Chapter 4. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology

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By Ewen Callaway Researchers have used the protein-structure-prediction tool AlphaFold to identify1 hundreds of thousands of potential new psychedelic molecules — which could help to develop new kinds of antidepressant. The research shows, for the first time, that AlphaFold predictions — available at the touch of a button — can be just as useful for drug discovery as experimentally derived protein structures, which can take months, or even years, to determine. The development is a boost for AlphaFold, the artificial-intelligence (AI) tool developed by DeepMind in London that has been a game changer in biology. The public AlphaFold database holds structure predictions for nearly every known protein. Protein structures of molecules implicated in disease are used in the pharmaceutical industry to identify and improve promising medicines. But some scientists had been starting to doubt whether AlphaFold’s predictions could stand in for gold standard experimental models in the hunt for new drugs. “AlphaFold is an absolute revolution. If we have a good structure, we should be able to use it for drug design,” says Jens Carlsson, a computational chemist at the University of Uppsala in Sweden. Efforts to apply AlphaFold to finding new drugs have been met with considerable scepticism, says Brian Shoichet, a pharmaceutical chemist at the University of California, San Francisco. “There is a lot of hype. Whenever anybody says ‘such and such is going to revolutionize drug discovery’, it warrants some scepticism.” Shoichet counts more than ten studies that have found AlphaFold’s predictions to be less useful than protein structures obtained with experimental methods, such as X-ray crystallography, when used to identify potential drugs in a modelling method called protein–ligand docking. © 2024 Springer Nature Limited

Keyword: Drug Abuse
Link ID: 29110 - Posted: 01.23.2024

Karla Kaun Many people are wired to seek and respond to rewards. Your brain interprets food as rewarding when you are hungry and water as rewarding when you are thirsty. But addictive substances like alcohol and drugs of abuse can overwhelm the natural reward pathways in your brain, resulting in intolerable cravings and reduced impulse control. A popular misconception is that addiction is a result of low willpower. But an explosion of knowledge and technology in the field of molecular genetics has changed our basic understanding of addiction drastically over the past decade. The general consensus among scientists and health care professionals is that there is a strong neurobiological and genetic basis for addiction. As a behavioral neurogeneticist leading a team investigating the molecular mechanisms of addiction, I combine neuroscience with genetics to understand how alcohol and drugs influence the brain. In the past decade, I have seen changes in our understanding of the molecular mechanisms of addiction, largely due to a better understanding of how genes are dynamically regulated in the brain. New ways of thinking about how addictions form have the potential to change how we approach treatment. Each of your brain cells has your genetic code stored in long strands of DNA. For all that DNA to fit into a cell, it needs to be packed tightly. This is achieved by winding the DNA around “spools” of protein called histones. Areas where DNA is unwound contain active genes coding for proteins that serve important functions within the cell. When gene activity changes, the proteins your cells produce also change. Such changes can range from a single neuronal connection in your brain to how you behave. This genetic choreography suggests that while your genes affect how your brain develops, which genes are turned on or off when you are learning new things is dynamic and adapts to suit your daily needs. © 2010–2024, The Conversation US, Inc.

Keyword: Drug Abuse; Epigenetics
Link ID: 29108 - Posted: 01.23.2024

By Lauren Peace Tampa Bay Times Nina Shand couldn’t stay awake. She had taken afternoon naps since she was a teenager to accommodate her “work hard, play hard” attitude, but when she was in her mid-20s the sleepiness became more severe. Menial computer tasks put her to sleep, and a 20-minute drive across her city, St. Petersburg, Florida, brought on a drowsiness so intense that her eyelids would flutter, forcing her to pull over. She knew something was really wrong when she no longer felt safe behind the wheel. In 2021, she received a diagnosis: narcolepsy, a rare disorder that causes excessive daytime sleepiness. Her doctor prescribed her Adderall, the brand-name version of the amphetamine-powered medication commonly known for treating attention-deficit/hyperactivity disorder. It worked. For the first time in years, Shand, now 28, felt energized. She was no longer struggling at work, sneaking naps, or downing coffees to trick her body into staying awake. She felt hope. But by 2022, a national Adderall shortage meant pharmacies were no longer able to fill her prescription. Shand and countless others across the country were being turned away, left to piece together a new — and often less effective — treatment plan with doctors scrambling to meet their needs. More than a year later, the shortage continues. In October, Democrats in the U.S. House of Representatives implored the FDA and Drug Enforcement Administration to work with drug manufacturers to ensure better supply. “We cannot allow this to be the continuing reality for Americans,” read their letter, led by Rep. Abigail Spanberger (D-Va.). But for now, it is.

Keyword: Sleep; Drug Abuse
Link ID: 29102 - Posted: 01.16.2024

By Meryl Davids Landau When Brian Meyer received a Stage 4 prostate cancer diagnosis three years ago at age 62, he was determined to make the most of his remaining years. He immediately retired from a decades-long career in the grocery business and took every opportunity to hike, camp and — his all-time favorite — fish for salmon. Brian and his wife, Cheryl, regularly visited their two grown children and three grandsons and spent time with their many friends. But it was sometimes hard to keep his mind off his pain and the reality that life was nearing an end. “It tugs at the heart all the time,” Meyer, from Vancouver Island, British Columbia, said in August. A calm person by nature, he found his anxiety skyrocketing. By November, though, despite a new, highly aggressive liver cancer that shrank his prognosis to months or weeks, Meyer felt calm much of the time. The prime reason: a 25-milligram dose of the psychedelic drug psilocybin he had taken several months earlier, due to a Canadian program being watched elsewhere for the emotional benefits it may offer people nearing death. In mid-August, Meyer and nine other people with terminal cancers had gathered in two rooms, and there, lying on plush floor mats with blankets covering their bodies, their eyes covered by sleeping masks and music piped in over headphones, they swallowed the psilocybin capsules. The consciousness-altering drug, administered by the nonprofit Vancouver Island wellness center Roots to Thrive, set Meyer and the others on a six-hour journey of fantastical images and thoughts. The hope was that this “trip” would lead to lasting improvements in mood and lessen their angst around death. It was accompanied by weeks of Zoom group therapy sessions before and after, along with an in-person gathering the evening before for a medical clearance and the opportunity for participants and their spouses to meet in person.

Keyword: Drug Abuse; Stress
Link ID: 29100 - Posted: 01.16.2024

By Christina Jewett and Noah Weiland Marijuana is neither as risky nor as prone to abuse as other tightly controlled substances and has potential medical benefits, and therefore should be removed from the nation’s most restrictive category of drugs, federal scientists have concluded. The recommendations are contained in a 250-page scientific review provided to Matthew Zorn, a Texas lawyer who sued Health and Human Services officials for its release and published it online on Friday night. An H.H.S. official confirmed the authenticity of the document. The records shed light for the first time on the thinking of federal health officials who are pondering a momentous change. The agencies involved have not publicly commented on their debates over what amounts to a reconsideration of marijuana at the federal level. Since 1970, marijuana has been considered a so-called Schedule I drug, a category that also includes heroin. Schedule I drugs have no medical use and a high potential for abuse, and they carry severe criminal penalties under federal trafficking laws. The documents show that scientists at the Food and Drug Administration and the National Institute on Drug Abuse have recommended that the Drug Enforcement Administration make marijuana a Schedule III drug, alongside the likes of ketamine and testosterone, which are available by prescription. The review by federal scientists found that even though marijuana is the most frequently abused illicit drug, “it does not produce serious outcomes compared to drugs in Schedules I or II.” Marijuana abuse does lead to physical dependence, the analysis noted, and some people develop a psychological dependence. “But the likelihood of serious outcomes is low,” the review concluded. The review also said there is some “scientific support” for therapeutic uses of marijuana, including treatment of anorexia, pain, and nausea and vomiting related to chemotherapy. © 2024 The New York Times Company

Keyword: Drug Abuse
Link ID: 29097 - Posted: 01.13.2024

By Aimee Cunningham Ask thousands of teens whether frequent use of certain substances brings a high risk of harm, and they mostly nail it: a majority say yes for cigarettes, alcohol, cocaine and heroin. But there’s one substance that many skip over — cannabis. Only 35 percent of 12- to 17-year-olds perceive a “great risk of harm” from smoking marijuana once or twice a week, according to the National Survey on Drug Use and Health. It’s a sentiment that some of their parents may share. Parents often don’t understand that the products used today “are not what they knew when they were in high school,” says Kelly Young-Wolff, a licensed clinical psychologist and research scientist at Kaiser Permanente Northern California Division of Research in Oakland. If their children are using cannabis, parents may think, “‘it’s not that bad, at least they’re not using this other drug that’s worse.’” But the cannabis products available now are leaps and bounds more potent — which may increase the risks for addiction and psychosis — than in the past. Marijuana plants have been bred to contain more delta-9-tetrahydrocannabinol, or THC, the main psychoactive chemical. In 1995, the total percent of THC by weight of marijuana plant material was around 4 percent; now marijuana with a THC potency of 20 percent or more is available. Trouncing that are concentrated cannabis products, including wax, budder and shatter, which can have a THC potency as high as 95 percent. Cannabis is legal for adults to use recreationally in 24 states and Washington, D.C., and is allowed for medical use in 38 states and D.C. The widespread availability of cannabis “promotes the idea that it’s safe,” says pediatrician Beth Ebel of the University of Washington School of Medicine and Seattle Children’s Hospital. But that “is an incorrect assumption.” THC can impact brain chemistry “in a way that wasn’t intended,” Ebel says. “Some of the worst effects can have lifelong health consequences, especially for a young person.” © Society for Science & the Public 2000–2024.

Keyword: Drug Abuse; Development of the Brain
Link ID: 29083 - Posted: 01.06.2024

By Catherine Pearson Dry January sounds like a simple proposition: No alcohol. For 31 days. And some enthusiasts jump in without much planning — perhaps even hungover after a rowdy New Year’s Eve. There is no data suggesting that those folks won’t be able to abstain from drinking, said Dr. David Wolinsky, an assistant professor of psychiatry and behavioral sciences with Johns Hopkins Medicine, who specializes in addiction. But starting the month with a few strategies in your back pocket — and with a clear sense of your goals — may help you get the most out of the challenge. “Most of the benefits of Dry January are probably going to be related to the intention with which you go into Dry January,” Dr. Wolinsky said. The challenge isn’t a stand-in for treatment for people with alcohol use disorder, he stressed, but those who are looking to get a fresh start to the year may benefit from the mental and physical reset it can offer, and the opportunity to adopt new habits. For instance, a 2016 study found that six months after Dry January ended, participants were drinking less than they were before. We spoke to Dr. Wolinsky and other experts about some strategies for a successful month. One of the simplest steps is to spread the word among friends and family that you intend to take the month off, said Casey McGuire Davidson, a sobriety coach and host of “The Hello Someday Podcast,” which focuses on “sober-curious” topics. Research has shown that accountability can play a critical role in helping habits stick, and you might find a friend or partner to join you, Ms. Davidson suggested. Even if you don’t, you may be surprised by how encouraging people are of your goal (though she said you should share it only with people you trust). “Dry January gives people a period of time when they can stop drinking with community and support,” she said, “without a lot of questions.” Ms. Davidson also recommended reading books that may help you evaluate your relationship with alcohol, or listening to sobriety podcasts. © 2023 The New York Times Company

Keyword: Drug Abuse
Link ID: 29071 - Posted: 12.31.2023

By Andrew Jacobs An autopsy report released by the Los Angeles County medical examiner on Friday said the death of “Friends” actor Matthew Perry, who was found face down and unresponsive in a hot tub at his home on Oct. 28, resulted from the “acute effects” of ketamine, an anesthetic with psychedelic properties. Ketamine has become increasingly popular as a therapy for treatment-resistant depression and other mental health issues. It is also used recreationally. Mr. Perry had publicly acknowledged his long struggle with alcohol and drug use, but the report said he had been sober for 19 months and little was known about his relationship to ketamine. What is ketamine, and is it legal? Ketamine is an injectable, short-acting dissociative anesthetic that can have hallucinogenic effects at certain doses. It distorts perceptions of sight and sound and makes users feel detached from pain and their surroundings. Developed as a battlefield anesthetic in the 1960s, ketamine has been legal since 1970 for use in both people and animals. It is frequently used as an anesthetic for children, especially in the developing world. But the psychiatric use of ketamine is still unapproved and unregulated, although it is increasingly used off label for treating depression, suicidal ideation and chronic pain In 2019, the Food and Drug Administration approved a derivative of ketamine called esketamine in a nasal spray for treatment-resistant depression. Ketamine has the potential for abuse, which may lead to moderate or low physical dependence or high psychological dependence, but experts consider it a safe medication. Those who use it recreationally often snort the drug in powder form or administer it intranasally by spray. © 2023 The New York Times Company

Keyword: Drug Abuse
Link ID: 29057 - Posted: 12.19.2023

By Anil Oza Krista Lisdahl has been studying cannabis use among adolescents for two decades, and what she sees makes her worried for her teenage son. “I see the data coming in, I know that he is going to come across it,” she says. As a clinical neuropsychologist at the University of Wisconsin–Milwaukee, she sees plenty of young people who have come into contact with the drug to varying degrees, from trying it once at a party to using potent preparations of it daily. The encounters have become more frequent as efforts to legalize cannabis for recreational use intensify around the world. In some of her studies, around one-third of adolescents who regularly use cannabis show signs of a cannabis use disorder — that is, they can’t stop using the drug despite negative impacts on their lives. But she wants more conclusive evidence when it comes to talking about the drug and its risks to young people, including her son. Deciding what to say is difficult, however. Anti-drug messaging campaigns have dwindled, and young people are forced to consider sometimes-conflicting messages on risks in a culture that increasingly paints cannabis and other formerly illicit drugs as harmless or potentially therapeutic. “Teenagers are pretty smart, and they see that adults use cannabis,” Lisdahl says. That makes blanket warnings and prohibitions practically useless. It’s now a decade since the drug was officially legalized for recreational use by adults aged 18 and older in Uruguay, and aged 21 and older in the states of Colorado and Washington. Many other states and countries have followed, and researchers are desperately trying to get a handle on how usage patterns are changing as a result; how the drug impacts brain development; and how cannabis use correlates with mental-health conditions such as depression, anxiety and schizophrenia. The data so far don’t tell clear stories: young people don’t seem to be using in greater numbers than before legalization, but there seem to be trends towards more problematic use. © 2023 Springer Nature Limited

Keyword: Drug Abuse; Schizophrenia
Link ID: 29041 - Posted: 12.13.2023

By Sabrina Malhi Cannabis use is associated with a greater risk of an unhealthy pregnancy outcomes, especially low birth weight, according to a study funded by the National Institutes of Health. While the study did not identity why cannabis use might have these effects, it underscores the potentially damaging impact of the substance on fetal health, the authors say. Many pregnant people use cannabis to help manage symptoms, including nausea and pain. The prevalence of the drug has surged in the past decade as more states have legalized its use for medicine or recreation, and many people believe it is relatively safe. But the impact cannabis has on pregnancy has been understudied. For the new study, researchers analyzed urine samples from more than 9,000 pregnant people between 2010 and 2013 to determine whether cannabis was used at any point during pregnancy, at how many weeks of gestation it was used and the amount. The team measured THC, the psychoactive substance in cannabis, at three different periods roughly tracking with trimesters and used that data to calculate total cannabis exposure throughout the entire pregnancy. Their findings were published in JAMA on Tuesday. The authors determined that pregnant people who used cannabis experienced unfavorable birth outcomes at rates of 25.9 percent, compared with 17.4 percent among those who did not use cannabis. Low birth weight and cannabis use had the strongest association out of all the adverse outcomes, the study found. Low birth weight is defined as weighing less than 5 lbs., 8 ounces at birth. This can lead to a range of health complications and long-term risks, including an increased likelihood of chronic conditions later in life. Experts say the study adds to a growing body of evidence that no amount of cannabis is safe during pregnancy.

Keyword: Drug Abuse; Development of the Brain
Link ID: 29040 - Posted: 12.13.2023

By Yasemin Saplakoglu Erin Calipari comes from a basketball family. Her father, John Calipari, has coached college and professional basketball since 1998, leading six teams to the NCAA Final Four, and her brother coaches men’s basketball at Vanderbilt University in Nashville, Tennessee, where she now works. But when she joined her college team as an undergraduate, she realized her strengths lay elsewhere. “I was fine. I wasn’t great,” she said. “It was pretty clear to me a couple years in that it was not a career path.” Off the court, as a biology major she gravitated toward hormones and neurotransmitters. She grew fascinated with the neurobiology of how and why drugs such as cocaine and opioids are addictive, as she learned about the effects of ecstasy on the serotonin system. “I thought drugs were so cool because they hijack the brain,” she said. “Drugs essentially take the normal systems we have in our body and drive them in a way that makes you want to take drugs again.” After pursuing graduate work in neuroscience, in 2017 Calipari set up her lab at Vanderbilt to explore how addiction is connected to the ways the brain learns and makes decisions. “Deciding what to do and what not to do is really fundamental to everything we do,” Calipari said. “You put your hand on a hot stove, you learn really quickly not to do that again.” Addiction can diminish a person’s ability to learn that drug use is hurting them, and also their ability to learn anything at all. Her world still collides with sports, for instance when she gives talks to athletes about the dangers of substance use. Athletes can be vulnerable to addiction when they are prescribed pain medicines, such as opioids, for injuries. There is a risk of dependence if opioids are taken for long periods of time, even when patients follow doctors’ orders — a fact that has led to a nationwide public health emergency. Tennessee is an epicenter of the opioid epidemic. In 2022, Nashville had the second-highest rate of overdose deaths in the country. All Rights Reserved © 2023

Keyword: Drug Abuse
Link ID: 29039 - Posted: 12.09.2023

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