Chapter 4. The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
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By DOUGLAS QUENQUA Why are some people able to use cocaine without becoming addicted? A new study suggests the answer may lie in the shape of their brains. Sporadic cocaine users tend to have a larger frontal lobe, a region associated with self-control, while cocaine addicts are more likely to have small frontal lobes, according to the study, which was published in the journal Biological Psychiatry. The scientists, at the University of Cambridge, collected brain scans and personality tests from people who had used cocaine over several years — some addicted, some not. While the nonaddicts shared a penchant for risk-taking behavior, the increased gray matter seemed to help them resist addiction by exerting more self-control and making more advantageous decisions. “They could take it or leave it,” said Karen Ersche, the lead author. The researchers believe the differences in brain shape predated the drug use rather than occurring as a result of it. Dr. Ersche said the findings reinforced the idea, now popular among addiction experts, that addiction depends less on character and more on biological makeup. “It’s not the Nancy Reagan approach, just say no or one day or another you will get addicted,” she said. “How the drugs work and how much you are at risk depends on what type of person you are and what type of brain you have.” © 2013 The New York Times Company
Keyword: Drug Abuse
Link ID: 17765 - Posted: 02.05.2013
By melody Yesterday, Alan Schwarz, reporting for the Sunday edition of The New York Times, published an alarmist piece on Adderall abuse. The story chronicles the short life of Richard Fee, a popular young pre-med who, after dabbling in fast-acting stimulants in college, faked his way into an ADHD diagnosis and, within months of filling his first prescription, began heavily abusing the drug, leading to severe addiction and psychosis, and ultimately to his suicide, two years ago, at the age of twenty-four. The story of Richard Fee is a tragic one, and one that highlights both the dangers of prescribing ADHD drugs to neurotypical adults and some of the problems endemic in psychiatric diagnosis. Regrettably, the reporter seems to believe that these problems are somehow specific to amphetamines, signaling “widespread failings in the system through which five million Americans take medication for ADHD”, and that Richard’s harrowing case, while undoubtedly rare, “underscores aspects of ADHD treatment that are mishandled every day with countless patients”. Schwarz is a Pulitzer-prize nominated journalist, renowned for exposing the danger of concussive head injuries in football. More recently, he has cast that same critical eye on how attention-deficit disorder is diagnosed. The question is – to what end? Presumably – in the case of this story – to tighten the restrictions on how amphetamines are prescribed to adults, and to ward against the kind of negligence and lack of oversight that characterized Richard’s case. But there is a delicate balance to be struck here between serving the needs of the ADHD population, many of whom benefit tremendously from the regulated use of stimulants, and potential drug addicts, like Richard. It is also far from clear, given the nature of psychiatric nosology, that there are any surefire ways of stopping con-artists and addicts from gaming the system. © 2013 Scientific American
By ALAN SCHWARZ VIRGINIA BEACH — Every morning on her way to work, Kathy Fee holds her breath as she drives past the squat brick building that houses Dominion Psychiatric Associates. It was there that her son, Richard, visited a doctor and received prescriptions for Adderall, an amphetamine-based medication for attention deficit hyperactivity disorder. It was in the parking lot that she insisted to Richard that he did not have A.D.H.D., not as a child and not now as a 24-year-old college graduate, and that he was getting dangerously addicted to the medication. It was inside the building that her husband, Rick, implored Richard’s doctor to stop prescribing him Adderall, warning, “You’re going to kill him.” It was where, after becoming violently delusional and spending a week in a psychiatric hospital in 2011, Richard met with his doctor and received prescriptions for 90 more days of Adderall. He hanged himself in his bedroom closet two weeks after they expired. The story of Richard Fee, an athletic, personable college class president and aspiring medical student, highlights widespread failings in the system through which five million Americans take medication for A.D.H.D., doctors and other experts said. Medications like Adderall can markedly improve the lives of children and others with the disorder. But the tunnel-like focus the medicines provide has led growing numbers of teenagers and young adults to fake symptoms to obtain steady prescriptions for highly addictive medications that carry serious psychological dangers. These efforts are facilitated by a segment of doctors who skip established diagnostic procedures, renew prescriptions reflexively and spend too little time with patients to accurately monitor side effects. © 2013 The New York Times Company
By Tanya Lewis and LiveScience Drug cravings can be brought on by many factors, such as the sight of drugs, drug availability and lack of self-control. Now, researchers have uncovered some of the neural mechanisms involved in cigarette craving. Two brain areas, the orbitofrontal cortex and the prefrontal cortex, interact to turn cravings on or off depending on whether drugs are available, the study reports today (Jan. 28) in the journal the Proceedings of the National Academy of Sciences. The researchers scanned the brains of 10 moderate-to-heavy smokers using functional magnetic resonance imaging (fMRI), which measures brain activity by changes in blood flow. Researchers measured activity while the participants watched video clips of people smoking as well as neutral videos. Before viewing, some subjects were told cigarettes would be available immediately after the experiment, while others were told they would have to wait 4 hours before lighting up. When participants watched the smoking videos, their brains showed increased activity in the medial orbitofrontal cortex, a brain area that assigns value to a behavior. When the cigarettes were available immediately as opposed to hours later, smokers reported greater cravings and their brains showed more activity in the dorsolateral prefrontal cortex. The researchers hypothesize that this area modulates value. In other words, it can turns up or down the "value level" of cigarettes (or other rewards) in the first area, the medial orbitofrontal cortex. The results show that addiction involves a brain circuit important for self-control and decision-making. © 2013 Scientific American,
Keyword: Drug Abuse
Link ID: 17740 - Posted: 01.30.2013
By Ashutosh Jogalekar G Protein-Coupled Receptors (GPCRs) are the messengers of the human body, key proteins whose ubiquitous importance was validated by the 2012 Nobel Prize in chemistry. As I mentioned in a post written after the announcement of the prize, GPCRs are involved in virtually every physiological process you can think of, from sensing colors, flavors and smells to the action of neurotransmitters and hormones. In addition they are of enormous commercial importance, with something like 30% of marketed drugs binding to these proteins and regulating their function. These drugs include everything from antidepressants to blood-pressure lowering medications. But GPCRs are also notoriously hard to study. They are hard to isolate from their protective lipid cell membrane, hard to crystallize and hard to coax into giving up their molecular secrets. One reason the Nobel Prize was awarded was because the two researchers – Robert Lefkowitz and Brian Kobilka – perfected techniques to isolate, stabilize, crystallize and study these complex proteins. But there’s still a long way to go. There are almost 800 GPCRs, out of which ‘only’ 16 have been crystallized during the past decade or so. In addition all the studied GPCRs are from the so-called Class A family. There’s still five classes left to decipher, and these contain many important receptors including the ones involved in smell. Clearly it’s going to be a long time before we can get a handle on the majority of these important proteins. Fortunately there’s something important that GPCR researchers have realized; it’s the fact that many of these GPCRs have amino acid sequences that are similar. If you know what experimental conditions work for one protein, perhaps you can use the same conditions for another similar GPCR. © 2013 Scientific American
Link ID: 17692 - Posted: 01.17.2013
By Ashutosh Jogalekar As marijuana is being legalized in Washington and Colorado states, its proliferation and use raise legitimate issues regarding its dose-dependent and long-term effects. One key question is whether pot leads to cognitive decline and a lowering of IQ, especially if its consumption is started at an early age. Answering this question is important for users, families and policy makers to have a realistic idea of personal and legal policies regarding widespread cannabis use. Last year, Madeline Meier and her group from Duke University reported results from the so-called Dunedin study which tracked a group of 1037 people from their birth to age 38. These volunteers’ pot smoking histories were monitored at periodic intervals from age 18 onwards. The study found a troubling decline of IQ and cognitive abilities among regular pot smokers, especially those whose habit kicked in during their teens. No explicit causal relationship was assigned between the two facts, but the correlation was positive and significant. The study naturally raised a lot of questions regarding the wisdom of early pot use, especially in light of its current legalization in two states. Now a study by Ole Rogeberg from the Ragnar Frisch Center for Research in Norway has called this study into question, both for its methodology and its conclusions. The first thing to realize about any such study, even if you don’t know the details, is that there are going to be several confounding socioeconomic factors in assessing any relationship between cannabis use and IQ. Medicine and psychology are not exact sciences, and following a large sample of people for 38 years and assessing correlation – let alone causation – between any two factors is going to be confounded by a large number of other correlated and uncorrelated variables in an inherently uncontrolled experiment. © 2013 Scientific American,
People taking opioid painkillers face higher risks of car accidents even at low doses, say Ontario researchers who want patients to be warned that the drugs can decrease alertness. Knowing that use of opioids like oxycodone, codeine and morphine has increased in North America and that driver simulation studies suggest that the drugs hinder alertness and act as a sedative, researchers at Toronto's Institute for Clinical Evaluative Sciences looked at emergency department visits among adults treated with opoids. They defined road trauma as motor vehicle crashes that required a visit to emergency. The increased risk for drivers taking opioids started with the lowest doses equivalent to 20 milligrams of morphine. The increased risk for drivers taking opioids started with the lowest doses equivalent to 20 milligrams of morphine. (iStock) Compared with very low doses of opioids, drivers prescribed low doses such as 20 milligrams of morphine showed 21 per cent increased odds of car accidents which rose to 42 per cent for those prescribed high doses, Tara Gomes and her co-authors reported in Monday's issue of the JAMA Internal Medicine, formerly Archives of Internal Medicine. "What was surprising to us was this increased risk started even at what many people consider to be fairly low doses of opioids," Gomes said in an interview. © CBC 2013
Arran Frood Cannabis rots your brain — or does it? Last year, a paper published in Proceedings of the National Academy of Sciences (PNAS)1 suggested that people who used cannabis heavily as teenagers saw their IQs fall by middle age. But a study published today2 — also in PNAS — says that factors unrelated to cannabis use are to blame for the effect. Nature explores the competing claims. What other factors might cause the decline in IQ? Ole Røgeberg, a labour economist at the Ragnar Frisch Centre for Economic Research in Oslo and the author of the latest paper, ran simulations which showed that confounding factors associated with socioeconomic status could explain the earlier result. For example, poorer people have reduced access to schooling, irrespective of cannabis use. Possibly. The data used in the original paper came from the Dunedin Study, a research project in which a group of slightly more than 1,000 people born in New Zealand in 1972–73 have been tracked from birth to age 38 and beyond. As with all such birth-cohort epidemiological studies (also called longitudinal studies), there is a risk of inferring causal links from observed associations between one factor and another. Past research on the Dunedin cohort shows3 that individuals from backgrounds with low socioeconomic status are more likely than others to begin smoking cannabis during adolescence, and are more likely to progress from use to dependence. Røgeberg says that these effects, combined with reduced access to schooling, can generate a correlation between cannabis use and IQ change. © 2013 Nature Publishing Group
by Sara Reardon In the dark expanses of the Sonoran desert in the US, a terrifying creature stalks the night, searching for fresh meat. Anything will do: crickets, rodents, tarantulas – the nastier the better. Even the poisonous scorpion cannot escape the savage monster's little pink paws. It fights bravely, stinging its attacker on the nose. To no avail. The mouse ignores the painful venom and cruelly breaks the scorpion's tail by pummelling it into the ground, then bites its head and feasts on its flesh. Throwing its head back, the murderous animal howls at the moon. No, it's not the mythical Chupacabra. It's the southern grasshopper mouse (Onychomys torridus), the only carnivorous mouse in North America. Its unique biology and resistance to scorpion venom may one day help researchers treat human pain disorders. But for now, it's just after blood. Natural born killer From the day they are born, grasshopper mice are natural killers. Even pups born and raised in captivity quickly figure out how to take down prey much larger than themselves. They appear to learn some of their aggression from their fathers: pups raised with two parents are more likely to bully other mice and attack insects more viciously than those raised by single mothers (Behavioral Biology, DOI: 10.1016/S0091-6773(77)91933-2) © Copyright Reed Business Information Ltd.
By DAN FROSCH ALBUQUERQUE — It has been almost four decades since Betty Jo Lopez started using heroin. Her face gray and wizened well beyond her 59 years, Ms. Lopez would almost certainly still be addicted, if not for the fact that she is locked away in jail, not to mention the cup of pinkish liquid she downs every morning. “It’s the only thing that allows me to live a normal life,” Ms. Lopez said of the concoction, which contains methadone, a drug used to treat opiate dependence. “These nurses that give it to me, they’re like my guardian angels.” For the last six years, the Metropolitan Detention Center, New Mexico’s largest jail, has been administering methadone to inmates with drug addictions, one of a small number of jails and prisons around the country that do so. At this vast complex, sprawled out among the mesas west of downtown Albuquerque, any inmate who was enrolled at a methadone clinic just before being arrested can get the drug behind bars. Pregnant inmates addicted to heroin are also eligible. Here in New Mexico, which has long been plagued by one of the nation’s worst heroin scourges, there is no shortage of participants — hundreds each year — who have gone through the program. © 2013 The New York Times Company
Keyword: Drug Abuse
Link ID: 17654 - Posted: 01.07.2013
By Lisa Raffensperger Among the many unpleasant side effects of chemotherapy treatment, researchers have just confirmed another: chemo brain. The term refers to the mental fog that chemotherapy patients report feeling during and after treatment. According to Jame Abraham, a professor at West Virginia University, about a quarter of patients undergoing chemotherapy have trouble focusing, processing numbers, and using short-term memory. A recent study points to the cause. The study relied on PET (positron emission tomography) brain scanning to examine brain blood flow, a marker for brain activity. Abraham and colleagues scanned the brains of 128 breast cancer patients before chemotherapy began and then 6 months later. The results showed a significant decrease in activity in regions responsible for memory, attention, planning and prioritizing. The findings aren’t immediately useful for treating or preventing the condition of chemo brain, but the hard and fast evidence may comfort those experiencing chemo-related forgetfulness. And luckily chemo brain is almost always temporary: patients’ mental processing generally returns to normal within a year or two after chemotherapy treatment ends.
Cannabis makes pain more bearable rather than actually reducing it, a study from the University of Oxford suggests. Using brain imaging, researchers found that the psychoactive ingredient in cannabis reduced activity in a part of the brain linked to emotional aspects of pain. But the effect on the pain experienced varied greatly, they said. The researchers' findings are published in the journal Pain. The Oxford researchers recruited 12 healthy men to take part in their small study. Participants were given either a 15mg tablet of THC (delta-9-tetrahydrocannabinol) - the ingredient that is responsible for the high - or a placebo. The volunteers then had a cream rubbed into the skin of one leg to induce pain, which was either a dummy cream or a cream that contained chilli - which caused a burning and painful sensation. Each participant had four MRI scans which revealed how their brain activity changed when their perception of the pain reduced. Dr Michael Lee, lead study author from Oxford University's Centre for Functional Magnetic Resonance Imaging of the Brain, said: "We found that with THC, on average people didn't report any change in the burn, but the pain bothered them less." BBC © 2012
by Karl Gruber Cigarettes leave you with more than a smoky scent on your clothes and fingernails. A new study has found strong evidence that tobacco use can chemically modify and affect the activity of genes known to increase the risk of developing cancer. The finding may give researchers a new tool to assess cancer risk among people who smoke. DNA isn't destiny. Chemical compounds that affect the functioning of genes can bind to our genetic material, turning certain genes on or off. These so-called epigenetic modifications can influence a variety of traits, such as obesity and sexual preference. Scientists have even identified specific epigenetic patterns on the genes of people who smoke. None of the modified genes has a direct link to cancer, however, making it unclear whether these chemical alterations increase the risk of developing the disease. In the new study, published in Human Molecular Genetics, researchers analyzed epigenetic signatures in blood cells from 374 individuals enrolled in the European Prospective Investigation into Cancer and Nutrition. EPIC, as it's known, is a massive study aimed at linking diet, lifestyle, and environmental factors to the incidence of cancer and other chronic diseases. Half of the group consisted of people who went on to develop colon or breast cancer 5 to 7 years after first joining the study, whereas the other half remained healthy. © 2010 American Association for the Advancement of Science.
By ADAM NAGOURNEY LOS ANGELES — Let Colorado and Washington be the marijuana trailblazers. Let them struggle with the messy details of what it means to actually legalize the drug. Marijuana is, as a practical matter, already legal in much of California. A man panhandled for pot recently on the boardwalk in Venice Beach, Calif., where a variety of marijuana-themed items are for sale. No matter that its recreational use remains technically against the law. Marijuana has, in many parts of this state, become the equivalent of a beer in a paper bag on the streets of Greenwich Village. It is losing whatever stigma it ever had and still has in many parts of the country, including New York City, where the kind of open marijuana use that is common here would attract the attention of any passing law officer. “It’s shocking, from my perspective, the number of people that we all know who are recreational marijuana users,” said Gavin Newsom, the lieutenant governor. “These are incredibly upstanding citizens: Leaders in our community, and exceptional people. Increasingly, people are willing to share how they use it and not be ashamed of it.” Marijuana can be smelled in suburban backyards in neighborhoods from Hollywood to Topanga Canyon as dusk falls — what in other places is known as the cocktail hour — often wafting in from three sides. In some homes in Beverly Hills and San Francisco, it is offered at the start of a dinner party with the customary ease of a host offering a chilled Bombay Sapphire martini. © 2012 The New York Times Company
By Scicurious Depression is a disease with a difficult set of symptoms. Not only are the symptoms difficult to describe (how do you really describe anhedonia, before you know the word for it?), symptoms of depression manifest in different ways for different people. One person will eat more, sleep all the time, move slowly. Another will eat almost nothing, never sleep, and be irritable and nervous. They are both depressed. The only universal symptom is the feeling of…depression, and the need for successful treatment. Treatments which often take several weeks to work, are often ineffective, and which come with a host of side effects. So I was particularly intrigued when Nature published two papers this week looking at the role of dopamine in depressive-like behavior. What I particularly like is that these two papers have somewhat opposite results, due to different behavioral methods, something which I think highlights some of the problems associated with studying depression. Ed Yong covered both of the studies together fabulously over at Not Exactly Rocket Science, but I’d like to look at them both separately, to take a deeper look at each one, see what they’ve achieved, and what other questions they raise. Today we are on the second of the two papers, one which has a similar angle to the first paper, but an entirely different result. Yesterday’s paper looked at how changes in dopamine cell firing from the ventral tegmental area (which projects to areas like the prefrontal cortex and the nucleus accumbens) can impact depressive-like behaviors in mice and rats. Today’s paper looks at the ventral tegmental area as well, but instead of cutting on or turning “off” cell firing, the authors of this study looked at different types of neuronal activity, and the effects in socially defeated mice. © 2012 Scientific American
Link ID: 17621 - Posted: 12.19.2012
By Judy Stone We’ve touched on some of the many disturbing things that happened during the clinical trial on which Dan Markingson committed suicide. In my first post, I asked how a psychotic, homicidal patient who was involuntarily hospitalized in a psychiatric hospital could give an informed consent for participation in a clinical trial. There appeared to have been abuse of a vulnerable patient and extraordinary coercion—participate in this trial or be committed to a psych hospital seems to have been the bottom line. In my second post, we looked at investigator responsibilities, delegation of authority, and Good Clinical Practice tenets, all of which were violated with no consequences. Now we turn to the need to disclose conflicts of interest (COI), again a basic clinical research ethics principle that was violated. There are so many obvious conflicts of interest that it is hard to know quite where to start. The most obvious and egregious COI was that shown by Dr. Stephen Olson, who acted as both Dan Markingson’s treating physician and as Principle Investigator on the CAFÉ study. As Dr. Harrison Pope, a Harvard expert, concluded in his testimony, Olson “failed to meet the standards for good clinical practice both as a principal investigator and as the study physician for Mr. Markingson.” He failed his ethical responsibilities to Dan. © 2012 Scientific American
Link ID: 17619 - Posted: 12.19.2012
By Anna-Marie Lever Health reporter, BBC News Smoking may worsen a hangover after drinking heavily, a US study reports, although the reason why is unclear. Researchers asked 113 US students to keep a diary for eight weeks, recording their drinking and smoking habits and any hangover symptoms. When they drank heavily - around six cans of beer an hour - those who also smoked suffered a worse hangover. Addiction charities hope this study may motivate smokers to cut down over the festive season. The study's findings are reported in the Journal of Studies on Alcohol and Drugs. One of the paper's authors, Dr Damaris Rohsenow, from the Centre for Alcohol and Addiction Studies at Brown University said: "At the same number of drinks, people who smoke more that day are more likely to have a hangover and have more intense hangovers. "And smoking itself was linked to an increased risk of hangover compared with not smoking at all. That raises the likelihood that there is some direct effect of tobacco smoking on hangovers." A spokesperson from the charity Action on Addiction called for further research, saying the interaction between alcohol and smoking "is complex". "We welcome evidence-based research in any areas which can be used assist with developing preventative campaigns, particularly for young people who are often experimenting in their teenage years with alcohol, drugs and cigarettes. BBC © 2012
Keyword: Drug Abuse
Link ID: 17587 - Posted: 12.10.2012
Naomi Piercey, Women's Health A throbbing headache isn't the only side effect of overloading on alcohol. Chug too many cocktails and you may be putting your actual gray matter at risk. According to a new study from Rutgers University, consumption of alcohol, from moderate-level drinking to binge drinking (drinking less during the week and more on the weekends), can decrease the creation of adult brain cells by as much as 40 percent. In this study researchers examined the brain cell development of rodents after consuming alcohol. When the blood alcohol level of the rats reached 0.08 percent--the legal driving limit--researchers found the number of nerve cells in the hippocampus of the brain were reduced by nearly 40 percent compared to those in the sober group. The hippocampus--where new neurons are made--is a section of the brain associated with long-term memory and some new types of learning. This stage of intoxication is equivalent to approximately 3-4 drinks for women and five drinks for men. "The purpose of the study was to underscore the long term effects of alcohol exposure," says Tracey J. Shors, PhD, professor of behavioral and systems neuroscience in the department of psychology at Rutgers University, who helped conduct the study. "It may not be detrimental to have one or two days of alcohol exposure, but week after week, you will have many fewer neurons in your brain," she said. © 2012 NBCNews.com
Scientists believe some people have a gene that hard-wires them for binge drinking by boosting levels of a happy brain chemical triggered by alcohol. The gene - RASGRF-2 - is one of many already suggested to be linked with problem drinking, PNAS journal reports. The King's College London team found animals lacking the gene had far less desire for alcohol than those with it. Brain scans of 663 teenage boys showed those with a version of the gene had heightened dopamine responses in tests. During a task designed to make them anticipate a reward, these 14-year-old boys had more activity in a part of the brain called the ventral striatum which is known to be involved in dopamine release. When the researchers later contacted the same boys at the age of 16 and asked them about their drinking habits, they found the boys with the 'culprit' variation on the RASGRF-2 gene drank more frequently. The NHS definition of binge drinking is drinking heavily in a short space of time to get drunk or feel the effects of alcohol. Lead researcher Prof Gunter Schumann explained that while this is not proof that the gene causes binge drinking, and it is likely that many environment factors and other genes are also involved, the findings help shed light on why some people appear to be vulnerable to the allure of alcohol. BBC © 2012
By James Gallagher Health and science reporter, BBC News The possibility that autism is linked to traffic pollution has been raised by researchers in California. Their study of more than 500 children said those exposed to high levels of pollution were three times more likely to have autism than children who grew up with cleaner air. However, other researchers said traffic was a "very unlikely" and unconvincing explanation for autism. The findings were presented in the Archives of General Psychiatry journal. Data from the US Environmental Protection Agency were used to work out levels of pollution for addresses in California. This was used to compare exposure to pollution, in the womb and during the first year of life, in 279 children with autism and 245 without. The researchers from the University of Southern California said children in homes exposed to the most pollution "were three times as likely to have autism compared with children residing in homes with the lowest levels of exposure". BBC © 2012