Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study
BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d738 (Published 01 March 2011) Cite this as: BMJ 2011;342:d738
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1. Observational studies on effects of premorbid behavioral exposures
on development of schizophrenia are rarely able to eliminate one of the
most important potential confounders. A high rate of odd behaviors, social
difficulties and subtle cognitive differences manifesting many years
before diagnosis of schizophrenia have repeatedly been documented (refs
can be provided). This suggests a greater probability of psychological or
social experiences that may themselves promote the decision to use and
continue using cannabis in young people at risk.(Similar problems apply to
studies showing association of teasing/bullying or poor parent-child
relationships with subsequent onset of schizophrenia.)
Observations on this general topic follow:
a.There was a massive increase (probably at least tenfold) in many
communities in use of cannabis in the cohorts who were 16 to 24 years of
age during the period from 1968 to 1972. Can we discern a surge in
schizophrenia diagnosis in this age cohort?
b. Many of us, both clinicians and others, have witnessed
"breakdowns" in people recently starting to use cannabis who showed no
prior evidence of mental dysfunction. A proportion of these are psychotic
illnesses, and a very small number may be "first break" schizophrenia. The
timing and course are so striking that the association of acute psychosis
and drug intoxication is almost certain. What studies usefully establish
who are at most risk for this relatively infrequent problem?
Competing interests: No competing interests
The article failed to specify whether the patients in the study were
using Cannabis indica, Cannabis sativa, or an indica/sativa hybrid.
Cannabis does not refer to one plant, but several, just as Canine refers
to several animals: dogs,wolves,foxes,& coyotes. The two main types of
cannabis are indica and sativa, which are as different as dogs and wolves.
Sativas have high relatively unopposed THC (hallucinogen) levels. This
tends to be activating, but in some people it can cause increased anxiety
and even paranoia. Long term use can result in effects similar to those of
long term high dose amphtamine use. Indicas have relatively higher
canabadiol (CBD) levels which moderate the effects of the THC that is
present. Indicas tend to be so sedating that most people can only use
indicas at night. I like to use the analogy of sativas being like wolves
and indicas being like dogs with as many strains as there are breeds of
dogs. Just as there are dog/wolf hybrids, there are also sativa/indica
cannabis hybrids. These are usually used duing the day to avoid the excess
sedation of the indica and the excess agitation of sativa. I have noted
that patients with bipolar disorder who use pure cannabis sativa tend to
develop psychosis. Bipolar patients who use only cannabis indica at night
or an indica at night and a hybrid (preferably indica dominate) during the
day, with no pure sativa, seem to stay stable.
I would like to see future studies which differentiate the use of C.
indica from C. Sativa.
Competing interests: As a part of my General Medical practice I also do addiction medicine and medical cannabis evaluations.
We thank Jauhar and Lawrie for their valuable comment. Diagnoses of
psychotic disorder in DSM and ICD have poor validity and reliability,
particularly in the context of general population studies, which is why in
EDSP the focus was on the full range of (attenuated) psychotic symptoms,
in combination with measures of functional impairment and help-seeking(1).
Contrary to previous CIDI studies, interviews in EDSP were conducted not
by lay interviewers but by psychologists who were allowed to probe with
follow-up clinical questioning - the advantage of this should be evident.
The focus on psychotic symptoms allowed us to conduct analyses regarding
the earliest expression of psychosis, long before the onset of clinical
disorder. We would argue that this perspective is highly relevant from a
clinical point of view. Population studies have shown that many
adolescents experience transitory developmental expression of attenuated
psychotic symptoms. Research, including previous research in the EDSP
cohort(2), has shown that in a minority, developmental expression of
psychosis persists, increasing the risk for later onset psychotic
disorder(2-4). Understanding the process of persistence of attenuated
psychotic symptoms therefore is the key to understanding the early
development of psychotic disorder, and how to intervene in the earliest
stages of psychosis. As there is evidence that persistence of attenuated
psychotic symptoms in adolescence is associated with environmental
exposures(5), the aim of our analysis was to examine cannabis specifically
in relationship to persistence of the earliest expression of attenuated
psychotic symptoms in young people. Research in psychiatry is moving
towards the earliest expression of risk in an attempt to intervene
earlier; in our view, extending this paradigm to the influence of
environmental exposures such as cannabis is urgently required.
1. Dominguez MD, Saka MC, Lieb R, Wittchen HU, van Os J. Early
expression of negative/disorganized symptoms predicting psychotic
experiences and subsequent clinical psychosis: a 10-year study. Am J
Psychiatry. 2010 Sep;167(9):1075-82.
2. Dominguez MD, Wichers M, Lieb R, Wittchen HU, van Os J. Evidence that
onset of clinical psychosis is an outcome of progressively more persistent
subclinical psychotic experiences: an 8-year cohort study. Schizophr Bull.
2011 Jan;37(1):84-93.
3. Wigman JTW, Van Winkel R, Raaijmakers Q, Ormel J, Verhulst FC,
Reijneveld SA, et al. Evidence for a persistent, environment-dependent and
deteriorating subtype of subclinical psychotic experiences: a six-year
longitudinal general population study. Psychol Med. 2011;in press.
4. Mackie CJ, Castellanos-Ryan N, Conrod PJ. Developmental trajectories of
psychotic-like experiences across adolescence: impact of victimization and
substance use. Psychol Med. 2010 Mar 29;Published online: 30/3/2010; DOI:
S0033291710000449 [pii]10.1017/S0033291710000449:1-12.
5. Cougnard A, Marcelis M, Myin-Germeys I, De Graaf R, Vollebergh W,
Krabbendam L, et al. Does normal developmental expression of psychosis
combine with environmental risk to cause persistence of psychosis? A
psychosis proneness-persistence model. Psychol Med. 2007 Apr;37(4):513-27.
Competing interests: No competing interests
We thank Jauhar and Lawrie for their valuable comment. Diagnoses of
psychotic disorder in DSM and ICD have poor validity and reliability,
particularly in the context of general population studies, which is why in
EDSP the focus was on the full range of (attenuated) psychotic symptoms,
in combination with measures of functional impairment and help-seeking(1).
Contrary to previous CIDI studies, interviews in EDSP were conducted not
by lay interviewers but by psychologists who were allowed to probe with
follow-up clinical questioning - the advantage of this should be evident.
The focus on psychotic symptoms allowed us to conduct analyses regarding
the earliest expression of psychosis, long before the onset of clinical
disorder. We would argue that this perspective is highly relevant from a
clinical point of view. Population studies have shown that many
adolescents experience transitory developmental expression of attenuated
psychotic symptoms. Research, including previous research in the EDSP
cohort(2), has shown that in a minority, developmental expression of
psychosis persists, increasing the risk for later onset psychotic
disorder(2-4). Understanding the process of persistence of attenuated
psychotic symptoms therefore is the key to understanding the early
development of psychotic disorder, and how to intervene in the earliest
stages of psychosis. As there is evidence that persistence of attenuated
psychotic symptoms in adolescence is associated with environmental
exposures(5), the aim of our analysis was to examine cannabis specifically
in relationship to persistence of the earliest expression of attenuated
psychotic symptoms in young people. Research in psychiatry is moving
towards the earliest expression of risk in an attempt to intervene
earlier; in our view, extending this paradigm to the influence of
environmental exposures such as cannabis is urgently required.
1. Dominguez MD, Saka MC, Lieb R, Wittchen HU, van Os J. Early
expression of negative/disorganized symptoms predicting psychotic
experiences and subsequent clinical psychosis: a 10-year study. Am J
Psychiatry. 2010 Sep;167(9):1075-82.
2. Dominguez MD, Wichers M, Lieb R, Wittchen HU, van Os J. Evidence that
onset of clinical psychosis is an outcome of progressively more persistent
subclinical psychotic experiences: an 8-year cohort study. Schizophr Bull.
2011 Jan;37(1):84-93.
3. Wigman JTW, Van Winkel R, Raaijmakers Q, Ormel J, Verhulst FC,
Reijneveld SA, et al. Evidence for a persistent, environment-dependent and
deteriorating subtype of subclinical psychotic experiences: a six-year
longitudinal general population study. Psychol Med. 2011;in press.
4. Mackie CJ, Castellanos-Ryan N, Conrod PJ. Developmental trajectories of
psychotic-like experiences across adolescence: impact of victimization and
substance use. Psychol Med. 2010 Mar 29;Published online: 30/3/2010; DOI:
S0033291710000449 [pii]10.1017/S0033291710000449:1-12.
5. Cougnard A, Marcelis M, Myin-Germeys I, De Graaf R, Vollebergh W,
Krabbendam L, et al. Does normal developmental expression of psychosis
combine with environmental risk to cause persistence of psychosis? A
psychosis proneness-persistence model. Psychol Med. 2007 Apr;37(4):513-27.
Competing interests: No competing interests
The article states: "presence of psychotic experiences was broadly
defined as any rating of present on any of the 20 DIAX/M-CIDI core
psychosis items... The psychologist invited participants to read a list of
all the psychotic experiences and then asked them whether they ever
experienced such symptoms"
I have one concern about this statement, namely that heavy cannabis
intoxication could be counted as "psychotic experience" simply because the
definition of psychotic experience was purposefully very broad. If acute
heavy intoxication (synesthesia and other possible effects) is sometimes
counted as psychosis, the results of this research would have a different
meaning. So... how did the authors account for this?
I have corresponded with the authors about this, and share Rebecca
Kuepper's response:
"Individuals being questioned were instructed to report only those
psychotic experiences that occurred independently of intoxication. So in
that sense, we did control for the effects of acute intoxication."
Hopefully this clarifies the issue to other readers.
Competing interests: No competing interests
Dear Editor
Really I congratulate Rebecca Kuepper,et al for their
well designed cohort study which concluded that; Cannabis use is a risk
factor for the development of incident psychotic symptoms. Continued
cannabis use might increase the risk for psychotic disorder by impacting
on the persistence of symptoms, other different studies also reported that
Patients with psychosis are more sensitive to both the psychosis-inducing
and mood-enhancing effects of cannabis. Data suggest that the positive
effects of cannabis on mood are acute, whereas its association with
psychotic experiences is sub-acute. For long years it has been known that
there is a reciprocal interaction between the endocannabinoid and dopamine
system which may explain the psychotogenic effects of cannabis in
individuals and it thought to play a crucial role in attributing salience
to stimuli in the environment. On the other hand, patients with a psychotic
disorder are more sensitive to the hallucinogenic effects of cannabis than
others. In addition epidemiological studies has identified several factors
that co- participate with THC in causing psychosis, as pre-existing
psychotic symptoms, exposure to childhood trauma and a functional
polymorphism in the catechol-O-methyltransferase gene have been shown to
moderate the effects of cannabis on psychosis outcome. "Cannabis increases
risk of psychosis in teens" was the title of a cross-sectional study of
more than 6,000 young people in Finland which suggests that teen users had
a greater risk of the "prodromal", or warning symptoms, of psychosis than
older users. However, the findings add to the evidence that there is a
link between use of cannabis and mental health. The researchers also found
that more intensive cannabis use was more strongly associated with these
symptoms. The researchers concluded that lifetime cannabis use is
associated with the incidence of early warning symptoms of psychosis.
When the findings are considered in light of a growing body of evidence of
a link between cannabis use and mental health problems such as
schizophrenia, mood disorders it seems wise to limit the use of the drug.
This is not only because of considerations of the effects on mental
health, but also the well-established risks for cancer and other diseases
that are associated with cannabis use. Report of Government Crackdown on
Cannabis revealed that Cannabis use has fallen significantly across all
age ranges and this is a testament to the success of the previous ten year
Drug Strategy. However, the reduction in cannabis use must not be allowed
to reverse. Reclassification of cannabis reflects the fact that skunk, a
much stronger type of the drug, now dominates the cannabis market. It
accounts for 81 per cent of cannabis available on our streets compared to
just 30 per cent in 2002. The average age of first use is 13 years old and
young people may binge on skunk in the same way as alcohol, trying to
achieve the maximum effect. If they do, the independent Advisory Council
on the Misuse of Drugs found that the consequences of this 'may be serious
to their mental health.'(Source ;The Home Office). Regarding medicinal use
of cannabis The Home Secretary has made it clear that he is willing to
amend the misuse of drugs legislation as necessary, to allow the
prescribing of a cannabis-based medicine as a form of pain relief.
Our mental health users should be educated that:
* Cannabis remains
illegal and it is a criminal offence to possess cannabis.
* Passing drugs
among friends is an offence.
* Driving a vehicle while unfit through
drugs, including cannabis, is an arrestable offence.
* A drug conviction
could affect your job prospects, or prevent you getting a visa to travel
abroad.
Cannabis has Harmful effects which include damage to people's
ability to learn and carry out many tasks, including operating machinery
and driving vehicles. Acute cannabis intoxication can also lead to panic
attacks, paranoia and confused feelings. The chronic effects include
damage to mental functioning and in particular to learning difficulties,
which in prolonged and heavy users may not necessarily be reversible. It
is clear that most users of the more dangerous drugs used cannabis earlier
in their careers, but most cannabis users do not go on to use other drugs
regularly.
References
1. Stokes PR, Mehta MA, Curran HV, Breen G, Grasby PM. Can recreational
doses of THC produce significant dopamine release in the human striatum?
NeuroImage 2009; 48: 186 -90.[CrossRef][Medline]
2. Henquet C, Di Forti M,
Morrison P, Kuepper R, Murray RM. Gene- environment interplay between
cannabis and psychosis. Schizophr Bull 2008; 34: 1111 -21.
3. Arseneault
L, Cannon M, Witton J, Murray RM. Causal association between cannabis and
psychosis: examination of the evidence. Br J Psychiatry 2004; 184: 110 -7.
Dr Osama Hammer MBBch.,MSc.,MRCPsych
Competing interests: No competing interests
Evidence is mounting that cannabis consumption is related to
subclinical psychotic subjective experiences.1 However support for
transition to schizophrenia is less convincing. Were this so, even in
a minority of users who otherwise would remain unaffected, there should be a
population-based increase in incidence, if only of small effect. However
this does not appear to be the case. For example Ireland, in common with
other European countries, has seen a substantial rise in comsumption of the
drug, particularly in young persons, over the past 20 years.2 Contemporaneously
first additions to psychiatric in-patient care nationally have decreased
from 30.1 per 100,000 population in 1989 to 18.0 in 2009, including in
young persons.3 While use of alternatives to hospitalisation may be a
confounder there is nothing to suggest an increase in community-based
incidence. Furthermore there is no indication that other eoological
precipitants have decreased over these 20 years.
References
1 Kuepper R, van Os j,Lieb R, Wittchen H-U, Hofler M, Henquet C.
Continued cannabis use and risk of incidence and persistence of psychotic
symptoms:10 year follow-up cohort study.BMJ 2011;342;d738
2 Long J.Cannabis use in Ireland. Drugnet Ireland. 2009;29:7.
3 Daly A, Walsh D. Activities of Iriah psychiatric units and
hosopitals 2009. Health Research Board, Dublin 2010.
Competing interests: No competing interests
Dear Editor,
Kuepper and colleagues have shown, in their large prospective study,
that the risk of psychotic symptoms, as assessed by the DIA-X/M-CIDI, is
increased in those who have previously used (and continue to use)
cannabis, and by controlling for confounders have refuted the "self
medication" hypothesis as an explanation of the association between
cannabis use and psychosis. They further assert that, based on these
results, "continued cannabis use might increase the risk for psychotic
disorders." (1)
Though they point out some failings of the DIA-X/M-CIDI, it should be
underlined that this is not a valid diagnostic tool, and therefore any
clinical interpretation of these results alone should be made cautiously.
The CIDI itself was devised as an epidemiological tool, and the psychosis
component has been shown to have poor predictive validity when compared to
clinical measures, such as hospital registers and clinical judgement
(2,3). A Finnish population-based study has shown that "only one third of
the subjects with non-affective psychotic disorders or substance-induced
psychotic disorder...would have been found by the CIDI psychotic symptoms
screen", and in a study conducted by one of the authors of the current
article, the M-CIDI for psychotic disorders was found to have a positive
predictive value (PPV) of about 0.2 and specificity of 0.6 (3). Although
the authors have tried to improve the validity of the CIDI by using
interviewers trained to the level of clinical psychologists, it is unclear
how they corrected for these deficiencies within the instrument, and
whether this would improve validity (with no explicit use of a gold
standard).
Crucially, no mention is made of the number of symptoms expressed
using the DIA-X/M-CIDI, or whether those scoring positive on any symptom
were requesting help or receiving any psychiatric treatment. In other
words, elegant large-scale epidemiological studies such as this are able
to clarify and here largely exclude the role of potential confounders, but
this study in itself is concerned with cannabis-induced psychotic
symptoms. Whether or not cannabis increases the risk for psychotic
disorders, which it probably does, requires more clinically oriented
studies using validated diagnostic instruments.
References
1. Kuepper R, van Os J, Lieb R, Wittchen H, Hofler M, Henquet C.
Continued cannabis use and risk of incidence and persistence of psychotic
symptoms: 10 year follow-up cohort study. BMJ. 2011 3;342(mar01 1):d738-
d738.
2. Perala J, Suvisaari J, Saarni SI, Kuoppasalmi K, Isometsa E,
Pirkola S, et al. Lifetime Prevalence of Psychotic and Bipolar I Disorders
in a General Population. Arch Gen Psychiatry. 2007 Jan 1;64(1):19-28.
3. Reed V, Gander F, Pfister H, Steiger A, Sonntag H, Trenkwalder C,
et al. To what degree does the Composite International Diagnostic
Interview (CIDI) correctly identify DSM-IV disorders? Testing validity
issues in a clinical sample. Int. J. Method. Psychiat. Res. 1998
8;7(3):142-155
Competing interests: No competing interests
(1) This study is self-described as being on the "subclinical
expression of psychosis" which is also associated with people who are less
bound to social/cultural norms -- as one would expect many cannabis users
might be. The very rejection of these social/cultural norms is considered
by some to be a "subclinical expression of psychosis". This seems a less
than ideal threshold to set considering the subject matter.
(2) Selection Bias - The exclusion of prior cannabis users prior to
the cut-off period excludes people who would have exhibited no psychotic
symptoms so there is a selection bias in the study for those users which
only start using cannabis during the study. Data for both sets of users
would have been informative. Given the age range in question this seems
even more relevant as it is a time when many adolescents would be
experimenting with such things.
(3) Purity/Control - Was the cannabis consumed tested for purity, and
did it contain any biological (mold) or chemical contaminates (pesticides,
other drugs)? How was it grown? How was it obtained (from a safe, legal
source or from illegal sources)? How was the cannabis consumed (smoked
alone, smoked w/tobacco, vaporized, ingested, other)?
(4) Cannabis vs THC - The study also needs to be controlled against
pharmacy-grade THC/CBD exposure to differentiate between cannabis the
plant and the active ingredients. THC/CBD could be perfectly safe but
something else in the plant could be responsible for any issues.
(5) How is it known that only cannabis was consumed by these users
(was there any tobacco or alcohol exposure)? Were biological samples
(hair, blood, etc) taken to ensure no other drug or drug interactions were
responsible for any psychotic symptoms?
(6) And perhaps more importantly, patient history -- did their mother
consume tobacco or alcohol during pregnancy (or possibly even during early
childhood for second-hand smoke exposure)? I bring this up because
another study published in BJP 2009
http://bjp.rcpsych.org/cgi/content/full/195/4/294 found "Maternal cannabis
use was not associated with psychotic symptoms." while both tobacco and
alcohol were.
Thank you.
Competing interests: No competing interests
Re: Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study
I'm confused DSM & ICD have been used by CIDI, but DSM & ICD only cover psychotic disorders not subclinical psychotic experiences which I thought was the outcome?
Where can you find the criteria for subclinical psychosis?
In the results have clinical psychotic experiences been pooled with subclinical psychotic experiences? What about the participants who developed clinical psychosis?
many questions but quite confused- any reply would be appreciated!
Competing interests: No competing interests