Reasons for increased substance use in psychosis
Lynsey Gregg⁎, Christine Barrowclough, Gillian Haddock
Division of Clinical Psychology, School of Psychological Sciences, University of Manchester, Unit 4, Ground Floor, Rutherford House,
Manchester Science Park, Lloyd Street North, Manchester M15 6SZ, United Kingdom
Received 19 July 2006; accepted 29 September 2006
Around half of all patients with schizophrenia are thought to abuse drugs or alcohol and there is good evidence to suggest that
they have poorer outcomes than their non substance using counterparts. However, despite more than twenty years of research there
is still no consensus on the aetiology of increased rates of substance use in people with psychosis. There is a clear need to
understand the reasons for such high rates of substance use if treatments designed to help patients abstain from substance use are to
be successful. This paper provides an update of the literature examining the reasons for substance use by people with psychosis,
and includes a comprehensive review of the self report literature. The main theories as to why people with psychosis use substances
are presented. There is evidence to suggest that cannabis may have a causal role in the development of psychopathology but not for
other substances. The self report literature provides support for an ‘alleviation of dysphoria’ model of substance use but there is
little empirical support for the self medication hypothesis, or for common factor models and bidirectional models of comorbidity. It
is likely that there are multiple risk factors involved in substance use in psychosis and more work to develop and test multiple risk
factor models is required.
© 2006 Elsevier Ltd. All rights reserved.
Keywords: Psychosis; Schizophrenia; Drug use; Alcohol use; Comorbidity
A substantial number of patients with schizophrenia are known to abuse drugs and alcohol (Mueser, Yarnold, &
Bellack, 1992; Regier et al., 1990) and rates of substance use are significantly higher in this group than in the general
population (Regier et al., 1990). Comorbidity has profound implications for the course and treatment of schizophrenia:
there is good evidence to suggest that people with schizophrenia who abuse drugs and alcohol have poorer outcomes
than both their non substance using counterparts and substance users in the general population (e.g. Drake & Wallach,
1989; Margolese, Malchy, Negrete, Tempier, & Gill, 2004). Whilst substance use disorders have such negative
consequences for this patient group, motivation for reduction of substance use in clients with psychosis is usually low
(Baker et al., 2002; Barrowclough et al., 2001) Hence there is a clear need to understand the reasons for such high rates
use of substance if treatments designed to help patients reduce their substance use are to be successful. The aim of this
Clinical Psychology Review 27 (2007) 494–510
⁎Corresponding author. Tel.: +44 161 275 8486; fax: +44 161 275 8487.
E-mail address: firstname.lastname@example.org (L. Gregg).
0272-7358/$ - see front matter © 2006 Elsevier Ltd. All rights reserved.
paper is to review the literature which examines the causes of and reasons for substance use by people with
schizophrenia, and to critically review research on the self reported reasons for substance use by this client group.
Research examining the relationship between psychosis and substance use has continued apace since the publication
of previous reviews (e.g. Batel, 2000; Blanchard, Brown, Horan, & Sherwood, 2000; Mueser, Drake, & Wallach, 1998)
and a number of good quality studies have been conducted with the aim of investigating reasons for increased
comorbidity in this client group. Six prospective cohort studies examining the link between cannabis use and psychosis
have been reported in the past five years and eight investigations of the self reported reasons for substance use have
been conducted. Prior to 2000 there was little in the way of longitudinal research and the studies examining the self
reported effects or reasons for substance use had significant methodological limitations (Green, Kavanagh, & Young,
2004). Hence an updated review of the literature in this area is timely. To provide a context to the review, the prevalence
of substance use by patients with schizophrenia will first be discussed and the correlates and the consequences of
substance use by this patient group will be described.
2. Substance use prevalence
Estimates of lifetime prevalence for individuals with schizophrenia are around 50% (Mueser, Bennet, & Kushner,
1995; Regier et al., 1990) and rates for current substance use have been reported to be as high as 65% in some samples
(Mueser et al., 1992). Estimates vary significantly across studies, primarily because of methodological differences such
as the way that such “dual diagnosis” is defined. Such differences include the diagnostic criteria for both psychosis and
substance use; the validity of the measures employed to assess both disorders; the population that is being investigated
(for example, whether inpatient or outpatient) and the location of that population (the country the research is taking
place in and whether the population is rural or urban) but nevertheless, the overwhelming majority of studies have
reported that substance use disorders are more prevalent in patients with psychosis than in the general population.
In the largest prevalence study conducted in the US (the Epidemiologic Catchment Area Study, ECA, Regier et al.,
1990) more than twenty thousand structured interviews were conducted. More than a quarter (27%) of those with
schizophrenia had experienced a drug abuse disorder in comparison to 6.1% of the general population and one third
(33.7%) had an alcohol disorder compared to 13.5% in the general population. For individuals with schizophrenia, the
odds of having an alcohol disorder were three times higher than in the general population and the odds of having
another substance use disorder were six times higher. Overall, 47% of people with schizophrenia had experienced some
substance abuse or dependence. The US National Comorbidity study (Kessler, Crum et al., 1997) reported comparable
lifetime comorbidity rates to the ECA.
The UK studies have tended to reveal lower lifetime prevalence rates than those in the US. The UK national
psychiatric morbidity survey (Farrell et al., 1998) reported a lifetime substance use prevalence rate of 7% for those with
schizophrenia, delusional disorders or schizoaffective disorders and Duke, Pantelis, McPhillips, and Barnes (2001)
reported a lifetime prevalence rate of 16% for substance use by patients with schizophrenia in a London based survey.
More recently, the West London First-Episode Schizophrenia study (Barnes, Mutsatsa, Hutton, Watt, & Joyce, 2006)
reported lifetime rates of 27% for problems with alcohol use and 68% for lifetime substance use.
2003) in the UK and are broadly comparable to those reported in the US (Kessler, Crum et al., 1997; Swartz et al., 2006).
Research in Germany (Soyka et al., 1993); Finland (Korkeila et al., 2005) Italy (Mauri et al., 2006); Canada
(Margolese et al., 2004; Van Mastrigt, Addington, & Addington, 2004); Australia (Jablensky et al., 2000) and Brazil
(Rossi Menezes & Ratto, 2004) has demonstrated considerable variability in both prevalence rates and in patterns of
use across countries. Undoubtedly some of this variability will be due to methodological differences between the
studies but it may also indicate that substance use comorbidity depends on environmental and cultural differences,
including drug availability.
The types of substance used by patients with schizophrenia vary widely (Schneier & Siris, 1987). Alcohol and
cannabis are the substances used most commonly in both US and UK samples (e.g. Kessler, Crum et al., 1997; Weaver
et al., 2003) but patterns of stimulant and opiate use vary across studies. For many ‘dually diagnosed’ patients multiple
drug and alcohol use is common, with a significant number of patients with schizophrenia abusing more than one
substance (Baigent, Holme, & Hafner, 1995; Drake, Osher, & Wallach, 1989). In the study by Weaver et al. (2003)
40.2% of those reporting problem drug use also reported harmful alcohol use. This polysubstance use means that it is
often difficult to disentangle the correlates of and the effects of different substances or classes of substances.
495L. Gregg et al. / Clinical Psychology Review 27 (2007) 494–510
3. Correlates of substance use
The demographic correlates of substance use are well documented (e.g. Kavanagh et al., 2004; Sevy et al., 2001).
Demographic profiles vary according to the type of substance used (Mueser et al., 1992), for example alcohol users
tend to be older than users of non-alcoholic substances (Salyers & Mueser, 2001), but there is some consistency in the
other main correlates identified. People with schizophrenia who also have substance use disorders are more likely to be
male than their non substance using counterparts, they also tend to be younger (with the exception of alcohol users),
less well educated and are more likely to have a family history of substance use problems (e.g. Barnes et al., 2006;
Cantwell, 2003; Kavanagh et al., 2004; Menezes et al., 1996; Mueser et al., 1995). Problem substance use has also been
associated with an earlier onset of schizophrenia (Kovasznay, Fleischer, & Tanenberg-Karant, 1997; Mauri et al.,
2006). Other, less reliable correlates include higher IQ (Sevy et al., 2001) and racial origin (Mueser et al., 1992).
Relatively few studies have investigated the relationship between substance use and psychiatric history but those that
have have reported that substance use is associated with better premorbid functioning (e.g. Carey, Carey, & Simons,
2003; Dixon, Haas, Weiden, & Frances, 1991; Sevy et al., 2001). People with schizophrenia who are more socially
active are reported to have increased exposure to substances through their social networks (Salyers & Mueser, 2001).
The only reliable clinical correlate to be identified is antisocial personality disorder (e.g. Kavanagh et al., 2004).
Studies have shown that patients with schizophrenia and antisocial personality disorder (ASPD) are more likely to have
comorbid substance use disorder than patients without ASPD (Caton, Shrout, Eagle, Opler, & Felix, 1994; Mueser
et al., 2000). Furthermore, Mueser, Drake et al. (1997), Mueser, Valentiner, and Agresta (1997) found that for patients
with schizophrenia and substance use disorder ASPD is associated with a more severe course of substance use disorder
including earlier age of onset and larger quantities of substance use.
4. Consequences of substance use
In addition to the negative impacts on a person's internal state caused by substance use (for example depressed
mood, increased perceptual and cognitive anomalies, increased arousal, unpleasant withdrawal symptoms) and the
physical consequences of drug or alcohol use (for example liver damage) there are a number of long term social and
clinical consequences associated with drug and alcohol use. In common with substance users in the general population,
substance users with schizophrenia are likely to experience financial problems associated with that use. They are also at
increased risk of illness and injury (Dickey, Azeni, Weiss, & Sederer, 2000) including problems associated with risky
behaviours such as unprotected sex and needle sharing, for example HIV (Carey et al., 2004). It has been argued that
people with psychosis are particularly sensitive to the negative effects of certain substances (Chambers, Krystal, & Self,
2001; Verdoux, Gindre, Sorbara, Tournier, & Swendsen, 2003) and that negative consequences result from lower levels
of use than in the general population (Drake et al., 1989).
Clinically, substance users with schizophrenia are at increased risk of poorer symptomatic and functional outcomes
than their non substance using counterparts. Substance use is associated with more positive symptoms (Pencer &
Addington, 2003) and with more relapses and hospitalizations (Linszen, Dingemans, & Lenior, 1994; Swofford,
Kasckow, Scheller-Gilkey, & Inderbitzin, 1996). The study by Menezes et al. (1996) reported that inpatient admission
rates among dually diagnosed patients were almost double those of patients with psychosis alone. Patients with
schizophrenia who abuse drugs and/or alcohol have increased rates of suicidal ideation (Bartels, Drake, & McHugo,
1992; Hawton, Sutton, Haw, Sinclair, & Deeks, 2005; Kamali et al., 2000) increased aggression and violence (Cuffel,
Shumway, Choulgian, & MacDonald, 1994; Fulwiler, Grossman, Forbes, & Ruthazer, 1997) and higher rates of
treatment noncompliance (Coldham, Addington, & Addington, 2002; Drake & Wallach, 1989; Janssen et al., 2006;
Owen, Fischer, Booth, & Cuffel, 1996) including medication non-adherence and failure to attend appointments. As a
result, comorbid patients are more likely to be offered typical antipsychotic medication via depot injection. Substance
users also tend to report greater extrapyramindal symptoms than abstinent patients (Potvin et al., 2006) and are at
greater risk of tardive dyskinesia (Dixon, Weiden, Haas, Sweeny, & Frances, 1992). Other consequences of substance
use in this patient group include interpersonal conflict and stress (Barrowclough, Ward, Wearden, & Gregg, 2005;
Kashner et al., 1991) for example, conflict with relatives, partners and service providers who disapprove of substance
use and blame clients for worsening their situation. People with schizophrenia who use substances are also at increased
risk of social exclusion (Todd et al., 2004) and ultimately, homelessness and housing instability (Drake, Osher, &
496L. Gregg et al. / Clinical Psychology Review 27 (2007) 494–510
5. Explanations of comorbidity
Four broad explanations of substance use in schizophrenia have been suggested (Kushner & Mueser, 1993; Mueser
et al., 1998): (1) substance use causes schizophrenia; (2) substance use is a consequence of schizophrenia; (3)
schizophrenia and substance use share a common origin; and (4) schizophrenia and substance use interact and maintain
each other. The bulk of the existing research literature has focused on the first two explanations of aetiology.
An understanding of the temporal relationship between the onset of schizophrenia and substance may help to
elucidate whether either of the two disorders is primary (if substance use is generally found to occur prior to
schizophrenia the second hypothesis would be less plausible). However, temporal order is extremely difficult to
establish. Both schizophrenia and substance use disorder tend to develop gradually after beginning in adolescence or
early adulthood, and the marked functional decline that accompanies them both makes it difficult to determine the most
relevant factor. The studies that have attempted to establish temporal order have so far been contradictory. Silver and
Abboud (1994), for example, reported that 60% of patients with schizophrenia who used drugs had done so before their
first admission and Linszen et al. (1994) reported that cannabis use preceded onset of schizophrenia in 23 out of the 24
patients in their study. Cantwell et al.'s (1999) study of 168 patients with first episode schizophrenia found that over a
third (37%) reported substance use before presentation to services. In contrast, the US national comorbidity survey
(Kessler, Crum et al., 1997) noted that in patients with co-occurring mental health and substance related disorders the
mental disorder developed first in the vast majority of cases. Hambrecht and Hafner (1996) conducted a retrospective
study with 232 patients with schizophrenia and found that one third of patients had a drug problem for more than one
year before the schizophrenia began, for another third the onset of schizophrenia occurred at a similar time to the onset
of substance use and for the final third the began more than a year before the substance use. Hambrecht and Hafner
interpreted these findings in terms of a vulnerability-stress-coping model stating that the first group might suffer have
their vulnerability threshold reduced or their coping resources diminished as a result of their substance use. The second
group might contain people who are already vulnerable to schizophrenia for whom substance misuse is a stress factor
precipitating the onset of psychosis whilst the third group uses substances for self medicating against or ‘coping with’
the symptoms of schizophrenia.
The results of these studies are difficult to interpret and compare because of the choice of marker used to date illness
onset. For Silver and Abboud (1994) the date of the first psychiatric admission was taken to be the onset of
schizophrenia but for some patients, the first symptoms of schizophrenia appear months or even years before admission
and may still, therefore, predate substance use. In other studies, onset of illness is based on patient reports but the use of
retrospective patients' reports is also problematic: patients' memories of past states are likely to be unreliable,
especially when complicated by intoxication.
5.1. Does substance use cause psychosis?
The studies that are best positioned to test whether substance use causes psychosis are prospective cohort studies
(preferably from birth) but few of these exist and those that do have focused exclusively on the link between cannabis
use and psychosis.
5.1.1. Cannabis and psychosis
There is now a huge literature on the relationship between cannabis and psychosis: 180+ articles have been indexed
on PubMed since 2000 with over 100 of these appearing in the last two years. Estimates of cannabis use by people with
schizophrenia are high. Green, Young, and Kavanagh (2005) analysed prevalence data from 53 English language
treatment studies and reported a prevalence rate for current use of 23% and 11.3% for current misuse. Lifetime
prevalence rates for use and misuse were 42.1% and 22.5% respectively. A large number of studies have reported a
significant association between cannabis use and psychosis and there is abundant evidence of the link between the two
in epidemiological studies involving the general population (e.g. Cuffel, Heithoff, & Lawson, 1993; Degenhardt &
component of cannabis) provides evidence of an association between cannabis and psychosis: Δ-9-THC produces
schizophrenia-like positiveand negative symptomsin healthy individuals (D'Souza etal.,2004) and transiently increases
497 L. Gregg et al. / Clinical Psychology Review 27 (2007) 494–510
patients with schizophrenia are more vulnerable to the effects of Δ-9-THC than those without. Whilst confirming that
cannabis can cause transient psychosis or transiently exacerbate existing psychosis these studies to not show whether
cannabis can actually cause schizophrenia or other functional psychotic illness in the long term.
Evidence for a more long term causal association comes from the cohort studies which have examined the link in
prospective longitudinal studies. The first of these studies was conducted by Andreasson, Allebeck, Engstrom, and
Rydberg (1987). More than forty-five thousand soldiers who had been conscripted into the Swedish army were
followed up for fifteen years. Data on substance use at the time of conscription were available and psychiatric
diagnoses for the fifteen years after conscription were obtained. A strong relationship between history of cannabis use
at baseline and presence of schizophrenia at follow up was reported. The ‘heavy’ cannabis users (defined as at least 50
occasions of use) were six times more likely to have a diagnosis of schizophrenia at follow up than less frequent users
or those who had never used cannabis. Significantly, no such associations were found for any of the other drugs used.
The follow up to this study (Zammit, Allebeck, Andreasson, Lundberg, & Lewis, 2002) reported that those who were
‘heavy cannabis users’ by the age of 18 were 6.7 times more likely to be diagnosed with schizophrenia. This result held
even when the polysubstance users were excluded from the analysis and was reduced (but was still significant) when
other confounds (low IQ, cigarette smoking, growing up in a city) were controlled for. The authors reported these
results to be “consistent with a causal relationship between cannabis use and schizophrenia”.
The results of the Swedish study have since been replicated in six more prospective cohort studies: two conducted in
the Netherlands (Ferdinand et al., 2005; van Os et al., 2002), one conducted in Germany (Henquet et al., 2005), two in
New Zealand (Arseneault et al., 2002; Fergusson, Horwood, & Ridder, 2005) and one in Israel (Weiser, Knobler, Noy,
& Kaplan, 2002). The first Netherlands study (van Os et al., 2002) used data from the Netherlands Mental Health
Survey and Incidence Study and followed 4045 people between 1996 and 1999. Participants with no psychotic disorder
at baseline who were also cannabis users were at increased risk of clinically significant psychotic symptoms at the end
of follow up (OR=3.5–3.7). This association was independent of any comorbid non-psychotic psychiatric disorder or
use of other substances at baseline. The second Netherlands study (Ferdinand et al., 2005) was a 14 year follow up of
1580 young adults in the ‘Zuid Holland’ study.In this sample, cannabis use significantly predicted psychotic symptoms
in participants who did not have psychotic symptoms before they began using cannabis (OR=2.8). However, psychotic
symptoms in those who had not used cannabis before the onset of psychotic symptoms also predicted future cannabis
use (OR=1.7). The German study (Henquet et al., 2005) followed 2437 young people aged 14 to 24 for four years
between 1996 and 1999. Any cannabis use at baseline was reported to increase the risk of psychotic symptoms at the
four year follow up in a dose–response fashion, regardless of confounders. The association was much stronger for
those who had been identified as being prone to psychosis at baseline. Again, the relationship was significant even
when the analysis was corrected for baseline use of other substances. Significantly, Henquet et al. (2005) report an
increased risk of cannabis use in those who had displayed psychotic experiences 3 to 4 years earlier and who had not
used cannabis before (OR=1.4). The first New Zealand study (Arseneault et al., 2002) was a birth cohort based on
1037 people born in Dunedin, New Zealand between 1972 and 1973. Cannabis use at age 15 and 18 increased the risk
of presenting with psychotic symptoms or schizophreniform disorder at age 26 (OR=11.4 for those who had used
cannabis before the age of 15). Like the other cohort studies, this relationship was independent of the use of other
substances. Significantly, this study also assessed the presence of psychotic symptoms at age 11 and was therefore able
to demonstrate that the observed association between cannabis use and increased risk of psychosis was independent
from pre-existing psychotic symptoms. The second New Zealand study (Fergusson et al., 2005) followed 1011
individuals taking part in the Christchurch health and development study from birth. Assessments were conducted
annually until age 16 and then again at 18, 21 and 25. Those who were daily users of cannabis had rates of psychotic
symptoms that were between 2.3 and 3.3 times higher than the rates for those who did not use cannabis. The study
conducted in Israel (Weiser et al., 2002) was a population-based cohort of 50413 adolescent males aged 16 to 17. Those
who were later hospitalized for schizophrenia were more likely to have smoked cannabis at baseline than those who
were not hospitalized (adjusted OR=2.0).
A Greek study (Stefanis et al., 2004) conducted a cross sectional analysis of data from an existing cohort involving
3500 representative 19-year olds. Cannabis use was associated with both positive and negative dimensions of
psychosis. First use of cannabis below 16 years of age was associated with a much stronger effectthan first use after age
16 years, independent of lifetime frequency of use.
Research on non-clinical samples has shown a relationship between cannabis use and psychosis proneness or
schizotypy (e.g. Barkus, Stirling, Hopkins, & Lewis, 2006; Dumas et al., 2002; Verdoux et al., 2003; Williams,
498L. Gregg et al. / Clinical Psychology Review 27 (2007) 494–510
Wellman, & Rawlins, 1996).Recently, Verdoux et al. (2003) used the experience sampling method (ESM) to assess the
temporal relationship between cannabis use and psychotic experiences over a one week period. ESM is a diary
technique which uses a signalling device, usually a watch, to alert participants to fill out self reports when an alarm
sounds and provides a representative sample of moments in a person's daily life (De Vries, 1992). Participants with
high psychosis vulnerability were more likely to report abnormal perceptions and thought influence when they used
cannabis. Barkus et al. (2006) found that cannabis use per se was not related to schizotypy in their sample of healthy
volunteers but that high scoring schizotypes were more likely to report psychosis-like experiences and unpleasant after-
effects associated with cannabis. Kwapil et al. (1996) conducted a 10 year follow up of a high risk sample and reported
psychosis proneness to be predictive of substance use. Not all studies involving psychosis prone people have reported
an association between cannabis use and psychosis, however. A 12 month prospective study of high risk individuals
(Phillips et al., 2002) did not find cannabis use at baseline to be associated with the onset of psychosis but there were
low levels of substance use in their sample.
Although the evidence from the prospective cohort studies seems to suggest a causal link between cannabis use and
psychosis we know that most people who smoke cannabis do not go on to develop schizophrenia and in countries
where there has been a documented increase in rates of cannabis use in the general population (e.g. Australia) there has
not been a corresponding increase in rates of schizophrenia (Degenhardt, Hall, & Lynskey, 2003). If the relationship
between cannabis and psychosis is indeed causal but not all cannabis users go on to develop psychosis then we must
consider the possibility that some individuals are more vulnerable to the effects of cannabis than others. Van Os et al.
(2005) suggest a gene-environment interaction, with some individuals being genetically vulnerable to the effects of
cannabis. Caspi et al. (2005) tested this hypothesis in a longitudinal birth cohort study and found that a functional
polymorphism of the catechol-O-methyltransferase (COMT) gene moderated the influence of adolescent cannabis use
on adult psychosis: carriers of the COMT valine158allele were more likely to experience psychotic symptoms after
cannabis consumption than carriers of the COMT methionine allele. Recent experimental work also supports this link.
Henquet et al. (2006) exposed patients with a psychotic disorder and their relatives to delta-9-tetrahydrocannabinol in a
double-blind placebo controlled study and found that carriers of the valine allele were most sensitive to Δ-9-THC
induced psychotic experiences. Significantly, this finding was conditional on pre-existing psychosis liability.
5.1.2. Alcohol and psychosis
Studies have shown alcohol dependence to be predictive of psychotic experiences in the general population (e.g.
Johns et al., 2004; Tien & Anthony, 1990) but not alcohol use per se. There is some evidence that patients with
psychotic symptoms are more likely to abuse alcohol than those who do not have psychotic symptoms (e.g. Olfson et
al., 2002) but it is generally accepted that although alcohol abuse may worsen the symptoms of those with
schizophrenia and precipitate relapse it does not actually cause schizophrenia (Bernadt & Murray, 1986; Hambrecht &
Hafner, 1996). Given that alcohol is reported to be the most commonly used substance by people with schizophrenia
(Regier et al., 1990) this may limit the significance of models of drug-induced schizophrenia (Mueser et al., 1998).
5.1.3. Amphetamines and psychosis
The phenomenon of brief amphetamine-induced psychosis is well documented but the extent to which amphetamine
use contributes to schizophrenia is not known. Baker et al. (2004) found a high rate of mental health problems among
regular amphetamine users. More than a quarter (26.7%) of those with mental health problems were diagnosed with
psychosis and the majority of these (71.4%) reported that they had received this diagnosis after commencing regular
amphetamine use. Dawe, Saunders, Kavanagh, and Young (2005) reported that 20% of injecting methamphetamine
users had had a psychiatric admission but that for 43% of these the admission was prior to the onset of regular
amphetamine use. Chen et al. (2003) investigated 445 amphetamine users and found that amphetamine users with
psychosis were younger when amphetamine use was first initiated and used larger amounts of amphetamines than those
Curran, Byrappa, and McBride (2004) systematically reviewed 54 studies investigating stimulants and psychosis and
with schizophrenia and pre-existing acute psychotic symptoms. Those with schizophrenia who do not have acute
psychotic symptoms respond, but less frequently (30%). Thus, individuals who are already experiencing psychosis are
more likely to have a psychotic reaction to stimulants. However, there is little evidence to suggest that stimulant use
results in chronic psychosis or schizophrenia.
499L. Gregg et al. / Clinical Psychology Review 27 (2007) 494–510
5.1.4. Cocaine and psychosis
As with amphetamines, a number of studies have reported that cocaine can induce psychotic symptoms in some
users but comparatively little research has been conducted to date. Brady, Lydiard, Malcolm, and Ballenger (1991)
interviewed 55 individuals consecutively admitted for treatment of cocaine dependence. Fifty-three percent (29/55)
reported that they had experienced transient cocaine-induced psychosis.
Floyd, Boutros, Struve, Wolf, and Olivia (2006) assessed 51 cocaine dependent subjects and found that 36 (71%) had
experienced psychotic symptoms during cocaine use. However, all participants in the study were polysubstance users.
5.1.5. Opiates and psychosis
Research into the relationship between opiate use and psychosis is limited.
Studies have generally shown a low comorbidity rate between opiate use and psychosis (Brooner, King, Kidorf,
Schmidt, & Bigelow, 1997; Dalmau, Bergman, & Brismar, 1999; Margolese et al., 2004; Schneier & Siris, 1987) and
there is evidence to suggest that heroin users may actually be at lower risk of psychosis than users of other substances
(Farrell et al., 2002). Thus the available data do not appear to support the hypothesis that opiate use causes
It is clear that large numbers of patients presenting to mental health services for the first time are already using
substances. The evidence from prospective longitudinal studies suggests that for some patients at least, cannabis can
have a causal role in the development of psychopathology. However, there is little evidence to suggest that other
substances, including alcohol, are a causative factor in psychosis.
5.2. Does psychosis cause substance use?
The most well known model which states that substance use disorder is a consequence of psychiatric problems is the
self-medication hypothesis (Khantzian, 1985, 1997) and it is this model that has received the most attention in the
research literature, perhaps because of its intuitive appeal. The model proposes that substance abuse is an attempt to
self-medicate psychiatric symptoms. It assumes that people with mental health problems use substances to reduce their
symptoms and that problematic use develops as a result. The hypothesis suggests that substances are not chosen at
random. Rather, there is selective matching of specific substances with specific symptoms. As Khantzian (1985) states:
“The drugs that addicts select are not chosen randomly. Theirdrug of choice is the result of an interaction between the
psychopharmacologic action of the drug and the dominant painful feelings with which they struggle” (p. 1259). The
theory applies not just to the positive symptoms of severe mental illness (i.e. hallucinations and delusions) but also the
negative symptoms. Variants of the self-medication model postulate that drugs and alcohol are also used to self
medicate extrapyramidal symptoms caused by neuroleptic medication (Schneier & Siris, 1987) or to alleviate
dysphoria. Dixon et al. (1991) go as far as to suggest that dysphoria might actually be the common factor underpinning
increased comorbidity. “Perhaps only those patients whose symptoms (positive, negative or extrapyramidal) lead to
distress or depression are the ones who abuse drugs” (Dixon et al., 1991, p. 75).
According to Mueser et al. (1998) three types of evidence would provide support for the self medication hypothesis:
(1) if epidemiological studies suggested that clients with particular psychiatric diagnoses were more prone to abusing
specific types of substances, (2) if psychiatric clients with more severe symptoms were more likely than less
symptomatic clients to abuse substances and (3) if clients with dual disorders described beneficial effects of substance
use on symptoms.
Empirical data do not suggest a consistent relationship between substance use and specific diagnoses. The review by
symptoms (e.g. cocaine, amphetamines and cannabis) to those which have predominantly sedative effects (e.g. opiates
and alcohol) and that people with schizophrenia were more likely to use stimulants than those with different diagnoses.
Similarly, Dixon et al. (1989) found that patients with schizophrenia preferred activating drugs (e.g. cocaine, cannabis,
stimulants and hallucinogens) whereas bipolar patients preferred sedative/hypnotics and alcohol. In contrast, Regier
et al. (1990) and Mueser et al. (1992) found that the patterns of use observed by people with schizophrenia is similar to
that found in patients with other diagnoses. Mueser et al. (1992) suggest that it is the availability of different types of
substances rather than their subjective effects that determine which substances are abused.
A number of studies have attempted to assess the link between severity of symptoms and levels of substance use but
again, the evidence to date has been contradictory. Brunette, Mueser, Xie, and Drake (1997) and Dervaux et al. (2001)
500L. Gregg et al. / Clinical Psychology Review 27 (2007) 494–510
found no relationships between severity of symptoms and substance abuse whereas Pencer and Addington (2003)
reported that substance use was associated with more severe positive symptoms. Recently, Talamo et al. (2006) tested
the hypothesis that comorbid patients had more positive versus negative symptoms than non-comorbid patients by
conducting a meta analysis of 8 previously published cross sectional studies (n=725) and found that comorbid patients
had significantly higher positive symptom scores and significantly lower negative symptoms scores (assessed using the
Positive and negative symptom scale, PANSS, Kay, Fiszbein, & Opler, 1987). Chapman, Labhart, and Schroeder,
(1996) found that alcohol users had a higher PANSS composite score: those who were currently abusing alcohol had an
overall greater severity of positive relative to negative symptoms. Scheller-Gilkey, Moynes, Cooper, Kant, and Miller
(2004) compared the PANSS scores of schizophrenia patients with a history of substance against those with no such
history and found no differences in either the positive or negative symptom scales. However, patients with a history of
substance abuse had significantly higher general psychopathology scale scores. Comorbid patients displayed more
somatic concern, guilt feelings, depression and poorer impulse control.
5.2.1. The self report literature
We reviewed the literature to identify articles containing self reported reasons for substance use. Studies for review
were identified following a search for combinations of the key words schizophrenia, psychosis, dual diagnosis,
comorbidity, drug use, drug abuse, substance use, substance abuse, alcohol use, alcohol abuse in two main abstract
National Library of Medicine). In addition, the bibliographies of articles were examined in order to identify further
citations. English language studies that asked patients with psychosis to report their current reasons for substance use
were included. Thirteen studies were identified. Two of these summarized their findings without reporting the numbers
of patients endorsing each reason for use and were therefore excluded.
Table 1 contains the remaining eleven studies. Reasons for use were grouped into five main categories: intoxication
effects, social reasons, dysphoria relief, psychotic symptoms and medication side effects. As the table shows, there is
considerable variability between studies. Between 35 and 95% endorsed the intoxicating effects of drugs and alcohol as
a reason for their consumption (‘to get high’, ‘for the buzz’, ‘to feel good’). Between 8 and 81% endorsed social reasons
(‘to get on with others better’, ‘to fit in with the crowd’). Between 2 and 86% reporting using drugs and/or alcohol to
relieve dysphoria (feelings of depression, anxiety, depression and other negative emotional states). Between 0 and 42%
used drugs and/or alcohol to either alleviate or cope with the symptoms of psychosis (hallucinations, feelings of
suspicion and paranoia) and between 0 and 48% reported using substances to reduce or cope with medication side
effects. A range of ‘enhancement’ reasons for use were also endorsed in five of the studies (Addington & Duchak,
1997; Dixon et al., 1991; Goswami, Mattoo, Basu, & Singh, 2004; Gregg, Haddock, & Barrowclough, submitted for
publication; Warner et al., 1994). These studies reported that patients use drugs and or alcohol to ‘increase pleasure’
(62–95%); ‘to feel more energetic’ (24–56%); ‘to increase emotions’ (13–49%), ‘to talk more’ (18–61%) and to
improve concentration (13–33%).
Some of the apparent variability in reported reasons for use will be attributable to differences in sampling and in
methodology. Not all patients included in these studies actually met the criteria for a substance use disorder; some were
merely substance ‘users’. Some studies required patients to select their reasons for use from predetermined lists whilst
others used free response or open ended questions. Some requested patients to list all of the reasons they used
substances for whilst others requested only the ‘main’ reason. Significantly, none of the studies outlined employed self
report methods with known validity and reliability for this patient group. Additionally, these studies have failed to
examine reasons for use in the context of the known demographic risk factors such as age and gender. Do males report
different reasons for use to females? Are younger patients with schizophrenia more likely to report certain reasons for
substance use? What other factors (both illness-related and demographic) influence self reported reasons for use?
Nevertheless, despite their shortcomings, the evidence from these self report studies provides some support for the self
medication hypothesis, in particular the ‘alleviation of dysphoria’ version of the hypothesis. In the majority of studies,
the most frequently endorsed reasons for use are from this category. Interestingly, some of the studies report that for
some patients, their stated reasons for substance use and their outcome expectancies for the effects of that substance are
incongruous with the actual achieved effect. For example, in Addington and Duchak's (1997) study, participants
reportedusing drugs to increase pleasure, to get high and to reduce depression. However,subjective effectsof increased
depression and positive symptoms were also reported. Some patients may report using drugs and alcohol to make them
feel better yet report feeling worse afterwards.
501L. Gregg et al. / Clinical Psychology Review 27 (2007) 494–510
Self reported reasons for use by substance users with psychosis
AuthorsSampleMethodologyReasons for use
(to get high, to feel good)’
Allness, and Ripp (1989)
27 drug and/or alcohol users with
schizophrenia or schizoaffective
53 drug and/or alcohol users with
schizophrenia, schizoaffective or
55 drug and/or alcohol users with
schizophrenia, schizoaffective or
41 drug and/or alcohol users with
194 drug and/or alcohol users with
Free response and inspection
of a list
Dixon et al. (1991)Questionnaire (‘Stated reasons
scale, SRS’ developed for the study)
Warner et al. (1994)
Interview (adapted from Test et al., 1989)–
Addington and Duchak (1997) Questionnaire (SRS, Dixon et al., 1991)Alcohol (74%)
Fowler, Carr, Carter, and
Gearon, Bellack, Rachbeisel,
and Dixon (2001)
25 drug and alcohol users with
schizophrenia or schizoaffective
Questionnaire (Inventory of Drug Taking
Situations (Annis, Turner, & Sklar, 1997);
‘Self medication questionnaire’ developed
for the study
Interview. Baker et al. (2002)160 drug and/or alcohol using
81%Goswami et al. (2004)22 male drug and alcohol users
45 male cannabis users with
49 cannabis users with psychosis
45 drug and alcohol users with
schizophrenia or schizoaffective
Questionnaire modified SRS
(Dixon et al., 1991)
Telephone interview Green et al. (2004)–
Schofield et al. (2006)
Gregg et al. (submitted
Questionnaire (SRS, Dixon et al., 1991)
AuthorsReasons for use
Social reasons (to facilitate
social interaction/to fit in)
Dysphoria relief (to relieve
boredom; to relax)
Psychotic symptoms (to alleviate/
cope with hallucinations/
feelings of suspicion/paranoia)
Test et al. (1989)
Dixon et al. (1991)
Warner et al. (1994)
Addington and Duchak (1997) Alcohol 56%
Fowler et al. (1998)
Gearon et al. (2001)
Baker et al. (2002)
Goswami et al. (2004)
Green et al. (2004)
Schofield et al. (2006)
Gregg et al. (submitted
⁎These studies combined illness related and medication related reasons for substance use.
502L. Gregg et al. / Clinical Psychology Review 27 (2007) 494–510
5.2.2. Are some people with schizophrenia ‘supersensitive’ to the effects of substances?
An alternative secondary substance use model is the supersensitivity model (Mueser et al., 1998) which
hypothesizes that certain individuals with schizophrenia have biological and psychological vulnerabilities that are a
result of genetic and early environmental effects in their lives: these vulnerabilities can interact with stressful life events
to cause psychiatric disorder. Substance use is believed to increase this vulnerability so that people with schizophrenia
are more likely to experience negative consequences as a result of substance use than people in the general population.
Furthermore, these negative consequences result from lower levels of use than those needed by the general population
(Drake et al., 1989; Drake & Wallach, 1993). In short, these individuals are “supersensitive” to the effects of certain
substances. According to the hypothesis, dually diagnosed individuals should be more likely to be diagnosed with a
substance abuse as opposed to a substance dependence diagnosis and experience greater negative consequences
associated with lower levels of use when compared to substance users without schizophrenia. The first empirical test of
the hypothesis has recently been conducted. Gonzalez, Bradizza, Vincent, Stasiewicz, and Paas (in press) compared 42
individuals with substance use disorder (SUD) to 53 dually diagnosed individuals (DD). Although the DD group had
significantly greater levels of psychological symptoms they did not experience greater negative consequences. Rates of
substance use were comparable between the two groups and the DD group had higher proportions of individuals
meeting substance use dependence criteria.
5.3. Do substance use and psychosis share a common origin?
Common factor models propose that substance use and schizophrenia share a common origin. These common
factors could be biological, individual or social. There is a good deal of evidence to suggest that genetic factors
independently contribute to schizophrenia (e.g. Gottesman & Shields, 1976) and to substance use disorder (e.g. Rhee
et al., 2003; Tsuang, Bar, Harley, & Lyons, 2001) although it is not clear which genes are involved and how genetic
predisposition is transmitted. The extent to which the two disorders share a common genetic vulnerability, however, is
unknown. The main method of assessing the role of genetic factors in the co-development of schizophrenia and
substance use disorder has been to examine family history but the studies that have been conducted to date have been
conflicting. For such a link to be supported studies would be expected to find that patients with schizophrenia have
more relatives with substance use disorders than people in the general population or that people with substance use
disorder would be more likely to have family members with schizophrenia. Whilst some studies have reported that
dually diagnosed patients are more likely to have family members with substance use disorders than patients with
schizophrenia alone (e.g. Noordsy, Drake, Biesanz, & McHugo, 1994) other studies have not found this to be the case
(Gershon et al., 1988). It is possible that genetic vulnerability may contribute to the development of comorbid
substance use in some patients but the available evidence does not appear to support the idea that increased comorbidity
is a result of a common genetic basis for both disorders.
Another common factor that could potentially influence both substance use and schizophrenia is neuropathology i.e.
that the neuropathology of schizophrenia impacts on the neural circuitry mediating drug reward and reinforcement
resulting in an increased vulnerability to addictive behaviour. Put simply, patients with schizophrenia might be
biologically vulnerable to the rewarding effects of drug abuse. The dopamine opioid neurotransmission systems have
been implicated. In these models schizophrenia and substance use are thought to be independent manifestations of the
same disease. (see Chambers et al., 2001 for a review).
These results may actually imply a common underlying vulnerability for both disorders in which the pathology of
the cannabinoid system in schizophrenia patients is associated with both increased rates of cannabis use and increased
risk for schizophrenia (Weiser & Noy, 2005). Further research is needed to determine the relevant underlying
neuropathological processes before firm conclusions can be drawn.
Social and environmental factors that could potentially underpin both disorders have also been hypothesized, for
example family dysfunction (Fergusson, Horwood, & Lynskey, 1994) and economic and social disadvantage. Another
possible mechanism is traumatic early childhood experience. We know that members of the general population who
report physical or sexual abuse in childhood are more likely to abuse substances in adulthood (Kessler, Davis, &
Kendler, 1997) and that for some, childhood abuse can also contribute to psychosis (Briere, Woo, McRae, Foltz, &
Sitzman, 1997). Scheller-Gilkey et al. (2004) compared 70 patients with schizophrenia and a history of substance abuse
with 52 patients without a history of substance abuse and found that the former had significantly higher scores on a
measure of childhood traumatic events and on a PTSD scale. The available evidence suggests that the relationship may
503 L. Gregg et al. / Clinical Psychology Review 27 (2007) 494–510
be bidirectional: PTSD precedes the onset of substance use in some people with schizophrenia but may also put people
with schizophrenia at increased risk of subsequent retraumatisation. Mueser et al. (1998) present evidence suggesting
that ASPD and its childhood correlate conduct disorder might be a common factor. Studies have shown that patients
with schizophrenia and antisocial personality disorder (ASPD) are more likely to have comorbid substance use disorder
than patients without ASPD (Caton et al., 1994; Mueser et al., 2000) and for patients with schizophrenia and substance
use disorder ASPD is associated with a more severe course of substance use disorder including earlier age of onset and
larger quantities of substance use (Mueser, Drake et al., 1997).
Impairments in cognitive functioning have also been hypothesized to have an impact (Tracy, Josiassen, & Bellack,
1995), as have poorer coping skills, lower educational attainment, lower socioeconomic status, poor interpersonal and
socialproblem solvingskills.Itmustbenotedthatitisunlikely thatanyofthese cognitiveandsocialriskfactorsoperate
independently to increase rates of comorbidity but their cumulative effects might. Few multiple risk factor models have
been proposed but the cross sectional literature does seem to suggest that some of these factors may play a part.
5.4. Do psychosis and substance use interact and maintain each other?
Bidirectional models propose that psychosis and substance use problems may both trigger and maintain each other.
For example, substance use may serve as a stressor precipitating onset of schizophrenia in vulnerable individuals and
mental health problems are then subsequently maintained by continued substance use due to socially learned cognitive
factors such as beliefs, expectancies and motives for substance use (Mueser et al., 1998). Thus bidirectional models
tend to involve multiple risk factors but although a variety of different models have been proposed there have been no
5.4.1. Multiple risk factor models
Blanchard et al. (2000) proposed an affect regulation model of substance which in common with the self medication
literature suggests that patients with schizophrenia use drugs and alcohol to cope with negative emotions and problems.
The proposed model emphasizes the role of enduring personality characteristics stating that stable personality traits,
stress and coping are the factors underlying long term risk for substance use. Aspects of this model find some support in
the literature: the self report literature shows that people with schizophrenia report using substances to regulate negative
affects such as dysphoria and anxiety and a handful of empirical studies have shown that substance use is related to
Barrowclough et al. (2007) propose a model of substance use maintenance in psychosis which incorporates the key
features of Marlatt and Gordon's social-cognitive model of addiction (Marlatt & Gordon, 1985). The model proposes
that certain situations and cues trigger drug or alcohol related thoughts which in the absence of alternative coping
strategies and in the context of low self efficacy for resisting use and positive expectancies from use make the person
vulnerable and more likely to use substances. This interaction between situations and cognitive/emotional reactions
becomes the basis of a repeated cycle which maintains drug or alcohol use. As the self report literature outlined above
shows, people with schizophrenia indicate that situations and cues triggering use may be related to psychotic symptoms
and to the negative consequences of the disorder, particularly dysphoria and distress.
Studies have shown that people with schizophrenia often experience difficulty in coping with stresses (Corrigan &
Toomey, 1995; Mueser, Drake et al., 1997; Mueser, Valentiner, & Agresta, 1997) and that they may possess a relatively
limited repertoire of coping strategies (Rollins, Bond, & Lysaker, 1999). A number of studies have investigated coping
in relation to psychotic symptoms (e.g. Falloon & Talbot, 1981; Kinney, 1999; Lobban, Barrowclough, & Jones, 2004),
affective symptoms (e.g. Brier & Strauss, 1983) and negative symptoms (e.g. Mueser, Drake et al., 1997; Rollins et al.,
1999) in patients with schizophrenia. Such studies have highlighted that individuals with schizophrenia use a diverse
range of strategies to influence symptoms. People with schizophrenia use mainly avoidant coping strategies and tend to
have a greater array of coping strategies for positive symptoms than for negative symptoms (Rollins et al., 1999). From
the perspective of social learning theory (e.g. Bandura, 1977) both drug and alcohol use are seen as habitual
maladaptive coping responses employed by people who hold positive beliefs about the effects of that substance,
coupled with inefficient coping resources (Abrams & Niaura 1987). According to this perspective, deficiencies in
general coping skills and positive expectancies about the effects of drug and alcohol operate independently and jointly
to contribute to the use of drugs or alcohol as a coping mechanism. Substance use could be viewed as a general coping
mechanism invoked in situations where more appropriate coping responses are either unused or not available. Social
504 L. Gregg et al. / Clinical Psychology Review 27 (2007) 494–510
learning theory assumes that the coping functions of a substance are learned through initial exposure to that substance
and in subsequent use in different situations, hence the salience of particular functions should show considerable
variation across individuals (Wills & Hirky, 1996).
6. Summary and conclusions
We have presented a review of the main models that have been proposed to explain the etiological relationship
between substance use and psychosis. Although these four models have no doubt served to clarify our understanding of
the reasons for substance use by people with schizophrenia, it is clear that no single model is able to adequately explain
all comorbidity. The hypothesis that substance use causes schizophrenia is not supported sufficiently or consistently.
Evidence from recent prospective cohort studies suggests that cannabis can have a causal role in the development of
psychopathology and studies involving psychosis prone individuals indicate that cannabis use might precipitate
psychosis among vulnerable individuals but there is little evidence to suggest that other substances, including alcohol,
are a causative factor in psychosis. The literature provides little support for the self-medication hypothesis in its original
formulation i.e. that specific substances are chosen for their specific pharmacological properties. The self report studies
do show that some people with schizophrenia report using substances in an attempt to alleviate specific
psychopathological symptoms or medication side effects but there has been little research to show whether substances
are selected differentially. There is greater support for an ‘alleviation of dysphoria’ model of comorbidity than
Khantzian's (1985) original self medication formulation: patients report using substances to alleviate or to cope with
unpleasant affective states (e.g. boredom, depression, anxiety and loneliness). Common factor models have implicated
both genetics and neuropathology but no common gene has yet been identified and the neurobiological evidence is not
consistent. Additional research is required. It may even be the case that some other as yet unresearched variable or
variables may account for the relationship between substance use and schizophrenia.
It is likely that there are multiple risk factors involved in substance use in psychosis. We know that a number of
demographic factors (such as age, gender and socioeconomic status) and contextual factors (such as family history
of substance use) predict substance use in schizophrenia. Social networks, quality of living environment, poverty
and stressful life events influence substance use as do individual differences in personality, coping, interpersonal
skills and social functioning but the extent to which these explain increased comorbidity is not known: there are
few well developed multiple risk factors models. More work to develop and test multiple risk factor models is
Bidirectional models integrating aspects of the different causative models outlined in this review suggest that
separate factors may be responsible for the initiation and maintenance of substance use by people with schizophrenia. It
is possible, for example, that substance users whose drug use precipitated or caused their schizophrenia (perhaps
because of biological vulnerability) may continue using cannabis in order to alleviate or cope with the symptoms of
schizophrenia better. As yet, however, there have been no empirical investigations of bidirectional models.
Longitudinal prospective cohort studies would be ideally placed to identify the factors related to the development and
maintenance of substance use and psychosis and the factors which mediate and moderate the paths between the two.
Such studies would also allow for the causal hypotheses to be tested. The existing longitudinal research is constrained
by a failure to assess the predictive impact of substances other than cannabis on psychosis and has largely ignored the
relationships between current symptomatology, substance use and other potential risk factors.
The dually diagnosed population is a heterogeneous group and as Mueser et al. (1998) suggest, it is likely that
different models may account for comorbidity in different groups of people and multiple models may apply for some
individuals. The challenge now it is to identify which models apply to which people if we are to be able to develop
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