Previous studies identified clusters of first-episode psychosis (FEP) patients based on cognition and premorbid adjustment. This study examined a range of socio-environmental risk factors associated with clusters of FEP, aiming a) to compare clusters of FEP and community controls using the Maudsley Environmental Risk Score for psychosis (ERS), a weighted sum of the following risks: paternal age, childhood adversities, cannabis use, and ethnic minority membership; b) to explore the putative differences in specific environmental risk factors in distinguishing within patient clusters and from controls.

A univariable general linear model (GLS) compared the ERS between 1,263 community controls and clusters derived from 802 FEP patients, namely, low (n = 223) and high-cognitive-functioning (n = 205), intermediate (n = 224) and deteriorating (n = 150), from the EU-GEI study. A multivariable GLS compared clusters and controls by different exposures included in the ERS.

The ERS was higher in all clusters compared to controls, mostly in the deteriorating (β=2.8, 95% CI 2.3 3.4, η2 = 0.049) and the low-cognitive-functioning cluster (β=2.4, 95% CI 1.9 2.8, η2 = 0.049) and distinguished them from the cluster with high-cognitive-functioning. The deteriorating cluster had higher cannabis exposure (meandifference = 0.48, 95% CI 0.49 0.91) than the intermediate having identical IQ, and more people from an ethnic minority (meandifference = 0.77, 95% CI 0.24 1.29) compared to the high-cognitive-functioning cluster.

High exposure to environmental risk factors might result in cognitive impairment and lower-than-expected functioning in individuals at the onset of psychosis. Some patients’ trajectories involved risk factors that could be modified by tailored interventions.

Cannabis is the most commonly used illicit substance in Ireland and globally. It is most likely to be used in adolescence, a period of biopsychosocial vulnerability to maladaptive behaviours. This study aims to investigate the risk and protective factors for cannabis use among adolescents.

This study is a secondary analysis of the cross-sectional Planet Youth survey (2021). The sample comprised 4,404 adolescents aged 15–16 from one urban and two rural areas in Ireland. The outcome of interest was current cannabis use, defined as cannabis use within the last 30 days. Independent variables i.e., risk and protective factors, were selected a priori following a literature review. Associations between cannabis use and the independent variables were explored using mixed-effects logistic regressions.

The prevalence of current cannabis use was 7.3% and did not differ significantly between males and females. In fully-adjusted models, significant risk factors for cannabis use were: Having peers that used cannabis (Adjusted Odds Ration (aOR) 10.17, 95% CI: 5.96–17.35); Parental ambivalence towards cannabis use (aOR 3.69, 95% CI: 2.41–5.66); Perception of cannabis as non-harmful (aOR 2.32,95% CI 1.56–£.45): Other substance use (aORs ranging from 2-67–3.15); Peer pressure to use cannabis (aOR 1.85,95% CI 1.05–3.26), and Low parental supervision (aOR 1.11, 95% CI: 1.01–1.22).

This study identified key individual, peer-to-peer and parental risk factors associated with adolescent cannabis use, several of which have the potential to be modified through drug prevention strategies.

Markers of inflammation and cannabis exposure are associated with an increased risk of mental disorders. In the current study, we investigated associations between cannabis use and biomarkers of inflammation.

Utilizing a sample of 914 participants from the Avon Longitudinal Study of Parents and Children, we investigated whether interleukin-6 (IL-6), tumor necrosis factor α (TNFα), C-reactive protein (CRP), and soluble urokinase plasminogen activator receptor (suPAR) measured at age 24 were associated with past year daily cannabis use, less frequent cannabis use, and no past year cannabis use. We adjusted for a number of covariates including sociodemographic measures, body mass index, childhood trauma, and tobacco smoking. We found evidence of a strong association between daily or near daily cannabis use and suPAR.

We did not find any associations between less frequent cannabis use and suPAR. We did not find evidence of an association between IL-6, TNFα or CRP, and cannabis use.

Our finding that frequent cannabis use is strongly associated with suPAR, a biomarker of systemic chronic inflammation implicated in neurodevelopmental and neurodegenerative processes is novel. These findings may provide valuable insights into biological mechanisms by which cannabis affects the brain and impacts the risk of serious mental disorders.

The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.

Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.

In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.

Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.

Observational studies consistently report associations between tobacco use, cannabis use and mental illness. However, the extent to which this association reflects an increased risk of new-onset mental illness is unclear and may be biased by unmeasured confounding.

A systematic review and meta-analysis (CRD42021243903). Electronic databases were searched until November 2022. Longitudinal studies in general population samples assessing tobacco and/or cannabis use and reporting the association (e.g. risk ratio [RR]) with incident anxiety, mood, or psychotic disorders were included. Estimates were combined using random-effects meta-analyses. Bias was explored using a modified Newcastle–Ottawa Scale, confounder matrix, E-values, and Doi plots.

Seventy-five studies were included. Tobacco use was associated with mood disorders (K = 43; RR: 1.39, 95% confidence interval [CI] 1.30–1.47), but not anxiety disorders (K = 7; RR: 1.21, 95% CI 0.87–1.68) and evidence for psychotic disorders was influenced by treatment of outliers (K = 4, RR: 3.45, 95% CI 2.63–4.53; K = 5, RR: 2.06, 95% CI 0.98–4.29). Cannabis use was associated with psychotic disorders (K = 4; RR: 3.19, 95% CI 2.07–4.90), but not mood (K = 7; RR: 1.31, 95% CI 0.92–1.86) or anxiety disorders (K = 7; RR: 1.10, 95% CI 0.99–1.22). Confounder matrices and E-values suggested potential overestimation of effects. Only 27% of studies were rated as high quality.

Both substances were associated with psychotic disorders and tobacco use was associated with mood disorders. There was no clear evidence of an association between cannabis use and mood or anxiety disorders. Limited high-quality studies underscore the need for future research using robust causal inference approaches (e.g. evidence triangulation).

Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls.

We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables.

FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123–2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368–0.997 and OR = 0.646, CI 0.457–0.913 respectively) and JTC bias (OR = 0.625, CI 0.422–0.925 and OR = 0.602, CI 0.460–0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297–2.578, FRP deficits (OR = 1.393, CI 1.031–1.882, and JTC (OR = 1.661, CI 1.271–2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups.

Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.

Epidemiologic research suggests that youth cannabis use is associated with psychotic disorders. However, current evidence is based heavily on 20th-century data when cannabis was substantially less potent than today.

We linked population-based survey data from 2009 to 2012 with records of health services covered under universal healthcare in Ontario, Canada, up to 2018. The cohort included respondents aged 12–24 years at baseline with no prior psychotic disorder (N = 11 363). The primary outcome was days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder according to validated diagnostic codes. Due to non-proportional hazards, we estimated age-specific hazard ratios during adolescence (12–19 years) and young adulthood (20–33 years). Sensitivity analyses explored alternative model conditions including restricting the outcome to hospitalizations and ED visits to increase specificity.

Compared to no cannabis use, cannabis use was significantly associated with psychotic disorders during adolescence (aHR = 11.2; 95% CI 4.6–27.3), but not during young adulthood (aHR = 1.3; 95% CI 0.6–2.6). When we restricted the outcome to hospitalizations and ED visits only, the strength of association increased markedly during adolescence (aHR = 26.7; 95% CI 7.7–92.8) but did not change meaningfully during young adulthood (aHR = 1.8; 95% CI 0.6–5.4).

This study provides new evidence of a strong but age-dependent association between cannabis use and risk of psychotic disorder, consistent with the neurodevelopmental theory that adolescence is a vulnerable time to use cannabis. The strength of association during adolescence was notably greater than in previous studies, possibly reflecting the recent rise in cannabis potency.

We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.

We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.

The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).

The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Evidence suggests that cannabis may be a causal factor for development of schizophrenia. We aimed to investigate whether use of antipsychotic medication, benzodiazepines, and psychiatric service use differs among patients with schizophrenia depending on whether psychosis was precipitated by a diagnosis of cannabis use disorder (CUD).

We utilized the nationwide Danish registries to identify all individuals with an incident diagnosis of schizophrenia from 1995 to 2016. We also collected information on whether first CUD diagnosis preceded schizophrenia and thus defined a group of potentially cannabis-related schizophrenia. We compared the cannabis-related schizophrenia group both with all non-cannabis-related patients with schizophrenia and with non-cannabis-related patients with schizophrenia that were propensity-score matched to cases using a range of potentially confounding variables.

We included 35 714 people with incident schizophrenia, including 4116 (11.5%) that were cannabis-related. In the unmatched-comparison analyses, there were no clear differences over time in use of antipsychotics and benzodiazepines related to whether the diagnosis of schizophrenia was cannabis-related. After propensity-score matching, use of antipsychotics and benzodiazepines was significantly lower among cannabis-related cases of schizophrenia. In the unmatched comparison, the cannabis-related group had significantly more days admitted than the non-cannabis-related group. This was markedly attenuated after propensity-score matching.

Our findings indicate the importance of considering cannabis-related cases of schizophrenia as a potentially distinct disorder in terms of prognosis. It is unclear, however, if these differences are due to different biological types of schizophrenia being compared or if they rather indicate behavioral differences such as reduced adherence and treatment-seeking.

In patients with a psychotic disorder, rates of substance use (tobacco, cannabis, and alcohol) are higher compared to the general population. However, little is known about associations between substance use and self-reported aspects of social functioning in patients with a psychotic disorder.

In this cross-sectional study of 281 community-dwelling patients with a psychotic disorder, linear regression models were used to assess associations between substance use (tobacco, cannabis, or alcohol) and self-reported aspects of social functioning (perceived social support, stigmatization, social participation, or loneliness) adjusting for confounders (age, gender, and severity of psychopathology).

Compared to nonsmokers, both intermediate and heavy smokers reported lower scores on loneliness (E = −0.580, SE = 0.258, p = 0.025 and E = −0.547, SE = 0,272, p = 0.046, respectively). Daily cannabis users reported less social participation deficits than non-cannabis users (E = −0.348, SE = 0.145, p = 0.017). Problematic alcohol use was associated with more perceived social support compared to non-alcohol use (E = 3.152, SE = 1.102, p = 0.005). Polysubstance users reported less loneliness compared to no users (E = −0.569, SE = 0.287, p = 0.049).

Substance use in patients with psychosis is associated with more favorable scores on various self-reported aspects of social functioning.

Obstructive sleep apnea (OSA) is a sleep disorder with no widely accepted pharmacological therapy. Cannabinoids have been suggested to reduce OSA severity in small human studies. The purpose of this retrospective cohort study was to explore the association of self-reported cannabis use on OSA severity and sleep parameters in a large cohort of adults undergoing in-laboratory polysomnography.

Sleep and medication data were collected for all consecutive adults who completed diagnostic polysomnography at Sunnybrook Health Sciences Centre from 2010 to 2022. Multivariable linear regression models were employed that adjusted for age, sex, and BMI (minimally adjusted model), as well as medication and comorbidity data (maximally adjusted model). An exploratory subgroup analysis was additionally run in patients with moderate to severe OSA.

Of 6,958 individuals (mean age 54.7 ± 16.3, BMI 29.1 ± 6.8, 51.0% female), 71 reported cannabis use. In our minimally adjusted models, cannabis use predicted a reduced respiratory disturbance index (RDI) (β: −4.8 [95% CI: −9.4, −0.2]; p = 0.042); this association became nonsignificant in the fully adjusted models. In an exploratory analysis of patients with moderate to severe OSA (n = 613), cannabis use (n = 7) predicted increased stage N3 sleep (β: 33.5 [95% CI: 15.6, 51.4]; p < 0.001) and decreased REM sleep (β: 16.0 [95% CI: 0.3, 31.7]; p = 0.046).

Self-reported cannabis use was not associated with OSA severity after adjusting for confounders. In an exploratory subgroup analysis of patients with moderate to severe OSA, cannabis use impacted sleep architecture. Future studies should further explore these findings.