Biological Psychology Links

by Catherine de Lange FROM the relaxing effects of cannabis to the highs of LSD and ecstasy, illegal drugs are not generally associated with the lab bench. Now, for the first time in decades, that is starting to change. For almost 40 years, mainstream research has shied away from investigating the therapeutic benefits of drugs whose recreational use is prohibited by law. But a better understanding of how these drugs work in animal studies, and the advancement of brain-imaging techniques, has sparked a swathe of new research. What's more, clinical trials of MDMA (ecstasy), LSD and other psychoactive drugs are starting to yield some positive results. This could lead to a call for governments to take a new approach to the funding and regulation of research into the potential benefits of such chemicals. LSD was developed in the 1940s (see "The highs and lows of LSD") but by the 1970s it and many other drugs became classed as schedule 1 in many countries - described as "abuse" drugs with no accepted medical use. "Research on psychedelics was severely restricted and interest in the therapeutic use of these drugs faded," says Franz Vollenweider of the neuropsychopharmacology and brain-imaging unit at the Zurich University Hospital of Psychiatry, Switzerland. The classification of LSD as schedule 1 was a mistake born of "ignorance and taboo", says Amanda Feilding, director of the Beckley Foundation, a charitable trust that promotes investigation into consciousness and its modulation, based in Oxford, UK. © Copyright Reed Business Information Ltd.

By RICHARD A. FRIEDMAN, M.D. Of all the things that people do, few are as puzzling to psychiatrists as compulsive drug use. Sure, all drugs of abuse feel good — at least initially. But for most people, the euphoria doesn’t last. A patient of mine is all too typical. “I know this will sound strange,” he said, as I recall, “but cocaine doesn’t get me high any more and still I can’t stop.” When he first started using the drug, in his early 30s, my patient would go for days on a binge, hardly eating or drinking. The high was better than anything, even sex. Within several months, though, he had lost the euphoria — followed by his job. Only when his wife threatened to leave him did he finally seek treatment. When I met him, he told me that he would lose everything if he could not stop using cocaine. Well, I asked, what did he like about this drug, if it cost him so much and no longer made him feel good? He stared at me blankly. He had no clue. Neither did most psychiatrists, until recently. We understand the initial allure of recreational drugs pretty well. Whether it is cocaine, alcohol, opiates, you name it, drugs rapidly activate the brain’s reward system — a primitive neural circuit buried beneath the cortex — and release dopamine. This neurotransmitter, which is central to pleasure and desire, sends a message to the brain: This is an important experience that is worth remembering. Copyright 2010 The New York Times Company

Smoking marijuana does help relieve a certain amount of pain, a small but well-designed Canadian study has found. People who suffer chronic neuropathic or nerve pain from damage or dysfunction of the nervous system have few treatment options with varying degrees of effectiveness and side-effects. Neuropathic pain is caused by damage to nerves that don't repair, which can make the skin sensitive to a light touch. Cannabis pills have been shown to help treat some types of pain but the effects and risks from smoked cannabis were unclear. To find out more, Dr. Mark Ware, an assistant professor in family medicine and anesthesia at Montreal's McGill University, and his colleagues conducted a randomized controlled trial — the gold standard of medical research — of inhaled cannabis in 21 adults with chronic neuropathic pain. Investigators used three different strengths of the active drug — THC levels of 2.5 per cent, six per cent and 9.4 per cent, as well as a zero per cent placebo. "We found that 25 mg herbal cannabis with 9.4 per cent THC, administered as a single smoked inhalation three times daily for five days, significantly reduces average pain intensity compared with a zero per cent THC cannabis placebo in adult subjects with chronic post traumatic/post surgical neuropathic pain," the study's authors concluded in Monday's online issue of the Canadian Medical Association Journal. Study participants inhaled the 25-milligram dose through a pipe for five days and then took no marijuana for nine days. Then they rotated through the other doses of THC. © CBC 2010

By Nathan Seppa In case it isn’t already clear that amphetamine abuse is a bad idea, researchers now report that abusers face more than three times the risk of developing a tear in the aorta, the huge artery carrying blood out of the heart. Physicians consider such a tear an emergency with catastrophic potential. The new findings appear in the August American Heart Journal. An aortic tear, also called aortic dissection, brings on “the most horrible chest pain imaginable,” says David Waters, a cardiologist at San Francisco General Hospital and the University of California, San Francisco. “Patients say, ‘I think I’m going to die,’ and they’re right,” he says. Without treatment, the fatality rate is ultimately about 75 percent, according to the Merck Manual Online. In the new study, researchers scanned the medical records of nearly 31 million patients nationwide, ages 18 to 49, who were hospitalized between 1995 and 2007. Codes on these records showed that 3,116 had an aortic dissection. The researchers also took note of codes that revealed amphetamine abuse or dependence. Use of methamphetamines, an increasingly popular street drug, would show up in the codes as amphetamines. Amphetamine abusers faced 3.3 times the risk of developing a torn aorta that nonusers did, the data showed. Researchers calculated that amphetamine abuse or dependence accounted for slightly less than 1 percent of all aortic dissections in the database. © Society for Science & the Public 2000 - 2010

By LARRY O'HANLON Everyone looks better after you've tipped back a pint or two, and now we may know why. It turns out that alcohol dulls our ability to recognize cockeyed, asymmetrical faces, according to researchers who tested the idea on both sober and inebriated college students in England. To find out if alcohol interfered with the ability to distinguish faces where the left and right sides were uneven, he and his colleagues designed an experiment involving images of faces that were tinkered with to make them perfectly symmetrical or subtly asymmetrical. The results of the study were published by Halsey, Joerg Huber, Richard Bufton and A.C. Little in a recent issue of the journal Alcohol. "Over an evening Joerg, Richard and I went out to the university campus bars with a laptop and asked students to participate," Halsey said. Men appear to be less prone to losing this ability than women when drinking. This included students taking a quick breathalyzer test to confirm their alcohol consumption. The students were classified as either sober or intoxicated, then examined the images. © 2010 ABC News Internet Ventures.

By David Biello Ketamine—a powerful anesthetic for humans and animals that lists hallucinations among its side effects and therefore is often abused under the name Special K—delivers rapid relief to chronically depressed patients, and researchers may now have discovered why. In fact, the latest evidence reinforces the idea that the psychedelic drug could be the first new drug in decades to lift the fog of depression. "We were trying to figure out what ketamine was doing to produce this rapid response," which can take as little as two hours to begin to act, says neuroscientist Ron Duman of the Yale University School of Medicine. So Duman and his colleagues gave a small amount of ketamine (10 milligrams per kilogram of body weight) to rats and watched the drug literally transform the animals' brains. "Ketamine… can induce a rapid increase in connections in the brain, the synapses by which neurons interact and communicate with each other, " Duman says. "You can visually see this response that occurs in response to ketamine." More specifically, as the researchers report in the August 20 issue of Science, ketamine seems to stimulate a biochemical pathway in the brain (known as mTOR) to strengthen synapses in a rat's prefrontal cortex—the region of the brain associated with thinking and personality in humans. And the ketamine helped rats cope with the depression analog experience brought on by forcing the rodents to swim or exposing them to inescapable stress. "Preclinical and clinical studies show that repeated stress or depression can cause a decrease in connections and an atrophy of connections in the same region of the brain," Duman explains, noting that magnetic resonance imaging shows that some depressed patients have a smaller prefrontal cortex as a result. "Ketamine has the opposite effect and can oppose or reverse the effects of depression" for roughly seven days per dose. © 2010 Scientific American

By Ferris Jabr Dig through enough recent psychology research and you might walk away thinking that some scientists seem to have a gambling addiction. You would be half right: researchers turn to gambling again and again, but they are not in it to rack up money. Psychologists are interested in gambling as a powerful tool for investigating risk-taking, decision-making, and how the brain responds to personal gains and losses. Two recent gambling studies offer insights not only into general human behavior, but into the psychology of gambling itself—that is, how our minds work when we hit the casino or pull out our favorite deck of cards for an evening's entertainment with friends. The studies suggest that the best "poker face" is not a neutral expression, but a trustworthy one, and that even when we are merely spectators, our brains respond as though we have something tangible to win or lose. In a study published online July 21 in PLoS ONE, Wellesley College psychologist Erik Schlicht and his colleagues examined how our opponents' faces influence the way we bet in poker. Schlicht recruited 14 adult participants for the study, most of whom were novices that played fewer than 10 hours of poker a year. The experimenters asked the participants to sit down at computers and individually run though hundreds of scenarios in a simulated and highly simplified version of Texas hold 'em. On the computer screen, participants saw their two-card starting hand, any one of 100 digitally animated faces to represent a computer opponent, and two poker chips representing each player's bets. In the study's tweaked version of poker, the participants always bet 100 chips and the computer always bet 5,000 chips. © 2010 Scientific American

By NICHOLAS BAKALAR A new study suggests that a 50-year-old drug commonly used as an anesthetic for humans and animals — and abused, as the drug called Special K — may deliver almost instant relief in some of the most troublesome cases of bipolar depression. It has been known for several years that small doses of the drug, ketamine, can relieve major depression. But this study, done by researchers at the National Institute of Mental Health, is the first to demonstrate efficacy in patients with treatment-resistant bipolar depression. Indeed, the researchers said, the effect on this group appeared to be even stronger. Although the study was small, with just 18 patients, it was conducted under the highest standards for a drug study: it was randomized, placebo-controlled and double-blinded. In bipolar disorder, sometimes called manic-depressive illness, patients cycle between periods of elation and severe depression, and the depressive phase carries a high risk of suicide. It is commonly treated with mood stabilizers, including lithium, anticonvulsants and some antipsychotics, often in complex combinations. Both mania and depression usually improve on these drugs. But when the depression remains, it is notoriously difficult to treat, so a fast-acting medicine with lasting effects would have obvious advantages. Ketamine probably acts by limiting the action of one type of brain receptor that moves nerve signals between neurons. Copyright 2010 The New York Times Company

by Nazlie Latefi People who smoke pot can feel lost in time—for some, it's part of the draw. Now researchers may have figured out one reason why cannabinoids, the psychoactive compounds in marijuana and hashish, make people feel this way; they disrupt the body's internal clock. Sleeping, eating, and other activities are all part of a 24-hour physiological cycle known as the circadian rhythm. This internal clock is controlled by neurons in a region of the brain called the suprachiasmatic nucleus (SCN). The SCN normally uses light to reset the clock. That's what happens when you travel from one time zone to another. But absent any sensory input, SCN neurons will still maintain a circadian rhythm: People and animals kept in total darkness continue to eat and sleep at the usual times. Several years ago, researchers discovered that SCN neurons possess receptors for cannabinoids. In the new study, a team led by Yale University circadian biologist Anthony van den Pol tried to figure out what role these receptors play. The researchers housed 42 mice in total darkness for 2 weeks to synchronize their internal clocks. In this environment the animals cycled through active and inactive phases lasting about 12 hours each. After 2 weeks, the researchers shined a light into some of the cages shortly after the mice had entered their active phase. Because mice are nocturnal, they became active about 2 hours later in the day than did mice not exposed to light, a phenomenon called "phase delay." But mice given brain injections of cannabinoids before light exposure exhibited much less of a phase delay; they became active only 1 hour later than did animals not exposed to light. © 2010 American Association for the Advancement of Science.

By Katherine Harmon Binge-shoppers and serial daters might perpetually be living at the whim of their latest impulse, and now research is getting to the biological basis of their seemingly random behavior. "Individuals vary widely in their capacity to deliberate on the potential consequences of their choices before they act," note the authors of a new study on the impulsive tendency. "Highly impulsive people frequently make rash, destructive decisions." Impulsivity has long been linked to the neurotransmitter dopamine, which is involved in learning and reward. And a new model helps to illuminate the connection between the two. The work is described in a study published online July 29 in Science. A team of researchers led by Joshua Buckholtz, a PhD candidate in neuroscience at Vanderbilt University, proposed that people who were more impulsive might have less active dopamine receptors in their midbrain but their brains would be more likely to fire off large quantities of the neurotransmitter when stimulated. To verify their hypothesis, the researchers used PET scans to watch the brains of 32 healthy and psychiatrically normal test subjects ages 18 to 35 (who had no history of substance abuse) while they were taking a classic test to measure impulsivity. Before the first testing round, subjects had taken a placebo pill, but before the second, they were given an oral dose of amphetamine, which can stimulate the brain's reward pathways, mobilizing dopamine. © 2010 Scientific American

By Emma Wilkinson Health reporter, BBC News A combination pill of two drugs used to treat addiction may help people lose weight, say US researchers. The Lancet reports that Naltrexone, commonly used to treat alcoholics and heroin addicts, and the anti-smoking drug bupropion led to greater weight loss than diet and exercise alone. It is thought the treatment may help beat food cravings. However, one UK expert said he would like to see much higher weight loss for the drug to be used in clinics. Professor Nick Finer, an obesity expert from University College London (UCL), said the drug may prove more useful if researchers can better identify who would benefit. In the study, 1,700 overweight and obese adults were all offered a weight-loss programme with diet and exercise advice. Two-thirds were also given the combination treatment (in one of two doses) and a third were given a placebo, or dummy pill, to take twice a day. Only half completed the trial, which lasted a year. Overall those taking the treatment lost an average of 5% to 6% of their weight depending on the dose, compared with 1.3% in the placebo group. The researchers said if only those who completed the trial were included, weight loss was 8% of body weight for those on the anti-addiction drugs. The treatment was not without side effects which included nausea, headaches, constipation, dizziness, vomiting and a dry mouth. (C)BBC

Ecstasy may help boost therapy success in patients with post-traumatic stress disorder, say researchers. A small trial in 20 patients has shown use of the drug is safe and seems to improve the effects of psychotherapy. The US team has now gained approval for a larger study in military veterans, but stresses more research is needed to confirm the finding. It is thought the drug reduces fear enabling patients to get more out of their therapy sessions. Writing in the Journal of Psychopharmacology, the team said patients were selected on strict criteria - they had to have had post-traumatic stress disorder (PTSD) for many years and have failed with conventional treatments. Doctors also excluded those with a history of psychosis or addiction. In the trial, patients were offered two eight-hour psychotherapy sessions scheduled a few weeks apart, with 12 of them given a dose of ecstasy and eight a placebo. Two months later, 10 of the 12 patients given ecstasy responded to the treatment, the researchers said. In contrast, just two out of eight patients offered a placebo showed an improvement. BBC © MMX

By Bruce Bower Here’s some not-so-sobering news for party people, barhoppers and clubgoers. Individuals who inherit a particular gene variant that tweaks the brain’s reward system are especially likely to drink a lot of alcohol in the company of heavy-boozing peers. That’s the preliminary indication of a new study directed by psychology graduate student Helle Larsen of Radboud University Nijmegen in the Netherlands. Adults carrying at least one copy of a long version of the dopamine D4 receptor gene, dubbed DRD4, imbibed substantially more alcohol around a heavy-drinking peer than did others who lacked that gene variant, Larsen’s group reports in a paper published online July 7 in Psychological Science. “Carriers of the long gene may be more attuned to, and influenced by, another person’s heavy drinking than noncarriers are,” Larsen says. Her study provides the first evidence that a gene influences human alcohol use in social situations. Scientists have yet to decipher the precise brain effects of DRD4’s long form. Larsen hypothesizes that in the presence of heavy drinkers, the gene variant may increase dopamine activity in brain areas that amplify alcohol’s appeal as a rewarding social activity. © Society for Science & the Public 2000 - 2010

Mice might turn up their noses at alcohol, but not the prairie vole. This usually upstanding rodent, famous for mating for life and sharing pup-raising duties, apparently likes a stiff drink. “They not only drink alcohol, they prefer it over water,” Allison Anacker, a neuroscience graduate student at Oregon Health & Science University told The Oregonian. Anacker, working under behavioral neuroscience professor Andrey Ryabinin, was looking for a model organism to study some humans’ troubled relationship with alcohol. Mice and rats fail in this role–it’s unusual to find ones that want even a sip of the stuff. In a study published in Addiction Biology last month, Ryabinin’s team records the drunken misadventures of prairie voles. After chugging their preferred 6 percent alcohol drink (about the equivalent of beer), some thirsty voles shoved off parental responsibilities and even walked out on their mates. Though some drank responsibility, others drank to excess, stumbling away from the bar/spiked water bottle. The study suggests that like humans, the voles also make drinking buddies, seemingly encouraging each other to have another. When caged together, the voles appear to match one another drink for drink, a practice that apparently has nothing to do with who’s buying the next round.

By GINA KOLATA If you had to choose one public health problem to attack, which would it be: teenage smoking or childhood obesity? To answer that question, you might want to pose another. Who will have the harder road in life, or indeed the longer one: the teenage puffer or the chubby child? Pitting smoking against obesity is tricky because it can mean comparing apples and bonbons, but there is some suggestion that a kind of weird zero-sum game is actually going on. And some smoking opponents fear that a choice has been made — with obesity the winner, quite possibly for the wrong reasons. “Obesity is the new kid on the block, relatively speaking,” said Kenneth E. Warner, dean of the University of Michigan’s school of public health. “Tobacco is old news.” When it comes to smoking, said Stanton A. Glantz, director of the University of California at San Francisco’s Center for Tobacco Control Research and Education, “we really haven’t had anyone pushing it to the top of the agenda.” That is a problem. “It’s not that I am for obesity,” he said, but he finds it less than encouraging, for example, that the hugely influential Robert Wood Johnson Foundation is pulling back from its anti-smoking efforts while directing its money and resources to preventing childhood obesity. Then there is Michelle Obama’s campaign, Let’s Move, to prevent childhood obesity. And in May, the White House Task Force on Childhood Obesity announced its goal — reduce the rate of childhood obesity, now 17 percent, to 5 percent by 2030. Copyright 2010 The New York Times Company

By Tina Hesman Saey Little things can make a big difference in the brain. Case in point: A tiny snippet of RNA may help guard cocaine-using rats against addiction to the drug, a new study shows. The minuscule molecular guard is a hairpin-shaped piece of RNA known as a microRNA. Raising levels of a microRNA called miR-212 in the brains of cocaine-using rats led the animals to take less of the drug than rats with normal microRNA levels, researchers report in the July 8 Nature. Similarly, blocking the microRNA’s action increased the rats’ cocaine use. If the results hold true in people, researchers may be able to develop new therapies for treating addiction to cocaine and other drugs of abuse. “Once you get out of whack, this is something that might help bring you back,” says Yale neuroscientist Marina Picciotto, who was not involved in the study. It’s unlikely that the research will lead to gene therapy to raise levels of microRNAs in people’s brains. But small-molecule drugs that mimic the microRNA’s action might be helpful. Just 21 to 23 RNA units long, microRNAs are major regulatory molecules (SN: 3/1/08, p. 136) that govern part of the process by which instructions contained in DNA are transformed into proteins. The molecules generally block protein production. So it was a surprise to find levels of a protein called CREB increase with rising levels of miR-212, says Paul Kenny, a neuroscientist at the Scripps Research Institute in Jupiter, Fla. © Society for Science & the Public 2000 - 2010

By Christine Soares A restful night’s sleep might make a cup of coffee less of a desperate need first thing in the morning. But pharmaceutical companies are looking into whether the latest pills to promise sound, natural sleep could also play an active role in overcoming even the most powerful addictions. The new sleep aids block the activity of brain peptides called orexins. These tiny proteins keep us wide awake and attentive during the day, and they also govern some stimulating effects of addictive drugs. Orexins do not cause addiction or relapse directly, but neither happens without the peptides’ participation. The intriguing connection between sleep and addiction has long been observed in people who suffer from narcolepsy—a disorder that causes sudden-onset sleep. Although narcoleptics were sometimes treated with potent amphetamines to help them stay awake, they never became addicted to the drugs. By 1998 genetic detective work had traced the cause of narcolepsy to mutations in the genes for orexins or their receptors—discoveries that revealed both the peptides’ existence and their critical role in keeping the brain awake. Efforts to turn those insights into novel insomnia treatments have led to several compounds that are now in late-stage clinical trials. The same companies developing these sleep aids are also investigat-ing orexins’ role in addiction through research in animals. In a recent study Davide Quarta and his co-workers at GlaxoSmithKline Medicines Research Center in Verona, Italy, confirmed that when the company’s experimental orexin blocker SB-334867 was administered to rats along with amphetamine their brains released less dopamine and they became less sensitized to the stimulant than controls did, even with repeated doses. Sensitized neurons grow extra receptors for the craved drug, demanding more of it to achieve stimulation, thereby fueling a cycle that leads to addiction. © 2010 Scientific American,

By Nathan Seppa In science’s struggle to keep up with life on the streets, smoking cannabis for medical purposes stands as Exhibit A. Medical use of cannabis has taken on momentum of its own, surging ahead of scientists’ ability to measure the drug’s benefits. The pace has been a little too quick for some, who see medicinal joints as a punch line, a ruse to free up access to a recreational drug. But while the medical marijuana movement has been generating political news, some researchers have been quietly moving in new directions — testing cannabis and its derivatives against a host of diseases. The scientific literature now brims with potential uses for cannabis that extend beyond its well-known abilities to fend off nausea and block pain in people with cancer and AIDS. Cannabis derivatives may combat multiple sclerosis, Crohn’s disease and other inflammatory conditions, the new research finds. Cannabis may even kill cancerous tumors. Many in the scientific community are now keen to see if this potential will be fulfilled, but they haven’t always been. Pharmacologist Roger Pertwee of the University of Aberdeen in Scotland recalls attending scientific conferences 30 years ago, eager to present his latest findings on the therapeutic effects of cannabis. It was a hard sell. “Our talks would be scheduled at the end of the day, and our posters would be stuck in the corner somewhere,” he says. “That’s all changed.” © Society for Science & the Public 2000 - 2010

By Joshua DavisPage 1 of 4 next » Bryan Peterson sat on the toilet in the master bathroom of his Palm Springs, California, home and tried to find a vein between his knuckles. It was virgin territory - he had never injected himself in a spot he couldn't cover up. But now that he'd been fired from his job in the estimating department of a construction company, he didn't care about covering up anymore. Plus, he couldn't find a vein in his arms, which were swollen with pools of pus and heroin. The thin, translucent blue veins snaking across the back of his hand filled him with joy. He slid the needle in beside his knucklebone. It hurt. Two weeks later, he'd blown out all the tiny veins in his hands and feet. Unable to absorb all that fluid, they burst, adding more blood to the already toxic mix festering under his skin. He started plunging the needle deep into his bicep, shooting heroin directly into the muscle. The drug seemed to sizzle as he injected it. Peterson was 36 and had been addicted for three years. Before that, he was just a normal working guy who liked to play guitar in a local rock band. Over the past two and a half years, he'd tried to kick his habit cold turkey three times and attended a few Narcotics Anonymous meetings. He'd make it through the first step - acknowledging that he was powerless over his addiction - and that was it. Even with the group therapy sessions and encouragement from fellow addicts, he couldn't stay clean for more than 10 days. The withdrawal pains were so unbearable, he fantasized about cutting off his legs to stop the aching. And when the pain subsided for a moment, he was racked with nausea and diarrhea. His body was holding him hostage: Either take the drug, it said, or you'll feel so much pain you'll want to die. Then one day Peterson was talking to a friend who mentioned a miracle treatment gaining popularity in the Los Angeles area. © Copyright© 1993-2005/ © Copyright 2005, Lycos, Inc.

Just several doses of the drug Ecstasy, taken in the course of an evening, may increase a person’s risk for developing certain neurological disorders later in life, suggests a new study on monkey and baboons. The findings appear in the journal Science, published by the American Association for the Advancement of Science. In both primate species, two or three sequential doses of Ecstasy, or “MDMA,”—equivalent to what young adults typically take during an all-night dance party—caused more brain cell damage than was previously expected, the authors report. The newly-identified type of damage occurs in dopaminergic neurons, a set of nerve cells in the brain that help control movement, as well as emotional and cognitive responses, and the ability to feel pleasure. “The most worrisome implication [of the findings] is that, as a consequence of MDMA-induced dopaminergic injury, young adults may be increasing their risk for developing Parkinsonism, a condition with symptoms similar to Parkinson’s disease, as they get older” according to lead author George A. Ricaurte of the Johns Hopkins University School of Medicine.

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