Yale Psychiatry Grand Rounds: "Cannabis and Mental Health"

January 05, 2024

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January 5, 2024

"Cannabis and Mental Health"

Speaker: Sir Robin Murray, Sir Robin Murray, Professor of Psychiatric Research, King's College London

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00:00And thank you also John, can people see,
00:04see my slides can you put. Yes. Good.
00:07So it's a it's a pleasure and indeed
00:11an honour to be invited to contribute
00:15to your grand rounds particularly
00:17at the time of the the the the
00:20development of the of the new centre.
00:22But I'm conscious of course that with
00:24Cyril and the centre you probably know
00:26a lot about cannabis and mental health.
00:28So I'll try.
00:29I'll try not to be repetitive and if people
00:32I I've given similar lectures to this
00:34before so I know what I'm going to say.
00:37It's not it's not it's not new to me
00:39so if people want to interrupt I make
00:42it more lively then I'll be very happy.
00:45I guess you could do that by sticking up
00:49your hand or or or putting a question in
00:52the chat and no doubt Cyril will read it out.
00:56So I've received various payments
00:58for non promotional lectures.
00:59I don't do promotional lectures from
01:02from various say, drug companies,
01:04no cannabis companies. Of course.
01:08We psychiatrists talk about
01:11the downside of cannabis use.
01:14I we don't talk about the fact that
01:17millions of people enjoy using it
01:20and we don't generally talk about the
01:23indications for medicinal cannabis,
01:25but just to very briefly remind
01:28ourselves that this is,
01:30this is the review of the National
01:32Academy of Science that cannabis has a
01:36modest beneficial effect on chronic pain.
01:40Not a,
01:41not a very a powerful effect,
01:43a bit like a couple of aspirins.
01:46But of course if you have chronic pain
01:48and you get an analgesic effect and a
01:51little bit of euphoria, then that's good.
01:53That's good.
01:54To help a intractable nausea,
01:57you'll know that Nebulon A,
02:00which is A
02:04is similar to THTHC is very useful in
02:09people who are having chemotherapy or
02:12other intractable causes of nausea.
02:14Though I understand from there been a
02:17survey in Colorado of a charity centre
02:23lady looking pregnant into into a
02:26hundred A marijuana dispensaries and
02:29found that 75% of them recommended
02:33a a cannabis for for nausea during
02:37pregnancy which is clearly counter
02:41counter indicated a multiple sclerosis.
02:44That I I don't know whether it
02:46has a licence in the USA,
02:48but a drug called Sativex which is
02:51a combination low of low dose of THC
02:54and CBD which you take by inhalation,
02:57is useful for a spasticity.
03:00And I'll come back to Sativex later on.
03:02But the the the, the,
03:04the poster boy really of the
03:07effectiveness of cannabinoid drugs
03:09is ACBD for childhood epilepsy
03:12where it can have very spectacular
03:15effects on these poor children who
03:18have a maybe 100 or 150 fits a day.
03:22They can be greatly reduced or in
03:24some cases abolished by by CBD.
03:28Of course,
03:29if you go on the Internet there are
03:32indications without but without
03:34RCT evidence that that I think is.
03:36I'll be pleased if people know of any other.
03:39They are more recent RCTs,
03:41but as far as I know that's the only a real,
03:44real hard evidence of the effectiveness
03:47of medicinal cannabis.
03:48But on the Internet,
03:51cannabis and and it's components are
03:56suggested to be of value on absolutely
03:59everything from opioid addiction,
04:01from depression, anxiety, PDSD, insomnia.
04:06Just at the beginning of COVID,
04:07I said to my wife,
04:10I bet people will be advocating a
04:14cannabis as a treatment for COVID.
04:16And of course soon enough this this occurred.
04:18But there there's no evidence for for,
04:20for, for these in the UK.
04:24Most of the hype cannabis is say
04:26is legal for medicinal use in the
04:30UK and has been for five years,
04:32but doctors don't prescribe it.
04:34By and large,
04:36the British doctors have been
04:39indoctrinated that you only prescribed
04:42drugs for when there is say,
04:45when, when, when,
04:46when,
04:46when there is proper scientific
04:48evidence for their effectiveness
04:50and we have a thing called NICE
04:53which advises you whether there
04:54is evidence for this or that.
04:56So in in the five years less than
04:591000 people have have received a
05:03medicinal cannabis from from the state
05:07psychiatric or the state services.
05:09That's what we call the National
05:11Health Service.
05:11There are private practitioners in
05:13in the UK who have realised that
05:16there's a gap here and so they have
05:19been a prescribing a a medicinal
05:22cannabis for in the same way.
05:24I think that it is often prescribed
05:27in the in the USA without much
05:30much evidence but in in the UK you
05:36can buy CBD and health shops but
05:39it because of course it's quite
05:42difficult to get pure T pure CBD
05:45because you have to extract the
05:47THC and that is quite expensive.
05:50So in our shops what they mostly
05:53sell is water
05:55with a a very little IACBD in it but
05:59but it's very fashionable and lots of
06:02people swear that this CBD flavoured
06:05water is is very very helpful.
06:08There have been there has as you
06:12know there's often it's often
06:14suggested that THC or CBD are various
06:17combinations may be useful for
06:19treatment of psychiatric disorders.
06:21The last meta analysis I know is this
06:24one by Black and Degenhardt and they
06:28really found no evidence from RCTs
06:31that cannabinoids are beneficial.
06:33But of course you all know this
06:37is not what patients say and what
06:40many cannabis doctors in the USA
06:42and now I guess in the UK also say.
06:45And one question is why?
06:48Why do people,
06:52why do people think that a
06:55a cannabis helps anxiety,
06:57depression and and PTSD?
07:00One problem of course is that many
07:03of the people who feel that that
07:05anxiety or the depression or indeed
07:07their insomnia is benefited are people
07:10who are already dependent on a a
07:13cannabis and therefore if they stop
07:15cannabis they can't sleep for example.
07:17And then they find that they taking
07:19the cannabis does benefit them.
07:21So it's difficult to disentangle
07:23whether you're taking or people are
07:25taking the cannabis for a genuine
07:28effect or I an effect to relieve
07:32withdrawal which of course is genuine.
07:34Also they in our in our department
07:38Paul Morrison in particular and Phil
07:42McGuire has added a large doses of
07:46oral CBD to the treatment of people
07:50with chronic schizophrenia and who
07:53were already on antipsychotics and
07:54they found a modest improvement
07:57on this in this not all studies
08:01they've been several negative
08:03studies including one from Yale I.
08:05So it's a little unclear whether
08:10this the what the status is
08:11and even if there is an effect.
08:12Is that due to the effect of
08:15this the the pharmacogenetic
08:17pharmacological effect of the CBD?
08:19Or is it due to some interference
08:22with the metabolism of the
08:25antipsychotics resulting in higher,
08:27higher blood level of antipsychotics.
08:31The for
08:35really the the vast majority of
08:37research in cannabis use and mental
08:40health has been on psychosis,
08:41which I'll come to.
08:43But there are increasing numbers
08:45of studies looking at depression
08:48and anxiety and a suicide.
08:51And here is a meta analysis by a
08:56Gabriella Gobby from Montreal showing
08:58that in adolescence that the risk
09:01of depression is increased in people
09:03who are taking cannabis and so also
09:06is the the the risk of of suicide.
09:09They didn't find an effect a
09:12an adverse effect for anxiety.
09:14So it's sort of paradoxical that lots
09:18of people are taking cannabis for to
09:21to get benefits of depression and anxiety.
09:25But what little evidence we have
09:28regarding these non psychotic conditions
09:30is that actually that actually
09:33using cannabis is associated with
09:36increased risk of these conditions.
09:40You all know that people can
09:42develop cannabis dependence.
09:43It used to be thought that about
09:4610% of people who were taking daily
09:48cannabis would become dependent on it.
09:50But now with the increase in potency,
09:53there are suggestions that maybe
09:54up to 30% of people taking a daily
09:58cannabis may become a dependent.
10:01So obviously there's lots of control,
10:04there's craving, you don't have this problem.
10:07But in Europe and in the UK,
10:10nearly everybody smokes their
10:12cannabis a mixed with tobacco.
10:14You think they think it,
10:15it burns better with tobacco.
10:18So when people stop,
10:20they get withdrawal from the
10:21cannabis and they also get withdrawal
10:24from the tobacco of course,
10:26which makes it more difficult to stop.
10:28Whoops,
10:29There's there's lots of evidence for
10:32tolerance and that is withdrawal.
10:34But this is not immediate because cannabis
10:36can still be detected up for up to a month.
10:39So I you know,
10:41if if any of us go out and
10:44get drunk within 24 hours,
10:46most of the alcohol is as is
10:48out of our system.
10:49But if we go out and take a lot of cannabis,
10:52it will still be detected for up to a month.
10:54So the withdrawal symptoms tend not
10:56to occur until a four or five days.
11:01I guess you all know that, say,
11:03the main ingredients of cannabis
11:05are tetrahydrocannabinol.
11:06THC, which is a partial
11:09agonist at CB1 receptor,
11:11causes euphoria and enjoyment,
11:13which is why people take it.
11:17If you if you try,
11:18you try and talk to somebody who's
11:20don't you know that they they they
11:23may think they're getting new sick,
11:24new new insights into the
11:26secrets of the universe,
11:27but they can't often remember
11:31what question you've asked them
11:32or they don't remember the
11:33beginning of their reply when they
11:35get to the end of the sentence.
11:36So attention and memory can be impaired
11:39particularly with higher doses.
11:41And we and I guess Suttle and
11:44colleagues are very familiar with
11:45the fact it's very easy to induce
11:47paranoia with THC in our hands.
11:49It's actually easier to induce paranoia
11:52with THC than it is with amphetamine,
11:56but then that's with high doses obviously.
11:58I CBD on the other hand
12:01is not hallucinogenic.
12:02The mechanism of action is
12:04still very contentious.
12:05Some people say it's an inverse agonist.
12:07Other people say it's got a a range
12:10of of of indirect indirect effects on
12:15the the endogenous cannabinoid system.
12:19It has anxiety relieving properties
12:21and there's been some question
12:23as to whether it can antagonize
12:25THC in very large doses.
12:27So we were quite enthusiastic about
12:30this last last piece of information
12:35that if we gave huge doses of CBD we
12:39could prevent some of the effects of THC.
12:42But in fact when we actually
12:44gave modest doses of CBD,
12:46the sort the sort of doses that you
12:48would get in old fashioned cannabis,
12:50then it had no effect.
12:52So it does seem that that for
12:56all practical points of view
13:00sort of real world amounts of CBD,
13:03we don't ameliorate the
13:05effect of THC and cannabis.
13:07So the crucial thing is the is the
13:10potency of the other the the the potency
13:13of the of the cannabis of of THC.
13:16And you know, yeah,
13:17I'm sure you'll, you'll know this.
13:19This is the percentage of THC and
13:21CBD and cannabis samples in the USA
13:24from 1995 and the red is THC and
13:27you can see the steady increase
13:30from about 3 or 4% up to about 15%.
13:34This is a smoked cannabis and you
13:37can see also that CBD has tended
13:40to be declining much the same as
13:43been happening in in in in the UK.
13:47This is say from I study of in
13:53the Netherlands and this is just
13:56showing the relationship between
13:57a potency and dependence.
14:00So the the red is the potency of
14:03THC and you can see that from
14:06two 2000 it was about 8% THC and
14:12it went up to about 20% and then
14:15slightly came down to about 15%.
14:17And you can see that there was
14:19a lag and then people coming to
14:21treatment that came after a few years
14:24later and you can see that the the
14:26people number of people coming into
14:29treatment steadily increased and
14:31then a few years after the peak of
14:35a potency then as the potency fell,
14:39so did the number of people coming
14:40to treatment.
14:43So apart from psychosis,
14:46there's the question of cognitive impairment.
14:50And the most spectacular evidence from
14:53this came from the Dunedin Study that
14:57that between the ages of of 16 and 38,
15:03regular cannabis users lost
15:05about 8 points in IQ.
15:07And nobody has ever replicated this.
15:09And they I I I personally
15:12find it difficult to believe,
15:15But certainly while people are I intoxicated,
15:19they're cognitive,
15:20they're cognitively impaired,
15:21and we don't yet know whether this
15:24totally recovers when they stop or not.
15:27The increased risk of violence has not had
15:30been as much attention as I think it merits.
15:34I in the UK there is a national
15:37survey of all the people who I commit
15:41murder and a of those people with
15:46schizophrenia who commit murder,
15:47about half a are a abusing alcohol and
15:52just under that are abusing cannabis.
15:55So it seems that cannabis and
15:58alcohol are equally irrelevant
15:59to people with schizophrenia.
16:01Who I who commit murder oops.
16:05I can see who my cat has appeared
16:08behind if they this is a strategy
16:10I I I use to keep you awake
16:17anyway so so I I think there's a
16:21creeping evidence that a cannabis
16:24does does increase risk of violence
16:26and we we are just completing a
16:30meta analysis on this on on this
16:32issue it seems to be pretty clear
16:33that it it does have an effect
16:38so cannabis and psychosis the first
16:42study a really to adopt A systematic
16:47approach to this is an Indian study
16:50and was back in the 1890s and the
16:53the British Raj that this this
16:56was colonial times had built a big
16:59mental hospitals around some of the
17:01major cities and they were very
17:04concerned that these asylums seem
17:06to be filling up with people who
17:09were a with cannabis users or AI.
17:13So I they they introduced a a review
17:19and there's a it's actually a very
17:22thorough review with thousands of pages.
17:27And they the here is here is just
17:31a quote from one of the the the the
17:34the Indian doctors who said the
17:37majority of habitual users of a
17:41cannabis become permanently insane
17:43never to be confused or cured.
17:46Then somewhat contradictory,
17:47he says somebody can't come temporarily
17:50so and become sane on breaking off the
17:53habit but symptoms are apartment to be
17:55reintroduced and resuming the habit.
17:57Now I I several knows this say
18:01the British rash.
18:02I was quite smart in some ways.
18:05So this this committee that they
18:07had the set up,
18:09had Indian psychiatrists on it and
18:12it also had British administrators
18:14and people from the tax office
18:16because they were worried that the,
18:18the,
18:19the cannabis was legal at the time
18:21and the the the the the colonial,
18:23the colonial administration made
18:25quite a lot of money out of taxing cannabis.
18:28So they arranged that there would be
18:31more administrators than there were a
18:33psychiatrist and doctors on the committee.
18:35So the committee eventually
18:37concluded that it should stay,
18:38it should stay legal because of the,
18:42I think probably because of the tax income.
18:44And this is this is very reminiscent I think,
18:46of some of the discussions that you've been
18:49having in different states than the USA,
18:51where politicians have been very
18:53keen on the idea of legalizing
18:55cannabis because of the amount of
18:57money that they would get in taxes.
18:59But the the the British colonialists
19:03thought of this 130 years ago.
19:07So there are now three meta analysis
19:10which point to cannabis use as a
19:13risk factor for psychotic disorders.
19:16This is a summary produced by Evangelis
19:19Vasos and each of these studies or excuse me,
19:23each of these lines is a different
19:27cannabis use and psychosis study.
19:29Along the bottom is the amount of
19:32cannabis people are taking and
19:34then the vertical axis is the odds
19:37ratio for for psychosis.
19:38And you can see that at the at the
19:42right hand side the 20% people who
19:45had smoked the most cannabis had a
19:48greater risk of psychosis than the 20 people,
19:5120% of people who had smoked the least
19:54cannabis or had spoke no cannabis at all.
19:57But you'll notice that there's
19:59quite a a a spread that in on on how
20:03high the risk is in heavy users.
20:05And if you look at the grey line at the
20:08bottom, that is TN in 1990 in the USA.
20:12And at that time of course cannabis was
20:14still quite a was not potent at all.
20:16It was quite weak with low low.
20:18No percentage of THC, but if you look
20:21at say if you look at say the red,
20:24that's South London in 2000 and 2011.
20:29So and the odds ratio goes up to about 7:00.
20:33But overall it's the pooled
20:35odds ratio was about four.
20:40Now of course there's been
20:42a lot of argument about it.
20:45Could this be because people
20:47are taking other drugs,
20:48amphetamines and and studies
20:51have tried to exclude this?
20:54I could also be that people were
20:58rather strange and and we're taking
21:01the the cannabis to try and prevent
21:03them to try and prevent psychiatric
21:06service symptoms and they've been
21:08studies where they excluded people
21:10in the prodrome or excluded people
21:13who were abnormalized children and
21:15they they've still had still shown
21:18an effect for for for cannabis on
21:20on on risk the the the the major I
21:25mean one of one of the the the the
21:28the things which tends to convince
21:30people is say the evidence of the
21:34effect of experimental experimentally
21:37giving THC and and you've done a lot
21:40of this work in the early days in
21:42Yale we've done a sort of variant
21:44on the kids that kind of studies
21:47that settle and colleagues have
21:49been doing this here we have 121
21:51people chosen because they were a
21:53bit ****** they were ****** tipple
21:56and so they they we we sent out lots
21:59of lots of questionnaires on on the
22:01Internet and then we selected people
22:03who scored highly on on ****** tippy
22:06and they we're really trying to
22:10select people who are particularly
22:12likely to have a a a psychotic
22:15reaction to to to to to cannabis.
22:18So they they they they they either
22:21get THC or placebo and they get
22:24they go into a virtual reality
22:29set up and what they see is like going
22:32into the London Underground or Subway
22:35and they and then they see the train
22:38comes in and the doors open and they
22:40look in and they go in and there are
22:43various human like figures there.
22:46And interestingly normal people,
22:48well non patients differ very
22:51strikingly in the reaction.
22:53For example you can think of a normal
22:56individual who saw this man here
22:58and he looks up and she says oh he
23:01looked at me as if I was attractive.
23:03Maybe he fancies me And then
23:05another lady said, oh,
23:07this man looked at me in a very hostile way.
23:09I I don't know what he's
23:12got against people like me.
23:14So we then compared the people who had had
23:17the THC but the people who had the placebo.
23:20And you can see that they've
23:23the mean scores on a store score
23:25called the called the Green
23:29a paranoia scale. The the the people
23:32who had the THC were twice as likely
23:35to or had a paranoia score a twice
23:39that of the people on on the placebo.
23:42Now of course you think to yourself,
23:43why would people pay good money in order to
23:46get a drug which will make them paranoid.
23:49But of course this is a high dose
23:51intravenously and it's also it's
23:53not that this is not spoken cannabis
23:55with your mates on a Saturday night.
23:57This is in in in a medical set up where
24:01you know you're being you're you're
24:03being watched or monitored rather the
24:09I think the evidence that this that
24:15that I'm sorry I should have said
24:18that amongst these studies of cannabis
24:20there and risk of psychosis there are
24:23there are a number of prospective
24:25studies on the same way that that we
24:29discovered that tobacco use increases
24:33the the later risk of lung cancer.
24:36You take up a a sample of the general
24:38population to divide them into those
24:40who smoke tobacco or in this case
24:43smoke cannabis and then follow them
24:45up and see what happens to them.
24:47And of course the people who are smoking
24:50cannabis have a higher risk of psychosis.
24:52But one question has been do people
24:55smoke cannabis because they have a
24:58genetic predisposition to psychosis?
25:00And we have looked at this in
25:02several studies,
25:03and there have been some genetic studies
25:06where they did show an effect of the
25:09apologetic risk score for schizophrenia.
25:11So it's a it's a means of a
25:15of a assessing the the, the,
25:18the genetic predisposition to psychosis.
25:21And they've been some studies
25:23which have suggested that this did
25:25have a small effect on cannabis,
25:27on cannabis use in the general population.
25:30And we've done studies where we have,
25:32I found no effect on cannabis
25:35use in the general population.
25:37And also one study in the UK,
25:40Biobank,
25:40which is a huge study of about
25:42half a million people,
25:43where there did seem to be a small effect of
25:48cannabis use on variance in cannabis use.
25:51But it was of the order of about
25:53say less than 2% of the variance in
25:56cannabis use appeared to be related to
25:58the the palogenic risk score for for
26:02schizophrenia. I think it's myself.
26:04It's a bit probably a bit like
26:06alcohol and alcoholism.
26:07The majority of people who become alcoholic.
26:10But why do how how does this happen.
26:12Well they they they like alcohol
26:14they're they're they're in the army
26:17and all their friends are drinking
26:19or they work in pubs or the rest of
26:21their own business and there's a lot
26:23of available alcohol or in Britain
26:25they they they they they play rugby
26:27and after the rugby they they they
26:29all go out drinking.
26:31So most people become alcoholic
26:33because they like the alcohol but as
26:35you know there is there is a small
26:37proportion of people who find that
26:39in the at a later point in their
26:42life often that
26:43alcohol can produce some immediate
26:45relief from anxiety or a depression.
26:49So I think probably cannabis has
26:54a similar sort of effect that
26:57majority of people are not taking
27:00it because I for medicinal reasons
27:03but some people are self medicating.
27:06The more important question is
27:09does say genetic predisposition?
27:12How does genetic predisposition
27:15relate to cannabis use?
27:18Do they are the effects additive
27:21or indeed are they are they more
27:25than additive And this is this
27:27is a study where oh excuse me I
27:29should just I'm sure you all know
27:31about apologetic risk scores.
27:32But just to remind you that say you
27:35take a blood sample you do AG was
27:39and they they're now they're now have
27:42been very large studies which they
27:45have shown that say people with with
27:50with schizophrenia have about 280
27:53A loci on the genome which differ
27:56between them and the controls And
27:59that you can also use the similar
28:02set of methods to to assess the
28:05genetic liability in the general
28:08population by allogenic risk score.
28:10So you can take the polygenic risk
28:13score for schizophrenia and then run
28:15it through people who have a by who
28:20have psychosis and psychosis for example,
28:24induced by are associated with with cannabis.
28:29So this is a study that we've just sent off
28:34for
28:37to a journal. So if any any of
28:40you are likely to be reviewers,
28:43I hope you'll you'll treat us kindly.
28:46But essentially this is a study called
28:49EUGI which is a big trans European study
28:51that I'll come back to and where we have.
28:56So this really looks at the Scott,
28:59the the liability to be not
29:02a case but a control.
29:04So it's a case control study Along
29:05the bottom is your score on the
29:08polygenic risk score for schizophrenia.
29:09So long at the right hand side you have
29:12a high predisposition to schizophrenia.
29:13On the on the left you have a low
29:16predisposition to schizophrenia
29:18and the different colours are
29:20how much cannabis you use.
29:23So for example if you look down in the
29:26bottom in this brownie set of colour,
29:29these are people who have a oh the red one,
29:33which removes me.
29:33The the sort of orange ones are people
29:36who've never used cannabis and the ones
29:39in brown are those two rarely used a
29:42old fashioned low potency cannabis.
29:43And you can see that say that say
29:46they have a low likelihood of being
29:48psychotic if they don't have a high
29:51apollogenic risk score for schizophrenia.
29:53But if they have a high apollogenic
29:55risk score for schizophrenia then
29:57they certainly can develop psychosis.
29:59On the other hand the the the ones
30:02who are daily using a cannabis which
30:05is in this purple colour here you
30:08can see that A that at at low levels
30:13of polygenic risk score they have a
30:16higher risk of developing psychosis.
30:18That the one that the number users tend
30:22to catch up a bit but a they they but
30:26the ones who are who are a a heavily using,
30:30who are who have a high apollogenic
30:33risk score are still more likely to go
30:36psychotic than the ones with a hypologenic
30:38risk score who are not using cannabis.
30:41So this just seems to be a
30:43sort of summation effect.
30:44So there's no interaction or evidence
30:46of a biological interaction here.
30:48These are independent effects an
30:50effect of cannabis on site or risk
30:53of psychosis and an effect of the
30:55apollogenic risk score on psychosis.
30:57So obviously the apollogenic risk or is
30:59a very crude thing and one really wants
31:02to know what is the effect of people
31:04who have differences in the end the
31:06genes for the endocannabinoid system And
31:09so various people are looking at that.
31:13What about the characteristics
31:15of cannabis associated psychosis?
31:17I should say that we are lucky or
31:20unlucky in that say in South London
31:23we have the highest consumption
31:25of cannabis in in the UK,
31:28so about 60% of our patients with
31:30the first episode of psychosis.
31:36The cannabis associated psychotic patients,
31:39I they they they just look they
31:42can they can look very they they
31:44just in many ways look the same
31:47as people with schizophrenia,
31:48but they have an earlier onset
31:50than the non cannabis users.
31:52They have more prominent positive symptoms,
31:54especially paranoia,
31:55and less in the way of negative symptoms.
31:59They have a higher premorbid IQ
32:01and better premorbid function than
32:03many other schizophrenia patients.
32:06You know as you know a proportion of
32:10schizophrenia is neurodevelopmental
32:11and therefore these people have always
32:15had carbon cognitive difficulties
32:16throughout their childhood and their life.
32:19And so they are performed The the
32:22average IQ of somebody in the in
32:25England who develops a A psychosis
32:28is not 100 as it should be,
32:31but it's 95 S The the the non
32:34cannabis users have a slightly
32:37decreased premorbid function.
32:38The cannabis users start off doing
32:40very well and they're very clever
32:42and often they're very sociable
32:44because they have friends that
32:46can introduce them to cannabis
32:47dealers when they're 13 or 14.
32:51I this is a just to show I that
32:55the the effect of a whether you,
32:58whether you continue or don't
33:01continue using cannabis.
33:03So this is a lady called Tabia Scholar
33:05who was a APHD student with us.
33:08Whoops excuse me?
33:09And here a there is a follow up of
33:11people with their first episode of
33:14psychosis for two years and here is
33:17the proportion who relapsed and you
33:20can see in the down here in the brown
33:27so the the sorry the blue are the
33:31blue is say I've never used cannabis.
33:34The the green here are people who
33:37continue to use cannabis and they the
33:43the former cannabis users are are,
33:45are are down here.
33:47So essentially the people who've never
33:49used cannabis are in the middle.
33:51The people who stop using cannabis have
33:53the the worst outcome and are likely to
33:56relapse but you have a very good outcome.
33:58Well a pretty good outcome if you've
34:00been using cannabis and you then stop.
34:05One of the problems least to the
34:07UK is who is going to treat you.
34:10And if you go to the if you're a
34:14cannabis associated psychosis and
34:16you go to the addiction services,
34:18they won't be interested because they say,
34:21well you're psychotic.
34:22You need to be treated by the people
34:24who look at the adult psychiatrists
34:27who look after psychosis.
34:28And if you go to the psychosis services,
34:31well they'll,
34:32they'll admit you when you're psychotic,
34:34but when you're when you're
34:36discharged they say, well,
34:37you just got to stop smoking cannabis,
34:39but they don't do any more than that.
34:41And if you come back to the outpatient clinic
34:44and you started smoking cannabis again,
34:47and then the usual reaction of a British
34:49psychiatrist is to shout at the patient,
34:51see why were you?
34:52Why are you using a cannabis?
34:54This is ridiculous.
34:55Of course what this does just ensures
34:57the patient will never come back again.
35:00So I the problem is that there isn't.
35:03There isn't service focused on
35:08cannabis induced psychosis,
35:10but it's such a big problem in our services.
35:13As I said,
35:14more than 60% of our first orven
35:16said psychotic patients are taking
35:18cannabis and the patients who are under
35:21compulsion for potential violence,
35:22over 87% of them are using a cannabis.
35:27So my wife Martha, the 40I,
35:31whose picture is down in the left here,
35:33she has developed a cannabis
35:37clinic for patients with psychosis.
35:39And you can see this is a logo for it,
35:42and it's a very optimistic logo.
35:44On the left you can see these poor souls.
35:46Their brain is full of cannabis.
35:48They're miserable and depressed,
35:50They're smoking furiously.
35:52And then they come to the clinic and
35:54then you can see on the right hand side,
35:56whoa, they've stopped using the cannabis.
35:58They're they're learning to play the guitar.
36:00They're reading furiously.
36:02They're writing.
36:04They're taking up exercise and they've
36:06got a girlfriend. So this is this.
36:09Obviously we don't we don't manage
36:12this in in the majority of patients
36:14but we we we do in some I so this
36:19say this is offered to all patients
36:24in our services who are using high
36:27potency cannabis and are also
36:29psychotic and they have one to one
36:33meetings with a therapist for up
36:36to up to 15 or 2020 sessions.
36:39And we also have a weekly peer
36:43group that is an online peer group.
36:46And at that we usually get a,
36:51we usually get some expert from
36:54somewhere in the world that come and
36:56they talk for 10 to 15 minutes and
36:58then there's a general discussion.
37:00Actually, we always ask the
37:01the expert to choose a song.
37:03So usually people choose
37:05a song about marijuana,
37:06but we've had one visiting speaker visit,
37:09visiting speaker who actually
37:10brought his band.
37:11And so that was Cyril who brought his
37:14jazz band and I took to great enthusiasm.
37:18I introduced his session
37:22by by playing very delightful
37:24jazz with his colleagues.
37:26So anyway, so we get about,
37:29say up to about 45 people come to this,
37:32this virtual peer group.
37:34It's in some ways a bit
37:37like Alcoholics Anonymous.
37:39And of course the patients benefit
37:41much more from discussion with
37:43you know being told to stop your
37:46cannabis by an old Scotsman.
37:48I mean they they are 20 year olds.
37:51Not going to think he's going
37:52to think this old fella.
37:53He doesn't think anybody
37:55should enjoy themselves.
37:56But if they're told,
37:57if they're told the same by a 25
38:00year old who says that my life was
38:02a total mess mess before I stopped
38:05cannabis and and now I'm getting on fine,
38:07this is likely to have a much bigger effect.
38:11So I patients with cannabis induced
38:16psychosis they can suffer withdrawal
38:18and what we use is to cover with
38:22Sativex which I mentioned the this
38:24say drug which has both say CBD and
38:27THC in it and they in our situation
38:30they also get tobacco withdrawal
38:32when they're admitted to hospital.
38:34So we give them a the the nicotine
38:38replacement in in some form one
38:42thing that not all that many people
38:45I take into consideration as what
38:48antipsychotic to get to give to
38:50cannabis and just psychotic people.
38:52As you know well many of you will
38:54know that drug dependent individuals
38:56have low dopamine in the ventral
38:59striatum and antipsychotics.
39:00We give antipsychotics to try and block
39:03dopamine in the associative striatum,
39:06but of course by accident we also
39:08decrease it in the ventral striatum.
39:10And people who are the drug dependent,
39:14they want their craving for the
39:16drug in order to increase their
39:18eventual strength of dopamine.
39:20So if you give things like haloperidol
39:23and risperidone ID 2 blockers,
39:25you may actually increase the craving.
39:27So drugs which are which have
39:30a less less high ID 2 blockade,
39:34particularly adiprazole or clozapine
39:38or maybe maybe quetiapine or or
39:42olanzapine are are are are better.
39:45This just shows you the results of
39:48people coming to the cannabis clinic.
39:51On the left is money spent per week
39:54on cannabis. This is about £75.
39:56That would be about $100 a week
39:58at the beginning of the baseline.
40:01This is 40 patients.
40:03The endpoint,
40:04the average spent was down to 20 lbs.
40:07Here is the frequency of use.
40:10Initially 100% every day.
40:11At the end
40:17.2020202020% were were using once a week.
40:20So these people are worth a lot
40:24of investment because they're
40:26they've premorbidly they were
40:28smart and they were socially able.
40:31So you have a much better chance
40:33of getting them back to work than
40:36many other people with schizophrenia
40:38and this just shows the decrease a
40:41particularly in delusions and there
40:42you can see in the right hand side
40:44after the the cannabis use decreases.
40:50So we've been interviewed Sunday Times
40:53as the the main Sunday newspaper that
40:57intelligent people would read in the
40:59UK and a couple of years ago we had
41:02a big article on this clinic and here
41:04is somebody saying, no, the clinic.
41:06I'm looking at life in a whole different way.
41:08My brain is starting to work again.
41:10I'm doing an apprenticeship that
41:12has changed my life.
41:14So this,
41:15this really was my wife wife's initiative,
41:18this cannabis clinic.
41:20And I was a little bit cautious
41:22at the beginning,
41:22but there's no doubt that it
41:25can have very beneficial effect.
41:27So I'm becoming quite evangelical about it.
41:31So the the, the, the switching.
41:36What about if we accept that cannabis
41:40use can have a causal impact on psychosis?
41:43Is it big enough to impact the incidence
41:47of psychosis in different countries?
41:49So this is a big study from the EU.
41:52Across the EU 16 sites in Europe
41:56and in each country a big city like
41:58London and a smaller place like
42:01Cambridge are in in in France,
42:05Paris and then a rural area
42:08called Clermont from Barcelona,
42:10Madrid and three Spanish centres.
42:132 modest cities in middle class
42:17cities in Italy,
42:19Verona and Bologna and a Palermo,
42:22a big poor city in the South.
42:24So everybody was trained to to to
42:29try and get every case of psychosis
42:32presenting A to psychiatrist to
42:35secondary services in from a particular area.
42:38And this is popular possible in Europe
42:41because we tend to have socialised
42:43systems and everybody was trained
42:45diagnosed in the same way and there
42:48was a lot of a lot of emphasis
42:51on all using the same methods.
42:53So if you're thinking here you
42:55are in midwinter in in Yale,
42:57you're thinking I'd like to go to to to
42:59to to Europe for the for my summer holidays.
43:02But you think I spend all my time
43:04looking after psychotic patients.
43:05I'd like to go somewhere,
43:06but I won't meet a lot of
43:08psychotic patients in the street.
43:10So where would you go?
43:11Well,
43:12for sure you wouldn't come to London.
43:14This is the incidence of a psychosis
43:17across different parts of Europe and
43:20you can see the highest incidence of
43:22psychosis is 61 per 100,000 in London,
43:25followed by Amsterdam 47 and Paris 44.
43:29Southern Europe,
43:30Excuse me,
43:32I should say that in Northern Europe
43:34the rates are much lower in smaller
43:37towns and that's an epidemiological
43:39dogma in many ways and but in
43:42Southern Europe the rates are all
43:45much lower and there isn't much
43:48difference between big cities and
43:51and and the countryside.
43:53Again if I quote my wife who is from,
43:57who's from Palermo, she says that
44:00she has done a very risky thing from
44:03moving from Palermo to to to London.
44:05Her risk of psychosis has gone up five
44:08times but she's a bit not she's OK so far.
44:11So it's it's it's it's been all
44:14right so far but the question is what
44:16what is the reason And there are
44:18there are various possible reasons
44:20but looking at cannabis this is,
44:23this is this slide shows both the frequency,
44:26the frequency of cannabis use
44:28and the rate of psychosis.
44:30So in in grey is the adjusted
44:33psychosis incidence.
44:34We've taken out migrants.
44:36So this is just natives of
44:38these different countries.
44:40You can see that still London,
44:42Amsterdam and Paris are highest, and
44:45places like Palermo and Barcelona are low.
44:50And here is the daily cannabis use,
44:53and you can see that it tracks
44:56the incidents pretty well.
44:57Not .8, quite surprisingly well actually.
45:00So this is compatible with the
45:02idea that cannabis use is a cause,
45:06One of the causes is a contributory cause
45:09of psychosis in these different centres,
45:12and that is has a big enough effect to cause
45:15differences in the incidence of psychosis.
45:18Now you may say to yourself,
45:19but this is just correlational
45:21and statistics can prove anything.
45:23So let's think about another
45:26recreational substance based on natural
45:28ingredients that people might use
45:30differently or consume differently
45:33across different parts of Europe.
45:36What about ice cream?
45:37So if here here am I in the pink shirt
45:41in in an ice cream parlour in Palermo,
45:45along with my godson and the
45:47man with the ice,
45:48the the the ice cream shop here, Mr.
45:50Franco,
45:51so do you think there would be any
45:54relationship between daily ice cream
45:57use and the incidence of psychosis?
46:01But you you probably think there won't be,
46:03but you would be wrong.
46:05So and this is the relationship with
46:07the frequency ice cream consumption
46:09which you can find out from the from
46:12across the EU and the rate of psychosis.
46:15So here is psychosis in the grey,
46:18as we've seen before And here is London,
46:21where hardly anybody uses ice
46:24cream every day. Amsterdam.
46:26Similarly I and here is Madrid.
46:30Twitter they're using a bit more ice cream.
46:32Ice cream.
46:34And here is Palermo,
46:35where they're taking ice cream.
46:36More than half the population
46:38takes ice cream every day.
46:39This is actually true because
46:42Palermo ice cream is wonderful.
46:44People have children have it for
46:46their breakfast in A roll before
46:48they go to they go to school.
46:50But as you can see that,
46:53say,
46:53places where there's a lot of ice cream
46:56I consumed have a low incidence of psychosis,
46:58and Pearl London,
46:59where there's not much ice cream consumed,
47:02then there's a high incidence of psychosis.
47:04So probably some of you are still
47:06using antipsychotics.
47:07Maybe you should be sending your
47:09patients down to the ice cream parlour,
47:11No, they said this is just a
47:13statistical artefact. Or mostly,
47:15though you might see that maybe teenagers
47:18in Sicily at this point had not
47:21discovered cannabis and they were still
47:23hanging about the ice cream parlour.
47:25But what we really need
47:27is a proper replication.
47:29So this is a study called
47:31Intrepid in three countries,
47:34Chennai or near Chennai in India,
47:38Nigeria, Ibadan, a big city,
47:42and Trinidad and Tobago and the Caribbean.
47:45And it's mostly done by Craig Morgan.
47:49And this is the incidence,
47:51the same sort of study as the EUGI study.
47:54So here is India.
47:56This is the incidence of psychosis in
47:59Kashnipuram, which is near Chennai.
48:01Pretty low.
48:02Here is Ebadan, a bigger,
48:04a big city, pretty low in Nigeria.
48:07Here is Trinidad, very high.
48:10So what is the reason that Trinidad
48:13is different?
48:13What about looking at cannabis?
48:15So this is the same sort of study,
48:17the same sort of figure as you saw before,
48:19except this time psychosis
48:21incidence is in black,
48:23showing it's much higher in Trinidad and I.
48:27Here is cannabis use frequent
48:29cannabis use in controls,
48:31uncommon in rural India,
48:34a little more common in than in men,
48:38but much more common in Trinidad.
48:41People in Trinidad,
48:42half have come from Africa and
48:44half have come from India.
48:46And it's people,
48:47particularly the people from Africa,
48:49who use a lot of cannabis and have
48:52the highest incidence of psychosis.
48:54So this really replicates the EU
48:57study and does suggest that that's
49:01a the heavier use of cannabis is
49:05associated with high incidence of psychosis.
49:08The the the average THC in cannabis
49:11in by Trinidad is say is say about
49:1725% so higher certainly than in
49:19London and these are amongst the
49:22highest psychosis rates in the world.
49:24So
49:27the amount of cannabis used in different
49:29countries affects the incidence of psychosis.
49:31What about taking one country and
49:34seeing whether changes in the pattern
49:36of cannabis associated with changes
49:38in the incidence of psychosis?
49:40So some of you will maybe know this study
49:42from Carsten Horshop in in Denmark.
49:47This is the incidence of schizophrenia
49:50in Denmark. And of course during this
49:54period the consumption of cannabis and
49:56its potency has increased and this is
49:59the population attributable fraction.
50:01So this is the proportion of
50:03kind of schizophrenia which the,
50:05the and where the individual with
50:08schizophrenia had previously been
50:09hospitalized for cannabis use disorder.
50:12So there's very severe cannabis use and
50:14you can see that say the proportion of
50:18schizophrenia attributable to cannabis,
50:19cannabis use dependent cannabis
50:22dependence was steadily increasing.
50:25We've done a study a similar study in London.
50:30We have good data on schizophrenia.
50:33This is not psychosis.
50:34This is schizophrenia since the
50:361960s and that's in blue.
50:38Here you can see it started off low.
50:41So this is 11 per 100,000 that
50:45schizophrenia not psychosis.
50:46It had doubled by the the the 1990s
50:50and then it had trebled by a 2012
50:54and the orange shows the the rise
50:57at the same time in cannabis use.
51:00So again,
51:00this is correlational but suggestive.
51:05The place in the world which smokes
51:07the most cannabis is Canada,
51:09and a consumption of cannabis has
51:13been steadily rising since it was
51:17legalised for medicinal use in 2006.
51:20And you can see that the black here,
51:23psychotic disorder,
51:24the number of hospitalizations
51:26for psychotic disorder has has
51:30trebled over a 10 year period.
51:36And here again this is the the in in,
51:39so in 2000, in 2001 they
51:43legalized for medicinal use,
51:45in 2018 legalised for recreational use.
51:50And the green is showing visits to emergency
51:55clinics for cannabis use, a disorder.
51:59So you can see a steady increase as we've
52:02already alluded to when they legalised.
52:05At first there was a lot of confusion
52:08and the cannabis shops hadn't opened
52:11and they couldn't say they they they
52:15couldn't get a available cannabis.
52:17And of course it was also the time of COVID,
52:20so the legalization didn't seem
52:21to make a lot of difference.
52:23But once the shops all opened and the
52:26big commercial operations got going and
52:29chains of cannabis use a cannabis say
52:32the dispensaries opened then you could
52:34see that consumption increased and so
52:36did a visits to the emergency clinic.
52:40You may and wonder what are these brown the
52:42brown rates is methamphetamine psychosis.
52:45So you can see that methamphetamine
52:48psychosis has also been steadily
52:51increasing in in this isn't this
52:53excuse me this is Ontario.
52:58You'd as you know there's been a race
53:02to more potent forms of cannabinoids
53:04and I'm sure you have much greater
53:06experience of of this than than I have.
53:09You can now get up to 90% or 95% a a cannabis
53:17and here is the this is the the regular
53:25assessment of THC potency in the
53:28brown is in a smoked cannabis and here
53:32is the green is an edible cannabis
53:34going up to an average of 60% THC.
53:40So my last slide will legalisation and
53:44commercialisation of cannabis use increase
53:47the incidence and prevalence of psychosis?
53:50Well, I I think it ought to be possible
53:54to legalise cannabis and not increase
53:58its use and not increase its potency.
54:01But no western country has done that so far.
54:05Whatever, by legalization where whatever
54:08the rules for legalization have relaxed,
54:12there's been an increase in the
54:14use and an increase in the potency.
54:17But I think this is often driven by
54:19commercialization that say again,
54:21I guess as again as you,
54:23you'll probably know that that's the sort
54:26of little local the the the the local.
54:30The idea was that the local poor or
54:34minority people who are drug dealers
54:37would become legalised and then they
54:39would run a they would run medicinal
54:42or recreational cannabis dispensaries,
54:44but in fact they these have all
54:46been bought out by,
54:47or mostly bought out by
54:49big cannabis companies.
54:51Here is the the the US cannabis retail sales.
54:55We're currently in 2023 and you can see
55:00that the sales are about say 35 billion
55:05I think and they're expected to go up
55:09to over to about 60 billion by 2026.
55:14So this is big business and of course a lot
55:18of a lot of companies have empty factories,
55:21a particularly tobacco companies.
55:24So cigarette companies are not selling so
55:27much in the way of cigarettes in the West.
55:31So they're looking around for new products.
55:33So they've been buying into
55:35cannabis companies and of course
55:37hedge funds have also been putting,
55:39putting a lot of money into
55:41cannabis companies.
55:42So I think the question is I how would you?
55:48In a sense we we have the same people
55:51who brought us lung cancer are now
55:54investing heavily in a cannabis
55:55in the cannabis industry.
55:57And the question is it took us 60
56:01years to wake up to the effect of
56:05of tobacco and lung cancer.
56:06How long is it going to take before
56:09politicians and the country as a
56:11whole wake up to the effects of
56:14cannabis on psychosis or the the
56:17commercialisation of cannabis on psychosis?
56:19So I will stop at at that point and
56:24I'm very happy to answer questions
56:26or this have discussion or argument
56:28and I'm very interested to learn of
56:31your experience because we don't
56:34have we have unofficial legalization
56:41you can be arrested by a policeman
56:43for smoking cannabis but they say
56:45only if you blow the smoke in his
56:47face otherwise they they they they
56:50won't they'll just they tell you not
56:52to do it and and go on your way.