Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis

Dragt S, Nieman DH, Schultze‐Lutter F, van der Meer F, Becker H, de Haan L, Dingemans PM, Birchwood M, Patterson P, Salokangas RKR, Heinimaa M, Heinz A, Juckel G, Graf von Reventlow H, French P, Stevens H, Ruhrmann S, Klosterkötter J, Linszen DH, on behalf of the EPOS group. Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis. Objective: Numerous studies have found a robust association between cannabis use and the onset of psychosis. Nevertheless, the relationship between cannabis use and the onset of early (or, in retrospect, prodromal) symptoms of psychosis remains unclear. The study focused on investigating the relationship between cannabis use and early and high‐risk symptoms in subjects at clinical high risk for psychosis. Method: Prospective multicenter, naturalistic field study with an 18‐month follow‐up period in 245 help‐seeking individuals clinically at high risk. The Composite International Diagnostic Interview was used to assess their cannabis use. Age at onset of high risk or certain early symptoms was assessed retrospectively with the Interview for the Retrospective Assessment of the Onset of Schizophrenia. Results: Younger age at onset of cannabis use or a cannabis use disorder was significantly related to younger age at onset of six symptoms (0.33 < r_s < 0.83, 0.004 < P < 0.001). Onset of cannabis use preceded symptoms in most participants. Conclusion: Our results provide support that cannabis use plays an important role in the development of psychosis in vulnerable individuals. Cannabis use in early adolescence should be discouraged.     

Cannabinoids and Schizophrenia: Risks and Therapeutic Potential

A convergence of evidence shows that use of Cannabis sativa is associated with increased risk of developing psychotic disorders, including schizophrenia, and earlier age at which psychotic symptoms first manifest. Cannabis exposure during adolescence is most strongly associated with the onset of psychosis amongst those who are particularly vulnerable, such as those who have been exposed to child abuse and those with family histories of schizophrenia. Schizophrenia that develops after cannabis use may have a unique clinical phenotype, and several genetic polymorphisms may modulate the relationship between cannabis use and psychosis. The endocannabinoid system has been implicated in psychosis both related and unrelated to cannabis exposure, and studying this system holds potential to increase understanding of the pathophysiology of schizophrenia. Anandamide signaling in the central nervous system may be particularly important. Δ⁹-Tetrahydrocannabinol in cannabis can cause symptoms of schizophrenia when acutely administered, and cannabidiol (CBD), another compound in cannabis, can counter many of these effects. CBD may have therapeutic potential for the treatment of psychosis following cannabis use, as well as schizophrenia, possibly with better tolerability than current antipsychotic treatments. CBD may also have anti-inflammatory and neuroprotective properties. Establishing the role of CBD and other CBD-based compounds in treating psychotic disorders will require further human research.

Electronic supplementary material

The online version of this article (doi:10.1007/s13311-015-0382-6) contains supplementary material, which is available to authorized users.Key Words: Cannabinoids, schizophrenia, psychosis, cannabidiol, cannabis, endocannabinoid     

The effect of cannabis use and cognitive reserve on age at onset and psychosis outcomes in first-episode schizophrenia

Objective: Cannabis use is associated with a younger age at onset of psychosis, an indicator of poor prognosis, but better cognitive function, a positive prognostic indicator. We aimed to clarify the role of age at onset and cognition on outcomes in cannabis users with first-episode schizophrenia as well as the effect of cannabis dose and cessation of use.Methods: Ninety-nine patients without alcohol or substance abuse other than cannabis were divided into lifetime users and never-users of cannabis and compared on measures of premorbid function, cognition, and clinical outcome.Results: Cannabis users demonstrated better cognition at psychosis onset, which was explained by higher premorbid IQ. They also showed better social function and neither measure changed over the subsequent 15 months. Cannabis users had an earlier age at onset of psychosis, and there was a strong linear relationship between age at first cannabis use and age at onset of both prodromal and psychotic symptoms. Cannabis use spontaneously declined over time with 3-quarters of users giving up altogether. Later age at first cannabis use predicted earlier cessation of use and this in turn was linked to fewer positive psychotic symptoms and days in hospital during the first 2 years.Conclusions: Cannabis use brings forward the onset of psychosis in people who otherwise have good prognostic features indicating that an early age at onset can be due to a toxic action of cannabis rather than an intrinsically more severe illness. Many patients abstain over time, but in those who persist, psychosis is more difficult to treat.     

Prevalence and correlates of cannabis use in developed and developing countries

PURPOSE OF REVIEW: The aim of this article is to review recent research on the prevalence, antecedents and correlates of cannabis use in young adults in developed and developing countries. RECENT FINDINGS: Cannabis is the most widely used illicit drug globally and its use appears to be increasing in developed and developing countries. In developed countries rebelliousness, antisocial behaviour, poor school performance, and affiliation with drug-using peers are risk factors for early and regular cannabis use. Similar antecedents are now being reported in developing countries. Dependence is an underappreciated risk of cannabis that affects one in six to seven adolescents who use cannabis in developed countries. Adolescent cannabis dependence is correlated with an increased risk of using other illicit drugs, symptoms of depression, and symptoms of psychosis. The plausibility of cannabis playing a contributory causal role has increased for symptoms of psychosis in longitudinal studies but remains contentious. In the case of other illicit drug use and mood disorders common causal explanations remain difficult to exclude. SUMMARY: Early and regular cannabis use in adolescence predicts an increased risk of cannabis dependence which in turn predicts an increased risk of using other illicit drugs, and reporting symptoms of mood and psychotic disorders.     

Genetic liability, illicit drug use, life stress and psychotic symptoms: preliminary findings from the Edinburgh study of people at high risk for schizophrenia

Background: Studies of groups at high risk of developing schizophrenia have tended to be based on subjects recruited to the study in their infancy. This paper reports on subjects at genetic high risk for schizophrenia assessed as young adults, close to the age when most onsets of schizophrenia occur. Methods: One hundred and fifty-five young people at elevated risk for the development of schizophrenia and 36 controls not at increased risk were assessed on entry to the Edinburgh High Risk Study. The measures included current psychotic symptoms, past and present cannabis and other drug use, lifetime life events and two aspects of genetic liability to schizophrenia. Results: Cannabis and other illicit drug use were significantly associated with symptoms in both groups. The same held true for the more upsetting life events experienced, but not for less upsetting ones. Within the high-risk group, there was no relationship between symptoms and a measure of genetic loading, but there was some slight evidence of a higher risk of symptoms when affected relatives were on the father's rather than the mother's side of the family. Conclusions: Cannabis use, use of other illicit substances and upsetting life events may all lead to psychotic symptoms in vulnerable young people. Accepted: 26 April 2001     

Cannabis use and non‐clinical dimensions of psychosis in university students presenting to primary care

Skinner R, Conlon L, Gibbons D, McDonald C. Cannabis use and non‐clinical dimensions of psychosis in university students presenting to primary care. Objective: To explore the relationship between cannabis use and self‐reported dimensions of psychosis in a population of university students presenting for any reason to primary care. Method: One thousand and forty‐nine students attending the Student Health Unit, National University of Ireland, Galway, completed self‐report questionnaires on alcohol and substance misuse, non‐clinical dimensions of psychosis [Community Assessment of Psychic Experiences (CAPE)], anxiety and depression [Hospital Anxiety and Depression Scale (HADS)]. Association of cannabis use with psychiatric symptoms was explored whilst controlling for confounds. Results: More frequent cannabis use was independently associated with greater intensity of positive, negative and depressive psychotic symptoms. The earlier the age of onset of cannabis use, the more positive psychotic symptoms were reported. Conclusion: These findings support the hypotheses that cannabis use increases the risk of developing psychotic symptoms and that this risk is further increased in those individuals who use cannabis more heavily and commence it at a younger age.     

Cannabis and First-Episode Psychosis: Different Long-term Outcomes Depending on Continued or Discontinued Use

Objective: To examine the influence of cannabis use on long-term outcome in patients with a first psychotic episode, comparing patients who have never used cannabis with (a) those who used cannabis before the first episode but stopped using it during follow-up and (b) those who used cannabis both before the first episode and during follow-up. Methods: Patients were studied following their first admission for psychosis. They were interviewed at years 1, 3, and 5. At follow-up after 8 years, functional outcome and alcohol and drug abuse were recorded. Patients were classified according to cannabis use: 25 had cannabis use before their first psychotic episode and continuous use during follow-up (CU), 27 had cannabis use before their first episode but stopped its use during follow-up (CUS), and 40 never used cannabis (NU). Results: The 3 groups did not differ significantly in symptoms or functional outcome at baseline or during short-term follow-up. The CUS group exhibited better long-term functional outcome compared with the other 2 groups and had fewer negative symptoms than the CU group, after adjusting for potential confounders. For the CUS group, the effect size was 1.26 (95% confidence interval [CI] = 0.65 to 1.86) for functional outcome and −0.72 (95% CI = −1.27 to −0.14) for negative symptoms. All patients experienced improvements in positive symptoms during long-term follow-up. Conclusion: Cannabis has a deleterious effect, but stopping use after the first psychotic episode contributes to a clear improvement in outcome. The positive effects of stopping cannabis use can be seen more clearly in the long term.     

Association of cannabis use with prodromal symptoms of psychosis in adolescence

Recent interest has focused on the association between cannabis use and risk of psychosis. In the largest unselected, population-based study on this topic to date, we examined cannabis use and prodromal symptoms of psychosis at age 15-16 years among 6330 adolescents. Those who had tried cannabis (n=352; 5.6% of the total sample) were more likely to present three or more prodromal symptoms even after controlling for confounders including previous behavioural symptoms (OR=2.23; 95% CI 1.70-2.94). A dose-response effect was seen. We conclude that cannabis use is associated with prodromal symptoms of psychosis in adolescence.     

Age at Initiation of Cannabis Use Predicts Age at Onset of Psychosis: The 7- to 8-Year Trend

We investigated the existence of a temporal association between age at initiation of cannabis use and age at onset of psychotic illness in 997 participants from the 2010 Survey of High Impact Psychosis (SHIP) in Australia. We tested for group differences in age at onset of psychotic illness and in the duration of premorbid exposure to cannabis (DPEC). Analyses were repeated in subgroups of participants with a schizophrenia-spectrum disorder (SSD), a diagnosis of lifetime cannabis dependence (LCD), and a comorbid SSD/LCD diagnosis. The association between age at initiation of cannabis use and age at onset of psychotic illness was linear and significant, F(11, 984) = 13.77, P < .001, even after adjusting for confounders. The effect of age at initiation of cannabis use on DPEC was not significant (mean duration of 7.8 years), and this effect was similar in participants with a SSD, LCD, and comorbid SSD/ LCD diagnosis although a shift toward shorter premorbid exposure to cannabis was noted in the SSD/LCD subgroup (mean duration of 7.19 years for SSD/LCD). A temporal direct relationship between age at initiation of cannabis use and age at onset of psychotic illness was detected with a premorbid exposure to cannabis trend of 7–8 years, modifiable by higher severity of premorbid cannabis use and a diagnosis of SSD. Cannabis may exert a cumulative toxic effect on individuals on the pathway to developing psychosis, the manifestation of which is delayed for approximately 7–8 years, regardless of age at which cannabis use was initiated.Key words: cannabis, psychosis, schizophrenia, age at onset, causality, DIP, SHIP     

Cannabis use and the mental health of young people

OBJECTIVE: To review the evidence on the mental health and psychosocial consequences of rising rates of cannabis use among young people in developed countries. METHOD: This paper critically reviews epidemiological evidence on the following psychosocial consequences of adolescent cannabis use: cannabis dependence; the use of heroin and cocaine; educational underachievement; and psychosis. Leading electronic databases such as PubMed have been searched to identify large-scale longitudinal studies of representative samples of adolescents and young adults conducted in developed societies over the past 20 years. RESULTS: Cannabis is a drug of dependence, the risk of which increases with decreasing age of initiation. Cannabis dependence in young people predicts increased risks of using other illicit drugs, underperforming in school, and reporting psychotic symptoms. Uncertainty remains about which of these relationships are causal although the evidence is growing that cannabis is a contributory cause of psychotic symptoms. CONCLUSIONS: We face major challenges in communicating with young people about the most probable risks of cannabis use (dependence, educational underachievement and psychosis) given uncertainties about these risks and polarized community views about the policies that should be adopted to reduce them.     

Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism

Estrada G, Fatjó‐Vilas M, Muñoz MJ, Pulido G, Miñano MJ, Toledo E, Illa JM, Martín M, Miralles ML, Miret S, Campanera S, Bernabeu C, Navarro ME, Fañanás L. Cannabis use and age at onset of psychosis: further evidence of interaction with COMT Val158Met polymorphism. Objective: To examine, in a sample of young psychiatric patients, (n = 157, mean age 17.01 years (SD = 3.6)) whether i) age at first cannabis use and age at emergence of psychiatric disorders are related and ii) such a relationship is modulated by the Val158Met polymorphism in the COMT gene. Method: Cannabis use profiles and COMT Val158Met genotypes were obtained from 80 inpatients with schizophrenia‐spectrum disorders and 77 inpatients with other non‐psychotic disorders. Results: First, age at first cannabis use correlates with age at onset in both schizophrenia‐spectrum and other psychiatric disorder groups: those who started using cannabis earlier had an earlier age at onset of psychiatric disorders. Second, the distribution of the Val158Met genotypes was not different either between diagnosis groups or between cannabis users and non‐users. Third, an interaction between Val158Met genotypes and cannabis use was observed specifically on age at emergence of psychotic disorders, with Val/Val genotype carriers showing an earlier age at onset than Met carriers. Conclusion: Our results suggest the importance of brain maturation timing in which exposure to cannabis occurs. The COMT Val158Met genotype seems to modulate the association between cannabis and age at onset of psychotic disorders. These results are consistent with previous studies.     

Associations Between Maternal Prenatal C-Reactive Protein and Risk Factors for Psychosis in Adolescent Offspring: Findings From the Northern Finland Birth Cohort 1986

Prenatal infection is associated with brain structural and functional abnormalities and may increase the risk for psychosis through a direct effect on neurodevelopment. Various infections may exert their effect through a proinflammatory immune response but studies of prenatal maternal inflammatory markers and offspring neurodevelopment are scarce. Using the longitudinal Northern Finland Birth Cohort 1986 study, we examined the associations of maternal prenatal C-reactive protein (CRP) levels with psychosis risk factors in adolescent offspring. CRP was measured in maternal sera collected in pregnancy. In offspring, school performance was measured at age 7 years, while school performance, psychotic experiences, and cannabis use were measured at age 16 years. We tested associations of CRP with offspring measures using regression analysis controlling for offspring sex, maternal education level, and prenatal maternal body mass index, smoking and alcohol use in pregnancy, place of birth, maternal psychiatric admission, paternal psychiatric admission, mothers age at birth, and gestational week of CRP sample. We also tested if adolescent cannabis use mediated the associations between maternal CRP and offspring outcomes. Controlling for covariates, maternal CRP was associated with academic performance at age 16 years (beta = .062, 95% CI = 0.036–0.088), but not with possible psychotic experiences at 16 years (odds ratio [OR] = 1.09, 95% CI = 0.96–1.24). Maternal CRP was also associated with adolescent cannabis use (OR = 1.24, 95% CI = 1.07–1.43). These findings suggest that prenatal inflammation may influence later mental illness risk by affecting neurodevelopment and also indirectly by increasing the risk of exposure to cannabis.     

Daily Use,Especially of High-Potency Cannabis,Drives the Earlier Onset of Psychosis in Cannabis Users

Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16–1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11–1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06–1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.Key words: psychotic disorders, age of onset, gender, cannabis, survival plots, drug use, high-potency cannabis     

3-Year Follow-up of Lower Risk Cannabis Use Patterns: Evidence from a Longitudinal Survey

Objectives:Following recommendations from the Lower Risk Cannabis Use Guidelines, we evaluated how lower risk cannabis use (late initiation and low use frequency) was associated with the risk of developing cannabis abuse/dependence over a 3-year follow-up period compared to 12-month abstinence (controls) or higher risk cannabis use (early initiation and higher use frequency). We also explored the effect of cannabis quantity.Methods:Data were obtained from the U.S. nationally representative survey, National Epidemiologic Survey on Alcohol and Related Conditions wave I (2001 to 2002) and wave II (2004 to 2005), which included 31,464 respondents with no lifetime history of cannabis abuse/dependence at the first interview. We applied multiple logistic regression and propensity score matching analyses to examine the association between different use patterns at wave I and cannabis abuse/dependence at wave II, adjusting for covariates. Lower risk cannabis use and the transition to higher use frequency were also assessed.Results:For propensity score analysis, lower risk cannabis use at wave I was associated with higher risk of cannabis use/dependence at wave II compared to controls (odds ratio [OR]: 4.27; 95% confidence interval [95% CI], 1.57 to 11.61); however, there was no association with use frequency increase (OR: 2.52; 95% CI, 0.88 to 7.17). Higher risk use had a greater risk of cannabis use/dependence than controls (OR: 6.27; 95% CI, 2.56 to 15.38) and lower risk use (OR: 2.69; 95% CI, 1.12 to 6.47). Logistic regression analyses showed similar results, except that lower risk use was significantly associated with use frequency increase (OR: 2.49; 95% CI, 1.22 to 5.08). For the lower risk use group, 1 to 3 joints/day of use was significantly associated with cannabis abuse/dependence.Conclusions:We found that following recommended use patterns can significantly lower one’s risk of cannabis abuse/dependence. However, risk of cannabis abuse/dependence is still 4 times higher than staying abstinent. Updated recommendations on safe cannabis exposure levels are needed to guide cannabis use in the general population after cannabis legalization.     

Do cognitive schema mediate the association between childhood trauma and being at ultra-high risk for psychosis?

Exposure to childhood trauma has been associated with psychotic symptoms, being at ultra-high risk for psychosis (UHR), and psychotic disorders such as schizophrenia. Negative self-beliefs have been shown to partially mediate the relationship between childhood trauma and paranoia and have been shown to be characteristic of patients with psychosis. However, whether the association between childhood trauma and being at high risk of developing psychosis (e.g., UHR) and paranoia symptoms is mediated by altered cognitive schema is unknown and warrants investigation to inform preventive interventions. Data was collected on 30 UHR patients from Outreach and Support in South London about exposure to childhood trauma, cognitive schema, paranoia and cannabis use. Relative to healthy controls (n = 38), UHR patients were significantly more likely to report exposure to various types of childhood trauma (emotional and sexual abuse, and emotional and physical neglect), had more negative schema and less positive schema about themselves and others, and were more likely to use cannabis more than once a month. Emotional neglect was found to be significantly associated with UHR status even after controlling for the effects of previous exposure to cannabis use (b = 0.262, 95% CI: 0.115–0.408), and this association was partially mediated by negative self-schema (b = 0.045, 95% CI: 0.004–0.159). Similarly, emotional neglect was significantly associated with paranoia (b = 1.354, 95% CI: 0.246-2.462), and this association was partially mediated by negative self-schema (b = 0.988, 95% CI: 0.323-1.895). These findings provide preliminary evidence about the cognitive mechanisms that may underlie the association between childhood trauma and later risk for psychosis.     

Schizophrenia and the Environment: Within-Person Analyses May be Required to Yield Evidence of Unconfounded and Causal Association—The Example of Cannabis and Psychosis

Hypotheses about the link between cannabis use and psychosis apply to the within-person level but have been tested mostly at the between-person level. We used a within-person design, in which a person serves as his own control, thus removing the need to consider confounding by any fixed (genetic and nongenetic) characteristic to study the prospective association between cannabis use and the incidence of attenuated psychotic experiences, and vice versa, adjusted for time-varying confounders. We combined 2 general population cohorts (at baseline: Early Developmental Stages of Psychopathology Study, n = 1395; Netherlands Mental Health Survey and Incidence Study-2, n = 6603), which applied a similar methodology to study cannabis use and attenuated psychotic experiences with repeated interviews (T0, T1, T2, and T3) over a period of approximately 10 years. The Hausman test was significant for the adjusted models, indicating the validity of the fixed-effects model. In the adjusted fixed-effects model, prior cannabis use was associated with psychotic experiences (aOR = 7.03, 95% CI: 2.39, 20.69), whereas prior psychotic experiences were not associated with cannabis use (aOR = 0.59, 95% CI: 0.21, 1.71). Longitudinal studies applying random-effects models to study associations between risk factors and mental health outcomes, as well as reverse causality, may not yield precise estimates. Cannabis likely impacts causally on psychosis but not the other way round.     

Influence of cannabis use on incidence of psychosis in people at clinical high risk

Aims

Evidence for case–control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome.

Methods

Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale.

Results

During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome.

Conclusions

These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder.     

Psychosis risk as a function of age at onset

BACKGROUND: Little is known about late-onset psychosis (onset after the age 45 years) and how it relates to early-onset psychosis (before age 45 years). The aims of this study were to calculate the incidence of non-affective, non-organic psychotic symptoms across the life span and to explore the contribution of different sets of risk factors in relation to age at onset. METHODS: Data were obtained from the three measurements of the Netherlands Mental Health Survey and Incidence Study. Symptoms of psychosis were assessed in individuals aged 18-64 years using the Composite International Diagnostic Interview. All individuals reporting first-onset of psychotic symptoms within a three-year interval were included. The degree to which sets of risk factors affected the psychosis outcome similarly across age groups was assessed. RESULTS: The number of subjects displaying incident psychotic symptoms was similar across age groups. Cumulative incidence rates ranged from 0.3% to 0.4%. Age differences were found for life-time depressive symptoms (risk difference = 5%, 95% CI = 1%, 9%) and baseline neuroticism (risk difference = 3%, 95% CI = 0%, 6%), indicating that late-onset psychosis was less often preceded by these. In contrast, no effect modification by age was observed for female sex, hearing impairment, being single, or life-time cannabis use. CONCLUSIONS: Onset of psychotic symptoms in late life is no rare event. Compared to early onset psychosis, the late-onset counterpart less often arises in a context of emotional dysfunction and negative affectivity, suggesting qualitative differences in aetiology and more effective premorbid coping styles.     

Cannabis use is not associated with the development of psychosis in an 'ultra' high-risk group

BACKGROUND: The association between cannabis use and the development of a first psychotic episode was studied in a group of 100 young people identified as being at very high risk for the onset of psychosis. METHOD: The 'ultra' high risk cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-two per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of cannabis use by participants in the year prior to enrollment in the study was assessed at intake. RESULTS: Cannabis use or dependence in the year prior to recruitment to this study was not associated with a heightened risk of developing psychosis over the following 12-month period and therefore did not appear to contribute to the onset of a psychotic disorder. CONCLUSION: The results of this study suggest that cannabis use may not play an integral role in the development of psychosis in a high-risk group. While this study does not support a role for cannabis in the development of first-episode psychosis, we cannot conclude that cannabis use should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study (the low level of cannabis use in the current sample, the lack of monitoring of cannabis use after intake) suggest that it may be premature to dismiss cannabis use as a risk factor for the development of psychosis and further research is urged in this area.     

The initiation of cannabis use in adolescence is predicted by sex‐specific psychosocial and neurobiological features

Cannabis use initiated during adolescence might precipitate negative consequences in adulthood. Thus, predicting adolescent cannabis use prior to any exposure will inform the aetiology of substance abuse by disentangling predictors from consequences of use. In this prediction study, data were drawn from the IMAGEN sample, a longitudinal study of adolescence. All selected participants (n = 1,581) were cannabis‐naïve at age 14. Those reporting any cannabis use (out of six ordinal use levels) by age 16 were included in the outcome group (N = 365, males n = 207). Cannabis‐naïve participants at age 14 and 16 were included in the comparison group (N = 1,216, males n = 538). Psychosocial, brain and genetic features were measured at age 14 prior to any exposure. Cross‐validated regularized logistic regressions for each use level by sex were used to perform feature selection and obtain prediction error statistics on independent observations. Predictors were probed for sex‐ and drug‐specificity using post‐hoc logistic regressions. Models reliably predicted use as indicated by satisfactory prediction error statistics, and contained psychosocial features common to both sexes. However, males and females exhibited distinct brain predictors that failed to predict use in the opposite sex or predict binge drinking in independent samples of same‐sex participants. Collapsed across sex, genetic variation on catecholamine and opioid receptors marginally predicted use. Using machine learning techniques applied to a large multimodal dataset, we identified a risk profile containing psychosocial and sex‐specific brain prognostic markers, which were likely to precede and influence cannabis initiation.