Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis.

Cannabis use has been reported to induce long-lasting psychotic disorders and a dose-response relationship has been observed. We performed a systematic review of studies that investigate the association between the degree of cannabis consumption and psychosis and a meta-analysis to quantify the magnitude of effect. Published studies were identified through search of electronic databases, supplemented by manual searches of bibliographies. Studies were considered if they provided data on cannabis consumption prior to the onset of psychosis using a dose criterion (frequency/amount used) and reported psychosis-related outcomes. We performed random effects meta-analysis of individual data points generated with a simulation method from the summary data of the original studies. From 571 references, 18 studies fulfilled inclusion criteria for the systematic review and 10 were inserted in the meta-analysis, enrolling a total of 66 816 individuals. Higher levels of cannabis use were associated with increased risk for psychosis in all the included studies. A logistic regression model gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to the nonusers. Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis. Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs.

Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study.

BACKGROUND: The risk of individuals having adverse effects from drug use (eg, alcohol) generally depends on the frequency of use and potency of the drug used. We aimed to investigate how frequent use of skunk-like (high-potency) cannabis in south London affected the association between cannabis and psychotic disorders. METHODS: We applied adjusted logistic regression models to data from patients aged 18-65 years presenting to South London and Maudsley NHS Foundation Trust with first-episode psychosis and population controls recruited from the same area of south London (UK) to estimate the effect of the frequency of use, and type of cannabis used on the risk of psychotic disorders. We then calculated the proportion of new cases of psychosis attributable to different types of cannabis use in south London. FINDINGS: Between May 1, 2005, and May 31, 2011, we obtained data from 410 patients with first-episode psychosis and 370 population controls. The risk of individuals having a psychotic disorder showed a roughly three-times increase in users of skunk-like cannabis compared with those who never used cannabis (adjusted odds ratio [OR] 2·92, 95% CI 1·52-3·45, p=0·001). Use of skunk-like cannabis every day conferred the highest risk of psychotic disorders compared with no use of cannabis (adjusted OR 5·4, 95% CI 2·81-11·31, p=0·002). The population attributable fraction of first-episode psychosis for skunk use for our geographical area was 24% (95% CI 17-31), possibly because of the high prevalence of use of high-potency cannabis (218 [53%] of 410 patients) in our study. INTERPRETATION: The ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies. FUNDING: UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, SLaM and the Institute of Psychiatry at King's College London, Psychiatry Research Trust, Maudsley Charity Research Fund, and th European Community's Seventh Framework Program grant (agreement No. HEALTH-F2-2009-241909 [Project EU-GEI]).

Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.

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

What can we learn about schizophrenia from studying the human model, drug-induced psychosis?

When drug-induced psychoses were first identified in the mid-20th century, schizophrenia was considered a discrete disease with a likely genetic cause. Consequently, drug-induced psychoses were not considered central to understanding schizophrenia as they were thought to be phenocopies rather than examples of the illness secondary to a particular known cause. However, now that we know that schizophrenia is a clinical syndrome with multiple component causes, then it is clear that the drug-induced psychoses have much to teach us. This article shows how the major neuropharmacological theories of schizophrenia have their origins in studies of the effects of drugs of abuse. Research into the effects of LSD initiated the serotonergic model; amphetamines the dopamine hypothesis, PCP and ketamine the glutamatergic hypothesis, while most recently the effects of cannabis have provoked interest in the role of endocannabinoids in schizophrenia. None of these models account for the complete picture of schizophrenia; rather the various drug models mimic different aspects of the illness. Determining the different molecular effects of those drugs whose pharmacological effects do and do not mimic the various aspects of schizophrenia has much to teach us concerning the pathogenesis of the illness.

Antipsychotic medication in adolescents suffering from schizophrenia: a meta-analysis of randomized controlled trials.

BACKGROUND: The aim was to perform a meta-analysis on the efficacy, safety and tolerability of antipsychotic drugs in adolescents aged between 13 and 17 suffering from schizophrenia. METHODS: Enclosed studies - were multicentric, randomized, double-blind clinical trials; - included only adolescents (aged 13-17) with DSM-IV diagnosis of schizophrenia; - used standardized scales to assess efficacy, safety and tolerability of antipsychotics. RESULTS: All treatments resulted in significant improvements in Positive and Negative Syndrome Scale (PANSS) total score (p < 0.001), in PANSS positive subscale score (p < 0.001) and in Clinical Global Impression Scale-Severity of Illness score (p < 0.001) at the endpoint. Patients with a considerable weight gain were significantly higher in the olanzapine-treated group. Data about extrapyramidal side-effects were not available for olanzapine. Risperidone group was associated with a significantly major incidence of akathisia, tremor and dystonic events than controls. High dose of aripiprazole was associated with a significant major incidence of tremor and Parkinsonism (p < 0.01) than controls. CONCLUSIONS: Results demonstrated that antipsychotic treatment with risperidone, olanzapine or aripiprazole in adolescents affected by schizophrenia led to significant improvements in symptomatology. A pharmacological treatment for adolescents suffering from schizophrenia must fulfil several prerequisites, to grant the most favourable outcomes, avoiding acute and long term side-effects. Treatment with a 10 mg daily dose of aripiprazole was associated with the lowest incidence of extrapyramidal symptoms and showed no significant weight gain. If a treatment with antipsychotic drugs associated with significant weight gain as olanzapine or risperidone is needed, compensative measures should be soon considered.

[Obstetric complications and early-onset schizophrenia: a case-control study]. / Complicanze ostetriche e schizofrenia a esordio precoce: uno studio caso-controllo.

AIM: Research has suggested an association between obstetric complications and schizophrenia. METHODS: In this study data based on the obstetric birth case-notes of adolescent patients with diagnosed schizophrenia were compared to those of normal "healthy" same-aged control subjects. RESULTS: Complications involving a clear damaging potential (Level > 4 in the McNeil-Sjöström Scale) were seen significantly more often among cases than control subjects: 7% vs 2%, Fisher's exact test p < 0.04, odds ratio 4, 95%, CI: 1.048-15.26. DISCUSSION: Brain-damaging due to obstetric complications would seem to be a possible antecedent to a diagnosis of schizophrenia. Moreover, results support the evidence that obstetric adversity exerts an independent influence on the age at first presentation with schizophrenia. This finding suggests the existence of a causal relationship between obstetric adversity and age at onset of schizophrenia even if the small samples size limits the power of this study.