Ouanouche 

et al. Middle East Current

Middle East Current Psychiatry (2022) 29:12
https://doi.org/10.1186/s43045-022-00173-5 Psychiatry

RESEARCH Open Access

Cannabis and schizophrenia:
characterisation of a risk factor in a sample
of Moroccan patients hospitalised for psychosis
El Hassan Ouanouche1*  , Hicham Elmostafi1, Naoufal Amarat1, Ouahid Wafaa2, Tamouza Ryad3,
Aboubaker El Hessni1 and Abdelhalem Mesfioui1 

Abstract 
Background:  In addition to the biological plausibility widely described through a very large number of studies, the
causal link between cannabis uses and schizophrenia disorders has become illicit internationally and given the scar-
city of similar studies in Morocco. Our study consists of a prospective descriptive study in the psychiatric department
of the Moulay ben Abdallah Hospital in Essaouira. The sample consisted of 95 patients diagnosed with schizophrenia
according to the DSM5 criteria. The diagnostic assessment included the Positive and Negative Syndrome Scale to
assess the severity of positive and negative symptoms of schizophrenia as well as the patient’s general psychopathol-
ogy, the Clinician-Rated Dimensions of Psychosis Symptom Severity to assess the symptom severity of the psychotic
dimensions according, and the Cannabis Abuse Screening Test to assess the extent of cannabis use.
Results:  The mean age of the patients recruited in the study was 33.7 ± 9.37 years with a clear male predominance
(p < 0.0001). Cannabis users compared to non-users were younger and comprised only men. Cannabis users also have
a lower educational and economic level than non-users. Furthermore, a clear dose effect of cannabis uses on the
onset of positive and negative symptoms of schizophrenia. The temporality criterion is clear in our study, since the
predictivity of the parameter: “age of onset of cannabis use” is highly significant (p = 0.000). These results suggest that
cannabis use can be considered as the most illicit risk factor for the development and/or onset of schizophrenia.
Conclusions:  These results suggest that there is a causal relationship between cannabis use and/or dependence
(problematic use) and the onset and/or worsening of schizophrenic disorder. This means that problematic cannabis
use can be considered as a real risk factor for the emergence and development of schizophrenic disorder.
Keywords:  Addiction, Cannabis users, Schizophrenia, Disorder and predictivity

Background large-scale studies, the Epidemiologic Catchment Anea

Whether it is occasional use or dependence, the asso- (ECA) survey published in 1990, estimated that this
ciation between problematic cannabis use and schizo- comorbidity affected 47% of people with schizophrenia,
phrenia is the rule rather than the exception. Indeed, compared to 13.5% in the general population, and more
epidemiological studies have confirmed for the last than half of people with schizophrenia have a history of
twenty years that addictive comorbidities in schizo- substance abuse [3]. In a cohort of 45,570 Swedes, Ander-
phrenia concern most patients [1, 2]. One of the first son 1987 et  al. showed that increased cannabis use was
associated with a sixfold increased risk (OR = 6.09; 95%
CI 4.0–8.9) of developing schizophrenia [4]. This asso-
*Correspondence: elhassanouanouche@gmail.com
1
Biology and Health Laboratory, Department of Biology, Faculty ciation between the development of schizophrenia and
of Sciences, University Ibn Tofail, FSK, Kenitra, Morocco cannabis use is dose-dependent [5]. In 2002, in a 6-year
Full list of author information is available at the end of the article prospective study of 14–15-year-old students, Patton

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Ouanouche et al. Middle East Current Psychiatry (2022) 29:12 Page 2 of 8

et al. showed that daily cannabis use increased the risk of [15] has stated that it wants to change the situation by
developing anxiety-depressive mood disorders (negative announcing that the mental health sector will be a prior-
schizophrenia disorders) by five times (OR = 5.6; 95% CI: ity of the Moroccan government to better respond to the
2.6–12). This risk is only twice as high for weekly users expectations of patients and their families. In Morocco,
[6]. This would suggest that these are predisposed indi- few studies have focused on the co-morbidities between
viduals with a certain vulnerability to mood disorders, the use of active substances such as cannabis and schizo-
where cannabis use is the triggering factor [7]. phrenia; indeed, a study done in the hospital of the city of
Several factors have been identified to explain the Fez showed that the prevalence of substance use is 60.2%
mechanisms of this high comorbidity. The hypothesis including cannabis and that early identification of risk
of a common genetic vulnerability to both disorders has factors for substance use in patients with schizophrenia
been proposed. This is supported by the observation of a could improve the prognosis of patients by reducing the
shared heredity; on the one hand, a high rate of addiction number of relapses and promote adherence to care [16].
problems in non-psychotic relatives of schizophrenic Given the lack of official data on addictive comorbidi-
patients and on the other hand a high rate of schizo- ties in schizophrenic patients and the scarcity of stud-
phrenia in relatives of addicted patients [8]. Many social ies on this subject, our study aims firstly to draw up a
and economic factors are also shared by addicted and socioeconomic profile of schizophrenic patients in the
psychotic patients (precariousness, isolation, accultura- study area and secondly to assess the role of cannabis as
tion, etc.) [9]. Psychological vulnerability is the subject a “risk factor” in the development of schizophrenic disor-
of numerous studies on the links between schizophrenia der or the emergence of psychotic symptoms related to
and cannabis. Early cannabis use considerably increases schizophrenia.
the risk of schizophrenia. The risk is four times higher
when use begins before the age of 1 5[10], suggesting the Methods
need to consider the developmental dimension in inter- Type of study
action with the genetic and environmental mechanisms This is a prospective study of two groups of schizo-
involved in vulnerability to schizophrenia. Cannabis use phrenic patients hospitalised at the Moulay ben Abdallah
at age 16 increases the risk of emergence of psychosis Hospital in Essaouira (HMBAE): a group that had never
at age 19 and, conversely, the emergence of psychosis at used cannabis and another that had used it.
age 16 predicts cannabis use at age 19 [11]. Certain cog-
nitive and affective disturbances could be predictive of Recruitment of the sample
later psychotic and addictive pathologies [12]. Unfortu- The sample of participants was exhaustive including all
nately, follow-up studies show the stability of addictive patients with schizophrenia according to the diagnostic
behaviours acquired during adolescence in patients suf- criteria of the fifth version of the Diagnostic and Statis-
fering from schizophrenia, which may explain the switch tical Manual of Mental Disorders DSM-5, consecutively
to other products, particularly alcohol, which is easier to admitted to the psychiatry department of the HMBAE
access than cannabis. over a period of 12 months (between 1 January and 31
In Morocco, the national survey on the prevalence of December 2017) for psychotic break. Data collection
mental disorders in the general population aged 15 years is done in the morning to ensure the presence of the
and over (ENPTM, 2003–2006) revealed that 5.6% suf- head doctor and nurses, and patients are calmer in the
fer from psychotic disorders and that more than 200,000 morning and can interact well with the proposed scale
Moroccans aged 15 years and over suffer from schizo- questionnaires.
phrenia [13], which is 0.5% in a recent study conducted The data were collected using an anonymous self-
by our laboratory in a town in Taza (eastern Morocco) administered questionnaire distributed to the depart-
with 1.5% drug addiction in a sample of 3803 patients ment and the CMS by the investigators (2 nurses from
[14]. On the other hand, the Mediterranean survey on the psychiatry department of the Moulay Mohamed ben
the use of alcohol and other drugs in schools [15], con- abdallâh Hospital in Essaouira, given their experience
ducted on 7000 Moroccan students, found that 9.0% of with schizophrenic patients). For each patient, we filled
15–17-year-olds use cannabis. In the general population, in an exploitation form and the questionnaires evaluating
cannabis is the most used drug (3.94%) after tobacco. In the severity of the psychiatric disorders were filled in and
Morocco, a study dealing with this comorbidity in a sam- questioned by our team.
ple of 106 schizophrenic patients showed that 9.4% of The study exclusion criteria for both groups were the
patients were dependent on cannabis [14]. In addition, presence of a confusional state, dementia, or age less than
the psychiatric sector is a public health problem, and the 18 years or more than 80 years; the final sample size was
Moroccan Ministry of Health in its “Health Plan 2025” 95 patients.
 Ouanouche et al. Middle East Current Psychiatry (2022) 29:12 Page 3 of 8

Study variables cannabis use patterns of the users were calculated and
The diagnostic assessment included the Positive and reported in terms of means and proportions. The analyti-
Negative Syndrome Scale (PANSS) to assess the severity cal study used Student’s t test for the comparison of con-
of positive and negative symptoms of schizophrenia as tinuous variables between the user and non-user groups,
well as the patient’s general psychopathology, the Clini- and the chi-squared test for categorical variables. A cor-
cian-Rated Dimensions of Psychosis Symptom Severity rection by the Fisher exact method was made for cat-
(CRDPSS) to assess the symptom severity of the psy- egorical variables with small numbers. The multivariate
chotic dimensions according to DSM V criteria, and the analysis was based on logistic regression of cannabis use
Cannabis Abuse Screening Test (CAST) to assess the parameters potentially predictive of schizophrenic disor-
extent of cannabis use. der. ORs with 95% confidence intervals (CIs) and p-val-
On the other hand, patients admitted to the psychiat- ues were reported for each predictor. A p-value < 0.05
ric department of the HMBAE during the same period was considered significant. The analysis was performed
for substance use disorders and with a history of canna- on the SPSS 20 software.
bis use were interviewed for an underlying schizophrenic
disorder. Results
The comparison between the results of cannabis users Over a 12-month period, we recruited 95 schizophrenic
and non-users was carried out on the following elements: patients, 69 of whom had a history of cannabis use. Of
these 69 patients, 21 were admitted for substance use dis-
– Socio-demographic parameters: age, gender, place of orders and were included in the study after a diagnosis
residence, economic level, education level of schizophrenia. Twenty-three patients approached by
– Quality of social adjustment: occupation, marital sta- the evaluators could not be included in the study due to
tus lack of criteria for schizophrenic disorder or refusal to
– Family and personal history: behavioural disor- participate.
ders, suicidal threat, addictive behaviour, psychotic
relapse, somatic complaints, delusions, anxiety, and Socio‑demographic characteristics
sudden mutism The average age of the 95 schizophrenic patients included
– Clinical: symptoms of schizophrenia according to in the study was 33.7 ± 9.37 years with a clear male pre-
DSM-5, age at diagnosis of the disease; duration and dominance (Table  1). Cannabis users compared to non-
number of hospital admissions users were younger and comprised only men. Cannabis
– Use of other psychoactive substances (PAS), includ- users also have a lower level of education and a lower
ing psychotropic drugs economic level than non-users. On the other hand, we
– Cannabis use: amount consumed in number of joints did not find any significant difference between the two
(unit) per use, frequency of use (once/day; once/ groups concerning the place of residence and marital
week; once/2 weeks; once/month; < once/month), status.
date of start and stop of use
Characteristics of cannabis users
Seventy-two out of one hundred patients admitted to the
Data collection study had used cannabis at least once in their lifetime
Data collection was carried out under the guidance of a (Table  2). Of these, 55.1% were still using. The average
medical specialist and two experienced nurses using two age of onset of use was 14.4 years. The average frequency
methods, a chart review coupled with an interview with of use was 13.9 times/month, and the average number
the same patient and a closed questionnaire targeting the of joints smoked per use was 3.3 joints. Patients had a
risk factors sought. Data collection was carried out with mean CAST score of 12.4 (SD = 7.9). Among the canna-
respect to anonymity and confidentiality. All included bis users, 43.4%, 23.1%, and 5.7% were at high, medium,
patients were informed about the principles and objec- and low risk for cannabis addiction, respectively. About
tives of the study and gave their consent to participate. 74% of cannabis users used at least one other substance
The data was collected by our team and the nurses either of abuse. Among these substances, tobacco (86%), kif
through direct contact with the patients or from informa- (75%), maâjoun (street drug) (53%), and alcohol (47%) are
tion in their medical records the most common among cannabis users.
A multivariate analysis of demographic variables pre-
Statistical analysis dictive of cannabis use was conducted. Male gender, low
Descriptive statistics regarding the demographic and education level, and young age were more associated
clinical characteristics of the participants and the with cannabis use than female gender, high education
Ouanouche et al. Middle East Current Psychiatry (2022) 29:12 Page 4 of 8

Table 1 
Comparison of sociodemographic characteristics Table 2  Characteristics of cannabis users
between cannabis users and non-users
Average (DS)
Non-users of Cannabis users P Age of onset (years) 14.4 (5.3)
cannabis
Age of cessation (years,n = 31) 32.1 (3.4)
Gender,n(%) < 0.0001 Consumption period (years) 13.5 (5.8)
  Male 21 (80.7) 69 (100) Frequency of consumption (/month) 15.1 (13.9)
  Woman 5 (19.2) 0 (0) Number of joints per episode 3.3 (4.5)
Economic level,n(%) 0.0052 CAST score 12.4 (7.9)
  Top 2 (7.6) 4 (5.7) n (%)
  Medium 16 (61.5) 28 (40.5) Current cannabis user 38 (55.1)
  Bottom 8 (30.7) 37 (53.6) Cannabis addiction (CAST score > 7) 45 (65.2)
Residence,n(%) 0.3201 Consumption of other PPS 51 (73.9)
  Urban 14 (53.8) 42 (60.8)   Tobacco 60 (86.9)
  Rural 12 (46.1) 27 (39.1)   Kif 52 (75.3)
Marital status,n(%) 0.6203   Maâjoun (street product) 37 (53.6)
  Single 16 (61.5) 37 (53.6)   Organic solvents 18 (26.0)
  Married 8 (30.7) 20 (28.9)   Alcohol 33 (47.8)
  Divorced 2 (7.6) 12 (17.3)   Psychotropic drugs 17 (24.6)
Level of education,n(%) 0.0121   Cocaine 7 (10.1)
  Illiterate 2 (7.6) 28 (40.5)   Other 6 (8.6)
  Primary 3 (11.5) 18 (26.1) Total,n(%) 69 (100.0)
  College 6 (23.1) 15 (21.7) Psychotropic drugs: sedatives, hallucinogens, stimulants, benzhexol
  Secondary 10 (38.4) 8 (11.5) (Trihexyphenidyl), gamma hydroxybutyrate (GHB)
  Academic 5 (19.2) 0 (0) SD Standard deviation, SPA Psychoactive substance
Age, average (SD) 41 (10.6) 32.6 (8.2) 0.0012
Total,n(%) 26 (27.3) 69 (72.6) 0.0023 The multiple linear regression study revealed a strong
SD Standard deviation, p p-value interdependent relationship between the different
variables and the onset of schizophrenia symptoms as
evidenced by the PANSS score; age of onset and fre-
level, and older age. There was also a linear relationship quency of cannabis use were highly associated with the
between education level and cannabis use. emergence of schizophrenic disorder (***p  = 0.000 and
**p = 0.001 respectively). The same was true for the rest
Characteristics of schizophrenic disorder of the parameters studied.
The mean age at diagnosis of schizophrenic disorder
among the total population was 25.8 years, and the mean
Dose‑effect relationship
number of previous hospitalisations was 4.4 hospitali-
Our study shows the existence of a dose-effect relation-
sations or 0.5 hospitalisations per year since diagnosis
ship between the frequency of cannabis use and the onset
of the disorder (Table  3). Cannabis users compared to
of schizophrenic disorder in our patients. Indeed, this
non-users started their disorder at a younger age (21.2
risk is 2.5 times higher if the CAST score is higher than 7
vs 30.5 years; p = 0.0026). They had more previous hos-
as shown in Fig. 1.
pitalisations (4.3 vs 3.7; NS). In total, 67% of the schizo-
The dose effect also seems to be very clear in our study;
phrenic patients included in the study were hospitalised
Fig. 2 shows that the PANSS score increases considerably
for a manic episode, 2% for a hypomanic episode, 23% for
if the dose of cannabis use is high; indeed, it increases
a major depressive episode, and 8% for substance abuse
from 51 to 185 when the frequency of use increases from
intoxication. Of the admissions for major depressive epi-
once a month to several times a day (Fig. 2).
sode, 73.9% of the patients were female.

Predictors of schizophrenia Discussion

Multiple regression analysis was performed to identify The rush of governments to exploit the positive effects
predictors of schizophrenic disorders among the col- of cannabis should not hide the reality that cannabis
lected data (Table 4: only significant **p < 0.05 or highly appears to be a risk factor for many diseases other than
significant ***p < 0.001). psychiatric ones. This study shows some relationship
 Ouanouche et al. Middle East Current Psychiatry (2022) 29:12 Page 5 of 8

Table 3  Clinical characteristics of schizophrenia and psychiatric history in cannabis users and non-users
Non-users of cannabis Cannabis users P

Age at diagnosis, mean (SD) 30.5 (6.8) 21.2 (9,3) 0.0026

History of hospitalisation, n (%) 16 (61.5) 46 (66.6) 0.5033
  Annual hospitalisations
  Average number (DS) 3.7 (2.5) 4.3 (3.3) 0.6701
  Average duration (days ± SD) 31.6 (7.8) 29.2 (6.0) 0.5428
  Reasons for hospitalisation, n (%) 0.1037
  Behavioural problems 17 (65.3) 31 (44.9)
  Suicidal threat 0 (0) 7 (10.1)
  Addictive behaviour 3 (11.5) 16 (23.1)
  Psychotic relapse 20 (76.9) 58 (84.0)
  Other 10 (38.4) 25 (36.2)
Family history, n (%)
  PANSS score, average (DS)
  Positive scale 18 (4.3) 39 (6.6)
  Negative scale 29 (7.8) 41 (8.0)
  General psychopathology scale 67 (12.6) 102 (13.1)
  Total score (/210) 104 (8.2) 181 (15.4) 0.0001
  CRDPSS score, average (SD)
  Hallucinations 1 (0.0) 3 (1.6)
  Delusional ideas 0 (0.0) 2 (0.7)
  Disorganised speech 1 (1.2) 4 (0.0)
  Abnormal psychomotor behaviour 2 (0.3) 3 (1.2)
  Negative symptoms 2 (1.3) 3 (1.3)
  Cognitive deficit 1 (0.8) 2 (0.8)
  Depression 2 (1.6) 4 (0.6)
  Mania 1 (1.2) 3 (1.2)
  Total score (/32) 10 (3.4) 25 (4.7) 0.0021
Under the term “Other,” we have grouped the reasons: somatic complaints, delusions, anxiety, and sudden mutism
SD Standard deviation

Table 4  Summary of the regression of the variable “total score in PANSS” (R2 = 0.82; F = 7.03; p = 0.000)
Independent variables BETA BETA standard error t P

Smoked cannabis alone 0.53 0.06 5.09 0.000

Tobacco consumption 0.80 0.23 6.13 0.000
Frequency of tobacco use 0.42 0.12 3.43 0.001
Age of onset of cannabis use − 0.91 0.15 − 4.74 0.000
Often smoked cannabis alone 0.91 0.39 7.20 0.000
Perception of risk related to tobacco and cannabis use 0.15 0.21 2.13 0.039
Representations of the unpleasant psychological effects and physi‑ − 0.32 0.65 − 3.85 0.000
cal risks of cannabis
Representations of positive school effects of cannabis 0.37 0.19 2.53 0.016
Representations of dependency 0.47 0.72 5.31 0.000
Cannabis dependence − 0.45 0.09 − 3.59 0.001
R2 Multiple correlation coefficient, F F-statistic
Ouanouche et al. Middle East Current Psychiatry (2022) 29:12 Page 6 of 8

Fig. 1  Dose-effect relationship between frequency of cannabis use and PANSS Total score

Fig. 2  Dose-effect relationship between cannabis dependence (CAST score) and PANSS total score
 Ouanouche et al. Middle East Current Psychiatry (2022) 29:12 Page 7 of 8

between cannabis use and the emergence and develop- as the predictivity of the parameter: “age of onset of can-
ment of schizophrenic disorders. nabis use” is highly significant (p = 0.000), which means
Our sample comprises a young population with an that there is probably a causal relationship between can-
average age of 33.7 ± 9.37 years. Therefore, negative pub- nabis use and the onset of schizophrenia, that is, expo-
lic opinion can have serious consequences on them and sure to cannabis use precedes the emergence of the
their families; it prevents social integration, interferes schizophrenic disorder. According to a study in France
with the performance of social roles, and reduces expec- [27] cannabis use is a risk factor, with two consistent
tations and quality of life. These factors can be major bar- data: a high level of use and an age of use below 15 years.
riers to recovery, impact on long-term prognosis, and Still in France in 2014, another study of patients suffer-
lead to disability [17]. It is also noted that the percent- ing from schizophrenia in hospital found a prevalence
age of single people is higher, which is probably due to of cannabis use of 33.6%, 88% of whom were dependent
the socio-cultural context, where the man often has the patients [26]. In other studies, the effect of reciprocal
financial responsibility for his family. Consequently, the reinforcement of the pathology and the use of cannabis
repercussions of stigmatisation such as lack of work and is still accepted [27]. This reproducibility of results indi-
lack of housing limit the resources of these subjects and cates a possible causal relationship between cannabis use
hinder their autonomy [18]. Finding a job in these condi- and the onset of schizophrenia.
tions is often difficult, and they are considered less intel-
ligent, with limited abilities, or simply unable to carry out Conclusions
the tasks assigned to them. These results are confirmed The link between substance abuse and the emergence of
by the literature [19]; in Spain, 95% of the general pop- psychotic disorders has become illicit, particularly for
ulation and 69% of the families of patients think they schizophrenia, which now represents a heavy burden
cannot study, 33% think they have limited abilities, and internationally as well as nationally.
81.1% of employers in Germany would not hire a former Our study aims to add to the scientific repertoire and to
psychiatric patient. Thus, the working life of patients is further explore the existence of causal links (or risk fac-
affected, not only by the nature of the disorder, but above tors) between cannabis use and the emergence and devel-
all by the prejudices and the fragility of the social support opment of schizophrenia. Our results show that:
it encounters, which are all barriers to the integration
and development of patients [20]. The rate of urbanicity – The strength of the relationships revealed by the
found in both groups is quite high, which is consistent study of the prediction of the parameters studied is
with the result of the national survey [21]. The work of quite significant
Penn et al. [22] on 20 populations showed the dominance – Temporality, which suggests the importance of age at
of psychiatric disorders in urban settings. In addition, a onset of cannabis use
study conducted in rural and urban Canada concluded – The frequency of use which indicates a clear dose-
that urban origin was a risk factor for psychiatric disor- effect relationship
ders. This study implicated the lack of social support in – The reproducibility of the results proved by a multi-
urban settings as opposed to rural settings [23]. tude of studies having given similar results
The interrelationships revealed by our study suggest that
the risk of emergence of schizophrenic symptomology These results suggest that there is a causal relationship
increases with several parameters related to cannabis use, between cannabis use and/or dependence (problematic
(age and history of use, duration, ...). Indeed, this risk is 2.5 use) and the onset and/or worsening of schizophrenic
times higher if the CAST score is higher than 7 as shown disorder. This means that problematic cannabis use can
in Fig. 1; the same result was found by another study [24]. be considered as a real risk factor for the emergence and
The dose effect also seems very clear in our study; Fig. 2 development of schizophrenic disorder. On the other
shows that the PANSS score increases considerably if the hand, our results recommend more vigilance towards the
dose of cannabis use is high; indeed, it increases from 51 exploitation of the positive effects of cannabis and to give
to 185 when the frequency of use increases from once a the necessary importance to the careful practice of this
month to several times a day (Fig. 2). This result is sup- substance in pharmaceutical fields.
ported by the result of a pioneering study in 2004 by DC
Abbreviations
D’Souza et al. [25], showing a clear dose effect of canna- DSM-5: Diagnostic and Statistical Manual of Mental Disorders; HMBA: Hospi-
bis use on the onset of positive and negative symptoms of talised at the Moulay ben Abdallah Hospital in Essaouira; PANSS: The Positive
schizophrenia [26], in a population of non-schizophrenic and Negative Syndrome Scale; CRDPSS: The Clinician-Rated Dimensions of
Psychosis Symptom Severity; CAST: The Cannabis Abuse Screening Test.
volunteers. The temporality criterion is clear in our study,
Ouanouche et al. Middle East Current Psychiatry (2022) 29:12 Page 8 of 8

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