Cannabis use and age of diagnosis of schizophrenia

Background and objectivesObservational studies have reported earlier onset of psychosis in schizophrenic patients with a history of cannabis use. Earlier age of onset of schizophrenia has been associated with a poorer outcome. We aimed to examine whether cannabis use determined an earlier onset of schizophrenia in a sample of first episode patients, in an area with one of Europe's highest rates of cannabis use.Methods116 subjects with first episode psychosis and subsequent diagnosis of schizophrenia (after a 12-month follow-up) were included Age at first antipsychotic treatment (A1T) was used as proxy for age of psychosis onset, and acted as dependent variable for the statistical analysis. Cannabis use was evaluated retrospectively, and divided into three groups according to peak frequency (never, sporadic/frequent, daily).Results46 (39.7%) subjects had never used cannabis, 23 (19.9%) had done so sporadically/frequently, and 47 (40.5%) daily. A1T differed between the three groups (mean, in years and [SD]: 27.0 [4.94]; 25.7 [4.44] and 24.5 [4.36]; p = 0.033) and diminished as cannabis use increased (linear tendency; p = 0.009). Post-hoc analysis showed that cannabis use (irrespective of frequency) was significantly associated with decrease in A1T (p = 0.033), as shown by the first contrast [1 ?1/2 ?1/2]. Post-hoc contrast showed that cannabis users had a significantly lower age of onset of psychosis (mean decrease, in years: 1.93; CI (confidence interval) 95%: 0.17–3.70; p = 0.033).ConclusionsCannabis use was significantly associated with a decrease in age of onset of schizophrenia. Age of onset of the disease correlated with frequency of cannabis use.     

First-Episode Psychosis Patients Who Deteriorated in the Premorbid Period Do Not Have Higher Polygenic Risk Scores Than Others: A Cluster Analysis of EU-GEI Data

Cluster studies identified a subgroup of patients with psychosis whose premorbid adjustment deteriorates before the onset, which may reflect variation in genetic influence. However, other studies reported a complex relationship between distinctive patterns of cannabis use and cognitive and premorbid impairment that is worthy of consideration. We examined whether: (1) premorbid social functioning (PSF) and premorbid academic functioning (PAF) in childhood and adolescence and current intellectual quotient (IQ) define different clusters in 802 first-episode of psychosis (FEP) patients; resulting clusters vary in (2) polygenic risk scores (PRSs) for schizophrenia (SCZ_PRS), bipolar disorder (BD_PRS), major depression (MD_PRS), and IQ (IQ_PRS), and (3) patterns of cannabis use, compared to 1,263 population-based controls. Four transdiagnostic clusters emerged (BIC = 2268.5): (1) high-cognitive-functioning (n = 205), with the highest IQ (Mean = 106.1, 95% CI: 104.3, 107.9) and PAF, but low PSF. (2) Low-cognitive-functioning (n = 223), with the lowest IQ (Mean = 73.9, 95% CI: 72.2, 75.7) and PAF, but normal PSF. (3) Intermediate (n = 224) (Mean_IQ = 80.8, 95% CI: 79.1, 82.5) with low-improving PAF and PSF. 4) Deteriorating (n = 150) (Mean_IQ = 80.6, 95% CI: 78.5, 82.7), with normal-deteriorating PAF and PSF. The PRSs explained 7.9% of between-group membership. FEP had higher SCZ_PRS than controls [F(4,1319) = 20.4, P < .001]. Among the clusters, the deteriorating group had lower SCZ_PRS and was likelier to have used high-potency cannabis daily. Patients with FEP clustered according to their premorbid and cognitive abilities. Pronounced premorbid deterioration was not typical of most FEP, including those more strongly predisposed to schizophrenia, but appeared in a cluster with a history of high-potency cannabis use.     

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.     

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.     

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     

Associations Between Canada's Cannabis Legalization and Emergency Department Presentations for Transient Cannabis-Induced Psychosis and Schizophrenia Conditions: Ontario and Alberta, 2015–2019

ObjectiveCannabis legalization in many jurisdictions worldwide has raised concerns that such legislation might increase the burden of transient and persistent psychotic illnesses in society. Our study aimed to address this issue.MethodsDrawing upon emergency department (ED) presentations aggregated across Alberta and Ontario, Canada records (April 1, 2015–December 31, 2019), we employed Seasonal Autoregressive Integrated Moving Average (SARIMA) models to assess associations between Canada''s cannabis legalization (via the Cannabis Act implemented on October 17, 2018) and weekly ED presentation counts of the following ICD-10-CA-defined target series of cannabis-induced psychosis (F12.5; n = 5832) and schizophrenia and related conditions (“schizophrenia”; F20-F29; n = 211,661), as well as two comparison series of amphetamine-induced psychosis (F15.5; n = 10,829) and alcohol-induced psychosis (F10.5; n = 1,884).ResultsED presentations for cannabis-induced psychosis doubled between April 2015 and December 2019. However, across all four SARIMA models, there was no evidence of significant step-function effects associated with cannabis legalization on post-legalization weekly ED counts of: (1) cannabis-induced psychosis [0.34 (95% CI −4.1; 4.8; P = 0.88)]; (2) schizophrenia [24.34 (95% CI −18.3; 67.0; P = 0.26)]; (3) alcohol-induced psychosis [0.61 (95% CI −0.6; 1.8; P = 0.31); or (4) amphetamine-induced psychosis [1.93 (95% CI −2.8; 6.7; P = 0.43)].ConclusionImplementation of Canada''s cannabis legalization framework was not associated with evidence of significant changes in cannabis-induced psychosis or schizophrenia ED presentations. Given the potentially idiosyncratic rollout of Canada''s cannabis legalization, further research will be required to establish whether study results generalize to other settings.     

Generalized Anxiety Disorder 7-Item (GAD-7) Scores in Medically Authorized Cannabis Patients—Ontario and Alberta,Canada

ObjectivesDespite increasing rates of legalization of medical cannabis worldwide, the current evidence available on its effect on mental health outcomes including anxiety is of mixed results. This study assesses the effect of medical cannabis on generalized anxiety disorder 7-item (GAD-7) scores in adult patients between 2014 and 2019 in Ontario and Alberta, Canada.MethodsAn observational cohort study of adults authorized to use medical cannabis. The GAD-7 was administered at the time of the first visit to the clinic and subsequently over the follow-up time period of up to 3.2 years. Overall changes in GAD-7 scores were computed (mean change) and categorized as: no change (<1 point); improvement; or worsening—over time.ResultsA total of 37,303 patients had initial GAD-7 scores recorded and 5,075 (13.6%) patients had subsequent GAD-7 follow-up scores. The average age was 54.2 years (SD 15.7 years), 46.0% were male, and 45.6% noted anxiety symptoms at the baseline. Average GAD-7 scores were 9.11 (SD 6.6) at the baseline and after an average of 282 days of follow-up (SD 264) the average final GAD-7 score recorded was 9.04 (SD 6.6): mean change −0.23 (95% CI, −0.28 to −0.17, t[5,074]: −8.19, p-value <0.001). A total of 4,607 patients (90.8%) had no change in GAD-7 score from their initial to final follow-up, 188 (3.7%) had a clinically significant decrease, and 64 (1.3%) noted a clinically significant increase in their GAD-7 scores.ConclusionsOverall, there was a statistically significant decrease in GAD-7 scores over time (in particular, in the 6–12-month period). However, this change did not meet the threshold to be considered clinically significant. Thus, we did not detect clinical improvements or detriment in GAD-7 scores in medically authorized cannabis patients. However, future well-controlled clinical trials are needed to fully examine risks or benefits associated with using medical cannabis to treat anxiety conditions.     

Temporal relationship of first-episode non-affective psychosis with cannabis use: A clinical verification of an epidemiological hypothesis

Background

We analyzed the association of age at onset of psychosis treatment (AOPT) with having a history of cannabis use in patients with a first episode of non-affective psychosis. We also investigated the impact on the AOPT of exposure to cannabis in adolescence, compared with young adulthood, and of the additional exposure to cocaine.

Method

We recruited 112 consecutive patients (66 men and 46 women; age range, 18-57 years) with a first psychotic episode. The composite international diagnostic interview (CIDI) was used to assess drug use and to define the age at onset of heaviest use (AOHU) of a drug, defined as the age when drug was used the most for each patient. The effect of cannabis and cocaine AOHU on AOPT was explored through Kruskal-Wallis and Mann-Whitney tests, and logistic regression. Sex-adjusted cumulative hazard curves and Cox regression models were used to compare the AOPT of patients with and without a history of cannabis use, or associated cocaine use.

Results

We found that the AOPT was significantly associated with the use of cannabis, independently of sex, use of cocaine, tobacco smoking or excessive alcohol consumption. There was a dose-response relationship between cannabis AOHU and AOPT: the earlier the AOHU the earlier the AOPT. Hazard curves showed that patients with a history of cannabis use had a higher hazard of having a first-episode psychosis than the rest of the patients (sex-adjusted log-rank χ² = 23.43, df = 1, p < 0.001). Their respective median AOPT (25th, 75th percentiles) were 23.5 (21, 28) and 33.5 years (27, 45) (for log-transformed AOPT, t = 5.6, df = 110, p < 0.001). The sex-adjusted hazard ratio of psychosis onset comparing both groups was 2.66 (95% CI, 1.74-4.05).

Conclusions

Our results are in favor of a catalytic role for cannabis use in the onset of psychosis.     

Cannabis use and depression: a longitudinal study of a national cohort of Swedish conscripts

ABSTRACT: BACKGROUND: While there is increasing evidence on the association between cannabis use and psychotic outcomes, it is still unclear whether this also applies to depression. We aim to assess whether risk of depression and other affective outcomes is increased among cannabis users. METHODS: A cohort study of 45 087 Swedish men with data on cannabis use at ages 18[EN DASH]20. Diagnoses of unipolar disorder, bipolar disorder, affective psychosis and schizoaffective disorder were identified from inpatient care records over a 35-year follow-up period. Cox proportional hazard modeling was used to assess the hazard ratio (HR) of developing these disorders in relation to cannabis exposure. RESULTS: Only subjects with the highest level of cannabis use had an increased crude hazard ratio for depression (HR 1.5, 95% confidence interval (CI), 1.0-2.2), but the association disappeared after adjustment for confounders. There was a strong graded association between cannabis use and schizoaffective disorder, even after control for confounders, although the numbers were small (HR 7.4, 95% CI, 1.0-54.3). CONCLUSION: We did not find evidence for an increased risk of depression among those who used cannabis. Our finding of an increased risk of schizoaffective disorder is consistent with previous findings on the relation between cannabis use and psychosis.     

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.     

Hospital Admission With Infection During Childhood and Risk for Psychotic Illness—A Population-based Cohort Study

A growing body of literature suggests that exposure to infections, particularly maternal infections, during pregnancy confers risk for later development of psychotic disorder. Though brain development proceeds throughout childhood and adolescence, the influence of infections during these ages on subsequent psychosis risk is insufficiently examined. The aim of this study was to investigate the potential association between infections during childhood and nonaffective psychoses in a large population-based birth cohort with follow up long enough to include peak incidence of nonaffective psychosis. We included all individuals born in Sweden between 1973 and 1985, (N = 1172879), with follow up on first time inpatient care with nonaffective psychosis from age 14 years until 2006, (N = 4638). Following adjustment for differences in sex, socioeconomic status, family history of psychosis, and hospital admissions involving noninfectious, nonpsychiatric care, we observed a small but statistically significant association between hospital admissions for infections, in general, throughout childhood (0–13 years) and a later diagnosis of nonaffective psychosis, hazard ratio (HR) = 1.10 (95% CI 1.03–1.18), and this association seemed to be driven by bacterial infection, HR = 1.23 (95% CI 1.08–1.40). Bacterial infections and central nervous system infections during preadolescence (10–13 years) conferred the strongest risk, HR 1.57 (95% CI 1.21–2.05) and HR 1.96 (95% CI 1.05–3.62), respectively. Although preadolescence appeared to be a vulnerable age period, and bacterial infection the most severe in relation to psychosis development, the present findings can also indicate an increased susceptibility to hospital admission for infections among children who will later develop nonaffective psychosis due to social or familial/genetic factors.Key words: psychosis, prenatal, schizophrenia, epidemiology, cohort study     

Clinical characteristics influencing age at onset in psychotic disorders

Background

Age at onset of psychosis may carry clinical significance across psychotic disorders and appears to be associated with specific genetic abnormalities.

Methods

We used the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) to examine clinical characteristics contributing to age at onset variability in patients with schizophrenia (n = 80), schizoaffective disorder (n = 61), and bipolar disorder with psychotic features (n = 92).

Results

Age at onset did not differ across DSM-IV diagnostic groups. Multiple regression analyses revealed that comorbid lifetime cannabis, but not alcohol, abuse/dependence was associated with a statistically significant 3 years earlier age at onset of psychosis. Patients developed cannabis abuse/dependence an additional 3 years before psychosis. Patients with comorbid lifetime panic disorder also had a 4-year earlier age at onset of psychosis. The effects of panic disorder and cannabis abuse/dependence were independent of one another.

Conclusions

Early onset of psychosis, regardless of the specific DSM-IV diagnosis, is characterized by differential clinical features, notably a history of lifetime cannabis abuse/dependence. Panic disorder comorbidity is also associated with earlier age at onset of psychosis. Our findings indicate that examination of clinical and biological characteristics of patients with psychosis regardless of DSM-IV diagnosis can uncover relevant information.     

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.     

Depressive symptoms and cognitive impairment: A 10-year follow-up study from the Survey of Health,Ageing and Retirement in Europe

BackgroundDepressive symptoms and cognitive impairment often coexisted in the elderly. This study investigates the effect of late-life depressive symptoms on risk of mild cognitive impairment (MCI).MethodsA total of 14,231 dementia- and MCI free participants aged 60+ from the Survey of Health, Ageing, and Retirement in Europe were followed-up for 10 years to detect incident MCI. MCI was defined as 1.5 standard deviation (SD) below the mean of the standardized global cognition score. Depressive symptoms were assessed by a 12-item Europe-depression scale (EURO-D). Severity of depressive symptoms was grouped as: no/minimal (score 0–3), moderate (score 4–5), and severe (score 6–12). Significant depressive symptoms (SDSs) were defined as EURO-D score ≥ 4.ResultsDuring an average of 8.2 (SD = 2.4)-year follow-up, 1,352 (9.50%) incident MCI cases were identified. SDSs were related to higher MCI risk (hazard ratio [HR] = 1.26, 95% confidence intervals [CI]: 1.10–1.44) in total population, individuals aged 70+ (HR = 1.35, 95% CI: 1.14–1.61) and women (HR = 1.28, 95% CI: 1.08–1.51) in Cox proportional hazard model adjusting for confounders. In addition, there was a dose–response association between the severity of depressive symptoms and MCI incidence in total population, people aged ≥70 years and women (p-trend <0.001).ConclusionsSignificant depressive symptoms were associated with higher incidence of MCI in a dose–response fashion, especially among people aged 70+ years and women. Treating depressive symptoms targeting older population and women may be effective in preventing MCI.     

Does Change in Cannabis Use in Established Psychosis Affect Clinical Outcome?

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 prospectively 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.     

Early exposure to cannabis and risk for psychosis in young adolescents in Trinidad

Objective: Cannabis use increases the risk for psychosis, but psychotogenic effects of cannabis may be restricted to exposure during early adolescence. Method: Four hundred and seventy‐two participants (aged 12–23 years), randomly selected from the general population in Trinidad, completed questionnaires on past and current cannabis use and psychotic symptoms (using the Community Assessment of Psychic Experiences). Results: Cannabis use increased the risk of experiencing psychotic symptoms and this effect was conditional on early exposure, defined around the mean age of onset of cannabis use. Thus, exposure before but not after the age of 14 years predicted psychotic symptoms (respectively β: 0.71, 95% CI 0.22; 1.19, P = 0.004 and β: ?0.11, 95% CI ?0.57; 0.36, P = 0.66). The developmental effect of cannabis use was independent of use of other drugs or current use of cannabis. Conclusion: Early adolescence may be a critical period with regard to the psychotogenic effect of cannabis across geographical settings and ethnic groups.     

The Impact of Cannabis Use on Clinical Outcomes in Recent Onset 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 prospectively with repeated measures of substance use antecedent to psychopathology at baseline, 4.5, 9, and 18 months. We used random 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.Key words: psychosis, cannabis, substance use, dual diagnosis