"Cannabis..." "It's merely a plant, a wild weed... but it produces a range of effects that is unmatched." "but it produces a range of effects that is unmatched." "For some, it's a blissful release..." "It is nice." "It is so nice." "It is nicer than nice." "It is..." "I don't know if I can say this on camera, but it's almost as nice as sex." "While for others, it's something that seems to have unravelled their minds and emptied their lives." "I'm an addict and" "I loathe myself, I really do." "I'm ruled by it, I'm ruled." "And I don't think it'll ever stop until I'm dead." "I hear the voice of a girl I used to know." "Sometimes she's told me to commit suicide and things, but I tend to just ignore it." "In this film, I want to get to the bottom of this conflict by asking the most basic questions about cannabis." "Can it really cause schizophrenia?" "The vulnerable group are children under 15 receiving high doses or concentrations of THC repeatedly." "Can it lead you to take harder drugs?" "You don't have enduring biological changes that occur because of the cannabis exposure." "Or, could cannabis even be good for you?" "With all the publicity around the link with cannabis smoking and the potential of increasing the risk of psychosis, here we have a component of the plant which itself is anti-psychotic." "The science is so often obscured by opinion but what does the latest research reveal about the world's favourite drug?" "In my job as a psychologist, I deal with addiction." "I work with people with heroin and crack cocaine dependence." "But with heroin and crack cocaine.." "I regularly see people brought to their knees, lives ruined, even deaths." "But by comparison, for cannabis, it seems to me the effects are like a walk in the park." "And yet this is the one drug that's rarely out of the public eye, and shrouded in controversy." "And that's because more people use cannabis than all other illicit drugs put together." "According to a United Nations report, almost one in 20 adults across the globe uses it each year." "Of the people watching this programme, one in three will have tried it, and thousands will be smoking it now." "I've tried cannabis." "I've smoked it a few times." "And yes, I've inhaled." "Did I like it?" "Not really." "I was giggly, and having said that, though, I felt a bit uneasy and a bit behind the conversation, a bit thick, to be honest." "And it wasn't really for me." "But I can see the attraction, I can see that feeling out of control, relaxed and enjoying the flow of a conversation would be, for many people, a good thing to do." "But I want to know why one simple weed has such a profound impact on all our lives." "The story of the cannabis plant begins 50 million years ago, in an unexpected place." "This is Kazakhstan." "I'm hoping to find out why this psychoactive plant might have evolved here, of all places." "Professor Kanat Sarsenbaev is Kazakhstan's national cannabis expert." "He takes me to the nearby mountains to explain." "So here we are in the Tian Shan mountains." "Is this the origin of cannabis?" "I think so, because cannabis evolved in this place many million years ago," "After evolving, it distributed through the Tian Shan chain to China." "After this, to all the world." "The Tian Shan mountain chain stretches 2,500km, reaching into China and Pakistan." "While it's hard to know exactly where along this chain cannabis evolved, what it evolved from is clear." "Cannabis is a close relative of the hop plant, but with one crucial difference." "Cannabis contains a chemical called THC, tetra-hydro-cannabinol, the active ingredient, which gets you stoned." "Here we are." "We're in the mountains here and it's not in great abundance but here it is, here's a specimen of cannabis." "This plant has been here for millions of years but what I don't understand is why would this plant have evolved THC, this psychoactive compound." "What was the reason for the cannabis plant?" "I consider that accumulation of THC gives a lot of privilege to cannabis." "This plant very resistant to ultra-violet." "Extremely." "So it's a defence against ultra-violet light at this altitude?" "Another thing, the taste of the leaves.. you can taste if you want." "I'll have a little bite here." "Yes, it's not so good." "Oh, yeah, that's really bad." "Yes, cattle consider the same and they don't eat leaves and plant during the vegetation period." "So just like any other plant, cannabis evolved defences to enable it to survive." "It just so happens that in the case of cannabis, these defences took the form of the chemical, THC." "But the reason why THC gets you stoned is due to another, entirely unrelated accident of evolution." "The origins of our response to cannabis strangely preceded the existence of the plant... ..and can be traced back millions of years to primitive creatures living in the ancient oceans." "And those creatures still exist today, in the more familiar waters of Portsmouth." "What we're looking for are some buoys, or a boat that has been here a while, and maybe on the underside we'll see hanging off the bottom of the buoy hundreds of these creatures." "In a minute we can take a look with a camera, so if I just set that up now as we're coming here." "Shall I grab this monitor?" "Yeah, grab the monitor." "You should hopefully, as I go under the water now start to see one or two of the sea squirts." "Oh, yes!" "Let's go further down, and you can see one there right now in the light." "Can you see it?" "Oh, yes, now I can see." "Close-up." "And there's more here." "There we are." "But what on Earth does a sea-squirt have to do with the way cannabis affects the human brain?" "Well, if we go back say 500 million years ago to the oceans that would have been full of creatures like these before there were fish and animals with backbones in the sea." "We would find living in the oceans, thriving, creatures such as these sea-squirts, that we find here on the marina today." "And they have within them, very simple nervous systems that operate in much the same way that our nervous systems operate." "In all animals, the nervous system is made of the same components - large numbers of nerve cells carrying electrical signals, and wherever these cells meet, the signal is passed from one cell to a receptor in the next cell," "by a chemical messenger called a neurotransmitter." "Across the brain there are different types of these neurotransmitters such as dopamine and serotonin." "All animals from donkeys to humans have inherited this basic structure." "But way back in time, the sea squirt evolved an innovation to this system." "What happened was the nervous system acquired a new chemical, a chemical if you like that had a new flavour, a new type of chemical, and it's this chemical that is related in structure and a similar shape" "to the chemical that's found in cannabis." "Because of this similarity, these new signals came to be known as cannabinoids." "On this buoy here, you can see quite a lot of them." "And, what's been found is that these compounds, the cannabinoid type compounds, they affect the time it takes for the siphon to close in response to touch." "It in fact takes longer for the siphon to close when they've been exposed to these cannabinoid compounds." "Once the cannabinoid receptor evolved in the sea-squirt then it was inherited by every other vertebrate animal which followed including us humans." "It was only a matter of time before one of these creatures would encounter the cannabis plant, so that THC and the cannabinoid receptor would meet." "Since it was here in East Asia that cannabis first proliferated, it was probably here that that first meeting took place." "It's not really difficult to imagine how it happened," "I mean no-one knows for sure when THC and the cannabinoid receptor first came together but it has to have been here in these mountains." "And whether it was an animal who, hungry, overcame the unpleasant taste and had a good munch on a cannabis bush, or it was a bird flying around, or a rodent... the first stoned animal is lost to history." "In that very first stoned animal," "THC from the cannabis plant flowed from its gut into its bloodstream and was carried to its brain." "There, it met the cannabinoid receptor evolved so many millions of years earlier in the humble sea-squirt." "And it just so happened to fit... like a key in a lock." "It was inevitable that eventually cannabis would meet its perfect partner...us." "It's not known exactly when humans started consuming cannabis, but there's evidence that it's been used in this region for nearly three thousand years." "Nomadic tribes passing through Kazakhstan would pick the plant and then distribute it selling it along the silk road and other ancient supply routes, to China, to India and to other countries to the west, And in a way cannabis joined" "the ancient commodities of salt and tea, and its progress from that point on became unstoppable." "From 2700BC cannabis was used in China, as a treatment for pain, malaria and constipation." "From there, as it spread along trade and slave routes, cannabis became more closely entwined with human history than any other illicit drug." "Despite the global and enduring popularity of cannabis, modern science is only just beginning to comprehend its effects." "Here, just outside Washington DC, scientists are trying, for the first time, to find the density and location of the cannabinoid receptors in the human brain." "Conducting the research is Dr Garth Terry." "What stage are you at, what's happening?" "We have our volunteer here who is being put into the scanner." "First we have to make sure his head's in the right position, so he has this white mask on his face." "What are you injecting him with?" "We're injecting him with the radioactive drug, it works like a dye." "It targets only the cannabinoid receptors throughout the entire body and we're imaging the cannabis receptors in the brain." "So this drug will accumulate in the brain and we'll get a picture of where those cannabinoid receptors are and how dense they are throughout the entire brain." "By mapping out where cannabinoid receptors exist in the brain, and in what density, it should help shed light on the role of the cannabinoid system which scientists are only just beginning to understand." "What would you say the function is of these endo-cannabinoid chemicals?" "They act like a dimmer switch for other neurotransmitters, like dopamine, when they're released in large quantities." "You need to have a way to turn down that signal, sort of turn down the amount of neurotransmitter released." "Why do these other chemical messengers need regulating?" "That's a good question." "If you have too much of a signal, it can actually be toxic to some brain cells." "Imagine the case in epilepsy." "A lot of message is getting across, it's not being regulated it's all garbled, it's being sent all at once, in full force." "In cases such as epilepsy, too much of a neurotransmitter is released, flooding through the brain and activating too many nerve cells." "But when the cannabinoid receptors are activated, they cause the nerve cells to reduce the amount of neurotransmitter they release." "In this way, the cannabinoid system keeps the brain stable, with levels of neurotransmitters at a happy medium." "After five hours, the scan is complete." "So Garth, have you got the results in?" "Yes, we finished our five-hour scan and let me show you what we have." "So this is an image from our subject from today." "The receptors are highlighted in what colour?" "In bright red." "Well, any colour you see, there are receptors, and red is the really dense areas, and you can see there's a lot of red and yellow." "Green and blue are the really not dense areas, where there are not many receptors." "So they really are everywhere?" "Yes." "They are the densest receptors in the brain, the most populated throughout the entire brain." "Are they only in the brain or are they in other parts of the body?" "I can show you an image of a whole body scan we've done here, here's one." "Oh, my god, look at that." "You can see it goes right into the brain, look how hot that is." "But there's also cannabinoid receptors in the liver." "Look at the bone marrow, the vertebral column, the ribs." "So how does what we're seeing in this image relate to the experience of using cannabis?" "Well, look at the amount of cannabinoid receptors in the brain - a lot of them." "A lot of the effects of cannabis use are in the brain." "Euphoria..." "As an anxiolytic, it dissolves your anxiety or it can even cause your anxiety." "So cannabis abusers or cannabis users talk about having this high, this euphoria, that's probably from some of the deep structures in the brain." "Garth's research shows that the cannabinoid system protects the brain by regulating the other neurotransmitters within it." "And the fact that it is so widespread is reflected in the range of sensations it brings." "I have one spliff, nice and relaxed." "Another one, more relaxed." "By the third I might start giggling." "I could do anything." "Right now I could run in this sand." "I could run in the sand from here to the pier and back, and probably just barely have a sweat." "How to explain the coming up bit I guess..." "It's just... slipping in to a nice warm bath, I think is the best way to..." "At the end of the day, slipping into a nice warm bath, maybe a Jacuzzi going on, few bubbles, little yellow duck." "It's just sort of that sort of like, "aaah..."" "That the cannabis plant should have evolved to produce a chemical that fits the highly complex receptors in our brain to cause these effects feels like a wild coincidence." "But it's not as strange as you might think." "There are hundreds of thousands of plant species and they create thousands of chemicals and it would be just remarkable if there wasn't one that didn't interact with the human brain." "And they do, there's the opium poppy and the tobacco plant, and both of those act on the brain." "These plants can affect our body chemistry because they're made of the same building blocks as we are." "Cannabis is no exception." "Whether you like it or not, each and every one of us is fundamentally wired to respond to cannabis." "So has it simply been the victim of prejudice?" "How real is the dark side of cannabis?" "It's like I married cannabis," "I never had a relationship of me own except with cannabis." "That was my relationship..." "with cannabis." "I did have chances in the past but I blew it because I married that thing." "I feel powerless over this drug, I despise it." "I gave up on life ten years ago." "I thought... that's me doomed now because I can't stop this insidious addiction." "John, not his real name, began his relationship with cannabis in his early 20s." "It was 1991 and I got in with the wrong crowd, going to rave clubs and things." "Some of the lads would be smoking spliffs and I wanted to fit in." "Everybody else was doing it, even me mates round where I grew up, they were all doing it... and I thought, well, you know just to join the club like, and..." "But I got stuck with it, it started to rule my life and it was on my mind constantly, and I knew there was going to be a problem there." "Now, every day of John's life is structured around cannabis." "This morning I've been up since four o'clock and I've smoked about six, seven, eight spliffs, I don't know." "My usual day is sad, but true..." "I'll get up in the morning whatever time it may be." "I'll brew up, have a cup of tea, have a cup of coffee, spliff in between..." "Then I might go out for a walk round the park sometimes or feed the birds and then I'll have some more spliffs, cup of tea." "Then come the evening time, seven o'clock," "I might have a couple of glasses of wine, spliff, spliff." "Then I'll roll a spliff which I'll smoke when I'm in bed." "And that's Groundhog Day." "And that happens most days in the week." "And today is no exception." "Right now..." "I have to be perfectly honest, I want youse to go for a bit while" "I skin up and make a spliff and then perhaps come back in half an hour." "John can now barely imagine life without cannabis." "I think to myself, if I stop, if I stop, how am I going to cope in the real world?" "That's how I feel." "How am I going to function?" "How am I gonna mix with people?" "How am I gonna converse with people?" "I'm not used to doing that." "I've spent 17 or 18 years puffing away on cannabis." "It's like I'd have to start all over again..." "And I think it's too late now, it's too late." "I've squandered my opportunities." "I'm an addict, I loathe meself, I really do." "Listening to John, he sounds like he needs cannabis to live." "It's undoubtedly an addiction, but not in the same way as harder drugs." "Heroin users that I see, there's no question really, that if they don't take the drug on a regular basis, they're going to be sick." "They're going to get physical withdrawal symptoms and those symptoms are going to get worse and worse unless they take more of the drug." "And that's I suppose, a classical definition of physical dependence." "Cannabis is clearly much more subtle." "It's not physical addiction, in that if they stop, they're not going to be physically ill." "But if they stop they'll feel craving... a strong need to take the drug again." "That is psychological addiction, and I don't think of it as a sort of lesser cousin to physical addiction, it's equally serious." "So while it can be very damaging, addiction to cannabis is not a physical process in the body." "Yet cannabis has been accused of permanently changing the brain in other ways." "Does cannabis somehow make us more likely to abuse other, stronger, drugs such as cocaine or heroin?" "To answer that question, scientists have turned to rats." "Their brain chemistry is similar to ours, but unlike humans, it's possible to give them cannabis in controlled amounts to see if this increases their taste for heroin." "Dr Steve Goldberg has been measuring the effects." "Well, in this room, we've got two groups of chambers, one either side." "We're working with rats on this side that have had a previous exposure to cannabis." "On the other side, the animals are control animals that have not had the exposure to cannabis." "And we're looking at the differences between these two groups in terms of how much heroin they take and how hard they work for it." "What does this individual rat have to do here?" "He's in a test situation, a light comes on, tells him that heroin's available." "In order to get the heroin, he has to poke his nose through a hole, and he gets a dose of heroin." "The flashing light is now him receiving a dose of heroin." "He's just had a dose of heroin?" "Yes." "Each group of rats, those who have been exposed to THC and the control group who haven't, have the opportunity to take heroin by poking their noses against a dispenser." "The number of nose-pokes or doses that each rat takes is measured automatically." "Steve then compares the results to see whether the past exposure to THC makes the rats more likely to take more frequent doses of heroin." "So what results have you found for this rat and for other rats in his group?" "We found that rats that had exposure to cannabis in the past will work for and obtain more heroin each session than the control rats that didn't have the cannabis exposure." "Actually, that's quite shocking that you found a connection between cannabis and heroin." "The history of cannabis exposure produces a tolerance-like effect where they're less sensitive to the drug and that carries over to heroin, so they need a bigger dose to get the same effect." "Tolerance just refers to the amount of a drug required to get you high when used repeatedly." "It is not the same as addiction or desire for a drug, which is better measured by the effort made to get it." "But if you then go on and in both groups and increase the number of times they have to nose-poke to get the heroin, in other words increase the price for getting heroin, then the two groups are the same." "Steve gradually increases the number of nose-pokes required for one dose of heroin." "As the workload rises, they reach a point, around 75 nose-pokes where both groups give up and stop working for the heroin." "So with increased effort, the effect between the two groups disappeared." "That's true." "This shows there's no difference in the drive to get heroin between rats who have had cannabis and rats who have not." "So what's the human implication?" "Basically, that you don't have enduring biological changes that occur because of the cannabis exposure that predetermine that you're going to go on and become addicted to other hard drugs." "It says it's more of a social and historical thing that drives it." "As ever, the picture is more complicated than a chemical switch in the brain." "It seems it's more likely to be your peer group or life-stresses such as unemployment or the end of a relationship, that lead people from cannabis on to harder drugs." "Yet there's another accusation levelled at cannabis." "That it triggers one of the most severe of all mental disorders." "Permanent psychosis, or schizophrenia." "This is our family." "This is Mark who's 28," "Natalie who's 25 this is Paul who's 19 and this is his twin, Melissa." "And, as far as we know, none of them suffer from any mental illness of any kind, so we think it's probably the cannabis which has caused the difficulties with Paul." "Paul Floyd started smoking skunk, one of the most potent strains of cannabis, four years ago at the age of fifteen." "After a year, he started to have strange experiences." "'At first when I heard the voices," "'I thought it was God talking to me, and I had delusions about God' and they were causing me to believe that I was Jesus and that I'd rise to heaven and things if I took it." "I first started hearing them when I was on skunk and then they began to just start happening in normal every day life, as well." "At first, Paul's parents were confused by his behaviour." "It was a gradual change which we didn't really recognise for what it was, at the time." "So there were things like staring very intently at members of the family, other people, weren't there?" "Um, laughing to himself when there was nothing to laugh about." "And some strange sort of body posturing sometimes, it's quite hard to describe, like some strange sort of gestures." "Almost boxing at times, wasn't it?" "Yes." "Quite peculiar, really." "After that, Paul's behaviour changed rapidly, as over time, twelve separate voices appeared and gave him instructions." "'They used to tell me to throw things away 'like I'd throw away my CD collection.'" "They were saying I should bring about the downfall of, like, the music industry by throwing CDs away." "Other people would follow through some sort of mind link or something." "Sometimes the voices would speak to Paul through the radio or television." "From programmes like Coronation Street, the characters would say to clean things." "I had to buy a lot of cleaning products and they had to be matching in every room of the house, matching colours, he got quite distressed if they weren't the same colours in each room." "I've got a shed full of mops and buckets that he persuaded me to buy when he was very fixated on cleaning." "Yet even at this point, Sheila and Dave didn't connect Paul's behaviour with cannabis... because they didn't even know he was smoking it." "Innocently, every week, we would give him an allowance..." "Even then we didn't make the link between how he was behaving and the fact that he smoking that necessarily, did we?" "I know that sounds probably a bit naive now." "It was only once Sheila and Dave took Paul to a psychiatrist that they connected his problems with cannabis." "Paul was diagnosed with schizophrenia, and prescribed anti-psychotic medication which he may have to take for the rest of his life." "But although the connection between Paul's cannabis use and schizophrenia may seems clear... it's extremely hard to demonstrate." "Proving the link between cannabis and psychosis is never going to be easy." "It's a bit like a chicken and the egg situation." "Does the drug cause mental illness, or is it that people with mental illness in some way seek out cannabis?" "'One person trying to untangle this puzzle is Dr Cathy Fernandes.'" "Tell me, how are you studying the link between cannabis and schizophrenia?" "What we're really interested in is the long-lasting effects of cannabis." "We're using mice to do this because we can control when they have the cannabis, what age they have it, and for how long." "So this is the centre of your experiment." "What goes on here?" "This is a behavioural task called the Morris Water Maze." "It's a spatial memory task, so we are looking at differences in memory and learning." "They have to learn the location of a hidden platform in the pool, so here we have the platform that's hidden below the level of the water." "The water's sort of opaque, isn't it?" "That's right, it hides the platform under the water." "So really they have to learn to navigate by using cues or objects outside the room, so if you look around the room, we have various objects outside the pool and these help the animals to navigate, so when they reach the platform, they can look up and try and locate themselves." "So we're looking at how fast and how quickly they reach the platform, and whether they can swim in a straight direction when they reach the platform." "So Cathy took two groups of mice." "The first group were exposed to THC when they were juveniles, equivalent to age 10 to 15 in humans." "So we gave them something equivalent to two or three joints a day..." "And we treated them for two weeks, when they were young, then we stopped their drug treatment we waited for them to grow up, until they were adults, about two months later." "so now we're ready to test them, they're drug free, don't have any THC on board now." "'The first mouse goes in.'" "But what can a swimming mouse tell you about psychosis?" "We don't know if any normal mice would ever have schizophrenia." "But we do know there are some very important core features of schizophrenia we can study in animals." "One of those features is a memory impairment." "We can look at that directly in mice, using this sort of task here, we can pick up differences in memory after giving the mice cannabis." "You have to say, he doesn't look as if he's remembered the location of the platform." "You can see he's swimming around but really not finding the location of the platform." "If he does find it, you'd have to conclude that it was by chance, I think." "That's right." "He has already been swimming for a while so now I will guide him to the platform location." "And there he is." "'Cathy repeats the memory test with a squad of 12 mice, 'before moving on to a second group of mice who received THC 'when they were slightly older, equivalent to teenagers aged 15 and over.'" "And straight there." "That's right, so you see a much straighter, a more directed action to the one he found it much quicker." "'Once more twelve mice are tested before Cathy compares the results 'of the two groups against a control group.'" "So this is the track data that we have from the computer system that we use, it's able to give us really accurate recording and measures... not just the time it takes for the mice to reach the platform," "but also how far they've swam, the distance they've swam." "So the first mice we have here, these are the black mice that received THC when they were very young adolescents, and if you look at the track, they're really swimming all over the pool, not in a very straight pattern, and taking a long time to reach the location." "So if we now compare to the mice who received the THC when they were teenagers or young adults, you can see they really have learnt the location of the platform, so clearly giving THC when you're an older age doesn't seem to cause an impairment." "Can you quantify the difference between the two?" "We do find a very large significant difference, as much as 25% deficit in the THC-treated young adolescent mice, so we really are fairly sure that there's a strong impact in giving" "THC to young adolescents, there's a lasting effect on their memory performance when they're adult." "Could you translate that to human development?" "We think that would indicate the vulnerable group are children under 15 receiving high doses or concentrations of THC repeatedly." "It's a worrying trend because the number of children who are now taking cannabis is really on the rise." "So we know that in the UK at least, 40% of 15-year-olds have tried cannabis already, and this is the point at which they might be developmentally vulnerable to the effects of THC." "Cathy's research implies that just a few years can make a critical difference to how cannabis affects your brain." "But for schizophrenia to develop is rare." "The likelihood of developing schizophrenia in your lifetime is 1%." "Occasional cannabis use can raise this to 2% while heavy use might raise the lifetime risk to 6%." "The problem is, anyone using cannabis won't know whether they are vulnerable until it's too late." "Now Paul is trying to rebuild his life." "We're immensely proud of him." "The way he's got through things, he's back at college..." "We're really, really proud of him, he's coped amazingly well with it all." "I'm hoping to learn to drive and possibly go to uni and study further, and I'd like to go to Africa and build a school and things like that." "Despite stopping smoking cannabis and starting medication, the voices in Paul's head have not left him entirely." "Now I hear the voice of a girl I used to know " "I didn't know her very well, but for some reason she stuck in my head." "I hear her voice most of the day and before I go to sleep is the worst time." "Sometimes she's told me to commit suicide and things but I tend to just ignore that." "The thought that he will always be hearing that is really difficult to contemplate because I can hardly imagine what that must be like." "Paul's story shows what long-term effects cannabis might have on the human brain." "Now, research into the short-term effects of using cannabis suggests that there may be a link with schizophrenia here too." "The first studies of the immediate effects of THC on the human brain are now being made by Dr Zerrin Atakan." "I really want to see how cannabis does its effect, especially in the brain, because this is the most widely used drug in the world and we still know not too much about it." "Especially how it works in the brain." "Zerrin was particularly interested in how THC can affect the brain's internal control over your behaviour and inner thoughts." "As you know, when people smoke cannabis sometimes they can have, some of them, have difficulty in controlling their behaviour, and that's why we chose a task that could measure this." "And the task is called response inhibition, or how you stop yourself from doing something, or how you put the brakes on." "OK." "Can you show me the task?" "Yeah." "When volunteer lies in the scanner, this is what he sees." "He sees an arrow pointing right or left, and he is asked to press the button right or left accordingly." "And then occasionally there will be an arrow pointing upwards, and he is asked not to press the button." "So in a sense he is asked to do nothing?" "He is asked to stop himself from pressing the button and this was the particular bit of the task that we were interested in." "And this is how we put the brakes on..." "So I guess that sort of braking is the sort of control over behaviour that we do all the time." "Yeah." "So Zerrin gave this task to volunteers, inside a brain scanner." "Each of them had received THC equivalent to smoking one joint." "She then repeated the experiment with a placebo for comparison." "What she was looking for was the brain activity in each group as they tried not to press the button in response to the up arrow." "This is the average of 15 volunteers." "And this is the placebo condition, basically this is the normal situation." "This is the normal brain responding to that task." "As you can see certain areas are looking red there which are activated, that is the pre-frontal cortex... and this is what you would expect in a normal situation, when we are stopping yourself from doing something." "This is the average of again 15 people this time who have taken THC, cannabis." "And what you see, very clearly, that in fact the normal areas are not working, there's no activity." "Zerrin believes that the inactivation of these frontal areas of the brain which interpret our surroundings might explain some effects of cannabis such as paranoia." "If your brakes aren't on, you might misinterpret or you could maybe see a shadow or hear a sound." "Normally you would say this is just a branch or this is just the wind, but if you already misinterpreting what is going on, you're not putting the brakes on, you might interpret that as someone following you." "So this is showing how cannabis affects the brain." "And would that be a similar way in which the brain of a schizophrenic might be working?" "Yes, there are similarities, I agree, especially if you think that cannabis can affect people in a way that they become suspicious and same thing you see also in people with schizophrenia, that they can be over-suspicious about their environment," "and again we know that this area is a suspect area in severe mental illness like schizophrenia." "Zerrin's research is preliminary but implies that when the brain is under the influence of THC, the effects can be similar to those seen in schizophrenia." "It reinforces the idea that smoking cannabis can, in a small number of cases, trigger the condition." "But cannabis has another face entirely." "Here in California, people are using it to improve their health." "Following a legal statute called the Compassionate Use Act, passed in 1996, those with a medical problem can obtain cannabis from a high street dispensary." "There's quite a strong smell of cannabis." "Oh look, look." "These are all edible forms of cannabis, I guess - green label cakes, single shot cakes, triple-X cakes, vegan chocolate chip, vanilla brownie, down here various forms of soda, tea and so forth," "chocolate chip, vanilla, rich berries, mango, all cannabis ice-cream." "There's two condensed buds of cannabis." "Oh, and look - a joint itself." "And here's the centre of the operation, and lo and behold it's a sort of bank of cannabis there." "One of the people making medical use of marijuana, as it's known in the US, is Allison Stanley." "When I started to look into this" "I thought "No way, this is just another gimmick," ""this is for potheads, this is for druggies," you know," ""I don't want to get addicted"." "I wasn't for it in the beginning." "But after exhausting all conventional treatments, she had to reconsider." "I was in a very serious car accident last summer, where I was shoved under the dashboard, and I had a detached colon as a result of it," "I had a knee injury, I have a shoulder injury, and I'm going through multiple surgeries." "And my doctors weren't able to address the pain issue, or the lack of sleep that I was getting." "I keep it in my bedroom, and only in my bedroom." "All you do is insert this..." "and you do this." "It helps with the pain, definitely, and it definitely helps me sleep at night." "So it's brought life back to me." "Elsewhere in Los Angeles, Tom is using medical marijuana for entirely different reasons." "I smoke medical marijuana, cannabis, because it makes me relaxed." "It helps me deal with day-to-day stress in life." "It really helps me with anxiety, and I have incredible anxiety attacks where I just get stressed out, I can't deal with reality." "Previously I had a prescription to anxiety drugs and those anxiety drugs, taking them so much and it was just really, really bad for me." "It was the strain of the business world that drove Tom to find a release." "The corporate world made me stressed, extremely stressed." "Totally stressed." "I am so happy I'm out of the corporate world, it's amazing." "TOM COUGHS" "I'm not very social when I don't smoke marijuana." "I like smoking marijuana..." "It calms me down." "I just feel totally at ease, everybody knows me " ""Smoke a little marijuana, Tom, you'll be great." ""Everything's gonna be fine, you know." "Take a hit!"" "Usually I'll do that, just smoking large quantities with other patients and we're all medicating together, collectively, and so we'll do that in more of a social environment where we're medicating, yet being social." "So it's not that we're socially smoking the marijuana, we're medicating it for use, but we're doing it together." "For Tom and Alison, obtaining cannabis is straightforward." "They go about it the same way as you would obtain any other medicine, by going to a doctor." "Alan, how does your practice work here?" "It works just like my internal medicine office, patients call in, they come in, they're evaluated by myself," "I make a diagnosis and if appropriate I recommend medical cannabis for them." "What are some of the complaints people come in with?" "The common complaints are either Chronic Pain Syndrome of some sort, and that can be a specific back or hip injury, anxiety's a very common one, depression, insomnia." "What proportion would you say come in with the common mental health disorders, anxiety and depression?" "Probably anxiety, depression represent about half the patients." "As many as that." "Couldn't that make their problems worse?" "If somebody has mild daily anxiety, they're just trying to feel 25% better." "Is it reasonable for them to try using a little plant extract, if you look at it that way, it's kind of hard to argue against." "It's just it's been built up as being such a scary, scary thing." "And it just isn't." "What if I walked into your practice on a Monday morning, and I sat down and I said," ""Dr Frankel, my mood's good, I don't have any pain," ""but you know what, I just can't seem get over writer's block." ""I'm sitting at my PC and I'm just not getting it" ""and I've been stuck for a week," ""can you give me anything for my creativity?"" "I know that people would disagree with it, with me for saying this, but to me that's a reasonable, I think, human right, to try and improve your situation by doing constructive things under a professional's care." "And could that include cannabis?" "Yes." "In my opinion." "Would it be fair for me to think that it doesn't really matter what people come in with, if they're the right age, they've got general pain or psychological problems, the answer from Dr Frankel's point of view is cannabis." "Yes, if I were a cardiologist and patients were coming into me, they'd leave with cardiology medications." "If I'm a cannabiologist and they're coming to me cos they've tried so many other things and they've failed, the likelihood is they'll leave with a cannabis recommendation." "While the system in place here runs smoothly enough, it worries me that it's open to abuse, but more than that, it's an experiment that is being stretched beyond any available evidence." "I don't really have a problem buying into the view of cannabis as being connected to treating pain, you know, that seems to be pretty clear." "Whether we can make a much greater leap of faith towards buying into the treatment of common mental disorders such as anxiety and depression with cannabis is a bigger order and I'm still pretty sceptical about that." "To add to the uncertainty, although medical cannabis is approved by California state law, it's still illegal under federal law, so even here where residents have voted for medical cannabis, the relationship is still a confused one." "It's a surprising situation for a plant that's been with us so long." "Other plant-based drugs with medical uses, such as aspirin, cocaine and heroin, have all been exploited for their full benefits." "But cannabis lags behind." "In fact only now is the world's first legal medicine based on the cannabis plant being produced, deep in the English countryside." "I'm going there for a rare glimpse." "Even though it's all done completely legally, with the permission of the Home Office, the security arrangements means the exact location has to remain a secret." "That means we're gonna have to turn the camera off." "Come on through, John." "Thank you." "So this is it?" "This is it, you can see here, one of our growing areas." "And a fairly wide selection of plants." "Come on in, have a look." "Thank you." "Gosh, there's loads of it!" "How many plants have we got here?" "There's about 5,000 plants here and every year we grow about 30,000." "And how much volume of cannabis would this produce per year?" "The payload, the botanical raw materials it's called, about a tonne." "Gosh." "To turn it into a saleable pain relief medicine, the cannabis is first dried." "Each and every plant is a clone, so that the exact properties are known and consistent." "It's like hanging out the washing." "let's go in here now." "After you." "We need to get into this kit I'm afraid." "Next it is milled and heated... ." "So we See raw material, will be put into the mill and its grounded down to particals of about a millimeter." "At this stage nothing's wasted..." "Yes, it all goes in there exactly." "The plant material is reduced to a concentrate And then it ends up in here, spinning down to about 60 degrees and all the liquid just evaporates away." "To give you an idea of the sort of material it is, it's sort of treacle like." "It's quite sticky." "It really is quite sticky, and that makes it quite hard to work with therefore." "Let's have a look at that." "Oh, gosh." "The final product is a liquid which the patient sprays into their mouth so removing the need for harmful smoking." "Yet, despite this meticulous processing, it's still not widely available." "It's not exactly taking it's place in the pharmacies across the country." "Is that because the effects are quite weak?" "No, they're not weak at all." "I think that cannabis wouldn't have survived over the millennia as a medicinal...entity if it had been weak." "And cannabis-medicines aren't weak." "It's simply that we're dealing with a group of patients who have tried all the standard medicines and haven't responded before they ever come into the medical clinical trials with this drug." "Dealing with outcome measures which are really vague " "Pain and spasticity are very hard to quantify in a research situation." "Despite this, so far, the only available product is a treatment for pain caused by multiple sclerosis, and this is licensed only in Canada." "But there's a possibility of treating many more ailments thanks to an unexpected property of the plant." "If you look in the microscope, you can see some glistening golfball-like structures." "And those are the glandular trichomes in the inflorescence of the plant which contain the chemicals we're interested in for making a medicine." "It's not just THC." "These trichomes contain CBD, another valuable chemical." "There's a lot of CBD in that particular one as well, cannabidiol, another cannabinoid, a non-psychoactive cannabinoid, an important component to the medicine." "So, from your point of view, in terms of developing medications, cannabidiol, CBD, what role does that have?" "We hope it's gonna..." "We're fascinated by this stuff, which has tremendous potential as an anti-inflammatory but also as an anti-psychotic." "So you're telling me CBD could be a treatment for psychosis?" "Yes, isn't that ironic?" "With all the tremendous publicity around the link between cannabis smoking and the potential of increasing the risk of psychosis, here we have a component of the plant which itself is anti-psychotic." "And we're saying..." "Within the same plant, you have a chemical which has an opposite effect and which therefore be protective to some extent?" "I think it's a level of concern that some of the recreational cannabis that's out there contains no CBD at all and that is a modern phenomenon." "Previously, it was much more usual for people to be smoking cannabis some CBD in it at least." "As recreational cannabis plants are grown for higher THC content, so their CBD content falls, simply because the plant isn't able to produce high levels of both." "So your trick, as a developer of medication, is, I suppose, to change the relative balance of THC and CBD." "Exactly so..." "Getting that proportion right for different conditions is going to be key." "We think for pain and spasticity, a roughly equal balance of THC and CBD is good, because each has their own type of pharmacology, quite separate mechanisms of action, and they interact together in a helpful way." "Probably along with other plant constituents too." "But for other conditions like inflammation or psychosis, you wouldn't want, probably, any THC at all." "You'd want some of the other plant components, but you'd want the CBD mainly, alongside those other components." "For a plant that's been known and used medicinally for almost 3,000 years, it's surprising that new chemicals and uses are still being discovered." "What I find even more surprising is that the medicinal use of cannabis is so far from being widely accepted." "It seems to me that across the world, our relationship with cannabis remains confused." "And not without reason." "For many people, it brings them a great deal of pleasure." "Unless you've actually tried it, you can't say how good it feels." "All I know is that I feel absolutely fantastic." "But all drug use comes with a price." "It's like the old record says - you reap what you sow." "And it's so true." "Because I'm reaping what I sowed, and I regret it, I've just wasted my life." "I've just let life pass me by because I've been sat in the chair just smoking cannabis." "From what I've seen, unlike heroin and crack cocaine, the drugs that I deal with as a psychologist, cannabis is just not in the same league." "It can't kill you, and it's very unlikely to ruin your life." "But that's not to say it's entirely safe." "Actually, I'm quite impressed with how much evidence has been gathered about the dangers." "It seems to me that cannabis has no place in the developing brain." "And although the numbers of people likely to be affected is tiny, there does appear to be a link between early use of cannabis and mental health problems." "For our family, it's been absolutely devastating." "Paul is still suffering the effects, still hears the voices." "And possibly always will do." "Yet these extreme effects are rare." "In the end, it's my impression that the most significant damage caused by cannabis is subtle." "It's not at the extremes, it's the thousands of regular smokers whose lives are held back." "It's the apathy." "It's the sitting around, smoking, not getting things done." "The valuable, precious opportunities of life are lost." "Subtitles by Red Bee Media Ltd"