Part I
Routes to addiction
Chapter 1
From substance use to addiction
Willm Mistral
Introduction
We all use psychoactive substances which have the possibility of leading to addiction. We might take medication from a pharmacist or doctor to manage physical or mental illness; or drink coffee to keep us going through the day; or take a glass or two of wine, whisky, or beer to unwind; or smoke cigarettes; or share a marijuana joint; or snort cocaine; or inject heroin; or use other substances which have relatively minor or profound effects on our psychological or physiological state. The use of potentially addictive substances is commonplace. We are not, however, all addicted.
The Diagnostic and Statistical Manual of Mental Disorders, now in its Fifth Edition DSM-5 (American Psychiatric Association, 2013), is generally considered the gold standard text on the diagnostic features of every recognised mental illness, and this includes substance use disorders. DSM-5 recognises substance-related disorders from the use of a range of different drug classes including alcohol, caffeine, cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, stimulants (including amphetamine-type substances, cocaine and other stimulants), and tobacco.
DSM-5 lists 11 criteria from which a diagnosis of an addictive disorder may be made:
1 Taking the substance in larger amounts or for longer than you meant to.
2 Wanting to cut down or stop using the substance but not managing to.
3 Spending a lot of time getting, using, or recovering from use of the substance.
4 Experiencing cravings and urges to use the substance.
5 Not managing to do what you should at work, home, or school, because of use.
6 Continuing to use, even when it causes problems in relationships.
7 Giving up important social, occupational, or recreational activities because of use.
8 Using substances again and again, even when it puts you in danger.
9 Continuing to use, even when you know you have a physical or psychological problem that could have been caused or made worse by the substance.
10 Needing more of the substance to get the desired effect (tolerance).
11 Development of withdrawal symptoms which can be relieved by taking more of the substance.
DSM-5 bases the severity of an addictive disorder on the number of criteria met:
ā¢ 2ā3 indicate a mild disorder
ā¢ 4ā5 a moderate disorder
ā¢ 6 or more indicate a severe disorder.
So, standards have been established that allow substance use disorder, or addiction, to be diagnosed, and these are accepted by a large proportion of professionals working in the field of addiction. Now, this begs the question: how common is addiction?
Alcoholism is a common addictive disorder, particularly in the developed countries of the west. The Global Status Report on Alcohol and Health (World Health Organization, 2014) states that in the UK, 16.3 per cent of men and 6 per cent of women have an alcohol use disorder, while in the US these percentages are 10.7 per cent and 4.2 per cent respectively. Furthermore the same report states that, worldwide in 2012, 3.3 million deaths were attributable to harmful use of alcohol.
For obvious reasons, it is more difficult to come to firm conclusions about the use of, and problematic use of, illegal drugs. However, the World Health Organization (WHO) has estimated that in 2010 between 153 million and 300 million people aged 15ā64 (3.4 per cent to 6.6 per cent of the world population in that age group) had used an illicit substance at least once in the previous year. And, in 2010, there were an estimated 15.5 million to 38.6 million problem drug users (almost 12 per cent of illicit drug users). It is also estimated that there were between 99,000 and 253,000 deaths globally as a result of illicit drug use (WHO, 2012).
In order to prevent or ameliorate problems deriving from substance use, it is useful to know why some people move from use to addiction, and how that process occurs within both body and mind. There has been a substantial amount of research seeking to identify risk factors for the development of addiction and, although these factors are often found to be inter-related, it can be helpful to consider them under different headings: Neurological, Genetic, Psychosocial, and Resilience.
Neurological factors
The DSM-5 (American Psychiatric Association, 2013) tells us that central to problems arising from psychoactive substance use is activation of the reward system in the brain. The reward system originally developed to promote survival by rewarding behaviour such as feeding, drinking, seeking shelter, and sexual reproduction. Many psychoactive drugs stimulate this same reward pathway. Although different types of drugs operate via different pharmacological mechanisms, all substances capable of leading to addiction have one thing in common, and that is that they increase the activity of the neurotransmitter dopamine in the reward pathway of the brain. Dopamine is produced when the brain receives a stimulus coupled with a reward, and will reinforce a behaviour because it produces a feeling of pleasure, and so is the driver of both intentional behaviours and desire. The reward pathway crosses the limbic region, or emotional centre, of the brain and connects with the orbito-frontal cortex or decision-making area. When drugs are used to excess, they may take over the normal functioning of the reward pathway. Drug molecules can merge with the brainās communication system and disrupt the way that nerve cells normally send, receive, and process information. New research has proposed that addictive behaviours are the product of an imbalance between separate, interacting neural systems which accounts for poor decision-making leading to increased risk of addiction and relapse (NoĆ«l, Brevers and Bechara, 2013).
Neuroadaptation or tolerance
Drugs such as heroin have a similar chemical structure to that of neurotransmitters naturally produced in the brain, and this similarity allows them to have a powerful effect. Other drugs, such as cocaine, ecstasy, or crystal methamphetamine, cause the release of large amounts of natural neurotransmitters, and can also block the process by which they are metabolised. This results in the brain becoming flooded with neurotransmitters. A number of biological responses attempt to restore the rate of neurotransmission to normal levels, and the mechanism of regulating neurotransmission is called homeostasis.
The term neuroadaptation, or tolerance, is used to describe this effort to maintain homeostasis. The concept of tolerance is important for understanding addictive behaviour, as a user has to keep increasing the dose to get that same effect. A long-term heroin user may need to inject four or five times a day, and use larger doses, to achieve the same effect compared with a less experienced user who may inject once or twice a day with relatively small doses. Over time, regular stimulation of the reward system by a psychoactive substance causes the brain to produce less dopamine and also to reduce activity within the dopamine receptors. In other words, the brain adapts to the presence of the drug and if the drug is stopped, the brain chemistry is no longer in balance and can take a considerable amount of time to re-adapt. The effects of this, once tolerance has developed and the drug effect starts to wear off, is that a person begins to experience a range of uncomfortable withdrawal symptoms such as nausea, depression, or aches and pains. These symptoms may last from a few hours to a few days but can be stopped immediately by re-taking the drug. This provides a strong motivation to keep on using.
Once tolerance is developed to one drug, it applies to all drugs in the same class. If tolerance is developed to heroin, for example, it will apply to other opiates such as morphine, codeine, and methadone. Without tolerance, reducing the amount of drugs used and gradually stopping use altogether would be considerably easier. However, tolerance does diminish during periods of abstinence and drug users become more susceptible to the effects of the drug. This accounts for the fact that, for drug users who return to use after release from prison, overdose rates peak and there is a high risk of drug-related death in the first few weeks (e.g. Merrall et al., 2010; Binswanger et al., 2012).
Genetic factors
The extent to which addiction may be influenced by heritable factors can be derived from genetically informative research designs, including family, adoption, and twin studies. Although family studies conclude that substance use disorders cluster in families, simply looking at familial similarity in behaviour cannot distinguish whether the influences on behaviour patterns are genetic or environmental (Agrawal and Lynskey, 2008). Well-designed adoption studies, however, can map any correlation between offspring behaviour with regard to problematic substance use, and the characteristics of both the biological and adoptive parents. Similarity between offspring and biological parents suggests genetic influences on that behaviour, while similarity between offspring and adoptive parents suggests environmental influences. One study in Sweden (Kendler et al., 2012) included a national sample of 18,115 adopted children born between 1950 and 1993; 78,079 biological parents and siblings; and 51,208 adoptive parents and siblings. Risk for addiction was found to be significantly increased in the adopted children of biological parents with addiction problems. But, liability to addiction was also affected by a range of environmental factors in the adoptive home including marital instability, psychopathology, and criminal behaviour. However, the adverse environmental effects on addictive behaviours were seen to be more pathogenic in individuals with high levels of genetic risk. The authors concluded that problematic substance use is an aetiologically complex syndrome strongly influenced by diverse genetic risk factors including a specific liability to addiction, and a general vulnerability to other criminal or psychiatric problems (Kendler et al., 2012). This study confirmed and extended previous studies (e.g. Kendler et al., 2000; Lynskey et al., 2002) showing a strong contribution of genetic factors to the aetiology of addictive problems.
Agrawal and Lynskey (2008) argue that twin studies have several advantages over both family and adoption designs for the study of addiction. For adoptive studies, neither biological nor adoptive parents may be representative of the population. This is because biological parents whose children are put up for adoption are more likely to have higher rates of disorders, including psychiatric problems and drug dependence, while conversely, adoptive parents are less likely to have recognised disorders, as well as, on average, being older and relatively socially advantaged.
The gold-standard twin study utilises identical (monozygotic or MZ) and fraternal (dizygotic or DZ) pairs of twins, each pair brought up together so as to nullify any confusion between the effects of genetic and environmental influences on any measured outcome. MZ twin pairs share, on average, 100 per cent of genetic influences while DZ twin pairs share 50 per cent of genetic influences. Shared environmental factors overlap 100 per cent between twin pairs raised together, presuming no one individual receives or perceives specifically different environmental input.
Following a review of a range of research evidence, including adoption, family and twin studies, Agrawal and Lynskey (2008) concluded that a convergence of findings provided compelling evidence that addiction to alcohol, nicotine, and illicit drugs is influenced by inheritance. Nonetheless, efforts to identify individual gene contributions to addictive disorders have been unsuccessful. It seems that multiple genes have a small, interactive and cumulative effect which shapes a liability to addictive behaviours.
It is important to remember, however, that there is nothing deterministic about this genetic influence, and findings vary considerably between different studies. Research has been cited indicating that between 48 per cent and 66 per cent of the variation in alcohol dependence is heritable (Agrawal et al., 2012); and large scale studies of opioid addiction show that, in men, between 23 per cent (Kendler et al., 2000) and 54 per cent (Tsuang et al., 1998) is attributable to genetic factors. This means that environmental, or psychosocial, factors may wield a considerable amount of influence. With rapid advances in gene technology there is likely to be an acceleration of discoveries which could identify specific genes conveying increased risks, or at least increase understanding of how genetic and environmental risks interact to shape liability to addiction.
Interaction of genes and environment
Different ways have been theorised in which genetic and environmental influences may be associated. One way is referred to as passive correlation. For example, children of parents who engage in problematic use of alcohol or other drugs may inherit genetic risk factors and, at the same time, be exposed to parental modelling of excessive use of alcohol or drugs, and have easy access to these substances, thus encouraging use. A second form of association is known as active correlation. This occurs when individuals with particular genetic propensities to alcohol or other drug use are moved to actively seek out corresponding environments. A third form of interplay is referred to as evocative correlation and occurs when genetically mediated traits in a child stimulate particular reactions in other people who then influence the childās environment (Lenroot and Giedd, 2011).
Of course, as well as applying to addictive or other pathological behaviours, these geneāenvironment interactions may equally influence more positive behaviours. For example, children who have a genetic tendency towards sport, music, or some other creative activity may either be raised in or seek out environments that encourage and support these activities. These positive interactions may encourage and support resilience and provide protection against addictive behaviours even if these children experience early-life environmental stressors. So, genetic and environmental factors may be correlated or interact in a range of different ways, both positive and negative. There is a growing literature demonstrating differences in gene expression as a function of environmental experience, and which shows the significant effects that the social world can exert on gene expression (Dick, 2011). We can safely say that the concept of nature versus nurture is obsolete, and there is little evidence that genes and environment act independently of each other (Moffitt, Caspi and Rutter, 2005; Agrawal and Lynskey, 2008).
However, in the light of research showing the powerful effects of environmental factors on substance misuse and addiction, an argument has been made from a public health standpoint that the benefits of genetic research in this area are relatively small. This is because genetic variants have relatively minor effect sizes, while environmental factors have a strong influence, are easier to identify, and are probably easier to modify (e.g., Merikangas and Risch, 2003). It is argued, therefore, that efforts to prevent exposure and use would be a far more effective intervention, even if gene-based treatment strategies should emerge. However, Agrawal et al. (2012) counter that the goal of genetic research is to provide a therapeutic alternative for people who remain addicted despite numerous repeated environmental interventions and treatment.
Psychosocial factors
Strong evidence related to psychosocial influences and an increased risk of addiction has come from longitudinal studies that follow individuals from an early age. Some research evidence suggests that variation in some genes may simply increase the risk of the development of addictive disorders in individuals who have experienced significant childhood stress (Heath and Nelson, 2003). A comprehensive evaluation of the influence of early-life stress has shown this to be a non-specific predictor of many forms of psychopathology and pathological behaviours, including early-onset drinking and adult addiction to alcohol and other drugs (Enoch, 2011). Nevertheless, of children exposed to severe maltreatment only 50 per cent or fewer go on to develop psychopathology, including addictive disorders, by early adulthood (DuMont, Widom and Czaja, 2007). This balance of risk and resilience with regard to vulnerability may result from a complex interaction between genetic and social-environmental influences (see Enoch, 2012, for a detailed discussion).
One UK study, involving a survey of over 5,700 school-students with an age range of 13ā15 years, gathered robust information on a wide range of social influences on their levels of alcohol consumption (Bremner et al., 2011). It developed evidence of how different psychosocial influences work together, including demographic characteristics, individual behaviours, and family and local context, as well as media and celebrity influences. The study found that 70 per cent of younger students and 89 per cent of the older cohort had drunk alcohol, with regular drinking significantly more frequent amongst the older cohort. Overall the stu...