Category: Drugs

Abnormal brain structures hint at poor self-control and vulnerability to drug addiction

By Ed Yong | February 2, 2012 2:00 pm

Our lives are full of instances where have to hold ourselves back. We stop ourselves from eating that tempting slice of cake to avoid putting on weight. We bite our tongues to avoid insulting our friends. We slam on the brakes to avoid killing a pedestrian.  To quote Yoda: “Control! Control! You must learn control.”

People with drug problems clearly have a problem with this. Their ability to resist their own impulses falters at the promise of the next hit. Now, scientists are starting to understand the changes in the brain that underlie these problems.

Karen Ersche from the University of Cambridge found that drug users have abnormalities in parts of the brain that are important for inhibiting unwanted actions. These same anomalies even exist in the brains of their siblings, who don’t have any drug problems themselves. They could act as a marker for people who are vulnerable to addiction. “Our findings provide further evidence for drug addiction being a brain-based disorder,” says Ersche.

This is far from the first study to examine the brains of drug users. But it’s never been clear whether changes in such brains were caused by drugs, or made people vulnerable to addiction in the first place. Both are possible. Stimulant drugs typically act on parts of the brain involved in motivation, and interfere with those that inhibit our impulses. But these effects could be worse if these neural circuits are already weak.

To separate these possibilities, Ersche studied 50 volunteers who had a long history of drug abuse. She compared them to their siblings, who had no drug problems, and to 50 unrelated volunteers who were also drugs-free. All of the recruits sat through a stop-signal test – a commonly used way of measuring self-control. Volunteers have to respond as quickly as possible to a stream of on-screen symbols – say, by pressing a key. If they hear a tone, which pops up unpredictably, they have to restrain themselves. (Try it yourself here).

The drug users struggled with the test compared to the unrelated volunteers, and needed more time to withhold their responses. Critically, their siblings fared just as badly, even though they weren’t using drugs. This strongly suggests that poor self-control isn’t the result of the drugs themselves, but of a shared (and probably inherited) vulnerability. “If you have brain with existing problems, the drugs have an easier play. It’s easier for them to take over,” says Ersche.

Ersche found the same pattern when she looked at her volunteers’ brains. First, she focused on their white matter tracts – the fibres that transmit signals from one area to another. These are the brain’s communications network, and their density indicates how good different areas are at shuttling information between them.

These connections were weaker among both the drug users and their relatives, compared to the healthy unrelated volunteers. The fibres were particularly sparse around the right inferior frontal cortex (IFC), an area involved in controlling our inhibitions. These abnormalities were linked to the volunteers’s scores on the stop-signal test – the weaker the connections, the slower their reaction times. With its communication lines weakened, the IFC was less able to exert its suppressive influence.

The siblings also shared anomalies in the size of some brain areas. Their putamens and medial temporal lobes were bigger, and their posterior insulas were smaller. All of these areas have been implicated in learning and memory. “This may be an indicator of an enhanced propensity to form habits,” says Ersche.

From these results, a cohesive picture emerges. Some parts of the brain are larger, increasing the attractiveness of potential rewards, and the odds of habitual, addictive behaviour. The IFC, which would normally suppress such desires, has less of a say because the fibres connecting it to other parts of the brain are weaker. It’s like having a mob of reckless friends who are egging each other on over fast broadband connections, while their sensible parents send them words of caution on a dial-up modem.

This is uncannily similar to what happens in  the teenage brain, where areas associated with reward mature before the prefrontal areas that exercise restraint. Other scientists have suggested that this gap in timing explains why teens are so prone to risky and impulsive behaviours. They’re not making thoughtless decisions – they simply weigh risks and rewards in a different way to adults. Perhaps people who are vulnerable to addiction never grow out of this asymmetry between desire and inhibition. “It does look like a developmental problem,” says Ersche, “but we really need to compare these brains to those of adolescents to know for sure.”

“This is a very important and well-designed study,” says Susan Tapert from the University of California, San Diego. She adds, “It will be important to understand how the non-drug dependent volunteers were able to avoid drug problems given same brain features as their siblings.”

This is a key point. Drug dependence runs in families, and it is clearly influenced by a person’s genes. But genes do not determine behaviour; they merely influence it. The non-addicted siblings in Ersche’s study illustrate the point beautifully. “They share so much,” says Ersche. “They have the same vulnerabilities as their drug-dependent brothers and sisters. They had a lot of domestic violence and troubled childhoods but they didn’t get into drugs. Their average age was 33. They may have had many opportunities to develop dependence, but they didn’t.”

Perhaps the other one had environmental influences that set them down a different path. Perhaps they also had inherited some “resilience factors” that their siblings did not.  In an earlier study with some of the same siblings, Ersche found that all of them are more impulsive, but only the drug users were “sensation-seekers”. These are subtly different traits. “Impulsive people act on the spur of the moment,” Ersche explains, “but sensation-seekers crave excitement and adventure. In contrast to the drug-dependent individuals, their siblings do not seem to crave for excitement and sensations, which might have protected them from taking drugs in the first place.

In the meantime, Ersche’s study suggests that the white fibre tracts around the IFC could be used as a marker for vulnerability to addiction. That’s useful for two reasons. We could use it to identify people who are most at risk of abusing drugs, before they actually encounter any problems. We could also see if people can strengthen the connections in this critical area. Many scientists have developed programmes for improving self-control at an early age. Monitoring the IFC’s white matter could provide an objective way of measuring whether those programmes are working. As Tapert says, “We might be able to modify these risky brain characteristics, to see if the misuse of drugs can be reduced.”

Reference: Ersche, Jones, Williams, Turton, Robbins & Bullmore. 2011. Abnormal Brain Structure Implicated in Stimulant Drug Addiction. Science

Alcohol tastes and smells better to those who get their first sips in the womb

By Ed Yong | March 9, 2009 5:00 pm

Blogging on Peer-Reviewed ResearchPregnant women are generally advised to avoid drinking alcohol and for good reason – exposing an unborn baby to alcohol can lead to a range of physical and mental problems from hyperactivity and learning problems to stunted growth, abnormal development of the head, and mental retardation.

But alcohol also has much subtler effects on a foetus. Some scientists have suggested that people who get their first taste of alcohol through their mother’s placenta are more likely to develop a taste for it in later life. This sleeper effect is a long-lasting one – exposure to alcohol in the womb has been linked to a higher risk of alcohol abuse at the much later age of 21. In this way, mums could be inadvertently passing down a liking for booze to their children as a pre-birthday present.

Now, Steven Youngentob from SUNY Upstate Medical University and Jon Glendinning from Columbia University have found out why this happens. By looking at boozing rats, they have found that those first foetal sips of alcohol make the demon drink both taste and smell better.

The duo raised several pregnant rats on diets of either chow, liquids or liquids that had been spiked with alcohol. The third group eventually had a blood alcohol concentration of about 0.15%, a level that would cause a typical human to slur, stagger or become moody.

When the females eventually gave birth, month-old pups born to boozy mothers were more likely to lick an alcohol-coated feeding tube than those whose mothers were tee-total. These rats had been born with more of a taste for booze.

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CATEGORIZED UNDER: Drugs, Epigenetics, Medicine & health

Beta-blocker drug erases the emotion of fearful memories

By Ed Yong | February 16, 2009 7:45 am

Blogging on Peer-Reviewed ResearchThe wiping of unwanted memories is a common staple of science-fiction and if you believe this weekend’s headlines, you might think that the prospect has just become a reality. The Press Association said that a “drug helps erase fearful memories“, while the ever-hyperbolic Daily Mail talked about a “pill to erase bad memories“. The comparisons to The Eternal Sunshine of the Spotless Mind were inevitable, but the actual study, while fascinating and important, isn’t quite the mind-wiper these headlines might have you believe.

The drug in question is propranolol, commonly used to treat high blood pressure and prevent migraines in children. But Merel Kindt and colleagues from the University of Amsterdam have found that it can do much more. By giving it to people before they recalled a scary memory about a spider, they could erase the fearful response it triggered.

The critical thing about the study is that the entire memory hadn’t been erased in a typical sci-fi way. Kindt had trained the volunteers to be fearful of spidery images by pairing them with electric shocks. Even after they’d been given propranolol, they still expected to receive a shock when they saw a picture of a spider – they just weren’t afraid of the prospect. The drug hadn’t so much erased their memories, as dulled their emotional sting. It’s more like removing all the formatting from a Word document than deleting the entire file. Congatulations to Forbes and Science News who actually got it right.

Kindt’s work hinges on the fact that memories of past fears aren’t as fixed as previously thought. When they are brought back to mind, proteins at the synapses – the junctions between two nerve cells – are broken down and have to be created from scratch. This process is called “reconsolidation” and scientists believe that it helps to incorporate new information into existing memories. The upshot is that when we recall old memories, they have to be rebuilt on some level, which creates an opportunity for changing them.

A few years ago, two American scientists managed to use propranolol to banish fearful responses in rats. They injected the animals in their amygdalae, a part of their brains involved in processing emotional memories. The drug didn’t stop a fearful memory from forming in the first place, but it did impair the memory when the rats tried to retrieve it. Now, Kindt has shown that the chemical has the same effect in humans.

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Impulsive minds are primed for drug addiction

By Ed Yong | October 19, 2008 10:00 am


Blogging on Peer-Reviewed ResearchWe’ve all acted impulsively before, and we have the horrendous clothes, echoing bank accounts and hilarious memories to show for it. But science is beginning to show that impulsive people may be particularly vulnerable to drug addiction, and there is little funny or harmless about that.

img_0046_o.jpgAccording to Government statistics, half a million people in the UK are addicted to class A drugs like cocaine, heroin and amphetamines. All too often, drug addiction and other compulsive disorders like obesity are dismissed as issues of ‘willpower’ and those who succumb to temptation are labelled as ‘weak’. But this attitude is, at best, wrong and, at worst, stigmatising and self-righteous. And it provides no clues for ways of helping people with these problems.

In fact, the evidence suggests that drug addiction is linked to certain personality traits. Being impulsive is one of them, and a tendency to seek out new sensations (often described as “living life to the full”) is another. But do these traits drive people towards drug addiction, or are they a result of the drugs themselves?

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The brain's addiction centre

By Ed Yong | October 12, 2008 10:00 am


Blogging on Peer-Reviewed ResearchIt’s mid-October. For most of us, our New Year’s resolutions have long been forgotten and our bad habits remain frustratingly habitual. The things that are bad for us often feel strongly compelling, be they high-fat foods, gambling or alcohol. And nowhere is the problem of addiction more widespread, serious and dangerous than the case of cigarette smoking.

800px-papierosa_1_ubt_0069.jpgSmoking is the leading preventable cause of death in the developed world, and in the UK, it kills five times more people than all non-medical causes combined. The dangers of smokers are both well-established and well-known, and surveys repeatedly show that the majority of smokers want to quit. But weaning oneself off a substance as addictive as nicotine is not easy.

People often view quitting smoking as a question of willpower – a problem of the mental world. But like all mental processes, addiction eventually boils down to physical matter, to our brains and the chemicals that reside within. Neurological studies have found that smoking causes long-term changes to various parts of the brain including the dopamine system involved in feelings of pleasure, and the amygdala, involved in emotional responses. Even cues associated with smoking such as the smell of smoke or the sight of a cigarette, can trigger distinctive patterns of activity in these areas, and are likely to contribute to the urges that smokers feel.

Now, Nasir Naqvi and colleagues from the University of Iowa have tracked down the neurons that control the addictive urges of smokers to a part of the brain called the insula. Located deep inside the brain, the insula is involved in emotion. It collects and processes sensory information from the rest of the body, and translates them into conscious emotional experiences, such as cravings, hunger or pain. And in doing this, the insula could control cravings for cigarettes in response to smoking-related cues.

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Brain-enhancing drugs work by focusing brain activity… for better or worse

By Ed Yong | April 18, 2008 4:48 pm

Blogging on Peer-Reviewed Research
It’s late at night and although I want to finish this post, I’m pretty shattered. At the moment, I sorely need to boost my concentration and attentiveness and stave off the effects of fatigue. In lieu of actually getting some sleep, the ability to pop a little pill that will have the same effect sounds pretty enticing. Unfortunately (or perhaps luckily), the closest thing I have available is some coffee in the kitchen.

ritalin.jpgBut for many people, taking a pill to sharpen your mental faculties – a so-called “cognitive enhancer” – is a much easier deal. A large number of prescription drugs can indeed give you a little mental boost, including amphetamine and methylphenidate (more familiarly known by its brand name Ritalin). Both the use and the range of such drugs are on the rise and they seem capable of stimulating debate just as readily as they do the brain.

They have their medical uses; as Ritalin, methylphenidate is used to treat attention deficit hyperactivity disorder (ADHD) and, less commonly, narcolepsy. Even this is not without controversy, but the fact that they seem to have the same enhancing effects in healthy people opens up the potential for recreational use, and that is far more divisive.

Last year, Nature published a commentary which looked into the ethics of such drugs and sparked off a heated debate in a Nature Network forum and among fellow bloggers. More recently, the magazine released the results of an informal survey of over 1,400 readers, which showed that about 20% admitted to using cognitive enhancers for non-medical reasons and a far higher proportion approved of such use.

The ethical issues at stake are incredibly broad, but one specific problem is that cognitive enhancers represent a case of technology outpacing science. Common though these drugs are, we still don’t fully understand how some of them work. Take methylphenidate, for example. At a basic level, we know that it interferes with protein pumps that import two signalling molecules – dopamine and norepinephrine – into neurons and as a result, these molecules build up in the spaces between neurons, the synapses. But why should such a build-up improve a person’s performance?

Nora Volkow, Director of the National Institute on Drug Abuse, thinks she has the answer. By studying the metabolic activity of brains dosed up with methylphenidate, she has found evidence that the drug works by focusing the brain’s activity and making it more efficient. And crucially, the benefits (and costs) you reap from that may depend on how focused your brain already is.

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