Introduction: According to the literature, early initiation to cannabis use and a dependent pattern of use are important risk factors for the development of mental health disorders. However, there are few cohort studies which look at the development of mental health disorders associated with cannabis use among young people with cannabis use disorder (CUD). The aim of the study was to determine the cumulative incidence of mental health disorders and the risk of developing mental health disorders among minors who commenced treatment for CUD in Catalonia during 2015–2019. Methods: This was a retrospective fixed cohort study, matched for confounding variables, based on data from the Catalan Health Surveillance System. The exposed cohort comprised young people who entered treatment for CUD during 2015–2019 (n = 948) and who were minors on the date of commencing treatment. Matching was done with a paired cohort (n = 4,737), according to confounding variables. Individuals with a diagnosis of a mental health disorder prior to the study period were excluded. The cumulative incidence was calculated for mental health disorders for the exposed and the paired cohorts and stratified by type of mental disorder. Incidence rate ratios were estimated using the conditional Poisson model with robust variance, stratified by sex. Results: The cumulative incidence for development of a mental health disorder was 19.6% in the exposed cohort and 3.1% in the paired cohort; with higher incidence among females (females 32.7%; males 15.8%). The exposed cohort had an 8.7 times increased risk of developing a mental health disorder than the paired cohort. The most frequent diagnoses were reaction to severe stress, adjustment disorder, and personality disorders. Conclusion: This study confirmed that the exposed cohort was at increased risk of developing mental health disorders compared to the paired cohort. To date, few studies have analyzed the association between cannabis use and the development of mental health disorders, considering cannabis dependence. Further studies should be undertaken considering CUD. In addition, more studies are needed to understand the factors that determine the development of CUD. Further research in these areas would contribute to the design of prevention strategies aimed at those young individuals with a higher risk of developing cannabis dependence and suffering its consequences.

Cannabis is the most consumed illicit drug in the world, with particularly high rates of use among adolescents [1]. The European Drug Report 2020 showed that approximately 15% of young people aged between 15 and 34 years used cannabis in the past year [2]. In Catalonia, according to the 2018 Spanish Survey on Drug Use in High Schools, cannabis is the most consumed illegal drug among 14- to 18-year-old students. The survey found that 39.4% of this population had used cannabis at least once in their life, 23.1% reported using cannabis in the month prior to the survey, and 4% showed risky cannabis use according to the cannabis abuse screening test [3]. Furthermore, in 2020, cannabis was the main substance of use in 94.7% of admissions to treatment for substance use disorders in minors in Catalonia [4].

Scientific evidence supports a relationship between drug use and mental health disorders, especially among adolescents and young adults [5, 6]. The risks of developing mental disorders among cannabis users are associated with genetic predisposition [7], higher frequency of use, and initiation to use at a young age [8]. Adolescence is a stage of neural and cerebral development. Therefore, young cannabis users could be more vulnerable to the effects of tetrahydrocannabinol, the principal active ingredient in cannabis [9, 10]. Early initiation to cannabis use and regular use are predictors of greater risk of dependency and of developing mental health disorders such as psychosis, mood disorders, and antisocial behaviors [8‒11].

Regarding the association between cannabis use and mental disorders, the association with psychotic disorders has been the most studied, with high rates of cannabis use disorder (CUD) seen among people experiencing a first psychotic episode. Substance use disorders are observed in 20–60% of people experiencing psychotic episodes, with CUD being the most common [12]. In addition, numerous studies suggest a temporal association between age at initiation to cannabis use and age of onset of psychotic illness [13, 14]. The association between cannabis use and affective disorders is less consistent [15‒18]. However, various studies support an association between cannabis use and depression [19], highlighting age of initiation to use as a risk factor, observing a greater association among females [20, 21]. Bipolar and personality disorders may also be associated with cannabis use, although the evidence is less consistent [22]. Regarding the association between cannabis use and attention-deficit hyperactivity disorder (ADHD), the evidence is even less consistent. Some prospective studies have shown that use of cannabis increased the risk of developing ADHD in adulthood [23, 24]. However, the evidence is not as strong. Regarding risk of starting cannabis use, numerous studies suggest that having a mental health disorder, especially externalizing disorders, is a risk factor for starting cannabis use and for ongoing use [25, 26].

To date, most research is derived from general population studies and does not analyze the differences between frequent cannabis users with and without dependence. Therefore, dependent frequent users could have magnified the observed association between cannabis use and the development of mental health disorders. According to the literature, those who use cannabis differ from the general population in terms of sex, age, nationality, education, employment status, and experience of childhood adversity. However, those differences have not been found between dependent and nondependent cannabis users. In the literature which does consider frequent and dependent use, frequent users have been found to be at higher risk for any mental disorder than the general population and dependent users have been found to have higher rates of mental disorders than nondependent users [27].

Therefore, early cannabis use and a dependent pattern of use are important risk factors in the development of mental health disorders. However, there are few cohort studies which look at the development of mental health disorders associated with cannabis use among young people with CUD.

In Catalonia, cannabis accounts for more than 90% of treatment initiations for substance use disorders in minors [4].Therefore, the objective of this study was to estimate the incidence of mental health disorders and the risk of developing these, after initiation to cannabis use, in minors who sought treatment for CUD in Catalan Drug Dependence Centres (CAS) during 2015–2019.

This was a retrospective fixed cohort study, paired for the following confounding variables: age, sex, socioeconomic level, and degree of urbanization of the place of residence (e.g., mountains, rural, semi-urban, urban) [5, 25].

Study Population

The exposed cohort was selected from the Catalan Information System on Drug Dependence (SIDC). It comprised individuals under 18 years who commenced treatment for CUD during 2015–2019, in Catalonia’s CAS (n = 1,448). Those with a mental health diagnosis prior to initiation of cannabis use were excluded (n = 500). Therefore, the final exposed cohort was comprised of 948 individuals.

The paired cohort was identified from the Central Register of Insured Persons (RCA). This cohort was paired by the following confounding variables: year of birth, socioeconomic level, and degree of urbanization of their residence. The paired cohorts were first paired using a ratio of 1:8. Following exclusion of those with a mental health condition diagnosed prior to the study period, 5 people were randomly selected for each exposed person. The final paired cohort comprised 4,737 people. Therefore, there were 946 matchings using a ratio of 1:5, one matching with a ratio of 1:4, and one with a ratio of 1:3 (Fig. 1). The exposed person’s year of initiation to cannabis use was assigned as the beginning of the study period.

Fig. 1.

Cohort selection flowchart.

Fig. 1.

Cohort selection flowchart.

Close modal

Data Set

Study data were obtained from three sources. First, the SIDC database; from this, we obtained data related to the sex and age of individuals who commenced treatment for CUD; age at first use of cannabis; and treatment admission date.

Second, the Catalan Health Surveillance System (CHSS) comprising the RCA and the Registry of the Minimum Basic Dataset (CMBD). The RCA is an automated database that manages individual health identifiers and includes 99.6% of the population of Catalonia. From the RCA, we were able to obtain individual-level information (age and sex) related to the paired cohort. This database also records individual pharmacy co-payment information and economic benefits received through the social security system; this information was used to define the socioeconomic position (SEP) for each individual and the municipality of residence of the paired and exposed cohort [28].The CMBD contains information on diagnoses made in the health system, coded according to the International Classification of Disease (ICD-10) [29]. Each type of medical service has a CMBD, and those included in the study were the CMBD of primary healthcare, the CMBD of outpatient mental health centers, the CMBD of psychiatry outpatient resources, and the CMBD of psychiatric hospitals. This allowed us to identify mental health diagnoses made before and after the start of the study period.

Finally, from the Statistical Institute of Catalonia (IDESCAT), information was sourced on the population registered in each municipality (2015), allowing us to identify the degree of urbanization of each participant’s place of residence [30]. All data were linked using an anonymous individual health identifier.

Variables

Independent Variables

The individual sociodemographic variables were sex (male or female), age (continuous variable), nationality (Spanish or not Spanish), SEP (very low or others). Very low SEP was defined as people exempt from the pharmaceutical co-payment, those receiving unemployment benefits, and those receiving a noncontributory pension [31].

The contextual sociodemographic variable was the degree of urbanization of residence as defined by the Spanish National Institute of Statistics [32]. This was categorized by four groups as follows: mountain (≤5,000 residents), rural (>5,000 and ≤20,000 residents), semi-urban (>20,000 and ≤100,000 residents), and urban (>100,000 residents).

Variables related with CUD were age at first use of cannabis, age at commencement of treatment, and time between first use and treatment initiation. All were expressed in years as continuous variables.

The follow-up period for the exposed cohort was from the year of first use of cannabis, reported at treatment initiation, until December 31, 2019. The follow-up period for the paired cohort was the year of first use of cannabis of their corresponding exposed person until December 31, 2019.

Dependent Variables

The dependent variable was a diagnosis of a mental health condition during the study period. The mental health diagnoses included were those conditions associated with cannabis use in the relevant literature [6, 8, 19] (see the online suppl. File; for all online suppl. material, see https://doi.org/10.1159/000530331), with the exception of gambling addiction and substance use disorders. Mental health diagnoses were obtained from the CMBD of outpatient mental health centers, the CMBD of psychiatry outpatient services, and the CMBD of psychiatric hospitals. The primary healthcare CMBD was not used because it is not a specialized mental health service.

Data Analysis

We performed a descriptive analysis of independent variables for both cohorts. The results are presented in absolute and relative frequencies for categorical variables and with medians and interquartile ranges (IQRs) for continuous variables. All results were stratified by cohorts and by sex. Statistically significant differences were determined by p values with the χ2 test for categorical variables and the Mann-Whitney test for continuous variables.

To study the association between CUD and the development of mental health conditions, we calculated the cumulative incidence of developing a mental health condition in the exposed group. For both cohorts, we also calculated the cumulative incidence for each of the specific mental health conditions considered in the study. Finally, a conditional Poisson regression with robust variance was done, stratified by sex [33‒35]. This allowed estimating incidence rate ratios (IRRs). To analyze the proportion of mental health disorders in the exposed cohort associated with CUD, we calculated the attributable risk percent for the exposed cohort. The confidence interval was 95% (95% CI). The significance level was set at 5%. Stata software, version 15 was used.

Description of the Exposed Cohort

Table 1 shows the sociodemographic characteristics of those in the exposed cohort. The cohort was 77.4% male, with a median (IQR) age of 16.7 years (15.8–17.4) and a median (IQR) age at first use of cannabis of 14 years (13–15); 80% (76.6% of males; 91.5% of females) had Spanish nationality; 6.9% (7.2% of males; 5.6% of females) had a very low SEP; and 76% lived in urban or semi-urban areas.

Table 1.

Sociodemographic characteristics of the cannabis exposed cohort admitted to treatment by sex

MalesFemalesTotalp value
N = 734 (77.4%)N = 214 (22.6%)N = 948
Age, years 
 Median (IQR) 16.8 (15.9–17.4) 16.2 (15.4–17.1) 16.7 (15.8–17.4) <0.001 
 Total 734 214 948 
Age at first use, years 
 Median (IQR) 14.0 (13.0–15.0) 14.0 (13.0–15.0) 14.0 (13.0–15.0) <0.001 
 Total 734 214 948 
Time between first use and treatment initiation 
 Median (IQR) 2.0 (1.0–3.0) 2.0 (1.0–3.0) 2.0 (1.0–3.0) 0.89 
 Total 734 214 948 
Very low SEP, n (%) 
 No 681 (92.8) 202 (94.4) 883 (93.1) 0.41 
 Yes 53 (7.2) 12 (5.6) 65 (6.9) 
 Total 734 214 948 
Nationality, n (%) 
 Spanish 561 (76.6) 195 (91.5) 756 (80.0) <0.001 
 Not Spanish 171 (23.4) 18 (8.5) 189 (20.0) 
 Total 732 213 945 
Degree of urbanization, n (%) 
 Mountainous 38 (5.2) 10 (4.7) 48 (5.1) 0.78 
 Rural 138 (18.8) 42 (19.6) 180 (19.0) 
 Semi-urban 202 (27.5) 52 (24.3) 254 (26.8) 
 Urban 356 (48.5) 110 (51.4) 466 (49.2) 
 Total 734 214 948 
MalesFemalesTotalp value
N = 734 (77.4%)N = 214 (22.6%)N = 948
Age, years 
 Median (IQR) 16.8 (15.9–17.4) 16.2 (15.4–17.1) 16.7 (15.8–17.4) <0.001 
 Total 734 214 948 
Age at first use, years 
 Median (IQR) 14.0 (13.0–15.0) 14.0 (13.0–15.0) 14.0 (13.0–15.0) <0.001 
 Total 734 214 948 
Time between first use and treatment initiation 
 Median (IQR) 2.0 (1.0–3.0) 2.0 (1.0–3.0) 2.0 (1.0–3.0) 0.89 
 Total 734 214 948 
Very low SEP, n (%) 
 No 681 (92.8) 202 (94.4) 883 (93.1) 0.41 
 Yes 53 (7.2) 12 (5.6) 65 (6.9) 
 Total 734 214 948 
Nationality, n (%) 
 Spanish 561 (76.6) 195 (91.5) 756 (80.0) <0.001 
 Not Spanish 171 (23.4) 18 (8.5) 189 (20.0) 
 Total 732 213 945 
Degree of urbanization, n (%) 
 Mountainous 38 (5.2) 10 (4.7) 48 (5.1) 0.78 
 Rural 138 (18.8) 42 (19.6) 180 (19.0) 
 Semi-urban 202 (27.5) 52 (24.3) 254 (26.8) 
 Urban 356 (48.5) 110 (51.4) 466 (49.2) 
 Total 734 214 948 

Very low, people exempt from the pharmaceutical co-payment, those receiving unemployment subsidies, and those receiving a noncontributory pension. p values for categorical variables χ2 test and for continuous variables Mann-Whitney test. α = 0.05.

IQR, interquartile range; SEP, socioeconomic position.

The males who commenced treatment were slightly older than the females, with a median (IQR) age of 16.8 years (15.9–17.4) and 16.2 years (15.4–17.1), respectively. The median (IQR) number of years between first use of cannabis and entry to treatment was two (1–3).

Cumulative Incidence of Mental Health Disorders

Figure 2 shows that after the start of the study period (median 4.5 years, IQR: 3.5–6.5 years), 19.6% (n = 186) (95% CI: 17.2–22.3%) of the young people in the exposed cohort had a diagnosis of a mental health disorder, with the incidence in females twice as high as in males (32.7% vs. 15.8%). In the paired cohort, the cumulative incidence was 3.1% (n = 146) (95% CI: 2.6–3.6%). As in the exposed cohort, it was higher among females (4.2% vs. 2.8%). There were statistically significant differences between both cohorts (p < 0.0001). In both cohorts, significant differences were seen between males and females (exposed: p < 0.0001; paired: p = 0.0157).

Fig. 2.

Cumulative incidence of mental health disorders.

Fig. 2.

Cumulative incidence of mental health disorders.

Close modal

We calculated the incidence of developing each of the mental health disorders included in the study, from first use of cannabis until December 2019. The same person could have been diagnosed with more than one disorder. In the exposed cohort, 5.5% presented reaction to severe stress and adjustment disorders (males: 4.1%; females: 10.3%); 4.7%, personality disorders (males: 3.4%; females: 9.3%); 4.3%, ADHD (males: 3.8%; females: 3.3%); 3.8% conduct disorders (males: 4%; females: 3.3%); 2.2% anxiety disorders (males: 1%; females: 6.5%); and 2% major depression (males: 1%; females: 5.6%) (See Fig. 3). In the paired cohort, 1.2% presented reaction to severe stress and adjustment disorders (males: 1.7%; females: 1.0%); 0.7%, ADHD (males: 0.7%; females: 0.8%); and 0.6%, anxiety disorders (males: 0.6%; females: 0.8%).

Fig. 3.

Cumulative incidence of mental disorders by type.

Fig. 3.

Cumulative incidence of mental disorders by type.

Close modal

Conditional Poisson Analysis

Analysis of the association between CUD and development of mental health disorders showed that the exposed cohort had 8.7 (95% CI: 6.8–11.0; p < 0.0001) times increased risk of developing a mental health disorder than the paired cohort (Fig. 4). Stratified for sex, a much higher risk was seen among females (IRR: 14; 95% CI: 9.4–20.7) compared to males (IRR: 6.9; 95% CI: 5.2–9.1).

Fig. 4.

IRR and attributable fractions in the exposed cohort.

Fig. 4.

IRR and attributable fractions in the exposed cohort.

Close modal

Attributable Fraction

The results of the analyses of the attributable fractions showed that 88.5% (95% CI: 85.3–90.9%) of the mental health disorders developed in the exposed cohort (males: 85.5% [95% CI: 80.8–89%]; females: 92.3% [95% CI: 89.4–95.2%]) could have been avoided if the individuals didn’t have CUD.

Of the 948 minors who commenced treatment for CUD, 19.6% (15.8% of males; 32.7% of females) developed a mental health disorder in the years following the onset of cannabis use. This was significantly higher than in the paired group where the cumulative incidence was 3.1% (2.8% of males; 4.2% of females). In Spain, the prevalence of mental health disorders in the general population aged 15–24 years is 3.2% in males and 4.8% in females [36].

This study shows that young people with CUD have an 8.7 times higher risk of developing a mental health disorder in their youth compared with those without a diagnosis of CUD. As in other studies, the observed prevalence of CUD was higher among males [37, 38]. However, in both cohorts, there was a higher incidence of mental health disorders among females. The magnitude of the ratio of females to males was higher in the exposed cohort than in the paired cohort (2.1 vs. 1.5).

There is increasing evidence that among females with CUD, the time between first use of cannabis and development of dependency is shorter than among males and that females are more susceptible to the effects of cannabis [39]. In the present study, differences between the sexes were not observed in the median number of years between first use and commencing treatment. Nonetheless, the differences between the sexes seen in the development of mental health disorders among young people with CUD are important. The evidence suggests that these differences could be explained by neurochemical differences in the endocannabinoid system, pharmacokinetics, pharmacodynamics, and the influence of sex hormones. However, more studies are needed in humans to explain these differences [40].

Moreover, females face greater barriers to accessing drug treatment centers than males, due to greater stigma and discrimination [41, 42]. Delayed access to treatment could explain the increased severity of the CUD at treatment initiation and therefore greater risk of developing mental health disorders in a shorter time period.

Recent studies estimate that 50% of mental health disorders present before 18 years of age [43] and that age and sex are factors which determine the onset of symptoms [44]. The present study had a median of follow-up of only 4.5 years, and the median (IQR) age of the study population at the end of the study period was 19.1 (17.9–20.6) years. Therefore, this could affect the observed results. The disorders most seen in the exposed cohort, in both sexes, were reaction to severe stress and adjustment disorders. Regarding ADHD, 4.3% of the exposed cohort developed ADHD compared to only 0.8% of the paired cohort, which may suggest that CUD is also associated with ADHD [24]. Regarding psychotic disorders, only 2% of people in the exposed cohort and 0.3% of the paired cohort developed a psychotic disorder. It should also be noted that some studies show that the association between cannabis use and psychosis is observed from 23 years in males and from 26 years in females [44].

This study has certain limitations that cannot be avoided. Minors with CUD who did not enter treatment were not included. Therefore, possible selection bias must be considered, and these results should only be extrapolated to people with CUD who are in treatment. The follow-up period varied according to the year of first cannabis use, and some mental health conditions may take a longer time to present associated symptoms. Therefore, some conditions may not have been diagnosed during the study period. The paired cohort was constructed considering sociodemographic confounders; however, this study only included those diagnosed with CUD in the public health system. Therefore, we do not know if those in the paired cohort were diagnosed for CUD in private health centers or if they use cannabis. Another limitation is that it was not possible to control both cohorts for genetic predisposition to developing a mental health disorder [45, 46].

Regarding strengths, the large sample size and matched design are strengths of the study, as is the exclusion of people with a mental health disorder diagnosed prior to the study period. This allowed studying the relationship between CUD and the development of mental health disorders. This is also one of the first studies using data from the CMBD, which are exhaustive, valid registries of morbidity reported by all the public health centers in Catalonia.

The results of the present study are consistent with previous studies [16, 20]. Although the results cannot be extrapolated to the general population who use cannabis or to minors with CUD who are not in treatment, this study confirms that minors with CUD have an increased risk of developing a mental health disorder. Therefore, it highlights the need to focus prevention actions on those most at risk of developing CUD. It also confirms the high prevalence of dual pathology among minors with CUD and raises the need to address both conditions simultaneously to be effective. Dual diagnosis adds complexity to assessment, diagnosis, treatment, and recovery and can be associated with increased incidences of relapse and poorer health. Moreover, during the last decade, the potency of the tetrahydrocannabinol consumed has increased, which could be a determining factor in the association with developing a mental health disorder [47, 48]. Future research should also further study the differences in outcomes seen between the sexes and the impact of cannabis use within a socioeconomic and cultural context [49] and consider if the individuals have CUD.

The authors thank Cristina Casajuana for revising the manuscript and all the centers within the Catalan Drug Dependence Network for collecting the admission to treatment indicator.

The data used for the present analysis had already been collected as part of the standard data collection procedures of the Government of Catalonia and CHSS database. Only two investigators had access to the anonymized data and generated summary tables for the other investigators. For these reasons, the requirement for informed consent was waived.

Moreover, according to Spanish legislation, the approval of an Ethics Committee is not needed when doing observational studies without medicines and which do not involve interventions or use of biological samples. It was therefore not necessary to obtain approval from an Ethics Committee as this study only uses clinical registers and other anonymous personal data. The study was performed in accordance with the STROBE statement for reporting observational studies in epidemiology.

The authors have no conflicts of interest to declare.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Regina Muñoz-Galán, Irene Lana-Lander, and Marta Coronado Piqueras reviewed the literature and conceived and designed the study. Regina Muñoz-Galán performed the data extraction. Regina Muñoz-Galán and Irene Lana-Lander cleaned and analyzed the data and drafted the initial version of the manuscript. Regina Muñoz-Galán, Irene Lana-Lander, Marta Coronado Piqueras, Lidia Segura, and Joan Colom reviewed the initial draft, made critical contributions to the interpretation of the data, and approved the manuscript.

The data that support the findings of this study are not publicly available due to contain sensitive data. Further inquiries can be directed to the corresponding author.

1.
Bagot
KS
,
Milin
R
,
Kaminer
Y
.
Adolescent initiation of cannabis use and early-onset psychosis
.
Subst Abus
.
2015
;
36
(
4
):
524
33
.
2.
Observatorio Europeo de las Drogas y las Toxicomanías
Informe Europeo sobre Drogas 2020: cuestiones clave
Luxemburgo
Oficina de Publicaciones de la Unión Europea
2020
. Available from: www.emcdda.europa.eu/system/files/publications/13238/TD0420439ESN.pdf (accessed 15 March 2022).
3.
de Catalunya Generalitat
Informe dels resultats per a Catalunya Enquesta sobre l’ús de drogues a l’ensenyament secundari a Espanya (ESTUDES) 2018
Barcelona (Spain)
Departament de Salut
2018
. Available from: https://drogues.gencat.cat/web/.content/minisite/drogues/professionals/epidemiologia/2018/INFORME-ESTUDES-2018.pdf (accessed 15 March 2022).
4.
Subdirecció General de Drogodependències
Sistema d’Informació sobre drogodependències de Catalunya. Informe anual 2020
Barcelona (Spain)
Departament de Salut
2020
. Available from: https://drogues.gencat.cat/es/professionals/observatori/indicadors-epidemiologics/inicis-de-tractament/ (accessed 15 March 2022).
5.
Esmaeelzadeh
S
,
Moraros
J
,
Thorpe
L
,
Bird
Y
.
Examining the association and directionality between mental health disorders and substance use among adolescents and young adults in the U.S. and Canada-a systematic review and meta-analysis
.
J Clin Med
.
2018
;
7
(
12
):
543
.
6.
Moore
TH
,
Zammit
S
,
Lingford-Hughes
A
,
Barnes
TR
,
Jones
PB
,
Burke
M
.
Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review
.
Lancet
.
2007
;
370
(
9584
):
319
28
.
7.
Arendt
M
,
Mortensen
PB
,
Rosenberg
R
,
Pedersen
CB
,
Waltoft
BL
.
Familial predisposition for psychiatric disorder: comparison of subjects treated for cannabis-induced psychosis and schizophrenia
.
JAMA Psychiatry
.
2008
;
65
(
11
):
1269
74
.
8.
Fernández-Artamendi
S
,
Fernández-Hermida
JR
,
Secades-Villa
R
Cannabis y Salud Mental
.
Cannabis and mental health
.
Actas Esp Psiquiatr
.
2011
;
39
(
3
):
180
90
.
9.
Schneider
M
.
Puberty as a highly vulnerable developmental period for the consequences of cannabis exposure
.
Addict Biol
.
2008
;
13
(
2
):
253
63
.
10.
Hurd
YL
,
Manzoni
OJ
,
Pletnikov
MV
,
Lee
FS
,
Bhattacharyya
S
,
Melis
M
.
Cannabis and the developing brain: insights into its long-lasting effects
.
J Neurosci
.
2019
;
39
(
42
):
8250
8
.
11.
Yurasek
AM
,
Hadley
WC
.
Commentary: adolescent marijuana use and mental health amidst a changing legal climate
.
J Pediatr Psychol
.
2016
;
41
(
3
):
287
9
.
12.
Baeza
I
,
Graell
M
,
Moreno
D
,
Castro-Fornieles
J
,
Parellada
M
,
González-Pinto
A
.
Cannabis use in children and adolescents with first episode psychosis: influence on psychopathology and short-term outcome (CAFEPS study)
.
Schizophr Res
.
2009
113
2–3
129
37
.
13.
Stefanis
NC
,
Dragovic
M
,
Power
BD
,
Jablensky
A
,
Castle
D
,
Morgan
VA
.
Age at initiation of cannabis use predicts age at onset of psychosis : the 7- to 8-year trend
.
Schizophr Bull
.
2013
;
39
(
2
):
251
4
.
14.
Large
M
,
Sharma
S
,
Compton
MT
,
Slade
T
,
Nielssen
O
.
Cannabis use and earlier onset of psychosis: a systematic meta-analysis
.
Arch Gen Psychiatry
.
2011
;
68
(
6
):
555
61
.
15.
Van Laar
M
,
Van Dorsselaer
S
,
Monshouwer
K
,
De Graaf
R
.
Does cannabis use predict the first incidence of mood and anxiety disorders in the adult population
.
Addiction
.
2007
;
102
(
8
):
1251
60
.
16.
Hayatbakhsh
MR
,
Najman
JM
,
Jamrozik
K
,
Mamun
AA
,
Alati
R
,
Bor
W
.
Cannabis and anxiety and depression in young adults: a large prospective study
.
J Am Acad Child Adolesc Psychiatry
.
2007
;
46
(
3
):
408
17
.
17.
Crippa
JA
,
Zuardi
AW
,
Martín-Santos
R
,
Bhattacharyya
S
,
Atakan
Z
,
McGuire
P
.
Cannabis and anxiety: a critical review of the evidence
.
Hum Psychopharmacol
.
2009
;
24
(
7
):
515
23
.
18.
Windle
M
,
Wiesner
M
.
Trajectories of marijuana use from adolescence to young adulthood: predictors and outcomes
.
Dev Psychopathol
.
2004
;
16
(
4
):
1007
27
.
19.
Johns
A
.
Psychiatric effects of cannabis
.
Br J Psychiatry
.
2001
;
178
:
116
22
.
20.
Patton
GC
,
Coffey
C
,
Carlin
JB
,
Degenhardt
L
,
Lynskey
M
,
Hall
W
.
Cannabis use and mental health in young people: cohort study
.
BMJ
.
2002
;
325
(
7374
):
1195
8
.
21.
Fleming
CB
,
Mason
WA
,
Mazza
JJ
,
Abbott
RD
,
Catalano
RF
.
Latent growth modeling of the relationship between depressive symptoms and substance use during adolescence
.
Psychol Addict Behav
.
2008
;
22
(
2
):
186
97
.
22.
Lev-Ran
S
,
Le Foll
B
,
McKenzie
K
,
George
TP
,
Rehm
J
.
Bipolar disorder and co-occurring cannabis use disorders: characteristics, co-morbidities and clinical correlates
.
Psychiatry Res
.
2013
;
209
(
3
):
459
65
.
23.
Murray
RM
,
Quigley
H
,
Quattrone
D
,
Englund
A
,
Di Forti
M
.
Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis
.
World Psychiatr
.
2016
;
15
(
3
):
195
204
.
24.
Fergusson
DM
,
Boden
JM
.
Cannabis use and adult ADHD symptoms
.
DrugAlcohol Depend
.
2008
95
1–2
90
6
.
25.
Von Sydow
K
,
Lieb
R
,
Pfister
H
,
Höfler
M
,
Wittchen
HU
.
What predicts incident use of cannabis and progression to abuse and dependence? A 4-year prospective examination of risk factors in a community sample of adolescents and young adults
.
Drug Alcohol Depend
.
2002
;
68
(
1
):
49
64
.
26.
García-Cabeza
I
,
Epifanio-Gutiérrez
MM
,
Medina
O
,
Vidal
J
,
Arango
C
.
Prevalencia del consumo de drogas en adolescentes con patología mental grave
.
Trastor Adict
.
2008
;
10
(
1
):
32
41
.
27.
Van der Pol
P
,
Liebregts
N
,
De Graaf
R
,
Ten Have
M
,
Korf
DJ
,
Van den Brink
W
.
Mental health differences between frequent cannabis users with and without dependence and the general population
.
Addiction
.
2013
;
108
(
8
):
1459
69
.
28.
Servei Català de la Salut
. Població de referència del Servei Català de la Salut per a l’any 2020. Dades per ABS i UP]. Registre central de població del CatSalut; 2020. Available from: https://catsalut.gencat.cat/ca/proveidors-professionals/registres-catalegs/registres/central-poblacio/(accessed 20 March 2022).
29.
Generalitat de Catalunya: CatSalut.Servei Català de la Salut. Conjunt mínim bàsic de dades (CMBD). Available from: https://catsalut.gencat.cat/ca/proveidors-professionals/registres-catalegs/registres/cmbd/ (accessed 20 March 2022).
30.
de Catalunya Generalita. Institut d'estadística de Catalunya. Available from: https://www.idescat.cat/tema/xifpo?lang=es (accessed 20 March 2022).
31.
Agència de Qualitat i Avaluació Sanitàries de Catalunya (AQuAS). Informe Central de Resultats. Àmbit de salut mental i addiccions. Barcelona (Spain): AQuAS. Departament de Salut. Generalitat de Catalunya 2013. Available from: http://www.researchgate.net/profile/Julieta_Corral/publication/279059768_Resultats_en_la_cirurgia_oncolgica_digestiva/links/5589628008ae9076016f85f7.pdf (accessed 20 March 2022).
32.
Instituto Nacional de Estadistica. Available from: https://www.ine.es/index.htm (accessed 20 March 2022).
33.
Armstrong
BG
,
Gasparrini
A
,
Tobias
A
.
Conditional Poisson models: a flexible alternative to conditional logistic case cross-over analysis
.
BMC Med Res Methodol
.
2014
;
14
(
1
):
122
6
.
34.
Richardson
DB
,
Langholz
B
.
Background stratified Poisson regression analysis of cohort data
.
Radiat Environ Biophys
.
2012
;
51
(
1
):
15
22
.
35.
Cummings
P
,
McKnight
BGS
,
Greenland
S
.
Matched cohort methods for injury research
.
Epidemiol Rev
.
2003
;
25
:
43
50
.
36.
Fernández-Artamendi
S
,
Martínez-Loredo
V
,
López-Núñez
C
.
Sex differences in comorbidity between substance use and mental health in adolescents: two sides of the same coin
.
Psicothema
.
2021
;
33
(
1
):
36
43
.
37.
Duncan
SC
,
Gau
JM
,
Farmer
RF
,
Seeley
JR
,
Kosty
DB
,
Lewinsohn
PM
.
Comorbidity and temporal relations of alcohol and cannabis use disorders from youth through adulthood
.
Drug Alcohol Depend
.
2015
;
149
:
80
6
.
38.
Goldstein
RB
,
Dawson
DA
,
Chou
SP
,
Grant
BF
.
Sex differences in prevalence and comorbidity of alcohol and drug use disorders: results from wave 2 of the national epidemiologic survey on alcohol and related conditions
.
J Stud Alcohol Drugs
.
2012
;
73
(
6
):
938
50
.
39.
Khan
SS
,
Secades-Villa
R
,
Okuda
M
,
Wang
S
,
Pérez-Fuentes
G
,
Kerridge
BT
.
Gender differences in cannabis use disorders: results from the national epidemiologic survey of alcohol and related conditions
.
Drug Alcohol Depend
.
2013
130
1–3
101
8
.
40.
Schlienz
NJ
,
Budney
AJ
,
Lee
DC
,
Vandrey
R
.
Cannabis withdrawal: a review of neurobiological mechanisms and sex differences
.
Curr Addict Rep
.
2017
;
4
(
2
):
75
81
.
41.
Becker
JB
,
McClellan
ML
,
Reed
BG
.
Sex differences, gender and addiction
.
J Neurosci Res
.
2017
95
1–2
136
47
.
42.
McHugh
RK
,
Votaw
VR
,
Sugarman
DE
,
Greenfield
SF
.
Sex and gender differences in substance use disorders
.
Clin Psychol Rev
.
2018
;
66
:
12
23
.
43.
Solmi
M
,
Radua
J
,
Olivola
M
,
Croce
E
,
Soardo
L
,
Salazar de Pablo
G
.
Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies
.
Mol Psychiatry
.
2022
;
27
(
1
):
281
95
.
44.
Leadbeater
BJ
,
Ames
ME
,
Linden-Carmichael
AN
.
Age-varying effects of cannabis use frequency and disorder on symptoms of psychosis, depression and anxiety in adolescents and adults
.
Addiction
.
2019
;
114
(
2
):
278
93
.
45.
Bramness
JG
,
Gundersen
ØH
,
Guterstam
J
,
Rognli
EB
,
Konstenius
M
,
Løberg
EM
.
Amphetamine-induced psychosis: a separate diagnostic entity or primary psychosis triggered in the vulnerable
.
BMC Psychiatry
.
2012
;
12
:
221
.
46.
Løberg
EM
,
Helle
S
,
Nygard
M
,
Berle
,
Kroken
RA
,
Johnsen
E
.
The cannabis pathway to non-affective psychosis may reflect less neurobiological vulnerability
.
Front Psychiatry
.
2014
;
5
:
159
.
47.
McDonald
AJ
,
Roerecke
M
,
Mann
RE
.
Adolescent cannabis use and risk of mental health problems-the need for newer data
.
Addiction
.
2019
;
114
(
10
):
1889
90
.
48.
Manthey
J
,
Freeman
TP
,
Kilian
C
,
López-Pelayo
H
,
Rehm
J
.
Public health monitoring of cannabis use in Europe: prevalence of use, cannabis potency, and treatment rates
.
Lancet Reg Health Eur
.
2021
;
10
:
100227
.
49.
Tirado-Muñoz
J
,
Lopez-Rodriguez
AB
,
Fonseca
F
,
Farré
M
,
Torrens
M
,
Viveros
MP
.
Effects of cannabis exposure in the prenatal and adolescent periods: preclinical and clinical studies in both sexes
.
Front Neuroendocrinol
.
2020
;
57
:
100841
.