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Cannabis Use and Risk of Psychotic Or Affective Mental Health Outcomes

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Cannabis Use and Risk of Psychotic Or Affective Mental Health Outcomes Articles Cannabis use and risk of psychotic or aff ective mental health outcomes: a systematic review Theresa H M Moore, Stanley Zammit, Anne Lingford-Hughes, Thomas R E Barnes, Peter B Jones, Margaret Burke, Glyn Lewis Summary Background Whether cannabis can cause psychotic or aff ective symptoms that persist beyond transient intoxication is Lancet 2007; 370: 319–28 unclear. We systematically reviewed the evidence pertaining to cannabis use and occurrence of psychotic or aff ective See Editorial page 292 mental health outcomes. See Comment page 293 Academic Unit of Psychiatry Methods We searched Medline, Embase, CINAHL, PsycINFO, ISI Web of Knowledge, ISI Proceedings, ZETOC, (T H M Moore MSc, BIOSIS, LILACS, and MEDCARIB from their inception to September, 2006, searched reference lists of studies selected S Zammit PhD, A Lingford-Hughes PhD, for inclusion, and contacted experts. Studies were included if longitudinal and population based. 35 studies from G Lewis PhD) and Department 4804 references were included. Data extraction and quality assessment were done independently and in duplicate. of Social Medicine (M Burke MSc), University of Findings There was an increased risk of any psychotic outcome in individuals who had ever used cannabis (pooled Bristol, Bristol, UK; Department of Psychological Medicine, adjusted odds ratio=1·41, 95% CI 1·20–1·65). Findings were consistent with a dose-response eff ect, with greater risk in Cardiff University, Cardiff , UK people who used cannabis most frequently (2·09, 1·54–2·84). Results of analyses restricted to studies of more clinically (S Zammit); Department of relevant psychotic disorders were similar. Depression, suicidal thoughts, and anxiety outcomes were examined separately. Psychological Medicine, Findings for these outcomes were less consistent, and fewer attempts were made to address non-causal explanations, Imperial College, London, UK (T R E Barnes DSc); and than for psychosis. A substantial confounding eff ect was present for both psychotic and aff ective outcomes. Department of Psychiatry, Cambridge University, Interpretation The evidence is consistent with the view that cannabis increases risk of psychotic outcomes Cambridge, UK (P B Jones PhD) independently of confounding and transient intoxication eff ects, although evidence for aff ective outcomes is less Correspondence to: strong. The uncertainty about whether cannabis causes psychosis is unlikely to be resolved by further longitudinal Dr Stanley Zammit, Department of Psychological Medicine, studies such as those reviewed here. However, we conclude that there is now suffi cient evidence to warn young people Cardiff University, Cardiff that using cannabis could increase their risk of developing a psychotic illness later in life. CF14 4XN, UK zammits@cardiff .ac.uk Introduction data.15–19 We have systematically reviewed longitudinal Cannabis, or marijuana, is the most commonly used studies of cannabis use and subsequent psychotic or illegal substance in most countries, including the UK aff ective mental health outcomes, and we have assessed and USA.1–3 About 20% of young people now report use the strength of evidence that cannabis use and these at least once per week or heavy use (use on >100 occa- outcomes are causally related. sions).4,5 Use has increased particularly during early ado- lescence, when the developing brain might be especially Methods susceptible to environmental exposures.6 Experi men- Study selection and data collection tal studies7–10 and surveys of users11–13 provide strong Studies were included if they were population-based evidence that cannabis intoxication can produce transient, longitudinal studies, or case-control studies nested and usually mild, psychotic and aff ective exper iences. Of within longitudinal designs. We excluded cohorts of greater concern are chronic symptoms that persist people with mental illness or substance-use-related beyond, or occur independently of, intoxi cation eff ects. problems, studies of prison populations, and RCTs of Whether cannabis increases the incidence of estab- cannabis for medical use.14 lished syndromes such as schizophrenia or depression is Diagnostic outcomes for psychosis included unclear, but this question is important because these schizophrenia, schizophreniform, schizoaff ective, or disorders lead to substantial distress for individuals and psychotic disorders, non-aff ective or aff ective psychoses, their families, and to public burden from health-care psychosis not otherwise specifi ed, psychotic symptoms, costs. Randomised controlled trials (RCTs) of cannabis delusions, hallucinations, or thought disorder. Presence for medical use14 are unlikely to be helpful in addressing of delusions, hallucinations, or thought disorder was a the question of causality because there are substantial requirement for all psychosis outcomes. Aff ective, mood, diff erences between the pharmacokinetic profi les of such or bipolar disorder, aff ective disorder not otherwise preparations and of cannabis used as a recreational drug. specifi ed, depression, suicidal ideation or suicide The typically short follow-up periods of such trials also attempts, anxiety, neurosis, and mania were included for substantially hinder interpretation of results. aff ective outcomes. Previous reviews in this fi eld have not been very We searched the following databases from their systematic, have examined broad psychosocial outcomes inception to Sept 5, 2006: Medline, Embase, and the rather than mental illness, or have included cross-sectional Cumulative Index to Nursing and Allied Health Literature www.thelancet.com Vol 370 July 28, 2007 319 Articles (CINAHL) on OVID; PsycINFO on WebSPIRS; ISI Web statistic.21 Presence of publication bias was investigated of Knowledge and ISI Proceedings; ZETOC (a British by use of funnel plots and Egger’s Test.22 A summary of library database of journal and conference contents); compliance with MOOSE guidelines23 is available on GL’s BIOSIS on EDINA; and Latin American and Caribbean departmental website. Health Sciences (LILACS) and Caribbean Health Sciences Literature (MEDCARIB). We searched using the format Role of the funding source “([psychosis or schizophrenia or synonyms] or [aff ective The sponsor of the study had no role in study design, disorder or depression or synonyms]) and (cannabis or data collection, data analysis, data interpretation, or synonyms)”, using text words and indexing (MeSH) writing of the report. The corresponding author had full terms (full details are available on GL’s departmental access to all the data in the study and had fi nal For Glyn Lewis’s departmental website). responsibility for the decision to submit for publication. website see bristol.ac.uk/Depts/ The search was restricted to studies on human beings Psychiatry/research/psychotic. but was not limited by language or study design. We Results html searched reference lists of included studies, and wrote to Searches of electronic bibliographic databases, expert experts in the fi eld and researchers responsible for advice, and searches of reference lists of included studies studies to fi nd other published and unpublished studies and other reviews yielded 4804 references. On the basis of relevance. We examined all titles and abstracts, and of their titles and abstracts, we judged that 175 (3·6%) of obtained full texts of potentially relevant papers. Working these references potentially contained enough detail to independently and in duplicate, we read the papers and be relevant. 143 of these references were excluded as not determined whether they met inclusion criteria using relevant when we had read the whole paper. Details of eligibility record forms (available on the corresponding the studies that were excluded at this stage, including author’s departmental website). We resolved disagree- those that we regarded as near misses, are available on ments by consensus, and extracted data independently GL’s departmental website. and in duplicate. We found 11 studies of psychosis; these reports We assessed study quality by recording how potential presented data from seven cohort studies. There were non-causal explanations, particularly bias and confound- fi ve adult population-based cohorts: the Epidemiological ing factors, were accounted for in each study. We assessed Catchment Area (ECA) study based in the USA;24 the information on sampling strategy, response rates, missing Early Developmental Stages of Psychopathology (EDSP) data, attrition, and attempts to address reverse causation, study based in Germany;25 the Netherlands Mental Health intoxication eff ects, and confounding factors. Survey and Incidence Study (NEMESIS);26 the National Psychiatric Morbidity Survey (NPMS) based in the UK;27 Data synthesis and the 1969 Swedish Conscript Cohort.28–30 There were Where study characteristics were judged reasonably also two birth cohorts, from Dunedin31,32 and Christchurch homogeneous, we grouped studies together and pooled (CHDS)33,34 in New Zealand. For the Swedish conscripts data in a meta-analysis; otherwise, we present a narrative and CHDS cohorts, data from the most recent reports29,34 synthesis of data. We pooled studies using the were included in each case because these had longer DerSimonian and Laird random-eff ects model20 and the follow-up to cover more events, and had more metan command in Stata (9·0). Where studies presented comprehensive analyses to keep reverse causation and data only in subgroups, these were incorporated as confounding eff ects to a minimum. Omission of separate studies.
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