Episode 59      32 min 05 sec
Cannabis and Your Brain

Researchers Assoc Prof Dan Lubman and Prof Ian McGregor discuss latest understanding of the effects of cannabis on brain and behavior.

"But what we do know is that regular cannabis use, particularly before the age of 17 or 18, increases the risk for the later development of psychotic illness.  So you’re increasing your risk by twofold."  - Assoc Prof Dan Lubman




           



Assoc Prof Dan Lubman
Assoc Prof Dan Lubman

Associate Professor Dan Lubman is a Consultant Psychiatrist and Associate Professor at the ORYGEN Research Centre, University of Melbourne, where he heads a clinical research unit that investigates problematic substance use and co-occurring mental health issues in youth. He has partnered with a broad range of drug and alcohol services and research centres, both nationally and internationally.

He is a chief investigator on a number of large research projects investigating substance use amongst young people, including studies within primary care, drug treatment and mental health settings.

In 2004, he was invited to become a member of the Scientific Advisory Board for Addiction Neuroscience Network Australia (ANNA), a national body promoting neurobiological research into addiction.

Assoc Prof Dan Lubman is Chair of the RANZCP Section for Addiction Psychiatry, which is responsible for overseeing drug and alcohol training and policy for the College. He is also a member of the Advisory Committee of the newly established National Cannabis Prevention and Information Centre.

Dan has lectured widely on the neurobiology of addiction, as well issues related to dual diagnosis and substance use in youth.  He has published over 70 peer-reviewed scientific papers and book chapters, mostly relating to substance use topics, such as comorbidity, drug use in young people or the neurobiology of addiction.

Prof Iain McGregor
Prof Iain McGregor

Professor Iain S. McGregor is director of the Psychopharmacology laboratory at the University of Sydney and is also highly involved in teaching various pharmacology courses. He completed his undergraduate degree in Experimental Psychology at the University of Oxford and gained his PhD in Psychology at the University of Sydney. 

Iain has broad research interests in the areas of neuroscience and psychopharmacology. Current interests include (1) the neural, behavioural and cognitive effects of recreational drugs including MDMA ("Ecstasy"), cannabis and cocaine, (2) alcohol craving and alcohol abuse, (3) animal models of human psychopathologies including anxiety disorders and depression, and (4) olfactory neurobiology, olfactory learning and memory.

Other research has explored the effects of chronic cannabis exposure on brain protein expression, particularly in the hippocampus and if the adolescent brain is more vulnerable to adverse effects of cannabis.

Prof McGregor is a fellow of the International Behavioral Neuroscience Society, he is the recipient of countless awards included the NHMRC achievement award.

Iain is a much sought after speaker and has given numerous invited keynote addresses and presentations around the world. He also lectures extensively to psychology undergraduates and trainee clinical psychologists.

Credits

Host: Jennifer Cook
Producers: Kelvin Param and Eric van Bemmel
Audio Engineer: Craig McArthur
Theme Music performed by Sergio Ercole. Mr Ercole is represented by the Musicians' Agency, Faculty of Music
Voiceover: Paul Richiardi

Series Creators: Eric van Bemmel and Kelvin Param

Special thanks to Orygen Youth Health for their assistance.

Melbourne University Up Close is brought to you by the Marketing and Communications Division in association with Asia Institute.

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Cannabis and Your Brain


VOICEOVER
Welcome to Melbourne University Up Close, a fortnightly podcast of research, personalities, and cultural offerings of the University of Melbourne, Australia. Up Close is available on the web at upclose.unimelb.edu.au. That’s upclose.u-n-i-m-e-l-b.edu.au.

JENNIFER COOK
Hello and welcome to Up Close, coming to you from the University of Melbourne, Australia. I’m Jennifer Cook.  In today’s episode of Up Close, we’re examining the latest scientific breakthroughs surrounding cannabis.  It’s thought to have been one of the first crops cultivated by mankind, and the Hindus believed it was a gift from Shiva.  Of course, in modern culture the plant is forever linked with the flower power generation of the 60s, and today cannabis still claims the title of one of the most popular of illegal drugs.  
But surprisingly, it’s only been in the last decade that scientists have begun to understand exactly how and why cannabis works on the brain.  Just what does it do, and what implications does the drug have on our mental health?  In today’s episode of Up Close, we’re speaking with two top experts in the field to explain these latest discoveries.
Dan Lubman is a consultant psychiatrist and associate professor at the ORYGEN Research Centre at the University of Melbourne.  He heads a clinical research unit that investigates problematic substance use and co-occurring mental health issues in youth.  
And Professor Iain McGregor is the director of the psychopharmacology laboratory at the University of Sydney, and he’s undertaking some fascinating research on rats, examining, among other things, the crucial question of whether the adolescent brain is more vulnerable to the effects of cannabis.  
Iain, if I could begin by asking you just how cannabis works on the brain?

IAIN McGREGOR
Well, it’s a very interesting question and one that we’re still wrestling with, because when you smoke cannabis it’s a very complex mixture of chemicals that enter your system.  We think that of the many thousands of chemicals in cannabis smoke, the one which is called THC, tetrahydrocannabinol, is the main one that’s responsible for the psychoactive effects of cannabis.  THC travels in the blood stream to the brain, where it’s able to bind to special proteins called cannabinoid receptors.  These are located on neurons, and when THC binds to these cannabinoid receptors, you get alterations and firing rates of neurons which are then expressed, I guess, in terms of changes in mood and consciousness and in behaviour.
So, I guess discovering these receptors in the brain which occurred about 20 years ago or so was a major breakthrough and one which allowed us to understand that THC was perhaps the most important compound in cannabis smoke, in terms of changing our mood and behaviour.  

JENNIFER COOK
Now, just on that question of THC, has that become more concentrated in crops these days?

IAIN McGREGOR
Yes, certainly, you’ve probably heard of hydro and skunk, which are the high potency varieties of cannabis.  And in the good old days, I guess, when the hippies were smoking cannabis, we maybe had a THC content of one to four per cent in marijuana.  More recent varieties are up about seven to eight per cent typically, and the really strong stuff that people can buy in Amsterdam can have THC contents of about 20 per cent, which is very potent stuff indeed and almost unprecedented compared to what we used to smoke.  

DAN LUBMAN
What has changed over the last 20 years is the way in which people are taking cannabis.  So for example, people now tend to take much more of the more potent parts of the plants like the flowering buds, particularly in the female plants when they’re unfertilised, compared to the leaves which are less potent in terms of their concentration of THC.  
Also, people tend to be smoking at a much younger age, and using much more cannabis at an earlier age.  And finally, the way in which people smoke cannabis is slightly different as well.  People tended to smoke much more joints, as you say, about 20 years ago, but now people are also using bongs which means that people actually inhale much more cannabis into their system and hold onto it.  
And again, those combinations of using bongs, using much more potent parts of the plants and using at an earlier age I think has led to growing concerns about the way in which cannabis is actually affecting young people.  

JENNIFER COOK
And let’s talk about the actual effects of it.  How does it affect your mood, your perception, people using it for pain relief?  

DAN LUBMAN
That’s right.  Cannabis works on particular receptors in the brain, in the cannabinoid system.  What we know is that that system is particularly dense in certain parts of the brain, particularly the frontal part of the brain which is involved in regulating behaviour, in terms of decision making. It’s also very dense in areas involved in memory and learning such as the hippocampus, and areas involved in movement and the control of cognition such as the basal ganglia and the cerebellum.  
So when people take cannabis acutely, what it actually does, it affects those parts of the brain, so people start to have problems in terms of their attention and short term memory; the coordination of movement is slightly impaired; it impacts on the reward parts of the brain which mediate euphoria, so people have a pleasant feeling when they take it.  That’s probably what drives most people to take it.  
But what we also know is people can also experience quite unpleasant effects.  And some people when they take cannabis can feel quite nauseated, so-called ‘greening out’ and feeling really unsteady and needing to lie down.  People can have quite marked panic attacks or anxiety feelings, and some people report paranoia, having distortions in the way that they see things, and feeling that people are watching them or out to harm them in some way.

JENNIFER COOK
If you say more people are using marijuana at a younger age, let’s go now to what happens to the brain when it’s still developing, and the effects of cannabis.  I understand, Iain, you’ve done some studies with rats, looking at this?

IAIN McGREGOR
Yes, we’ve got an inclination from some human studies that were done over the last 10 to 20 years, that age of onset of cannabis use was a major determiner of adverse effects later in life.  So people that are smoking a lot at 14 and 15 seem to be much more prone to problems with various psychopathologies and cognitive disruption, compared to people that have a later onset of use.  
It’s very, very hard to do such studies in human beings, because drug taking is often chaotic and people who use cannabis often use lots of other drugs and alcohol.  So this is where rats and mice can come in quite handy.  You can run nice tight controlled experiments.  

JENNIFER COOK
I was going to say, we shouldn’t really compare rats with teenagers, but in this way they’re almost a purer sample, are they?  

IAIN McGREGOR
Well, they are, and they’re a much  more intelligent species overall.  But in any case, we were able to take adolescent rats – because rats actually go through an adolescent period much like human beings do.  Around the age of 28 days, rats get kicked out of the nest by their mums and told to go and find a different place to stay.  They’re very playful and they’re very sociable at that age, and sensation-seeking and novelty-seeking.  So we were able to give adolescent rats and matched adult rats equivalent doses of THC, which is the psychoactive constituent of cannabis, and look both at the short-term effects of the drug, but also look at the long-term effects, long after the drug had left the system.  
And we found a few very interesting things.  First of all, the adolescents seemed to quite like THC, but the adults hated it.

JENNIFER COOK
That’s interesting.  

IAIN McGREGOR
It was very interesting indeed.  So the adolescents would tend to return to a place where they were administered cannabis, showing that they quite liked to be in the place where cannabis was administered, whereas the adults would avoid that place strenuously.  We also noticed some vocalisations, some squeaks in the adults, which suggested that – they squeaked in a way that suggested they didn’t like the drug very much.  You can actually detect vocalisation that rats make, and we’ve got a sort of rat vocabulary, phrase book.

JENNIFER COOK
That is fascinating.  

IAIN McGREGOR
And there was no aversive squeaks in the adolescents, but there were certainly a lot in the adults, which was interesting.  So there’s something fundamental about the adolescent brain, it would appear, that finds cannabis more rewarding.

JENNIFER COOK
Or the adult grows out of it?

IAIN McGREGOR
Or the adult grows out of it.  And certainly there’s a lot of anecdotal reports at least in adults trying cannabis for the first time, that they don’t enjoy the experience, whereas adolescents seem to get into it.  In fact, most people even who’ve smoke cannabis give up by the time they’re 30.  So it’s very much an adolescent and early adulthood drug.  So maybe the  brain changes as you go into adulthood in a way that finds that sort of mental state incompatible with mortgages and reliable jobs, and being a good parent and so on.  
So anyway, these were the acute effects.  There was something fundamental in these rats that were adolescents, in their acute reaction to the drug.  And then we waited a few weeks, let the drug completely wash out of the system, and we looked at a variety of different behaviours.  And also looked at the brains of these animals post mortem.  
What we found was that memory function in both the adults and the adolescents showed a long-term impairment.  even though they’d had no drug for several weeks …

JENNIFER COOK
That’s so interesting.  

IAIN McGREGOR
… we could still show that their memory was poor relative to rats that had never had the drug.  So there was some enduring effect on memory.  We also found an enduring effect on social behaviour.  So when we took these rats that had had cannabis in the past and paired them up together with a strange rat that they’d never met before and measured how much social interaction occurred, both the adults and the adolescents that had had cannabis before showed decreased social interaction.  
So there seemed to be  a long-term antisocial effect of the drug which we only saw in rats that had been pre-exposed to cannabis.  But we saw that in both adults and adolescents.  So the adolescents and adults were both socially impaired long-term it appeared as a result of cannabis exposure.  And the adolescents were particularly impaired in term of their memory.

JENNIFER COOK
So how much of that can we overlay on the human experience, because it’s so tempting just to take that and run with it, isn’t it?

IAIN  McGREGOR
It is, it is very tempting.  The other thing that was interesting was that we removed part of the brain called the hippocampus from all of these animals and we used an advance technique in neuroscience which is called proteomics. The brain is made up of hundreds of thousands of different types of proteins that genes code for.  The brain is basically a very cleverly assembled protein machine, you know.  So we can use proteomics to actually look at specific protein changes that have occurred, in this case the hippocampus, which is an important part of the brain for memory, in these animals that had been pre-exposed to cannabis.  
And what we found was that the adolescents, given exactly the same doses as the adults, showed far greater changes in proteins in the hippocampus.  So there was a much greater and longer-lasting impact of this cannabis exposure in the adolescent brain, which endured long after the cannabis had left the system.

JENNIFER COOK
See, that goes against the conventional wisdom that, you know, you can smoke your joint, the effects are gone, you’re okay, a couple of weeks it’s out of the system, there’s no long-term effects.

IAIN McGREGOR
That’s right.  I know that Dan and his group have done some interesting work with the hippocampus as well in human users tracing long-term changes, which I think fit quite well with what we were discovering in the rats.  Perhaps you can tell us a wee bit about that?  

DAN LUBMAN
I suppose it’s really interesting particularly either seeing consistency across different scientific arenas, in the animal world and what we find in human studies.  And I think the first thing to say that I think is a really important caveat, is that even though cannabis is the most commonly used illicit drug, what we actually really know about its long-term effects on the brain and brain function is actually quite limited given how much research has been conducted in other major health disorders.  
So until recently I suppose with the advent of brain imaging technologies and our ability to actually look much more precisely at different parts of the brain and tease that out, we started to see some patterns that were evident particularly in heavy long-term cannabis users.
And as Iain said, we did a recent study where we looked at certain parts of the brain where the cannabinoid receptors are pretty dense, in the amygdala and in the hippocampus, parts of the brain involved in emotional processing and in memory and learning.  Consistent with Iain’s findings, we actually found that in heavy long-term cannabis users that the hippocampus was actually reduced in size by around 10 to 12 per cent.  

JENNIFER COOK
Goodness.

DAN LUBMAN
And the amygdala round about eight per cent.  You know, if we actually look at the neuropsychological literature, so we would look at what is the impact of regular heavy cannabis use on cognitive function, what’s consistent in that literature is problems in terms of memory, and particularly verbal learning memory, so problems underpinned by the hippocampus, suggesting that long-term heavy use is indeed effected, with changes in parts of the brain that look after the memory functions.
In terms of its impact on adolescents, I think really the ball’s up in the air, and most of the literature actually comes from most of the work that Iain and others have been doing in the animal world.  And it’s only recently, I suppose, in the human literature that we’ve actually started to explore the impact of drug use on adolescents, and trying to follow up cohorts of young people to understand the long-term impact.

JENNIFER COOK
You’re listening to Up Close, coming to you from the University of Melbourne, Australia.  I’m Jennifer Cook, and I’m talking with Associate Professor Dan Lubman and Professor Iain McGregor on the latest breakthroughs in cannabis research.  
We know teenagers are now exposed, or have access, to a wide range of drugs, alcohol, cannabis.  Could you talk a bit about that combined effect on a young person?  

DAN LUBMAN
Certainly when I was at medical school, I was quite clearly told that the brain reached its adult size around the age of five, and then from that point on you gradually lost neurones until you ended up in a nursing home.   What we know now, though, that’s not quite true, that the brain does actually increase in size to its adult size by the age of five, but what happens during adolescence, the connections that are sub-optimal, the connections that are inefficient are actually pruned away.  
And what’s really interesting about that developmental process is that different regions are changing at different times.  So one of the first parts of the brain that are actually changing is parts of the brain in the limbic area, the areas involved in emotion, in drive, in motivation.  So that might account for increased risk-taking and novelty-seeking, the behaviours that Iain’s described that are very important for going out and learning new skills for independent living.  
But what we know is the front part of brain, the part of the brain involved in regulating behaviour, in weighing up the pros and cons of what you should and shouldn’t do, that part of the brain we now know doesn’t fully mature until the age of 25.  We know that by the age of around 18, around 30 per cent of young people in Australia will have tried cannabis.  But what we don’t know is why is it that some people can use and experiment and then put it away and carry on, whereas other people use it, and then continue to use it and have problems with it.  
And certainly, what we know from epidemiological studies, that early on use that Iain’s alluded to, is associated with a number of adverse outcomes, problems in school, so akin to Iain’s findings, educational underachievement, dropping out of school, having poor outcomes in the workplace, more likely to go on and use other drugs.  And we also know they’re at a much higher risk for developing a whole range of mental health problems, particularly depression and psychosis.  

JENNIFER COOK
Let’s talk about that, because I know that’s a huge fear with parents, with their child experimenting with drugs.  But there’s a lot of anecdotal evidence out there in the community of kids using marijuana, having a schizophrenic episode, ending up with serious mental health problems.  What’s your response to that?

DAN LUBMAN
In terms of acute responses to cannabis, certainly increasing paranoia is certainly an adverse effect.  But obviously it goes away after the effects of the drug wear off.  In terms of an enduring mental health problem, having psychotic disorders is around about one to two per cent of the population, so it’s quite a low prevalent disorder.  But what we do know is that regular cannabis use, particularly before the age of 17 or 18, increases the risk for the later development of psychotic illness.  So you’re increasing your risk by twofold.  And we certainly know that the more you smoke, the younger you are, the greater the risk you are of developing psychosis.  

JENNIFER COOK
Iain, I’m really interested in a study I hear you’ve been doing on the question of THC, the thought that that could be released from fat stores back into the blood, to cause re-intoxification?  

IAIN McGREGOR
Yeah, maybe I could backtrack a little bit and just talk further on the genetic aspect, because that’s rather interesting.  And one development over the last 10 years in basic neuroscience has been the development of a mouse that completely lacks cannabinoid receptors in the brain.  So this is a technique that’s increasingly used in neuroscience.  
If you wonder what a particular protein does in the brain, you can actually genetically engineer a mouse that’s missing that protein, or has that protein over-expressed.  So this is called a CB1 knockout mouse, and there’s been quite a lot of work done  with this mouse, looking at it.  If you give a normal mouse a large dose of THC, then you get a very stoned mouse.  It’s a mouse that barely moves, that is very poor in terms of cognitive function, and under certain conditions will show huge amounts of munchies as well.  

JENNIFER COOK
I was going to say, ordering out for pizza.

IAIN McGREGOR
Well, that’s right.  Mouse pizza is definitely on the menu when you give them THC.  But with this CB1 knockout mouse, you can give what you might call Rastafarian doses of cannabis to this mouse and nothing happens.  It’s completely immune to the effects of cannabis.  So it shows the absolute importance of this CB1 receptor and the CB1 receptor gene that manufacturers the receptor protein in mediating the effects of THC.  
So one possibility, going on to the human scenario, we’ve got the cannabinoid receptor gene as well.  It could be that it’s differentially expressed in people, that some people have a lot of the receptors, some people have less; there might be subtly different versions of the receptor, and that might mediate your response to the drug.  Why do some people get ravenous on THC and others don’t?  Why do some people get paranoid and others don’t?  
I mean, there was actually an identical twin study which showed that your likelihood of getting hostile and suspicious and paranoid on THC was genetically mediated.  So if one twin showed the effect, then their identical twin was highly likely to also show a suspicious paranoid reaction to the drug.
So we know that the CB1 receptor gene is important.  Also the COMT gene that has got a very interesting role, not only in your vulnerability to psychosis, but also the extent to which your cognitive function is impaired by cannabis seems to depend on that COMT gene as well.
And no doubt there’s other genes that we’ll discover that are mediators or moderators of cannabis’s effects.  And then we might start to better understand the vulnerability to psychosis that cannabis produces and why it only happens in some people.  And also, I guess, why there are these wide individual differences in the rewarding effects of cannabis, why some people love it and other people hate it; why some people get addicted and other’s don’t.  
So it’s a dynamic and fluid field at the moment that’s unfolding in a most interesting fashion.  

DAN LUBMAN
As Iain mentioned at the beginning of the interview, the cannabis plant actually has thousands of chemicals and there’s a whole family of cannabinoid-type compounds.  And what we’ve become increasingly interested in over the past few years is a particular type of cannabinoid called cannabidiol, which seems to have some of the opposite effects actually of THC.  So it seems that the more cannabidiol actually you have in the cannabis that you might be smoking, actually influences how much of a high you might get, how anxious you might become.  
Cannabidiol actually has a completely opposite effect to THC.  And in fact, there’s been some trials recently looking at cannabidiol actually as an antipsychotic, to using it in people who have chronic psychotic disorders like schizophrenia, and actually showing it actually might be a new medication, a new pharmacotherapy for the treatment of psychotic disorders.  
And it seems that maybe, when we think about who is more vulnerable to developing psychosis, or having other adverse consequences, the point that Iain made about genetics is incredibly important, but it also could be the make-up of actually the plant that you’re actually smoking.  So if your plant has much more cannabidiol in ratio to the THC, it actually might mean that you have much less adverse effects from it.  

JENNIFER COOK
You’re listening to Up Close, coming to you from the University of Melbourne, Australia.  I’m Jennifer Cook and I’m talking with Associate Professor Dan Lubman and Professor Iain McGregor on the latest breakthroughs in cannabis research.  
Iain, I must know of this question of that re-intoxification.  Did that bear out in your studies, that it could be stored in the fat?

IAIN McGREGOR
Yes, this was an interesting story that unfolded largely through legal cases.  We were contacted by a toxicology lab who had basically come across a number of cases where abnormally high THC levels were found post mortem, where it could actually be established that the person hadn’t smoked cannabis for quite a long time.  So one example was a sky diver whose parachute didn’t open and I guess had two minutes to ponder his imminent demise as he plummeted to earth.  It was pretty clear that not much cannabis had been smoked prior to that in the weeks before that episode, yet large amounts of THC appeared.
There’s also drowning victims that showed a similar story.  There was an interesting forensic case where a guy had to keep giving drug-free urines in order to stay out of jail as part of the drug court program in New South Wales.  And this was someone who’d smoked cannabis for about 25 years very heavily, and was about 120 kilos, and decided that he wanted to get fit and lose weight in conjunction with staying drug-free.  And so he lost about 25 kilos, but was unable to give drug-free urines during that time.  Took on a lot of very physical labour and did a lot of exercise, and during that time found it impossible to keep THC out of his urine.  
So it was put to us that perhaps what was happening was that THC was getting stored in large quantities in fat, which is certainly the case.  THC is a highly lipophilic molecule.  Lipophilic means that fat can store it long-term.  It’s one of the most lipophilic molecules that we have.  So it does get stored in fat.  
And obviously there are certain conditions where we burn a lot of fat.  One is where we don’t eat, we switch our fat stores to fuel the body so you metabolise a lot of fat there.  But also when we’re stressed as well, we tend to engage fat stores and mobilise them as an energy source.
So we started doing a little bit of work just looking at whether in rats given large quantities of THC and then abstinent for a few days, we could encourage THC back into the blood stream, either by restricting the food that they had or exposing them to stress.  And we also asked the question, well, if this does happen, is the THC coming back to a level where the rats will be intoxicated?  And the answer to both questions appeared to be yes.  Te perceptions of the rats, particularly  their ability to do what’s called an auditory discrimination task, which means ‘make a response when you hear this tone, but ignore this tone’, and that’s very much impaired by cannabis.  
So we found that rats, in the re-intoxicated state, who were food-deprived after pre-exposure to THC, were impaired on that auditory discrimination task, which suggested that they were being intoxicated by this THC coming out of fat.

JENNIFER COOK
So this high just kept on coming?  

IAIN McGREGOR
That’s right.  You’re not high until you’re confronted with either stress or you decide not to eat for a day or two.  So going back to these forensic cases where you think perhaps the parachutist plummeting to earth released so much ACTH, the stress hormone, that the THC came flooding out of fat and into the bloodstream.  And similarly with the guy who decided to get fit and lose 25 kilos.  No wonder he couldn’t give a drug-free urine.  
So we have a lot more work to do on this, and there’s a lot of really basic questions that are quite interesting to do with the fact that cannabinoid receptors are located on fat cells, and we’re looking at that too.  One of the best ways to actually lose fat is to take a drug that blocks these cannabinoid receptors.  And there’s a drug called Rimonabant which has been used a bit in Europe and also in the US, with the explicit idea of actually helping people lose weight.  In the way that THC promotes appetite and promotes fat storage, this drug which is a sort of THC blocker, is able to have the opposite effect.  So it’s a cannabinoid antagonist drug.

JENNIFER COOK
So there’s all kinds of intriguing and fascinating flow-ons from all this research?

IAIN McGREGOR
Well, I think that as we understand the cannabinoid system of the brain more and more, I think it’s more and more likely that the old idea of cannabis as a therapeutic will come to the fore again.  But we’ll be able to come up with better drugs that work on the endocannabinoid system of the brain and body and that have a much more selective effect.  And you may actually be able to tweak the system with drugs without necessarily getting the person intoxicated.  
Another really interesting  thing is depression, although Dan’s alluded to a link between heavy cannabis use and depression.  The brain has its own cannabis, which is called anandamide, so the reason we have these cannabinoid receptors in the brain is because we have a neurotransmitter that in everyone’s brain performs a very important function.

JENNIFER COOK
I just find that intriguing, we actually have cannabis in our brain.

IAIN McGREGOR
Yes, anandamide was discovered in 1992, and they pulverised dozens of pigs’ brains to extract very tiny quantities of this chemical that was shown to bind to cannabinoid receptors, the CB1 receptors.  So even the most ardent opponents of cannabis are walking around with anandamide in their brain.  They have their own cannabis on board, and I guess technically you could say they are intoxicated with cannabinoids every moment of the day.

JENNIFER COOK
Can’t you hear the teenagers now, telling their mums and dads ‘You’ve got cannabis in your brain’?

IAIN McGREGOR
Now, what does anandamide do?  Well, it’s a really interesting chemical.  It plays a role in all sorts of different functions.  So it’s part of the appetite system, surprise, surprise.  It regulates mood.  It seems to make people happy.  Plays an important role in memory, particularly helps, I think, people  forget things that we would rather not remember, which is important.  If you think of all the stupid things you’ve done in life, it’s very important to have a forgetting mechanism, and I think anandamide plays that role.  
But what was interesting in terms of moods was that Rimonabant which is the cannabinoid antagonist, when it was given to people who were trying to lose weight, it had inadvertently caused a lot of them to become depressed.  There was a raised incidence of suicide in fact in am American  study where people were given this cannabis blocker in order to help them lose weight.  And what that seems to tell us is that anandamide, the brain’s own cannabis, plays an important role in regulating moods, such that if you block the anandamide receptors, the cannabinoid receptors in the brain, then you disregulate mood, and people get depressed.  
So the brain’s own cannabis, anandamide, seems to play a fairly critical  role in regulating your emotional wellbeing.  But smoking large amounts of THC is still not an advisable option for making you happy long-term, because what you may well be doing is disregulating that system over time by flooding your brain with too much cannabinoid action.

JENNIFER COOK
Yes.  So Dan, where can people go if they want to find more information about cannabis, or if they need help, if they’re worried about their usage, or their children’s usage?

DAN LUBMAN
Well, in recognition of the impact that cannabis has, the Australian Government has funded a national initiative, the National Cannabis Prevention and Information Centre.  And they have a web page at www.ncpic.org.au.  And at that site you’ll find a lot of resources, materials, fact sheets, the latest information, the latest research.  It’s for young people, families and professionals.  
And that will give you a lot  of information for your listeners around exploring some of these issues we’ve raised today, in greater depth and understanding what they can do and where they can seek help.  

JENNIFER COOK
And we’ll make sure we have that address on our website as well.  Well, thankyou both for the most intriguing and enlightening and thought-provoking discussion about a simple herb.  
We’ve been speaking with Associate Professor Dan Lubman and Professor Iain McGregor on the latest breakthroughs into cannabis research.  Thankyou both for your time.

IAIN McGREGOR
Thankyou.  

DAN LUBMAN
It’s been a pleasure.  

JENNIFER COOK
You’ve been listening to Up Close, from the University of Melbourne, Australia.  Relevant links, a full transcript and more information on this episode can be found on our website at upclose.unimelb.edu.au.  You can leave a comment on any of the sites of Up Close by clicking at the link at the bottom of the page.  Melbourne University Up Close is brought to you by the Marketing and Communications Division in association with Asia Institute at the University of Melbourne, Australia.  
Up Close is created and produced by Eric van Bemmel and Kelvin Param.  Our audio producer is Craig McArthur, and our theme music was performed by Sergio Ercole.  I’m Jennifer Cook, until next time, thankyou for joining Up Close.  Goodbye.  

VOICEOVER
You’ve been listening to Melbourne University Up Close, a fortnightly podcast of research, personalities and cultural offerings of the University of Melbourne, Australia. Up Close is available on the web at upclose.unimelb.edu.au.  That’s upclose.u-n-i-m-e-l-b.edu.au. Copyright 2009, University of Melbourne.


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