Cannabis legalisation has undergone a rapid global transformation, with varying policy approaches and public health implications across different geographic areas and social contexts.

Several arguments have been proposed to support cannabis legalisation, ranging from control of the quality and potency of the market products, harm reduction, addressing the black market activities, reducing crime, and economic benefit. However, cannabis use has been associated with public health concerns, and it has been established as the most preventable risk factor for psychotic disorders.

This work aims to dissect the key arguments supporting cannabis legalisation through the following objectives: 1) reviewing the relationship between cannabis legalisation and the incidence and prevalence of psychotic disorders in countries where cannabis has been legalised, as well as changes in incidence rates over time in those countries where legalization is currently under debate; 2) examining the relationship between cannabis use and psychopathological outcomes using a syndemic approach; and 3) presenting original data from the epidemiological branch of the EC-1 study, aiming to identify risk factors for psychopathology, violence, and aggression in South London.

None Declared

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.

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 the COVID-19 pandemic was accompanied by an increased exposure to risk factors for psychosis, such as psychological stress, substance use, social isolation and deprivation, as well as a potential direct biological impact of the COVID-19 infection on psychosis. However, the impact of the COVID-19 pandemic on the rates of first-episode psychosis (FEP) has not yet been examined.

The aims of the current study were to 1) establish the FEP incidence between March 2019 and March 2021 in an inner London catchment area; 2) compare FEP incidence rates for the first year of the COVID-19 pandemic (March 2020 – February 2021), with those for the year prior (March 2019 – February 2020).

We screened the clinical records of all individuals living in the London boroughs of Southwark and Lambeth who were referred to the early intervention in psychosis services before (from 1 March 2019 to 28 February 2020) and during (from 1 March 2020 to 28 February 2021) the COVID-19 pandemic. We used Office for National Statistics (ONS) data to estimate the risk populations stratified by sex and age group. We computed crude and sex-age standardised FEP incidence per 100,000 persons-year. We used Poisson regression to calculate the incidence rate ratio (IRR) before and during the COVID-19 pandemic and to examine the incidence variation by sociodemographic factors.

A total of 321 incident cases of FEP were identified during the COVID-19 pandemic accounting for a crude rate of 70.1 (95% CI 62.4 - 77.7) per 100,000 person-year. The crude rate for the year before was 47.5 (95% CI 41.2 - 53.8). The incidence variation between the two years accounted for an adjusted IRR of 1.46 (95% CI 1.23 – 1.76). The increased FEP rates were equally observed across the boroughs of Southwark and Lambeth and men and women. Individuals aged 20-24 (IRR 1.66; 95% CI 1.13 – 2.42) and those from the black ethnic group (IRR 1.61; 95% CI 1·24 – 2·09) showed the greatest incidence increases.

To the best of our knowledge, this is the first study establishing the variation in FEP incidence before and during the COVID-19 pandemic across all adult age groups. We provide the first evidence that the COVID-19 pandemic resulted in a 46% increase in the incidence of psychotic disorders in South London. The increase was higher for young individuals and ethnic minorities. This finding should inform public health research and demonstrates the need for adequate resources for mental health secondary services.

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Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis.

The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use.

After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1–3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2–2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (β = −2.3; p ⩽ 0.001; 95% CI [−3.7 to −0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0–1.8]); however, these results were no longer significant after controlling for cannabis use.

Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample.

Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of ‘Genetic’ models (solely fitted with PRS-SZ), ‘Environmental’ models (solely fitted with each environmental stressor), ‘Independent’ models (with PRS-SZ and each environmental factor), and ‘Interaction’ models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models.

There were no genes-environment associations. PRS-SZ was associated with positive dimensions (β = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension.

This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.

Personal Health Budget (PHB) has been provided to consumers with severe mental illness within a policy shift toward a person-tailored mental healthcare treatment based on individual unmet needs. PHB is an amount of money to support patient’s health and wellbeing needs, which is planned and agreed between patients and their local NHS team. It is not new money, but it may mean spending money differently so that patients can get the care that they need. However, evidence of beneficial effects of PHB is still scarce.

The aim of this study was to provide preliminary data on clinical and social benefits of adding PHB to a standard pharmacotherapy in patients with severe mental illness across a 24-month follow-up period.

137 individuals with severe mental illness (aged 18–50 years) were recruited in one of the adult mental health services of an Italian Department of Mental Health. They completed the Global Assessment of Functioning scale, the Health of the Nation Outcome Scale and the Brief Psychiatric Rating Scale. Friedman’s test for repeated measure was used to assess the longitudinal stability of functioning and clinical parameters. A linear regression analysis was also performed.

A significant decrease in all GAF scale, HoNOS and BPRS scores along the 24 months of follow-up was observed. Regression analysis results specifically showed a relevant association between a PHB multiaxial intervention and the longitudinal reduction in BPRS ‘Negative Symptoms’ and HoNOS ‘Social Problems’ subscores.

Our findings support the useful implementation of a PHB approach for severe mental illness patients within the Italian mental health service network.

No significant relationships.

We have previously shown that the association between frequent cannabis use and psychosis is more likely in subgroups with low-grade inflammation than subgroups without (PMID: 33736715). The role of immune-related polymorphisms remains unknown.

To explore whether polymorphisms affecting the function of key immune regulatory proteins moderate the association between cannabis and psychosis, namely: ENTPD1 and NT5E, involved in the synthesis of CD39, CD73, respectively, and anti-inflammatory adenosine; CTLA4 and FOXP1, essential for Treg functional capacity.

We genotyped blood samples from 283 community-based controls and 140 recent-onset psychosis patients in Brazil (EU-GEI consortium, Ribeirão Preto/SP) for twelve polymorphisms (ENTPD1: rs3814159, rs3176891, rs10748643; NT5E: rs9444348, rs2295890; CTLA4: rs3087243, rs231775, rs5742909, rs4553808; FOXP1: rs6803008, rs6786408, rs830599; Illumina Human Core Exome-24). Cannabis frequency (daily, less than daily, never) was assessed by self-report (Cannabis Experience Questionnaire). Binary logistic regression models (OR,95%CI) included case status as the outcome, genotype (dominant model), cannabis frequency, and an interaction term between the two as exposure, adjusting for confounders (age, sex, ethnicity, tobacco smoking).

We found significant interactions between cannabis use and polymorphisms for ENTPD1 (rs3814159), NT5E (rs9444348), and FOXP1 (rs6786408). Less than daily or daily use were, in a dose-response fashion, only associated with psychosis in those with the variant and heterozygous genotypes; less than daily: ENTPD1 AG/GG (3.34,1.71-6.50); NT5E AG/AA (3.71,1.87-7.33); FOXP1 AC/CC (2.98,1.54-5.77); daily: ENTPD1 AG/GG (16.81;5.89-47.96); NT5E AG/AA (21.20,6.81-66.01); FOXP1 AC/CC (13.75,5.22-36.21).

Variation in genes that affect Treg function appears to modify the effect of cannabis consumption on psychosis in keeping with Treg hypofunction hypothesis (PMID:33713699).

No significant relationships.

Identifying distinct dimensions of negative symptoms in First Episode Schizophrenia (FES) might result in a better understanding and treatment of this invalidating symptomatology.

Aim of this study was to examine negative symptom structure in FES patients using the Positive and Negative Syndrome Scale (PANSS).

All 147 participants, aged 12–35 years, completed the PANSS and the Global Assessment of Functioning (GAF) scale. A principal component analysis with varimax rotation was performed to investigate PANSS negative symptom structure in the FES total sample.

A 2-factor model (i.e. “Expressive Deficits” and “Asociality” dimensions) was identified. Only “Expressive Deficits” domain had a significant negative correlation with baseline GAF score.

This bipartite solution seems to be adequate to describe the phenomenological variety of negative symptoms experienced by FES individuals at the point of entry in early intervention services.

No significant relationships.

QTc interval prolongation is considered a risk factor for fatal polymorphic ventricular tachycardia, which can result in sudden cardiac death. Most psychotropic drugs have a dose-dependent potential to prolong the QTc interval. However, other factors require appropriate consideration, including: age; gender; other medications; electrolyte abnormalities; severe comorbid conditions, such as co-occurring alcohol or substances abuse/dependence.

The objective was to study the potential mediating roles of alcohol/substances abuse on QTc prolongation.

The Italian research group STAR Network, in collaboration with the Young Italian Psychiatrists Association, aimed to evaluate the frequency of QTc interval prolongation in a sample of patients under treatment with psychotropic drugs through a cross-sectional national survey.

A sample of 2411 unselected patients were enrolled after performing an ECG during the recruitment period. Sociodemographic and clinical characteristics were collected from medical records. Collected data underwent statistical analysis.

A total of 11.2% of patients reported alcohol abuse, and only 8.9% psychotropic substances. According to the threshold, less than 20% of patients had a borderline value of QTc, and 1% a pathological value. Patients with co-occurring alcohol misuse and drug abuse were more likely to have longer QTc interval.

The present study describes the frequency of QTc prolongation in real-world clinical practice. Before prescribing a psychotropic drug, the physician should carefully assess its risks and benefits to avoid this type of adverse reaction, particularly when additional risk factors are present. The potential role of alcohol and substances on QTc length could be particularly useful in emergency settings.

The authors have not supplied their declaration of competing interest.

Jumping to conclusions (JTC), which is the proneness to require less information before forming beliefs or making a decision, has been related to formation and maintenance of delusions. Using data from the National Institute of Health Research Biomedical Research Centre Genetics and Psychosis (GAP) case–control study of first-episode psychosis (FEP), we set out to test whether the presence of JTC would predict poor clinical outcome at 4 years.

One-hundred and twenty-three FEP patients were assessed with the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and the probabilistic reasoning ‘Beads’ Task at the time of recruitment. The sample was split into two groups based on the presence of JTC bias. Follow-up data over an average of 4 years were obtained concerning clinical course and outcomes (remission, intervention of police, use of involuntary treatment – the Mental Health Act (MHA) – and inpatient days).

FEP who presented JTC at baseline were more likely during the follow-up period to be detained under the MHA [adjusted OR 15.62, 95% confidence interval (CI) 2.92–83.54, p = 0.001], require intervention by the police (adjusted OR 14.95, 95% CI 2.68–83.34, p = 0.002) and have longer admissions (adjusted IRR = 5.03, 95% CI 1.91–13.24, p = 0.001). These associations were not accounted for by socio-demographic variables, IQ and symptom dimensions.

JTC in FEP is associated with poorer outcome as indicated and defined by more compulsion police intervention and longer periods of admission. Our findings raise the question of whether the implementation of specific interventions to reduce JTC, such as Metacognition Training, may be a useful addition in early psychosis intervention programmes.