Welcome, ladies and gentlemen, to this lecture on the science of addiction and how it affects people and how it affects society. My name is William Hart and I’m the Executive Director of the National Neuroscience Facility here and it’s my great pleasure to introduce this series of discussions which is part of an international series of events occurring in many countries around the globe to celebrate International Brain Awareness Week.

International Brain Awareness Week has been a significant series of events in Europe and the US for many years now but only recently have we coordinated such a series in Australia. In fact, last year we went into partnership with the Australian Neuroscience Society and the Australian Brain Foundation to put on a series of events around Australia for Brain Awareness Week. We ended up with 36 partners in the series of events that were run and 22 separate events run around Australia. This year, there are a total of 49 partners involved in putting on the events including the partners that you’re going to be introduced to shortly here for this Addiction Neuroscience series.

So the Addiction Neuroscience Network of Australia is the host for this evening’s events and I’m really only here to introduce the coordinator of this evening’s session. I did however want to spend just a moment telling you about the objectives of the Brain Awareness Week. They are basically to improve public awareness of the impact of brain and mind disorders, and addiction, of course, is one of those very, very serious brain and mind disorders. We’re beginning to learn something in terms of brain function and how it can lead to cravings and the inability to deal with problems of addiction, addiction being one of the brain and mind disorders that can affect up to 75 per cent of Australians either directly or indirectly in terms of physical brain disorders and mental health. And so this Brain Awareness Week is a joint effort between Neurosciences Australia, which I’m the Chief Executive of, together with the Australian Neuroscience Society and the Brain Foundation of Australia.

It’s now my great pleasure to introduce Professor Mal Horne. Professor Horne is going to coordinate the rest of the evening. He is the Deputy Director of the Howard Florey Institute. One of the founders of ANNA, the Addiction Neuroscience Network, and he’ll introduce the speakers for the evening. Professor Horne, thank you very much.

Thank you William. I’m not Fred Mendelson who should be here. He’s up meeting the Queen so I just had to fill in and I won’t spend a lot of time talking about what this is going to be about but let the speakers go directly into the matter. The first speaker is Adrian Dunlop and Adrian is Head of Medical Services at Turning Point Drug and Alcohol Centre at the back of it St Vincent’s. Adrian has been working with alcohol and drug clients since 1993 as a clinician, and his PhD was at the University of New South Wales where he examined the treatment of ethnic Vietnamese heroin users. So Adrian, to you.

Thanks Mal. I’m the first speaker tonight, and we’re going to try to give you a snapshot – a bit more than a snapshot actually, a detailed discussion about alcohol and drug use. I’m going to start off by talking to you about some statistics about alcohol and drug use in Australia to give you a sense of how common alcohol and drug use is, especially amongst young people which is the focus for tonight.

I guess we shouldn’t need to ask why is it important to discuss this and what are some of the impacts on our society, but it’s worth just going over some of this information briefly. It’s not all about money, but money is an important thing in determining what we do and how we respond to problems in society. So this is a study to look at the costs of drug use in our country going back a few years ago now, and you can see it’s a significant cost. Something like $35 billion dollars is spent in our society on the impacts of drug use, predominantly nicotine – predominantly nicotine, but also alcohol and illicit drug use. How do those costs impact on us as a society? Most of it is lost opportunity, lost productivity in the home and in the work place. That accounts for nearly two thirds of the costs, but the cost of motor vehicle accidents are significant at about 11 per cent, crime is about 20 per cent, and health care costs account for 7 per cent of the total.

Another way of trying to understand this is to think about other impacts like deaths. Again, you see that nicotine is responsible for far many more deaths than other drugs in our society, but alcohol is also up there with something like 3,200 deaths in 1998, and for illicit drugs there was something like 1,000 deaths. This is across our country, across Australia.

Another way of trying to understand the cost of drug use is hospital discharges. You see the same pattern yet again. The bulk of it is nicotine but alcohol is certainly well up there and the illicit drugs are represented.

But I want to particularly focus on young people in tonight’s talk and give you some details about what we know about youth alcohol use and youth drug use. One way of trying to think about this, and we’ll come back to this theme several times across tonight, is the importance of the adolescent years as being key learning years and key developmental years for young people, and drug use can have a real impact, especially if it occurs during those years. So you’ll be aware of developmental changes, going through late childhood, adolescence, through to adulthood and some of the important things that happen. The stages of development of thinking, concrete thought has developed by late childhood and then going through to adolescence, this concept, this capacity for abstract thought starts to develop and of course, you know it goes on over a number of years, and drug use, during this time can be really critical in terms of development. We’ll hear both Murat and Andy talk about some of the impacts of this, especially in those years.

And why is it important? It’s important particularly because these are the times when young people experiment. That’s a normal part of adolescent development, but whether these experiments go okay or whether they go awry are particularly determined by the resilience of young people. And some of the attachments that they have with other people, especially with key adults, are essential in those years. We’ll come back to that over the course of the evening.

Now I want to talk about patterns of alcohol and drug use, and to do that, I’m going to use a study that’s been done in the last couple of years in Victoria called the Victorian Youth Alcohol and Drug Survey. It looks at the use of drugs and alcohol in 16 to 24 year olds. In the most recent sample in 2004 about 6,000 young people were surveyed. It’s a random telephone interview, and being a telephone interview means that it can only make contact with people who have homes and have telephones. So, it doesn’t include homeless people and it’s not representative of some of the more high-risk groups. Towards the end of my talk I’ll give you a snapshot of what drug use in high-risk populations can be like.

This is a big slide but I’ll just to take you through some of the key messages here. A question asked of those 16 to 24 year olds was have you used this drug in the last 12 months? And you can see alcohol use is extremely common in our society. Nine out of ten young people have used alcohol. I guess that’s not a great surprise. You’d also be aware that tobacco use is not uncommon. So over 40 per cent of young people have used tobacco in the last 12 months. Cannabis use, similarly, is not uncommon at all. Something like one in four young people have used cannabis in the previous 12 months. Even drugs like ecstasy and amphetamines; again, you can see something like 12 per cent and 10 per cent have used ecstasy or amphetamines in the previous 12 months. Other drugs like cocaine; LSD; other hallucinogens like magic mushrooms; abuse, not use, but abuse of analgesics–over-the-counter pain type preparations, tranquilisers, sleeping pills, things like valium – something like 2 per cent of young people in this survey reported using these in the previous 12 months, and a similar amount for inhalants. Heroin, not as much, less than 1 per cent but it’s still there. Now again, it’s just worth emphasising, this is a snapshot of a cross section across the population. It doesn’t target particular high-risk groups and high, risky, or problematic drug use can be more common in some of those populations, homeless populations, that you don’t make contact through a telephone survey.

Just to unpack some of that information, alcohol use is seen as being normal by many young people in our population. The average age of first drink is about 15 years. There are some concerns, especially in the last couple of years, that binge drinking may be becoming more popular. In this survey, something like 45 per cent of young people reported that in the last 12 months they’ve gotten too drunk to remember what happened. So basically got as drunk as they could get. Having more than 20 drinks– that’s 20 standard drinks, 20 pots of beer, 20 100ml glasses of wine, 20 nips of spirits or more – nearly 50 per cent of young men and one in four young women, so it’s not insignificant.

The other thing of concern, of course, is risky behaviours. Something like one in four young people had verbally abused someone else when they were drunk and a bit over 10 per cent had driven a motor vehicle while they were drunk. Smoking – I’ll just quickly take you through smoking – is not uncommon. Exposure to smoking is very prevalent for young people. Something like 20 per cent of teenagers had smoked in the last week and roughly 10 per cent of those smoked daily. And we do see a trend of young women starting to smoke more than young men, especially around that 16, 17 year-old age group, women are smoking about twice as commonly on a daily pattern. In terms of illicit drugs, the trend over the last couple of years, and this is just the Victorian data, a small drop in cannabis use but an increase in ecstasy use and illicit drug use tends to peak around age 20, 21.

Now Nick, the next speaker, is going to talk to you a bit more about some of the things that impact and influence drug use, some of the things that might either lead to drug use or protect young people against drug use. So I don’t want to go into detail other than to mention it at this stage. One of the things that can impact upon whether young people use drugs or alcohol is what they think about it obviously – do they think it’s good or do they think it’s bad? And if they particularly think it’s wrong, that there’s something bad about using a substance, then they’re less likely to do it. I guess it’s not that surprising. So in this sample again, something like more than 10 per cent thought that alcohol use was bad. A much greater proportion thought that cannabis use was bad and again, a greater proportion thought that ecstasy use was bad. That’s one of the factors; it’s not the only factor.

Another influence is whether your peers are using drugs. Now alcohol and nicotine use is much higher so I’m not talking about that in this slide, but it’s interesting to know. The question here is, do your friends use drugs? So you can see that asking a young person in this survey, did they know someone, was one of their friends exposed or using any of these drugs? You can see for cannabis use, something like eight out of ten, ecstasy use six out of ten, amphetamine use nearly five out of ten young people answered yes. So young people are getting exposed. They do know people who can get these drugs and who are using these drugs. Maybe not that surprising.

To quickly touch on, do people know where to get help? And I guess one thing I should really emphasise here is that using a drug doesn’t necessarily mean that people are going to have problems. Some people use drugs and use alcohol and don’t have problems, but it is important that people should know where to get help. And you can see that a significant proportion of young people don’t know where to get help so that’s something to think about. Supports are really critical. We’ll come back to that theme tonight.

We’ve talked about a survey but to give you a sense at the other end of the scale of a more problematic pattern of drug use, and I can talk to you here from experience of treating young people in a residential withdrawal unit. When we opened up this residential withdrawal unit we didn’t expect that we’d see that many people who were using enough drugs to get sick when they stopped, but lo and behold we did. An example is a young women that I still see now. She had experienced abuse and neglect at a very young age, when she was less than ten. She lived in an environment where nicotine use, at least, was very common, and her friends also used substances. As she got older substance use was very common, she was always in an environment where people were taking chrome paints, chroming, sniffing things, smoking cannabis, etc. So it was not surprising at all that she started to get exposed to drug use.

She became homeless when she was in her mid teens so again, at a higher risk of being exposed to drug use and having less resources to combat those stresses. She left school. Eventually she became heroin dependant, became a benzodiazepine user, a valium user as well and experienced several overdoses. Having not experienced good stable patterns at home; she experienced violence from serial boyfriends. She has had three children now to two different men and from both of them she experiences abuse and neglect. So part of the thinking that we need to do is how do we respond to that? How to respond to that not only on an individual level but also on a society level and we’re going to pick up some of these themes about what are some of the things that determine whether young people to go on to use drugs or not.

So just to summarise, alcohol and other drug use is extremely common. Young people in our society are exposed to them. Almost all of them are exposed to alcohol use. A very high proportion to smoking. But other drugs like cannabis, ecstasy, inhalants are common too. They’re not uncommon at all. They are occurring at a key age where experimentation is seen as being normal. It’s normal for young people to experiment, to question society, to question things. And one of the key issues here is that the number of supports and the resilience they develop through those years is essential. I’m going to pass you back to Mal who’s going to introduce Nick our next speaker and we’re going to take questions at the end together as a panel.

Thank you Adrian and as Adrian said, there will be questions at the end so store them up and get ready to go because there’ll be quite a long period of time to be able to ask the panel questions. The next speaker is Nick Walsh. Nick is also from Turning Point where he’s the Public Health Registrar in Addiction. He’s again, a clinician and Nick is in the middle of doing his PhD. He tells me he’s in the second year chronologically and as I asked him, does that mean that he’s got a delayed or an enhanced development, so you can judge for that yourself. His clinical role is providing treatment to individuals and families who are struggling with substance abuse issues such as heroin, amphetamines and alcohol dependence. Nick also has worked for a number of years with remote indigenous communities in the Northern Territory and recently looked at the effectiveness of drug and alcohol treatment services in the top end.

Okay thanks Mal. I’m going to talk to you about some of the social and cultural influences on drug use during adolescence and build on a little bit of what Adrian said then lead into what Murat is going to talk about which is the brain itself. I guess there are really two points that I want to make. One is that, and Adrian’s already made this point, that use itself doesn’t equal problems. Use is almost normal experimentation, but it doesn’t equate with problems, it doesn’t equate with continued use or dependence.

The other thing I want to illustrate is that the pathways to dependence, the pathways to continued drug use from adolescence and into adolescence are complex, they’re dynamic and there are interactions between the brain itself and the environment within in which it lives. So if we look at a schematic of a young person who gets exposed to a particular substance – doesn’t matter which one it is; it could be nicotine, alcohol, heroin – there’s a number of environmental modifiers. So this may be family, this may be the school, this may be the drug policy environment in which they live, their friends, all will determine which path they take. Do they go on to use intermittently? It can be intermittently without problems, it can be intermittently with problems, for example binge drinking with alcohol and subsequent DUI or motor vehicle accident. It can be no use. People experiment and then they don’t go on to use after that. But there’s a bunch of people, it’s only small, probably less than 5 per cent, that go on to develop a dependence as a result of their initial exposure.

This is an illustration of complexity, of multiple different factors; there is a dynamic, continuous interaction between biology and experience. You can see that certain people have a genetic predisposition to drug use, their childhood environment will affect their personality development which may impact on their peers, the peer group that they stick to, the group they learn from. This is all done in the context of their own family and the educational and employment opportunities that their family and themselves get during their lifetime.

A number of different people have tried to develop a model that explains this. Again, I want to emphasise that it is a complex relationship. You can see that the macro-environmental factors such as legislation, the social capital of the society, there is a whole host of major overarching influences on an individual. But there are smaller influencing factors too, such as the local environment in which a young person lives, their peers, their school environment, their own socio-economic status, all this feeds into the family that they live within, how the family functions, and the socio-economic status of their own particular family. And finally, this feeds into the individual themselves, which feeds into their own drug use behaviour. But it is a complex interactive environment at all points along the timeline.

This is, I guess, more what Murat is going to talk about but just to illustrate that brain development is not really complete until 25. Murat is going to tell you this again, but the teenage years are crucial and crucial for social functioning. You get all the basic skills in the early years of life but your high cognitive function, the way you conceptualise relationships, the way you develop your emotional system, are happening during the teenage years so it’s a vulnerable period.

So why do people, young people, why do they use drugs? Why do they turn to drugs? Well as Adrian mentioned, mostly it’s curiosity and peer pressure. Probably curiosity is the major driver. There are certain types of personalities that are predisposed to this. People who are novelty seeking, are experiential, are much more likely to experiment with different drugs as opposed to someone who’s just really scared to try anything new, a harm avoiding personality.

There are influences during adolescence as a result of teenage culture. Adolescence is a collectivist culture. I mean, people want to adhere to the group norm, they want to have an affiliation with the group and validation from the group. So obviously, if someone is hanging out with people that are using then they’re going to be influenced. Different people get influenced in different ways. Boys are probably more susceptible to the influence of their own peers. Girls, as a generalisation, are probably more susceptible to the person they’re having a relationship with. Clearly it’s dependent on an individual’s inner personal skills, how they can negotiate the social environment within which they live.

And of course, there are a bunch of people who have difficult childhoods, who have a difficult time and use drugs in order to cope with their problems. Generally, this is a minority of people and I’m just going to talk about this now. Look, this is complex slide. I don’t want you to look at everything, just the coloured squares. This illustrates the young woman Adrian talked about. Someone who came from a family where her mother was using, was nicotine dependent during pregnancy. Obviously, that affects inter-uterine development. She came from an invalidating environment and abusive family and was unable to develop any self regulation of emotions, which meant that she was going to always develop problems with her peer relationships and probably wasn’t going to engage in school. As a result, there was no validation from her peers, from her environment and a negative thinking pattern developed leading to mental health consequences.

And then we have the influence of peers, which lead a person to use a particular drug, whatever that is, and for her it was ultimately heroin. And she’s in a cycle now of self harm, substance dependence, institutionalisation and it’s very difficult to break. You have to break it at multiple points along the continuum but sometimes it doesn’t work out. Sometimes it does, of course.

On a more positive note, we can look at it another way. Again, this is a complex slide, but just look at the colours. For example, here is a young man whose mum and dad may be together, maybe not, but mum puts every effort into ensuring that the pregnancy is optimal. Born into a validating environment, he has an extended family to rely on to develop a number of relationships. He sees his father as a role model, or for example, develops a strong relationship with his uncle, and his mother is supportive. He goes to school and develops a small peer set there. He happens to be talented at a particular sport and gets validation from that. He isn’t too bad academically, gets a little bit of validation from that. He develops a self belief, a belief that he can control his own destiny, which is called self efficacy, and ultimately he is able to achieve a social competence which protects him against developing problematic substance use.

Now this individual may have been exposed to drugs, but placed priority on the other things, on the other events in his life. So it is complex and I’ve given you the two extremes. There are a bunch of people in between and there is obviously interaction between the two pathways, but I think we do need to focus on resilience as well. So if we look at resilience, how do we protect our kids from drug use? If they have a supportive and engaging parenting environment, leading to validation, they are able to develop an internal locus of control, so they are the captain steering the ship through the rough sea rather than just bobbing in the ocean. It’s really important.

Role models, I don’t think we can overestimate their importance, particularly people with resilient character traits in mid adolescence. Certainly having appeal to others and areas of talent are important for validation because you do develop some kind of self efficacy. Hopefully, it won’t be too much and you’ll develop a certain level of confidence, but group affiliation is really important. This is a strength of religion but also of other clubs and other social sets to which you might belong.

And certainly if you’re not in the bottom rung of socio-economic status, you’re at an advantage. It is harder for people who materially have relatively less rather than absolutely less. And similarly, the social capital, the social environment, the policy environment in which we live is really important. You see the difference between the policy environment of say Europe for example versus the United States. And of course there’s luck. I don’t think you can underestimate luck. I mean, bad things happen, good things happen and it’s all important.

Last slide, there are a couple of other things I think are important. One is stress. The issue here is not the degree of stress, although there is a critical breaking point and we see that for example in abuse, in sexual abuse, in emotional abuse. But the issue is the duration of the stress. So the longer one endures the stress, the more difficult the environment is and it does reduce social capital. Material security is a cause of stress of course and obviously associated with a low socio-economic status.

But the final one, attachment, I think this is really crucial. We know that alienation itself, people that feel alienated from society, is a real predictor of drug use and that’s why we need to be cohesive and inclusive in society. We know that alienation results in adverse outcomes. The reason is that people who develop secure attachments, particularly in the early years of adolescence, are much more likely to be socially competent and therefore not be so affected by adverse life events. So just an overview, adolescence is obviously a vulnerable period. We need to focus on resilience and that’s an individual characteristic but I think ultimately the policy environment is a really important determinant of the soci-cultural environment within which an adolescent might live.

Our next speaker is Dr Murat Yücel. Murat’s a Senior Lecturer in Psychiatry at the University of Melbourne and is a Senior Research Fellow in the Melbourne Neuropsychiatry Centre in Melbourne Health Research Institute. And Murat has a particular interest in drug and alcohol abuse research and is part of the substance use research and recovery focus program at ORYGEN Research Centre here at the University of Melbourne. And he’s also suffering from using a Macintosh but is it working now?

Okay, is that clear? Alright. Some of the slides look like they may not work but hopefully all the important ones will. We’ll see how we progress.

Okay, so Nick and Adrian have talked a bit about teenage drug use and the kind of influences there are that exist on that kind of drug use ranging from genetics, though we haven’t really talked about genetics, up into environmental factors and cultural factors and economic factors. So all of these are important. And what I want to do in the next 15 minutes is to just summarise for you what we’ve learnt about brain development and just pad that out a bit so we can better understand the causes and consequences of drug use by understanding brain development. And so let’s give that a go.

If we’re going to talk about adolescent brain development, we need to define what adolescence is and despite the fact that that seems quite easy, it’s not. You know when someone’s going through adolescence, but the end points, the ins and outs of adolescence is actually quite hard to define. In an arbitrary social sense, we expect someone to go to bed the night before their 18th birthday and wake up as an adult, but I can tell you from the brain’s perspective that that’s not going to happen. And it’s probably not until your 25th birthday that you’re going to wake up as an adult ,if not beyond, from the brain’s perspective and that has important implications for teenage drug use.

So if you look at adolescent behaviour, we know that it is characterised by impulsive decisions, emotional decisions, things that aren’t always well thought out. And this risky, novelty sensation-seeking kind of behaviour is thought to be a part of people feeling their boundaries, getting to know themselves, who they are, developing their independence and that’s all a part of normal adolescence. And it used to be thought for a long time that a lot of the underpinnings of this behaviour is this raging hormone syndrome that hits at about adolescence. And that’s probably largely true for why people engage in a lot of those behaviours. You know, whether it’s romantically, peer, physically, there’s a lot of risk taking novelty and that raging hormone syndrome probably explains a lot. But we’ve underestimated the influence of brain development and what impact that may have on risk-taking behaviour, because what we know now is that the parts of the brain, these frontal areas that are very much involved in regulating emotions, in planning, in making judgements, in weighing out the pros and cons of a decision for the long term outcomes is actually not fully mature until mid 20s. And so from the brain’s perspective, it leaves you more vulnerable to making these impulsive emotional decisions as well. It’s not just the hormones.

This slide hasn’t quite worked out but you’ve already seen this one. Nick’s already presented this one and I just overlaid a brain on it. But essentially what it’s showing is that by the time you’re aged two or three, one of the early things that develops is your sensory pathways, your vision, your hearing and you need these and these need to develop early and that’s important. And the language system then comes on and then there’s a much more protracted period of development of higher cognitive functioning. And by cognitive, again, it’s those things that I’m saying about planning, reasoning, weighing up the pros and cons, and regulating emotions is also a part of cognition. This takes a lot longer to develop. And while on this slide it shows that it seems to mature at about age 16, we’re getting better at measuring these things, and we know from our own studies and those of a lot of people around the world that we could extend that line to mid-20s. And so again, from a cognition perspective, you’re not fully mature in making decisions that are fully thought out cognitively until your mid-20s, and this is in line with what we know about brain development.

I’m going to talk to you about three aspects of brain development. Its volume, something called myelination and something called pruning. And these are three important properties of the brain that will help put a bit of context on adolescent brain development. Firstly, let’s talk about volume, just purely how big or how small the brain is. And we know that by the time you’re born, the size of you – I should just orient you to this graph, something that’s up on this graph means that it’s changing at this part of life, okay? So brain volume is changing a lot very early on and very little through adolescence. You are born with about a third to a quarter of the full size of an adult brain, so you’re about a quarter of the way there at birth. By the time you’re about age six or seven, you’ve pretty much reached full adult level of brain size. And it’s for this reason that about 20 years ago it was thought that once you reach age six or seven, the brain doesn’t change very much, it’s pretty static from that point on. But we now know that this is actually not true. And it does make sense because a lot of behaviour changes from after six or seven and can hormones explain everything?

We know now that a lot of things start to change in the brain beginning at age six or seven and really start to ramp up, and one of these is called pruning. It’s basically a trimming that occurs in the brain. If we take a part of the cortex, which is the grey matter of the brain where your thinking occurs and the cells are stored, and put it under a microscope it might look something like this when you’re born. Now these are the cells and these are the connections and you can see when you’re born you have very few connections but by the time you’re six, there is immense growth of connections. It’s really, really connected and these connections are one of the most important and powerful features of the brain. These connections are what make it so good at what it does. .This abundance of connectivity is what is thought to facilitate kids learning language, learning motor skills, to walk, talk, to do sport, learn how to use the remote control easily and so on. But beyond age six, there is actually a loss of these connections for the next 20 years.

So your cortex actually, your grey matter, starts to get thinner and this is quite a new concept and something that we wouldn’t have thought or predicted that you actually lose connections, that’s normal and that’s a good thing. And it’s a good thing because you’re not losing connections just randomly; you’re losing them very selectively. You’re losing the ones that are redundant, the ones that you don’t need or don’t use very much so the overall net effect of this process is that the efficiency of the brain gets much better. And this is occurring quite substantially through the adolescent period.

The other thing that comes on is this process called myelination which is occurring very early on but again, through the adolescent period as well. Myelination is a protective covering around the connections between cells to make them more resilient. It also improves the speed at which information travels up and down that axon at about one hundred fold compared to what it was before. So you can imagine the combined effect of this process really improves the system.

And the important thing is that this isn’t occurring equally across the brain at the same time. It’s starting at the back of the brain and working through your sensory systems and so by the time you’re aged three or four, this process of pruning and myelination has probably already occurred. And it works through to your motivational and emotional systems and finally, it starts working on your higher cognitive thinking. The other thing to say is that we know adolescence is characterised by intense emotions about some things and complete lack of emotions about other things. It’s almost like there’s this inappropriateness between the two and that’s what we expect of adolescents to some degree, but you grow out of it and the thing is – well most people do.

We could partly explain this from brain development again. During late adolescence this connectivity and myelination process is connecting the cognitive systems with the emotional system so that there is more of a balance between the two. In that way you don’t make as impulsive, emotional and risky decisions. If you do, you’ve at least weighed up the pros and cons, reasoned through the choices and if you still want to do it, it’s a much more informed choice compared to before.

What has all this got to do with adolescent drug use? Well we know that adults who have been using for quite a while problematically have problems with their thinking. They have smaller brains, they have disturbed connections and overall, their brain function is altered. This study looked at people who had been using marijuana for a long time and got them to engage in a decision making process. They had to weigh up the pros and cons of engaging in the task in order to obtain beneficial long-term outcomes. Controls, people who hadn’t used marijuana problematically, performed better than moderate cannabis users and heavy cannabis users.

These people were in a MRI machine and scanned while they were doing this decision-making task so we could measure which parts of the brain were working hard to make those decisions. And you see this is a cut through the middle of the head showing the front, that’s the eyeball there and just above that is the frontal lobe. The frontal lobe is very much engaged when a person is making the decision about outcome, and the more they engaged their frontal system, the better outcomes. Compared to controls, the moderate cannabis users did not engage that frontal system as much. Similarly, heavy users engaged the frontal system even less and performed even worse. So it seems there is something about cannabis use over a long time that affects the way in which these frontal systems are working to produce better outcomes.

One of the things we don’t know is when those adverse outcomes actually occurred. Were they always there and led to the person using the substance or did they occur as a consequence of using? We still don’t know the answer to that, but what we do know is that when you asked people about the patterns of their use, the earlier they report using substances problematically, the more these problems seem to be characteristic of who they are in their brain. So there seems to be something about adolescent earlier use that makes you more vulnerable to the adverse affects. And we think the reason that is, is because there’s this change going on in the brain still and the fact that there’s a change going on means that you’re more vulnerable, you haven’t quite stabilised the system. The implications of this are that as a teenager you’re prone to making decisions that are more motivationally, emotionally driven, more impulsive. There is less weighing up the pros and cons and regulating. Even if you weigh up the pros and cons, you may not be able to regulate those emotions, which is a part of what adolescent development and brain connectivity help you do. The brain is still under construction so there’s a period there where you are going to do risky behaviours.

But if we could negotiate our way through that period successfully and let our brains develop in the best way they can, we may end up with a more balanced system where we make decisions which are a combination of emotions and well thought out cognitions. If we can get there, then that sets the foundations of better dealing with stress, better dealing with mental illness should it hit, and it does hit more commonly than people think. To be able to gain a better education, job opportunities, career and other opportunities, all of which, some of those complex slides that Nick showed are related to patterns of substance use.

It’s also important not to forget that this is just a representative scheme of this emotional gas that hits about adolescence and the brakes, the cognitive brakes, that try and catch up. This gap can be thought of not only as a period of vulnerability for people engaging in risky behaviour but if you can change it and kind of channel it in more positive ways, that emotional gas could be used in more constructive ways whether it’s risk taking in sport or music or socially, whatever. It can be channelled in positive ways as well so it’s not just negative. And it can be thought of as a period of opportunity as well.

So what are the take home messages and can these adverse affects be prevented? The answer is yes and I guess we’ve known for a long time that teenagers do use drugs, they experiment with them. But we haven’t known for that long that the brain is still developing and is more vulnerable to the adverse effects of drugs during the adolescent period; potentially long-term adverse effects. So we need to be talking about these both to teenagers, to peers and parents and clinicians and getting more awareness and education about this out. If we can do this and if there is a possibility of stopping adolescent drug use or at least delaying it, then that’s a good thing because for every year that substance use is delayed, the chances of problematic use down the track is significantly reduced. And that significantly reduces the potential adverse affects that may result. Even if you are using substances, if you try and abstain and reduce the substance use given what we’ve just talked about, that the brain is still changing and improving it’s efficiency until 25, you’ve still got a chance to catch up some of those efficiencies and reverse them, if not completely, at least partially.

And finally, just changing our attitudes about drugs. So for example, referring to cannabis as a softer recreational drug. That may be true for adults, but it doesn’t seem to be in an adolescent context and we need to be aware of that, that it’s not a soft drug, it’s not recreational. And referring to drug use as a part of normal adolescence is maybe not appropriate either. Risk taking is a part of adolescence but drug use doesn’t necessarily have to be that risk taking. It can be channelled in more constructive ways. That’s it.

Thanks very much Murat. The next speaker is Dr Andrew Lawrence who is a NH & MRC Senior Research Fellow at the Howard Florey where he runs the Addiction Neuroscience Laboratory and is particularly interested in the brain functions particularly related to alcohol addiction. One of the other activities that Dr Lawrence is involved in is the Australian Neurosciences Society which is the peak neuroscience body for Australian scientists and he’s the Treasurer of that particular society, and this is an important function that distracts him from the laboratory.

Thanks Mal. Thanks everybody and I’ll also, before I start, I’d just like to thank L.E. Ohman sitting down the front for putting all this together and making it happen. So you’ve just been hearing from three speakers whose subjects have two legs. Well, my subjects have four legs plus a tail and that’s because obviously there are certain things that you simply cannot do in humans, and we have to turn to animal models to understand the fundamental biology behind the process of addiction to enable us to develop better therapeutic strategies or therapeutic approaches. So over the next 10 or 15 minutes I’m going to talk to you about some experiments that we’ve been doing in animals to look at addictive processes, to look at the vulnerability of using addictive substances during that period of adolescence and seeing where we can go and how we integrate that with some of the previous talks.

You’ve already heard that teenage years are typified by experimentation and risky behaviour, everybody knows that, everybody was a teenager once and you can all remember back to things that you did and probably wish you hadn’t done. But it’s also quite clear now that particularly early adolescent drug use is a very strong predisposing factor towards later adult drug use and drug abuse and also for major psychiatric disorders, particularly major depressive disorders and antisocial personality disorders and things like that.

Now you’ve seen right from the very first talk that over 90 per cent of Australians over the age of 14 admit to using alcohol and over 40 per cent admit experimentation with illicit drugs. One thing that we haven’t touched on yet tonight is that not only do people in teenage years take substances that can be abused for recreational purposes, but some take them for therapeutic purposes as well. And the last figures that were available which covered the year 2000, there was 63,000 young Australians between six and 17 years of age on prescription stimulants such as amphetamine and amphetamine analogs for Attention Deficit Hyperactivity Disorder and such problems. And so we have asked collectively, what effect does this exposure have on the developing brain, what risk does that pose for subsequent behaviour into adulthood, and the kinds of behaviours I’m going to talk about are motivation to self administer drugs or cognitive impairments.

And so this is an experimental design that we’ve taken up. This is the age of the rat in days, PND means how many days old they are after they were born and a teenage rat is five to eight weeks old, roughly speaking. There are three groups of teenage rats. One is a control group, they are just treated with saline. The others are treated with varying doses of amphetamine, either what we call a low amphetamine group or a high amphetamine group. Now these animals get this drug every day for ten days and then we do nothing to them, we just let them grow up and become adult rats. When they become adult rats we split each group in half and give them either saline or a very low dose of amphetamine.

This is the apparatus that we use – can everybody see at the back or do you need the lights dimmed? This is a rat set in the corner of a locomotor cell and these grey squares shoot infrared beams across so that every time the animal breaks a beam we can get an idea of its activity. It doesn’t hurt the animal. The animal doesn’t feel a thing. And when we rechallenge the animals, this is what we see. These letters on the bottom curve represent how they were treated when they were a teenager and how they were treated when they were an adult. So S stands for saline and A stands for amphetamine. These animals, were treated every day for ten days with saline when they were teenagers and were given saline again when they were adults. As you can see, when we put them into the apparatus to measure activity they’re quite active for about ten minutes and then they just stabilise out and sit in a corner, curl up and go to sleep which rats typically do during daylight hours.

If we take rats that have been treated as teenagers with saline and then in adulthood treat them with amphetamines, we see this dramatic hyperactivity that persists for the entire hour. So they’re just charging around, they’re very up there, very active and it persists for quite a reasonable point in time – and that’s a low dose of amphetamine.

Now if we take the rats that were treated with amphetamine during their teenage years and give them a very low dose of amphetamine as adults, we see an exaggerated behavioural reaction to the amphetamine in adulthood. We see this in rats that received the high and low doses of amphetamine as teenagers. This is called sensitisation, but that doesn’t matter, the important point is that they seem to be hyperactive to the drug when they’re given it again in adulthood. This behavioural paradigm in animals is thought to represent, to a degree, the compulsive nature of a relapse type scenario in a human drug user.

Now after we monitored the behaviour of these animals in that way I’ve just described, we looked at their brains. Here you can see a part of the brain that is involved in integrating that hyperactive locomotor activity but it’s also involved in other things. Now hopefully you can see lots and lots of little black dots here and not so many there. This is a brain from one of the animals that had the high dose amphetamine as a teenager and then was given a very low dose of amphetamine as an adult. And you can see that there is a dramatic excitation of nerve cells in this part of the brain that occurs when this exaggerated behavioural response occurs. The interesting thing is though, the rats that received the low dose of amphetamine as teenagers don’t show this dramatic excitation of nerve cells, but they showed an exaggerated behavioural response to the drug as adults. Remember there’s two doses of amphetamine, a low dose and a high dose. It doesn’t matter which dose they get from the behavioural point of view, when they’re rechallenged in adulthood, they both show the exaggerated behaviour pattern. But when we look at the pattern of how the nerve cells in the brain have been excited, there is actually a dose relationship so that the ones that were treated with the low dose are no different to the ones that were exposed to amphetamine for the first time in adulthood.

So while from a behavioural point of view, these two groups of animals look the same, what’s going on inside their brain is actually quite different. The take home message from this slide is that the amount of drug that you take during the teenage years can also impact upon how your brain responds in adulthood if you get into a situation where you take the drug again. That’s the simplified take home message. So to summarise that study, we showed that adult rats do display an exaggerated behavioural response to amphetamine following an initial juvenile exposure and this is associated with a widespread activation of nerve cells throughout the brain.

We also looked at the part of the brain whose function is to regulate how fast your heart beats and how constricted your blood vessels are, i.e. what your blood pressure is. And we found that in those same group of animals that were given the high dose amphetamine as teenagers and rechallenged with amphetamine as adults showed a very profound activation of the part of the brain that regulates your cardiovascular system. And that may contribute to incidences of sudden cardiac death or stroke that are not infrequently seen in young adults following amphetamine and cocaine use.

We were also interested in looking at the motivation of the animals to give themselves a drug. To do this, we anaesthetise the rats and put a catheter into one of their veins and then teach them to press a little lever to get an injection of cocaine intravenously. They learn to inject themselves very quickly, even on day one, they’re getting about 30 infusions of cocaine in two hours. We actually have to put a time out after each infusion so that further responding doesn’t actually cause more infusions. But you see, compared to responding on an extra choice lever that has no programmed response, they learn very quickly to press a lever to get an intravenous infusion of cocaine which would suggest that they actually quite enjoy getting the intravenous hit of cocaine otherwise why would they do it even on the first day?

We then stopped their cocaine use by simply putting them back in their home cage, and three weeks later, we put them back in the environment where they were self infusing themselves with drugs. This time they don’t get the drug when they press the lever, but they start responding at almost twice the rate for nothing. And the reason they’re responding at almost twice the rate is because they’re really working hard thinking gee, if I keep pressing this long enough the drug’s going to come sooner or later. This shows that they are actually very highly motivated to take the drug. And this increase in responding on the lever associated with the drug, we call it reinstatement in animals, is a very good model for looking at relapse in humans and in fact, there’s very good concordance in this context between animal models and the human experience. We are currently investigating how adolescent amphetamine exposure alters the motivation to self administer drugs like cocaine or alcohol in adulthood. Hopefully I’ll be able to tell you about these experiments at this event next year.

Now Murat in particular was talking about cognitive consequences of experimenting with drugs whether it’s cannabis or heroin or whatever the drug of choice was during that period of time where the brain is still going through an intense period of reorganisation and maturation. So again, in parallel to these human studies, we’ve devised animal studies to try and address this issue. And so we’ve taken again, our teenage rats and we put them through these three treatment groups and done some behavioural testing to see how they think and how they remember and how they learn and in particular, how they respond to novelty. I have a little movie here, it is speeded up so I can get the message across.

This is called a Y maze and you can see in the first trial this animal only has access to two arms of the maze and he’s not allowed to go down the third arm, and there are visual cues at the end of each arm. Now hopefully what you can see that when we put him back in six days later, he goes straight down the arm that wasn’t available to him because he remembers being in the left arm and he remembers being in the right arm, but he remembers the fact that he couldn’t go down the third arm. Rats are naturally inquisitive animals and so on the retrial they will spend the majority of their time exploring the novel arm. Now just watch this and I think it speaks for itself. It doesn’t last very long. [we see another rat in the Y maze]

The only difference between this rat and the one before is that this rat had the high dose amphetamine treatment. And you can see it’s quite obvious, he doesn’t want to go down that novel arm. He’s very reticent and even when he does go down it, he doesn’t go down very far. He certainly doesn’t go down to the end like the other one did. You see, it’s quite obvious that he just doesn’t want to go down that new arm. And here’s just the numbers that show that – this is the important slide – the amount of time that he spends in that novel arm is dramatically reduced compared to the control animals or even – you see the low dose animals, they’re no different in this to the control animals and that gets back to the point from the data I showed you before with the exaggerated locomotor response. If you are using when you’re a teenager, try and cut back on the amount that you’re using because it’s not only use, it’s the amount that you use. We’ve got two quite separate paradigms here showing that the degree of impairment or the degree your brain responds to these drugs depends on how much you actually have, not only initially but when you’re an adult as well, months later or weeks later or years later in a human context.

So to summarise, we found that exposure to a high dose amphetamine as an adolescent really reduced performance on this Y maze. We did find that that effect renormalised within weeks, but weeks for a rat is a long time for a human because their life span is condensed into a couple of years as opposed to 75 years. In other experiments that I don’t have time to go into tonight, we showed there was no clear cut effect of this drug treatment on spatial learning and so we think this deficit is an impaired reaction to a novel situation.

I’m going move away from looking at substances directly and look at the interaction between our diet and how we respond to substances of abuse or how our diet may predispose us to self administering drugs of abuse. You know, everybody’s very keen on these catchphrases nowadays, we are what we eat. There’s the CSIRO Diet for a Healthy Being that’s sold over 100,000 copies and it’s quite clear to us that our general health status does relate to what we eat. You get out what you put in to a degree. But we’ve also asked the question, can diet actually impact upon drug seeking behaviour or can it impact upon the behavioural response to drugs of abuse?

And this is just another quick little movie. This is a rat that’s been trained. This is what I was talking about, that pressing a lever to get the cocaine. Well he’s pressing a lever to get a shot of alcohol.

When he presses it, the cue light comes on that tells him the alcohol’s been delivered and he consumes the alcohol. And like all good drinkers his elbow stays on the bar. This is just showing that we can train animals to self administer cocaine, we can train them to self administer alcohol. You could train them to self administer any drug of abuse you choose, just as humans do.

Rather than bore you with lots of more graphs I’m just going to tell you the bottom line is that we we’ve found is that a limited access, high carbohydrate diet during adolescence actually results in an exaggerated preference for alcohol and an exaggerated consumption of alcohol under free choice conditions in adult rats. Now these animals are not forced to drink alcohol. They are given a choice between alcohol and water and they choose to drink the alcohol. We’ve shown, and other researchers around the world have also shown, that this exact same dietary manipulation increases the behavioural response to amphetamines in adult animals as well.

So I’m not trying to frighten you and I’m not trying to tell you what to eat and what not to eat, but it does suggest that diet may predispose the brain to the effects of drugs of abuse. And other experimenters have shown akin to those pictures that Murat showed you of cells with their connections that your diet can alter the shape and the reorganisation of those connections.

So that’s it for me. I’d just like to acknowledge the people in the lab that performed the experiments and these people that paid for us to perform the experiments. And I’d like to remind you that ANNA is one of the major sponsors behind tonight’s event and I’d just like to flag to you that you may be interested, next year in Melbourne is the IBRO World Congress of Neuroscience. So there’ll be about 3,000 neuroscientists from all around the world in Melbourne next July and there will be a number of workshops in the evening of this event that will be based around patient advocate groups. On one evening we will be holding a workshop on addiction that will include some scientists and the Turning Point clinicians and international attendees. Thank you.

It’s that time of night where I have to close things off. I’d like to thank the people who have done the work here, particularly L.E. Ohman, and also Merrin Rafferty and to thank ANNA and Neurosciences Australia for their support. I’d also like to thank you, the audience for your interest and particpation. Please join me in thanking the speakers. Thank you, good night and have a safe trip home.