BBC Cannabis, ce que les ados doivent savoir.
Updated: Sunday, 19 June, 2005, 21:24 GMT 22:24 UK
and our genes
following is an edited transcript of an interview with Dr Robin
Murray, Head of Psychiatry at the Institute of Psychiatry, in which
he discusses the effect cannabis can have on our brain and its
relationship with our genetic make-up.
and the Brain
to the research
and genetic susceptibility to psychosis
schizophrenia and cannabis
Cannabis and the Brain and Background to
is a huge amount for us to understand about cannabis and the brain.
almost nothing was known until the 1990s and really the bulk of the
research has only happened in the last five years.
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.
but this is not a drug that anybody paid any attention to.
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",
you take cannabis?",
of course I take cannabis, but that's not a drug, that's a natural
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.
it's increasing consumption, starting early and the availability of
much stronger variants.
is one of the things that puzzled a lot of liberal parents that took
cannabis themselves in the 1960s and 1970s.
never did them any harm.
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
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.
the actual cannabis has changed significantly over the last 40 years?
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.
the same with cannabis. As you become more dependent you need to take
more cannabis, then you shift more towards the skunk variety.
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.
I suppose I saw people like that, but traditionally people with
schizophrenia, many of them have had problems right throughout their
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
then happened was that I was seeing patients with psychosis who had
been very normal as 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.
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.
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.
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.
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.
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?
Cannabis and 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.
all the drugs that we use to treat psychosis, they decrease dopamine
in the mid-sections of the brain.
does the dopamine system do?
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.
in psychosis, what people find is that everything seems to catch
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.
think, "Gosh, these are really important to me" and begin
to connect them.
think one is connected to the other, they think that television is
talking to them, they think the neighbours are conspiring against
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.
it's the dopamine release that causes people to develop these
what role does cannabis play in the dopamine system?
the cannabis just revs up the dopamine.
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.
course this is one of the reasons why cannabis is useful for people
with multiple sclerosis or people with chronic pain.
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
this is one of the reasons why we like taking cannabis, we feel it's
other function of dopamine of course is that it's a reward chemical,
it's a pleasure chemical.
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.
the fact that cannabis directly affects the dopamine system suggests
to you that it's plausible that it plays a role in psychosis?
and genetic susceptibility to psychosis
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
really that's what we and other people have done.
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.
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.
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.
a gene called COMT and COMT metabolises dopamine, breaks down
dopamine in the frontal lobes of the brain.
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.
who had a mixture of a MET and a VAL, their risk went up two-fold if
they took cannabis.
who had just a VAL/VAL type of the gene, their risk went up 10 times
if they took cannabis in their adolescence
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.
many are in that very vulnerable group, the VAL/VAL group?
dans chaque groupe ?
quarter of the population are VAL/VAL, a quarter of the population
are MET/MET and the rest, half the population are a mixture.
quart de la population est VAL/VAL, un quart est MET/MET et le reste
la moitié de la population un mélange.
much does it increase your risk if you are VAL/VAL?
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.
being a VAL/VAL has no consequences whatsoever, it's just that it
makes people more vulnerable to the effects of cannabis.
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
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?
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
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.
cannabis is just one other factor on top of this that can push people
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.
there are a number of studies now going on looking at exactly what is
happening in the brain following taking cannabis.
it make a difference when you smoke your cannabis on the likelihood
of developing problems with mental health?
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.
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.
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.
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.
possibility is if you start early, in our studies, you are more
likely to become dependent.
you start early and you stay with it and it may be that you become
there are these two possibilities.
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.
that is the worrying possibility. We don't know this for sure, but
it's clearly a possibility that has to be investigated.
plausible is that?
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.
children, young adolescents who smoke cannabis may be permanently
altered in their brain, the way they think?
a possibility and again I would say, this is not a couple of puffs,
this is taking cannabis every day for a prolonged period.
schizophrenia and cannabis
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.
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
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.
Holland, Van Os found it was about 13%.
these studies were some time ago and the proportion may be
fact, in south London where I work, the frequency of schizophrenia
has doubled since the 1960s.
there may be several reasons for that, but I think drug consumption
is one factor.
it could just as well be that you are better at diagnosing
schizophrenia, that people are more alert to the symptoms of
is not like the psychiatric conditions which are difficult to
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.
not that difficult to diagnose psychosis, so it's not a change in the
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.
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
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.
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.
this has meant that the services are under a much greater strain than
they used to be.
the relationship between cannabis and psychosis become more obvious
once somebody's had a psychotic episode?
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
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.
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.
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
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.
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.
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?
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.
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.
I would accept that epidemiological studies cannot absolutely prove
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.
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?
I think I am much more confident.
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.
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?
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.
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.
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.