and young people
Use and Psychosis
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
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]
- Cause for Concern
- Making Causal Inferences
- A Cannabis Psychosis
Use and Schizophrenia
of cannabis use in schizophrenia
of the Association
- An Overall Evaluation
- Implications for
Patients and their Families
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
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
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 . Cannabis is widely
used by young Australians during late adolescence, 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 . 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
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.
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
, 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  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 , New Zealand , Scotland , South Africa
, Sweden [8, 17, 21], the United Kingdom [6-7, 13] and the United States [15-16].
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.
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
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 , 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  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 
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
Mathers et al  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  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 , 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  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 ). 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  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  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  compared the rate of psychoses in
30 chronic daily Jamaican cannabis users with that in 30 non-cannabis using controls.
Stefanis et al  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.
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.
). 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 ) collected over
6 years from a large geographic area in which heavy cannabis use was endemic (e-g.
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 . 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.
USE AND SCHIZOPHRENIA
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 . 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 .
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
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 . 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].
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 . 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) . These rates were higher than the rates in general population,
namely, 14% for alcohol disorders  and 6% for drug abuse . The ECA findings
have also been replicated in Edmonton, Alberta .
More recently, Cuffel et al  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
of the Association
One possible explanation of the association is that cannabis use precipitates
schizophrenic disorders in vulnerable persons (e.g. ). 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  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 .
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 . 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
et al  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  and Allebeck  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  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  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  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
. 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  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
. 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.
Clinical reports suggest that schizophrenic patients who continue to use cannabis
experience more psychotic symptoms , respond poorly to neuroleptic drugs ,
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  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  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 
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  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  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  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  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 , 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 . This is unlikely in the WHO schizophrenia
study  and the recent study of Linzen , 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 . 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  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  finding.
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 ,
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 . 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  have not reported results separately
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 , 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  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.
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 . Cannabinoids, such
as THC, increase dopamine release .
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.
there is very little direct evidence that genetic vulnerability increases the
risk that cannabis users will develop psychosis. McGuire et al  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 . But, according to Gottesman , 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  when
cannabis use increased among young adults in Australia and North America .
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 .
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) .
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 . 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  may pose difficulties for many patients with schizophrenia
who find social interaction difficult. These groups may also be opposed to using
 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.
 Donnelly N, Hall W. Patterns of Cannabis Use in Australia. National Drug Strategy
Monograph Series No. 27. Australian Government Publication Service, Canberra,
 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,
 Thornicroft G. (1990) Cannabis and psychosis: Is there epidemiological evidence
for association. British Journal of Psychiatry, 1990;157:25-33.
 Hall W. A simplified logic of causal inference. Australian arid New Zealand
Journal of Psychiatry, 1987; 21:507-513.
 Carney MWP, Bacelle L, Robinson B. Psychosis after cannabis use. British Medical
Journal, 1984;288: 1047.
 Drummond L. Cannabis psychosis: a case report. British Journal of Addiction,
 Bernardson G, Gunne LM. Forty-six cases of psychosis in cannabis abusers.
International Journal of Addictions, 1972;7: 9-16.
 Chopra GS, Smith JW. Psychotic reactions following cannabis use in East Indians.
Archives of General Psychiatry, 1974;30:24-27.
 Cohen S, Johnson K. Psychosis from alcohol or drug abuse. British Medical
 Eva J. Cannabis psychosis. Psychiatric Bulletin, 1992;16:310-311.
 Kolansky H, Moore RT. Effects of marihuana on adolescents and young adults.
Journal of the American Medical Association, 1971;216(3):486-492.
 Onyango RS. Cannabis psychosis in young psychiatric inpatients. British Journal
of Addiction, 1986;8l :419-423.
 Solomons K, Neppe VM, Kuyl JM. Toxic cannabis psychosis is a valid entity.
South African Medical Journal, 1990;78:476-481.
 Talbott JA, Teague JW. Marihuana psychosis: Acute toxic psychosis associated
with the use of cannabis derivatives. Journal of the American Medical Association,
 Tennant FS, Groesbeek CJ. Psychiatric effects of hashish. Archives of General
Psychiatry, 1972;27: 133-136.
 Tunving K. Psychiatric aspects of cannabis use in adolescents and young adults.
Pediatrician, 1987; 14:83-91.
 Wylie AS, Scott RTA, Burnett SJ. Psychosis due to "skunk". British Medical
 Harding T, Knight F. Marijuana-modified mania. Archives of General Psychiatry,
 Spencer DJ. Cannabis-induced psychosis. International Journal of the Addictions,
 Paisson A, Thulin SO, Tunviung K. Cannabis psychoses in South Sweden. Acta
Psychiatrica Scandinavica, 1982; 66:311-321.
 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.
 Gruber AJ, Pope HG. Cannabis psychotic disorder. Does it exist? American
Journal of the Addictions, 1994;3:72-83.
 Poole R, Brabbins C. Drug induced psychosis. British Journal of Psychiatry,
 Schuckit MA. Can marijuana cause a long-lasting psychosis? Drug Abuse and
Alcoholism Newsletter, 1994;23:1-4.
 Thacore VR, Shuckla SRP. Cannabis psychosis and paranoid schizophrenia. Archives
of General Psychiatry, 1976;33:383-386.
 Rottanburg D, Robins AH, Ben-Arie O, Teggin A, Elk R. Cannabis-associated
psychosis with hypomanic features. Lancet, 1982;2:1364-1366.
 Chaudry HR, Moss HB, Bashir A, Suliman T. Cannabis psychosis following bhang
ingestion. British Journal of Addiction, 1991 ;86: 1075-1081.
 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.
 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,
 Imade AGT, Ebie JC. A retrospective study of symptom patterns of cannabis-induced
psychosis. Acta Psychiatrica Scandinavica, 1991;8:134-136.
 Thornicroft G, Meadows G, Politi P. Is "cannabis psychosis" a distinct category?
European Psychiatry, 1992;7:277-282.
 McGuire P, Jones R, Harvey I, Bebbington P, Toone B, Lewis S, Murray, R.
Cannabis and acute psychosis. Schizophrenia Research, 1994;13:161-168.
 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.
 Tien AY, Anthony JC. Epidemiological analysis of alcohol and drug use as
risk factors for psychotic experiences. Journal of Nervous and Mental Disease,
 Thomas H. A community survey of adverse effects of cannabis use. Drug and
Alcohol Dependence, 1996;42:201-207.
 Beaubruhn M, Knight F. Psychiatric assessment of 30 chronic users of cannabis
and 30 matched controls. American Journal of Psychiatry, 1973;130:309-311.
 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.
 Boutros NN, Bowers MB. Chronic substance-induced psychotic disorders: state
of the literature. Journal of Neuropsychiatry and Clinical Neurosciences, 1996;8:262-269.
 American Psychiatric
Association. Diagnostic and Statistical Manual Forth Edition (DSM-IV). Washington,
DC: American Psychiatric Association, 1994.
 Lishman WA. Organic Psychiatry: The Psychological Consequences of Cerebral
Disorder. Second Edition. Blackwell Scientific Publications, Oxford, 1987.
 Schneier FR, Siris SG. A review of psychoactive substance use and abuse in
schizophrenia: patterns of drug choice. Journal of Nervous and Mental Disorders,
 Smith J, Hucker S. Schizophrenia and substance abuse. British Journal of
 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.
 Weller MPI, Ang PC, Latimer-Sayer DT, Zachary A. Drug abuse and mental illness.
Lancet, 1988; 1:977.
 Breakey WR, Goodell H, Lorenz PC, McHugh PR. Hallucinogenic drugs as precipitants
of schizophrenia. Psychological Medicine, 1974;4:255-261.
 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.
 Cuffel BJ. Prevalence estimates of substance abuse in schizophrenia and their
correlates. Journal of Nervous and Mental Disease, 1992;l80:589-592.
 Mueser KT, Beflack AS, Blanchard JJ. Comorbidity and substance abuse: Implications
for treatment. Journal of Consulting and Clinical Psychology, 1992;60:845-856.
 Hambrecht M,
Hafner H. Substance abuse and the onset of schizophrenia. Biological Psychiatry,
 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.
 Kavanagh DJ. An intervention for substance abuse in schizophrenia. Behaviour
Change, 1995; 12:20-30.
 Cuffel BJ, Heithoff KA, Lawson W. Correlates of patterns of substance abuse
among patients with schizophrenia. Hospital and Community Psychiatry, 1993;44:247-251.
 Drake RE,Wallach
MA. Substance abuse among the chronic mentally ill. Hospital and Community Psychiatry,
 Anthony JC, Helzer JE. Syndromes of drug abuse and dependence. In Robins
LN, Regier DA, eds. Psychiatric Disorders in America. Free Press, MacMillan, New
Arndt S, Tyrrell G, Flaum M, Andreasen NC. Comorbidity of substance abuse and
schizophrenia: the role of premorbid adjustment. Psychological Medicine, 1992;22:379-
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.
 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.
 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.
 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.
 Bland RC, Newman SC, Orn H. Schizophrenia: lifetime co-morbidity in a community
sample. Acta Psychiatrica Scandinavica, 1987;75:383-391.
 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.
 Allebeck P, Adamsson C, Engstrom, Rydberg U. Cannabis and schizophrenia:
a longitudinal study of cases treated in Stockholm county. Acta Psychiatrica Scandinavica,
 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.
 Andreasson S, Allebeck P, Engstrom A, Rydberg U. Cannabis and schizophrenia:
A longitudinal study of Swedish conscripts. Lancet, 1987;2:1483-1486.  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;
Andreasson S, Allebeck P, Rydberg U. Schizophrenia in users and nonusers of cannabis.
Acta Psychiatrica Scandinavica, 1989;79:505-510.
 Kandel D, Faust R. Sequence and stages in patterns of adolescent drug use.
Archives of General Psychiatry, 1975;32:923-932.
 Bell D. The experimental reproduction of amphetamine psychosis. Archives
of General Psychiatry, 1973;29:35-40.
 Connell PH. Amphetamine Psychosis. Maudlsey Monograph Number 5, Institute
of Psychiatry, Oxford University Press, London, 1959.
 Gawin PH, Ellinwood EH. Cocaine arid other stimulants: Actions, abuse and
treatment New England Journal of Medicine, 1988;3 18:1173-1182.
 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,
L. Drug abuse in Sweden. Part I. Bulletin On Narcotics, 1968a;20:(1) 1-31(a).
 Goldberg L. Drug abuse in Sweden. Part II. Bulletin On Narcotics, 1968b;20:(2)
A. Adverse reactions to marihuana. New England Journal of Medicine, l970;282:997-1000.
 Bowers MB,
Mazure CM, Nelson JC, Jatlow PI. Psychotogenic drug use and neuroleptic response.
Schizophrenia Bulletin, 1990; 16:81-85.
 Knudsen P, Vilmar T. Cannabis and neuroleptic agents in schizophrenia. Acta
Psychiatrica Scandinavica, 1984;69: 162-174.
 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.
 Turner WM,
Tsuang MT. Impact of substance abuse on the course and outcome of schizophrenia.
Schizophrenia Bulletin, 1990; 16:87-372.
 Negrete JC, Knapp WP, Douglas D, Smith WB. Cannabis affects the severity
of schizophrenic symptoms: results of a clinical survey. Psychological Medicine,
 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.
 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.
 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.
 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.
 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.
 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.
 Bergman HC, Harris M. Substance abuse among young adult chronic patients.
Psychosocial Rehabilitation Journal, 1985;9:49-54.
 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.
 Test MA, Wallisch LS, Aliness DJ, Tripp K. Substance use in young adults
with schizophrenic disorders. Schizophrenia Bulletin, 1989;15:465-476.
 Peralta V, Cuesta MJ. Influence of cannabis abuse on schizophrenic psychopathology.
Acta Psychiatrica Scandinavica 1992;85:127-30.
 Hamera E, Schneider JK, Deviney S. Alcohol, cannabis, nicotine and caffeine
use and symptom distress in schizophrenia. Journal of Nervous and Mental Disease,
 Stahl SM. Essential Psychopharmacology. Cambridge University Press, Cambridge,
IB, Martin BR. Cannabis: pharmacology and toxicology in animals and humans. Addiction,
 Gottesman II. Schizophrenia Genesis: The origins of madness. W.H. Freeman
and Co, New York, 1991.
 Der G, Gupta S, Murray RM. Is schizophrenia disappearing? Lancet, 1990;l:513-516.
 Jablensky A.
The epidemiology of schizophrenia. Current Opinion in Psychiatry, 1993;6:43-52.
 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.
 Warner R, de Girolamo G. Schizophrenia. World Health Organization, Geneva,
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.