What is addiction?

03 July 2018

Interview with

Dr Amy Milton, Cambridge University

What is addiction, and how does it work in the brain? Katie Haylor spoke to neuroscientist Amy Milton from the University of Cambridge...

Amy - So addiction, we normally think about in the context of drugs of abuse like opioids that we just heard about. In addiction, behaviour narrows very, very markedly to being really focused on drug seeking and drug taking behaviour and that’s to the exclusion of everything else. So people losing their jobs, their family, and so on. And the key characteristic of addiction is that there is a lot of control over that behaviour. So people are aware of the fact that these behaviours are hurting them, but they can’t do anything to stop doing it, and it’s a chronic and relapsing disorder. So people will often manage to get off drugs for a period of time but then they’re very at high risk of relapse for the rest of their lives actually.

Katie - Do we know how addictions work in the brain?

Amy - We have a pretty good idea. As you can imagine, for a complex mental health disorder there are lots of things that go wrong - there are a few key things though. One is that drugs of abuse massively increase the amount of dopamine within the brain, and dopamine is a really, really key chemical for learning about things that are motivationally relevant to you in your environment.

So we normally learn about rewards - natural rewards like food and mates and so on, with big increases in dopamine. Drugs of abuse increase dopamine massively more than natural rewards, so hundreds of times more. What this means is that the behaviours that lead to the drugs being obtained, are far more likely to be engaged in. There is a shift, very very quickly, because dopamine encourages this from goal directed behaviour - doing something because you want the outcome - to habitual behaviour where we just do it because that’s what we do in a particular environment.

Dopamine increases the influence that the environment has over behaviour, so cues in the environment that are predictive of drug rewards come to be far more attention grabbing and controlling of behaviour. And, the key clincher is that there is a loss of cognitive control mechanisms mediated by this area called the prefrontal cortex. Many drugs of abuse are very toxic to the prefrontal cortex, and people who tend to become addicted often have lower inhibitory control to start with and the drugs of abuse reduce that inhibitory control further. So that habit becomes a compulsive habit.

Katie - Can anything be addictive?

Amy - That’s a really good question. With drugs of abuse it’s very, very clear that there’s something unnatural in the body and that drugs of abuse hijack our natural reward system. When you’ve got a natural reward, so something like high fat, high sugar foods have been suggested as potentially addictive, gambling, other sorts of potentially behavioural addictions, it’s often harder to tell whether that’s a hijacking of a natural reward system, or it’s just a natural reward system itself. So sex addiction or food addiction is much, much harder to quantify and it really comes down to, is the behaviour having really adverse outcomes on the person who’s engaging in them.

Katie - So if someone is addicted to something, what happens if they don’t get their fix?

Amy - So they go into withdrawal, but there are at least two different types of withdrawal: physiological and psychological. Physiological withdrawal, it’s really obvious withdrawal signs. So if somebody stops using heroin for example and they have been using for a long time, they will show a particular set of symptoms like getting a really bad dose of flu, they often get quite bad diarrhoea, all these physical symptoms that are quite clearly there. What you get with psychological withdrawal is the system has been massively overstimulated for a really long period of time so the reward system has gotten used to being active at certain level. When the system like that is overstimulated, it becomes less sensitive. It's like the cells that are receiving the signal, kind of, put their hands over their ears. They are no longer listening unless they’re being shouted at.

So you take that drug away and you go back to normal physiological level of stimulation, those cells that are receiving the signal aren’t listening anymore. And so you get a rebound effect where people feel very depressed, they often feel very anxious. And the way of getting out of that state is by going and engaging in those drug seeking and drug taking behaviors again.

Chris - It was made as a joke at the Edinburgh festival by a comedian, but it sort of has a serious side to it which is this person said “why don’t you just take hundreds of drugs because then your body won’t know what to get addicted to”. But how do you, or how does your brain, make the association between a particular drug and you know you’re hooked on it?

Amy - All drugs of abuse, even though they all have very different actions in the brain, so nicotine, very different from heroin, very different from cocaine, all of them have this common action of increasing dopamine in a particular part of the brain called the nucleus accumbens. And every single drug that has abuse, that is addictive, has that effect, and you are very very good at learning in a completely unconscious way which environments or cues predict which particular outcomes and you can see variation. There are even experiments in rats showing that if you have rats who can self-administer cocaine or heroin in different environments, they tend to take heroin when they are in their home environment and they tend to take cocaine when they are out in a novel environment. So these environment really influence drug seeking and drug taking behavior as well in a quite a complicated way.

Chris - So if I fed someone pancakes, but also injected them with heroin without them realising it, would they form the addiction to pancakes so that they would then get the pleasure from the pancake because the reinforcement was there but they didn’t know it was heroin it was doing it, it was the pancake.

Amy - so I guess it would depend on how much experience they had with pancakes before. If they had experienced pancakes many times before and yet your pancakes are that much better, they will only seek out your pancakes and presumably you’ll give them heroin again. If they had not experienced pancakes before, then they may associate that euphoric rush with the taste of the pancakes. There may be a little bit of carry over to subsequent pancake experiences even without the heroin but i think they would very rapidly extinguish and just go back to normal pancake eating habits, unless they were getting your heroin laced pancakes again.

Katie - For someone who does have an addiction, what kinds of treatments are there?

Amy - So we are very limited in the treatments that we have at the moment. There are treatments that exist, like the 12 step programme, which don’t necessarily have a strong scientific understanding, but if they work for certain people then they should use them. But other drugs of abuse, like cocaine, there are no approved treatments. For other drugs like nicotine or heroin, we’re looking at replacement therapy as the alternative. For drugs like alcohol, there’s antabuse. But quite often people will stop using antabuse which produces hangover like symptoms rapidly when somebody drinks alcohol. What tends to happen is people will stop using the antabuse and carry on using the alcohol. So there is a real clinical treatment need and a real push for new treatment development, which is one of the things that my lab and other labs here in Cambridge are doing.

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