Cannabis use and transition to psychosis in people at ultra-high risk. Cannabis use and risk of schizophrenia: a Mendelian randomization study The temporal dynamics of relationships between cannabis, psychosis and depression among young adults with psychotic disorders: findings from a 10-month prospective study. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability The impact of cannabis use on clinical outcomes in recent onset psychosis. Does change in cannabis use in established psychosis affect clinical outcome? Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study Epidemiological analysis of alcohol and drug use as risk factors for psychotic experiences. Assessing causality in associations between cannabis use and schizophrenia risk: a two-sample Mendelian randomization study Course of cannabis use and clinical outcome in patients with non-affective psychosis: a 3-year follow-up study. Continued cannabis use and outcome in first-episode psychosis: data from a randomized, open-label, controlled trial. Cannabis abuse and the course of recent onset schizophrenic disorders The impact of substance use on brain structure in people at high risk of developing schizophrenia. Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: an observational study. An Experimental Study of Catechol-O-Methyltransferase Val158Met Moderation of Δ-9-Tetrahydrocannabinol-Induced Effects on Psychosis and Cognition Developmental sensitivity to cannabis use patterns and risk for major depressive disorder in mid-life: findings from 40 years of follow-up.
BACKGROUND Cannabis use is associated with an increased risk of developing a psychotic disorder but the temporal relationship between cannabis use and onset of illness is unclear . The objective of this study was to assess prospect ively the influence of cannabis use on transition to psychosis in people at ultra-high risk ( UHR ) for the disorder . METHOD Lifetime and continued cannabis use was assessed in a consecutively ascertained sample of 182 people ( 104 male , 78 female ) at UHR for psychosis . Individuals were then followed clinical ly for 2 years to determine their clinical outcomes . RESULTS Lifetime cannabis use was reported by 134 individuals ( 73.6 % ) . However , most of these individuals had stopped using cannabis before clinical presentation ( n=98 , 73.1 % ) , usually because of adverse effects . Among lifetime users , frequent use , early-onset use and continued use after presentation were all associated with an increase in transition to psychosis . Transition to psychosis was highest among those who started using cannabis before the age of 15 years and went on to use frequently ( frequent early-onset use : 25 % ; infrequent or late-onset use : 5 % ; χ(2)1=10.971 , p=0.001 ) . However , within the whole sample , cannabis users were no more likely to develop psychosis than those who had never used cannabis ( cannabis use : 12.7 % ; no use : 18.8 % ; χ(2)1=1.061 , p=0.303 ) . CONCLUSIONS In people at UHR for psychosis , lifetime cannabis use was common but not related to outcome . Among cannabis users , frequent use , early-onset use and continued use after clinical presentation were associated with transition to psychosis Cannabis use is observationally associated with an increased risk of schizophrenia  , but whether the relationship is causal is not known . Using a genetic approach , we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia . Genetic variants were employed as instruments to recapitulate a r and omized controlled trial involving two groups (  cannabis users vs nonusers ) to estimate the causal effect of cannabis use on risk of schizophrenia  in 34 241 cases and 45 604 controls from predominantly European descent . Genetically-derived estimates were compared with a meta- analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders . Based on the genetic approach , use of cannabis was associated with increased risk of schizophrenia ( odds ratio ( OR ) of schizophrenia for users vs nonusers of cannabis : 1.37 ; 95 % confidence interval ( CI ) , 1.09–1.67 ; P-value=0.007 ) . The corresponding estimate from observational analysis was 1.43 ( 95 % CI , 1.19–1.67 ; P-value for heterogeneity = 0.76 ) . The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association ( OR of schizophrenia for users vs nonusers of cannabis , adjusted for ever vs never smoker : 1.41 ; 95 % CI , 1.09–1.83 ) . This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia , by suggesting that the relationship is causal . Such robust evidence may inform public health messages about cannabis use , especially regarding its potential mental health consequences BACKGROUND The aim was to examine the temporal relationships over 10 months between cannabis use and symptoms of psychosis and depression in people with schizophrenia and related disorders . The design was a prospect i ve study of 101 patients with schizophrenia and related disorders who were assessed monthly over 10 months on medication compliance , cannabis and other drug use , symptoms of depression and symptoms of psychosis . METHOD Linear regression methods to assess relationships between cannabis use and symptoms of psychosis and depression while adjusting for serial dependence , medication compliance and other demographic and clinical variables . RESULTS Cannabis use predicted a small but statistically significant increase in symptoms of psychosis , but not depression , after controlling for other differences between cannabis users and non-users . Symptoms of depression and psychosis did not predict cannabis use . CONCLUSION Continued cannabis use by persons with schizophrenia predicts a small increase in psychotic symptom severity but not vice versa Objective To determine whether use of cannabis in adolescence increases the risk for psychotic outcomes by affecting the incidence and persistence of sub clinical expression of psychosis in the general population ( that is , expression of psychosis below the level required for a clinical diagnosis ) . Design Analysis of data from a prospect i ve population based cohort study in Germany ( early developmental stages of psychopathology study ) . Setting Population based cohort study in Germany . Participants 1923 individuals from the general population , aged 14 - 24 at baseline . Main outcome measure Incidence and persistence of subthreshold psychotic symptoms after use of cannabis in adolescence .  Cannabis use and psychotic symptoms were assessed at three time points ( baseline , T2 ( 3.5 years ) , T3 ( 8.4 years ) ) over a 10 year follow-up period with the Munich version of the composite international diagnostic interview ( M-CIDI ) . Results In individuals who had no reported lifetime psychotic symptoms and no reported lifetime cannabis use at baseline , incident cannabis use over the period from baseline to T2 increased the risk of later incident psychotic symptoms over the period from T2 to T3 ( adjusted odds ratio 1.9 , 95 % confidence interval 1.1 to 3.1 ; P=0.021 ) . Furthermore , continued use of cannabis increased the risk of persistent psychotic symptoms over the period from T2 to T3 ( 2.2 , 1.2 to 4.2 ; P=0.016 ) . The incidence rate of psychotic symptoms over the period from baseline to T2 was 31 % ( 152 ) in exposed individuals versus 20 % ( 284 ) in non-exposed individuals ; over the period from T2 to T3 these rates were 14 % ( 108 ) and 8 % ( 49 ) , respectively . Conclusion Cannabis use is a risk factor for the development of incident psychotic symptoms . Continued cannabis use might increase the risk for psychotic disorder by impacting on the persistence of symptoms Cannabis use is a heritable trait that has been associated with adverse mental health outcomes . In the largest genome-wide association study ( GWAS ) for lifetime cannabis use to date ( N = 184,765 ) , we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions . All measured genetic variants combined explained 11 % of the variance . Gene-based tests revealed 35 significant genes in 16 regions , and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers . The strongest finding across the different analyses was CADM2 , which has been associated with substance use and risk-taking . Significant genetic correlations were found with 14 of 25 tested substance use and mental health – related traits , including smoking , alcohol use , schizophrenia and risk-taking . Mendelian r and omization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use . Overall , our study provides new insights into the etiology of cannabis use and its relation with mental health . A GWAS of lifetime cannabis use reveals new risk loci , shows that cannabis use has genetic overlap with smoking and alcohol use , and indicates that the likelihood of initiating cannabis use is causally influenced by schizophrenia BACKGROUND There are inconsistencies in findings as to whether cannabis use has a negative impact on clinical outcomes for people with established psychosis . Effects may be more evident on patients with recent onset psychosis . AIM To investigate the relationship between cannabis use and clinical outcome , including whether change in cannabis use affects psychotic symptoms , affective symptoms , functioning and psychotic relapse in a sample of people in early psychosis with comorbid cannabis abuse or dependence . METHODS One hundred and ten participants were examined prospect ively with repeated measures of substance use antecedent to psychopathology at baseline , 4.5 , 9 , and 18 months . We used r and om intercept models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes . RESULTS There was no evidence of a specific association between cannabis use and positive symptoms , or negative symptoms , relapse or hospital admissions . However , a greater dose of cannabis was associated with subsequent higher depression and anxiety . Change in the amount of cannabis used was associated with statistically significant corresponding change in anxiety scores , but not depression . Additionally , reductions in cannabis exposure were related to improved patient functioning . CONCLUSIONS Reducing cannabis may be directly associated with improvements in anxiety and functioning , but not other specific symptoms BACKGROUND Cannabis use has been identified as a potent predictor of the earlier onset of psychosis , but meta- analysis has not indicated that it has a clear effect in established psychosis . AIM To assess the association between cannabis and outcomes , including whether change in cannabis use affects symptoms and functioning , in a large sample of people with established nonaffective psychosis and comorbid substance misuse . METHODS One hundred and sixty participants whose substance use included cannabis were compared with other substance users ( n = 167 ) on baseline demographic , clinical , and substance use variables . The cannabis using subgroup was examined prospect ively with repeated measures of substance use and psychopathology at baseline , 12 months , and 24 months . We used generalized estimating equation models to estimate the effects of cannabis dose on subsequent clinical outcomes and whether change in cannabis use was associated with change in outcomes . RESULTS Cannabis users showed cross-sectional differences from other substances users but not in terms of positive symptoms . Second , cannabis dose was not associated with subsequent severity of positive symptoms and change in cannabis dose did not predict change in positive symptom severity , even when patients became abstinent . However , greater cannabis exposure was associated with worse functioning , albeit with a small effect size . CONCLUSIONS We did not find evidence of an association between cannabis dose and psychotic symptoms , although greater cannabis dose was associated with worse psychosocial functioning , albeit with small effect size . It would seem that within this population , not everyone will demonstrate durable symptomatic improvements from reducing cannabis Papers pp 1195 , 1199 The strongest evidence that cannabis use may be a risk factor for later psychosis  comes from a Swedish cohort study which found that heavy cannabis use at age 18 increased the risk of later schizophrenia sixfold . 1 2 This study could not establish whether adolescent cannabis use was a consequence of pre-existing psychotic symptoms rather than a cause . We present the first prospect i ve longitudinal study of adolescent cannabis use as a risk factor for  adult schizophreniform disorder  , taking into account childhood psychotic symptoms3 antedating cannabis use . View this table : Association between  cannabis use in adolescence and schizophrenia and depressive symptoms and disorders at age 26 ( n=759 ) , controlling for childhood psychotic symptoms and use of other drugs in adolescence The Dunedin multidisciplinary health and development study ( a study of a general population birth cohort of 1037 individuals born in Dunedin , New Zeal and , in 1972 - 3)4 has a 96 % follow up rate at age 26 . It obtained information on psychotic symptoms at age 11 and drug use at ages 15 and 18 from self reports and assessed Clinical and laboratory studies link alcohol and other drug use to the occurrence of psychotic experiences , but epidemiologic evidence has been lacking . In this study , the quantitative relationships between alcohol or other drug use and psychotic experiences were examined by analysis of prospect i ve data from 4994 adult household residents sample d in a multisite survey of mental disorders in the population , the NIMH Epidemiologic Catchment Area Program . After control for sociodemographic factors and preexisting psychiatric conditions , the risk for onset of self-reported delusions or hallucinations was observed to be greater for daily users of marijuana or cocaine and for users of anxiolytics or sympathomimetics compared with nonusers . After control for daily cocaine use and alcohol disorder , the risk of onset of psychotic experiences for daily users of marijuana was double that for nonusers .  Alcohol disorder in men  was associated with eightfold risk and in women with threefold risk . Baseline depressive episodes , manic episodes , agoraphobia , and obsessive-compulsive disorder also were associated with increased risk of onset of psychotic experiences Background Observational associations between cannabis and schizophrenia are well documented , but ascertaining causation is more challenging . We used Mendelian r and omization ( MR ) , utilizing publicly available data as a method for ascertaining causation from observational data . Method We performed bi-directional two- sample MR using summary -level genome-wide data from the International Cannabis Consortium ( ICC ) and the Psychiatric Genomics Consortium ( PGC2 ) . Single nucleotide polymorphisms ( SNPs ) associated with cannabis initiation ( p < 10−5 ) and schizophrenia ( p < 5 × 10−8 ) were combined using an inverse-variance-weighted fixed-effects approach . We also used height and education genome-wide association study data  , representing negative and positive control analyses . Results There was some evidence consistent with a causal effect of cannabis initiation on risk of schizophrenia [ odds ratio ( OR ) 1.04 per doubling odds of cannabis initiation , 95 % confidence interval ( CI ) 1.01–1.07 , p = 0.019 ] . There was strong evidence consistent with a causal effect of schizophrenia risk on likelihood of cannabis initiation ( OR 1.10 per doubling of the odds of schizophrenia , 95 % CI 1.05–1.14 , p = 2.64 × 10−5 ) . Findings were as predicted for the negative control ( height : OR 1.00 , 95 % CI 0.99–1.01 , p = 0.90 ) but weaker than predicted for the positive control ( years in education : OR 0.99 , 95 % CI 0.97–1.00 , p = 0.066 ) analyses . Conclusions Our results provide some that cannabis initiation increases the risk of schizophrenia , although the size of the causal estimate is small . We find stronger evidence that schizophrenia risk predicts cannabis initiation , possibly as genetic instruments for schizophrenia are stronger than for cannabis initiation BACKGROUND Prospect i ve studies on the relationship between course of cannabis use and clinical outcome in patients with non-affective psychotic disorders are inconclusive . The current study examined whether ( 1 ) persistent , recently started , discontinued and non-cannabis-using patients with a psychotic disorder differed with regard to illness outcome at 3-year follow-up , and ( 2 ) whether timing of cannabis discontinuation was associated with course of clinical outcome . METHOD This 3-year follow-up study was part of a multi-center study in the Netherl and s and Belgium ( Genetic Risk and Outcome of Psychosis ; GROUP ) . We used mixed-model analyses to investigate the association between pattern of cannabis use and symptoms , global functioning and psychotic relapse . RESULTS In our sample of 678 patients , we found persistent users to have more positive and general symptoms , worse global functioning and more psychotic relapses compared with non-users and discontinued users [ Positive and Negative Syndrome Scale ( PANSS ) positive , p < 0.001 ; PANSS general , p < 0.001 ; Global Assessment of Functioning ( GAF ) symptoms , p = 0.017 ; GAF disability , p < 0.001 ; relapses , p = 0.038 ] . Patients who started using cannabis after study onset were characterized by worse functioning at baseline and showed an increase in general symptoms ( including depression and anxiety ) at the 3-year follow-up ( p = 0.005 ) . Timing of cannabis discontinuation was not associated with clinical outcome . CONCLUSIONS These findings suggest that cannabis use in patients with a psychotic disorder has a long-lasting negative effect on illness outcome , particularly when persistent . Treatment should focus on discouraging cannabis use OBJECTIVE Cannabis use has been found to increase the risk of psychosis .  It is unclear whether , after a first psychotic episode has occurred , continued cannabis use is associated with poor functional outcome of psychosis . METHOD As part of a r and omized , open-label , controlled trial , the association of cannabis use and measures for psychopathology and social role functioning after 2 years of follow-up and for the recently proposed outcome measures of symptomatic remission , functional remission , and clinical recovery was explored in a group of 124 patients suffering from nonaffective first-episode psychosis ( diagnosed according to DSM-IV and included from a catchment area in the Netherl and s of 3.1 million inhabitants from October 2001 through December 2002 ) . Other patient characteristics that were expected to be independently associated with outcome , among them alcohol and other drug use , were assessed at baseline . RESULTS Continued cannabis use was not associated with symptomatic or functional remission or clinical recovery . After 2 years , cannabis use was related to certain aspects of social role functioning ( economic and social activities ; explained variance 5.6 % and 8.4 % , respectively ) but not to psychopathology ( Positive and Negative Syndrome Scale Positive , Negative , or General symptoms ) . CONCLUSIONS Our findings support the notion that continued cannabis use after the onset of a first-episode psychosis is correlated with worse social outcome and should be discouraged whenever possible , but its role in outcome is modest in comparison to other factors . TRIAL REGISTRATION Nederl and s Trial Register : http://www.trialregister.nl ( ID : NTR 374 ) OBJECTIVE We sought to examine the relation between cannabis abuse and the symptomatic course of recent-onset schizophrenia and related disorders . DESIGN A prospect i ve cohort study over a year using monthly Brief Psychiatric Rating Scale assessment s. PARTICIPANTS  Cannabis-abusing patients ( n = 24 ) were compared with nonabusers ( n = 69 ) . Eleven patients were mild and 13 were heavy cannabis-abusing patients . RESULTS Significantly more and earlier psychotic relapses occurred in the cannabis-abusing group ( P = .03 ) . This association became stronger when mild and heavy cannabis abuse were distinguished ( P = .002 ) . No confounding effect of other variables , eg , other street drugs , was found . In all but one patient , cannabis abuse preceded the onset of the first psychotic symptoms for at least 1 year . CONCLUSIONS Cannabis abuse and particularly heavy abuse can be considered a stressor eliciting relapse in patients with schizophrenia and related disorders and possibly a premorbid precipitant Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia . Both are present in first episode subjects and may be detectable before the onset of clinical disorder . Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities . We employ a prospect i ve cohort study with nested case control comparison design to investigate the association between substance misuse , brain abnormality , and subsequent schizophrenia . Substance misuse history , imaging data , and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls . Regions exhibiting a significant relationship between level of use of alcohol , cannabis or tobacco , and structure volume were identified . Multivariate regression then eluci date d the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders . Finally , we established whether substance misuse was associated with later risk of schizophrenia . Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner . Alcohol consumption was associated with reduced frontal lobe volume . Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model . Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia . We provide prospect i ve evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis . A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances BACKGROUND Although cannabis use after a first episode of psychosis has been associated with relapse , little is known about the determinants of this most preventable risk factor for relapse of psychosis . Here we aim ed to study whether the effects on outcome vary depending on the type of cannabis consumed and usage pattern . METHODS In this observational study , we prospect ively recruited and followed up patients aged 18 - 65 years who presented with their first episode of psychosis to psychiatric services in south London , London , UK .  Relapse of psychosis within 2 years after onset of psychosis was defined as risk of subsequent admission to hospital . We classified patients into different patterns of cannabis use based on continuity of use after onset of psychosis , potency of cannabis consumed , and frequency of use after the onset of their illness . We used multiple regression analyses ( logistic or binominal ) to compare the different cannabis use groups and propensity score analysis to vali date the results . FINDINGS Between April 12 , 2002 , and July 26 , 2013 , 256 patients presented with a first episode of psychosis . We did follow-up assessment s for these patients until September , 2015 . Simple analyses showed that former regular users of cannabis who stopped after the onset of psychosis had the most favourable illness course with regards to relapse . In multiple analysis , continued high-frequency users ( ie , daily use in all 24 months ) of high-potency ( skunk-like ) cannabis had the worst outcome , indexed as an increased risk for a subsequent relapse ( odds ratio [ OR ] 3·28 ; 95 % CI 1·22 - 9·18 ) , more relapses ( incidence rate ratio 1·77 ; 95 % CI 0·96 - 3·25 ) , fewer months until a relapse occurred ( b -0·22 ; 95 % CI -0·40 to -0·04 ) , and more intense psychiatric care ( OR 3·16 ; 95 % CI 1·26 - 8·09 ) after the onset of psychosis . INTERPRETATION Adverse effects associated with continued use of cannabis after the onset of a first episode of psychosis depend on the specific patterns of use . Possible interventions could focus on persuading cannabis-using patients with psychosis to reduce use or shift to less potent forms of cannabis . FUNDING National Institute for Health Research ( NIHR ) Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase ( COMT Val158Met ) gene moderate the psychosis-inducing effect of cannabis . To replicate and extend this finding , a double-blind , placebo-controlled cross-over design was used in which patients with a psychotic disorder ( n=30 ) , relatives of patients with a psychotic disorder ( n=12 ) , and healthy controls ( n=32 ) were exposed to Δ-9-tetrahydrocannabinol ( Δ-9-THC , the principal component of cannabis ) or placebo , followed by cognitive assessment and assessment of current psychotic experiences . Previous expression of psychometric psychosis liability was also assessed . Models of current psychotic experiences and cognition were examined with multilevel r and om regression analyses to assess ( i ) main effects of genotype and condition , ( ii ) interactions between condition and genotype , and ( iii ) three-way interactions between condition , genotype , and psychometric psychosis liability . Carriers of the Val allele were most sensitive to Δ-9-THC-induced psychotic experiences , but this was conditional on prior evidence of psychometric psychosis liability . Δ-9-THC impacted negatively on cognitive measures . Carriers of the Val allele were also more sensitive to Δ-9-THC-induced memory and attention impairments compared to carriers of the Met allele . Experimental effects of Δ-9-THC on cognition and psychosis are moderated by COMT Val158Met genotype , but the effects may in part be conditional on the additional presence of pre-existing psychosis liability . The association between cannabis and psychosis may represent higher order gene – environment and gene – gene interactions BACKGROUND Evidence regarding the association between cannabis use and depression  remain conflicting , especially as studies have not typically adopted a longitudinal design with a follow-up period that was long enough to adequately cover the risk period for onset of depression . METHOD Males from the Cambridge Study in Delinquent Development ( CSDD ) ( N = 285 ) were assessed seven times from age 8 to 48 years to prospect ively investigate the association between  cannabis use and risk of  major depressive disorder ( MDD ) .  A combination of multiple analyses ( logistic regression , Cox regression , fixed-effects analysis ) was employed to explore the strength and direction of effect within different developmental stages . RESULTS Multiple regression analyses revealed that early-onset cannabis use ( before age 18 ) but not late-onset cannabis use ( after age 27 ) was associated with a higher risk and shorter time until a subsequent MDD diagnosis . This effect was present in high-frequency [ ( odds ratio ( OR ) 8.83 , 95 % confidence interval ( CI ) 1.29 - 70.79 ] ; [ hazard ratio ( HR ) 8.69 , 95 % CI 2.07 - 36.52 ) ] and low-frequency early-onset users ( OR 2.41 , 95 % CI 1.22 - 4.76 ; HR 2.09 , 95 % CI 1.16 - 3.74 ) . Effect of increased frequency of cannabis use on increased risk of subsequent MDD was observed only for use during adolescence ( age 14 - 18 ) but not at later life stages , while controlling for observed and non-unobserved time-invariant factors . Conversely , MDD in adulthood ( age 18 - 32 ) was linked to a reduction in subsequent cannabis use ( age 32 - 48 ) . CONCLUSIONS The present findings provide evidence implicating frequent cannabis use during adolescence as a risk factor for later life depression . Future studies should further examine causality of effects in larger sample
The results show that , in particular , frequent cannabis use , especially daily use , and the consumption of high-potency cannabis are associated with a higher risk of developing psychosis .
Moreover , several genotypes moderate the impact of cannabis use on psychosis risk , particularly those involved in the dopamine function , such as AKT1 .
Finally , cannabis use is associated with an earlier psychosis onset and increased risk of transition in individuals at a clinical high risk of psychosis .
These findings indicate that changing cannabis use behavior could be a harm reduction strategy employed to lower the risk of developing psychosis .
Increasing evidence indicates a relationship between  cannabis use and psychosis risk .
Specific factors , such as determinants of cannabis use or the genetic profile of cannabis users , appear to moderate this association .
The present systematic review presents a detailed and up-to- date literature overview on factors that influence the relationship between cannabis use and psychosis risk .