Chapter 4. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology

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Heavy drinkers are putting themselves at risk of dementia, according to the largest study of its kind ever conducted. Research published in the Lancet Public Health journal provides powerful evidence that people who drink enough to end up in hospital are putting themselves at serious risk of vascular dementia and Alzheimer’s disease. It will also raise questions for moderate drinkers about the possible long-term consequences of their social habit. The study, which used the French National Hospital Discharge database, looked at more than a million people diagnosed with dementia between 2008 and 2013. More than a third – 38% of the 57,000 cases of early-onset dementia – were directly alcohol-related and 18% had an additional diagnosis of alcohol use disorders. Overall, alcohol use disorders were associated with a three times greater risk of all types of dementia. Dr Sara Imarisio, head of research at Alzheimer’s Research UK, said: “As this study only looked at the people who had been admitted to hospital due to chronic heavy drinking, it doesn’t reveal the full extent of the link between alcohol use and dementia risk. Previous research has indicated that even moderate drinking may have a negative impact on brain health and people shouldn’t be under the impression that only drinking to the point of hospitalisation carries a risk.” Experts said the new research should change attitudes. “What is most surprising about this paper is that it has taken us so long to recognise that alcohol misuse and dependence are such potent risk factors for the development of dementia,” said Robert Howard, professor of old age psychiatry at University College London.

Keyword: Drug Abuse; Alzheimers
Link ID: 24682 - Posted: 02.21.2018

By Matt Warren The anesthesia medication ketamine has shown promise in treating depression, but its exact effects on the brain are unclear. Now, researchers have discovered that the drug changes the firing patterns of cells in a pea-size structure hidden away in the center of the brain. This could explain why ketamine is able to relieve symptoms of depression so quickly—and may provide a fresh target for scientists developing new antidepressants. “It’s a spectacular study,” says Roberto Malinow, a neuroscientist at the University of California, San Diego, who was not involved in the work. “It will make a lot of people think.” In clinical trials, ketamine appears to act much faster than existing antidepressants, improving symptoms within hours rather than weeks. “People have tried really hard to figure out why it’s working so fast, because understanding this could perhaps lead us to the core mechanism of depression,” says Hailan Hu, a neuroscientist at Zhejiang University School of Medicine in Hangzhou, China, and a senior author on the new study. Hu suspected the drug might target a tiny region in the middle of the brain called the lateral habenula, the so-called “anti–reward center.” This region inhibits nearby reward areas, which can be useful in learning; for example, if a monkey pulls a lever expecting a treat but never receives it, the lateral habenula will reduce the activity of reward areas, and the monkey will be less likely to pull the lever in the future. But research over the past decade has suggested that the area may be overactive in depression, dampening down those reward centers too much. © 2018 American Association for the Advancement of Science.

Keyword: Depression; Drug Abuse
Link ID: 24664 - Posted: 02.15.2018

Dean Burnett The internet is a weird place. Part of this is due to how things linger rather than disappear, as they tended to do with more “traditional” media. Nowadays, people’s jobs can (rightly or wrongly) be endangered for tweets they wrote years ago. The adage about “today’s news is tomorrow’s fish and chip papers” seems no longer to apply. This is particularly true when a headline or story from years ago can be found by a group or community on a social network that missed it previously, so they share it widely and it ends up in your feeds long after it’s been “forgotten”. It can be a bit confusing for those of us who grew up solely with televised news. It’s like watching the weekend football roundup when it’s suddenly interrupted by a report that the Berlin Wall has come down. Case in point: yesterday I saw several examples of a story from 2015 about how scientists have discovered that cheese triggers the same part of the brain as hard drugs. A lot of people seem to be sharing this again (even me, thinking it was new). You’d assume someone well-versed in neuroscience like myself would easily recognise an old story like this. So why didn’t I? Stories like this are hardly uncommon. You can barely go a month without some study or report describing something supposedly innocuous as having the same effect on the brain, or activating the same brain regions, as drugs of abuse, be it sugar, pornography, religion, sex, Facebook, music, or, apparently, cheese. Give it a week, something else will be cited as stimulating our brains just like the most powerful narcotics. Maybe walking on crunchy leaves or taking your bra off after a long day will be described as the equivalent of inhaling a bin-bag full of cocaine? © 2018 Guardian News and Media Limited

Keyword: Drug Abuse; Attention
Link ID: 24658 - Posted: 02.14.2018

By Marc Lewis Over the past year and a half, Scientific American has published a number of fine articles arguing that addiction is not a disease, that drugs are not the cause of addiction, and that social and societal factors are fundamental contributors to opioid addiction in general and the overdose crisis in particular. The dominant view, that addiction is a disease resulting from drug use, is gradually being eroded by these and other incisive critiques. Yet the disease model and its corollaries still prevail in the domains of research, policy setting, knowledge dissemination and treatment delivery, more in the United States than in any other country in the developed world. You might wonder: what are we waiting for? The disease model remains dominant in the U.S. because of its stakeholders. First, the rehab industry, worth an estimated $35 billion per year, uses the disease nomenclature in a vast majority of its ads and slogans. Despite consistently low success rates, that's not likely to stop because it pulls in the cash. Second, as long as addiction is labeled a disease, medical insurance providers can be required to pay for it. Of course they do so as cheaply as possible, to the detriment of service quality, but they at least save governments the true costs of dealing with addiction through education, social support, employment initiatives and anti-poverty mechanisms. Third, the National Institute on Drug Abuse (NIDA), a part of the National Institutes of Health (NIH) that funds roughly 90 percent of addiction research worldwide, is a medically oriented funder and policy setter, as are the American Society of Addiction Medicine and other similar bodies. © 2018 Scientific American

Keyword: Drug Abuse
Link ID: 24642 - Posted: 02.10.2018

Kratom, a coffee-like plant native to southeast Asia which has similar properties to heroin and morphine is readily available in Canada. (Earth Kratom) U.S. health authorities say an herbal supplement promoted as an alternative pain remedy contains the same chemicals found in opioids, the addictive family of drugs at the centre of a national addiction crisis. The U.S. Food and Drug Administration analysis, published Tuesday, makes it more likely that the supplement, kratom, could be banned by the federal government. The FDA also said it has identified 44 reports of death involving kratom since 2011, up from 36 reported in November. Sold in various capsules and powders, kratom has gained popularity in the U.S. as a treatment for pain, anxiety and drug dependence. Proponents argue that the substance is safer than opioid painkillers like OxyContin and Vicodin, which have contributed to an epidemic of drug abuse. More than 63,000 Americans died in 2016 from drug overdoses, mostly from opioids. FDA Commissioner Scott Gottlieb reiterated that there are no FDA-approved medical uses for kratom, which is derived from a plant native to Southeast Asia. "Claiming that kratom is benign because it's 'just a plant' is shortsighted and dangerous," Gottlieb said in a statement. "It's an opioid. And it's an opioid that's associated with novel risks because of the variability in how it's being formulated, sold and used recreationally." ©2018 CBC/Radio-Canada.

Keyword: Drug Abuse
Link ID: 24628 - Posted: 02.07.2018

By PAM BELLUCK More American children than previously thought may be suffering from neurological damage because their mothers drank alcohol during pregnancy, according to a new study. The study, published Tuesday in the journal JAMA, estimates that fetal alcohol syndrome and other alcohol-related disorders among American children are at least as common as autism. The disorders can cause cognitive, behavioral and physical problems that hurt children’s development and learning ability. The researchers evaluated about 3,000 children in schools in four communities across the United States and interviewed many of their mothers. Based on their findings, they estimated conservatively that fetal alcohol spectrum disorders affect 1.1 to 5 percent of children in the country, up to five times previous estimates. About 1.5 percent of children are currently diagnosed with autism. “This is an equally common, or more common, disorder and one that’s completely preventable and one that we are missing,” said Christina Chambers, one of the study authors and a professor of pediatrics at the University of California, San Diego. “If it truly is affecting a substantial proportion of the population, then we can do something about it. We can provide better services for those kids, and we can do a better job of preventing the disorders to begin with.” The range of fetal alcohol spectrum disorders (also called FASDs) can cause cognitive, behavioral and physical difficulties. The most severe is fetal alcohol syndrome, in which children have smaller-than-typical heads and bodies, as well as eyes unusually short in width, thin upper lips, and smoother-than-usual skin between the nose and mouth, Dr. Chambers said. A moderate form is partial fetal alcohol syndrome. Less severe is alcohol-related neurodevelopmental disorder, in which children have neurological but not physical characteristics and it is known that their mothers drank during pregnancy. © 2018 The New York Times Company

Keyword: Development of the Brain; Drug Abuse
Link ID: 24626 - Posted: 02.07.2018

Beth Marsh, Lilla Porffy, Meryem Grabski, Will Lawn January 2018 has come to an end and with it the month that people increasingly use to abstain from alcohol. It is still unknown whether Dry January has a lasting effect on drinking behaviours, and people with an alcohol dependency problem should always seek support from their GP before going through detox. Nonetheless, Dry January undoubtedly drives a critical conversation about alcohol use and provides an opportunity for us to reconsider our relationship with alcohol (one of the main goals of the charity Alcohol Concern, who support the challenge). While overall alcohol consumption in the UK is falling, alcohol abuse still represents the fifth biggest risk factor for illness, death and disability across all ages. With current treatments often failing to prevent relapse in the long term, researchers are investigating the possibility of using ketamine combined with psychological therapy to help people stay dry, and not just for January. Despite its often cited use as a recreational drug and “horse-tranquilizer” ketamine is also the most widely used anaesthetic in humans. Administered appropriately in a controlled and safe medical environment, ketamine may also have benefits in the treatment of drug problems. Evidence for this originally came from a research group in Russia in the 1980s. In this study, patients who had alcohol problems were given three weekly ketamine treatments in conjunction with psychological therapy. After one year, 66% of patients who underwent this treatment regime were abstinent, in comparison to 24% of patients who received treatment as usual, without any ketamine. This abstinence rate is much greater than those documented with any other relapse prevention method. © 2018 Guardian News and Media Limited

Keyword: Drug Abuse
Link ID: 24619 - Posted: 02.06.2018

By Kendall Powell “It’s impossible that we still struggle to decide if coffee is healthy or unhealthy,” says Giuseppe Grosso, a nutritional epidemiologist at the University of Catania in Italy: Good for hypertension one week. Bad for hypertension the next. To address this vexing situation, Grosso and his colleagues collected all studies on the health effects of coffee, systematically reviewed the evidence, then offered up their bottom line in the Annual Review of Nutrition. Specifically, they looked at 127 meta-analyses, which lump together and statistically analyze studies on similar topics. A few of the studies were randomized controlled trials on coffee or caffeine administration, but most were observational studies of real-world coffee and caffeine consumption habits. (None of the review’s authors were paid by any food or beverage company.) For each meta-analysis, the team calculated the strength of the study’s designs and conclusions and then ranked its evidence for relationships between coffee and health on a scale from “convincing” all the way down to “limited.” No studies showed a “convincing” level of evidence — not surprisingly, since observational studies lack the rigor of ­gold-standard trials that use placebo controls. But several found “probable” evidence that coffee-drinking is associated with a decreased risk of many common cancers — including breast, colorectal, colon, endometrial and prostate — with a 2 to 20 percent reduction in risk, depending on the cancer type. © 1996-2018 The Washington Post

Keyword: Drug Abuse
Link ID: 24612 - Posted: 02.05.2018

Ian Sample Science editor A nasal spray that delivers a natural painkiller to the brain could transform the lives of patients by replacing the dangerous and addictive prescription opioids that have wreaked havoc in the US and claimed the lives of thousands of people. Scientists at University College London found they could alleviate pain in animals with a nasal spray that delivered millions of soluble nanoparticles filled with a natural opioid directly into the brain. In lab tests, the animals showed no signs of becoming tolerant to the compound’s pain-relieving effects, meaning the risk of overdose should be far lower. The researchers are now raising funds for the first clinical trial in humans to assess the spray’s safety. They will start with healthy volunteers who will receive the nasal spray to see if it helps them endure the pain of immersing one of their arms in ice-cold water. “If people don’t develop tolerance, you don’t have them always having to up the dose. And if they don’t have to up the dose, they won’t get closer and closer to overdose,” said Ijeoma Uchegbu, a professor of pharmaceutical nanoscience who is leading the research through Nanomerics, a UCL startup. If the first human safety trial is successful, the scientists will move on to more trials to investigate whether the nasal spray can bring swift relief to patients with bone cancer who experience sudden and excruciating bouts of pain.

Keyword: Pain & Touch; Drug Abuse
Link ID: 24609 - Posted: 02.03.2018

By Lauren Aguirre Just over five years ago, a man suffering from amnesia following a suspected drug overdose appeared at Lahey Hospital and Medical Center in Burlington, Massachusetts, a Boston suburb. He was 22, and had injected what he believed to be heroin. When he woke up the next morning, he was extremely confused, repeatedly asking the same questions and telling the same stories. Doctors at Lahey quickly diagnosed the man with anterograde amnesia — the inability to form new memories. “I thought it was an extremely strange [brain] scan — it was almost hard to believe.” His brain scan revealed why. “I thought it was an extremely strange scan — it was almost hard to believe,” said Jed Barash, a neurologist working at Lahey at the time. In the scan, the twin, seahorse-shaped structures of the man’s hippocampi were lit up against the dark background of the rest of the brain — a clear sign of severe injury to just that one region. “It was strange because that was all there was,” Barash said. Memory researchers have known since the late 1950s that the hippocampi are responsible for turning short-term memories into lasting ones, so the amnesia was not surprising. Just how the damage occurred, however, remained a mystery. Lack of oxygen to the brain that would have occurred during the overdose could not be the only explanation. The number of survivors in the state that year could easily have numbered in the thousands, so why was there only one patient with this seemingly unique brain damage? Along with his colleagues, Barash — now medical director at the Soldiers’ Home health care facility in Chelsea, Massachusetts — figured that the opioids must have played a role, and that hunch became only more acute as three more patients — each fitting the same pattern — appeared at Lahey over the next three years. All had the same unique destruction of the hippocampi, all had amnesia, and all were suspected to have overdosed. By that point, the doctors at Lahey faced two fundamental questions: What was causing the strange new syndrome? And precisely how rare was it? Copyright 2018 Undark

Keyword: Learning & Memory; Drug Abuse
Link ID: 24590 - Posted: 01.30.2018

Sarah Varney Two-year old Maverick Hawkins sits on a red plastic car in his grandmother's living room in the picturesque town of Nevada City, Calif., in the foothills of the Sierra Nevada mountains. His playpal Delilah Smith, a fellow 2-year old, snacks on hummus and cashews and delights over the sounds of her Princess Peppa stuffie. It's playtime for the kids of the provocatively named FaceBook group "Pot Smoking Moms Who Cuss Sometimes." Maverick's mother, Jenna Sauter, started the group after he was born. "I was a new mom, a young mom — I was 22 — and I was just feeling really lonely in the house, taking care of him," she says. She wanted to reach out to other mothers but didn't want to hide her marijuana use. "I wanted friends who I could be open with," Sauter says — "like I enjoy going to the river and I like to maybe smoke a joint at the river." There are nearly 2,600 members now in the FaceBook group. Marijuana, which became legal for recreational use in California earlier this month, is seen by many group members as an all-natural and seemingly harmless remedy for everything from morning sickness to post-partum depression. Delilah Smith's mom Andria is 21 and a week away from her due date with her second child. She took umbrage when an emergency room physician recently suggested she take "half a Norco"— a pill akin to Vicodin, an opioid-based painkiller — for her excruciating back pain. © 2018 npr

Keyword: Development of the Brain; Drug Abuse
Link ID: 24582 - Posted: 01.29.2018

By Shawna Williams When the late organic chemist John Daly was on the hunt for poisonous frogs, he employed an unadvisable method: “It involved touching the frog, then sampling it on the tongue. If you got a burning sensation, then you knew this was a frog you ought to collect,” he once told a National Institutes of Health (NIH) newsletter writer. Daly survived to gather frogs from South America, Madagascar, Australia, and Thailand, and he extracted more than 500 compounds from their skin (many of which the frogs in turn had harvested from their insect diets). One of these compounds, the toxin epibatidine, turned out to have an analgesic effect 200 times more potent than morphine in rodents, Daly and his colleagues reported in 1992 (J Am Chem Soc, 114:3475-78, 1992); and rather than working through opioid receptors, epibatidine bound to nicotinic receptors. “To have a drug that works as well [as opioids] but is actually targeting a completely independent receptor system is really one of those holy grails of the drug industry,” says Daniel McGehee, who studies nicotinic receptors at the University of Chicago. But an epibatidine-related compound tested by Abbott Labs as an analgesic in the late 2000s caused uncontrollable vomiting, McGehee says. Although research on nicotinic receptors continues, he’s not aware of any epibatidine analogs currently in the drug development pipeline. But frogs may yet hold clues to killing pain. At least one frog does deploy an opioid: the waxy monkey tree frog (Phyllomedusa sauvagii), whose skin is laced with the peptide dermorphin. Although the compound does not appear to be a toxin that wards off predators, dermorphin has about 40 times the potency of morphine in a guinea-pig ileum assay, but it doesn’t effectively cross the blood-brain barrier, says pharmacologist Tony Yaksh of the University of California, San Diego. Dermorphin also boasts an unusual chemical property: the inclusion of a D-amino acid in its sequence. Almost all amino acids found in natural compounds are L-isomers, and dermorphin’s stereochemistry makes it resistant to metabolism and “certainly renders it more potent,” Yaksh writes in an email to The Scientist. © 1986-2018 The Scientist

Keyword: Pain & Touch; Drug Abuse
Link ID: 24577 - Posted: 01.27.2018

by Ariana Eunjung Cha A new class of epilepsy medications based on an ingredient derived from marijuana could be available as soon as the second half of 2018 in the United States, pending Food and Drug Administration approval. Officials from GW Pharmaceuticals, the company that developed the drug, on Wednesday announced promising results from a study on 171 patients randomized into treatment and placebo groups. Members of the group, ages 2 to 55, have a condition called Lennox-Gastaut syndrome and were suffering from seizures that were not being controlled by existing drugs. On average they had tried and discontinued six anti-seizure treatments and were experiencing 74 “drop” seizures per month. Drop seizures involve the entire body, trunk or head and often result in a fall or other type of injury. The results, published in the Lancet, show that over a 14-week treatment period, 44 percent of patients taking the drug, called Epidiolex, saw a significant reduction in seizures, compared with 22 percent of the placebo group. Moreover, more of the patients who got the drug experienced a 50 percent or greater reduction in drop seizures. Elizabeth Thiele, director of pediatric epilepsy at Massachusetts General Hospital and lead author of the study, said the results varied depending on the patient. “For some, it does not do a whole lot. But for the people it does work in, it is priceless,” she said. “One child who comes to mind had multiple seizures a day. She had been on every medication possible,” said Thiele, a professor of neurology at Harvard Medical School. Then the patient tried the cannabis-based treatment and has been seizure-free for almost four years. “She is now talking about college options. She would have never had that conversation before. It has been life-changing.” © 1996-2018 The Washington Post

Keyword: Epilepsy; Drug Abuse
Link ID: 24573 - Posted: 01.26.2018

Emmarie Huetteman Dr. Andrey Ostrovsky's family did not discuss what killed his uncle in 2015. The man was young, not quite two weeks past his 45th birthday, when he died, and had lost touch with loved ones in his final months. At the time, Ostrovsky wondered if his uncle had perhaps killed himself. Almost two years later, Ostrovsky was Medicaid's chief medical officer, grappling professionally with an opioid crisis that kills about 115 Americans each day, when he learned the truth: His uncle had died of a drug overdose. Family members knew the uncle's life had been turbulent for a while before his death; they'd watched as he divorced his wife and became estranged from his 4-year-old daughter and eventually lost his job as a furniture store manager. But Ostrovsky wanted to better understand what had happened to the man — his stepfather's younger brother. So last fall, when he found himself in southeastern Florida, where his uncle had died, Ostrovsky contacted one of the uncle's friends for what he expected would be a quick cup of coffee. Instead the friend "let loose," revealing that he and Ostrovsky's uncle had been experimenting with a variety of drugs the night of the death. It was the tragic culmination of more than a decade of substance abuse — a pattern of behavior much of the family knew nothing about. An autopsy showed there were opiates and cocaine in his uncle's system, Ostrovsky later learned. © 2018 npr

Keyword: Drug Abuse
Link ID: 24572 - Posted: 01.26.2018

By Alex Therrien Health reporter, BBC News Smokers need to quit cigarettes rather than cut back on them to significantly lower their risk of heart disease and stroke, a large BMJ study suggests. People who smoked even one cigarette a day were still about 50% more likely to develop heart disease and 30% more likely to have a stroke than people who had never smoked, researchers said. They said it showed there was no safe level of smoking for such diseases. But an expert said people who cut down were more likely to stop. Cardiovascular disease, not cancer, is the greatest mortality risk for smoking, causing about 48% of smoking-related premature deaths. While the percentage of adults in the UK who smoked had been falling, the proportion of people who smoked one to five cigarettes a day had been rising steadily, researchers said. Their analysis of 141 studies, published in the BMJ, indicates a 20-a-day habit would cause seven heart attacks or strokes in a group of 100 middle-aged people. But if they drastically cut back to one a day it would still cause three heart attacks, the research suggests. The researchers said men who smoked one cigarette a day had about a 48% higher risk of developing coronary heart disease and were 25% more likely to have a stroke than those who had never smoked. For women, it was higher - 57% for heart disease and 31% for stroke. Prof Allan Hackshaw at the UCL Cancer Institute at University College London, who led the study, told the BBC: "There's been a trend in quite a few countries for heavy smokers to cut down, thinking that's perfectly fine, which is the case for things like cancer. "But for these two common disorders, which they're probably more likely to get than cancer, it's not the case. They've got to stop completely." © 2018 BBC.

Keyword: Drug Abuse
Link ID: 24563 - Posted: 01.25.2018

Patti Neighmond Kids who vape and use other forms of e-cigarettes are likely to try more harmful tobacco products like regular cigarettes, but e-cigarettes do hold some promise for helping adults quit. That's according to the National Academies of Science, Engineering and Medicine, which published a comprehensive public health review of more than 800 studies on e-cigarettes on Tuesday. "There is conclusive evidence that most products emit a variety of potentially toxic substances. However the number and intensity is highly variable," says David Eaton, who heads the committee that wrote the report. He is also the dean and vice provost of the graduate school of the University of Washington, Seattle. "In some circumstances, such as their use by nonsmoking adolescents and young adults, their adverse effects clearly warrant concern. In other cases, such as when adult smokers use them to quit smoking, they offer an opportunity to reduce smoking-related illness." In fact, 15 of the studies NAS reviewed found that when teens and young adults use e-cigarettes, they are more likely to try regular tobacco within a year. "We found that kids who tried e-cigarettes, hookah, or smokeless tobacco or cigars — any non-cigarette tobacco product — were all twice as likely to try cigarettes a year later, compared to kids who hadn't used any of those other tobacco products," says Shannon Lea Watkins, a public policy researcher at University of California, San Francisco. Watkins and her colleagues also found that the effects of using non-cigarette products compound: "Kids using two or more non-cigarette products were four times as likely to report using cigarettes a year later." © 2018 npr

Keyword: Drug Abuse
Link ID: 24561 - Posted: 01.24.2018

By Ann Gibbons Humans are the ultimate social animals, with the ability to bond with mates, communicate through language, and make small talk with strangers on a packed bus. (Put chimpanzees in the same situation and most wouldn’t make it off the bus alive.) A new study suggests that the evolution of our unique social intelligence may have initially begun as a simple matter of brain chemistry. Neuroanatomists have been trying for decades to find major differences between the brains of humans and other primates, aside from the obvious brain size. The human brain must have reorganized its chemistry and wiring as early human ancestors began to walk upright, use tools, and develop more complex social networks 6 million to 2 million years ago—well before the brain began to enlarge 1.8 million years ago, according to a hypothesis proposed in the 1960s by physical anthropologist Ralph Holloway of Columbia University. But neurotransmitters aren’t preserved in ancient skulls, so how to spot those changes? One way is to search for key differences in neurochemistry between humans and other primates living today. Mary Ann Raghanti, a biological anthropologist at Kent State University in Ohio, and colleagues got tissue samples from brain banks and zoos of 38 individuals from six species who had died of natural causes: humans, tufted capuchins, pig-tailed macaques, olive baboons, gorillas, and chimpanzees. They sliced sections of basal ganglia—clusters of nerve cells and fibers in a region at the base of the brain known as the striatum, which is a sort of clearinghouse that relays signals from different parts of the brain for movement, learning, and social behavior. They stained these slices with chemicals that react to different types of neurotransmitters, including dopamine, serotonin, and neuropeptide Y—which are associated with sensitivity to social cues and cooperative behavior. Then, they analyzed the slices to measure different levels of neurotransmitters that had been released when the primates were alive. © 2018 American Association for the Advancement of Science.

Keyword: Aggression; Drug Abuse
Link ID: 24555 - Posted: 01.23.2018

By Jenny Rood Opioid drugs are well-established double-edged swords. Extremely effective at analgesia, they cause an array of harmful side effects throughout the body, including itching, constipation, and respiratory depression—the slowed breathing that ultimately causes death in overdose cases. What’s more, the body’s interaction with opioids is dynamic: our receptors for these compounds become desensitized to the drugs’ activity over time, requiring ever larger doses to suppress pain and eventually provoking severe dependence and protracted withdrawal. In the past few years, these side effects have plagued growing numbers of US citizens, plunging the country into the throes of a devastating opioid crisis in which nearly 100 people die from overdoses every day. Even so, opioids are still among the most effective pain-relief options available. “Over hundreds of years, [opioid receptors] have remained a target,” says Laura Bohn, a biochemist at the Scripps Research Institute in Jupiter, Florida. “Therapeutically, it works.” Since the early 2000s, intriguing evidence has emerged suggesting that opioids’ useful properties could be separated from their harmful attributes. (See “Pain and Progress,” The Scientist, February 2014.) In 2005, Bohn, then at the Ohio State University College of Medicine, and colleagues showed that shutting down one of the signaling pathways downstream of the opioid receptor targeted by morphine not only amped up the drug’s painkilling effects in mice, but also reduced constipation and respiratory depression (J Pharmacol Exp Ther, 314:1195-201). © 1986-2018 The Scientist

Keyword: Pain & Touch; Drug Abuse
Link ID: 24550 - Posted: 01.22.2018

By Dina Fine Maron One evening this past fall a patient stumbled into the emergency room at Brigham and Women’s Hospital in Boston. “I don’t feel so…” she muttered, before losing consciousness. Her breathing was shallow and her pupils were pinpoints, typical symptoms of an opioid overdose. Her care team sprang into action. They injected her with 0.4 milligram of naloxone, an overdose antidote—but she remained unresponsive. They next tried one milligram, then two, then four. In total they used 12 milligrams in just five minutes, says Edward Boyer, the physician overseeing her care that night. Yet the patient still had trouble breathing. They put a tube down her throat and hooked her to a ventilator. Twenty minutes later she woke up—angry and in drug withdrawal, but alive. The patient, whose identifying details may have been altered to protect patient confidentiality, had apparently injected herself with a synthetic opioid such as fentanyl right outside of the hospital building. That gave her just enough time to seek help. But many users of synthetic opioids are not so lucky. These drugs, which bear little chemical resemblance to any opioid derived from the opium poppy, are much more powerful than poppy-based heroin and semisynthetic opioids such as oxycodone or hydrocodone. Thus, the standard dose of naloxone employed by first responders (and sold in bystander overdose kits) is often not potent enough to save a synthetic opioid user’s life. © 2018 Scientific American

Keyword: Drug Abuse; Pain & Touch
Link ID: 24505 - Posted: 01.09.2018

Nicola Davis The prospect of a non-addictive alternatives to morphine and other opioids has moved a step closer as scientists say they have cracked a key challenge in developing safe and effective substitute painkillers. Overuse of highly addictive opioids has led to a health crisis across the world, especially in the US where more than 60,000 people died after overdoses in 2016 alone; president Donald Trump has declared the epidemic a public health emergency. Researchers looking for alternatives examined a receptor protein that interacts with opioids in the brain, and have now revealed its structure as it binds to a molecule related to morphine. While the structure of the receptor had previously been reported, this is the first time scientists have unveiled its structure as it interacts with a drug. The development, they say, could prove pivotal. The protein, known as the kappa opioid receptor, is one of four that interacts with opioids, but – crucially – while it can trigger pain-killing effects, it is not linked to problems including constipation, addiction risk and death as a result of overdose. “Tens of thousands of people are dying every year in the US because of opioid overdoses; in the last year more than 50,000 people died. That is as many as died in the Vietnam war in the US. It is a terrible, terrible crisis,” said Bryan Roth, co-author of the research from the University of North Carolina at Chapel Hill. © 2018 Guardian News and Media Limited

Keyword: Drug Abuse; Pain & Touch
Link ID: 24497 - Posted: 01.06.2018