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Cannabis and psychosis


									   Reefer Madness:
Moral panics and science
         Rob Poole
   the research suggests an increased risk of
    psychosis, and the growing consensus is
    that this is not just because users are
    more troubled to start off with.” The
    Guardian, 29th October 2007.
Moral panics
Similar events, different times
Daily Mirror 14/11/08
Jersey children's home probe: Top cop
 suspended as investigation collapses

        By Don Mackay 13/11/2008
  Top cop suspended in probe storm
The probe into the Jersey children's home
collapsed yesterday when police said there
  was no evidence of murder or torture.
     My values in this debate
 Cannabis is an unpleasant drug with a
  wide range of adverse effects
 No matter what we do, cannabis is not
  going to go away, and we have to learn to
  work with its adverse effects
 Science and intellectual rigour matter
 We can have an positive or negative effect
  on public debate
         Drug Induced Psychosis
         Poole and Brabbins 1996
   Intoxication mimicking functional psychosis
   Pathoplastic reactions
   Chronic hallucinosis
   Drug induced relapse
   Withdrawal states
   Clouding of consciousness
   Depressive crash
   Panic attacks
   True drug induced psychosis
   Risk factor (Andreasson, 1987)
-9 tetrahydrocannabinol (THC)
             A few myths
 Drug use is ever increasing
 Cannabis is up to x8 to x30 strength of the
  stuff we used to smoke in the 1970s
 Stronger cannabis leads to heavier
 Cannabis is non-addictive
 But…..
 It is a lot cheaper and is locally produced
      Does cannabis exacerbate
 About 15% of people with schizophrenia
  misuse drugs.
 About 30% misuse alcohol.
 More ill or just ill and stoned?
 Associated with more frequent relapse but
  many confounders.
 Not a good thing.
 Why do people with mental illness
        smoke cannabis?
 It‟s fun
 It‟s something to do
 It structures the day
 Drug using sub cultures are tolerant of
  deviant behaviour
 It‟s a „normal‟ place for stigmatised people
  to hang out
 It‟s a loser‟s game
    Alcohol and schizophrenia
 Number of data based papers 1995-2005:
 None
 Unpublished data, Liverpool Homeless
  Team 1998-2003:
 Drug users did much the same as other
  psychotic homeless people, whether they
  gave up or not.
 Drinkers had far worse outcome (death
  and permanent institutionalisation).
    Cannabis as a causal factor
 Andreasson, Allebeck, Engstrom and
  Rydberg, Lancet 1987: 15 year follow up.
  x6 increased risk, x2.3 if those with
  diagnosis excluded.
 Risk to very heavy users: 3%
     Zammit, Allebeck, Andreasson,
     Lundberg and Lewis, BMJ 2002
   50,000 subjects
   Linkage of government data
   Self report of drug use and background
   27 year f/u
   Excluded other drug use and cannabis preceded
   362 developed schizophrenia
   Odds ratio 2.2, adjusted 1.5
   Higher exposure led to higher risk
    Van Os et al, Am J Epid, 2002.
 Dutch prospective study, 1 and 3 year
  follow up, 4000 subjects, plus 60 with
 Users at baseline x3 rate of psychotic
  symptoms at follow up.
 Most of the effect due to big effect on
  those with symptoms at baseline.
 Baseline use had more effect than later
     Arsenault, Cannon, Poulton,
    Murray, Caspi, Moffitt, BMJ 2002
 Dunedin birth cohort. 1037 people born
 Heavy use at 15 and 18 years associated
  with increased risk of Sz by age 26.
 Risk higher the earlier the use but not all
  findings statistically significant when
  controlled for prodromal symptoms.
 Low numbers: 3/29 early users developed
  Sz versus 22/730 non-users.
    Cannabis as a causal factor
 Definite association between early heavy
  cannabis use and later schizophrenia.
 Not due to other drugs.
 Not due to self medication.
 Not a toxic effect of cannabis.
 How sure can we be that confounders
  have been fully factored out?
    Best guess on size of risk
 „Cannabis use and risk of psychotic or
  affective health outcomes: a systematic
 Lancet 2007
 Moore, Zammit, Lingford Hughes, Barnes,
  Jones, Burke, Lewis.
Summary of risk
    Biological Psychiatry, 2005
 Caspi, Moffitt, Cannon, McClay, Murray,
  Harrington, Taylor, Arsenault, Williams,
  Braithwaite, Poulton, Craig
 „Moderation of the effect of adolescent-
  onset cannabis use on adult psychosis by
  a functional polymorphism in the
  Catechol-O-Methyltransferase gene:
  Longditudinal evidence of a Gene X
  Environment Interaction‟
     Dunedin birth cohort again
 Obtained DNA samples from the entire
 Reanalysed previous data with genetic
 The combination of one version of gene
  (Val/Val genotype) and cannabis use
  accounted for most or all of the increased
  risk of schizophrenia for users.
 Three polymorphisms, Val/Val, Val/Meth,
 Different levels of biological activity
  (Val/Val most active).
 Right neurotransmitters and locations.
 Coded on chromosome 22.
 Long regarded as a candidate gene.
 But…..
 A lesion in search of a disorder: affective
  disorder, schizophrenia, ADHD, leimyoma,
 Low statistical power
 Long history of non-replication and
  withdrawal of such findings
    Discussion with researchers 2005
   Deprivation, maladjustment and marginalisation
    associated with both early substance misuse and
   What about cigarette smoking? Alcohol?
   Where‟s the epidemic?
   How much evidence do you need?
   What about the null hypothesis?
   „Doesn‟t contribute to the debate.‟
            BJPsych 2007
 Zammit et al. „Genotype effects of
  CHRNA7, CNR1 and COMT in
  schizophrenia: interactions with tobacco
  and cannabis use‟
 750 with Sz, 688 controls, smaller group
  with Sz used to study cannabis effect
 No effect from any of these, including
  COMT and cannabis use.
        Other COMT studies
 Can not exclude a role for COMT in Sz, but
  if so, its not straight forward
 Val/Val COMT plus cannabis equals later
  schizophrenia seems not to stand up.
          The public debate
 Mostly conducted around interviews with
  respectable researchers but…
 Misinformation
 Crusades
 Conflation of dangers and control
 The corruption of a generation of children
Article by RM, Guardian 17/9/02
   Cannabis causes psychosis. This has been
    known for years, the evidence only now
   People with schizophrenia have a miserable life.
   Bright, no problems, cannabis dependency in
    teens led to schizophrenia. Rethink is full of
    parents who believe their child‟s illness was
    caused by cannabis.
   Rate of Sz in South London has doubled,
    cannabis and cocaine could be the cause. This is
    why services are in a mess.
          Guardian 3/7/03
 Based on talk to RCPsych annual meeting
 “Very bright as a child, no obvious
  problems, cannabis dependence in teens,
  then schizophrenia”
          Guardian 7/1/04
 RM: Cannabis use is number one problem
  facing mental health services.
 80% of new cases of schizophrenia
  involve cannabis.
 Risk is x7
          Guardian 20/1/04
 RM: Cannabis main reason for set backs
  during in patient stays.
 Most harmful to people with established
  psychosis and to children with prodromal
 Classification irrelevant. Public should be
 cf evidence re Smoking and cancer in the
          BBC News 1/12/04
 Marjorie Wallace of SANE: Britain is
  cannabis capital of Europe. Clamp down
  on drug dealing in play grounds and
  hospital wards.
 Cliff Prior of Rethink: Reclassification has
  confused people.
       New Scientist 26/3/05
 JvO: Governments should focus on
  keeping cannabis out of teenagers‟ hands.
 Objections to the kind of people who hang
  around coffee shops.
 Mary Cannon: „This is a large effect,
  similar to the size of smoking and lung
    Panorama BBC1 Sunday 19/6/05
   RM: New type of person with schizophrenia who lacks
    antecedent problems other than cannabis.
   More patients with schizophrenia.
   Sz due to dopamine overactivity, and cannabis „revs up‟
   Frequency of Sz in South London (Brixton) has doubled
    since the 1960s: services are overwhelmed by the
    number of patients coming through, possibly because to
    the impact of cannabis.
   Once you‟ve had a psychotic episode your dopamine
    receptors are sensitised.
            Guardian 16/12/05
   Julie Lynn-Evans: „Heroin addiction is curable,
    the effects of skunk are not‟
   Modern cannabis x30 THC
   Uncorrected odds ratios (e.g. x6 risk)
   Marjorie Wallace: „…triggers a journey of life
    long disintegration‟
   Role of cannabis in causing violence
   Trevor Turner: it‟s down to confounding factors
   RM: Scare stories have reduced consumption
   It makes you paranoid (true) forgetful (true)
    and irritable (true)
 Bad Science, Guardian 28/7/07
 Reporting press reactions to Lancet‟s
  systematic review.
 Daily Mail: One joint increases risk by 40%
 175 studies (actually seven studies and 11
 40% increase in a low risk.
 Assumption that 800 cases can be
  prevented by reclassification or some
  other enforcement measure.
    Advisory Council on Misuse of
 Have tended to stick to the evidence
 Do not dismiss risk
 Have consistently advised against
  confusing health concerns and effective
  control methods
 Have been ignored or vilified
    Asked to review classification in
               July 2007
 Cannabis use is dropping
 Incidence of schizophrenia dropping
 Cannabis is stronger but people use less
 Risk, if it exists, is small
 Reclassification will criminalise users,
  because all users are suppliers.
    Government reclassify anyway
 Eminent experts have told Jacqui Smith
  about the awful effects
 Gordon Brown says skunk is lethal
 Whilst recognising the point made by
  ACMD are accurate, there is real public
  concern about the health risks
   More rhetorical heat than evidence.
   The debate has been affected by the
    reductionist biological paradigm that underlies
   Cannabis may cause schizophrenia, but there
    are other explanations that are equally
    compatible with the data.
   Distortions in our debate is adversely affecting
    public policy.
   What SHOULD we do with this kind of
    ambiguous finding?
 „Drug induced psychosis‟ is alive and well,
  even in Liverpool but
 Arendt et al, BJPsych 2005
 3 year follow up of 535 Danes with
  „cannabis induced psychosis‟
 44.5% of them re-diagnosised, mainly to
  schizophrenia, within 3 years
 Similar findings in Liverpool
Some recommended books
 This book is dedicated to
the late Leo Fender, whose
supreme mastery of the art
   of guitar design was
unencumbered by an ability
  to play the instrument

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