Review
Assessing evidence for a causal link between cannabis and psychosis: A review of cohort studies

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Abstract

Over the past five years, the release of cohort studies assessing the link between cannabis and psychosis has increased attention on this relationship. Existing reviews generally conclude that these cohort studies show cannabis has a causal relationship to psychosis, or at least that one cannot be excluded. Few studies have evaluated the relative strengths and limitations of these methodologically heterogeneous cohort studies, and how their relative merits and weaknesses might influence the way the link between cannabis use and psychosis is interpreted. This paper reviews the methodological strengths and limitations of major cohort studies which have looked at the link between cannabis and psychosis, and considers research findings against criteria for causal inference.

Cohort studies that assessed the link between cannabis and psychosis were identified through literature searches using relevant search terms and MEDline, PsycINFO and EMBASE. Reference lists of reviews and key studies were hand searched. Only prospective studies of general population cohorts were included. Findings were synthesised narratively.

A total of 10 key studies from seven general population cohorts were identified by the search. Limitations were evident in the measurement of psychosis, consideration of the short-term effects of cannabis intoxication, control of potential confounders and the measurement of drug use during the follow-up period. Pre-existing vulnerability to psychosis emerged as an important factor that influences the link between cannabis use and psychosis.

Whilst the criteria for causal association between cannabis and psychosis are supported by the studies reviewed, the contentious issue of whether cannabis use can cause serious psychotic disorders that would not otherwise have occurred cannot be answered from the existing data. Further methodologically robust cohort research is proposed and the implications of how evidence informs policy in the case of uncertainty is discussed.

Introduction

Over the past five years, the publication of cohort studies assessing the relationship between cannabis and psychosis has attracted considerable attention in the research literature, popular media, and the community generally (Andreasson et al., 1987, Arseneault et al., 2002, Caspi et al., 2005, Fergusson et al., 2005, Henquet et al., 2005a, van Os et al., 2002, Zammit et al., 2002). These studies have often been interpreted as demonstrating that cannabis use is causally related to psychotic disorders, such as schizophrenia (Smit, Bolier, & Cuijpers, 2004). Existing reviews have concluded that evidence from these cohort studies show that cannabis has a causal relationship to psychosis (Arseneault et al., 2004, Henquet et al., 2005b, Moore et al., 2007, Semple et al., 2005, Smit et al., 2004), or that the possibility of such a relationship cannot be excluded (Macleod et al., 2004a, Macleod et al., 2004b). However, a number of methodological limitations of these cohort studies raise uncertainties about whether cannabis use is causally related to psychotic disorders. Whilst a number of reviews of these cohort studies have been published (Arseneault et al., 2004, Hall, 2006a, Hall, 2006b, Macleod et al., 2004a, Macleod et al., 2004b, Moore et al., 2007), few have evaluated the relative strengths and limitations of these methodologically heterogeneous cohort studies (e.g., Moore et al., 2007), and how their relative merits and weaknesses might influence the way in which the link between cannabis use and psychosis is interpreted.

Psychosis describes a mental state characterised by the following symptoms: delusions, which involve having beliefs that are not true; hallucinations, which involve sensing things that are not there such as hearing voices; and gross disorganisation of speech and/or behaviour such that the sufferer's speech and actions do not make sense (American Psychiatric Association, 2000). Psychosis is usually thought of in association with schizophrenia, but is also present to varying degrees in over ten additional mental disorders (American Psychiatric Association, 2000). It should be noted that discrete psychotic symptoms can be experienced without necessarily being part of a psychotic disorder; such symptoms are not necessarily clinically significant, especially if they are transient or short lived. If the symptoms are severe enough, or there are multiple symptoms co-occurring for a sufficient time period, then a psychotic disorder, such as schizophrenia, may be diagnosed. To diagnose schizophrenia the following criteria need to be met: (a) experience of two or more characteristic symptoms (delusions, hallucinations, disorganised speech, grossly disorganised or catatonic behaviour, in addition to ‘negative symptoms’, which refer to a set of symptoms including lack of emotional expression, lack of speech, and/or lack of motivation) for a significant part of a one-month period of time; (b) social or occupational dysfunction; and (c) continuous signs of disturbance for at least six months (American Psychiatric Association, 2000).

This paper aims to review the methodological strengths and limitations of cohort studies which have looked at the link between cannabis and psychosis, and consider research findings against criteria for causal inference.

Section snippets

Search strategy and inclusion criteria

Cohort studies published from 1950 to 2008 that have assessed the link between cannabis and psychosis were identified in English language sources through literature searches using MEDline, PsycINFO and EMBASE. Standardised search terms used included combinations of: cannabis, marihuana, cannabinoid, hemp, ganja, bhang, THC, psychosis, psychotic, psychoses, schizo$ (‘$’ indicates truncation), cohort studies, and prospective studies. Relevant subject headings were ‘exploded’, so that subheadings

Results

The literature search returned 270 studies after duplicate studies were removed. On the basis of abstracts, 75 studies were judged as potentially relevant. Of these, 65 were excluded as not relevant after reading the whole paper and after expert advice. A total of 10 studies (from seven general population cohorts) were identified as relevant to the review (Table 1). The following major cohort studies were identified.

Discussion

All but one of the cohort studies reviewed here reported associations between cannabis use and subsequent ‘psychosis’, and the association often showed a dose–response relationship. These results, combined with the cross-sectional evidence for association, provide evidence that cannabis use, particularly early and frequent cannabis use, is associated with later ‘psychosis’. However, in a number of studies the associations between cannabis use and psychosis do not remain significant once factors

Conclusion

Although the studies reviewed here found a reasonably consistent relationship between cannabis and ‘psychosis’, only one study reported a significant relationship between cannabis use and the subsequent development of a psychotic disorder meeting diagnostic criteria, whilst controlling for confounding factors (Zammit et al., 2002). The population impact of experiencing one or two symptoms of psychosis – particularly when it is often unclear whether the symptoms occurred within the period of

Funding

Funding was provided by the Australian Government Department of Health and Ageing. Delyse Hutchinson was supported by a Vice-Chancellor's Post-Doctoral Research Fellowship from the University of New South Wales, Sydney.

Conflict of interest statement

All authors have no actual or potential conflict of interest to declare.

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