Smokers cling to the ciggies for dear life, knowing it will likely be a much shorter one.

An anti-smoking drug released in Australia targets nicotine receptors in the brain, working differently to traditional nicotine replacement therapies.

But are we too fixed on a quick fix for addiction?

And, the challenge of investigating post-marketing reports that the drug may trigger suicidal thoughts and behaviour in some users.

Real side effect of the meds, or part of nicotine withdrawal?

Transcript :

Liz: My friend goes everywhere with me and I never leave the house without my friend.

Anita Barraud: You're just about to give up your friend though, aren't you?

Liz: Yes, I'm trying but it's pretty hard to leave the cigarette packet behind. That friend is always there no matter what. Never walks away on me.

Anita Barraud: Even though he's doing you wrong, really.

Liz: Yeah...

Natasha Mitchell: Natasha Mitchell joining you for All in the Mind on ABC Radio National, welcome. Today, the insidious nature of cigarette addiction and the neurobiology of nicotine.

And a new anti-smoking drug on the market; its mechanics are quite different to traditional nicotine replacement therapies. But its launch in the USA and Britain has been shrouded in controversy over potentially nasty side effects. Now it carries a warning, but what's the drug, and what's part of the process of withdrawal? And are we too fixed on a quick fix for addiction anyway? Producer Anita Barraud is your guide today.

Robert West: One of the things that nicotine does when you take it in very rapidly from cigarette smoke is it sets up a kind of habit pattern where you have a cue, you smoke the cigarette, it causes neurochemical changes in the brain which tell the brain whatever you were doing just before that is a good thing to do and you should do it again.

So in that way it builds up a kind of loop or a cycle in which you feel the impulse to smoke whenever particular situations arise. But another thing that it does is that it makes other things that are slightly enjoyable in your life more enjoyable so it acts as a kind of pleasure amplifier.

Wayne Hall: It's probably one of the most rewarding of all of the drugs of dependence in animal models. Animals will self administer this drug at very high frequency and we are increasingly developing drugs that can assist people who want to stop to stop and stay stopped.

Anita Barraud: How many times have you attempted to give up and what kind of methods?

Liz: I've probably seriously tried about three times. In the past it's been the nicotine patches that I've used. The longest I went was for about six weeks, when I decided I wanted a cigarette I'd take one off and stick it on to my cigarette pack...oh God.

Anita Barraud: Liz ruefully admitting the psychological games we play when trying to quit. Now she's trying a new anti-smoking drug that targets the receptors in our brains that normally love nicotine. The medication makes smoking boring, or even disgusting, but there may be serious side effects, as we'll hear.

To understand how the drug works we first need to understand why some of us cling to the fags for dear life despite knowing life will be shorter as a result.

Smoker 1: I suppose addiction, you just feel like you want that. I've just had a cup of coffee, the morning cigarette, so that's the start of the day really.

Anita Barraud: You don't think you could start the day without a cigarette?

Smoker 1: Probably could but I'd be a bit stroppy, I think.

Smoker 2: I started very young and I have tried to quit many times but I've been unsuccessful so... And the reason I'm smoking right now is because with the society we live in with the stress and pressure smoking is the only thing I've got, I don't drink, I don't take drugs, smoking is the only thing where I can release my stress.

Anita Barraud: So it relieves your stress?

Smoker 2: Well sometimes yes, most of the time yes.

Anita Barraud: And what kind of methods have you tried to give up?

Smoker 2: Oh, I've tried it cold turkey, the patch, tried to slow it down, even the chewies, everything.

Robert West: The stress relief is a very strange thing because smokers report this very, very strongly as something which smoking does. But whenever you look at the literature, or you try to look at it experimentally you don't find that. You find that actually cigarettes make stress worse.

Anita Barraud: Robert West is Professor of Health Psychology at the University College London and part of the team responsible for Britain's quit programs.

Robert West: When you don't smoke—there have been changes in the brain due to chronic nicotine ingestion—so when you don't smoke your nicotine levels are depleted and you start to experience unpleasant mood and physical symptoms: irritability, depression, anxiety, restlessness, difficulty concentrating. And then when you have a cigarette these are relieved.

Now obviously as an individual you are not necessarily in the position to know, and neither is your brain, whether the stress was caused by nicotine withdrawal or whether it was caused by something else.

So from the smoker's perspective all they know is that smoking sometimes, or very often, helps to relieve stress and they generalise from that to other situations and so they kind of think well it will help in every situation. And the truth is it doesn't.

Anita Barraud: You believe that it's the delivery system, the cigarette itself that's responsible for that addiction.

Robert West: Essentially it is the act of smoking that people get addicted to, but they get addicted to it because of the nicotine.

Anita Barraud: But of course smoking is a nice easy delivery system, it goes straight into the lungs, it easily makes its way through the circulatory system and into the brain.

Robert West: Yes, and what that then does is tell the brain that the activity of smoking and all the sensations associated with smoking are a good thing to do. What that then means is that if you give nicotine via another route such as a nicotine patch it'll do something, it'll help to relieve withdrawal symptoms and cravings but it doesn't give you that satisfaction that you're used to getting from cigarettes.

So the nicotine patches, they do help people to stop smoking and so do these other medications, but they don't provide enough substitute for smoking. And almost all smokers want to stop, almost all smokers have tried to stop and they find it very difficult.

And the reason they find it difficult is because of these mechanisms of addiction—which operate at a level which is not the level of conscious rational choice, it's a much deeper more basic level in the brain—tbecause nicotine is tapping into pathways that evolved long, long before humans appeared on the scene.

Neal Benowitz: We are learning now that when someone becomes addicted to tobacco as well as other drugs there are long term changes in the brain; there are changes in proteins, there are changes in the connection between nerves and there's a type of learning and memory, so there are many changes that occur in the brain with addiction that last for many years and maybe indefinitely.

We all know cases where people have quit smoking for ten years and then with a stressful situation they have a cigarette and then all of a sudden within a week they are smoking a pack a day again.

Anita Barraud: So, our brain and body are permanently primed by our nicotine addiction. And from studies of twins which help estimate how much of a given characteristic is genetic, it appears 50% to 60% of being a smoker is in your genes. A large focus now is on trying to paint that genetic picture.

Neal Benowitz is Professor of Medicine, Psychiatry and Biopharmaceutical Sciences at the University of California and a world leader in smoking cessation research. He says that nicotine hijacks the action of one of the brain's own chemicals called acetylcholine.

Neal Benowitz: Nicotine when it goes to the brain acts on receptors which are these special proteins in the brain that bind substances and signal response. And these receptors are made for the brain's own chemicals. What nicotine does is basically hijacks a receptor that's meant for acetylcholine, a chemical that transmits information from one nerve cell to the next.

Nicotine binds to the same receptors that are meant for acetylcholine, when it binds with those receptors it then causes the release of other hormones, a number of different hormones, but the hormone that is most clearly related to addiction is one called dopamine.

Anita Barraud: That's the one that tells us that having a cigarette is very pleasurable.

Neal Benowitz: Dopamine signals pleasure of all sorts and whenever you feel something that's pleasurable dopamine releases a current. And when you smoke a cigarette you artificially stimulate dopamine release to higher levels than your body would normally release.

So someone releases dopamine and finds a cigarette pleasurable, there are other hormones that have got anti-anxiety effects, calming effects, there are hormones that have stimulating effects and when you talk to smokers about why they smoke a cigarette they actually get different benefits, or perceived benefits, at different times of day.

Transcript continued, plus audio podcast, at All in the Mind.

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