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UK: Cannabis: what teenagers need to know
Panorama BBC Online
Sunday 19 Jun 2005 Exploring the latest scientific research on the growing evidence of links between cannabis and psychotic illness in young people Panorama explores the latest scientific research on the effects of cannabis on the human mind. In particular, the programme will look at the growing evidence of links between cannabis and psychotic illness in young people. British youngsters are using Cannabis earlier and smoking more of it than any previous generation. Most don't even think of it as a drug, and the popular perception is that it has no serious long-term effects. However, the truth is that, until very recently, very little was known about how cannabis actually affects developing brains. The programme meets young people who have developed psychotic illnesses after heavy cannabis use and speaks to the psychiatrists who have found links between users' genetic makeup and the risk of developing mental illness. The programme features the work of scientists who have used the latest technology to look inside peoples' heads and see - quite literally - how cannabis changes the way people think. It meets the scientist whose unpublished new research suggests that cannabis can cause long-term chemical changes in users' brains and supports the idea that it can be a "gateway" making users more likely to take other drugs. Cannabis and psychosis Dr Philip Robson, Director of the Cannabinoid Research Institute, is an expert on the therapeutic potential of the components of cannabis. In 1996 he was commissioned by the Department of Health to carry out a critical review of the relevant scientific literature and in 1998 was called on to submit both written and verbal evidence to the House of Lords Science and Technology Committee investigation into cannabis. Dr Robson says that although cannabis is a drug that has a 5,000 year history of use by humans, the amount of really carefully gathered scientific information about it is relatively limited in humans. He is interested in the potential of cannabis as a medicine for a wide range of medical conditions. He doesn't say that it is a wonder drug but simply that it probably has a place in modern therapeutics, alongside existing standard medicine. He is convinced that "in the future there will be a role for cannabis-based medicines in areas of medicine alongside the standard medicines which are not performing as the patient deserves at the moment." The following is an edited transcript of Panorama's interview with Dr Robson in which he answers questions about cannabis and mental illness. What is cannabis, what are the active ingredients? I think it's a fascinating plant and it's one that historically has been very useful to humans. I think it's very important that we don't throw it away just because it's now a pariah drug as a result of its recreational use... It's a wonderfully interesting hotchpotch of hundreds of different chemicals, more than 60 of which in fact, are unique to the plant, they're called cannabinoids. THC is the best known of all, that's the psychoactive one that recreational smokers treasure. Then there's CBD which has all sorts of interesting interactions with THC but many interesting properties in its own right, medicinal properties that is, such as anti-inflammatory, pain relieving, antispasticity, you know.. antipsychotic potentially, even neuroprotective And then all these other cannabinoids have hardly really been examined yet. And then there are lots of other plant components like turpenoids and phenols which when you look at them as individuals also have some intriguing potentially therapeutic activities like anti-inflammatory, anti-bacterial, all sorts of things that they are capable of doing independently. It's a wonderfully interesting hotchpotch of hundreds of different chemicals, more than 60 of which in fact, are unique to the plant, they're called cannabinoids And then of course there's the combined effects of all these things what you might call the synergistic effects that people are only really now just beginning to explore. I think some researchers have referred to them as an entourage effect, that some vital chemical within the plant can't do its full job unless it's surrounded and supported by a whole lot of support acts, a whole lot of... the orchestra if you like, the supporting instruments. I don't know whether that will be provable in time and in science but it's certainly an intriguing theory, and of course there are... there's good evidence about the interaction between CBD and THC but these other interactions are very much in their infancy. So how much is known about cannabis, I mean how much has been known over the years about cannabis and its effects? The medicinal use certainly goes back several thousand years and has found a place in virtually every pharmacopoeia throughout the world actually at some time. It came of course to Europe relatively late, mainly in the 19th century, sprang into prominence, and by the middle of the 19th century actually it became one of the most fashionable drugs to use, and then gradually went into decline for various reasons, I mean cannabis could be purchased from the grocer, and that really was very unpopular with doctors and pharmacists. So as synthetic medicines became more available, as other means of giving medicines became more available, like the hypodermic syringe, so there would be a move towards that area and a move away from plant medicines. The medicinal use certainly goes back several thousand years and has found a place in virtually every pharmacopoeia throughout the world actually at some time But then the huge breakthrough comes in the 1980s of the discovery of the endocannabinoid system with its receptors, its endogenous ligands, it's the bodies own cannabinoids and how they influence normal physiology and may impact on a whole range of diseases. I think it's full role is only now being uncovered frankly, but it clearly has a role in cognition, in sort of interpreting the world in movement, in the appreciation of pain, in the control of a whole host of different organ systems to be honest, in a very subtle way... Some people will be surprised that we have a system that is designed to be responsive to the active ingredients of cannabis. Have we somehow evolved with cannabis? That's a very interesting one. I mean people have looked into this and there is some fascinating work being done. I think it's probably the case that the receptor system predates the plant in the world but we're talking millions of years back in both areas. It seems to be just a serendipitous interaction. But no, the cannabinoid receptor was there long before the plant was available, but we have tapped into it, much as we've tapped into the opium poppy to take benefit of the opiates. How much is known about the medicinal properties of cannabis? It's very much an emerging science clinically. A very large number of what you might call "pioneer studies" were done in the 20th century, but it's only recently that proper randomised control trials have been undertaken. If you've got a range of symptoms, not just pain but perhaps nausea, loss of appetite, weight loss, feeling pretty bad about life and the future, a drug which can actually impact several of those symptoms at the same time is potentially particularly useful, and it's also notable that the standard treatments for many of these diseases is very unsatisfactory, either because it only provides partial relief of symptoms like spasticity or because it's potentially very toxic, and that's the position that a lot of people with multiple sclerosis find themselves in actually: that they're taking all the available treatments that are around, but still they have unacceptable levels of spasticity, pain and other symptoms. If you've got a range of symptoms, not just pain... a drug which can actually impact several of those symptoms at the same time is potentially particularly useful Patients have been telling us frankly for decades, which is that there are a number of conditions which standard treatments do not deliver the answer at the moment which cannabis seems to be able to help to a certain extent. I'm not saying it's a wonder drug, I'm simply saying that it probably has a place in modern therapeutics, alongside existing standard medicine. I'm convinced that in the future there will be a role for cannabis-based medicines in areas of medicine alongside the standard medicines which are not performing as the patient deserves at the moment. There appears to be growing evidence of a close link between the use of cannabis particularly by adolescents and the development of psychotic illness. What role do you think cannabis is playing in the development of psychotic illness? Well can I say first of all I think that there's a clear consensus that smoking cannabis if you already have a mental illness is likely to make that worse. So let's take that as read because going on from that, there's an emerging literature which seems to suggest that it may actually be an independent risk factor to schizophrenia. Terms like psychotic symptom, psychosis, schizophrenia, represent very different things but they seem sometimes to be used interchangeably One has to take this research very seriously, but I think we do need to be cautious in interpreting it because it has a number of difficulties - there are a small number of studies that can be used to, as it were, base this association, less than ten, certainly, and one of the things I think which we have to start off by concerning ourselves about is a problem of definition. Terms like psychotic symptom, psychosis, schizophrenia, represent very different things but they seem sometimes to be used interchangeably. A psychotic symptom is really a misinterpretation of reality. So for example, if I think someone is looking at me strangely, but there's no evidence for that, that could be psychotic symptom. A psychosis is a bunch of those symptoms which causes me to lose touch with reality. And then schizophrenia is at the other end of the scale as the most devastating psychosis, one which is involved in with abnormalities of perception, emotion, thought, motivation, motor function, which devastates people's lives and has a terrible prognosis. But they're not all the same thing at all and I think one thing that concerns me in the research which usually focuses on psychotic symptoms is the assumption that that equals a risk of schizophrenia. The next point is that it's been established for millennia that cannabis can produce as part of intoxication psychotic symptoms. These are generally transient and pass away as the drug is metabolised from the body. Do you think there's any link between the possible antipsychotic properties of cannabis and the fact that many patients with mental illnesses do like to use cannabis? I think the answer is that no one really can explain the observation that many more people with psychosis do seem to smoke cannabis than the general population. CBD maybe have an impact, it may be that somehow they just feel better in the conditions that they found themselves in which often, after all, are pretty unpleasant being in a mental institution or being very scared by the experiences that you're having. Perhaps the drug makes them feel more relaxed. no one really can explain the observation that many more people with psychosis do seem to smoke cannabis than the general population There is an intriguing observation made by a psychiatrist in Africa that where the black market cannabis contains more CBD, it seems that cannabis-related psychotic episodes seem to be less marked than in areas where the street cannabis contains very little. Just an anecdotal observation but it all adds to this intriguing possibility that CBD may have, in the end, a role in the treatment of psychosis. So what is it about cannabis do you think that links it with psychotic symptoms because you say there is a strong link between cannabis and the development of temporary psychotic symptoms associated with it? I think that one of the very important things to consider is the context in which the drug is taken. If people are feeling relaxed, unthreatened, congenial company, know what to expect, they will interpret a particular symptom in a very different way to someone who is feeling depressed, fearful, in a dreadful... um... dreadful surroundings, and the same symptom could have very different meaning for those two different people. I think that one of the very important things to consider is the context in which the drug is taken... the same symptom could have very different meaning for those two different people It's very context related. If I'm a 14 year old smoking lots of cannabis, I'm basically participating in an illegal activity which is going to have many other effects potentially in my life, my family are not going to be very pleased with this problem. I may even fall out with my family completely. I may drop out of schooling or do very badly at school. I may be involved with a bunch of friends who are much less constructive than would otherwise be the case. I might be involved in other delinquent activities. All of those things that I've mentioned have a proven association with future mental illness and may not register in the research which is being done looking at the cannabis. So whilst I'm not saying that there isn't an association between cannabis smoking and the risk of later psychotic symptoms, I'm saying that there are a number of issues that perhaps lessen the power of that association in the existing research. Whilst I'm not saying that there isn't an association between cannabis smoking and the risk of later psychotic symptoms, I'm saying that there are a number of issues that perhaps lessen the power of that association in the existing research. I mean, I would like to say though, that all my instincts are that smoking cannabis or in fact using any psychoactive drug when your brain is still developing is terribly undesirable, and very much to be argued against. Does Cannabis lead to the development of schizophrenia? Having accepted that cannabis can actually cause acute psychotic symptoms in the context of intoxication it's very important in the research that's done to discriminate that from the longer term insidious functional psychotic symptoms that occur typically in schizophrenia. Some of the studies have tried to do this, not all, some of them have tried to do it but of course in order to do that you can only ask the person have you been smoking cannabis recently. There are no objective tests to rule that out. So if for example at the end of the study I'm a 25 year old and I'm being given a questionnaire of psychotic symptoms and I tick one of them and then find I'm labelled as psychotic, if I don't choose to tell the investigator that actually I did smoke a spliff last night, that effect could entirely be a transient toxic effect and not related to the much more sinister chronic psychosis that the investigators are interested in. At the moment a causal link between cannabis smoking and schizophrenia has not been established And just finally I would say that if there was a very strong association between smoking cannabis as a youngster and developing schizophrenia in later life, and I mean schizophrenia rather than psychotic symptoms or psychosis, then you would expect that if you were to monitor very carefully the rate of cannabis smoking in a particular country where you could show that it was going up very markedly, then you would expect to see the prevalence of schizophrenia going up markedly too. That hasn't been seen where it's been carefully looked for, for example, in Australia. So I think one has to say that this is an association which requires very careful future examination. But at the moment a causal link between cannabis smoking and schizophrenia has not been established. The key research Panorama's "Cannabis: what teenagers need to know" explored the latest scientific research on the effects of cannabis on the human mind. In particular, the growing evidence of links between cannabis and psychotic illness in young people. What follows is a guide to the main theories and research in this field. Four hypotheses have been proposed about the relationship between cannabis use and mental health: * The first, the causal hypothesis, suggests that heavy cannabis use can cause mental disorders such as psychosis. * Second, the dormant hypothesis argues that cannabis use may precipitate a mental disorder that was previously dormant in individuals prone to mental health disorders. * Third, the common cause hypothesis states that mental illness and cannabis use may simply occur together as a result of common variables, such as unemployment, family difficulties and other drug use. * The fourth is the self-medication hypothesis, that people use cannabis after experiencing signs of a mental health disorder in order to alleviate symptoms. Until recently the consensus amongst the scientific community was that the fourth hypothesis which stated that people suffering from psychosis or schizophrenia used cannabis to alleviate some of the symptoms they were experiencing was the most likely explanation. However the new research is generating more interest in the first hypothesis; namely that cannabis use itself can cause psychosis. This research is based on studies where large numbers of people are followed through a process of questionnaires over ten to twenty years. The conclusions drawn from these statistical analyses have shown that there is an association between cannabis use by adolescents who are predisposed to mental health problems and later mental health problems. The publication of a Swedish study in 1987 was the first to suggest a link between cannabis and long-term mental health problems. The records of all the young men who had done national service in the Swedish army in 1969 and 1970 - 50,087 in total, representing about 97 per cent of the male population aged 18 to 20, were analysed. The research team then examined each man's medical history up to the mid-1980s. They found that those who had smoked cannabis before being called up were six times as likely to end up in hospital with schizophrenia as non-users. This, the team concluded, provided clear evidence that smoking cannabis was a risk factor for psychosis. However critics pointed out methodological flaws which severely undermined the conclusions drawn. However the findings led others to examine the link with new studies that were better designed to avoid the mistakes of the Swedish study. One of the new studies from New Zealand found that those who had smoked cannabis three times or more before the age of 15 were much more likely to suffer symptoms of schizophrenia by the time they were 26. The team, which included Professor Murray, concluded that there is a vulnerable minority of teenagers for whom cannabis is harmful. "We're not saying that cannabis is the major cause of schizophrenia but it's a risk factor." A re-analysis of an original Swedish study from the 1980s also found similar results. Last year Dutch researcher Prof Jim van Os and his team published the results of following a group of nearly 2500 14 to 24-year-olds living in and around Munich, Germany, over four years. After correcting for all the additional factors they could think of, they found that smoking cannabis as an adolescent moderately raised the risk of developing signs of psychosis later on, from 16 per cent to 25 per cent. However when they focused on individuals who were known to be susceptible to psychosis - those who were showing signs of disturbed thought processes by age 11 - they found a much stronger link. Susceptible individuals who avoided cannabis had a 25 per cent chance of developing psychosis. Susceptible individuals who smoked it had a 50 per cent risk. And the more cannabis they smoked, and the earlier they smoked it, the worse the outcome. Criticisms of the link theory The big criticism of research on any link between cannabis and psychosis has been that its not clear whether the symptoms are caused by cannabis use or whether people who are likely to develop psychotic symptoms happen also to be more likely to be attracted to cannabis. David Fergusson (New Zealand - Christchurch 25-year study group) took all confounding factors into account and found: a clear increase in rates of psychotic symptoms after the start of regular use, with daily users of cannabis having rates that were over 150% those of non users. His findings clearly show cause and effect from cannabis to psychosis not other way round. However, critics of the new research point out that other factors which can also cause mental health issues cannot always be adequately accounted for and that they may serve to lessen the power of the association between cannabis and mental health that these studies revealed. They also point out that such epidemiological studies are notoriously bad at proving cause and effect. Apart from the problem of identifying all the potential other factors the critics say that many of the conclusions are based on very small statistical differences. They point to one of the studies, which followed over 700 people, where the number of people who had smoked cannabis three times by the age of 15 was only 29. Of those 29 only three went on to develop psychosis. The critics also point out that if cannabis really was causing schizophrenia then there should bean increased incidence to match the rise in teenage consumption of cannabis. However in 2003 researchers at the University of New South Wales in Sydney found that, despite a steep rise in cannabis use among Australian teenagers over the past 30 years, there had been no rise in the prevalence of schizophrenia. However most recently researchers involved in the New Zealand study have found that there might genetic factors at work as well. The team led by Dr Avshalom Caspi, re-analysed the data, this time looking at the genetic makeup of their subjects. They investigated a gene called COMT, is involved with the breaking down of key brain chemical called dopamine. Dopamine is thought to be involved in psychosis- people with psychosis have increased dopamine in one area of the brain COMT comes in two forms., The team found that in people with two copies of the "normal" version of COMT, smoking cannabis had little effect on their mental health. In people with one normal and one "bad" form of the gene, smoking cannabis slightly increased their risk of psychosis. But for people with two copies of the bad gene, smoking cannabis as a teenager increased their likelihood of developing psychosis by a factor of 10. According to Professor Murray, 25% of the UK population carry two 'bad' copies of the COMT gene. Cannabis and our genes Professor Robin Murray The following is an edited transcript of an interview with Dr Robin Murray in which he discusses the effect cannabis can have on our brain and its relationship with our genetic make-up. Cannabis and the Brain There is a huge amount for us to understand about cannabis and the brain. Essentially almost nothing was known until the 1990s and really the bulk of the research has only happened in the last five years. The cannabanoid receptor system has been discovered and people are beginning to understand how it works, it's important in the brain as a whole. But if you compare it with what we know about amphetamines or LSD or alcohol, we know hardly anything about the way it is metabolised in the brain. That's extraordinary because this is a drug that's been used for 1000s of years. Sure, but this is not a drug that anybody paid any attention to. This is a drug which everybody thought was safe and indeed most people don't even think it's a drug. For Rastafarians this is a sacred herb, for teenagers in south London if you ask them "Do you take any drugs?", they say "No no, I don't take drugs", "Do you take cannabis?", "Oh of course I take cannabis, but that's not a drug, that's a natural substance." Cannabis consumption in Europe has only increased rapidly since the 1960s, so in some societies cannabis has been used a lot, in other societies it hasn't been used. But of course one of the differences is that not only has cannabis consumption become much commoner in Europe and Westernised societies, consumption has been starting at an earlier age and of course then more and more stronger varieties. So it's increasing consumption, starting early and the availability of much stronger variants. This is one of the things that puzzled a lot of liberal parents that took cannabis themselves in the 1960s and 1970s. It never did them any harm. Of course, they just tended to take a joint when they went to a festival or at weekends and so on and of course this was something that contained 2% - 4% of THC (tetrahydrocannabinol) which is the active ingredient. Whereas, when their kids started taking cannabis, they though "that's not so bad, at least they are not going out and getting drunk at night", but they didn't know they were smoking every night, several joints and perhaps were then going onto skunk varieties which may contain 10%, 12%, 15% or more of THC. So the actual cannabis has changed significantly over the last 40 years? Well you can still get the old fashioned varieties and in a sense they are still the most popular, but people who take a lot of cannabis tend to migrate towards the more concentrated forms, just like the person who just takes a little alcohol tends to take a lager or shandy or glass of wine, whereas the dependent person tends to take vodka or whisky. It's the same with cannabis. As you become more dependent you need to take more cannabis, then you shift more towards the skunk variety. Back to top Background to the research I see people with schizophrenia and other psychosis, so people who behave in a bizarre fashion, who think that other people are out to get them, who see or hear things. So I suppose I saw people like that, but traditionally people with schizophrenia, many of them have had problems right throughout their life. They've maybe either had some developmental problems, or as children they've been to see child psychiatrists, they didn't get on with the other boys and girls at their school and then they gradually slipped into developing schizophrenia. What then happened was that I was seeing patients with psychosis who had been very normal as children. Children who had been great at school, who'd been academically successful, who'd been very sociable, who'd been very sporty, really kids that every parent would be proud of and wouldn't think there were any problems and then they went psychotic. Now that is much more unusual. In the late 1980s and the early 1990s we started seeing lots more patients who were psychotic who had delusions and hallucinations who were also taking a lot of cannabis. And at first we thought, well maybe they are taking this because they have so many problems, it's going to help them, they're trying to calm themselves down, maybe it helps their hallucinations. But then we realised that the people who were taking the cannabis actually did worse. The psychotics who were taking cannabis did worse than the people who were not taking cannabis. We followed up about 100 people for four years and we found that the people who kept taking cannabis were three times more likely still to be psychotic, still to be hearing voices, still to be being deluded after four years. So we got to thinking, maybe if once you're psychotic it makes you worse, could it actually have contributed to developing psychosis in the first place? Back to top Cannabis and psychosis Psychosis is due to an excess of dopamine in the middle of the brain and we know that if you have an excess of dopamine for any reason this can make people psychotic. Similarly all the drugs that we use to treat psychosis, they decrease dopamine in the mid-sections of the brain. What does the dopamine system do? Well dopamine is the chemical which grabs your attention, so if suddenly something exciting happens, then this is mediated by dopamine, you pay attention to something when dopamine is released. And in psychosis, what people find is that everything seems to catch their attention. A little noise or the way that somebody grimaces or somebody new comes in the door, or they hear something on the television, all of these things seem to be tremendously important and it's because the dopamine makes them important. They think, "Gosh, these are really important to me" and begin to connect them. They think one is connected to the other, they think that television is talking to them, they think the neighbours are conspiring against them. Stick them all together and they develop a sort of delusional explanation that all of these things are happening to me because I am tremendously important, or because the CIA are ganging up against me. And it's the dopamine release that causes people to develop these illusions. And what role does cannabis play in the dopamine system? Well the cannabis just revs up the dopamine. We know that from animal studies, there have been fewer human studies, but there are now increasing studies examining that question, exactly what happens when you give cannabis and put somebody in a scanner. Of course this is one of the reasons why cannabis is useful for people with multiple sclerosis or people with chronic pain. That is to say one of the beneficial effects is the effect of the dopamine and this can help relax some of the muscles of people with neurological disease. So this is one of the reasons why we like taking cannabis, we feel it's therapeutically beneficial. The other function of dopamine of course is that it's a reward chemical, it's a pleasure chemical. All the drugs that people take, everything from alcohol to cannabis to amphetamines, they all rev up the dopamine system and in most people that just gives pleasure, but some people appear to be vulnerable, that revving up the dopamine system can induce a psychosis. So the fact that cannabis directly affects the dopamine system suggests to you that it's plausible that it plays a role in psychosis? Yes. Cannabis and genetic susceptibility to psychosis The only way you can actually find out whether cannabis actually causes psychosis is to start with people who are healthy, just like the only way you can find out whether smoking tobacco causes lung cancer is to start with teenagers who are smoking and follow them through their life. So really that's what we and other people have done. It dawned on us as it dawns on everybody, everybody knows people who smoke cannabis every day and there doesn't really have any bad effects on them, so they just get the beneficial effects. Whereas, a minority of people go psychotic, so there has to be some difference in genetic susceptibility. So the obvious thing to do was to look at the genes which are involved dopamine. We think that cannabis has it's effect on the dopamine system, therefore we wondered whether people who differed in the genes which metabolise dopamine might contribute to the susceptibility. There's a gene called COMT and COMT metabolises dopamine, breaks down dopamine in the frontal lobes of the brain. So what we did was to look at the distribution of the different types of COMT. There's a MET type and there's a VAL type. People who had a mixture of a MET and a VAL, their risk went up two-fold if they took cannabis. People who had just a VAL/VAL type of the gene, their risk went up 10 times if they took cannabis in their adolescence So it made it more clear why some people can just smoke every day for years and they don't go psychotic, but other people are much more vulnerable and they can go psychotic after a much shorter period. How many are in that very vulnerable group, the VAL/VAL group? A quarter of the population are VAL/VAL, a quarter of the population are MET/MET and the rest, half the population are a mixture. How much does it increase your risk if you are VAL/VAL? Well if you take cannabis, then you would be 10 times more likely to go psychotic if you are a VAL/VAL than if you didn't take cannabis. Normally being a VAL/VAL has no consequences whatsoever, it's just that it makes people more vulnerable to the effects of cannabis. So we can say that this is people who took a lot of cannabis, but we also know from the work of one of our colleagues in Holland, Jim van Os, he did an experimental study and he gave cannabis, a standardised cannabis cigarette to volunteers. Those with the VAL/VAL unit type, they had a much bigger effect on their memory and on their perceptions immediately following taking the cannabis, than the MET/METs. So is that the end of the story? We know now that some people have a genetic predisposition to mental illness if they smoke cannabis, is that where the research stops? We know that people vary in their susceptibility to mental illness in general and then cannabis is just one other factor. I mean I am not, wouldn't want to suggest that cannabis is the major cause of schizophrenia. Schizophrenia is a bit like heart disease, there are a number of factors that predispose, you get some genetic predisposition, children who have had a difficult birth, who have been hypoxic, short of oxygen at birth have an increased risk and then there are a range of social situations that can increase their risk of psychosis. So cannabis is just one other factor on top of this that can push people into psychosis. What we really need to know now, and what we and others are doing is to study the exact metabolism and to know exactly in humans, as opposed to rats, what happens when you do take cannabis on a scanner. So there are a number of studies now going on looking at exactly what is happening in the brain following taking cannabis. Cannabis and adolescents Does it make a difference when you smoke your cannabis on the likelihood of developing problems with mental health? It seems to, and we don't have definitive knowledge about this, but the way that we have been able to show that cannabis can contribute to the onset of psychosis is by doing big, what we call cohort studies. By taking a whole series of people in childhood or adolescence and then following them up and comparing the ones who go onto to take cannabis to the ones who don't, because there's always been this argument, maybe the people who go psychotic were always peculiar. And what we've been able to show is that in a series of about six different studies that adolescents who take a lot of cannabis are more likely to go on and develop psychosis. And even if you take any of the adolescents who seem to be a bit odd, or seem to have the possibility they might go psychotic and you put them aside, even if you follow up the healthy 15 year olds, in our study a healthy 15-year-old, normal, successful 15-year- old, those who took cannabis on a regular basis, they were three times more likely to develop psychosis by the time they were 26. Now if they started by 18 they were only about one-and-a-half times more likely to go on to develop psychosis, so it does seem that the earlier you start, the bigger the risk. Another possibility is if you start early, in our studies, you are more likely to become dependent. So you start early and you stay with it and it may be that you become more dependent. So there are these two possibilities. The other and perhaps more worrying possibility is that if you start while your brain is still developing, we know that in adolescence there are a lot of changes in the dopamine receptors, that these are being sculpted into the final sort of pattern, adult pattern and maybe if you throw cannabis at your brain cells while they are still changing and maturing, maybe this can alter them permanently. So that is the worrying possibility. We don't know this for sure, but it's clearly a possibility that has to be investigated. How plausible is that? We know that from studies of rats that if you give a range of drugs from cocaine, amphetamines or cannabis to adolescent rats then you can alter their neuronal system permanently, yes. So children, young adolescents who smoke cannabis may be permanently altered in their brain, the way they think? It's a possibility and again I would say, this is not a couple of puffs, this is taking cannabis every day for a prolonged period. Psychosis, schizophrenia and cannabis Schizophrenia is a severe type of psychosis, so by and large many people with psychosis can recover, most people with schizophrenia have it for life, they may have a chronic illness or they may have repeated relapses, so schizophrenia really is a severe type of psychosis. If there is this change in cannabis use, young people are smoking more cannabis and smoking it earlier and if that cannabis use is associated with an increase risk of mental illness, wouldn't we expect to see a huge explosion in the number of people exhibiting the symptoms of psychosis becoming schizophrenic? Well, at first I should re-iterate that in our study in New Zealand we found that cannabis accounted for 8% of schizophrenia, so if you'd abolished all cannabis consumption in New Zealand, you'd have got rid of only 8% of schizophrenia. In Holland, Van Os found it was about 13%. However these studies were some time ago and the proportion may be increasing. In fact, in south London where I work, the frequency of schizophrenia has doubled since the 1960s. Now there may be several reasons for that, but I think drug consumption is one factor. But it could just as well be that you are better at diagnosing schizophrenia, that people are more alert to the symptoms of schizophrenia? No, it couldn't. Schizophrenia is not like the psychiatric conditions which are difficult to diagnose. People who go psychotic, their friends, their relatives, they notice that they go psychotic, they get taken along to see a psychiatrist and the criteria are fairly clear. It's not that difficult to diagnose psychosis, so it's not a change in the criteria. We've actually looked at that question, that it is genuinely is that psychosis in south London is twice as common as it used to be, which is one of the reasons why the mental health services in our big cities are in such a mess. It's sad to say this, but the treatment that we can offer to people coming into many psychiatric units in our big cities is rather poor and one of the reasons for that is that the service is overwhelmed by the number of people with psychosis and I am sure that drug consumption in general and cannabis consumption contributes to this, not only in increasing the number of people coming, but recycling people through the unit. Many people who develop psychosis would normally recover, but the people who develop psychosis, recover and then go down the road and meet their dealer and start smoking again. They come back into the unit, we treat them, they get better, they go out, they come back in. So our wards are now full of people who are re-cycling through them because they are dependent on cannabis and they don't give up. So this has meant that the services are under a much greater strain than they used to be. Does the relationship between cannabis and psychosis become more obvious once somebody's had a psychotic episode? Yes, once you have been psychotic then your dopamine receptors are sensitised and a number of factors can trigger off the psychosis again and it's quite common that people who have been psychotic, who are partially recovered, for example in our unit, where somebody gets better we say well, why don't you go out for the evening, meet your friends, they come back and the next morning they are psychotic again and if we say, well did you have a joint and they say yes, they are really surprised it could be just one joint. They say, well it used to be that I smoked every day and I didn't go psychotic, once you have de-sensitised your dopamine system it can be sort of triggered off relatively easily. Some people have compared the influence of cannabis on mental health and the influence of tobacco on lung cancer, do you think that is a fair comparison? I think it's perhaps more like alcohol actually than smoking, because cigarette smoking account for nearly all of lung cancer, whereas cannabis accounts only for a proportion of schizophrenia. Most people can drink alcohol and they don't get liver failure, they don't become an alcoholic, the more they drink, the more likely they are to develop problems and similarly with cannabis, that most people will get nothing but benefits from smoking cannabis, but a proportion of people will develop problems particularly if they smoke very heavily. You talk as if it's certain that the causal direction... the fact that cannabis may have a causal role in some mental illness is a matter of fact, yet the studies are actually very small populations of people who actually developed psychosis. Were they statistically significant, how robust is this research? Well the studies are not all small. The Swedish army study was a study of 50,000 men inducted into the Swedish army and then followed up for 25 years and they found that several hundred people went psychotic. And the people who had smoked cannabis when they were 18 heavily, they were six times more likely to go psychotic. Some of the other studies have been smaller and more intensive. But it's relatively unusually in epidemiology for all the studies to point in the same direction and since 2002 there have been six studies and they've al pointed in the same direction. Now I would accept that epidemiological studies cannot absolutely prove something. In order to prove that, if we go back to the link between cigarette smoking and lung cancer, the epidemiological studies could show a link, but it wasn't until animal studies were done, where rats were made to smoke cigarettes and they were shown to develop lung cancer. We really have to do some equivalent studies where we actually understand the mechanism in the brain in much greater detail than we understand it at present before it can be 100% proven. How confident are you that cannabis plays a role in the development of some mental illness, some psychosis? Oh I think I am much more confident. I would say I am convinced. Why am I convinced? Partly because of the evidence, but partly because of the patients I see and also the fact that when people who are psychotic, when they stop taking cannabis you can have such a dramatic improvement, so it seems fairly logical, if you stop doing something and you improve, maybe it contributed to it in the first place. You say that the epidemiological studies don't give us proof as yet, so are you convinced that cannabis plays a causal role in the development of some mental illness? I think that as a clinician one pays a lot of attention to the epidemiology, but one also pays attention to the patients one sees and what they and their relatives tell one. And in particular I've been impressed by some people with very severe psychosis, who I really was rather pessimistic about their future, but then they stopped taking cannabis and they did so much better. So if stopping banging your head against the wall relives the pain, well maybe banging your head against the wall actually contributed to the pain in your head. Featured Research Professor Robin Murray Research published in the British Journal of Psychiatry (2004) 181, p110 - 117 His research examines the evidence that cannabis causes psychosis using established criteria of causality. His team identified five studies that included a well-defined sample drawn from population-based registers or cohorts and used prospective measures of cannabis use and adult psychosis His team's findings were: 1./ On an individual level, cannabis use confers an overall twofold increase in the relative risk factor for later schizophrenia. 2./ At the population level, elimination of cannabis use would reduce the incidence of schizophrenia by approximately 8%, assuming a causal relationship. 3./ Cannabis use appears to be neither a sufficient nor a necessary cause for psychosis. It is a component cause, part of a complex constellation of factors leading to psychosis. His team concluded that cases of psychotic disorder could be prevented by discouraging cannabis use among vulnerable youths but also felt that further research is needed to understand the mechanisms by which cannabis causes psychosis Professor Yasmin Hurd Her research investigates the close relationship between psychiatric disorders and drug abuse. As drug abuse is 4-7 times more common in persons with depression or schizophrenic syndromes and 35-80% of drug abusers will suffer from psychiatric disorders during their lifetime. The strong association between drug abuse and psychiatric disorders suggests similar underlying neurobiological impairments. Her research team is focused on the systematic study of human brains from subjects with drug abuse (stimulants and opiates) and psychiatric disorders. Their goal is to identify and map specific genes in which regulate emotional functions, and are thereby relevant to the disorders of interest. Additional studies carried out by this group are designed to assess how drugs affect the development of the human brain during the foetal stage, which may later lead to psychiatric problems. As complement to studies of the human brain, animal models are used in this research group to simultaneously study changes in neurotransmitter levels (e.g., dopamine) during drug self-administration behaviour. Possible neural targets for the development of future treatments against depression and drug dependence have been identified and published by the research group. (Professor Hurd's results are unpublished and have not been replicated at this time). Further Reading Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyl transferase gene: longitudinal evidence of a gene X environment interaction. Caspi et al., Biological Psychiatry. 2005 May 15; 57(10) p1117-27 Arseneault L, Cannon M, Poulton R, et al, 2002, Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study, BMJ 2002; 325:1212 -1213 Arseneault L, Cannon M, Witton J, Murray R M, 2004, Causal association between cannabis and psychosis: examination of the evidence, Br. J. Psychiatry, 2004; 184: 110 - 117 Hall W, Solowij N, 1998, Adverse effects of cannabis, Lancet 1998; 352:1611-16 van Os J, Bak M, Hanssen M, Bijl R V, de Graaf R, Verdoux H, 2002, Cannabis Use and Psychosis: A Longitudinal Population-based Study, Am. J. Epidemiol. 2002; 156: 319 - 327 David Ferguson and John Horwood "Cannabis Use and Dependence in a New Zealand Birth Cohort" New Zealand Medical Journal 12/5/2000: 113 (1109): 1506-1508 Macleod J, Oakes R, Copello A, Crome I, Egger M, Hickman M, Oppenkowski T, Stokes-Lampard H, Davey Smith G. "Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies". Zammit S, Allebeck P, Andreasson S, Lundberg I, Lewis G (2002) Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ 325: 1199 Andreasson S, Allebeck P, Engstrom A, Rydberg U (1987) Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 2:1483-1486
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