̽��ֱ�� of Cambridge - Karen Ersche

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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̽��ֱ��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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Individuals with a low risk for cocaine dependence have a differently shaped brain to those with addiction

gm349 — Thu, 17 Jan 2013 16:15:37 +0000

People who take cocaine over many years without becoming addicted have a brain structure which is significantly different from those individuals who developed cocaine-dependence, researchers have discovered. New research from the ̽��ֱ�� of Cambridge has found that recreational drug userswho have not developed a dependence have an abnormally large frontal lobe, the section of the brain implicated in self-control. Their research was published in the journal Biological Psychiatry.

For the study, led by Dr Karen Ersche, individuals who use cocaine on a regular basis underwent a brain scan and completed a series of personality tests. ̽��ֱ��majority of the cocaine users were addicted to the drug but some were not (despite having used it for several years).

̽��ֱ��scientists discovered that a region in the frontal lobes of the brain, known to be critically implicated in decision-making and self-control, was abnormally bigger in the recreational cocaine users. ̽��ֱ��Cambridge researchers suggest that this abnormal increase in grey matter volume, which they believe predates drug use, might reflect resilience to the effects of cocaine, and even possibly helps these recreational cocaine users to exert self-control and to make advantageous decisions which minimize the risk of them becoming addicted.

They found that this same region in the frontal lobes of the brain was significantly reduced in size in people with cocaine dependence, confirming earlier research that had found similar results. They believe that at least some of these changes are the result of drug use, which causes drug users to lose grey matter.

They also found that people who use illicit drugs like cocaine exhibit high levels of sensation-seeking personality traits, but only those developing dependence show personality traits of impulsivity and compulsivity.

Dr Ersche, of the Behavioural and Clinical Neuroscience Institute (BCNI) at the ̽��ֱ�� of Cambridge, said: “These findings are important because they show that the use of cocaine does not inevitably lead to addiction in people with good self-control and no familial risk.

“Our findings indicate that preventative strategies might be more effective if they were tailored more closely to those individuals at risk according to their personality profile and brain structure.”

̽��ֱ��researchers will next explore the basis of the recreational users’ apparent resilience to drug dependence.

Dr Ersche added: “Their high level of education, less troubled family background or the beginning of drug-taking only after puberty may all play a role.”

Research provides unique insight into the often misunderstood world of addiction.

Our findings indicate that preventative strategies might be more effective if they were tailored more closely to those individuals at risk according to their personality profile and brain structure.

Dr Karen Ersche

Valerie Everett from flickr

Cocaine

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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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Siblings’ brain scans could hold the key to drug addiction

gm349 — Fri, 03 Feb 2012 09:47:38 +0000

Researchers funded by the Medical Research Council (MRC) at the ̽��ֱ�� of Cambridge have identified a brain abnormality which is found in drug-dependent individuals as well as their siblings who have had no history of drug addiction. ̽��ֱ��brain abnormality identified by the researchers makes it more difficult for individuals to exercise self-control.

This research will help understanding about why some people with a family history of drug abuse are at a higher risk of addiction than others. ̽��ֱ��findings are published today in the journal Science.

Led by Dr Karen Ersche, the researchers scanned the brains of 50 pairs of brothers and sisters, of whom one was dependent on cocaine while the other did not abuse drugs or alcohol. Their brains were compared with those of 50 unrelated healthy volunteers who had no personal or family history of drug addiction.

̽��ֱ��researchers found that both the drug-dependent and their non-dependent siblings shared the same abnormality in the parts of the brain associated with how we control our behaviour, known as the fronto-striatal systems. This kind of abnormality is typically seen in people who struggle with drug addiction.

Dr Karen Ersche, of the Behavioural and Clinical Neuroscience Institute (BCNI) at the ̽��ֱ�� of Cambridge, said: “It has long been known that not everyone who takes drugs becomes addicted, and that people at risk of drug dependence typically have deficits in self-control. Our findings now shed light on why the risk of becoming addicted to drugs is increased in people with a family history of drug or alcohol dependence: parts of their brains underlying self-control abilities work less efficiently. ̽��ֱ��use of addictive drugs such as cocaine further exacerbates this problem, paving the way for addiction to develop from occasional use.”

Dr Ersche added: “Given that some forms of drug addiction are thought to develop out of bad habits that get out of control, it’s intriguing that siblings who don’t abuse drugs show similar brain abnormalities as the ones who have been abusing drugs for many years. While we still have more work to do to fully address the reasons why some family members show a greater resilience against addiction, our results will provide the scientific basis for the development of more effective preventative and therapeutic strategies for people at risk of addiction.”

Professor Chris Kennard, chair of the Neuroscience and Mental Health Board at the Medical Research Council which funded the research, said: “Drug addiction devastates thousands of families in the UK and the MRC is leading a strategy for addiction and substance misuse research, by funding cross-discipline research that addresses the biological, medical, social and economic aspects of addiction and substance misuse. This research represents an important step towards understanding some of the factors which cause some members of a family to abuse drugs, while leaving others unaffected.”

̽��ֱ��next step will be to explore how the siblings who don’t take drugs manage to overcome their brain abnormality in their daily life. ̽��ֱ��scientists want to understand what makes the non-drug using siblings resilient to addiction. A better understanding of what may protect them from drug abuse may provide vital clues for developing more effective therapies for those trying to beat their addiction.

̽��ֱ��study was funded by the Medical Research Council and conducted within the Behavioural and Clinical Neuroscience Institute at the ̽��ֱ�� of Cambridge, which is co-funded by the MRC and the Wellcome Trust.

Research provides insight into why some individuals with a family history of drug abuse are at higher risk of addiction.

Our findings now shed light on why the risk of becoming addicted to drugs is increased in people with a family history of drug or alcohol dependence: parts of their brains underlying self-control abilities work less efficiently.

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

Image is copyrighted. Science

Brain scans from study

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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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