davon96720
2005-01-13 09:51:19 UTC
http://www.ukcia.org/research/can-psychosis.htm
Cannabis Use and Psychosis
Wayne Hall
National Drug and Alcohol Research Centre
(Funded by the National Drugs Strategy)
The University of New South Wales, Sydney, Australia
Paper presented at:
Problematic Alcohol & Drug Use & Mental Illness
Melbourne, February 1998.
ISBN: 0947229884
Copyright NDARC 1988
[Please Note: Originally published as Technical Report No. 55. This was a
mistake, it is an internal report only. - Alcohol and other Drug Council of
Australia]
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Table of Contents
a.. SUMMARY
b.. Cause for Concern
c.. Making Causal Inferences
d.. A Cannabis Psychosis
a.. Controlled Studies
e.. Overall Evaluation
f.. Cannabis Use and Schizophrenia
a.. CIinical Studies
b.. Correlates of cannabis use in schizophrenia
c.. Population Studies
g.. Explanations of the Association
h.. Precipipation of Schizophrenia
i.. Exacerbation of Schizophrenia
j.. Intervention Studies
k.. Self-Medication
l.. An Overall Evaluation
m.. Implications for Patients and their Families
n.. REFERENCES
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SUMMARY
This report reviews evidence on two hypotheses about the relationship
between cannabis use and psychosis. The first hypothesis is that heavy
cannabis use may cause a "cannabis psychosis" - a psychosis that would not
occur in the absence of cannabis use, the symptoms of which are preceded by
heavy cannabis use and remit after abstinence. The second hypothesis is that
cannabis use may precipitate schizophrenia, or exacerbate its symptoms.
Evaluation of these hypotheses requires evidence of an association between
cannabis use and psychosis, that is unlikely to be due to chance, in which
cannabis use precedes psychosis, and in which we can exclude the hypothesis
that the relationship is due to other factors, such as, other drug use, or a
personal vulnerability to psychosis.
There is some clinical support for the first hypothesis. If these disorders
exist they seem to be rare, because they require very high doses of THC, the
prolonged use of highly potent forms of cannabis, or a pre-existing (but as
yet unspecified) vulnerability. There is more support for the second
hypothesis in that a large prospective study has shown a linear relationship
between the frequency with which cannabis had been used by age 18 and the
risks over the subsequent 15 years of a diagnosis of schizophrenia. It is
still unclear whether this means that cannabis use precipitates
schizophrenia, whether it is a form of "self-medication", or whether the
association is due to the use of other drugs, such as amphetamines, which
heavy cannabis users are more likely to use. There is better evidence that
cannabis use can exacerbate the symptoms of schizophrenia. Mental health
services should identify patients with schizophrenia who use alcohol,
cannabis and other drugs and advise them to abstain or to greatly reduce
their drug use.
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CAUSE FOR CONCERN
There are good reasons to be concerned about the possibility that cannabis
use may be a cause of psychotic disorders. Psychoses are serious and
disabling disorders [1]. Cannabis is widely used by young Australians during
late adolescence[2], and high doses of tetrahydrocannabinol -the
psychoactive substance in cannabis - have been reported to produce psychotic
symptoms, such as, visual and auditory hallucinations, delusional ideas, and
thought disorder, in normal volunteers [3).
There are a number of hypotheses about the relationship between cannabis use
and psychosis that need to be distinguished [4]. The strongest hypothesis is
that heavy cannabis use causes a specific "cannabis psychosis". This assumes
that these psychoses would not occur in the absence of cannabis use, and
that the causal role of cannabis use can be inferred from the symptoms and
their relationship to cannabis us; e.g. they are preceded by heavy cannabis
use and remit after abstinence.
A weaker type of hypothesis is that cannabis use may precipitate an episode
of schizophrenia. This hypothesis assumes that cannabis use is one factor
among many others (including genetic predisposition and other unknown
causes) that bring about schizophrenia It does not assume that the role of
cannabis can be inferred from the symptoms of the disorder, or that it will
remit when cannabis use ceases.
Finally, if cannabis use can precipitate schizophrenia it is also likely
that it can exacerbate the symptoms of the disorder. It may exacerbate
symptoms of schizophrenia (even if it is not a precipitant of the disorder)
if it reduces compliance with treatment, or interferes with the effects of
the drugs used to treat it.
MAKING CAUSAL INFERENCES
In order to infer that cannabis use is a cause of psychosis in any of these
ways we need evidence: that there is an association between cannabis use and
psychosis; that chance is an unlikely explanation of the association; that
cannabis use preceded the psychosis; and that plausible alternative
explanations of the association can be excluded [5).
Evidence that cannabis use and psychosis are associated and that chance is
an unlikely explanation of the association are readily available. There are
a smaller number of prospective studies that show cannabis use precedes
psychoses. The most difficult task is excluding the hypothesis that the
relationship between cannabis use and psychosis is due to other factors
(e.g. other drug use, or a genetic predisposition to develop schizophrenia
and use cannabis).
Since ethical reasons preclude experimental humans studies and there are no
suitable animal models, epidemiological methods must be used to rule out
common causal hypotheses. These estimate the relationship between cannabis
use and the risk of developing a psychosis after adjusting for variables
that may affect the risk (e.g. personal characteristics prior to using
cannabis, family history of psychotic illness, and other drug use). If the
relationship persists after statistical adjustment, then we can be confident
that it is not due to the variables for which statistical adjustment has
been made.
"A Cannabis Psychosis"
There are a substantial number of case reports of cannabis psychoses [6-18].
These describe individuals who develop psychotic symptoms or disorders after
using cannabis.
Chopra and Smith [9], for example, described 200 patients who were admitted
to a psychiatric hospital in Calcutta between 1963 and 1968 with psychotic
symptoms following the use of cannabis. The most common symptoms "were
sudden onset of confusion, generally associated with delusions,
hallucinations (usually visual) and emotional lability... amnesia,
disorientation, depersonalisation and paranoid symptoms" (p 24). Most
psychoses were preceded by the ingestion of a large dose of cannabis and
there was amnesia for the period between ingestion and hospitalisation. They
argued that it was unlikely that excessive cannabis use was a sign of
pre-existing psychopathology because a third of their cases had no prior
psychiatric history, the symptoms were remarkably uniform regardless of
prior psychiatric history, and those who used the most potent cannabis
preparations experienced psychotic reactions after the shortest period of
use.
The findings of Chopra and Smith [9] have received some support from other
case series which suggest that large doses of potent cannabis products can
be followed by a "toxic" psychotic disorder with "organic" features of
amnesia and confusion. These disorders have been reported from a variety of
different places including: the Caribbean [19-20], India [9], New Zealand
[11], Scotland [18], South Africa [14], Sweden [8, 17, 21], the United
Kingdom [6-7, 13] and the United States [15-16].
These disorders have been attributed to cannabis use for combinations of the
following reasons: the onset of the symptoms followed closely upon ingestion
of large quantities of cannabis; the affected individuals often exhibited
"organic" symptoms, such as, confusion, disorientation and amnesia; some had
no reported personal or family history of psychoses prior to using cannabis;
their symptoms rapidly remitted after a period of enforced abstinence from
cannabis use, usually within several days to several weeks; recovery was
usually complete with the person having no residual psychotic symptoms of
the type often seen in persons with schizophrenia; and if the disorder
recurred it was after the individual starting using cannabis.
Some commentators have been critical of this evidence [4, 22-25]. They
criticise the poor quality of information on cannabis use and its
relationship to the onset of psychosis, and the person's premorbid
adjustment and their family history of psychosis. They also emphasise the
wide variety of clinical pictures of "cannabis psychoses" reported by
different observers. These weaknesses impair the evidential value of these
case series.
Controlled Studies
A small number of controlled studies have been conducted over the past 20
years. Some case-control studies have either compared persons with "cannabis
psychoses" with persons who have schizophrenia, or compared psychoses
occurring in persons who do and do not have biochemical evidence of cannabis
use prior to presenting for treatment. Their results have been mixed.
Thacore and Shuckla [26], for example, reported a case control study that
compared 25 cases who had a "cannabis psychosis" with 25 controls who were
diagnosed as having paranoid schizophrenia with no history of cannabis use.
Their cases had a paranoid psychosis resembling schizophrenia in which there
was a clear temporal relationship between the prolonged use of cannabis and
the development of psychosis on more than two occasions. Patients with the
"cannabis psychosis" displayed more odd and bizarre behaviour, violence,
panic, and insight, and less evidence of thought disorder, than those with
schizophrenia. They also responded swiftly to neuroleptic drugs and
recovered completely.
Rottanburg et at [27] conducted a similar study in which 20 psychotic
patients with cannabinoids in their urine were compared with 20 psychotic
patients who did not have cannabinoids in their urine. Psychotic patients
with cannabinoids in their urine had more symptoms of hypomania and
agitation, and less auditory hallucinations, flattening of affect,
incoherent speech and hysteria than controls. They also showed marked
improvements in symptoms by the end of a week, whereas there was no change
in the patients whose urine did not contain cannabinoids.
Chaudry et al [28] reported a comparison of 15 psychotic "bhang" users with
10 bhang users without psychosis. They found that their cases were more
likely to have a history of chronic cannabis use and past psychotic
episodes. They also were more likely to be uncooperative and to have
symptoms of excitement, hostility, grandiosity, hallucinations,
disorientation and unusual thought content. All cases remitted within 5 days
and had no residual psychotic symptoms.
Mathers et al [29] reported a study of patients presenting to two London
hospitals whose urine was analysed for the presence of cannabinoids. They
found a relationship between the presence of cannabinoids in urine and
having a psychotic diagnosis. Rolfe et al [30] reported a similar
association between urinary cannabinoids and psychosis in 234 patients
admitted to a Gambian psychiatric unit.
In contrast to these positive findings, a number of controlled studies have
not found such a clear association. Imade and Ebie [31], compared the
symptoms of 70 patients with cannabis-induced functional psychoses, 163
patients with schizophrenia, and 39 patients with mania. They reported that
there were no symptoms that were unique to cannabis psychosis, and none that
enabled them to distinguish a "cannabis psychosis" from schizophrenia.
Thornicroft et al [32] compared 45 cases who had a psychosis and a urine
positive for cannabinoids with 45 controls who had a psychosis but either
had a urine negative for cannabinoids or reported no cannabis use. They
found very few demographic or clinical differences between the groups.
McGuire et al [33-34] compared 23 cases of psychoses occurring in persons
whose urines were positive for cannabinoids with 46 psychotic patients whose
urines were negative for cannabinoids or who reported no cannabis use. The
two groups did not differ in their psychiatric histories or symptoms
profile, as assessed by "blind" ratings of clinical files using the PSE
(McGuire et al [33]). The cases, however, were more likely to have a family
history of schizophrenia.
Two studies have examined the relationship between cannabis use and
psychotic symptoms in the general population. Tien and Anthony [35] used
data from the Epidemiologic Catchment Area study to compare the drug use of
individuals who reported "psychotic experiences" during a twelve month
period. These psychotic experiences comprised 4 types of hallucinations and
seven types of delusional belief. They compared 477 cases who reported one
or more psychotic symptoms in the one year follow-up with 1818 controls who
did not. Cases and controls were matched for age and social and demographic
characteristics. Daily cannabis use was found to double the risk of
reporting psychotic symptoms (after statistical adjustment for alcohol use
and psychiatric diagnoses at baseline).
Thomas [36] reported the prevalence of psychotic symptoms among cannabis
users in a random sample of people drawn from the electoral role of a large
city in the North Island of New Zealand. One in seven (14%) cannabis users
reported "strange, unpleasant experiences such as hearing voices or becoming
convinced that someone is trying to harm you or that you are being
persecuted" after using cannabis.
Two studies have reported no difference in the prevalence of psychotic
disorders in chronic cannabis users and controls. Beaubruhn and Knight [37]
compared the rate of psychoses in 30 chronic daily Jamaican cannabis users
with that in 30 non-cannabis using controls. Stefanis et al [38] reported a
study of 47 chronic cannabis users in Greece and 40 controls. The small
number of cases and the low prevalence of psychosis in the population make
these negative findings unconvincing.
Overall Evaluation
The existence of a "cannabis psychosis" is still a matter for debate. In its
favour are case series of "cannabis psychoses", and a small number of
controlled studies that compare the characteristics of "cannabis psychoses"
with those of psychoses in individuals who were not using cannabis at the
time of hospital admission (e.g. [39]). Critics of the hypothesis emphasise
the fallibility of clinical judgements about aetiology, the poorly specified
criteria used in diagnosing these psychoses, the dearth of controlled
studies, and the striking variations in the clinical features of "cannabis
psychoses" [24).
It is a plausible hypothesis that high doses of cannabis can produce
psychotic symptoms. There is no compelling evidence, however, that there is
a specific clinical syndrome that is identifiable as a "cannabis psychosis".
The clinical symptoms reported by different observers have been mixed. These
symptoms seem to rapidly remit, with full recovery, after abstinence from
cannabis.
If cannabis-induced psychoses exist, they are rare or they only rarely
receive medical intervention in Western societies (e.g. [40-41]). The total
number of cases of putative "cannabis psychoses" in the 12 case series
reviewed was 397 and 200 of these came from a single series (Chopra and
Smith [9]) collected over 6 years from a large geographic area in which
heavy cannabis use was endemic (e-g. [9]).
There are a number of likely reasons for the rarity of "cannabis psychoses"
in Western societies. One is that they occur after the use of large doses of
THC, or long periods of sustained heavy use. Although lifetime use of
cannabis has increased in Western societies, the pattern of heavy cannabis
use remains rare [2]. A second possibility (discussed below) is that
cannabis psychoses only occur in persons who have a pre-existing
vulnerability to psychotic disorder A third possibility is that heavy
sustained use and vulnerability are both required.
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CANNABIS USE AND SCHIZOPHRENIA
Clinical studies
In case-control studies of cannabis and other psychoactive drug use among
schizophrenic patients [42-43], schizophrenic patients are more likely to
have used psychotomimetic drugs such as amphetamines, cocaine, and
hallucinogens than other psychiatric patients [42, 44-45] or normal controls
[46, 30]. The prevalence of substance use in schizophrenic patients varies
between studies but it is generally higher than comparable figures in the
general population [47). Rates of alcohol and stimulant use among
schizophrenic patients also appear to have increased over the past several
decades [48]. These variations are probably due to differences in the
sampling of patients, with younger samples of newly incident cases reporting
higher rates than older samples of chronic cases. Studies have also differed
in the criteria for diagnosing schizophrenia and in way that substance use
has been assessed [49].
Alcohol use abuse and dependence are probably more common in the
schizophrenic population than in the general population [42,48-49]. The
findings on cannabis use have been more mixed (e.g. [29, 42, 44, 49, 50].
Generally, cannabis is the next most commonly used drug after alcohol and
tobacco, although it is usually used with alcohol [49, 52].
Correlates of cannabis use in schizophrenia
The controlled clinical studies disagree about the correlates of substance
abuse in schizophrenia. Most have found that young males are
over-represented among cannabis users (e.g. [49, 53-54]), as in the general
community [55]. In some studies, substance abusers have been reported to
have an earlier onset of psychotic symptoms, a better premorbid adjustment,
more episodes of illness, and more hallucinations (e.g. [44, 46, 50, 54,
56]). But other well controlled studies have failed to replicate some or all
of these findings [53, 57-58].
Population studies
Surveys of psychiatric disorders in the community have reported higher rates
of substance abuse disorders among persons with schizophrenia The ECA study
found an association between schizophrenia and alcohol and drug abuse and
dependence [55]. Nearly half of the patients identified as schizophrenic in
the ECA study had a diagnosis of substance abuse or dependence (34% for an
alcohol disorder and 28% for another drug disorder) [59]. These rates were
higher than the rates in general population, namely, 14% for alcohol
disorders [60] and 6% for drug abuse [55]. The ECA findings have also been
replicated in Edmonton, Alberta [61].
More recently, Cuffel et al [53] have reported on patterns of substance
abuse among 231 cases of schizophrenia identified in the ECA study. They
found that the most commonly used substances were: alcohol (37%) and
cannabis (23%), followed by stimulants and hallucinogens (13%), narcotics
(10%) and sedatives (8%). Multiple drug use was common and the most common
combinations of drugs was alcohol and cannabis (31%).
Explanations of the Association
One possible explanation of the association is that cannabis use
precipitates schizophrenic disorders in vulnerable persons (e.g. [62]).
Proponents of this hypothesis cite the earlier age of onset of psychotic
symptoms among cannabis users (with their drug use typically preceding the
onset of symptoms), their better premorbid adjustment their fewer negative
symptoms, and their better treatment response (e.g. [42, 44, 63]).
Another suggestion is that the associations between cannabis use and an
early onset and good prognosis are spurious. Arndt et al [56] argue that
schizophrenics with a better premorbid personality are more likely to be
exposed to illicit drug use among peers than persons with schizophrenia who
are socially withdrawn. There is also evidence (e.g. [1, 64]) that persons
with acute onset psychoses usually have a better premorbid adjustment and a
better prognosis. They also have greater opportunities to use cannabis and
other illicit drugs than persons who have an insidious onset and are
socially withdrawn.
A third possibility is that cannabis use is a consequence (rather than a
cause) of schizophrenia. For example, cannabis and other drugs may be used
to medicate the unpleasant symptoms of schizophrenia, such as, depression,
anxiety, lethargy, and anhedonia, or the unpleasant side effects of the
neuroleptic drugs that are often used to treat the disorder [44].
Precipitation of Schizophrenia
The most convincing evidence that cannabis use may precipitate schizophrenia
comes from a 15-year prospective study of cannabis use and schizophrenia in
50,465 Swedish conscripts [65]. This study investigated the relationship
between self-reported cannabis use at age 18 and the risk of receiving a
diagnosis of schizophrenia in the subsequent 15 years, as indicated by
inclusion in the Swedish psychiatric case register.
Andreasson et al [67] found that the relative risk of receiving a diagnosis
of schizophrenia was 2.4 times higher among those who had tried cannabis by
age 18 compared to those who had not. There was also a dose-response
relationship between a diagnosis of schizophrenia and the number of times
that cannabis had been used by age 18. Compared to those who had not used
cannabis, the risk of developing schizophrenia was 1.3 times higher for
those who had used cannabis one to ten times, 3 times higher for those who
had used cannabis between one and fifty times, and 6 times higher for those
who had used cannabis more than fifty times.
These risks were substantially reduced after statistical adjustment for
variables that were independently related to the risk of developing
schizophrenia, namely, having a psychiatric diagnosis at conscription, and
having parents who had divorced (as a proxy for parental psychiatric
disorder). Nevertheless, after adjustment, the dose response relationship
remained statistically significant The adjusted relative risk of a diagnosis
of schizophrenia for those who had smoked cannabis from one to ten times was
1.5 times, and that for those who had used ten or more times was 2.3 times,
the risk for those who had never used cannabis. Andreasson et al [65] and
Allebeck [62] have concluded that cannabis use precipitates schizophrenia in
vulnerable individuals.
A number of alternative explanations of the Swedish finding have been
offered by other authors. First, there was a large temporal gap between
self-reported cannabis use at age 18 and the development of schizophrenia
over the next 15 years or so [66-67]. Because the diagnosis of schizophrenia
was based upon a case register there was no data on how many individuals
used cannabis up until the time that their schizophrenia was diagnosed.
Andreasson et al [65] argued that cannabis use persisted because cannabis
use at age 18 was also strongly related to the risk of attracting a
diagnosis of drug abuse.
A second possibility is that schizophrenia was misdiagnosed. On this
hypothesis, the excess rate of "schizophrenia" among the heavy cannabis
users was due to cannabis-induced psychoses which were mistakenly diagnosed
as schizophrenia [66, 67-8] examined 21 cases of schizophrenia among
conscripts in the case register (8 of whom had used cannabis and 13 of whom
had not). They found that 80% of these cases met the DSM-III requirement
that the symptoms had been present for at least six months, thereby
excluding the diagnoses of transient drug-induced psychotic symptoms.
A third hypothesis is that the relationship between cannabis use and
schizophrenia is due to the use of other drugs. Longitudinal studies of
illicit drag use indicate that persons who had used cannabis a large number
of times by late adolescence were at increased risk of subsequently using
other illicit drugs, such as, amphetamine [66, 69]. Amphetamines which can
produce an acute paranoid psychosis [70-72] were the major illicit drugs of
abuse in Sweden during the study period [73-75]. On this hypothesis,
amphetamine-induced psychoses may explain the spurious association between
cannabis use and schizophrenia. The evidence that psychotic symptoms
persisted beyond 6 months [68] would also seem to exclude this hypothesis.
A fourth hypothesis is that cannabis use at age 18 was a symptom of emerging
schizophrenia. Andreasson et al [68] rejected this hypothesis, noting that
the cannabis users who developed schizophrenia had better premorbid
personalities, a more abrupt onset, and more positive symptoms than the
non-users who developed schizophrenia [68]. Moreover, although 58% of the
heavy cannabis users had a psychiatric diagnosis at the time of
conscription, there was still a dose-response relationship between cannabis
use and schizophrenia among those who had no such history. The
persuasiveness of this evidence depends upon how confident we can be that a
failure to identity a psychiatric disorder at conscription meant that no
disorder was present.
A fifth hypothesis depends upon the validity of the self-reported cannabis
use at conscription. Andreasson et al [66] acknowledged that there probably
was under-reporting of cannabis use because this information was not
collected anonymously. They argued, however, that this would produce an
under-estimate of the relationship between cannabis use and the risk of
schizophrenia. This will be true if the schizophrenic and non-schizophrenics
conscripts were equally likely to under-report. If, for example,
pre-schizophrenic subjects were more candid about their drug use, then the
apparent relationship between cannabis use and schizophrenia could be due to
response bias [67]. This seems unlikely in view of the strong dose-response
relationship between the frequency of cannabis use by age 18, and the large
unadjusted relative risk of schizophrenia among heavy users.
Exacerbation of Schizophrenia
Clinical reports suggest that schizophrenic patients who continue to use
cannabis experience more psychotic symptoms [76], respond poorly to
neuroleptic drugs [77], and have a worse clinical course than those patients
who do not [78-80]. These reports have been supported by controlled studies.
Negrete et al [81] conducted a retrospective study of the relationship
between self-reported cannabis use and symptoms. They used clinical records
of symptoms and treatment seeking among 137 schizophrenic patients who had a
disorder of at least six months duration, and who had made three visits to
their psychiatric service during the previous six months. Negrete et al [81]
compared the prevalence of hallucinations, delusions and hospitalisations
among the active cannabis users with that in patients who had previously
used cannabis, and those who had never used cannabis. There were higher
rates of continuous hallucinations and delusions, and more hospitalisations
among active cannabis users. These relationships persisted after statistical
adjustment for age and sex differences between the user groups.
Negrete et al [81] argued that cannabis use exacerbated schizophrenic
symptoms. They rejected the alternative hypothesis that patients with a
poorer prognosis were more likely to use cannabis because those who no
longer used cannabis experienced fewer symptoms, and reported a high rate of
adverse effects when they did use it. They also discounted the possibility
that these were toxic psychoses because the minimum duration of symptoms had
been six months.
Cleghorn et al [82] compared the symptom profiles of schizophrenic patients
with histories of substance abuse, among whom cannabis was the most heavily
used drug. Drug abusers had a higher prevalence of hallucinations, delusions
and positive symptoms than those who did not abuse drugs.
Jablensky et al [64] reported a two year follow-up of 1202 first episode
schizophrenic patients enrolled in 10 countries as part of a WHO
Collaborative study. They found that the use of "street drugs", including
cannabis and cocaine, during the follow up period predicted more psychotic
symptoms and periods of hospitalisation. Martinez-Arevalo et al [83] also
reported that continued use of cannabis during a one year follow up of 62
DSM-diagnosed schizophrenic patients predicted a higher rate of relapse and
poorer compliance with anti-psychotic drug treatment.
Linszen et al [84] recently reported a prospective study of outcome in 93
psychotic patients whose symptoms were assessed monthly over a year. Twenty
four of their patients were cannabis abusers (11 were less than daily users
and 13 were daily cannabis users). Despite the small sample sizes, they
found that the cannabis users as a whole relapsed to psychotic symptoms
sooner, and had more frequent relapses. in the year of follow up, than the
patients who had not used cannabis. There was also a dose response
relationship, with the daily users relapsing earlier, and more often, than
the less than daily users who, in turn, relapsed sooner, and more often,
than the patients who did not use cannabis. These relationships persisted
after multivariate adjustment for premorbid adjustment, and alcohol and
other drug use during the follow up period.
Most but not all studies [58], indicate that cannabis use exacerbates
psychotic symptoms in patients with schizophrenia. The major cause of
uncertainty about this relationship is assessing the contribution of
confounding factors. It may be, for example, that the difference in
psychotic symptoms between schizophrenia patients who do and do not use
cannabis is due to differences in premorbid personality, family history, and
other characteristics [52]. This is unlikely in the WHO schizophrenia study
[64] and the recent study of Linzen [84], both of which used multivariate
statistical methods to adjust for many of these confounders.
The other difficulty is separating the contributions that cannabis and
alcohol make to exacerbations of schizophrenic symptoms. It is rare for a
schizophrenic patient to only use cannabis [49]. The concurrent use of
alcohol is common, and the heavier their cannabis use, the more likely they
are to use psychostimulants and hallucinogens. Only the Linszen et al [84]
study statistically adjusted for the effects of concurrent alcohol and drug
use and found that the relationship persisted. Our confidence that the
effect is attributable to cannabis would be increased by replications of the
Linszen et al [84] finding.
Intervention Studies
If we could reduce cannabis use among patients with schizophrenia who use
cannabis, then we could discover whether their disorders improved and
whether the risks of relapse were substantially reduced. The major
difficulty with this strategy is that it presupposes that we can
successfully treat substance abuse in persons with schizophrenia. Alcohol
and other substance abuse are difficult to treat [85], and many persons with
schizophrenia have characteristics that predict a poor treatment outcome,
namely, they lack social support, they may be cognitively impaired, they are
unemployed, and they do not comply with treatment [49, 52].
There are very few controlled outcome studies of substance abuse treatment
in schizophrenia [86]. Few of these have produced large enough benefits of
treatment, or treated a large enough number of patients, to provide an
adequate chance of detecting any positive impacts of abstinence on the
course of disorders [49, 52]. The few that have been large enough [87] have
not reported results separately by diagnosis.
Self-Medication
The reasons that most persons with schizophrenia give for using alcohol,
cannabis and other illicit drugs are similar to those given by persons who
do not have schizophrenia, namely, to relieve boredom, to provide
stimulation, to feel good and to socialise with peers (e.g. [49, 88-90]).
The drugs that are most often used by schizophrenic patients are also those
that are most readily available [48-49].
In favour of the self-medication hypothesis, is the evidence that some
schizophrenic patients report using cannabis because its euphoric effects
relieve negative symptoms and depression (e.g. [42, 44, 91]). Dixon et al
[44], for example; surveyed 83 patients with schizophrenia who reported that
cannabis reduced anxiety and depression, and increased a sense of calm but
at the cost of increased suspiciousness.
More recently, Hamera et at [90] have reported a time series study that
examined correlations over 84 consecutive days between self-reported:
psychotic symptoms, licit and illicit drug use, and medication compliance in
17 persons with schizophrenia. They only found relationships between
nicotine and prodromal psychotic symptoms and between caffeine use and
symptoms of anxiety and depression. No relationships were found between
psychotic symptoms and alcohol or cannabis use.
This study does have limitations. The difficulty of the self-monitoring task
probably selected patients who were more compliant and less disordered than
a representative sample of schizophrenics. There were also relatively low
rates of heavy drug use. The time period of 84 days may have been too short
to examine the relationship between drug use and major exacerbations of the
illness, and the task of self-monitoring may have had reactive effects on
drug use.
An Overall Evaluation
The epidemiological evidence is strongest that cannabis use exacerbates the
symptoms of schizophrenia in affected individuals. This is supported by the
findings of a number of retrospective and prospective studies which have
controlled for confounding variables. It is also biologically plausible.
Psychotic disorders involve disturbances in the dopamine neurotransmitter
systems since drugs that increase dopamine release produce psychotic
symptoms when given in large doses, and neuroleptic drugs that reduce
psychotic symptoms also reduce dopamine levels [93]. Cannabinoids, such as
THC, increase dopamine release [92].
It is also likely that cannabis use precipitates schizophrenia in persons
who are vulnerable because of a personal or family history of schizophrenia
(e.g. [22, 39, 41]). This hypothesis is consistent with the stress-diathesis
model of schizophrenia [39, 95] in which the likelihood of developing
schizophrenia is the product of stress acting upon a genetic "diathesis" to
develop schizophrenia.
Although plausible, there is very little direct evidence that genetic
vulnerability increases the risk that cannabis users will develop psychosis.
McGuire et al [34] reported that persons with a history of heavy cannabis
use who developed a psychosis were 10 times more likely to have a family
history of schizophrenia than persons. with a psychosis who had not used
cannabis. It is also difficult to identify a genetic diathesis in the
majority of cases of schizophrenia. Having a first degree relative (parent
or sibling) who has schizophrenia increases the risks of developing the
disorder between 9 and 18 times [95]. But, according to Gottesman [95], 81%
of persons with schizophrenia will not have a first degree relative with the
disorder, and 63% will not have an affected first or second degree relative.
The most contentious issue is whether cannabis use can cause schizophrenia
that would not have occurred in its absence. One cannot rule it out but it
is unlikely to account for more than a minority of cases. Most of the 274
conscripts who developed schizophrenia had not used cannabis, and only 21
were heavy cannabis users and at most 7% of cases of schizophrenia could be
attributed to cannabis use. The treated incidence of schizophrenia, and
particularly early onset, acute cases, has declined (or remained stable)
during the 1970s and 1980s [94] when cannabis use increased among young
adults in Australia and North America [2]. Although there are complications
in interpreting such trends [97-99] a large reduction in treated incidence
has been observed in a number of countries and it cannot be explained as a
diagnostic artefact [100].
--------------------------------------------------------------------------------
IMPLICATIONS FOR PATIENTS AND THEIR FAMILIES
Mental health services should identify patients with schizophrenia who use
alcohol, cannabis and other drugs, and discuss its impact on their disorder
with them. Although this paper has primarily focused on cannabis we, the
role alcohol should not be neglected. Cannabis is most often used with
alcohol and heavy alcohol use is a stronger predictor of psychotic symptoms
(OR = 7.9) than regular cannabis use (OR = 2.0) [35].
Patients whose drug use may be exacerbating their symptoms should be advised
to trial abstinence. Advice to abstain or to substantially reduce use may be
better received if accompanied by alternative suggestions about how to deal
with the negative symptoms and depression [52, 49]. if they are not prepared
to abstain, they may be prepared to reduce the frequency and quantity of
drug use [52]. A positive effect on well-being and social functioning may
motivate patients to consider longer term abstinence or a sustained
reduction in use.
In assisting patients who wish to become abstinent, we may need to notify
some traditional treatment methods [49, 52]. Alcoholics Anonymous and
Narcotics Anonymous group based approaches [52] may pose difficulties for
many patients with schizophrenia who find social interaction difficult.
These groups may also be opposed to using anti-psychotic medication.
--------------------------------------------------------------------------------
REFERENCES
[1] Bromet EJ, Dew A, Eaton W. Epidemiology of psychosis with special
reference to schizophrenia. In Tsuang MT, Tohen M, Zalmer GEP, eds. Textbook
in Psychiatric Epidemiology. John Wiley and Sons, New York, 1995.
[2] Donnelly N, Hall W. Patterns of Cannabis Use in Australia. National Drug
Strategy Monograph Series No. 27. Australian Government Publication Service,
Canberra, 1994.
[3] Hall W, Solowij N, Lemon J. The Health and Psychological Effects of
Cannabis Use. National Drug Strategy Monograph Series No.25. Australian
Government Publication Service, Canberra, 1994.
[4] Thornicroft G. (1990) Cannabis and psychosis: Is there epidemiological
evidence for association. British Journal of Psychiatry, 1990;157:25-33.
[5] Hall W. A simplified logic of causal inference. Australian arid New
Zealand Journal of Psychiatry, 1987; 21:507-513.
[6] Carney MWP, Bacelle L, Robinson B. Psychosis after cannabis use. British
Medical Journal, 1984;288: 1047.
[7] Drummond L. Cannabis psychosis: a case report. British Journal of
Addiction, 1986;81:139-140.
[8] Bernardson G, Gunne LM. Forty-six cases of psychosis in cannabis
abusers. International Journal of Addictions, 1972;7: 9-16.
[9] Chopra GS, Smith JW. Psychotic reactions following cannabis use in East
Indians. Archives of General Psychiatry, 1974;30:24-27.
[10] Cohen S, Johnson K. Psychosis from alcohol or drug abuse. British
Medical Journal, 1988;297:1270-1271.
[11] Eva J. Cannabis psychosis. Psychiatric Bulletin, 1992;16:310-311.
[12] Kolansky H, Moore RT. Effects of marihuana on adolescents and young
adults. Journal of the American Medical Association, 1971;216(3):486-492.
[13] Onyango RS. Cannabis psychosis in young psychiatric inpatients. British
Journal of Addiction, 1986;8l :419-423.
[14] Solomons K, Neppe VM, Kuyl JM. Toxic cannabis psychosis is a valid
entity. South African Medical Journal, 1990;78:476-481.
[15] Talbott JA, Teague JW. Marihuana psychosis: Acute toxic psychosis
associated with the use of cannabis derivatives. Journal of the American
Medical Association, 1969;210:299- 302.
[16] Tennant FS, Groesbeek CJ. Psychiatric effects of hashish. Archives of
General Psychiatry, 1972;27: 133-136.
[17] Tunving K. Psychiatric aspects of cannabis use in adolescents and young
adults. Pediatrician, 1987; 14:83-91.
[18] Wylie AS, Scott RTA, Burnett SJ. Psychosis due to "skunk". British
Medical Journal, 1995;311:125.
[19] Harding T, Knight F. Marijuana-modified mania. Archives of General
Psychiatry, 1973;29:635-637.
[20] Spencer DJ. Cannabis-induced psychosis. International Journal of the
Addictions, 1971;6:323-326.
[21] Paisson A, Thulin SO, Tunviung K. Cannabis psychoses in South Sweden.
Acta Psychiatrica Scandinavica, 1982; 66:311-321.
[22] Lewis A. A review of the international clinical literature. In Report
of the Advisory Committee on Drug Dependence. Cannabis. Her Majesty's
Stationary Office, London, 1968.
[23] Gruber AJ, Pope HG. Cannabis psychotic disorder. Does it exist?
American Journal of the Addictions, 1994;3:72-83.
[24] Poole R, Brabbins C. Drug induced psychosis. British Journal of
Psychiatry, 1996;168:135-138.
[25] Schuckit MA. Can marijuana cause a long-lasting psychosis? Drug Abuse
and Alcoholism Newsletter, 1994;23:1-4.
[26] Thacore VR, Shuckla SRP. Cannabis psychosis and paranoid schizophrenia.
Archives of General Psychiatry, 1976;33:383-386.
[27] Rottanburg D, Robins AH, Ben-Arie O, Teggin A, Elk R.
Cannabis-associated psychosis with hypomanic features. Lancet,
1982;2:1364-1366.
[28] Chaudry HR, Moss HB, Bashir A, Suliman T. Cannabis psychosis following
bhang ingestion. British Journal of Addiction, 1991 ;86: 1075-1081.
[29] Mathers DC, Ghodse H, Caan AW, Scott SA. Cannabis use in a large sample
of acute psychiatric admissions. British Journal of Addiction,
1991;86:779-784.
[30] Rolfe M, Tang CM, Sabally S, Todd JE, Sam EB, Hatib N'Jie AB. (1993)
Psychosis and cannabis abuse in The Gambia: A case-control study. British
Journal of Psychiatry, 1993;163:789-801.
[31] Imade AGT, Ebie JC. A retrospective study of symptom patterns of
cannabis-induced psychosis. Acta Psychiatrica Scandinavica, 1991;8:134-136.
[32] Thornicroft G, Meadows G, Politi P. Is "cannabis psychosis" a distinct
category? European Psychiatry, 1992;7:277-282.
[33] McGuire P, Jones R, Harvey I, Bebbington P, Toone B, Lewis S, Murray,
R. Cannabis and acute psychosis. Schizophrenia Research, 1994;13:161-168.
[34] McGuire P, Jones R, Harvey I, Williams M, McGuffin P, Murray R Morbid
risk of schizophrenia for relatives of patients with cannabis associated
psychosis. Schizophrenia Research, 1995; 15:277-281.
[35] Tien AY, Anthony JC. Epidemiological analysis of alcohol and drug use
as risk factors for psychotic experiences. Journal of Nervous and Mental
Disease, 1990;178:473-480.
[36] Thomas H. A community survey of adverse effects of cannabis use. Drug
and Alcohol Dependence, 1996;42:201-207.
[37] Beaubruhn M, Knight F. Psychiatric assessment of 30 chronic users of
cannabis and 30 matched controls. American Journal of Psychiatry,
1973;130:309-311.
[38] Stefanis C, Boulougouris J, Liakos A. Clinical and psychophysiological
effects of cannabis in long-term users. In Braude MC, Szara S, eds. The
Pharmacology of Marihuana. Raven Press, New York, 1976.
[39] Boutros NN, Bowers MB. Chronic substance-induced psychotic disorders:
state of the literature. Journal of Neuropsychiatry and Clinical
Neurosciences, 1996;8:262-269.
[40] American Psychiatric Association. Diagnostic and Statistical Manual
Forth Edition (DSM-IV). Washington, DC: American Psychiatric Association,
1994.
[41] Lishman WA. Organic Psychiatry: The Psychological Consequences of
Cerebral Disorder. Second Edition. Blackwell Scientific Publications,
Oxford, 1987.
[42] Schneier FR, Siris SG. A review of psychoactive substance use and abuse
in schizophrenia: patterns of drug choice. Journal of Nervous and Mental
Disorders, 1987;175:641-652.
[43] Smith J, Hucker S. Schizophrenia and substance abuse. British Journal
of Psychiatry, 1994;165:13-21.
[44] Dixon L, Haas G, Wedien PJ, Sweeney J, Frances AJ. Acute effects of
drug abuse in schizophrenic patients: clinical observations and patients'
self-reports. Schizophrenia Bulletin, 1990; 16:69-79.
[45] Weller MPI, Ang PC, Latimer-Sayer DT, Zachary A. Drug abuse and mental
illness. Lancet, 1988; 1:977.
[46] Breakey WR, Goodell H, Lorenz PC, McHugh PR. Hallucinogenic drugs as
precipitants of schizophrenia. Psychological Medicine, 1974;4:255-261.
[47] Warner R, Taylor D, Wright J, Sloat A, Springen G, Arnold S, Weinberg
H. Substance use among the mentally ill: prevalence, reasons for use and
effects on illness. American Journal of Orthopsychiatry, 1994;74:30-39.
[48] Cuffel BJ. Prevalence estimates of substance abuse in schizophrenia and
their correlates. Journal of Nervous and Mental Disease, 1992;l80:589-592.
[49] Mueser KT, Beflack AS, Blanchard JJ. Comorbidity and substance abuse:
Implications for treatment. Journal of Consulting and Clinical Psychology,
1992;60:845-856.
[50] Hambrecht M, Hafner H. Substance abuse and the onset of schizophrenia.
Biological Psychiatry, 1996;40:l155-1163.
[51] Mueser KT, Yamold PR, Levinson DF, Singh H, Bellack AS, Kee K, Morrison
RL, Yadalam KG. Prevalence of substance abuse in schizophrenia: demographic
and clinical correlates. Schizophrenia Bulletin, 1990; 16:31-56.
[52] Kavanagh DJ. An intervention for substance abuse in schizophrenia.
Behaviour Change, 1995; 12:20-30.
[53] Cuffel BJ, Heithoff KA, Lawson W. Correlates of patterns of substance
abuse among patients with schizophrenia. Hospital and Community Psychiatry,
1993;44:247-251.
[54] Drake RE,Wallach MA. Substance abuse among the chronic mentally ill.
Hospital and Community Psychiatry, 1989;4:1041-1046.
[55] Anthony JC, Helzer JE. Syndromes of drug abuse and dependence. In
Robins LN, Regier DA, eds. Psychiatric Disorders in America. Free Press,
MacMillan, New York, 1991.
[56] Arndt S, Tyrrell G, Flaum M, Andreasen NC. Comorbidity of substance
abuse and schizophrenia: the role of premorbid adjustment. Psychological
Medicine, 1992;22:379- 388.
[57] Kovasznay B, Bromet E, Schwartz JE, Ram R, Lavelle J, Brandon L.
Substance abuse and onset of psychotic illness. Hospital and Community
Psychiatry, 1993;44:567-571.
[58] Zisook S, Heaton R, Moranville J, Kuck J, Jernigan T, Braff D. Past
substance abuse and clinical course of schizophrenia. American Journal of
Psychiatry, 1992;149:552-553.
[59] Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK
(1990) Comorbidity of mental disorders with alcohol and other drug abuse:
results from the Epidemiologic Catchment Area (ECA) Study. Journal of the
American Medical Association, 1990;264:2511-2518.
[60] Helzer JE, Burnam A, McEvoy LT. Alcohol abuse and dependence. In Robins
LN, Regier DA, eds. Psychiatric Disorders in America: the Epidemiologic
Catchment Area Study. The Free Press, New York, 1991.
[61] Bland RC, Newman SC, Orn H. Schizophrenia: lifetime co-morbidity in a
community sample. Acta Psychiatrica Scandinavica, 1987;75:383-391.
[62] Allebeck P. Cannabis and schizophrenia: is there a causal association?
In Nahas GG, Latour C, eds. Physiopathology of Illicit Drugs: Cannabis,
Cocaine, Opiates Pergamon Press, Oxford, 1991.
[63] Allebeck P, Adamsson C, Engstrom, Rydberg U. Cannabis and
schizophrenia: a longitudinal study of cases treated in Stockholm county.
Acta Psychiatrica Scandinavica, 1993;88: 21-24.
[64] Jablensky A, Sartorius N, Ernberg G, Anker M, Korten A, Cooper JE, Day
R, Bertelsen A. Schizophrenia: manifestations, incidence and course in
different cultures. A World Health Organization Ten-Country Study.
Psychological Medicine Monograph Supplement No. 20, 1991.
[65] Andreasson S, Allebeck P, Engstrom A, Rydberg U. Cannabis and
schizophrenia: A longitudinal study of Swedish conscripts. Lancet,
1987;2:1483-1486. [66] Johnson BA, Sinith BL, Taylor P. Cannabis and
schizophrenia Lancet, 1988;l :592-593. [ 67] Negrete JC. Cannabis and
schizophrenia. British Journal of Addiction, 1989; 84:349-351.
[68] Andreasson S, Allebeck P, Rydberg U. Schizophrenia in users and
nonusers of cannabis. Acta Psychiatrica Scandinavica, 1989;79:505-510.
[69] Kandel D, Faust R. Sequence and stages in patterns of adolescent drug
use. Archives of General Psychiatry, 1975;32:923-932.
[70] Bell D. The experimental reproduction of amphetamine psychosis.
Archives of General Psychiatry, 1973;29:35-40.
[71] Connell PH. Amphetamine Psychosis. Maudlsey Monograph Number 5,
Institute of Psychiatry, Oxford University Press, London, 1959.
[72] Gawin PH, Ellinwood EH. Cocaine arid other stimulants: Actions, abuse
and treatment New England Journal of Medicine, 1988;3 18:1173-1182.
[73] Inghe G. The present state of abuse and addiction to stimulant drugs in
Sweden. In Sjoqvist F, Tottie M, eds. Abuse of Central Stimulants. Raven
Press, New York, 1969.
[74] Goldberg L. Drug abuse in Sweden. Part I. Bulletin On Narcotics,
1968a;20:(1) 1-31(a). [75] Goldberg L. Drug abuse in Sweden. Part II.
Bulletin On Narcotics, 1968b;20:(2) 9-36(b).
[76] Weil A. Adverse reactions to marihuana. New England Journal of
Medicine, l970;282:997-1000.
[77] Bowers MB, Mazure CM, Nelson JC, Jatlow PI. Psychotogenic drug use and
neuroleptic response. Schizophrenia Bulletin, 1990; 16:81-85.
[78] Knudsen P, Vilmar T. Cannabis and neuroleptic agents in schizophrenia.
Acta Psychiatrica Scandinavica, 1984;69: 162-174.
[79] Perkins KA, Simpson JC, Tsuang MT. Ten-year follow-up of drug abusers
with acute or chronic psychosis. Hospital and Community Psychiatry,
1986;37:481-484.
[80] Turner WM, Tsuang MT. Impact of substance abuse on the course and
outcome of schizophrenia. Schizophrenia Bulletin, 1990; 16:87-372.
[81] Negrete JC, Knapp WP, Douglas D, Smith WB. Cannabis affects the
severity of schizophrenic symptoms: results of a clinical survey.
Psychological Medicine, 1986;16:515-520.
[82] Cleghom JM, Kaplan RD, Szechtman B, Szechtman H, Brown GM, Franco S.
Substance abuse and schizophrenia: effect on symptoms but not on
neurocognitive function. Journal of Clinical Psychiatry, 1991;52:26-30.
[83] Martinez-Arevalo MJ, Calcedo-Ordonez A, Varo-Prieto JR. Cannabis
consumption as a prognostic factor in schizophrenia. British Journal of
Psychiatry, 1994;.164:679-681.
[84] Linszen DH, Dingemans PM, Lenior ME. Cannabis abuse and the course of
recent-onset schizophrenic disorders. Archives of General Psychiatry, l
994;51:273-279.
[85] Heather N, Tebbutt J, eds. The Effectiveness of Treatment for Drug and
Alcohol Problems: An Overview. National Campaign Against Drug Abuse
Monograph Series Number 11. Australian Government Publishing Service,
Canberra, 1989.
[86] Lehman AF, Herron JD, Schwartz RP, Myers CP. Rehabilitation for adults
with severe mental illness and substance use disorders: A clinical trial.
Journal of Nervous and Mental Disease, 1993;18l:86-90.
[87] Jerrell J, Ridgely MS. Comparative effectiveness of three approaches to
serving people with severe mental illness and substance abuse disorders.
Journal of Nervous and Mental Disease, 1995;183:566-576.
[88] Bergman HC, Harris M. Substance abuse among young adult chronic
patients. Psychosocial Rehabilitation Journal, 1985;9:49-54.
[89] Noordsy DL, Drake RE, Teague GB, Osher PC, Hulbut SC, Beaudett MS,
Parkus TS. Subjective experiences related to alcohol use among
schizophrenics. Journal of Nervous and Mental Disease, 1991,179:411-414.
[90] Test MA, Wallisch LS, Aliness DJ, Tripp K. Substance use in young
adults with schizophrenic disorders. Schizophrenia Bulletin,
1989;15:465-476.
[91] Peralta V, Cuesta MJ. Influence of cannabis abuse on schizophrenic
psychopathology. Acta Psychiatrica Scandinavica 1992;85:127-30.
[92] Hamera E, Schneider JK, Deviney S. Alcohol, cannabis, nicotine and
caffeine use and symptom distress in schizophrenia. Journal of Nervous and
Mental Disease, 1995;183:559-565.
[93] Stahl SM. Essential Psychopharmacology. Cambridge University Press,
Cambridge, 1996.
[94] Adams IB, Martin BR. Cannabis: pharmacology and toxicology in animals
and humans. Addiction, 1996;91 :1585-14.
[95] Gottesman II. Schizophrenia Genesis: The origins of madness. W.H.
Freeman and Co, New York, 1991.
[96] Der G, Gupta S, Murray RM. Is schizophrenia disappearing? Lancet,
1990;l:513-516.
[97] Jablensky A. The epidemiology of schizophrenia. Current Opinion in
Psychiatry, 1993;6:43-52.
[98] Kendell RB, Malcolm DE, Adams W. The problem of detecting changes in
the incidence of schizophrenia. British Journal of Psychiatry, 1993; 1
62:212-218.
[99] Warner R, de Girolamo G. Schizophrenia. World Health Organization,
Geneva, 1995.
[100] Joyce PR. Changing trends in first admissions and readmissions for
mania and schizophrenia in New Zealand. Australian and New Zealand Journal
of Psychiatry, 1987;21 :82-86.
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--
Cannabis Use and Psychosis
Wayne Hall
National Drug and Alcohol Research Centre
(Funded by the National Drugs Strategy)
The University of New South Wales, Sydney, Australia
Paper presented at:
Problematic Alcohol & Drug Use & Mental Illness
Melbourne, February 1998.
ISBN: 0947229884
Copyright NDARC 1988
[Please Note: Originally published as Technical Report No. 55. This was a
mistake, it is an internal report only. - Alcohol and other Drug Council of
Australia]
--------------------------------------------------------------------------------
Table of Contents
a.. SUMMARY
b.. Cause for Concern
c.. Making Causal Inferences
d.. A Cannabis Psychosis
a.. Controlled Studies
e.. Overall Evaluation
f.. Cannabis Use and Schizophrenia
a.. CIinical Studies
b.. Correlates of cannabis use in schizophrenia
c.. Population Studies
g.. Explanations of the Association
h.. Precipipation of Schizophrenia
i.. Exacerbation of Schizophrenia
j.. Intervention Studies
k.. Self-Medication
l.. An Overall Evaluation
m.. Implications for Patients and their Families
n.. REFERENCES
--------------------------------------------------------------------------------
SUMMARY
This report reviews evidence on two hypotheses about the relationship
between cannabis use and psychosis. The first hypothesis is that heavy
cannabis use may cause a "cannabis psychosis" - a psychosis that would not
occur in the absence of cannabis use, the symptoms of which are preceded by
heavy cannabis use and remit after abstinence. The second hypothesis is that
cannabis use may precipitate schizophrenia, or exacerbate its symptoms.
Evaluation of these hypotheses requires evidence of an association between
cannabis use and psychosis, that is unlikely to be due to chance, in which
cannabis use precedes psychosis, and in which we can exclude the hypothesis
that the relationship is due to other factors, such as, other drug use, or a
personal vulnerability to psychosis.
There is some clinical support for the first hypothesis. If these disorders
exist they seem to be rare, because they require very high doses of THC, the
prolonged use of highly potent forms of cannabis, or a pre-existing (but as
yet unspecified) vulnerability. There is more support for the second
hypothesis in that a large prospective study has shown a linear relationship
between the frequency with which cannabis had been used by age 18 and the
risks over the subsequent 15 years of a diagnosis of schizophrenia. It is
still unclear whether this means that cannabis use precipitates
schizophrenia, whether it is a form of "self-medication", or whether the
association is due to the use of other drugs, such as amphetamines, which
heavy cannabis users are more likely to use. There is better evidence that
cannabis use can exacerbate the symptoms of schizophrenia. Mental health
services should identify patients with schizophrenia who use alcohol,
cannabis and other drugs and advise them to abstain or to greatly reduce
their drug use.
--------------------------------------------------------------------------------
CAUSE FOR CONCERN
There are good reasons to be concerned about the possibility that cannabis
use may be a cause of psychotic disorders. Psychoses are serious and
disabling disorders [1]. Cannabis is widely used by young Australians during
late adolescence[2], and high doses of tetrahydrocannabinol -the
psychoactive substance in cannabis - have been reported to produce psychotic
symptoms, such as, visual and auditory hallucinations, delusional ideas, and
thought disorder, in normal volunteers [3).
There are a number of hypotheses about the relationship between cannabis use
and psychosis that need to be distinguished [4]. The strongest hypothesis is
that heavy cannabis use causes a specific "cannabis psychosis". This assumes
that these psychoses would not occur in the absence of cannabis use, and
that the causal role of cannabis use can be inferred from the symptoms and
their relationship to cannabis us; e.g. they are preceded by heavy cannabis
use and remit after abstinence.
A weaker type of hypothesis is that cannabis use may precipitate an episode
of schizophrenia. This hypothesis assumes that cannabis use is one factor
among many others (including genetic predisposition and other unknown
causes) that bring about schizophrenia It does not assume that the role of
cannabis can be inferred from the symptoms of the disorder, or that it will
remit when cannabis use ceases.
Finally, if cannabis use can precipitate schizophrenia it is also likely
that it can exacerbate the symptoms of the disorder. It may exacerbate
symptoms of schizophrenia (even if it is not a precipitant of the disorder)
if it reduces compliance with treatment, or interferes with the effects of
the drugs used to treat it.
MAKING CAUSAL INFERENCES
In order to infer that cannabis use is a cause of psychosis in any of these
ways we need evidence: that there is an association between cannabis use and
psychosis; that chance is an unlikely explanation of the association; that
cannabis use preceded the psychosis; and that plausible alternative
explanations of the association can be excluded [5).
Evidence that cannabis use and psychosis are associated and that chance is
an unlikely explanation of the association are readily available. There are
a smaller number of prospective studies that show cannabis use precedes
psychoses. The most difficult task is excluding the hypothesis that the
relationship between cannabis use and psychosis is due to other factors
(e.g. other drug use, or a genetic predisposition to develop schizophrenia
and use cannabis).
Since ethical reasons preclude experimental humans studies and there are no
suitable animal models, epidemiological methods must be used to rule out
common causal hypotheses. These estimate the relationship between cannabis
use and the risk of developing a psychosis after adjusting for variables
that may affect the risk (e.g. personal characteristics prior to using
cannabis, family history of psychotic illness, and other drug use). If the
relationship persists after statistical adjustment, then we can be confident
that it is not due to the variables for which statistical adjustment has
been made.
"A Cannabis Psychosis"
There are a substantial number of case reports of cannabis psychoses [6-18].
These describe individuals who develop psychotic symptoms or disorders after
using cannabis.
Chopra and Smith [9], for example, described 200 patients who were admitted
to a psychiatric hospital in Calcutta between 1963 and 1968 with psychotic
symptoms following the use of cannabis. The most common symptoms "were
sudden onset of confusion, generally associated with delusions,
hallucinations (usually visual) and emotional lability... amnesia,
disorientation, depersonalisation and paranoid symptoms" (p 24). Most
psychoses were preceded by the ingestion of a large dose of cannabis and
there was amnesia for the period between ingestion and hospitalisation. They
argued that it was unlikely that excessive cannabis use was a sign of
pre-existing psychopathology because a third of their cases had no prior
psychiatric history, the symptoms were remarkably uniform regardless of
prior psychiatric history, and those who used the most potent cannabis
preparations experienced psychotic reactions after the shortest period of
use.
The findings of Chopra and Smith [9] have received some support from other
case series which suggest that large doses of potent cannabis products can
be followed by a "toxic" psychotic disorder with "organic" features of
amnesia and confusion. These disorders have been reported from a variety of
different places including: the Caribbean [19-20], India [9], New Zealand
[11], Scotland [18], South Africa [14], Sweden [8, 17, 21], the United
Kingdom [6-7, 13] and the United States [15-16].
These disorders have been attributed to cannabis use for combinations of the
following reasons: the onset of the symptoms followed closely upon ingestion
of large quantities of cannabis; the affected individuals often exhibited
"organic" symptoms, such as, confusion, disorientation and amnesia; some had
no reported personal or family history of psychoses prior to using cannabis;
their symptoms rapidly remitted after a period of enforced abstinence from
cannabis use, usually within several days to several weeks; recovery was
usually complete with the person having no residual psychotic symptoms of
the type often seen in persons with schizophrenia; and if the disorder
recurred it was after the individual starting using cannabis.
Some commentators have been critical of this evidence [4, 22-25]. They
criticise the poor quality of information on cannabis use and its
relationship to the onset of psychosis, and the person's premorbid
adjustment and their family history of psychosis. They also emphasise the
wide variety of clinical pictures of "cannabis psychoses" reported by
different observers. These weaknesses impair the evidential value of these
case series.
Controlled Studies
A small number of controlled studies have been conducted over the past 20
years. Some case-control studies have either compared persons with "cannabis
psychoses" with persons who have schizophrenia, or compared psychoses
occurring in persons who do and do not have biochemical evidence of cannabis
use prior to presenting for treatment. Their results have been mixed.
Thacore and Shuckla [26], for example, reported a case control study that
compared 25 cases who had a "cannabis psychosis" with 25 controls who were
diagnosed as having paranoid schizophrenia with no history of cannabis use.
Their cases had a paranoid psychosis resembling schizophrenia in which there
was a clear temporal relationship between the prolonged use of cannabis and
the development of psychosis on more than two occasions. Patients with the
"cannabis psychosis" displayed more odd and bizarre behaviour, violence,
panic, and insight, and less evidence of thought disorder, than those with
schizophrenia. They also responded swiftly to neuroleptic drugs and
recovered completely.
Rottanburg et at [27] conducted a similar study in which 20 psychotic
patients with cannabinoids in their urine were compared with 20 psychotic
patients who did not have cannabinoids in their urine. Psychotic patients
with cannabinoids in their urine had more symptoms of hypomania and
agitation, and less auditory hallucinations, flattening of affect,
incoherent speech and hysteria than controls. They also showed marked
improvements in symptoms by the end of a week, whereas there was no change
in the patients whose urine did not contain cannabinoids.
Chaudry et al [28] reported a comparison of 15 psychotic "bhang" users with
10 bhang users without psychosis. They found that their cases were more
likely to have a history of chronic cannabis use and past psychotic
episodes. They also were more likely to be uncooperative and to have
symptoms of excitement, hostility, grandiosity, hallucinations,
disorientation and unusual thought content. All cases remitted within 5 days
and had no residual psychotic symptoms.
Mathers et al [29] reported a study of patients presenting to two London
hospitals whose urine was analysed for the presence of cannabinoids. They
found a relationship between the presence of cannabinoids in urine and
having a psychotic diagnosis. Rolfe et al [30] reported a similar
association between urinary cannabinoids and psychosis in 234 patients
admitted to a Gambian psychiatric unit.
In contrast to these positive findings, a number of controlled studies have
not found such a clear association. Imade and Ebie [31], compared the
symptoms of 70 patients with cannabis-induced functional psychoses, 163
patients with schizophrenia, and 39 patients with mania. They reported that
there were no symptoms that were unique to cannabis psychosis, and none that
enabled them to distinguish a "cannabis psychosis" from schizophrenia.
Thornicroft et al [32] compared 45 cases who had a psychosis and a urine
positive for cannabinoids with 45 controls who had a psychosis but either
had a urine negative for cannabinoids or reported no cannabis use. They
found very few demographic or clinical differences between the groups.
McGuire et al [33-34] compared 23 cases of psychoses occurring in persons
whose urines were positive for cannabinoids with 46 psychotic patients whose
urines were negative for cannabinoids or who reported no cannabis use. The
two groups did not differ in their psychiatric histories or symptoms
profile, as assessed by "blind" ratings of clinical files using the PSE
(McGuire et al [33]). The cases, however, were more likely to have a family
history of schizophrenia.
Two studies have examined the relationship between cannabis use and
psychotic symptoms in the general population. Tien and Anthony [35] used
data from the Epidemiologic Catchment Area study to compare the drug use of
individuals who reported "psychotic experiences" during a twelve month
period. These psychotic experiences comprised 4 types of hallucinations and
seven types of delusional belief. They compared 477 cases who reported one
or more psychotic symptoms in the one year follow-up with 1818 controls who
did not. Cases and controls were matched for age and social and demographic
characteristics. Daily cannabis use was found to double the risk of
reporting psychotic symptoms (after statistical adjustment for alcohol use
and psychiatric diagnoses at baseline).
Thomas [36] reported the prevalence of psychotic symptoms among cannabis
users in a random sample of people drawn from the electoral role of a large
city in the North Island of New Zealand. One in seven (14%) cannabis users
reported "strange, unpleasant experiences such as hearing voices or becoming
convinced that someone is trying to harm you or that you are being
persecuted" after using cannabis.
Two studies have reported no difference in the prevalence of psychotic
disorders in chronic cannabis users and controls. Beaubruhn and Knight [37]
compared the rate of psychoses in 30 chronic daily Jamaican cannabis users
with that in 30 non-cannabis using controls. Stefanis et al [38] reported a
study of 47 chronic cannabis users in Greece and 40 controls. The small
number of cases and the low prevalence of psychosis in the population make
these negative findings unconvincing.
Overall Evaluation
The existence of a "cannabis psychosis" is still a matter for debate. In its
favour are case series of "cannabis psychoses", and a small number of
controlled studies that compare the characteristics of "cannabis psychoses"
with those of psychoses in individuals who were not using cannabis at the
time of hospital admission (e.g. [39]). Critics of the hypothesis emphasise
the fallibility of clinical judgements about aetiology, the poorly specified
criteria used in diagnosing these psychoses, the dearth of controlled
studies, and the striking variations in the clinical features of "cannabis
psychoses" [24).
It is a plausible hypothesis that high doses of cannabis can produce
psychotic symptoms. There is no compelling evidence, however, that there is
a specific clinical syndrome that is identifiable as a "cannabis psychosis".
The clinical symptoms reported by different observers have been mixed. These
symptoms seem to rapidly remit, with full recovery, after abstinence from
cannabis.
If cannabis-induced psychoses exist, they are rare or they only rarely
receive medical intervention in Western societies (e.g. [40-41]). The total
number of cases of putative "cannabis psychoses" in the 12 case series
reviewed was 397 and 200 of these came from a single series (Chopra and
Smith [9]) collected over 6 years from a large geographic area in which
heavy cannabis use was endemic (e-g. [9]).
There are a number of likely reasons for the rarity of "cannabis psychoses"
in Western societies. One is that they occur after the use of large doses of
THC, or long periods of sustained heavy use. Although lifetime use of
cannabis has increased in Western societies, the pattern of heavy cannabis
use remains rare [2]. A second possibility (discussed below) is that
cannabis psychoses only occur in persons who have a pre-existing
vulnerability to psychotic disorder A third possibility is that heavy
sustained use and vulnerability are both required.
--------------------------------------------------------------------------------
CANNABIS USE AND SCHIZOPHRENIA
Clinical studies
In case-control studies of cannabis and other psychoactive drug use among
schizophrenic patients [42-43], schizophrenic patients are more likely to
have used psychotomimetic drugs such as amphetamines, cocaine, and
hallucinogens than other psychiatric patients [42, 44-45] or normal controls
[46, 30]. The prevalence of substance use in schizophrenic patients varies
between studies but it is generally higher than comparable figures in the
general population [47). Rates of alcohol and stimulant use among
schizophrenic patients also appear to have increased over the past several
decades [48]. These variations are probably due to differences in the
sampling of patients, with younger samples of newly incident cases reporting
higher rates than older samples of chronic cases. Studies have also differed
in the criteria for diagnosing schizophrenia and in way that substance use
has been assessed [49].
Alcohol use abuse and dependence are probably more common in the
schizophrenic population than in the general population [42,48-49]. The
findings on cannabis use have been more mixed (e.g. [29, 42, 44, 49, 50].
Generally, cannabis is the next most commonly used drug after alcohol and
tobacco, although it is usually used with alcohol [49, 52].
Correlates of cannabis use in schizophrenia
The controlled clinical studies disagree about the correlates of substance
abuse in schizophrenia. Most have found that young males are
over-represented among cannabis users (e.g. [49, 53-54]), as in the general
community [55]. In some studies, substance abusers have been reported to
have an earlier onset of psychotic symptoms, a better premorbid adjustment,
more episodes of illness, and more hallucinations (e.g. [44, 46, 50, 54,
56]). But other well controlled studies have failed to replicate some or all
of these findings [53, 57-58].
Population studies
Surveys of psychiatric disorders in the community have reported higher rates
of substance abuse disorders among persons with schizophrenia The ECA study
found an association between schizophrenia and alcohol and drug abuse and
dependence [55]. Nearly half of the patients identified as schizophrenic in
the ECA study had a diagnosis of substance abuse or dependence (34% for an
alcohol disorder and 28% for another drug disorder) [59]. These rates were
higher than the rates in general population, namely, 14% for alcohol
disorders [60] and 6% for drug abuse [55]. The ECA findings have also been
replicated in Edmonton, Alberta [61].
More recently, Cuffel et al [53] have reported on patterns of substance
abuse among 231 cases of schizophrenia identified in the ECA study. They
found that the most commonly used substances were: alcohol (37%) and
cannabis (23%), followed by stimulants and hallucinogens (13%), narcotics
(10%) and sedatives (8%). Multiple drug use was common and the most common
combinations of drugs was alcohol and cannabis (31%).
Explanations of the Association
One possible explanation of the association is that cannabis use
precipitates schizophrenic disorders in vulnerable persons (e.g. [62]).
Proponents of this hypothesis cite the earlier age of onset of psychotic
symptoms among cannabis users (with their drug use typically preceding the
onset of symptoms), their better premorbid adjustment their fewer negative
symptoms, and their better treatment response (e.g. [42, 44, 63]).
Another suggestion is that the associations between cannabis use and an
early onset and good prognosis are spurious. Arndt et al [56] argue that
schizophrenics with a better premorbid personality are more likely to be
exposed to illicit drug use among peers than persons with schizophrenia who
are socially withdrawn. There is also evidence (e.g. [1, 64]) that persons
with acute onset psychoses usually have a better premorbid adjustment and a
better prognosis. They also have greater opportunities to use cannabis and
other illicit drugs than persons who have an insidious onset and are
socially withdrawn.
A third possibility is that cannabis use is a consequence (rather than a
cause) of schizophrenia. For example, cannabis and other drugs may be used
to medicate the unpleasant symptoms of schizophrenia, such as, depression,
anxiety, lethargy, and anhedonia, or the unpleasant side effects of the
neuroleptic drugs that are often used to treat the disorder [44].
Precipitation of Schizophrenia
The most convincing evidence that cannabis use may precipitate schizophrenia
comes from a 15-year prospective study of cannabis use and schizophrenia in
50,465 Swedish conscripts [65]. This study investigated the relationship
between self-reported cannabis use at age 18 and the risk of receiving a
diagnosis of schizophrenia in the subsequent 15 years, as indicated by
inclusion in the Swedish psychiatric case register.
Andreasson et al [67] found that the relative risk of receiving a diagnosis
of schizophrenia was 2.4 times higher among those who had tried cannabis by
age 18 compared to those who had not. There was also a dose-response
relationship between a diagnosis of schizophrenia and the number of times
that cannabis had been used by age 18. Compared to those who had not used
cannabis, the risk of developing schizophrenia was 1.3 times higher for
those who had used cannabis one to ten times, 3 times higher for those who
had used cannabis between one and fifty times, and 6 times higher for those
who had used cannabis more than fifty times.
These risks were substantially reduced after statistical adjustment for
variables that were independently related to the risk of developing
schizophrenia, namely, having a psychiatric diagnosis at conscription, and
having parents who had divorced (as a proxy for parental psychiatric
disorder). Nevertheless, after adjustment, the dose response relationship
remained statistically significant The adjusted relative risk of a diagnosis
of schizophrenia for those who had smoked cannabis from one to ten times was
1.5 times, and that for those who had used ten or more times was 2.3 times,
the risk for those who had never used cannabis. Andreasson et al [65] and
Allebeck [62] have concluded that cannabis use precipitates schizophrenia in
vulnerable individuals.
A number of alternative explanations of the Swedish finding have been
offered by other authors. First, there was a large temporal gap between
self-reported cannabis use at age 18 and the development of schizophrenia
over the next 15 years or so [66-67]. Because the diagnosis of schizophrenia
was based upon a case register there was no data on how many individuals
used cannabis up until the time that their schizophrenia was diagnosed.
Andreasson et al [65] argued that cannabis use persisted because cannabis
use at age 18 was also strongly related to the risk of attracting a
diagnosis of drug abuse.
A second possibility is that schizophrenia was misdiagnosed. On this
hypothesis, the excess rate of "schizophrenia" among the heavy cannabis
users was due to cannabis-induced psychoses which were mistakenly diagnosed
as schizophrenia [66, 67-8] examined 21 cases of schizophrenia among
conscripts in the case register (8 of whom had used cannabis and 13 of whom
had not). They found that 80% of these cases met the DSM-III requirement
that the symptoms had been present for at least six months, thereby
excluding the diagnoses of transient drug-induced psychotic symptoms.
A third hypothesis is that the relationship between cannabis use and
schizophrenia is due to the use of other drugs. Longitudinal studies of
illicit drag use indicate that persons who had used cannabis a large number
of times by late adolescence were at increased risk of subsequently using
other illicit drugs, such as, amphetamine [66, 69]. Amphetamines which can
produce an acute paranoid psychosis [70-72] were the major illicit drugs of
abuse in Sweden during the study period [73-75]. On this hypothesis,
amphetamine-induced psychoses may explain the spurious association between
cannabis use and schizophrenia. The evidence that psychotic symptoms
persisted beyond 6 months [68] would also seem to exclude this hypothesis.
A fourth hypothesis is that cannabis use at age 18 was a symptom of emerging
schizophrenia. Andreasson et al [68] rejected this hypothesis, noting that
the cannabis users who developed schizophrenia had better premorbid
personalities, a more abrupt onset, and more positive symptoms than the
non-users who developed schizophrenia [68]. Moreover, although 58% of the
heavy cannabis users had a psychiatric diagnosis at the time of
conscription, there was still a dose-response relationship between cannabis
use and schizophrenia among those who had no such history. The
persuasiveness of this evidence depends upon how confident we can be that a
failure to identity a psychiatric disorder at conscription meant that no
disorder was present.
A fifth hypothesis depends upon the validity of the self-reported cannabis
use at conscription. Andreasson et al [66] acknowledged that there probably
was under-reporting of cannabis use because this information was not
collected anonymously. They argued, however, that this would produce an
under-estimate of the relationship between cannabis use and the risk of
schizophrenia. This will be true if the schizophrenic and non-schizophrenics
conscripts were equally likely to under-report. If, for example,
pre-schizophrenic subjects were more candid about their drug use, then the
apparent relationship between cannabis use and schizophrenia could be due to
response bias [67]. This seems unlikely in view of the strong dose-response
relationship between the frequency of cannabis use by age 18, and the large
unadjusted relative risk of schizophrenia among heavy users.
Exacerbation of Schizophrenia
Clinical reports suggest that schizophrenic patients who continue to use
cannabis experience more psychotic symptoms [76], respond poorly to
neuroleptic drugs [77], and have a worse clinical course than those patients
who do not [78-80]. These reports have been supported by controlled studies.
Negrete et al [81] conducted a retrospective study of the relationship
between self-reported cannabis use and symptoms. They used clinical records
of symptoms and treatment seeking among 137 schizophrenic patients who had a
disorder of at least six months duration, and who had made three visits to
their psychiatric service during the previous six months. Negrete et al [81]
compared the prevalence of hallucinations, delusions and hospitalisations
among the active cannabis users with that in patients who had previously
used cannabis, and those who had never used cannabis. There were higher
rates of continuous hallucinations and delusions, and more hospitalisations
among active cannabis users. These relationships persisted after statistical
adjustment for age and sex differences between the user groups.
Negrete et al [81] argued that cannabis use exacerbated schizophrenic
symptoms. They rejected the alternative hypothesis that patients with a
poorer prognosis were more likely to use cannabis because those who no
longer used cannabis experienced fewer symptoms, and reported a high rate of
adverse effects when they did use it. They also discounted the possibility
that these were toxic psychoses because the minimum duration of symptoms had
been six months.
Cleghorn et al [82] compared the symptom profiles of schizophrenic patients
with histories of substance abuse, among whom cannabis was the most heavily
used drug. Drug abusers had a higher prevalence of hallucinations, delusions
and positive symptoms than those who did not abuse drugs.
Jablensky et al [64] reported a two year follow-up of 1202 first episode
schizophrenic patients enrolled in 10 countries as part of a WHO
Collaborative study. They found that the use of "street drugs", including
cannabis and cocaine, during the follow up period predicted more psychotic
symptoms and periods of hospitalisation. Martinez-Arevalo et al [83] also
reported that continued use of cannabis during a one year follow up of 62
DSM-diagnosed schizophrenic patients predicted a higher rate of relapse and
poorer compliance with anti-psychotic drug treatment.
Linszen et al [84] recently reported a prospective study of outcome in 93
psychotic patients whose symptoms were assessed monthly over a year. Twenty
four of their patients were cannabis abusers (11 were less than daily users
and 13 were daily cannabis users). Despite the small sample sizes, they
found that the cannabis users as a whole relapsed to psychotic symptoms
sooner, and had more frequent relapses. in the year of follow up, than the
patients who had not used cannabis. There was also a dose response
relationship, with the daily users relapsing earlier, and more often, than
the less than daily users who, in turn, relapsed sooner, and more often,
than the patients who did not use cannabis. These relationships persisted
after multivariate adjustment for premorbid adjustment, and alcohol and
other drug use during the follow up period.
Most but not all studies [58], indicate that cannabis use exacerbates
psychotic symptoms in patients with schizophrenia. The major cause of
uncertainty about this relationship is assessing the contribution of
confounding factors. It may be, for example, that the difference in
psychotic symptoms between schizophrenia patients who do and do not use
cannabis is due to differences in premorbid personality, family history, and
other characteristics [52]. This is unlikely in the WHO schizophrenia study
[64] and the recent study of Linzen [84], both of which used multivariate
statistical methods to adjust for many of these confounders.
The other difficulty is separating the contributions that cannabis and
alcohol make to exacerbations of schizophrenic symptoms. It is rare for a
schizophrenic patient to only use cannabis [49]. The concurrent use of
alcohol is common, and the heavier their cannabis use, the more likely they
are to use psychostimulants and hallucinogens. Only the Linszen et al [84]
study statistically adjusted for the effects of concurrent alcohol and drug
use and found that the relationship persisted. Our confidence that the
effect is attributable to cannabis would be increased by replications of the
Linszen et al [84] finding.
Intervention Studies
If we could reduce cannabis use among patients with schizophrenia who use
cannabis, then we could discover whether their disorders improved and
whether the risks of relapse were substantially reduced. The major
difficulty with this strategy is that it presupposes that we can
successfully treat substance abuse in persons with schizophrenia. Alcohol
and other substance abuse are difficult to treat [85], and many persons with
schizophrenia have characteristics that predict a poor treatment outcome,
namely, they lack social support, they may be cognitively impaired, they are
unemployed, and they do not comply with treatment [49, 52].
There are very few controlled outcome studies of substance abuse treatment
in schizophrenia [86]. Few of these have produced large enough benefits of
treatment, or treated a large enough number of patients, to provide an
adequate chance of detecting any positive impacts of abstinence on the
course of disorders [49, 52]. The few that have been large enough [87] have
not reported results separately by diagnosis.
Self-Medication
The reasons that most persons with schizophrenia give for using alcohol,
cannabis and other illicit drugs are similar to those given by persons who
do not have schizophrenia, namely, to relieve boredom, to provide
stimulation, to feel good and to socialise with peers (e.g. [49, 88-90]).
The drugs that are most often used by schizophrenic patients are also those
that are most readily available [48-49].
In favour of the self-medication hypothesis, is the evidence that some
schizophrenic patients report using cannabis because its euphoric effects
relieve negative symptoms and depression (e.g. [42, 44, 91]). Dixon et al
[44], for example; surveyed 83 patients with schizophrenia who reported that
cannabis reduced anxiety and depression, and increased a sense of calm but
at the cost of increased suspiciousness.
More recently, Hamera et at [90] have reported a time series study that
examined correlations over 84 consecutive days between self-reported:
psychotic symptoms, licit and illicit drug use, and medication compliance in
17 persons with schizophrenia. They only found relationships between
nicotine and prodromal psychotic symptoms and between caffeine use and
symptoms of anxiety and depression. No relationships were found between
psychotic symptoms and alcohol or cannabis use.
This study does have limitations. The difficulty of the self-monitoring task
probably selected patients who were more compliant and less disordered than
a representative sample of schizophrenics. There were also relatively low
rates of heavy drug use. The time period of 84 days may have been too short
to examine the relationship between drug use and major exacerbations of the
illness, and the task of self-monitoring may have had reactive effects on
drug use.
An Overall Evaluation
The epidemiological evidence is strongest that cannabis use exacerbates the
symptoms of schizophrenia in affected individuals. This is supported by the
findings of a number of retrospective and prospective studies which have
controlled for confounding variables. It is also biologically plausible.
Psychotic disorders involve disturbances in the dopamine neurotransmitter
systems since drugs that increase dopamine release produce psychotic
symptoms when given in large doses, and neuroleptic drugs that reduce
psychotic symptoms also reduce dopamine levels [93]. Cannabinoids, such as
THC, increase dopamine release [92].
It is also likely that cannabis use precipitates schizophrenia in persons
who are vulnerable because of a personal or family history of schizophrenia
(e.g. [22, 39, 41]). This hypothesis is consistent with the stress-diathesis
model of schizophrenia [39, 95] in which the likelihood of developing
schizophrenia is the product of stress acting upon a genetic "diathesis" to
develop schizophrenia.
Although plausible, there is very little direct evidence that genetic
vulnerability increases the risk that cannabis users will develop psychosis.
McGuire et al [34] reported that persons with a history of heavy cannabis
use who developed a psychosis were 10 times more likely to have a family
history of schizophrenia than persons. with a psychosis who had not used
cannabis. It is also difficult to identify a genetic diathesis in the
majority of cases of schizophrenia. Having a first degree relative (parent
or sibling) who has schizophrenia increases the risks of developing the
disorder between 9 and 18 times [95]. But, according to Gottesman [95], 81%
of persons with schizophrenia will not have a first degree relative with the
disorder, and 63% will not have an affected first or second degree relative.
The most contentious issue is whether cannabis use can cause schizophrenia
that would not have occurred in its absence. One cannot rule it out but it
is unlikely to account for more than a minority of cases. Most of the 274
conscripts who developed schizophrenia had not used cannabis, and only 21
were heavy cannabis users and at most 7% of cases of schizophrenia could be
attributed to cannabis use. The treated incidence of schizophrenia, and
particularly early onset, acute cases, has declined (or remained stable)
during the 1970s and 1980s [94] when cannabis use increased among young
adults in Australia and North America [2]. Although there are complications
in interpreting such trends [97-99] a large reduction in treated incidence
has been observed in a number of countries and it cannot be explained as a
diagnostic artefact [100].
--------------------------------------------------------------------------------
IMPLICATIONS FOR PATIENTS AND THEIR FAMILIES
Mental health services should identify patients with schizophrenia who use
alcohol, cannabis and other drugs, and discuss its impact on their disorder
with them. Although this paper has primarily focused on cannabis we, the
role alcohol should not be neglected. Cannabis is most often used with
alcohol and heavy alcohol use is a stronger predictor of psychotic symptoms
(OR = 7.9) than regular cannabis use (OR = 2.0) [35].
Patients whose drug use may be exacerbating their symptoms should be advised
to trial abstinence. Advice to abstain or to substantially reduce use may be
better received if accompanied by alternative suggestions about how to deal
with the negative symptoms and depression [52, 49]. if they are not prepared
to abstain, they may be prepared to reduce the frequency and quantity of
drug use [52]. A positive effect on well-being and social functioning may
motivate patients to consider longer term abstinence or a sustained
reduction in use.
In assisting patients who wish to become abstinent, we may need to notify
some traditional treatment methods [49, 52]. Alcoholics Anonymous and
Narcotics Anonymous group based approaches [52] may pose difficulties for
many patients with schizophrenia who find social interaction difficult.
These groups may also be opposed to using anti-psychotic medication.
--------------------------------------------------------------------------------
REFERENCES
[1] Bromet EJ, Dew A, Eaton W. Epidemiology of psychosis with special
reference to schizophrenia. In Tsuang MT, Tohen M, Zalmer GEP, eds. Textbook
in Psychiatric Epidemiology. John Wiley and Sons, New York, 1995.
[2] Donnelly N, Hall W. Patterns of Cannabis Use in Australia. National Drug
Strategy Monograph Series No. 27. Australian Government Publication Service,
Canberra, 1994.
[3] Hall W, Solowij N, Lemon J. The Health and Psychological Effects of
Cannabis Use. National Drug Strategy Monograph Series No.25. Australian
Government Publication Service, Canberra, 1994.
[4] Thornicroft G. (1990) Cannabis and psychosis: Is there epidemiological
evidence for association. British Journal of Psychiatry, 1990;157:25-33.
[5] Hall W. A simplified logic of causal inference. Australian arid New
Zealand Journal of Psychiatry, 1987; 21:507-513.
[6] Carney MWP, Bacelle L, Robinson B. Psychosis after cannabis use. British
Medical Journal, 1984;288: 1047.
[7] Drummond L. Cannabis psychosis: a case report. British Journal of
Addiction, 1986;81:139-140.
[8] Bernardson G, Gunne LM. Forty-six cases of psychosis in cannabis
abusers. International Journal of Addictions, 1972;7: 9-16.
[9] Chopra GS, Smith JW. Psychotic reactions following cannabis use in East
Indians. Archives of General Psychiatry, 1974;30:24-27.
[10] Cohen S, Johnson K. Psychosis from alcohol or drug abuse. British
Medical Journal, 1988;297:1270-1271.
[11] Eva J. Cannabis psychosis. Psychiatric Bulletin, 1992;16:310-311.
[12] Kolansky H, Moore RT. Effects of marihuana on adolescents and young
adults. Journal of the American Medical Association, 1971;216(3):486-492.
[13] Onyango RS. Cannabis psychosis in young psychiatric inpatients. British
Journal of Addiction, 1986;8l :419-423.
[14] Solomons K, Neppe VM, Kuyl JM. Toxic cannabis psychosis is a valid
entity. South African Medical Journal, 1990;78:476-481.
[15] Talbott JA, Teague JW. Marihuana psychosis: Acute toxic psychosis
associated with the use of cannabis derivatives. Journal of the American
Medical Association, 1969;210:299- 302.
[16] Tennant FS, Groesbeek CJ. Psychiatric effects of hashish. Archives of
General Psychiatry, 1972;27: 133-136.
[17] Tunving K. Psychiatric aspects of cannabis use in adolescents and young
adults. Pediatrician, 1987; 14:83-91.
[18] Wylie AS, Scott RTA, Burnett SJ. Psychosis due to "skunk". British
Medical Journal, 1995;311:125.
[19] Harding T, Knight F. Marijuana-modified mania. Archives of General
Psychiatry, 1973;29:635-637.
[20] Spencer DJ. Cannabis-induced psychosis. International Journal of the
Addictions, 1971;6:323-326.
[21] Paisson A, Thulin SO, Tunviung K. Cannabis psychoses in South Sweden.
Acta Psychiatrica Scandinavica, 1982; 66:311-321.
[22] Lewis A. A review of the international clinical literature. In Report
of the Advisory Committee on Drug Dependence. Cannabis. Her Majesty's
Stationary Office, London, 1968.
[23] Gruber AJ, Pope HG. Cannabis psychotic disorder. Does it exist?
American Journal of the Addictions, 1994;3:72-83.
[24] Poole R, Brabbins C. Drug induced psychosis. British Journal of
Psychiatry, 1996;168:135-138.
[25] Schuckit MA. Can marijuana cause a long-lasting psychosis? Drug Abuse
and Alcoholism Newsletter, 1994;23:1-4.
[26] Thacore VR, Shuckla SRP. Cannabis psychosis and paranoid schizophrenia.
Archives of General Psychiatry, 1976;33:383-386.
[27] Rottanburg D, Robins AH, Ben-Arie O, Teggin A, Elk R.
Cannabis-associated psychosis with hypomanic features. Lancet,
1982;2:1364-1366.
[28] Chaudry HR, Moss HB, Bashir A, Suliman T. Cannabis psychosis following
bhang ingestion. British Journal of Addiction, 1991 ;86: 1075-1081.
[29] Mathers DC, Ghodse H, Caan AW, Scott SA. Cannabis use in a large sample
of acute psychiatric admissions. British Journal of Addiction,
1991;86:779-784.
[30] Rolfe M, Tang CM, Sabally S, Todd JE, Sam EB, Hatib N'Jie AB. (1993)
Psychosis and cannabis abuse in The Gambia: A case-control study. British
Journal of Psychiatry, 1993;163:789-801.
[31] Imade AGT, Ebie JC. A retrospective study of symptom patterns of
cannabis-induced psychosis. Acta Psychiatrica Scandinavica, 1991;8:134-136.
[32] Thornicroft G, Meadows G, Politi P. Is "cannabis psychosis" a distinct
category? European Psychiatry, 1992;7:277-282.
[33] McGuire P, Jones R, Harvey I, Bebbington P, Toone B, Lewis S, Murray,
R. Cannabis and acute psychosis. Schizophrenia Research, 1994;13:161-168.
[34] McGuire P, Jones R, Harvey I, Williams M, McGuffin P, Murray R Morbid
risk of schizophrenia for relatives of patients with cannabis associated
psychosis. Schizophrenia Research, 1995; 15:277-281.
[35] Tien AY, Anthony JC. Epidemiological analysis of alcohol and drug use
as risk factors for psychotic experiences. Journal of Nervous and Mental
Disease, 1990;178:473-480.
[36] Thomas H. A community survey of adverse effects of cannabis use. Drug
and Alcohol Dependence, 1996;42:201-207.
[37] Beaubruhn M, Knight F. Psychiatric assessment of 30 chronic users of
cannabis and 30 matched controls. American Journal of Psychiatry,
1973;130:309-311.
[38] Stefanis C, Boulougouris J, Liakos A. Clinical and psychophysiological
effects of cannabis in long-term users. In Braude MC, Szara S, eds. The
Pharmacology of Marihuana. Raven Press, New York, 1976.
[39] Boutros NN, Bowers MB. Chronic substance-induced psychotic disorders:
state of the literature. Journal of Neuropsychiatry and Clinical
Neurosciences, 1996;8:262-269.
[40] American Psychiatric Association. Diagnostic and Statistical Manual
Forth Edition (DSM-IV). Washington, DC: American Psychiatric Association,
1994.
[41] Lishman WA. Organic Psychiatry: The Psychological Consequences of
Cerebral Disorder. Second Edition. Blackwell Scientific Publications,
Oxford, 1987.
[42] Schneier FR, Siris SG. A review of psychoactive substance use and abuse
in schizophrenia: patterns of drug choice. Journal of Nervous and Mental
Disorders, 1987;175:641-652.
[43] Smith J, Hucker S. Schizophrenia and substance abuse. British Journal
of Psychiatry, 1994;165:13-21.
[44] Dixon L, Haas G, Wedien PJ, Sweeney J, Frances AJ. Acute effects of
drug abuse in schizophrenic patients: clinical observations and patients'
self-reports. Schizophrenia Bulletin, 1990; 16:69-79.
[45] Weller MPI, Ang PC, Latimer-Sayer DT, Zachary A. Drug abuse and mental
illness. Lancet, 1988; 1:977.
[46] Breakey WR, Goodell H, Lorenz PC, McHugh PR. Hallucinogenic drugs as
precipitants of schizophrenia. Psychological Medicine, 1974;4:255-261.
[47] Warner R, Taylor D, Wright J, Sloat A, Springen G, Arnold S, Weinberg
H. Substance use among the mentally ill: prevalence, reasons for use and
effects on illness. American Journal of Orthopsychiatry, 1994;74:30-39.
[48] Cuffel BJ. Prevalence estimates of substance abuse in schizophrenia and
their correlates. Journal of Nervous and Mental Disease, 1992;l80:589-592.
[49] Mueser KT, Beflack AS, Blanchard JJ. Comorbidity and substance abuse:
Implications for treatment. Journal of Consulting and Clinical Psychology,
1992;60:845-856.
[50] Hambrecht M, Hafner H. Substance abuse and the onset of schizophrenia.
Biological Psychiatry, 1996;40:l155-1163.
[51] Mueser KT, Yamold PR, Levinson DF, Singh H, Bellack AS, Kee K, Morrison
RL, Yadalam KG. Prevalence of substance abuse in schizophrenia: demographic
and clinical correlates. Schizophrenia Bulletin, 1990; 16:31-56.
[52] Kavanagh DJ. An intervention for substance abuse in schizophrenia.
Behaviour Change, 1995; 12:20-30.
[53] Cuffel BJ, Heithoff KA, Lawson W. Correlates of patterns of substance
abuse among patients with schizophrenia. Hospital and Community Psychiatry,
1993;44:247-251.
[54] Drake RE,Wallach MA. Substance abuse among the chronic mentally ill.
Hospital and Community Psychiatry, 1989;4:1041-1046.
[55] Anthony JC, Helzer JE. Syndromes of drug abuse and dependence. In
Robins LN, Regier DA, eds. Psychiatric Disorders in America. Free Press,
MacMillan, New York, 1991.
[56] Arndt S, Tyrrell G, Flaum M, Andreasen NC. Comorbidity of substance
abuse and schizophrenia: the role of premorbid adjustment. Psychological
Medicine, 1992;22:379- 388.
[57] Kovasznay B, Bromet E, Schwartz JE, Ram R, Lavelle J, Brandon L.
Substance abuse and onset of psychotic illness. Hospital and Community
Psychiatry, 1993;44:567-571.
[58] Zisook S, Heaton R, Moranville J, Kuck J, Jernigan T, Braff D. Past
substance abuse and clinical course of schizophrenia. American Journal of
Psychiatry, 1992;149:552-553.
[59] Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK
(1990) Comorbidity of mental disorders with alcohol and other drug abuse:
results from the Epidemiologic Catchment Area (ECA) Study. Journal of the
American Medical Association, 1990;264:2511-2518.
[60] Helzer JE, Burnam A, McEvoy LT. Alcohol abuse and dependence. In Robins
LN, Regier DA, eds. Psychiatric Disorders in America: the Epidemiologic
Catchment Area Study. The Free Press, New York, 1991.
[61] Bland RC, Newman SC, Orn H. Schizophrenia: lifetime co-morbidity in a
community sample. Acta Psychiatrica Scandinavica, 1987;75:383-391.
[62] Allebeck P. Cannabis and schizophrenia: is there a causal association?
In Nahas GG, Latour C, eds. Physiopathology of Illicit Drugs: Cannabis,
Cocaine, Opiates Pergamon Press, Oxford, 1991.
[63] Allebeck P, Adamsson C, Engstrom, Rydberg U. Cannabis and
schizophrenia: a longitudinal study of cases treated in Stockholm county.
Acta Psychiatrica Scandinavica, 1993;88: 21-24.
[64] Jablensky A, Sartorius N, Ernberg G, Anker M, Korten A, Cooper JE, Day
R, Bertelsen A. Schizophrenia: manifestations, incidence and course in
different cultures. A World Health Organization Ten-Country Study.
Psychological Medicine Monograph Supplement No. 20, 1991.
[65] Andreasson S, Allebeck P, Engstrom A, Rydberg U. Cannabis and
schizophrenia: A longitudinal study of Swedish conscripts. Lancet,
1987;2:1483-1486. [66] Johnson BA, Sinith BL, Taylor P. Cannabis and
schizophrenia Lancet, 1988;l :592-593. [ 67] Negrete JC. Cannabis and
schizophrenia. British Journal of Addiction, 1989; 84:349-351.
[68] Andreasson S, Allebeck P, Rydberg U. Schizophrenia in users and
nonusers of cannabis. Acta Psychiatrica Scandinavica, 1989;79:505-510.
[69] Kandel D, Faust R. Sequence and stages in patterns of adolescent drug
use. Archives of General Psychiatry, 1975;32:923-932.
[70] Bell D. The experimental reproduction of amphetamine psychosis.
Archives of General Psychiatry, 1973;29:35-40.
[71] Connell PH. Amphetamine Psychosis. Maudlsey Monograph Number 5,
Institute of Psychiatry, Oxford University Press, London, 1959.
[72] Gawin PH, Ellinwood EH. Cocaine arid other stimulants: Actions, abuse
and treatment New England Journal of Medicine, 1988;3 18:1173-1182.
[73] Inghe G. The present state of abuse and addiction to stimulant drugs in
Sweden. In Sjoqvist F, Tottie M, eds. Abuse of Central Stimulants. Raven
Press, New York, 1969.
[74] Goldberg L. Drug abuse in Sweden. Part I. Bulletin On Narcotics,
1968a;20:(1) 1-31(a). [75] Goldberg L. Drug abuse in Sweden. Part II.
Bulletin On Narcotics, 1968b;20:(2) 9-36(b).
[76] Weil A. Adverse reactions to marihuana. New England Journal of
Medicine, l970;282:997-1000.
[77] Bowers MB, Mazure CM, Nelson JC, Jatlow PI. Psychotogenic drug use and
neuroleptic response. Schizophrenia Bulletin, 1990; 16:81-85.
[78] Knudsen P, Vilmar T. Cannabis and neuroleptic agents in schizophrenia.
Acta Psychiatrica Scandinavica, 1984;69: 162-174.
[79] Perkins KA, Simpson JC, Tsuang MT. Ten-year follow-up of drug abusers
with acute or chronic psychosis. Hospital and Community Psychiatry,
1986;37:481-484.
[80] Turner WM, Tsuang MT. Impact of substance abuse on the course and
outcome of schizophrenia. Schizophrenia Bulletin, 1990; 16:87-372.
[81] Negrete JC, Knapp WP, Douglas D, Smith WB. Cannabis affects the
severity of schizophrenic symptoms: results of a clinical survey.
Psychological Medicine, 1986;16:515-520.
[82] Cleghom JM, Kaplan RD, Szechtman B, Szechtman H, Brown GM, Franco S.
Substance abuse and schizophrenia: effect on symptoms but not on
neurocognitive function. Journal of Clinical Psychiatry, 1991;52:26-30.
[83] Martinez-Arevalo MJ, Calcedo-Ordonez A, Varo-Prieto JR. Cannabis
consumption as a prognostic factor in schizophrenia. British Journal of
Psychiatry, 1994;.164:679-681.
[84] Linszen DH, Dingemans PM, Lenior ME. Cannabis abuse and the course of
recent-onset schizophrenic disorders. Archives of General Psychiatry, l
994;51:273-279.
[85] Heather N, Tebbutt J, eds. The Effectiveness of Treatment for Drug and
Alcohol Problems: An Overview. National Campaign Against Drug Abuse
Monograph Series Number 11. Australian Government Publishing Service,
Canberra, 1989.
[86] Lehman AF, Herron JD, Schwartz RP, Myers CP. Rehabilitation for adults
with severe mental illness and substance use disorders: A clinical trial.
Journal of Nervous and Mental Disease, 1993;18l:86-90.
[87] Jerrell J, Ridgely MS. Comparative effectiveness of three approaches to
serving people with severe mental illness and substance abuse disorders.
Journal of Nervous and Mental Disease, 1995;183:566-576.
[88] Bergman HC, Harris M. Substance abuse among young adult chronic
patients. Psychosocial Rehabilitation Journal, 1985;9:49-54.
[89] Noordsy DL, Drake RE, Teague GB, Osher PC, Hulbut SC, Beaudett MS,
Parkus TS. Subjective experiences related to alcohol use among
schizophrenics. Journal of Nervous and Mental Disease, 1991,179:411-414.
[90] Test MA, Wallisch LS, Aliness DJ, Tripp K. Substance use in young
adults with schizophrenic disorders. Schizophrenia Bulletin,
1989;15:465-476.
[91] Peralta V, Cuesta MJ. Influence of cannabis abuse on schizophrenic
psychopathology. Acta Psychiatrica Scandinavica 1992;85:127-30.
[92] Hamera E, Schneider JK, Deviney S. Alcohol, cannabis, nicotine and
caffeine use and symptom distress in schizophrenia. Journal of Nervous and
Mental Disease, 1995;183:559-565.
[93] Stahl SM. Essential Psychopharmacology. Cambridge University Press,
Cambridge, 1996.
[94] Adams IB, Martin BR. Cannabis: pharmacology and toxicology in animals
and humans. Addiction, 1996;91 :1585-14.
[95] Gottesman II. Schizophrenia Genesis: The origins of madness. W.H.
Freeman and Co, New York, 1991.
[96] Der G, Gupta S, Murray RM. Is schizophrenia disappearing? Lancet,
1990;l:513-516.
[97] Jablensky A. The epidemiology of schizophrenia. Current Opinion in
Psychiatry, 1993;6:43-52.
[98] Kendell RB, Malcolm DE, Adams W. The problem of detecting changes in
the incidence of schizophrenia. British Journal of Psychiatry, 1993; 1
62:212-218.
[99] Warner R, de Girolamo G. Schizophrenia. World Health Organization,
Geneva, 1995.
[100] Joyce PR. Changing trends in first admissions and readmissions for
mania and schizophrenia in New Zealand. Australian and New Zealand Journal
of Psychiatry, 1987;21 :82-86.
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No of SETI units returned: 1507
Processing time: 1 years, 329 days, 6 hours.
(Total hours: 16662)
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No of SETI units returned: 1507
Processing time: 1 years, 329 days, 6 hours.
(Total hours: 16662)
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