Elsevier

The Lancet

Volume 370, Issue 9584, 28 Julyā€“3 August 2007, Pages 319-328
The Lancet

Articles
Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review

https://doi.org/10.1016/S0140-6736(07)61162-3Get rights and content

Summary

Background

Whether cannabis can cause psychotic or affective symptoms that persist beyond transient intoxication is unclear. We systematically reviewed the evidence pertaining to cannabis use and occurrence of psychotic or affective mental health outcomes.

Methods

We searched Medline, Embase, CINAHL, PsycINFO, ISI Web of Knowledge, ISI Proceedings, ZETOC, BIOSIS, LILACS, and MEDCARIB from their inception to September, 2006, searched reference lists of studies selected for inclusion, and contacted experts. Studies were included if longitudinal and population based. 35 studies from 4804 references were included. Data extraction and quality assessment were done independently and in duplicate.

Findings

There was an increased risk of any psychotic outcome in individuals who had ever used cannabis (pooled adjusted odds ratio=1Ā·41, 95% CI 1Ā·20ā€“1Ā·65). Findings were consistent with a dose-response effect, with greater risk in people who used cannabis most frequently (2Ā·09, 1Ā·54ā€“2Ā·84). Results of analyses restricted to studies of more clinically relevant psychotic disorders were similar. Depression, suicidal thoughts, and anxiety outcomes were examined separately. Findings for these outcomes were less consistent, and fewer attempts were made to address non-causal explanations, than for psychosis. A substantial confounding effect was present for both psychotic and affective outcomes.

Interpretation

The evidence is consistent with the view that cannabis increases risk of psychotic outcomes independently of confounding and transient intoxication effects, although evidence for affective outcomes is less strong. The uncertainty about whether cannabis causes psychosis is unlikely to be resolved by further longitudinal studies such as those reviewed here. However, we conclude that there is now sufficient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life.

Introduction

Cannabis, or marijuana, is the most commonly used illegal substance in most countries, including the UK and USA.1, 2, 3 About 20% of young people now report use at least once per week or heavy use (use on >100 occasions).4, 5 Use has increased particularly during early adolescence, when the developing brain might be especially susceptible to environmental exposures.6 Experimental studies7, 8, 9, 10 and surveys of users11, 12, 13 provide strong evidence that cannabis intoxication can produce transient, and usually mild, psychotic and affective experiences. Of greater concern are chronic symptoms that persist beyond, or occur independently of, intoxication effects.

Whether cannabis increases the incidence of established syndromes such as schizophrenia or depression is unclear, but this question is important because these disorders lead to substantial distress for individuals and their families, and to public burden from health-care costs. Randomised controlled trials (RCTs) of cannabis for medical use14 are unlikely to be helpful in addressing the question of causality because there are substantial differences between the pharmacokinetic profiles of such preparations and of cannabis used as a recreational drug. The typically short follow-up periods of such trials also substantially hinder interpretation of results.

Previous reviews in this field have not been very systematic, have examined broad psychosocial outcomes rather than mental illness, or have included cross-sectional data.15, 16, 17, 18, 19 We have systematically reviewed longitudinal studies of cannabis use and subsequent psychotic or affective mental health outcomes, and we have assessed the strength of evidence that cannabis use and these outcomes are causally related.

Section snippets

Study selection and data collection

Studies were included if they were population-based longitudinal studies, or case-control studies nested within longitudinal designs. We excluded cohorts of people with mental illness or substance-use-related problems, studies of prison populations, and RCTs of cannabis for medical use.14

Diagnostic outcomes for psychosis included schizophrenia, schizophreniform, schizoaffective, or psychotic disorders, non-affective or affective psychoses, psychosis not otherwise specified, psychotic symptoms,

Results

Searches of electronic bibliographic databases, expert advice, and searches of reference lists of included studies and other reviews yielded 4804 references. On the basis of their titles and abstracts, we judged that 175 (3Ā·6%) of these references potentially contained enough detail to be relevant. 143 of these references were excluded as not relevant when we had read the whole paper. Details of the studies that were excluded at this stage, including those that we regarded as near misses, are

Discussion

We found a consistent increase in incidence of psychosis outcomes in people who had used cannabis. There was no statistical evidence of publication bias, although this finding was based on only seven studies. The pooled analysis revealed an increase in risk of psychosis of about 40% in participants who had ever used cannabis. However, studies tended to report larger effects for more frequent use, with most studies showing a 50ā€“200% increase in risk for participants who used most heavily. A

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