Chapter 4. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
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By MAIA SZALAVITZ Drug education is the only part of the middle school curriculum I remember — perhaps because it backfired so spectacularly. Before reaching today’s legal drinking age, I was shooting cocaine and heroin. I’ve since recovered from my addiction, and researchers now are trying to develop innovative prevention programs to help children at risk take a different road than I did. Developing a public antidrug program that really works has not been easy. Many of us grew up with antidrug programs like D.A.R.E. or the Nancy Reagan-inspired antidrug campaign “Just Say No.” But research shows those programs and others like them that depend on education and scare tactics were largely ineffective and did little to curb drug use by children at highest risk. But now a new antidrug program tested in Europe, Australia and Canada is showing promise. Called Preventure, the program, developed by Patricia Conrod, a professor of psychiatry at the University of Montreal, recognizes how a child’s temperament drives his or her risk for drug use — and that different traits create different pathways to addiction. Early trials show that personality testing can identify 90 percent of the highest risk children, targeting risky traits before they cause problems. Recognizing that most teenagers who try alcohol, cocaine, opioids or methamphetamine do not become addicted, they focus on what’s different about the minority who do. © 2016 The New York Times Company
Keyword: Drug Abuse
Link ID: 22715 - Posted: 09.30.2016
By Carl Hart In early August the Drug Enforcement Administration declined to reclassify marijuana under the federal Controlled Substances Act. The drug is currently listed on Schedule I, meaning that it is viewed as having “no currently accepted medical use in treatment” and is therefore technically banned by federal law. The proposed change would have moved it to Schedule II, where it would join morphine, opium and codeine. That would make marijuana potentially available by prescription nationwide. Such a change would have been good for patients and scientists, and it would have represented a big step toward resolving the hypocritical mess that characterizes current law. Despite many people's assumptions to the contrary, the existing law does not ban scientific investigation into the harms and benefits of the drug. It's true that scientists studying marijuana must jump through multiple bureaucratic and regulatory hoops, and one of these just became a bit easier to navigate. Currently researchers who want to study the drug must get it from the University of Mississippi, which is the only university now permitted to grow marijuana plants for research purposes. When the DEA announced in August that it would not reschedule marijuana, it did say that it would let other institutions apply for permission to start growing the plants as well. That was a step in the right direction—but it's not enough. Despite the regulatory barriers, dozens of scientists—myself included—have been engaged in research on the harms and benefits of marijuana for decades, and the evidence shows that the drug has many helpful therapeutic uses. For example, it stimulates appetite in HIV-positive patients, which could be a lifesaver for someone suffering from AIDS wasting syndrome. It is also useful in the treatment of neuropathic pain, chronic pain, and spasticity caused by multiple sclerosis. © 2016 Scientific American
Keyword: Drug Abuse
Link ID: 22710 - Posted: 09.30.2016
By Nick Purdon, Leonardo Palleja, CBC News If you met Lisa James, chances are you'd never guess she injects herself with heroin twice a day. She's a devoted mom to her daughter Tia, 24, who has a rare neurological disorder that causes tumours to grow on her spine and brain. She comforts Tia when she's overcome with nausea. She's by her side when she visits doctors. "My relationship with my daughter is better than it's ever been," says James, 48. But James says it wasn't so long ago, her days were spent doing absolutely anything to score heroin. She used to steal hundreds of dollars' worth of meat from grocery stores and sell it on the streets. She even stole from Tia. "I took $500 out of her account and because of the lovely girl that she is, she never wanted to make me feel bad," James says. "If someone had told me I would do something so despicable — I never would have believed it." She says that all changed when she was accepted to the Providence Crosstown Clinic in Vancouver's Downtown Eastside, where she's buzzed in every morning at 9 a.m. She sits down in a sterile room and injects a syringe full of free heroin into her arm. ©2016 CBC/Radio-Canada.
Keyword: Drug Abuse
Link ID: 22702 - Posted: 09.28.2016
Emma Yasinski Two often-overlooked medications might help millions of Americans who abuse alcohol to quit drinking or cut back. Public health officials, building on a push to treat people who abuse opioids with medications, want physicians to consider using medications to treat alcohol addiction. The drugs can be used in addition to or sometimes in place of peer-support programs, they say. "We want people to understand we think AA is wonderful, but there are other options," says George Koob, director of the National Institute of Alcohol Abuse and Alcoholism, a part of the federal National Institutes of Health. It is still rare for a person struggling with alcohol to hear that medication therapy exists. This partly reflects the tradition of treating addiction through 12-step programs. It's also a byproduct of limited promotion by the drugs' manufacturers and confusion among doctors about how to use them. A key study funded by the federal government reported last year that only 20 percent people who abuse alcohol will ever receive any form of treatment, which ranges from seeing a counselor or doctor to entering a specialized treatment program. The same is true for opioid addiction — about 80 percent of people dependent on opioids will never receive treatment. © 2016 npr
Keyword: Drug Abuse
Link ID: 22698 - Posted: 09.27.2016
By NICHOLAS BAKALAR Ants, like people and rats, can become addicted to morphine. Scientists divided 90 ants into three groups. The first received a solution containing morphine and sugar, which was gradually reduced until the ants were receiving pure morphine. The second group of ants got a sugar solution gradually reduced to pure water, and the third ate just sugar. Then the researchers offered all three groups the choice of sugar or morphine. The ants that had been gradually deprived of sugar and those never exposed to morphine went right back to sugar. But about two-thirds of the ants given morphine chose it over sugar. Ants are the first nonmammal to display drug-seeking behavior, the researchers said. © 2016 The New York Times Company
Keyword: Drug Abuse
Link ID: 22697 - Posted: 09.27.2016
By MICHAEL HEDRICK My father said on numerous occasions when I was growing up that he would see other families that had problems like divorce and drug use, and he would thank God that his family was so perfect. Things would change, though. They always do. And that perfect family would face just as much struggle as any other. Growing up in the mountains above Boulder, Colo., our life was good. My parents had left their life in Chicago behind for an ideal they saw in a piece of art they found at a flea market, a haphazardly painted picture of a cabin next to a river with the mountains towering in the background. Born in the early ‘80s, my brothers and I shared a bond as best friends in our small neighborhood, isolated from town, where we spent time outside sledding, building forts and making dams in the ditch that ran by our house. The biggest problems we seemed to face were bloody knees and the occasional broken bone from snowboarding and bike accidents. My dad, a subscriber to “Mother Earth News,” relished our family’s home in the mountains. There were backpacking trips to the national park 30 miles away, where he taught us how to build a fire and to hang our food from tree limbs to keep it out of reach of bears. Other times he would take us on long father-son road trips, where we would drive the long highways with nothing to look at but the passing fields and nothing to pay attention to but the books on tape from Focus on the Family that my father put on the car stereo. Those tapes provided a Christian look at what it meant to be a man, covering issues like lust, sex and puberty, and he’d answer our questions about girls and all manner of things relating to our growing into healthy young men. © 2016 The New York Times Company
By Mallory Locklear Men and women show different patterns of drug abuse, with women becoming addicted to some substances much more quickly. Now a study in rats has found that sex hormones can reduce opioid abuse. From studies of other drugs, such as cocaine and alcohol, we know that women are less likely to use these substances than men, but become addicted faster when they do. “There are a lot of data to indicate that women transition from that initial use to having a substance-use disorder much more rapidly,” says Mark Smith, a psychologist at Davidson College, North Carolina. Once addicted, women also seem to have stronger drug cravings. Tracking drug use throughout women’s menstrual cycles suggests that both these differences could be shaped by hormones – with more intense cravings and greater euphoria at particular times in the cycle, says Smith. Craving crash Now Smith’s team has investigated the effects of hormones on opioid addiction in rats. Their findings suggest that hormones such as oestrogen and progesterone may help women to kick the habit. The researchers allowed female rats to self-administer heroin, and measured how much they chose to take at different times in their oestrous cycle – a regular sequence of hormone fluctuations similar to those seen in the menstrual cycle in women. © Copyright Reed Business Information Ltd.
By Andy Coghlan You made a choice and it didn’t turn out too well. How will your brain ensure you do better next time? It seems there’s a hub in the brain that doles out rewards and punishments to reinforce vital survival skills. “Imagine you go to a restaurant hoping to have a good dinner,” says Bo Li of Cold Spring Harbor Laboratory in New York. “If the food exceeds your expectations, you will likely come back again, whereas you will avoid it in future if the food disappoints.” Li’s team has discovered that a part of the brain’s basal ganglia area, called the habenula-projecting globus pallidus (GPh), plays a crucial role in this process. They trained mice to associate specific sound cues either with a reward of a drink of water or a punishment of a puff of air in the face, and then surprised them by switching them around. When mice expecting a drink were instead punished with a puff of air, GPh neurons became particularly active. But when the mice were unexpectedly rewarded, the activity of these neurons was inhibited. Further experiments revealed that once activated GPh neurons enforce punishment in the brain, reducing levels of the reward chemical dopamine in regions of the brain that plan actions. © Copyright Reed Business Information Ltd.
Keyword: Drug Abuse
Link ID: 22681 - Posted: 09.22.2016
Martha Bebinger Five states are voting this fall on whether marijuana should be legal, like alcohol, for recreational use. That has sparked questions about what we know – and don't know – about marijuana's effect on the brain. Research is scarce. The U.S. Drug Enforcement Agency classifies marijuana as a Schedule I drug. That classification puts up barriers to conducting research on it, including a cumbersome DEA approval application and a requirement that scientists procure very specific marijuana plants. One long-term study in New Zealand compared the IQs of people at age 13 and then through adolescence and adulthood to age 38. Those who used pot heavily from adolescence onward showed an average 8 percent drop in IQ. People who never smoked, by contrast, showed slightly increased IQ. Critics pounced on the study, which was published in 2012, because it didn't adjust for many other things that affect IQ such as home life or family income. And there's no proof the IQ differences are due to pot. One of those critics, Nicholas Jackson, now a senior statistician at the University of California, Los Angeles, wondered what would happen if he could rule out some of those elements by comparing twins. "Individuals that share the same genes, grew up in the same household, where the difference between them was that one of the twins was using marijuana and one was not," Jackson says. © 2016 npr
Keyword: Drug Abuse
Link ID: 22648 - Posted: 09.13.2016
By Bob Grant Lab rats that compulsively drink are cured of their addiction by a drug that silences neural networks that strengthened as they became dependent on alcohol.FLICKR, SARAH LAVAL Alcohol dependence involves neural reward networks that are strengthened by the regular consumption of alcohol. Using rat models of compulsive drinking, researchers at The Scripps Research Institute (TSRI) have now shown that they can interfere with those specific networks to curb the behavior. They reported their findings last week (September 7) in The Journal of Neuroscience. “We can completely reverse alcohol dependence by targeting a network of neurons,” coauthor Olivier George, a TSRI neuroscientist, said in a statement. “It is very challenging to target such a small population of neurons in the brain, but this study helps to increase our knowledge of a part of the brain that is still a mystery,” added coauthor and TSRI postdoc Giordano de Guglielmo. The researchers used a drug called Daun02 to shut down a specific group of neurons in the amygdalas of rats that drank compulsively. The treated rats stopped imbibing as much, and this behavioral change lasted for several days. “With classic pharmacology we usually observe a 20-40 percent decrease in drinking because the individuals are highly dependent (we model heavy alcoholism),” George told Medical News Today. “Instead, here, the drinking went all the way back down to normal drinking, and without noticeable side effects; very unusual. And, usually, to have long lasting effects like that, you need daily treatment, not a single one; it shows that we might have found alcoholism's Achilles' heel.” © 1986-2016 The Scientist
Keyword: Drug Abuse
Link ID: 22647 - Posted: 09.13.2016
By JACK HEALY CINCINNATI — On the day he almost died, John Hatmaker bought a packet of Oreos and some ruby-red Swedish Fish at the corner store for his 5-year-old son. He was walking home when he spotted a man who used to sell him heroin. Mr. Hatmaker, 29, had overdosed seven times in the four years he had been addicted to pain pills and heroin. But he hoped he was past all that. He had planned to spend that Saturday afternoon, Aug. 27, showing his son the motorcycles and enjoying the music at a prayer rally for Hope Over Heroin in this region stricken by soaring rates of drug overdoses and opioid deaths. But first, he decided as he palmed a sample folded into a square of paper, he would snort this. As he crumpled to the sidewalk, Mr. Hatmaker became one of more than 200 people to overdose in the Cincinnati area in the past two weeks, leaving three people dead in what the officials here called an unprecedented spike. Similar increases in overdoses have rippled recently through Indiana, Kentucky and West Virginia, overwhelming ambulance crews and emergency rooms and stunning some antidrug advocates. Addiction specialists said the sharp increases in overdoses were a grim symptom of America’s heroin epidemic, and of the growing prevalence of powerful synthetic opiates like fentanyl. The synthetics are often mixed into batches of heroin, or sprinkled into mixtures of caffeine, antihistamines and other fillers. In Cincinnati, some medical and law enforcement officials said they believed the overdoses were largely caused by a synthetic drug called carfentanil, an animal tranquilizer used on livestock and elephants with no practical uses for humans. Fentanyl can be 50 times stronger than heroin, and carfentanil is as much as 100 times more potent than fentanyl. Experts said an amount smaller than a snowflake could kill a person. © 2016 The New York Times Company
By Clare Wilson Traffic fumes go to your head. Tiny specks of metal in exhaust gases seem to fly up our noses and travel into our brains, where they may contribute to Alzheimer’s disease. Iron nanoparticles were already known to be present in the brain – but they were thought to come from the iron naturally found in our bodies, derived from food. Now a closer look at their structure suggests the particles mostly come from air pollution sources, like traffic fumes and coal burning. The findings are a smoking gun, says Barbara Maher of Lancaster University in the UK. Iron is present harmlessly in our bodies in different forms, as it is part of many biological molecules. But the form known as magnetite, or iron oxide, which is highly reactive and magnetic, has been implicated in Alzheimer’s disease. Maher’s team looked at the brains of 37 people who had lived either in Manchester in the UK or Mexico City. All contained millions of magnetite particles per gram of brain tissue, detected by measuring how magnetic the brain tissue was. The surprise came when the team used electron microscopes to take a close look at particles in the front part of the brains of six people. Round particles of magnetite outnumbered angular magnetite crystals by about one hundred to one. Crystal forms are more likely to have a natural source – such as iron that has come out of the body’s cells. But round particles normally come from melting iron at high temperatures, which happens when fuel is burned. © Copyright Reed Business Information Ltd.
Link ID: 22632 - Posted: 09.06.2016
By Laurie McGinley The Food and Drug Administration, alarmed that increasing numbers of Americans are combining opioid painkillers and benzodiazepines, said Wednesday that it will require tough new warnings on the product labels that spell out the serious dangers of mixing the drugs. The agency said it will require “boxed warnings” — its strongest category — on 389 separate products and will mandate the warning on opioid-containing cough medications. The new language will list the hazards of using the medications in tandem, which include extreme sleepiness, respiratory depression, coma and even death. The agency noted that the misuse of opioids, powerful pain medications such as prescription oxycodone, hydrocodone and morphine, has “increased significantly” in the United States over the past two decades. Benzodiazepines are used to treat anxiety, insomnia and seizure disorders. Both classes of drugs depress the central nervous system and together can raise the risk of adverse outcomes. FDA officials said the number of patients prescribed both an opioid and a benzodiazepine increased by 41 percent — about 2.5 million people — between 2002 and 2014. From 2004 to 2011, the rate of emergency-department visits involving the non-medical use of both drug classes increased significantly and overdose deaths nearly tripled, the FDA said.
Merrit Kennedy More than 1,000 residents of a public housing complex in East Chicago, Ind., are now forced to relocate because of dangerously high lead levels in the area's soil. The West Calumet Housing Complex, which houses primarily low-income families, lies on the site of a former lead smelting company, as member station WBEZ reported. In July, the Environmental Protection Agency reported high lead levels in the soil in parts of the complex and notified the residents. The EPA advised parents to stop their kids from playing in the dirt, "to wash their children's toys regularly and to wash children's hands after they play outside." As WBEZ reported, the samples showed lead levels "three times higher than the federal safety standards and in some places even higher, much higher." After that, East Chicago Mayor Anthony Copeland "ordered the removal of 1,200 residents from the West Calumet housing project for safety concerns," according to the member station. The residents have now been informed that the 346-unit complex is set to be demolished. "Residents have been provided vouchers for temporary hotel living until their homes are done being cleaned. The residents will return to their homes for a few more months until vouchers for permanent housing are made available by the U.S. Department of Housing and Urban Development." © 2016 npr
By STEVE SILBERMAN In the late 1930s, Charles Bradley, the director of a home for “troublesome” children in Rhode Island, had a problem. The field of neuroscience was still in its infancy, and one of the few techniques available to allow psychiatrists like Bradley to ponder the role of the brain in emotional disorders was a procedure that required replacing a volume of cerebrospinal fluid in the patient’s skull with air. This painstaking process allowed any irregularities to stand out clearly in X-ray images, but many patients suffered excruciating headaches that lasted for weeks afterward. Meanwhile, a pharmaceutical company called Smith, Kline & French was facing a different sort of problem. The firm had recently acquired the rights to sell a powerful stimulant then called “benzedrine sulfate” and was trying to create a market for it. Toward that end, the company made quantities of the drug available at no cost to doctors who volunteered to run studies on it. Bradley was a firm believer that struggling children needed more than a handful of pills to get better; they also needed psychosocial therapy and the calming and supportive environment that he provided at the home. But he took up the company’s offer, hoping that the drug might eliminate his patients’ headaches. It did not. But the Benzedrine did have an effect that was right in line with Smith, Kline & French’s aspirations for its new product: The drug seemed to boost the children’s eagerness to learn in the classroom while making them more amenable to following the rules. The drug seemed to calm the children’s mood swings, allowing them to become, in the words of their therapists, more “attentive” and “serious,” able to complete their schoolwork and behave. Bradley was amazed that Benzedrine, a forerunner of Ritalin and Adderall, was such a great normalizer, turning typically hard-to-manage kids into models of complicity and decorum. But even after marveling at the effects of the drug, he maintained that medication should be considered for children only in addition to other forms of therapy. © 2016 The New York Times Company
Neuroscience News Researchers have identified a brain mechanism that could be a drug target to help prevent tolerance and addiction to opioid pain medication, such as morphine, according to a study by Georgia State University and Emory University. The findings, published in the Nature journal Neuropsychopharmacology in August, show for the first time that morphine tolerance is due to an inflammatory response produced in the brain. This brain inflammation is caused by the release of cytokines, chemical messengers in the body that trigger an immune response, similar to a viral infection. Researchers’ results show blocking a particular cytokine eliminated morphine tolerance, and they were able to reduce the dose of morphine required to alleviate pain by half. “These results have important clinical implications for the treatment of pain and also addiction,” said Lori Eidson, lead author and a graduate student in the laboratory of Dr. Anne Murphy in the Neuroscience Institute of Georgia State. “Until now, the precise underlying mechanism for opioid tolerance and its prevention have remained unknown.” Over 67 percent of the United States population will experience chronic pain at some point in their lives. Morphine is the primary drug used to manage severe and chronic pain, with 3 to 4 percent of adults in the U.S. receiving long-term opioid therapy. However, tolerance to morphine, defined as a decrease in pain relief over time, significantly impedes treatment for about 60 percent of patients. Long-term treatment with opioids is associated with increased risk of abuse, dependence and fatal overdoses.
Sara Reardon Neuroscientists have invented a way to watch the ebb and flow of the brain's chemical messengers in real time. They were able to see the surge of neurotransmitters as mice were conditioned — similarly to Pavlov's famous dogs — to salivate in response to a sound. The study, presented at the American Chemical Society’s meeting in Philadelphia, Pennyslvania, on 22 August, uses a technique that could help to disentangle the complex language of neurotransmitters. Ultimately, it could lead to a better understanding of brain circuitry. The brain’s electrical surges are easy to track. But detecting the chemicals that drive this activity — the neurotransmitters that travel between brain cells and lead them to fire — is much harder. “There’s a hidden signalling network in the brain, and we need tools to uncover it,” says Michael Strano, a chemical engineer at the Massachusetts Institute of Technology in Cambridge. In many parts of the brain, neurotransmitters can exist at undetectably low levels. Typically, researchers monitor them by sucking fluid out from between neurons and analysing the contents in the lab. But that technique cannot measure activity in real time. Another option is to insert a metal probe into the space between neurons to measure how neurotransmitters react chemically when they touch metal. But the probe is unable to distinguish between structurally similar molecules, such as dopamine, which is involved in pleasure and reward, and noradrenaline which is involved in alertness. © 2016 Macmillan Publishers Limited
Laura Sanders For some people, fentanyl can be a life-saver, easing profound pain. But outside of a doctor’s office, the powerful opioid drug is also a covert killer. In the last several years, clandestine drugmakers have begun experimenting with this ingredient, baking it into drugs sold on the streets, most notably heroin. Fentanyl and closely related compounds have “literally invaded the entire heroin supply,” says medical toxicologist Lewis Nelson of New York University Langone Medical Center. Fentanyl is showing up in other drugs, too. In San Francisco’s Bay Area in March, high doses of fentanyl were laced into counterfeit versions of the pain pill Norco. In January, fentanyl was found in illegal pills sold as oxycodone in New Jersey. And in late 2015, fentanyl turned up in fake Xanax pills in California. This ubiquitous recipe-tinkering makes it impossible for users to know whether they’re about to take drugs mixed with fentanyl. And that uncertainty has proved deadly. Fentanyl-related deaths are rising sharply in multiple areas. National numbers are hard to come by, but in many regions around the United States, fentanyl-related fatalities have soared in recent years. Maryland is one of the hardest-hit states. From 2007 to 2012, the number of fentanyl-related deaths hovered around 30 per year. By 2015, that number had grown to 340. A similar rise is obvious in Connecticut, where in 2012, there were 14 fentanyl-related deaths. In 2015, that number was 188. |© Society for Science & the Public 2000 - 2016.
Angus Chen Once people realized that opioid drugs could cause addiction and deadly overdoses, they tried to use newer forms of opioids to treat the addiction to its parent. Morphine, about 10 times the strength of opium, was used to curb opium cravings in the early 19th century. Codeine, too, was touted as a nonaddictive drug for pain relief, as was heroin. Those attempts were doomed to failure because all opioid drugs interact with the brain in the same way. They dock to a specific neural receptor, the mu-opioid receptor, which controls the effects of pleasure, pain relief and need. Now scientists are trying to create opioid painkillers that give relief from pain without triggering the euphoria, dependence and life-threatening respiratory suppression that causes deadly overdoses. That wasn't thought possible until 2000, when a scientist named Laura Bohn found out something about a protein called beta-arrestin, which sticks to the opioid receptor when something like morphine activates it. When she gave morphine to mice that couldn't make beta-arrestin, they were still numb to pain, but a lot of the negative side effects of the drug were missing. They didn't build tolerance to the drug. At certain dosages, they had less withdrawal. Their breathing was more regular, and they weren't as constipated as normal mice on morphine. Before that experiment, scientists thought the mu-opioid receptor was a simple switch that flicked all the effects of opioids on or off together. Now it seems they could be untied. © 2016 npr
By Robin Wylie Scientists have been searching for a genetic explanation for athletic ability for decades. So far their efforts have focused largely on genes related to physical attributes, such as muscular function and aerobic efficiency. But geneticists have also started to investigate the neurologicalbasis behind what makes someone excel in sports—and new findings implicate dopamine, a neurotransmitter responsible for the feelings of reward and pleasure. Dopamine is also involved in a host of other mental functions, including the ability to deal with stress and endure pain. Consequently, the new research supports the idea that the mental—not just the physical—is what sets elite athletes above the rest. In an effort to piece together what makes a great athlete great, researchers at the University of Parma in Italy collected DNA from 50 elite athletes (ones who had achieved top scores at an Olympic Games or other international competition) and 100 nonprofessional athletes (ones who played sports regularly, but below competitive level). They then compared four genes across the two groups that had previously been suggested as linked to athletic ability: one related to muscle development, one involved with transporting dopamine in the brain, another that regulates levels of cerebral serotonin and one involved in breaking down neurotransmitters. The researchers found a significant genetic difference between the two groups in only one of the genes: the one involved in transporting dopamine. Two particular variants of this gene (called the dopamine active transporter, or DAT) were significantly more common among the elite athletes than in the control group. One variant was almost five times more prevalent in the elite group (occurring in 24 percent of the elites versus 5 percent of the rest); the other variant was approximately 1.7 times more prevalent (51 percent versus 30 percent). The results were published in Journal of Biosciences. © 2016 Scientific American