Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: an observational study. Cannabis use and transition to psychosis in people at ultra-high risk. The impact of cannabis use on clinical outcomes in recent onset psychosis. Course of cannabis use and clinical outcome in patients with non-affective psychosis: a 3-year follow-up study. Does change in cannabis use in established psychosis affect clinical outcome? 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 outcome in first-episode psychosis: data from a randomized, open-label, controlled trial. Design paper: The CapOpus trial: A randomized, parallel-group, observer-blinded clinical trial of specialized addiction treatment versus treatment as usual for young patients with cannabis abuse and psychosis A phase-specific psychological therapy for people with problematic cannabis use following a first episode of psychosis: a randomized controlled trial. A multi-center, randomized controlled trial of a group psychological intervention for psychosis with comorbid cannabis dependence over the early course of illness Motivational Intervention to Reduce Cannabis Use in Young People with Psychosis: A Randomized Controlled Trial Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study The impact of substance use on brain structure in people at high risk of developing schizophrenia. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Are deficits in cognition associated with psychotic-like experiences after cannabis? Is cannabis an anti-antipsychotic? The experience in psychiatric intensive care. Motivational interviewing and interaction skills training for parents of young adults with recent-onset schizophrenia and co-occurring cannabis use: 15-month follow-up. An Experimental Study of Catechol-O-Methyltransferase Val158Met Moderation of Δ-9-Tetrahydrocannabinol-Induced Effects on Psychosis and Cognition Attitude toward antipsychotic medication as a predictor of antipsychotic treatment discontinuation in first-episode early-onset psychosis. Blunted Psychotomimetic and Amnestic Effects of Δ-9-Tetrahydrocannabinol in Frequent Users of Cannabis First-episode psychosis at the West Bologna Community Mental Health Centre: results of an 8-year prospective study. Psychiatric treatment following participation in the CapOpus randomized trial for patients with comorbid cannabis use disorder and psychosis Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? A psychosis proneness-persistence model.
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 ) 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 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 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 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 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 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 ) Background A number of studies indicate a link between cannabis-use and psychosis as well as more severe psychosis in those with existing psychotic disorders . There is currently insufficient evidence to decide the optimal way to treat cannabis abuse among patients with psychosis . Objectives The major objective for the CapOpus trial is to evaluate the additional effect on cannabis abuse of a specialized addiction treatment program adding group treatment and motivational interviewing to treatment as usual . Design The trial is design ed as a r and omized , parallel-group , observer-blinded clinical trial . Patients are primarily recruited through early-psychosis detection teams , community mental health centers , and assertive community treatment teams . Patients are r and omized to one of two treatment arms , both lasting six months : 1 ) specialized addiction treatment plus treatment as usual or 2 ) treatment as usual . The specialized addiction treatment is manualized and consists of both individual and group-based motivational interviewing and cognitive behavioral therapy , and incorporates both the family and the case manager of the patient . The primary outcome measure will be changes in amount of cannabis consumption over time . Other outcome measures will be psychosis symptoms , cognitive functioning , quality of life , social functioning , and cost-benefit analyses . Trial registration Clinical Trials.gov NCT00484302 BACKGROUND Cannabis use is high amongst young people who have recently had their first episode of psychosis , and is associated with worse outcomes . To date , interventions to reduce cannabis consumption have been largely ineffective , and it has been suggested that longer treatment periods are required . METHOD In a pragmatic single-blind r and omized controlled trial 110 participants were r and omly allocated to one of three conditions : a brief motivational interviewing and cognitive behavioural therapy ( MI-CBT ) intervention ( up to 12 sessions over 4.5 months ) with st and ard care from an early intervention service ; a long MI-CBT intervention ( up to 24 sessions over 9 months ) with st and ard care ; or st and ard care alone . The primary outcome was change in cannabis use as measured by Timeline Followback . RESULTS Neither the extended nor the brief interventions conferred benefit over st and ard care in terms of reductions in frequency or amount of cannabis use . Also the interventions did not result in improvements in the assessed clinical outcomes , including symptoms , functioning , hospital admissions or relapse . CONCLUSIONS Integrated MI and CBT for people with cannabis use and recent-onset psychosis does not reduce cannabis use or improve clinical outcomes . These findings are consistent with those in the published literature , and additionally demonstrate that offering a more extended intervention does not confer any advantage . Many participants were not at an action stage for change and for those not ready to reduce or quit cannabis , targeting associated problems rather than the cannabis use per se may be the best current strategy for mental health services to adopt BACKGROUND Patients who experience the onset of psychotic illness with a comorbid diagnosis of cannabis dependence experience poor clinical outcomes . Few studies have identified interventions that reduce cannabis use and improve clinical outcome in this population . AIMS We undertook a multi-center , r and omized controlled trial of a group psychological intervention for psychosis with comorbid cannabis dependence to determine whether there was any impact on cannabis use symptoms , global functioning , insight , attitudes to treatment and subjective quality of life . METHOD Across three centers , we compared a group psychological intervention , based on cognitive behavioral therapy and motivational interviewing , with treatment as usual among patients experiencing their first psychotic episode or early in the course of psychotic illness . Substance misuse and indices of clinical outcome were assessed at baseline , 3months and 1year . RESULTS At 3month and 1year follow-ups , there was no evidence for an intervention effect on cannabis use , symptoms , global functioning insight or attitude to treatment . However , the intervention improved subjective quality of life at 3months and this effect was sustained at 1year . CONCLUSIONS Over the early phase of psychotic illness , group psychological interventions for those with comorbid cannabis dependence improved subjective quality of life . However , this was not associated with reduction in use of cannabis or improvement in clinical outcomes Background : Cannabis use has a negative impact on psychosis . Studies are needed to explore the efficacy of psychological interventions to reduce cannabis use in psychosis . Our aim is to study the efficacy of a specific motivational intervention on young cannabis users suffering from psychosis . Methods : Participants ( aged less than 35 years ) were r and omly assigned to treatment as usual ( TAU ) alone , or treatment as usual plus motivational intervention ( MI + TAU ) . TAU was comprehensive and included case management , early intervention and mobile team when needed . Assessment s were completed at baseline and at 3 , 6 and 12 months follow-up . Results : Sixty-two participants ( 32 TAU and 30 MI + TAU ) were included in the study .  Cannabis use decreased in both groups at follow-up . Participants who received MI in addition to TAU displayed both a greater reduction in number of joints smoked per week and greater confidence to change cannabis use at 3 and 6 months follow-up , but differences between groups were nonsignificant at 12 months . Conclusions : MI is well accepted by patients suffering from psychosis and has a short-term impact on cannabis use when added to st and ard care . However , the differential effect was not maintained at 1-year follow-up . MI appears to be a useful active component to reduce cannabis use which should be integrated in routine clinical practice 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 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 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 Not all individuals who smoke cannabis report psychotic-like experiences . Given that risk factors for psychotic disorders are multifaceted , precipitating factors to psychotic-like experiences after cannabis are likely to be equally complex . Reduced neurocognitive performance is associated with both psychosis risk and cannabis use . Therefore , it is possible cognitive performance may differentiate those who report psychotic-like experiences after cannabis from those who do not . We determined whether those reporting psychotic/dysphoric experiences after cannabis had reduced neurocognitive performance compared to those reporting primarily euphoric experiences . METHODS Participants were recruited on the basis of responses to the cannabis high captured by the Psychosis-Dysphoric and Euphoric experiences subscales from the Cannabis Experiences Question naire ( CEQ ) . RESULTS Compared to participants reporting primarily euphoric cannabis experiences ( n = 36 ; 44 % male ; mean age ( SD ) = 28 ( 9 ) years ) , those who reported psychotic/dysphoric experiences ( n = 40 ; 45 % male ; mean age ( SD ) = 26 ( 5 ) years ) demonstrated significantly faster responses to a trial and error learning task . In the presence of distracters , those with psychotic/dysphoric experiences after cannabis made more errors on a Continuous Performance Task . CONCLUSIONS Those who report psychotic/dysphoric experiences after cannabis have subtle inefficiencies in their cognitive processes . The multiple factors which predict vulnerability to psychotic-like experiences after cannabis require further investigation BACKGROUND Cannabis use is a major problem in inner cities and has been causally implicated in psychosis . Very few of the available hospital-based studies of the implication s of cannabis usage have involved psychiatric intensive care units ( PICU ) ; but PICU receive many of the most challenging and re source -hungry- and incompletely understood- patients in the mental health system . AIMS To study the clinical impact of cannabis abuse in a PICU , and to compare the use of atypical and typical antipsychotics in this setting . METHOD 115 patients admitted to a PICU consented to take part in an open label naturalistic study .  BPRS , TCI-240 , weight , length of admission and routine bloods were evaluated in all participants . RESULTS There was a high rate of cannabis abuse ( 71.3 % ) in the PICU population . Patients who abused cannabis spent longer in PICU because their psychoses were more severe . They were younger at first hospital admission . Cannabis also had metabolic implication s , with higher blood glucose levels at admission and greater weight increase .  Atypical antipsychotics were effective in treating psychosis in patients positive to cannabis at admission . CONCLUSION Our findings suggest that cannabis abusers had a more severe psychotic illness , especially in schizophrenia . There are additional complications in terms of weight gain for cannabis users BACKGROUND There is a clear need for effective interventions to reduce cannabis use in patients with first-episode psychosis . This follow-up of a r and omized trial examined whether an intervention for parents , based on motivational interviewing and interaction skills ( Family Motivational Intervention , FMI ) , was more effective than routine family support ( RFS ) in reducing cannabis use in patients with recent-onset schizophrenia . METHOD In a single-blind trial with 75 patients in treatment for recent-onset schizophrenia , 97 parents were r and omly assigned to either FMI or RFS . Assessment s were conducted at baseline and at 3 and 15 months after the interventions had been ended . Analyses were performed on an intention-to-treat basis using mixed-effect regression models . RESULTS From baseline to the 15-month follow-up , there was a significantly greater reduction in FMI  compared to RFS in patients ' quantity ( p = 0.01 ) and frequency ( p < 0.01 ) of cannabis use . Patients ' craving for cannabis use was also significantly lower in  FMI  at 15 months follow-up ( p < 0.01 ) . Both groups improved in parental distress and sense of burden ; however , only  FMI parents ' appraisal of patients ' symptoms showed further improvement at the 15-month follow-up ( p < 0.05 ) . CONCLUSIONS The results support the sustained effectiveness of FMI in reducing cannabis use in patients with recent-onset schizophrenia at 15 months follow-up . Findings were not consistent with regard to the long-term superiority of FMI over RFS in reducing parents ' distress and sense of burden 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 Antipsychotic drug discontinuation is a key risk factor in psychotic relapses . Clinical relapse is related to poor outcome , especially in the earlier stages of psychotic illness . The attitude toward treatment during the acute phase of a first episode of psychosis has been proposed as one of the main determinants of treatment discontinuation . However , the relationship between attitude toward antipsychotic medication and treatment discontinuation in the adolescent population has not been properly assessed . METHODS Adolescents , aged 12 - 18 years old , consecutively admitted to an adolescent unit with a first lifetime admission for a first episode of psychosis were asked to participate in a r and omized , flexible-dose , 6-month controlled trial of olanzapine vs. quetiapine .  Attitude toward antipsychotic medication  was assessed using the 10-item Drug Attitude Inventory ( DAI ) . The outcome variable was all-cause treatment discontinuation over the 6-month follow- up . The study sample was composed of 42 patients [ 34 boys ( 82.9 % ) , eight girls ( 17.1 % ) , mean age ± SD : 16.1±1.3 ] . RESULTS Of the 42 patients , only 29 ( 69 % ) continued the medication throughout the entire 6-month follow-up , while 13 ( 31 % ) discontinued the medication . DAI scores were greater than zero at all assessment s , indicating that the general attitude of the patients toward medication was positive . Higher DAI scores at baseline were related to lower all-cause treatment discontinuation [ adjusted hazard ratio ( HR ) = 0.81 ( 95 % CI : 0.68 - 0.96 ) , P=0.016 ] , while DAI scores at 15 days were unrelated to treatment discontinuation [ adjusted HR=1.0 ( 95 % CI : 0.82 - 1.23 ) , P=0.998 ] . CONCLUSIONS A better attitude toward antipsychotic medication at a first lifetime psychiatric admission for a first early-onset psychotic episode was significantly related to lower all-cause antipsychotic treatment discontinuation Cannabis is one of the most widely used illicit substances and there is growing interest in the association between cannabis use and psychosis .  Delta-9-Tetrahydrocannabinol ( Δ-9-THC ) the principal active ingredient of cannabis has been shown to induce psychotomimetic and amnestic effects in healthy individuals . Whether people who frequently use cannabis are either protected from or are tolerant to these effects of Δ-9-THC has not been established . In a 3-day , double-blind , r and omized , placebo-controlled study , the dose-related effects of 0 , 2.5 , and 5 mg intravenous Δ-9-THC were studied in 30 frequent users of cannabis and compared to 22 healthy controls . Δ-9-THC ( 1 ) produced transient psychotomimetic effects and perceptual alterations ; ( 2 ) impaired memory and attention ; ( 3 ) increased subjective effects of ‘ high ’ ; ( 4 ) produced tachycardia ; and ( 5 ) increased serum cortisol in both groups . However , relative to controls , frequent users showed blunted responses to the psychotomimetic , perceptual altering , cognitive impairing , anxiogenic , and cortisol increasing effects of Δ-9-THC but not to its euphoric effects . Frequent users also had lower prolactin levels . These data suggest that frequent users of cannabis are either inherently blunted in their response to , and /or develop tolerance to the psychotomimetic , perceptual altering , amnestic , endocrine , and other effects of cannabinoids BACKGROUND Research mostly conducted in the UK and northern Europe has established that there are high rates of first-episode psychosis ( FEP ) in large cities and immigrant population s ; moreover , psychosis has been found to be associated with cannabis use and early trauma . The present study aim ed to evaluate the incidence rate of FEP and the distribution of several risk factors ( e.g. age , ethnicity , substance abuse ) in Bologna , Italy . METHOD The Bologna FEP ( BoFEP ) study is an 8-year prospect i ve study . All FEP patients , 18 - 64 years old , consecutively referred to the West Bologna Community Mental Health Centre ( CMHC ) from 2002 to 2009 were evaluated . Sociodemographic information , migration history and clinical data were collected through an ad-hoc schedule . Psychiatric diagnoses were recorded using the Schedule for Clinical Assessment of Neuropsychiatry ( SCAN ) . RESULTS The overall incidence rate ( IR ) in the BoFEP study was 16.4 per 100 000 person-years [ 95 % confidence interval ( CI ) 13.9 - 18.9 ] . The incidence was higher in young people , men and migrants ( MI ) . CONCLUSIONS The IR of FEP found by the Bologna study is lower than that found by other European studies . However , as in other studies , the incidence was higher in certain groups . This heterogeneity has implication s for policy and mental health service development , and for underst and ing the aetiology of psychosis BACKGROUND R and omized trials targeting cannabis use disorders in patients with psychosis have generally been unsuccessful . One of the largest such trials was the CapOpus trial , which had an impact on the number of monthly joints used , but not on the number of days with cannabis use or positive or negative symptoms . OBJECTIVE To investigate the effects of CapOpus on psychiatric treatment . METHODS Six-month r and omized trial on participants meeting ICD-10 criteria for cannabis use disorder and schizophrenia-spectrum psychosis . Participants were r and omized to treatment as usual ( TAU , n=51 ) alone versus TAU plus CapOpus ( n=52 ) consisting of  motivational interviewing and cognitive behavior therapy . Data regarding psychiatric treatment was obtained from complete nationwide registers . Analyses were intention-to-treat . Cox and poisson regression were used as appropriate . RESULTS Compared with treatment as usual , participants in the CapOpus group had an overall higher risk of having a psychiatric emergency room contact ( hazard ratio 2.02 , 95 % confidence interval 1.22 - 3.34 ) . Participants in CapOpus also had more contacts with psychiatric emergency rooms ( incidence rate ratio 3.47 ( 2.64 - 4.57 ) ) and more admissions to psychiatric hospitals ( incidence rate ratio 2.24 ( 1.65 - 3.03 ) ) ; conversely , CapOpus- participants spent fewer days admitted to psychiatric hospitals than treatment-as-usual participants ( incidence rate ratio 0.72 ( 0.68 - 0.75 ) ) . CONCLUSIONS CapOpus led to earlier and more psychiatric emergency room contacts and admissions that , however , were of fewer days . This pattern could indicate that participants receiving treatment as usual were inadequately treated . However , it can not be excluded that the differences might be an adverse reaction to the psychosocial intervention BACKGROUND Research suggests that low- grade psychotic experiences in the general population are a common but transitory developmental phenomenon . Using two independent general population sample s , the hypothesis was examined that common , non- clinical developmental expression of psychosis may become abnormally persistent when synergistically combined with developmental exposures that may impact on behavioural and neurotransmitter sensitization such as cannabis , trauma and urbanicity . METHOD The amount of synergism was estimated from the additive statistical interaction between baseline cannabis use , childhood trauma and urbanicity on the one h and , and baseline psychotic experiences on the other , in predicting 3-year follow-up psychotic experiences , using data from two large , longitudinal , r and om population sample s from the Netherl and s [ The Netherl and s Mental Health Survey and Incidence Study ( NEMESIS ) ] and Germany [ The Early Developmental Stages of Psychopathology ( EDSP ) study ] . RESULTS The 3-year persistence rates of psychotic experiences were low at 26 % in NEMESIS and 31 % in EDSP . However , persistence rates were progressively higher with greater baseline number of environmental exposures in predicting follow-up psychotic experiences ( chi2=6.9 , df=1 , p=0.009 in NEMESIS and chi2=4.2 , df=1 , p=0.04 in EDSP ) . Between 21 % and 83 % ( NEMESIS ) and 29 % and 51 % ( EDSP ) of the subjects exposed to both environmental exposures and psychotic experiences at baseline had persistence of psychotic experiences at follow-up because of the synergistic action of the two factors . CONCLUSION The findings suggest that environmental risks for psychosis act additively , and that the level of environmental risk combines synergistically with non- clinical developmental expression of psychosis to cause abnormal persistence and , eventually , need for care
INTERPRETATION Continued cannabis use after onset of psychosis predicts adverse outcome , including higher relapse rates , longer hospital admissions , and more severe positive symptoms than for individuals who discontinue cannabis use and those who are non-users .
BACKGROUND Although the link between cannabis use and development of psychosis is well established , less is known about the effect of continued versus discontinued cannabis use after the onset of psychosis .
We aim ed to summarise available evidence focusing on the relationship between continued and discontinued cannabis use after onset of psychosis and its relapse .