involved, the researchers saw a bi-directional link between excessive cannabis use and schizophrenia, meaning that the two conditions can influence each other. This finding is intriguing, says Marta Di Forti, a psychiatrist-scientist at King’s College London. Cannabis use “is the most preventable risk factor” for schizophrenia, she says, adding that the type of genetic data examined in the study could be used in future to identify and support people at increased risk of developing psychiatric disorders through cannabis use. © 2023 Springer Nature Limited

Keyword: Drug Abuse; Genes & Behavior
Link ID: 29015 - Posted: 11.22.2023

By Jan Hoffman Dr. Nic Helmstetter crab-walked down a steep, rain-slicked trail into a grove of maple and cottonwood trees to his destination: a dozen tents in a clearing by the Kalamazoo River, surrounded by the detritus of lives perpetually on the move. Discarded red plastic cups. A wet sock flung over a bush. A carpet square. And scattered across the forest floor: orange vial caps and used syringes. Kalamazoo, a small city in Western Michigan, is a way station along the drug trafficking corridor between Chicago and Detroit. In its parks, under railroad overpasses and here in the woods, people ensnared by drugs scramble to survive. Dr. Helmstetter, who makes weekly primary care rounds with a program called Street Medicine Kalamazoo, carried medications to reverse overdoses, blunt cravings and ease withdrawal-induced nausea. But increasingly, the utility of these therapies, developed to address the decades-old opioid crisis, is diminishing. They work to counteract the most devastating effects of fentanyl and heroin, but most users now routinely test positive for other substances too, predominantly stimulants such as cocaine and methamphetamine, for which there are no approved medications. Rachel, 35, her hair dyed a silvery lavender, ran to greet Dr. Helmstetter. She takes the medicine buprenorphine, which acts to dull her body’s yearning for opioids, but she was not ready to let go of meth. “I prefer both, actually,” she said. “I like to be up and down at the same time.” The United States is in a new and perilous period in its battle against illicit drugs. The scourge is not only opioids, such as fentanyl, but a rapidly growing practice that the Centers for Disease Control and Prevention labels “polysubstance use.” Over the last three years, studies of people addicted to opioids (a population estimated to be in the millions) have consistently shown that between 70 and 80 percent also take other illicit substances, a shift that is stymieing treatment efforts and confounding state, local and federal policies. “It’s no longer an opioid epidemic,” said Dr. Cara Poland, an associate professor at the Michigan State University College of Human Medicine. “This is an addiction crisis.” © 2023 The New York Times Company

Keyword: Drug Abuse
Link ID: 29001 - Posted: 11.13.2023

By Hallie Levine Every 40 seconds, someone in the United States has a stroke, and about three-quarters occur in people ages 65 and older. “As people age, their arteries have a tendency to become less flexible,” and clogged arteries are more likely, says Doris Chan, an interventional cardiologist at NYU Langone Health. This hikes the risk of an ischemic stroke — the most common type — when a blood vessel to the brain becomes blocked by a blood clot. But about 80 percent of all strokes are preventable, according to the Centers for Disease Control and Prevention. And the lifestyle steps you take can be especially powerful in fending off stroke. Here’s what you can do to reduce your risk. 1. Watch these issues. Keeping certain conditions at bay or managing them properly can cut the likelihood of a stroke. Take high blood pressure, which some research suggests is responsible for almost half of strokes. A heart-healthy eating plan may help control it. Also, try to limit sodium to less than 1,500 milligrams a day, maintain a healthy weight and exercise regularly, says Sahil Khera, an interventional cardiologist at the Mount Sinai Hospital in New York. If your blood pressure is high even with the above measures, ask your doctor what levels you should strive for and whether meds are appropriate. Staying out of the hypertensive range can be challenging with age because of the higher potential for medication side effects. While blood pressure below 120/80 can reduce cardiovascular risk, that target should be adjusted if side effects such as dizziness occur, says Hardik Amin, an associate professor of neurology at the Yale School of Medicine in New Haven, Conn. Another important condition to watch for is atrial fibrillation (AFib), an irregular and often rapid heartbeat, which affects at least 10 percent of people over age 80, according to a 2022 study in the Journal of the American College of Cardiology. People with AFib are about five times as likely to have a stroke.

Keyword: Stroke; Drug Abuse
Link ID: 28974 - Posted: 10.28.2023

By Laura Dattaro A brain is nothing if not communicative. Neurons are the chatterboxes of this conversational organ, and they speak with one another by exchanging pulses of electricity using chemical messengers called neurotransmitters. By repeating this process billions of times per second, a brain converts clusters of chemicals into coordinated actions, memories and thoughts. Researchers study how the brain works by eavesdropping on that chemical conversation. But neurons talk so loudly and often that if there are other, quieter voices, it might be hard to hear them. For most of the 20th century, neuroscientists largely agreed that neurons are the only brain cells that propagate electrical signals. All the other brain cells, called glia, were thought to serve purely supportive roles. Then, in 1990, a curious phenomenon emerged: Researchers observed an astrocyte, a subtype of glial cell, responding to glutamate, the main neurotransmitter that generates electrical activity. In the decades since, research teams have come up with conflicting evidence, some reporting that astrocytes signal, and others retorting that they definitely do not. The disagreement played out at conferences and in review after review of the evidence. The two sides seemed irreconcilable. A new paper published in Nature in September presents the best proof yet that astrocytes can signal, gathered over eight years by a team co-led by Andrea Volterra, visiting faculty at the Wyss Center for Bio and Neuro Engineering in Geneva, Switzerland. The study includes two key pieces of evidence: images of glutamate flowing from astrocytes, and genetic data suggesting that these cells, dubbed glutamatergic astrocytes, have the cellular machinery to use glutamate the way neurons do. The paper also helps explain the decades of contradictory findings. Because only some astrocytes can perform this signaling, both sides of the controversy are, in a sense, right: A researcher’s results depend on which astrocytes they sampled. All Rights Reserved © 2023

Keyword: Glia
Link ID: 28972 - Posted: 10.25.2023

By Mike Baker In a carpeted office suite, Alex Beck settled onto a mattress and, under the watch of a trained guide, began chomping through a handful of “Pumpkin Hillbilly” mushrooms. A Marine Corps veteran who was sexually assaulted during his time in the armed forces, Mr. Beck had long been searching unsuccessfully for a way to put those nightmarish years behind him. Now he was ready for a different kind of journey, a psychedelic trip through the nether regions of his own mind. As he felt his thoughts starting to spin, his “facilitator,” Josh Goldstein, urged him to surrender and let the mushrooms guide him. “It’s like the idea of planting a seed and then letting it go,” he said. Stigmatized in law and medicine for the past half-century, psychedelics are in the midst of a sudden revival, with a growing body of research suggesting that the mind-altering compounds could upend psychiatric care. Governments in several places have cautiously started to open access, and as Oregon voters approved a broad drug decriminalization plan in 2020, they also backed an initiative to allow the use of mushrooms as therapy. This summer, the state debuted a first-of-its-kind legal market for psilocybin mushrooms, more widely known as magic mushrooms. Far from the days of illicit consumption in basements and vans, the program allows people to embark on a therapeutic trip, purchasing mushrooms produced by a state-approved grower and consuming them in a licensed facility under the guidance of a certified facilitator. Mr. Beck, 30, was one of the first clients at a facility in the central Oregon city of Bend that began conducting sessions this summer in a building that on other days of the week offers chiropractic services. In his youth, Mr. Beck had experimented with psychedelics for recreation. But as he struggled with his lingering post-traumatic stress in adulthood, he learned about what seemed to be promising new research into plant-based psychedelics for mental health issues that did not respond to other treatments. He wondered if they could help him clear his head from the horrors of the past. © 2023 The New York Times Company

Keyword: Stress; Depression
Link ID: 28969 - Posted: 10.25.2023

By Alice Callahan Q: I routinely drink three or four cups of coffee per day, but often wonder if this is too much. Should I consider cutting back? Coffee can be many things: a morning ritual, a cultural tradition, a productivity hack and even a health drink. Studies suggest, for instance, that coffee drinkers live longer and have lower risks of Type 2 diabetes, Parkinson’s disease, cardiovascular conditions and some cancers. “Overall, coffee does more good than bad,” said Rob van Dam, a professor of exercise and nutrition sciences at the Milken Institute School of Public Health at George Washington University. But between your breakfast brew, lunchtime latte and afternoon espresso, is it possible to have too much? And if so, how can you tell? Coffee contains thousands of chemical compounds, many of which may influence health, said Marilyn Cornelis, an associate professor of preventive medicine at Northwestern University Feinberg School of Medicine. But coffee is also the largest source of caffeine for people in the United States, and that’s where most of the risks associated with coffee consumption come from, she said. Having too much caffeine can cause a racing heart, jitteriness, anxiousness, nausea or trouble sleeping, said Jennifer Temple, a professor of exercise and nutrition sciences at the University at Buffalo. But “most people are kind of well tuned with their response to caffeine,” Dr. Cornelis said, and when they begin to experience even mild symptoms of having too much, they cut back. © 2023 The New York Times Company

Keyword: Drug Abuse
Link ID: 28937 - Posted: 09.29.2023

By Taylor Majewski Rachel Nuwer’s “I Feel Love: MDMA and the Quest for Connection in a Fractured World,” is clearly aimed at a broad audience. It will resonate with readers who have experienced MDMA recreationally, probably at a rave, or therapeutically, probably to heal the emotional aftereffects of deep-seated trauma. Or both. But it’s also intended for readers who have never touched the drug, colloquially known as ecstasy or molly. Perhaps it’s especially for them. “I Feel Love” belongs to a growing family of nonfiction accounts of the fraught history of psychedelics and why, through compelling anecdotes and the latest science, we should reconsider them. Nuwer, a science journalist, chronicles the hopeful story of something both small and large — MDMA, the compound, and MDMA, the drug that’s repeatedly brought humans together across decades, continents, politics, and moral panics. The book is a natural successor to Michael Pollan’s 2018 bestseller “How to Change Your Mind,” which covered the mystical and medical benefits of LSD and psilocybin, and paved the way for a psychedelic renaissance of sorts, Nuwer writes in the introduction, “no such modern telling exists for MDMA.” Now, it does. “I Feel Love” is, above all, a time capsule. Nuwer begins with a crucial asterisk: “MDMA, also known as Ecstasy or Molly, is currently an illegal drug.” Today, most journalism around psychedelics is stipulated with this simple fact. Despite their potential to heal, drugs like psilocybin, LSD, and MDMA are still classified as Schedule I, the Drug Enforcement Administration’s highest category for controlled substances with no medical use, with a high potential for abuse. For MDMA specifically, that might be about to change.

Keyword: Drug Abuse
Link ID: 28922 - Posted: 09.23.2023

Kimberlee D'Ardenne Dopamine seems to be having a moment in the zeitgeist. You may have read about it in the news, seen viral social media posts about “dopamine hacking” or listened to podcasts about how to harness what this molecule is doing in your brain to improve your mood and productivity. But recent neuroscience research suggests that popular strategies to control dopamine are based on an overly narrow view of how it functions. Dopamine is one of the brain’s neurotransmitters – tiny molecules that act as messengers between neurons. It is known for its role in tracking your reaction to rewards such as food, sex, money or answering a question correctly. There are many kinds of dopamine neurons located in the uppermost region of the brainstem that manufacture and release dopamine throughout the brain. Whether neuron type affects the function of the dopamine it produces has been an open question. Recently published research reports a relationship between neuron type and dopamine function, and one type of dopamine neuron has an unexpected function that will likely reshape how scientists, clinicians and the public understand this neurotransmitter. Dopamine is involved with more than just pleasure. Dopamine neuron firing Dopamine is famous for the role it plays in reward processing, an idea that dates back at least 50 years. Dopamine neurons monitor the difference between the rewards you thought you would get from a behavior and what you actually got. Neuroscientists call this difference a reward prediction error. Understand new developments in science, health and technology, each week Eating dinner at a restaurant that just opened and looks likely to be nothing special shows reward prediction errors in action. If your meal is very good, that results in a positive reward prediction error, and you are likely to return and order the same meal in the future. Each time you return, the reward prediction error shrinks until it eventually reaches zero when you fully expect a delicious dinner. But if your first meal was terrible, that results in a negative reward prediction error, and you probably won’t go back to the restaurant. Dopamine neurons communicate reward prediction errors to the brain through their firing rates and patterns of dopamine release, which the brain uses for learning. They fire in two ways. © 2010–2023, The Conversation US, Inc.

Keyword: Drug Abuse; Learning & Memory
Link ID: 28917 - Posted: 09.21.2023

By Jim Crotty The opioid crisis continues to rage across the U.S., but there are some positive, if modest, signs that it may be slowing. Overdose deaths due to opioids are flattening in many places and dropping in others, awareness of the dangers of opioid abuse continues to increase, and more than $50 billion in opioid settlement funds are finally making their way to state and local governments after years of delay. There is still much work to be done, but all public health emergencies eventually subside. Then what? First, it’s important to realize that synthetic opioids like fentanyl will never fully disappear from the drug supply. They are too potent, too addictive, and perhaps most importantly, too lucrative. Opioids, like Covid-19, are here to stay, consistently circulating in the community but at more manageable levels. More alarming is what may take its place. Since 2010, overdoses involving both stimulants and fentanyl have increased 50-fold. Experts suggest this dramatic rise in polysubstance use represents a “fourth wave” in the opioid crisis, but what if it is really the start of a new wave of an emerging stimulant crisis? Substance abuse tends to move in cycles. Periods with high rates of depressant drug use (like opioids) are almost always followed by ones with high rates of stimulant drug use (like methamphetamine and cocaine), and vice versa. The heroin crisis of the 1960s and 1970s was followed by the crack epidemic of the 1980s and 1990s, which gave way to the current opioid epidemic. As the think tank scholar Charles Fain Lehman quipped, “As with fashion, so with drugs — whatever the last generation did, the next generation tends to abhor.” The difference now is the primacy of synthetic drugs — that is, illicit substances created in a lab that are designed to mimic the effects of naturally occurring drugs.

Keyword: Drug Abuse
Link ID: 28916 - Posted: 09.21.2023

Neurotransmitters are the words our brain cells use to communicate with one another. For years, researchers relied on tools that provided limited temporal and spatial resolution to track changes in the fast chemical chat between neurons. But that started to change about ten years ago for glutamate—the most abundant excitatory neurotransmitter in vertebrates that plays an essential role in learning, memory, and information processing—when scientists engineered the first glutamate fluorescent reporter, iGluSnFR, which provided a readout of neurons’ fast glutamate release. In 2013, researchers at the Howard Hughes Medical Institute collaborated with scientists from other institutions to develop the first generation of iGluSnFR.1 To create the biosensor, the team combined a bacteria-derived glutamate binding protein, Gltl, a wedged fluorescent GFP protein, and a membrane-targeting protein that anchors the reporter to the surface of the cell. Upon glutamate binding, the Gltl protein changes its conformation, increasing the fluorescence intensity of GFP. In their first study, the team showcased the utility of the biosensor for monitoring glutamate levels by demonstrating selective activation by glutamate in cell cultures. By conducting experiments with brain cells from the C. elegans worm, zebrafish, and mice, they confirmed that the reporter also tracked glutamate in vivo, a finding that set iGluSnFR apart from existing glutamate sensors. The first iGluSnFR generation allowed researchers to study glutamate dynamics in different biological systems, but the indicator could not detect small amounts of the neurotransmitter or keep up with brain cells’ fast glutamate release bouts. Making improvements © 1986–2023 The Scientist.

Keyword: Brain imaging
Link ID: 28901 - Posted: 09.10.2023

By Matt Richtel More than one-fifth of people who use cannabis struggle with dependency or problematic use, according to a study published on Tuesday in The Journal of the American Medical Association Network Open. The research found that 21 percent of people in the study had some degree of cannabis use disorder, which clinicians characterize broadly as problematic use of cannabis that leads to a variety of symptoms, such as recurrent social and occupational problems, indicating impairment and distress. In the study, 6.5 percent of users suffered moderate to severe disorder. Cannabis users who experience more severe dependency tended to be recreational users, whereas less severe but still problematic use was associated roughly equally with medical and recreational use. The most common symptoms among both groups were increased tolerance, craving, and uncontrolled escalation of cannabis use. ImageA person holding a lit joint while bags of cannabis sit on a black table in the Cannabis use is rising nationwide as more states have legalized it. The new findings align with prior research, which has found that around 20 percent of cannabis users develop cannabis use disorder. The condition can be treated with detoxification and abstinence, therapies and other treatments that work with addictive behaviors. The new study drew its data from nearly 1,500 primary care patients in Washington State, where recreational use is legal, in an effort to explore the prevalence of cannabis use disorder among both medical and nonmedical users. The research found that 42 percent of cannabis users identified themselves solely as medical users; 25 percent identified as nonmedical users, and 32 percent identified as both recreational and medical users. © 2023 The New York Times Company

Keyword: Drug Abuse
Link ID: 28888 - Posted: 08.30.2023

David Cox In June 2021, 32-year-old actor Kate Hyatt travelled to a farmhouse near Great Malvern in Worcerstershire for a plant medicine retreat that she hoped would improve her mental health after a difficult time during the pandemic lockdowns. While there, she is believed to have taken a substance called wachuma, or San Pedro cactus, a powerful hallucinogen used by Indigenous people in the Andes for thousands of years. But Hyatt did not experience relief; instead, her mental health worsened. Three months later, she described being in “some sort of psychotic break” and feeling as if her brain was going to explode. Later that autumn she took her own life. At the subsequent inquest, the coroner’s report linked her worsening symptoms to the hallucinogens she had consumed. Such tragedies represent the darker side of the psychedelics renaissance. These cases are often forgotten amid the feverish anticipation surrounding the therapeutic potential of these drugs, combined with exhaustive media coverage, the rapid rise of a billion-dollar industry – ranging from venture capital-backed startups to wellness retreats – and the hype around last year’s Netflix series How to Change Your Mind (based on Michael Pollan’s bestselling book). Yet without careful monitoring and scrutiny of who receives them, this class of drugs – which includes LSD, MDMA (commonly known as ecstasy or molly) and psilocybin (the active ingredient of magic mushrooms) – can be dangerous. There is evidence that they can destabilise vulnerable individuals who have experienced a previous psychotic episode or have a family history of psychosis. The substances are illegal to distribute and possess in the UK, although they are often obtained on the hidden market. Scientific researchers and biotechnology companies are able to use them in clinical trials only after obtaining a Home Office licence and applying extensive security arrangements. © 2023 Guardian News & Media Limited

Keyword: Depression; Drug Abuse
Link ID: 28873 - Posted: 08.19.2023

By David Ovalle The evolving overdose crisis in the United States is making another lethal turn, federal disease trackers reported Wednesday: Increasingly, people dying from opioids are also using stimulants such as cocaine and methamphetamine. An analysis by the Centers for Disease Control and Prevention shows that between 2011 and 2021, the age-adjusted rate of overdose deaths involving opioids and cocaine nearly quintupled, far outpacing the rate of deaths involving only cocaine. In 2021 alone, nearly 80 percent of the 24,486 cocaine overdose deaths recorded in the United States also involved an opioid. Experts say it represents the latest wave of the nation’s drug epidemic. For many users injecting or smoking fentanyl for some time, “adding a stimulant makes the drug feel like it did in the beginning,” said Daniel Ciccarone, a professor of addiction medicine at the University of California at San Francisco who has been studying the simultaneous use of stimulants and opioids. The federal analysis adds clarity to the staggering number of drug poisonings, largely driven by fentanyl, which can be up to 50 times more powerful than heroin. The CDC estimates that in 2022, more than 110,000 people succumbed to overdoses, edging past the previous year but representing a plateau from earlier spikes. Preliminary CDC data also suggest a slight increase in deaths in 2022 involving opioids taken with cocaine and psychostimulants such as meth. “These aren’t mutually exclusive categories. Someone can die of more than one drug,” said CDC researcher Merianne Rose Spencer, who led the analysis. The international cocaine market has thrived despite shutdowns associated with the coronavirus pandemic, according to the U.N.’s Global Report on Cocaine 2023, with record production in Latin America, new trafficking hubs in Africa and increased seizures.

Keyword: Drug Abuse
Link ID: 28848 - Posted: 07.19.2023

By Tammy Worth In two decades as a pediatrician, Jason Reynolds has had no success treating patients with opioid use disorder by sending them to rehab. But five years ago, when his Massachusetts practice, Wareham Pediatric Associates PC, became the first in the state to offer medication therapy to adolescent patients, he saw dramatic results. The first patient he treated with medication, a young man named Nate, had overdosed on opioids twice in the 24-hour period before seeing Reynolds. But that patient has had no opioid relapses since starting drug therapy. Reynolds’ success received a lot of media attention, and one interviewer, he recalls, asked Nate if any of his friends would also consider starting the treatment. Reynolds is among a small minority of pediatricians using medication to treat opioid use disorder in adolescents. Fewer than 2 percent of all physicians prescribing the medications are pediatricians, and many youth rehabilitation facilities don’t offer them at all. Medication for opioid use disorder (MOUD) uses buprenorphine or methadone to reduce cravings and withdrawal symptoms, or naltrexone to block the high that users would otherwise get if they decided to use opioids. Though MOUD is often used to treat adults, several barriers have prevented it from being adopted more widely for youth. Reynolds and a handful of other practitioners across the country are now working to provide education and training to other health care providers, hoping to increase use of this life-saving treatment. Opioid use among US youth is on the rise nationally, with diagnoses increasing from 0.26 per 100,000 person-years in 2001 to 1.51 in 2014. Overdose deaths have also spiked, more than doubling among youth ages 14 to 18, from 492 in 2019 to 1,146 in 2021. © 2023 Annual Reviews

Keyword: Drug Abuse; Development of the Brain
Link ID: 28844 - Posted: 07.06.2023

Alaina Demopoulos It was in 1975, when Carl Resnikoff and his girlfriend, Judith Gipson, took a bucolic ferry ride to Sausalito, a city located on the north end of Golden Gate Bridge, that a revolution in youth culture, music, emotion and imagination would take place. It was on that ride that the two undergraduates took capsules filled with MDMA powder for the very first time. Resnikoff, a biophysics major at Berkeley, had synthesized the drug himself. As the boat cut through the water of the San Francisco Bay, Gipson began to feel “a floating sense of euphoria … like some guy could come walking up to us asking for help and his guts are spilling out, and we’d be grooving on how beautiful it was.’” According to Rachel Nuwer’s book I Feel Love: MDMA and the Quest for Connection in a Fractured World, Resnikoff and his girlfriend’s romp was the first-ever documented instance of people taking MDMA recreationally. Nuwer is a science journalist who covered clinical trials for MDMA use in treating post-traumatic stress disorder (PTSD). While cannabis and psilocybin have undergone rebrands of late, going from countercultural tokens to the mainstream, she believes that the public is starting to open up to MDMA, too. “MDMA deserves its own story,” Nuwer said. “I wanted to bring together the history, culture, politics and science of the drug all in one place. This book is for anyone who’s interested in the drug, whether it’s someone who’s taken it 500 times on the dancefloor or who’s using it therapeutically for the first time.” Nuwer believes that MDMA will “follow the path of cannabis”, becoming legal medicinally first, then decriminalized, and perhaps fully legalized for all types of use. That cycle may have already started: three clinical trials have found that MDMA, which is also called ecstasy, can speed the recovery of PTSD. FDA approval for therapeutic use could come as early as next year. © 2023 Guardian News & Media Limited

Keyword: Drug Abuse
Link ID: 28834 - Posted: 06.28.2023

By Yasemin Saplakoglu Enough pints of beer can have you falling off your bar stool or loudly reciting lyrics to early 2000s jams to total strangers, because alcohol can get past one of the strongest defenses in the body. If you’ve ever been drunk, high or drowsy from allergy medication, you’ve experienced what happens when some molecules defeat the defense system called the blood-brain barrier and make it into the brain. Embedded in the walls of the hundreds of miles of capillaries that wind through the brain, the barrier keeps most molecules in the blood from ever reaching sensitive neurons. Much as the skull protects the brain from external physical threats, the blood-brain barrier protects it from chemical and pathogenic ones. While it’s a fantastic feat of evolution, the barrier is very much a nuisance for drug developers, who have spent decades trying to selectively overcome it to deliver therapeutics to the brain. Biomedical researchers want to understand the barrier better because its failures seem to be the key to some diseases and because manipulating the barrier could help improve the treatment of certain conditions. It’s really there to control the environment for proper brain function. “We’ve learned a lot over the last decade,” said Elizabeth Rhea, a research biologist at the University of Washington Medicine Memory and Brain Wellness Center. But “we’re definitely still facing challenges in getting substrates and therapeutics across.” Protection, but Not a Fortress Like the rest of the body, the brain needs circulating blood to deliver essential nutrients and oxygen and to carry away waste. But blood chemistry constantly fluctuates, and brain tissue is extremely sensitive to its chemical environment. Neurons rely on precise releases of ions to communicate — if ions could flow freely out of the blood, that precision would be lost. Other types of biologically active molecules can also twang the delicate neurons, interfering with thoughts, memories and behaviors. All Rights Reserved © 2023

Keyword: Drug Abuse
Link ID: 28831 - Posted: 06.21.2023

Sara Reardon Psychedelic drugs are promising treatments for many mental-health conditions, but researchers don’t fully understand why they have such powerful therapeutic effects. Now, a study in mice suggests that psychedelics all work in the same way: they reset the brain to a youthful state in which it can easily absorb new information and form crucial connections between neurons1. The findings raise the prospect that psychedelic drugs could allow long-term changes in many types of behavioural, learning and sensory system that are disrupted in mental-health conditions. But scientists caution that more research needs to be done to establish how the drugs remodel brain connections. The study was published on 14 June in Nature. Psychedelics such as MDMA (also known as ecstasy), ketamine and psilocybin — the active ingredient in magic mushrooms — are known for producing mind-altering effects, including hallucinations in some cases. But each compound affects a different biochemical pathway in the brain during the short-term ‘trip’, leaving scientists to wonder why so many of these drugs share the ability to relieve depression2, addiction and other difficult-to-treat conditions in the long term. Gül Dölen, a neuroscientist at Johns Hopkins University in Baltimore, Maryland, and her colleagues sought answers by studying how psychedelics affect social behaviour in mice. Mice can learn to associate socializing with positive feelings, but only during an adolescent ‘critical period’, which closes as they become adults. The scientists trained mice to associate one ‘bedroom’ in their enclosure with mousy friends and another room with solitude. They could then examine how psychedelics affected the rodents’ room choices — a proxy for whether the drug affects the critical period. © 2023 Springer Nature Limited

Keyword: Depression; Drug Abuse
Link ID: 28825 - Posted: 06.17.2023

By Daniel Bergner If severe mental illness, untreated, underlies the feeling of encroaching anarchy and menace around the homeless encampments of San Francisco or in the subways of New York City, then the remedy appears obvious. Let’s rescue those who, as New York’s mayor, Eric Adams, says, “slip through the cracks” of our mental health care systems; let’s give people “the treatment and care they need.” It sounds so straightforward. It sounds like a clear way to lower the odds of tragic incidents occurring, like the chokehold killing of Jordan Neely, a homeless, psychiatrically troubled man, or the death of Michelle Alyssa Go, who was pushed off a Times Square subway platform to her death by a homeless man with schizophrenia. Improving order and safety in public spaces and offering compassionate care seem to be convergent missions. But unless we confront some rarely spoken truths, that convergence will prove illusory. The problems with the common-sense approach, as it’s currently envisioned, run beyond the proposed solutions we usually read about: funding more beds on hospital psychiatric wards, establishing community-based programs to oversee treatment when people are released from the hospital and providing housing for those whose mental health is made increasingly fragile by the constant struggle for shelter. The most difficult problems aren’t budgetary or logistical. They are fundamental. They involve the involuntary nature of the care being called for and the flawed antipsychotic medications that are the mainstay of treatment for people dealing with the symptoms of psychosis, like hallucinatory voices or paranoid delusions, which can come with a range of severe psychiatric conditions. © 2023 The New York Times Company

Keyword: Schizophrenia
Link ID: 28810 - Posted: 06.03.2023

John Michael Streicher Opioid drugs such as morphine and fentanyl are like the two-faced Roman god Janus: The kindly face delivers pain relief to millions of sufferers, while the grim face drives an opioid abuse and overdose crisis that claimed nearly 70,000 lives in the U.S. in 2020 alone. Scientists like me who study pain and opioids have been seeking a way to separate these two seemingly inseparable faces of opioids. Researchers are trying to design drugs that deliver effective pain relief without the risk of side effects, including addiction and overdose. One possible path to achieving that goal lies in understanding the molecular pathways opioids use to carry out their effects in your body. How do opioids work? The opioid system in your body is a set of neurotransmitters your brain naturally produces that enable communication between neurons and activate protein receptors. These neurotransmitters include small proteinlike molecules like enkephalins and endorphins. These molecules regulate a tremendous number of functions in your body, including pain, pleasure, memory, the movements of your digestive system and more. Analysis of the world, from experts Opioid neurotransmitters activate receptors that are located in a lot of places in your body, including pain centers in your spinal cord and brain, reward and pleasure centers in your brain, and throughout the neurons in your gut. Normally, opioid neurotransmitters are released in only small quantities in these exact locations, so your body can use this system in a balanced way to regulate itself. The opioids your body produces and opioid drugs bind to the same receptors. The problem comes when you take an opioid drug like morphine or fentanyl, especially at high doses for a long time. These drugs travel through the bloodstream and can activate every opioid receptor in your body. You’ll get pain relief through the pain centers in your spinal cord and brain. But you’ll also get a euphoric high when those drugs hit your brain’s reward and pleasure centers, and that could lead to addiction with repeated use. When the drug hits your gut, you may develop constipation, along with other common opioid side effects. Targeting opioid signal transduction How can scientists design opioid drugs that won’t cause side effects? One approach my research team and I take is to understand how cells respond when they receive the message from an opioid neurotransmitter. Neuroscientists call this process opioid receptor signal transduction. Just as neurotransmitters are a communication network within your brain, each neuron also has a communication network that connects receptors to proteins within the neuron. When these connections are made, they trigger specific effects like pain relief. So, after a natural opioid neurotransmitter or a synthetic opioid drug activates an opioid receptor, it activates proteins within the cell that carry out the effects of the neurotransmitter or the drug. © 2010–2023, The Conversation US, Inc.

Keyword: Drug Abuse; Pain & Touch
Link ID: 28809 - Posted: 06.03.2023

By Christina Caron A new study suggests that, for some patients, the anesthetic ketamine is a promising alternative to electroconvulsive therapy, or ECT, currently one of the quickest and most effective therapies for patients with difficult-to-treat depression. The study is the largest head-to-head comparison of the two treatments. Patients who don’t respond to at least two antidepressants — about one-third of clinically depressed patients — have a condition that clinicians refer to as “treatment-resistant.” Their options for relief are limited. Doctors typically recommend up to 12 sessions of ECT, which has a long-established efficacy, but is tainted by the stigma of historical misuse and frightening Hollywood images of people strapped to tables, writhing in agony. Today’s ECT is much safer and done under general anesthesia, but the procedure remains underutilized. The study, published on Wednesday in The New England Journal of Medicine, found that ketamine, when administered intravenously, was at least as effective as ECT in patients with treatment-resistant depression who do not have psychosis. (For people with psychosis, ketamine, even in very low doses, can worsen psychosis-like symptoms.) “The results were very surprising to us,” said Dr. Amit Anand, lead author of the study and a professor of psychiatry at Harvard Medical School who studies mood disorders at Mass General Brigham. His team had initially hypothesized that ketamine would be nearly as effective as ECT. Instead, Dr. Anand said, they found that ketamine performed even better than that. This is significant in part because some patients are uncomfortable with ECT’s potential side effects, such as temporary memory loss, muscle pain or weakness. (In rare cases it can result in permanent gaps in memory.) © 2023 The New York Times Company

Keyword: Depression; Drug Abuse
Link ID: 28806 - Posted: 05.31.2023