̽��ֱ�� of Cambridge - cocaine

Cocaine addiction leads to build-up of iron in brain

cjb250 — Tue, 21 Feb 2017 15:00:33 +0000

Cocaine is one of the most widely-used illicit drugs in the Western world and is highly addictive. A report last year by the UK government’s Advisory Council on the Misuse of Drugs found that almost one in 10 of all 16-to 59-year-olds have used cocaine in their lifetime. Cocaine use was implicated in, but not necessarily the cause of 234 deaths in Scotland, England and Wales in 2013. However, despite significant advances in our understanding of the biology of addiction – including how the brains of people addicted to cocaine may differ in structure – there is currently no medical treatment for cocaine addiction; most individuals are treated with talking or cognitive therapies.

A team of researchers led by Dr Karen Ersche from the Department of Psychiatry at Cambridge examined the brains of 44 people who were addicted to cocaine and 44 healthy control volunteers. In the cocaine group, they detected excessive amounts of iron in a region of the brain known as the globus pallidus, which ordinarily acts as a ‘brake’ for inhibiting behaviour.

Particularly striking was the fact that the concentration of iron in this area was directly linked with the duration of cocaine use – in other words, the longer that participants had used cocaine, the greater the accumulation of iron. At the same time, the increased iron concentration in the brain was accompanied by mild iron deficiency in the rest of the body, suggesting that iron regulation in general is disrupted in people with cocaine addiction.

“Given the important role that iron plays in both health and disease, iron metabolism is normally tightly regulated,” explains Dr Karen Ersche from the Department of Psychiatry. “Long-term cocaine use, however, seems to disrupt this regulation, which may cause significant harm.

“Iron is used to produce red blood cells, which help store and carry oxygen in the blood. So, iron deficiency in the blood means that organs and tissues may not get as much oxygen as they need. On the other hand, we know that excessive iron in the brain is associated with cell death, which is what we frequently see in neurodegenerative diseases.”

̽��ֱ��Cambridge researchers now aim to identify the precise mechanisms by which cocaine interacts with iron regulation. Dr Ersche believes the most likely mechanism is that cocaine disrupts iron metabolism, possibly by reducing the absorption of iron from food, increasing the permeability of the blood-brain-barrier so that more iron enters the brain, where it can accumulate.

Although excess iron in the brain is associated with neurodegeneration, there is no suggestion that cocaine addiction leads to an increased risk of Alzheimer’s or Parkinson’s disease. ̽��ֱ��mechanism underlying the increase in iron in the brain in Parkinson’s disease, for example, is different to that in cocaine addiction, as are the affected brain regions.

As an essential micronutrient, iron can only be obtained through our diet and cannot be excreted, other than through blood loss. ̽��ֱ��researchers now want to find out whether means of correcting the disruptions in iron metabolism might slow down or even reverse the accumulation of iron in the brain, and ultimately help affected individuals to successfully recover from cocaine addiction.

This work was funded by the Medical Research Council and was conducted at the NIHR Cambridge Biomedical Research Centre and the Behavioural and Clinical Neuroscience Institute.

Reference
Ersche, KD et al. Disrupted iron regulation in the brain and periphery in cocaine addiction. Translational Psychiatry; 21 Feb 2017; DOI: 10.1038/tp.2016.271

Cocaine addiction may affect how the body processes iron, leading to a build-up of the mineral in the brain, according to new research from the ̽��ֱ�� of Cambridge. ̽��ֱ��study, published today in Translational Psychiatry, raises hopes that there may be a biomarker – a biological measure of addiction – that could be used as a target for future treatments.

Given the important role that iron plays in both health and disease, iron metabolism is normally tightly regulated. Long-term cocaine use, however, seems to disrupt this regulation, which may cause significant harm

Karen Ersche

D. Sinclair Terrasidius

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Carrots and sticks fail to change behaviour in cocaine addiction

cjb250 — Thu, 16 Jun 2016 18:00:35 +0000

“Addiction does not happen overnight but develops from behaviour that has been repeated over and over again until individuals lose control,” said Dr Karen Ersche from the Department of Psychiatry, who led the research.

In a study reported today in the journal Science, Dr Ersche and colleagues tested 125 participants, of whom 72 were addicted to cocaine and 53 had no history of drug addiction, on their inclination to develop habits. They found that people with cocaine addiction were much more likely than healthy participants to make responses in an automatic fashion, but only if they had previously been rewarded for responding in the same way. ̽��ֱ��addicted individuals simply continued repeating the same responses they had previously learned, regardless of whether their actions made sense or not.

In a different context, however, where participants had to perform an action to avoid electrical shocks, people with cocaine addiction did not develop habits. In fact, they were much less inclined than the control participants to make an effort to avoid the electric shock in the first place.

“Our experiments highlight the particular difficulties faced when it comes to changing behaviour in people with cocaine addiction: they are highly responsive if their behaviour is rewarded – for example a ‘high’ from drug use – but then quickly switch to autopilot, becoming unable to change that behaviour in light of different consequences,” said Dr Ersche. “By contrast, when cocaine users are facing adversity, they are less inclined than healthy people to do something about it.

“These findings have significant implications for the treatment of people with cocaine addiction. Clearly punitive approaches are ineffective, as the prospect of something bad happening to them won’t make cocaine users more likely to change their behaviour. Interventions that build on their particular strength in developing habits, by training the implementation of more desirable habits to replace drug-taking habits, are likely to be more effective. Our findings also suggest that cocaine users would need to be actively protected from – rather than simply warned about – adverse consequences, because they will likely fail to avoid them if left to their own devices.”

There is currently no medical treatment for cocaine addiction – most individuals are treated with talking or cognitive therapy. According to Dr Ersche, the results show that a different approach to treating cocaine addiction might be of enhanced benefit to cocaine users. ̽��ֱ��researchers are now aiming to better understand the brain systems underlying cocaine users’ proneness to habits and their lack of avoidance, and to use this knowledge to develop more effective treatments for cocaine addiction.

In the first experiment conducted by Ersche and her colleagues, participants were asked to learn the relationship between pictures, and a correct response was rewarded with points. After a long training period, participants were informed that some pictures were no longer worth any points. Participants with cocaine addiction were less likely to take on board the information about the change in reward, and were also more likely to continue responding in an automatic way, regardless of whether they were rewarded or not.

In a second experiment, the same participants were shown two different pictures on a screen, which they learned to associate with receiving an electric shock. Participants were then taught a strategy on how they could avoid the shocks by pressing a foot pedal. Those participants with cocaine addiction were less good at avoiding the electric shocks in the first place, possibly due to learning and/or motivational impairment, and subsequently did not develop avoidance habits.

̽��ֱ��work was funded by the Medical Research Council and was conducted at the NIHR Cambridge Biomedical Research Centre and the Behavioural and Clinical Neuroscience Institute.

Reference
Ersche, KD et al. Carrots and sticks fail to change behavior in cocaine addiction. Science; 17 Jun 2016; DOI: 10.1126/science.aaf3700

People who are addicted to cocaine are particularly prone to developing habits that render their behaviour resistant to change, regardless of the potentially devastating consequences, suggests new research from the ̽��ֱ�� of Cambridge. ̽��ֱ��findings may have important implications for the treatment of cocaine addiction as they help explain why such individuals take drugs even when they are aware of the negative consequences, and why they find their behaviour so difficult to change.

CB Du Rietz

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Highway to addiction: how drugs and alcohol can hijack your brain

cjb250 — Thu, 25 Feb 2016 15:14:44 +0000

There is a road down which those with substance addiction travel. Its beginnings are influenced by circumstances and genetics; it becomes well trodden, habitual, initially reinforced by pleasurable effects and then by cues; and, for some, it will become a road they can never leave.

Addiction is a chronic, relapsing psychiatric disease, with complex behavioural processes and equally complex changes to brain circuits. ̽��ֱ��brain of a person who has drunk alcohol or taken drugs is different to the brain of one who has not, as pharmacologist Dr David Belin describes: “I like whisky. I started drinking whisky when I was 20 and I have only a small amount now and then. But if I were to scan my brain, it changed that very first time, and it continues to be changed.”

And because drugs change the brain in ways that foster compulsive drug and alcohol abuse, quitting is difficult, even for those who want to. Belin and Professor Barry Everitt, from the Department of Pharmacology, have shown that some are more vulnerable than others to developing addiction – and to relapsing.

Their recent research, published in Nature Communications, uncovers a new neural ‘short cut’, or ‘back door’, in rat brains that could explain why some cocaine addicts relapse without intending to. ̽��ֱ��results, they believe, could suggest new forms of behavioural and pharmacological therapies.

A decade ago, both Belin and Everitt, independently, were the first to show that addiction manifests itself differently in different individuals and that, for some, compulsive cocaine-seeking behaviour would continue despite adverse circumstances. In a rat model, around 20% of animals addicted to cocaine still sought the drug despite the risk of receiving mild electric shocks on doing so.

“This was the first time in the field of addiction that the idea of inter-individual differences in vulnerability to compulsive drug seeking was raised,” explains Belin, who is funded by the Wellcome Trust. “With regard to psychiatric disorders, we are not equally vulnerable.”

Drug addiction had largely been regarded as the end point of a progressive loss of control over drug seeking resulting from a failure of part of the brain – the prefrontal cortex – that deals with decision making.

“Certainly, chronic exposure to drugs alters the prefrontal cortex, which governs motivation, inhibitory control and choice. But it also alters an area of the brain called the basolateral amygdala, which is associated with the link between a stimulus and an emotion,” explains Belin.

To explain further he gives the example of choosing to eat a cake or an apple. “ ̽��ֱ��basolateral amygdala stores the pleasurable memories associated with eating the cake, but the prefrontal cortex manipulates this information, helping you to weigh up whether or not you should eat another slice or choose the apple instead. If you eat the slice, regions of the ventral striatum, the structure that processes reward and links emotions to actions, are activated.”

However, Belin and Everitt’s latest research has shown that this is not the only neuronal circuit that underlies cocaine-seeking behaviour.

Using their rat model, they identified a completely new highway that links impulses with habits. This brain circuit links the basolateral amygdala indirectly with the dorsolateral striatum, which is the neural locus of habits.

“Because it doesn’t recruit the prefrontal cortex it doesn’t involve choice,” explains Belin. “It’s a short cut or back door directly to habit. It means that addicts can have internal urges they are not aware of that drive drug seeking. It’s a newly recognised function of this brain circuitry.

“It would explain situations in which individuals who have been abstinent for five years suddenly relapse, telling their counsellor ‘I was walking in the street and I found myself with a glass of wine – and I promise you I didn’t want it.’ This has often been dismissed as ‘weakness of the will’ and then denial. This may also happen, but what our results in rats suggest is that there are occasions in which the stimuli go via motivation straight to the habit part of the brain without an individual even being aware of it.”

̽��ֱ��researchers believe that this is a breakthrough in understanding how drugs like cocaine can hijack the brain with such devastating consequences. “We can speculate that the subset of individuals currently using drugs who are especially vulnerable to addiction might have a stronger pathway – a ‘superhighway’ to habit formation.”

̽��ֱ��finding could explain the puzzling feature of why substance abusers repeatedly do something they know is bad for them. This is an area that interests Dr Valerie Voon in the Department of Psychiatry. “There appears to be a form of impulsivity called ‘waiting impulsivity’ that doesn’t involve choice and that predisposes to drug addiction.”

Waiting impulsivity is seen when a runner takes off before the starter pistol, or when someone interrupts inappropriately. Voon has devised a way of measuring it in humans based on tasks studied in rats. She also uses another task that teases apart decisions that are made through choices that are goal directed (i.e. taking into account the goal or outcome) from those that are habitual (i.e. relying rather automatically on past rewarding choices).

“We find that alcohol addiction correlates with waiting impulsivity. Once you’re abstinent, the compulsivity or habits also improve. Now that we have this test we can start to cut across other addictions – is there an underlying neural process shared by all? Can we ascribe causality? Can we suggest new treatments?”

Belin suggests that a combination of behavioural and pharmacological treatments might be the answer to helping addicts quit.

Treatments such as cognitive behavioural therapy aim to restore the function of the prefrontal cortex so that emotions don’t automatically elicit habits. “But if people are not aware of their impulses then they can’t subjectively or cognitively apprehend the motivation and the impulse to take drugs or drink,” says Belin. “It’s possible that mindfulness might be beneficial in helping them identify the impulses.”

Although there is currently no effective pharmacological treatment for cocaine addiction, his team has recently shown that N-acetylcysteine might be a possibility, but only if used early enough on the road to addiction when the individual still has the motivation to stop.

̽��ֱ��researchers now plan to extend their study of cocaine addiction to compulsive alcohol- and heroin-seeking behaviour. They and Voon would like to understand to what degree behavioural traits such as impulsivity, novelty preference and anxiety – using brain imaging to identify neural correlates – can be used as a predictor of compulsive drug seeking.

“Drug taking is always volitional to begin with – you take drugs because you want to experience something,” adds Belin. “Unfortunately they hijack the learning mechanisms in your brain so that you don’t really take them because you want them but because stimuli in your environment tell you to do so. We want to work out how we can help people become aware that their impulses are wrongly triggering their habits.”

̽��ֱ��discovery of a brain circuit ‘shortcut’ could explain why some addicts unintentionally relapse, and suggests that a shift in focus for therapies might help those who want to stay off drugs.

I started drinking whisky when I was 20 and I have only a small amount now and then. But if I were to scan my brain, it changed that very first time, and it continues to be changed

David Belin

̽��ֱ��District

Highway to addiction

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Cocaine addiction: Scientists discover ‘back door’ into the brain

cjb250 — Tue, 12 Jan 2016 00:17:37 +0000

A second study from the team suggests that a drug used to treat paracetamol overdose may be able to help individuals who want to break their addiction and stop their damaging cocaine seeking habits.

Although both studies were carried out in rats, the researchers believe the findings will be relevant to humans.

Cocaine is a stimulant drug that can lead to addiction when taken repeatedly. Quitting can be extremely difficult for some people: around four in ten individuals who relapse report having experienced a craving for the drug – however, this means that six out of ten people have relapsed for reasons other than ‘needing’ the drug.

“Most people who use cocaine do so initially in search of a hedonic ‘high’,” explains Dr David Belin from the Department of Pharmacology at the ̽��ֱ�� of Cambridge. “In some individuals, though, frequent use leads to addiction, where use of the drug is no longer voluntary, but ultimately becomes a compulsion. We wanted to understand why this should be the case.”

Drug-taking causes a release in the brain of the chemical dopamine, which helps provide the ‘high’ experienced by the user. Initially the drug taking is volitional – in other words, it is the individual’s choice to take the drug – but over time, this becomes habitual, beyond their control.

Previous research by Professor Barry Everitt from the Department of Psychology at Cambridge showed that when rats were allowed to self-administer cocaine, dopamine-related activity occurred initially in an area of the brain known as the nucleus accumbens, which plays a significant role driving ‘goal-directed’ behaviour, as the rats sought out the drug. However, if the rats were given cocaine over an extended period, this activity transferred to the dorsolateral striatum, which plays an important role in habitual behaviour, suggesting that the rats were no longer in control, but rather were responding automatically, having developed a drug-taking habit.

̽��ֱ��brain mechanisms underlying the balance between goal-directed and habitual behaviour involves the prefrontal cortex, the brain region that orchestrates our behaviour. It was previously thought that this region was overwhelmed by stimuli associated with the drugs, or with the craving experienced during withdrawal; however, this does not easily explain why the majority of individuals relapsing to drug use did not experience any craving.

Chronic exposure to drugs alters the prefrontal cortex, but it also alters an area of the brain called the basolateral amygdala, which is associated with the link between a stimulus and an emotion. ̽��ֱ��basolateral amygdala stores the pleasurable memories associated with cocaine, but the pre-frontal cortex manipulates this information, helping an individual to weigh up whether or not to take the drug: if an addicted individual takes the drug, this activates mechanisms in the dorsal striatum.

However, in a study published today in the journal Nature Communications, Dr Belin and Professor Everitt studied the brains of rats addicted to cocaine through self-administration of the drug and identified a previously unknown pathway within the brain that links impulse with habits.

̽��ֱ��pathway links the basolateral amygdala indirectly with the dorsolateral striatum, circumventing the prefrontal cortex. This means that an addicted individual would not necessarily be aware of their desire to take the drug.

“We’ve always assumed that addiction occurs through a failure or our self-control, but now we know this is not necessarily the case,” explains Dr Belin. “We’ve found a back door directly to habitual behaviour.

“Drug addiction is mainly viewed as a psychiatric disorder, with treatments such as cognitive behavioural therapy focused on restoring the ability of the prefrontal cortex to control the otherwise maladaptive drug use. But we’ve shown that the prefrontal cortex is not always aware of what is happening, suggesting these treatments may not always be effective.”

In a second study, published in the journal Biological Psychiatry, Dr Belin and colleagues showed that a drug used to treat paracetamol overdose may be able to help individuals addicted to cocaine overcome their addiction – provided the individual wants to quit.

̽��ֱ��drug, N-acetylcysteine, had previously been shown in rat studies to prevent relapse. However, the drug later failed human clinical trials, though analysis suggested that while it did not lead addicted individuals to stop using cocaine, amongst those who were trying to abstain, it helped them refrain from taking the drug.

Dr Belin and colleagues used an experiment in which rats compulsively self-administered cocaine. They found that rats given N-acetylcysteine lost the motivation to self-administer cocaine more quickly than rats given a placebo. In fact, when they had stopped working for cocaine, they tended to relapse at a lower rate. N-acetylcysteine also increased the activity in the brain of a particular gene associated with plasticity – the ability of the brain to adapt and learn new skills.

“A hallmark of addiction is that the user continues to take the drug even in the face of negative consequences – such as on their health, their family and friends, their job, and so on,” says co-author Mickael Puaud from the Department of Pharmacology of the ̽��ֱ�� of Cambridge. “Our study suggests that N-acetylcysteine, a drug that we know is well tolerated and safe, may help individuals who want to quit to do so.”

Reference
Murray, JE et al. Basolateral and central amygdala differentially recruit and maintain dorsolateral striatum-dependent cocaine-seeking habits. Nature Comms; 16 December 2015

Ducret, E et al. N-acetylcysteine facilitates self-imposed abstinence after escalation of cocaine intake. Biological Psychiatry; 7 Oct 2015

Individuals addicted to cocaine may have difficulty in controlling their addiction because of a previously-unknown ‘back door’ into the brain, circumventing their self-control, suggests a new study led by the ̽��ֱ�� of Cambridge.

Most people who use cocaine do so initially in search of a hedonic ‘high’. In some individuals, though, frequent use leads to addiction, where use of the drug is no longer voluntary, but ultimately becomes a compulsion

David Belin

D. Sinclair Terrasidius

relaxing after work_MMVI (cropped)

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̽��ֱ��skinny on cocaine

gm349 — Fri, 09 Aug 2013 09:45:22 +0000

Chronic cocaine use may reduce the body’s ability to store fat, new research from the ̽��ֱ�� of Cambridge suggests.

̽��ֱ��scientists found that cocaine use may cause profound metabolic changes which can result in dramatic weight gain during recovery, a distressing phenomenon that can lead to relapse. It was previously widely believed that cocaine suppresses the appetite and that the problematic weight gain during rehabilitation was a result of patients substituting food for drugs.

Dr Karen Ersche, from the Behavioural and Clinical Neuroscience Institute at the ̽��ֱ�� of Cambridge, said: “Our findings challenge the widely held assumptions that cocaine use leads to weight loss through appetite suppression. Rather, they suggest a profound metabolic alteration that needs to be taken into account during treatment.

“Notable weight gain following cocaine abstinence is not only a source of major personal suffering but also has profound implications for health and recovery. Intervention at a sufficiently early stage could have the potential to prevent weight gain during recovery, thereby reducing personal suffering and improving the chances of recovery.”

Led by Dr Ersche, the researchers scanned over sixty men to evaluate body composition, diets and eating behaviours. Half of the men in the sample had a dependency on cocaine while the other half had no personal or family history of drug abuse. They also measured the volunteers’ leptin, a hormone which plays an important role in regulating appetite and energy use.

̽��ֱ��researchers discovered that cocaine users expressed a preference for fatty foods and carbohydrates and also had patterns of uncontrolled eating. Yet, despite cocaine users’ fatty diets they often experienced weight loss, and their body fat was significantly reduced compared to the control group. Levels of the hormone leptin were also low in cocaine users and were associated with the duration of the user’s stimulant use. A decrease in plasma leptin together with a high fat diet suggests an impaired energy balance, which typically leads to weight gain rather than weight loss.

̽��ֱ��results suggest that overeating in regular users of cocaine pre-dates the recovery process, this effect being disguised by a lack of weight gain. As a result, when cocaine users in recovery discontinue using cocaine but continue consuming their high fat diets - now without the effects of cocaine on their metabolism - they gain weight.

Dr Ersche said: “We were surprised how little body fat the cocaine users had in light of their reported consumption of fatty food. It seems that regular cocaine abuse directly interferes with metabolic processes and thereby reduces body fat. This imbalance between fat intake and fat storage may also explain why these individuals gain so much weight when they stop using cocaine.

“For most people weight gain is unpleasant but for people in recovery, who can gain several stones, this weight gain goes far beyond an aesthetic concern but involves both psychological and physiological problems. ̽��ֱ��stress caused by this conspicuous body change can also contribute to relapse. It is therefore important that we better understand the effects of cocaine on eating behaviour and body weight to best support drug users on their road to recovery.”

Professor Hugh Perry, chair of the Neurosciences and Mental Health Board at the Medical Research Council who funded the study, said “Credible scientific studies like this one, which help to dispel misconceptions and address common preconceptions with reliable data, can only benefit individuals in the longer term. This research has clear implications for our understanding of how the body processes fat during chronic cocaine dependency and also how the body adjusts during withdrawal and recovery from dependency.”

̽��ֱ��research was published in the journal Appetite.

Dr Ersche and her team will next investigate more closely the underlying factors contributing to the marked weight gain in abstinent cocaine-dependent individuals to develop interventions to better support drug users in recovery.

This work was funded by the Medical Research Council and received institutional funds from the Behavioural and Clinical Neuroscience Institute (BCNI), which is jointly funded by the Medical Research Council and the Wellcome Trust.

New research suggests chronic cocaine use causes profound metabolic changes, reducing the body’s ability to store fat.

Valerie Everitt from Flickr

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Chronic cocaine use may speed up ageing of brain

gm349 — Tue, 24 Apr 2012 11:37:46 +0000

New research by scientists at the ̽��ֱ�� of Cambridge suggests that chronic cocaine abuse accelerates the process of brain ageing. ̽��ֱ��study, published today in Molecular Psychiatry, found that age-related loss of grey matter in the brain is greater in people who are dependent on cocaine than in the healthy population.

For the study, the researchers scanned the brains of 120 people with similar age, gender and verbal IQ. Half of the individuals had a dependence on cocaine while the other 60 had no history of substance abuse disorders.

̽��ֱ��researchers found that the rate of age-related grey matter volume loss in cocaine-dependent individuals was significantly greater than in healthy volunteers. ̽��ֱ��cocaine users lost about 3.08 ml brain volume per year, which is almost twice the rate of healthy volunteers (who only lost about 1.69 ml per year). ̽��ֱ��accelerated age-related decline in brain volume was most prominent in the prefrontal and temporal cortex, important regions of the brain which are associated with attention, decision-making, and self-regulation as well as memory.

Previous studies have shown that psychological and physiological changes typically associated with old age such as cognitive decline, brain atrophy and immunodeficiency are also seen in middle-aged cocaine-dependent individuals. However, this is the first time that premature ageing of the brain has been associated with chronic cocaine abuse.

Dr Karen Ersche, of the Behavioural and Clinical Neuroscience Institute (BCNI) at the ̽��ֱ�� of Cambridge, said: “As we age, we all lose grey matter. However, what we have seen is that chronic cocaine users lose grey matter at a significantly faster rate, which could be a sign of premature ageing. Our findings therefore provide new insight into why the cognitive deficits typically seen in old age have frequently been observed in middle aged chronic users of cocaine.”

̽��ֱ��scientists also highlight concerns that premature ageing in chronic cocaine users is an emerging public health concern. ̽��ֱ��United Nations Office on Drugs and Crime estimates that cocaine is used by up to 21 million individuals worldwide, with approximately 1 per cent of these individuals becoming dependent.

Dr Ersche said: “Our findings clearly highlight the need for preventative strategies to address the risk of premature ageing associated with cocaine abuse. Young people taking cocaine today need to be educated about the long-term risk of ageing prematurely.”

̽��ֱ��concern of accelerated ageing is not limited to young people but also affects older adults who have been abusing drugs such as cocaine since early adulthood.

Dr Ersche added: “Our findings shed light on the largely neglected problem of the growing number of older drug users, whose needs are not so well catered for in drug treatment services. It is timely for heath care providers to understand and recognise the needs of older drug users in order to design and administer age-appropriate treatments.”

Research shows chronic users’ brains age dramatically faster than their non-drug using peers.

As we age, we all lose grey matter. However, what we have seen is that chronic cocaine users lose grey matter at a significantly faster rate, which could be a sign of premature ageing.

Dr Karen Ersche, of the Behavioural and Clinical Neuroscience Institute (BCNI) at the ̽��ֱ�� of Cambridge

Image Dr Karen Ersche

Molecular Psychiatry

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Possible tool to help cocaine users kick the habit

ns480 — Thu, 06 Oct 2011 14:38:47 +0000

Unlike heroin users who may benefit from methadone when attempting to quit, there is currently no medication which has proven to be an effective tool in assisting cocaine and amphetamines users when attempting to quit.

“Treatment for stimulant dependence is difficult and often individuals battling addiction relapse several times,” said Dr Karen Ersche, of the Behavioural and Clinical Neuroscience Institute (BCNI) at the ̽��ֱ�� of Cambridge, who led the research.

“At the moment, the standard treatment for people dependent on cocaine and amphetamines mainly involves behavioural approaches such as counselling and cognitive-behavioural therapy – which are useful. However, our research provides important insight into the potential development of medications which could help curb the desire of those plagued with addiction, increasing the likelihood of a successful recovery.”

For the research, Dr Ersche and her Cambridge colleagues asked stimulant-dependent individuals and volunteers who do not use drugs to perform a learning task while their brains were scanned. They found that stimulant-dependent people had problems with adjusting their behaviour when one of the rules was changed - they persistently responded to the previously correct stimulus despite being repeatedly told that the rule had changed and their responses were wrong.

Dr Ersche added: “Their inflexible performance on the task resembles their drug-taking habits in as much as stimulant-dependent people do almost everything to take drugs even when there are negative consequences such as job loss, debts, or relationship breakups.”

̽��ֱ��brain scans which were conducted while the patients performed the learning task showed that this persistent behaviour was directly linked with reduced activation in the brain reward system. However, when the drug users were given a medication that increased the chemical dopamine in the brain reward centre, their performance improved and their brain activation normalised.

Dr Ersche concluded: “However, before this medication can be used for the treatment of stimulant-dependent individuals in clinical practice, more research would be needed using multiple doses over longer period of time.”

Previous research by the same research group had found that parts of the brain reward system where cocaine exerts its actions were significantly enlarged in cocaine users, which the scientists believe renders these individuals more vulnerable to the effects of the drugs.

̽��ֱ��study was funded and sponsored by GlaxoSmithKline and conducted within the GlaxoSmithKline Clinical Unit Cambridge and BCNI (which is co-funded by the MRC and the Wellcome Trust).

Medicines which increase levels of the brain chemical dopamine may hold the key to helping those addicted to cocaine and amphetamines kick the habit, researchers from the ̽��ֱ�� of Cambridge have found.

Treatment for stimulant dependence is difficult and often individuals battling addiction relapse several times.

Dr Karen Ersche

A close up of a young woman snorting cocaine during the 1920s

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Abnormal brain structure linked to chronic cocaine abuse

gm349 — Tue, 21 Jun 2011 01:02:26 +0000

Researchers at the ̽��ֱ�� of Cambridge have identified abnormal brain structures in the frontal lobe of cocaine users’ brains which are linked to their compulsive cocaine-using behaviour. Their findings were published today, 21 June, in the journal Brain.

Led by Dr Karen Ersche, the Cambridge researchers scanned the brains of 120 people, half of whom had a dependence on cocaine. They found that the cocaine users had widespread loss of grey matter that was directly related to the duration of their cocaine abuse (i.e. the longer they had been using cocaine, the greater the loss of grey matter), and that this reduction in volume was associated with greater compulsivity to take cocaine.

̽��ֱ��scientists also found that parts of the brain reward system where cocaine exerts its actions (the basal ganglia) were significantly enlarged in cocaine users; but the size of the enlargement was not related to the duration of cocaine use. ̽��ֱ��researchers believe this may suggest that alterations in the brain’s reward system predate cocaine abuse, possibly rendering these individuals more vulnerable to the effects of the drug.

Dr Ersche, of the Behavioural and Clinical Neuroscience Institute (BCNI) at the ̽��ֱ�� of Cambridge, said: “This research gives us important insight into why some people are more vulnerable to drug addiction. Not only is this important for the future development of more effective therapeutic interventions for people who have become dependent on drugs, it will also inform improved strategies to prevent drug addiction in the first place.”

Cocaine, one of the most addictive drugs on the illicit drug market, exerts its effects on the brain by changing the way a person thinks and feels. People addicted to cocaine feel an overwhelming, uncontrollable need for the drug, even in the face of aversive consequences.

Dr Ersche added: “People with cocaine dependence describe their out-of-control drug use as a ‘compulsion’ to use cocaine. Our current work has laid the foundation for a better understanding of cocaine dependence and why this compulsion occurs.”

̽��ֱ��researchers also showed that changes in other brain structures of chronic cocaine users were linked to debilitating attention problems.

Dr Ersche added: “Our findings are important because they show a clear relationship between the brain, the duration of cocaine use and some of the common attention problems that people with cocaine dependence report. These data show that cocaine dependence is a disorder of the brain, which is very relevant information for the treatment of people who are trying to beat their addiction.”

̽��ֱ��researchers will next explore whether there is an inherited vulnerability to develop cocaine dependence. Although cocaine is a highly addictive drug, not everyone who uses develops an addiction. They will research whether people with an enlarged brain reward system are more at risk of becoming dependent on cocaine as well as what the effects of recreational cocaine use has on the brain.

̽��ֱ��study was funded and sponsored by GlaxoSmithKline and conducted within the GlaxoSmithKline Clinical Unit Cambridge and BCNI (which is co-funded by the MRC and the Wellcome Trust).

Research gives insight into why some people develop addiction.

This research gives us important insight into why some people are more vulnerable to drug addiction.

Dr Karen Ersche

Karen Ersche

Brain

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