̽��ֱ�� of Cambridge - drug addiction

Substance use disorders linked to poor health outcomes in wide range of physical health conditions

cjb250 — Fri, 04 Nov 2022 00:13:39 +0000

In a study published today in ̽��ֱ��Lancet Psychiatry, researchers looked at the risk of mortality and loss of life-years among people who developed 28 different physical health conditions, comparing those who had previously been hospitalised with substance use disorder against those who had not.

They found that patients with most of the health conditions were more likely than their counterparts to die during the study period if they had been hospitalised with substance use disorder prior to the development of these conditions. For most subsequent health conditions, people with substance use disorders also had shorter life-expectancies than did individuals without substance use disorders.

One in twenty people worldwide aged 15 years or older lives with alcohol use disorder, while around one in 100 people have psychoactive drug use disorders. Although substance use disorders have considerable direct effects on health, they are also linked to a number of physical and mental health conditions. Consequently, the presence of these contributes to higher risk of mortality and shorter lifespan in people with substance use disorders.

To explore this link further, researchers analysed patient records from Czech nationwide registers of all-cause hospitalisations and deaths during the period from 1994-2017. They used a novel design, estimating the risk of death and life-years lost after the onset of multiple specific physical health conditions in individuals with a history of hospitalisation for substance use disorders, when compared with matched counterparts without substance use disorder but with the same physical health condition.

Although the study only looked at people living in Czechia, the researchers believe the results are likely to be similar in other countries, too.

They found that people with pre-existing substance use disorders were more likely than their counterparts to have died during the study following the development of 26 out of 28 physical health conditions. For seven of these conditions – including atrial fibrillation, hypertension, and ischaemic heart disease – the risk was more than doubled. In most cases, people with substance use disorders have shorter life-expectancies than their counterparts.

Lead author Tomáš Formánek, a PhD student at the National Institute of Mental Health, Czechia, and the ̽��ֱ�� of Cambridge, said: “Substance use disorders seem to have a profound negative impact on prognosis following the development of various subsequent physical health conditions, in some cases dramatically affecting the life expectancy of the affected people.”

It is not clear why this should be the case, though the researchers say there are a number of possible reasons. It is already known that substance use has a direct negative impact on physical health and is associated with lifestyle factors that affect our health, such as smoking, lack of exercise, and poor diet. Similarly, people with substance use disorders are less likely to take part in screening and prevention programmes for diseases such as cancer and diabetes and are less likely to use preventive medication, such as drugs to prevent hypertension. There are also some factors not directly related to substance use, such as diagnostic overshadowing, meaning the misattribution of physical symptoms to mental disorders. Such misattribution can subsequently contribute to under-diagnosis, late diagnosis, and delayed treatment in affected individuals.

Senior author Professor Peter Jones from the Department of Psychiatry, ̽��ֱ�� of Cambridge, added: “These results show how important it is not to compartmentalise health conditions into mind, brain or body. All interact leading here to the dramatic increases in mortality from subsequent physical illnesses in people with substance use disorders. There are clear implications for preventive action by clinicians, health services and policy developers that all need to recognise these intersections.”

Co-author Dr Petr Winkler from the National Institute of Mental Health, Czechia, said: “It is also important to consider that the majority of people with substance use disorders go undetected. They often do not seek a professional help and hospitalisations for these conditions usually come only at very advanced stages of illness. Alongside actions focused on physical health of people with substance use disorders, we need to equally focus on early detection and early intervention in substance use disorders.”

̽��ֱ��research was funded by the National Institute for Health and Care Research (NIHR) Applied Research Collaboration East of England at Cambridge and Peterborough NHS Foundation Trust.

Reference
Formánek, T et al. Mortality and life-years lost following subsequent physical comorbidity in people with pre-existing substance use disorders: a national registry-based retrospective cohort study of hospitalised individuals in Czechia. ̽��ֱ��Lancet Psychiatry; 3 Nov 2022; DOI: 10.1016/S2215-0366(22)00335-2

People who have a past history of hospitalisation because of substance use disorders have much worse outcomes following the onset of a wide range of physical health conditions, according to researchers in the UK and Czechia.

Substance use disorders seem to have a profound negative impact on prognosis following the development of various subsequent physical health conditions, in some cases dramatically affecting the life expectancy of the affected people

Tomáš Formánek

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Woman holding a glass of whisky

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Identification of brain region responsible for alleviating pain could lead to development of opioid alternatives

sc604 — Tue, 27 Feb 2018 08:00:00 +0000

̽��ֱ��team, led by the ̽��ֱ�� of Cambridge, have pinpointed an area of the brain that is important for endogenous analgesia – the brain’s intrinsic pain relief system. Their results, published in the open access journal eLife, could lead to the development of pain treatments that activate the painkilling system by stimulating this area of the brain, but without the dangerous side-effects of opioids.

Opioid drugs such as oxycodone, hydrocodone and fentanyl hijack the endogenous analgesia system, which is what makes them such effective painkillers. However, they are also highly addictive, which has led to the opioid crisis in the United States, where drug overdose is now the leading cause of death for those under 50, with opioid overdoses representing two-thirds of those deaths.

“We’re trying to understand exactly what the endogenous analgesia system is: why we have it, how it works and where it is controlled in the brain,” said Dr Ben Seymour of Cambridge’s Department of Engineering, who led the research. “If we can figure this out, it could lead to treatments that are much more selective in terms of how they treat pain.”

Pain, while unpleasant, evolved to serve an important survival function. After an injury, for instance, the persistent pain we feel saps our motivation, and so forces us towards rest and recuperation which allows the body to use as much energy as possible for healing.

“Pain can actually help us recover by removing our drive to do unnecessary things - in a sense, this can be considered ‘healthy pain’,” said Seymour. “So why might the brain want to turn down the pain signal sometimes?”

Seymour and his colleagues thought that sometimes this ‘healthy pain’ could be a problem, especially if we could actively do something that might help - such as try and find a way to cool a burn.

In these situations, the brain might activate the pain-killing system to actively look for relief. To prove this, and to try and identify where in the brain this system was activated, the team designed a pair of experiments using brain scanning technology.

In the first experiment, the researchers attached a metal probe to the arm of a series of healthy volunteers - and heated it up to a level that was painful, but not enough to physically burn them. ̽��ֱ��volunteers then played a type of gambling game where they had to find which button on a small keypad cooled down the probe. ̽��ֱ��level of difficulty was varied over the course of the experiments - sometimes it was easy to turn the probe off, and sometimes it was difficult. Throughout the task, the volunteers frequently rated their pain, and the researchers constantly monitored their brain activity.

̽��ֱ��results found that the level of pain the volunteers experienced was related to how much information there was to learn in the task. When the subjects were actively trying to work out which button they should press, pain was reduced. But when the subjects knew which button to press, it wasn't. ̽��ֱ��researchers found that the brain was actually computing the benefits of actively looking for and remembering how they got relief, and using this to control the level of pain.

Knowing what this signal should look like, the researchers then searched the brain to see where it was being used. ̽��ֱ��second experiment identified the signal in a single region of the prefrontal cortex, called the pregenual cingulate cortex.

“These results build a picture of why and how the brain decides to turn off pain in certain circumstances, and identify the pregenual cingulate cortex as a critical ‘decision centre’ controlling pain in the brain,” said Seymour.

This decision centre is a key place to focus future research efforts. In particular, the researchers are now trying to understand what the inputs are to this brain region, if it is stimulated by opioid drugs, what other chemical messenger systems it uses, and how it could be turned on as a treatment for patients with chronic pain.

Reference
Suyi Zhang et al. ‘ ̽��ֱ��control of tonic pain by active relief learning.’ eLife (2018). DOI: https://doi.org/10.7554/eLife.31949

Researchers from the UK & Japan have identified how the brain’s natural painkilling system could be used as a possible alternative to opioids for the effective relief of chronic pain, which affects as many as one in three people at some point in their lives.

Pain can actually help us recover by removing our drive to do unnecessary things - in a sense, this can be considered ‘healthy pain’.

Ben Seymour

Penn State

Prescription bottle for Oxycodone tablets and pills on metal table

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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

Sträng

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Living with adversity: What Tupac and Eminem can tell us about risk factors for mental health

cjb250 — Tue, 12 Apr 2016 08:40:56 +0000

Tupac Shakur and Eminem are often touted as two of the greatest rappers of all time. While Tupac, who was shot dead in 1996, is African American and Eminem is Caucasian, their lyrics have similar narrative story telling styles that are filled with anguished suffering and anger conveyed in their hip-hop songs. ̽��ֱ��characters they portray in their lyrics are often surrounded by challenging environments – alcohol and drug addiction, parental abuse and gun crime, for example.

Two songs that describe important issues of adversity reflecting strong emotional turmoil in their lyrics are ‘Death around the corner’ from Tupac Shakur’s album, ‘Me Against ̽��ֱ��World’, and ‘Cleaning out my closet’ by Eminem from his album, ‘ ̽��ֱ��Eminem Show’. In both songs, whether knowingly or unwittingly, the artists’ characters reveal many of the symptoms of mental illness – and also paint a picture that suggests why these problems have arisen.

In ‘Death around corner’, Tupac portrays a fictional character preoccupied with paranoia about a perceived threat to his own life and to his family. He feels the need to protect himself and his family from perceived targeted violence.

Straight away, the song opens with a skit, a dialogue between Tupac’s character, his partner, and their son. Tupac’s character is standing by the window with an AK47 firearm. His son is confused about his father’s strange behaviour and his wife is exasperated with her partner and feels he is consumed by his paranoia. She refers to Tupac’s character as “being crazy” and notes that he is neglecting his family (“you don’t work…you don’t do a…thing”). It is apparent that she does not share his concerns about their family’s safety and appears very irritated that he is preoccupied by his worries. What is particularly concerning is that the character – who is likely paranoid without justification – is carrying a potentially loaded gun at home whilst a vulnerable child and partner present and witnessing this behaviour.

̽��ֱ��first verse makes reference to his need to stay ‘high’, probably through use of either a stimulant or cannabis, which are both risk factors for developing psychosis and paranoia.

̽��ֱ��character describes his harsh urban environment as being where the “skinny” people “die” – in other words, where the weak are killed or exploited. ̽��ֱ��environment appears to be a place where vulnerable individuals can develop social defeat, which research has shown is a risk factor for psychosis.

Tupac’s character alludes to his daddy being “madder than a motherfucker”, which may indicate that the character has an increased risk of developing psychosis due to genetic factors, as we know people with a family history – particularly a parent or sibling – are at increased risk. He subsequently goes to bed “with my pistol in my sheets” due to feeling paranoid.

In the first verse, Tupac mentions his character’s use of “endo” (cannabis) and how it relieves his stress and paranoia. In the next verse, though, he mentions how smoking “…too much weed got me paranoid, stressed”. Is he contradicting himself here? Not necessarily: it depends on the type of cannabis that Tupac’s character has smoked which could explain both the increases in his paranoia and his relief from it – while some forms of cannabis are relatively benign, others, such as ‘skunk’, have been shown to increase the risk of psychosis.

Later, Tupac goes on to describe how his character was “raised in the city, shitty” at an early age, “drinking liquor out my momma’s titty” (a reference to his mother’s excessive alcohol use during early childhood whilst breast feeding), and possibly being exposed to second-hand cannabis smoke from an early age. All these risk factors highlight a chaotic household, which may have had an adverse effect on his developing brain – again leading to the development of psychosis in later life.

It’s clear from these lyrics that Tupac’s character has a family history of psychosis, that he abuses stimulants or cannabis, and that he lives in a harsh environment. All of these factors we know alter an individual’s brain chemistry and in particular how it responds to the key neurotransmitter dopamine, which research has shown leads people to fixate on or give too much emphasis to things in our environment or within our own thoughts, feelings or senses – and hence drive mental health issues such as paranoia and psychosis.

There is another way of looking at Tupac’s character, though: it’s possible that he is experiencing some form of Post Traumatic Stress Disorder (PTSD) following experiencing and witnessing life threatening situations from living in a violent hood “..I guess I seen too many murders…”. His behaviour certainly seems to match some of the common symptoms for PTSD: the frequent looking out of the window and paranoia could be seen as hypervigilance and hyperarousal which are prominent symptoms. His mention of seeing death around the corner could be referencing intensive flashbacks, ‘reliving’ of murders he has witnessed, and his use of “weed” might reflect the use of cannabis for ‘self-medication’.

Eminem’s song 'Cleaning out my closet' follows a similar trend of highlighting early adverse experiences. ̽��ֱ��song deals with Eminem’s angst against his mother.

In the first verse, Eminem highlights how he can’t keep his emotion in check and describes them as “the oceans exploding” attributing it to his parents relationship, their “tempers flaring”.

̽��ֱ��chorus indicates that Eminem wishes to exorcise his emotional demons by voicing his angst in his lyrics. He uses the metaphor “but tonight I’m cleaning out my closet” to acknowledge that he would rather reveal his “skeletons” than allow them to eat away at him.

It appears he is trying to reach out to listeners as though they are psychotherapists. His character discloses his secrets in order to feel free from torment. Sigmund Freud described depression as anger turned inwards, often towards traumatic childhood experiences, hence we can see Eminem’s psychotherapy with the listeners as an opportunity to let go of the buried anger in an attempt to protect himself from depression.

̽��ֱ��rest of the second verse involves Eminem making accusations against his detached, absent father, and Eminem promises to be different by being present for his daughter. It also reveals Eminem avoiding killing his ex-girlfriend and her partner (for the sake of his daughter), therefore he’s able to control his angry impulses.

̽��ֱ��next verse explores his mother’s addiction to prescription pills, which echoes Eminem’s self-declared battle with addiction to prescription pills. This also highlights his increased risk of substance misuse partly due to his familial genetic predisposition.

Eminem’s character accuses his mother of Munchausen’s syndrome by proxy – where a mother fakes her child’s symptoms (or even worse, causes real symptoms) to make the child seem sick – describing himself as a “victim of Munchausen’s syndrome”. In this syndrome, it is believed that the intention of the caregiver is to gain attention and to receive commendation as the rescuer of the child for saving the child in their care from the illness. They do this to fulfill their need for attention by placing the sick role on to their child.

Eminem ends the song by accusing his mother of being jealous of his success and reveals his intention of not allowing her access to his daughter to protect her from becoming a victim of the abuse he experienced.

Interestingly, in a song released by Eminem later in 2013, entitled ‘Heights’, he regrets these harsh views toward his mother as previously written in ‘Cleaning out my closet’ and instead acknowledges his mother’s difficulty raising him as a single parent.

̽��ֱ��suffering and painful feelings revealed by Tupac and Eminem’s characters offer us a valuable insight to examine mental health themes related to psychosis and social adversity. By utilising the interests of individuals who listen to hip-hop music – especially young people – we aim to enhance their understanding about mental health by delivering medical information in a context-enhanced manner. Perhaps this urban influenced approach will help empower and encourage individuals to examine what adversity is around the corner for them personally, and to explore what risk factors may still be locked away in their own closets.

Hip-hop artists Tupac and Eminem are among the most iconic music artists of the past two decades, and as Dr Akeem Sule and Dr Becky Inkster, co-founders of HIP-HOP-PSYCH, write, their lyrics can provide a valuable insight into the lives of some of the people most at risk of developing mental health issues.

̽��ֱ��suffering and painful feelings revealed by Tupac and Eminem’s characters offer us a valuable insight to examine mental health themes related to psychosis and social adversity.

Eminem - Cleanin' Out My Closet

Paal K.

Tupac banner (cropped)

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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)

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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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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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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