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David Nutt outlines what is understood about the complex relationship between addiction and the brain. Ed.


pleasurable activities, often extremely so. This had lead to the theory that they hi-jack the brain’s pleasure-reward systems so that naturally rewarding activities become devalued and the more excessive addiction behaviours take over.


Addiction and the brain


Addiction is a major health problem that costs as much as all other mental illnesses combined and about as much as cancer and cardiovascular disease. In essence, addiction is a state of altered brain function that leads to fundamental changes in behaviour that are usually resisted – though unsuccessfully – by the addict. The key features of addiction are a state of habitual behaviour such as drug taking or gambling that is initially rewarding though can eventually become self-sustaining or habitual. The urge to engage in this behaviour can become so powerful that it interferes with normal life, overtaking work, personal relationships and family ties to the point that the addict’s whole being is directed to their addiction. Moreover feelings of intense distress emerge when the addiction is thwarted and these can lead to dangerously impulsive and sometimes aggressive actions. In the case of addiction to drugs, the situation is compounded by the occurrence of withdrawal reactions which cause further distress and motivate desperate attempts to find more of the addictive agent; this urge to get the drug may be so overpowering that addicts will commit seemingly random crimes to get the resources to buy more of the drug. It has been estimated that about 70% of all acquisitive crime is associated with drug and alcohol use.


Addiction is occasioned by a complex set of internal and external factors. Although most addiction is to alcohol and other drugs, addiction to gambling and other behaviours, for example sex and spending, can occur. These tell us that the brain can develop hard-to- control urges independent of changing its chemistry with drugs. All addictions share a common thread of being initially


be seen as a loss- of-control over what starts out as a voluntary behavior. This is not as some like to suggest simply a lifestyle choice but reflects an enduring, probably permanent change in brain function…


“…addiction can


However, not everyone who engages in drug use or other rewarding behaviours becomes addicted to them so clearly other factors are important. These are not well understood but include concepts such as excessive rewarding effects in some people, a failure of adaptive coping strategies in others and aberrant habit learning as well. Some addicts may have a mixture of several of these vulnerability factors and there are also genetic predispositions to some of them. Also a significant amount of drug use is for self-medication for example cannabis for insomnia, alcohol to reduce anxiety, opioid for pain, stimulant for undiagnosed/untreated attention deficit hyperactivity disorder (ADHD) and this use can develop into addiction in some people though by no means all.





The rewarding effects of addictions are mediated either through the release of dopamine (cocaine, amphetamine and nicotine) or through activation of endogenous opioid systems (heroin) or both (alcohol). The pleasures are then laid down as deep-seated memories, probably through the changes in glutamate and GABA-A receptors that are involved in all memories. These memories link the location, persons and experiences of drug use (or other addictive behavior) with their pleasurable effects. These memories are often some of, if not the most powerfully positive ones the person may ever experience, which explains why so much effort is put into recreating them. When they re-occur in abstinence, they are experienced as cravings that can be profound, urgent and lead to relapse.


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A great deal of research has been conducted into the role of dopamine in addiction and we now know that a low density of dopamine receptors seems to predispose to excessive dopamine response from stimulant use. This excessive response is thought to initially occur in the reward centre of the brain (the nucleus accumbens) but then move into other dopamine-rich areas especially the caudate/putamen where habits are laid down. This shift from voluntary choice- use to involuntary habit-use explains well a common complaint of addicts that they don’t want to continue with their addictions, and even that they don’t enjoy the behaviour anymore, but can’t stop themselves. In this sense addiction can be seen as a loss-of-control over what starts out as a voluntary behavior. This is not as some like to suggest simply a lifestyle choice but reflects an enduring, probably permanent change in brain function which can be modeled in animals.


We know that personality traits such as impulsivity predict excess stimulant use and in animals this can be shown to correlate with low dopamine and high opioid receptor levels. Similarly in humans, low dopamine and high opioid receptor levels predict drug use and craving. These observations give new approaches to treatment, both psychological interventions such as behavioural control, and anti-impulse drugs such as those used for ADHD for example atomoxetine and modafinil. Another major relapse precipitant is stress; this may work through increasing dopamine release in the brain so priming this pathway or by interactions with other neurotransmitters such as the peptide substance P. As antagonists of these neurotransmitters are now available they are being tested in human addictions.


Professor David Nutt, Chair in Neuropsychopharmacology Imperial College London


Further reading


Nutt DJ Lingford-Hughes A (2008) Addiction the clinical interface Brit J Pharmacology 1-9


Nutt DJ, Law FD (2008) Pharmacological and Psychological aspects of drug abuse. New Oxford Textbook of Psychiatry 2nd


edition


Robbins TR, Everitt B, Nutt DJ (2010) The Neurobiology of Addiction – New Vistas. OUP


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