23 November 2011

Is addiction a disease?

From social disorder to chronic disease: new research is bringing drug addiction out of the shadows, says Karen McGhee.

NOT SO LONG AGO, addiction was seen mostly as a social issue with moral parameters. Now scientists are increasingly considering addiction from a biological perspective.

The transition kick-started in the late 1980s and was propelled through the 1990s by rapidly developing technologies in neurophysiology. It’s been possible to actually see the impacts on the brains and central nervous systems of laboratory animals – and to a lesser extent people – exposed to mood-altering substances.

And genetic research – notably studies of twins and families – has increasingly pointed to a heritable basis for addiction, particularly for alcohol and nicotine, but also for methamphetamine, heroin and cocaine.

Where heritability is concerned, it’s significant also that there’s evidence of addiction and mental illness ‘comorbidity’ – the simultaneous occurrence in an individual of two or more disorders or illnesses. About 60% of people with addiction problems also suffer from mental illness. Scientists don’t believe it’s a case of one causing the other; instead, the research indicates that there are common genetic factors predisposing individuals to both.

The consensus is that whatever the genetic basis might be for addiction, it’s not going to be simple: it’s likely there is a range of genes involved, and how they function may have a lot do with the environment in which they operate. Nature, say researchers, is probably only 50% of the story. Nurture may be equally involved in how relevant genes are expressed; and if, in fact, they are expressed at all.

Away from the likely heritability issue, there is another emerging genetic angle to drug addiction. Epigenetic studies are looking at the way drugs may actually influence genes during an individual’s lifetime. For example, whether the actions of genes is altered when the DNA in our brain cells is bathed in a mood-altering substance, as early evidence indicates.

In the U.S., at least, this research has led to a major push for drug addiction to be viewed as a disease. “A chronic, relapsing disease of the brain,” is how Alan Leshner described it in a landmark commentary in the American Psychiatric Association publication Focus in 2003.

From 1994 to 2001 Leshner was director of the U.S. National Institute on Drug Abuse (NIDA), which claims to support 85% of research worldwide on the health aspects of drug abuse and addiction. His view has been actively promulgated by NIDA’s present director, Nora Volkow, and further supported by evidence from her own research. Her cutting-edge application of brain imaging to study drug effects has been instrumental in identifying mechanisms involved in the development of addiction, particularly the dopamine pathways. Also of significance, she has documented how changes in the brain’s prefrontal cortex contribute to and sustain addiction.

It’s not the first time there’s been a push from science to increase recognition of a condition to the status of mental disorder. NIDA’s current acting deputy director, David Shurtleff, offers the example of schizophrenia, now acknowledged as a diagnosable and significant brain disease. Yet, right up until the latter stages of last century, the symptoms of schizophrenia were widely thought to arise in people with unemotional mothers who hadn’t hugged them enough as children.

Of course, Shurtleff points out, addiction differs from other diseases in that it requires the taking of a drug in the first place for it to progress. But from that point on, the disease takes hold. “With chronic drug use, the brain changes in fundamental ways,” he says. “And that’s related to this compulsive drug seeking, drug craving, that becomes addiction.”

Addiction treatments in the U.S continue to take a multi-pronged approach, where behavioural therapy remains a major component. “But what the [science] has given us is biological targets,” says Shurtleff. “We now understand how every drug of abuse acts in the brain; we know the key targets and where the drug acts, and by knowing those key targets we can think about developing medications that can help improve treatment outcome.”

In Australia, the paradigm of addiction as a disease is not quite so entrenched, and its acceptance seems to be influenced by the area of research in which a scientist works. Those researching addiction at the cellular and molecular levels, for example, seem less resistant to the disease model.

Neuroscientist Andrew Lawrence, associate director of Melbourne’s Florey Neuroscience Institutes, has no reservations about labelling addiction as a disease.

“It’s a brain disorder, as far as I’m concerned, no different to any other,” he says. “The bottom line is that it’s a brain disorder that’s been propagated by drug-induced adaptations in the way the brain functions. And once a person is addicted, they’ve got a brain disorder because they want to stop taking the drug but there’s a number of factors happening inside their brain that’s making that very hard to do.”

Lawrence’s current research is aimed at understanding the cellular and molecular shifts that take place in the brain when addiction takes hold: what processes underpin the transition from casual social drug use to compulsive addicted drug use. Once that’s understood, science will potentially have a much better way of targeting therapies. And it might also one day be possible to assess the likelihood of an individual becoming an addict.

Drug use is widespread in the community, particularly in people under 30, says Lawrence, and yet the majority of people who experiment with drugs do not become addicted. “It’s the minority that become addicted, and that tells us straight away that it’s more than just the drug that causes addiction,” he explains. “Obviously some people are more prone to becoming addicted than others.”

This is borne out by animal studies in which addiction rates are similar to those of humans. “If you let animals self-administer for extended periods of time – so you can really see them becoming addicted to a compound, rather than just casually using a compound – you get a very similar proportion of animals that demonstrate addiction-like symptoms versus those that behave more like casual users.”

And so that presents the opportunity to investigate what’s happening in the brains of animals that are prone to addiction compared to those that aren’t. The field has already identified some specific neuronal pathways where there is dysfunction in addiction-prone animals that is not obvious in more ‘resilient’ animals.

“How that dysfunction occurs remains to be answered,” says Lawrence. “But once we get on top of those issues, we will have a much better understanding of the molecular sequence of the events that may dictate an individual’s propensity to become addicted. The reality at the moment is that it’s Russian roulette, because you just don’t know what trajectory you’re going to pass through.”

Michael Farrell, Australia’s new director of the National Drug and Alcohol Research Centre, based at the University of New South Wales in Sydney, is reluctant to use the term ‘disease’ when it comes to drug addiction. Not everyone working in the field, he says, is comfortable with the disease paradigm for drug addiction.

“Condition, disorder, disease; it’s all a bit semantic,” he says. “I think the challenge for us is that this is a behaviour with a spectrum to it, so that actually trying to get it into one little box probably doesn’t do justice to the range of behaviours, particularly when we look at it from a health promotion point of view.”

All the new research and understanding surrounding drug addiction should not, Farrell says, be about removing personal responsibility for drug use in the first place – and the disease model risks doing that. “These things still retain personal responsibility and always retain personal responsibility,” he says. “But [the research] is actually about improving our ability to find and develop new ways to intervene to help people who have got rather life-destroying conditions.”

There is, he says, a significant message about drug use that’s being reinforced by the improved understanding. “And the message is clearly, ‘Be careful, be very controlled, be responsible,'” Farrell says. “I don’t think the idea is that you then turn over to some system where you say, ‘Well, it’s a brain disease, therefore we can’t do anything about it’. It shouldn’t be that way, it should be far more: ‘Yes, we need to understand more about it, but we also need to understand the social context and the broader responses.'”

There is a positive spin, however, on the promotion of addiction as a disease, first suggested by Leshner and then Volkow. “What they’ve been trying to do is make it respectable, because addiction is probably the most stigmatised and marginalised condition,” Farrell says. “And people exert, unwittingly and understandably, moral judgement on behaviours they see as not good. Part of the issue is trying to get people to understand that some of these conditions aren’t simply bad behaviour.”

Karen McGhee is a science writer based in Sydney.

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