Results In individuals who had no reported lifetime psychotic symptoms and no reported lifetime cannabis use at baseline, incident cannabis use over the period from baseline to T2 increased the risk of later incident psychotic symptoms over the period from T2 to T3 (adjusted odds ratio 1.9, 95% confidence interval 1.1 to 3.1; P=0.021). Furthermore, continued use of cannabis increased the risk of persistent psychotic symptoms over the period from T2 to T3 (2.2, 1.2 to 4.2; P=0.016). The incidence rate of psychotic symptoms over the period from baseline to T2 was 31% (152) in exposed individuals versus 20% (284) in non-exposed individuals; over the period from T2 to T3 these rates were 14% (108) and 8% (49), respectively.

Introduction

Cannabis is the most commonly used illicit drug in the world, particularly among adolescents.1 2 The use of cannabis is consistently associated with mental illness,3 in particular psychotic disorder.4 5 6 7 8 9 It remains a matter of debate, however, whether the association between cannabis and psychosis is causal, or whether early psychotic experiences might in fact prompt cannabis use as a means of self medication.10 11 This issue can be resolved only if incident cannabis use is investigated in relation to later incident psychotic symptoms or disorder. Rarely have studies been able to examine the longitudinal relation between cannabis use and psychosis in this fashion.

The issue of self medication was addressed by Henquet and colleagues,6 using data from the German prospective early developmental stages of psychopathology study.12 13 The authors investigated the association between cannabis use at baseline and subsequent development of psychotic symptoms at four year follow-up and reported that after adjustment for pre-existing psychotic symptoms, cannabis use at baseline still remained significantly associated with psychotic symptoms at follow-up. There was no evidence of an effect of self medication as pre-existing psychotic symptoms did not significantly predict later cannabis use.6 Ferdinand and co-workers investigated the role of pre-existing self reported psychotic symptoms and showed a bi-directional association between cannabis and psychotic symptoms over a 14 year follow-up study in the general population.11 They showed that cannabis use predicted later psychotic symptoms in individuals with no evidence of psychotic symptoms before starting to use cannabis and that the reverse was also true, in that psychotic symptoms predicted cannabis use in those who had not used cannabis before the onset of those symptoms.11 A prospective population based cohort study also found evidence for a self medication effect.14 Individuals with self reported hallucinations at the age of 14 had a higher risk of using cannabis on a daily basis at the age of 21. In a sibling pair analysis, however, this study also suggested an independent effect of cannabis use on self reported delusional ideation later in life.14 Thus, although the cannabis-psychosis link has been investigated in many studies, results on the temporal association between cannabis use and psychotic symptoms remain conflicting. Longitudinal cohort studies with multiple repeated interview based measures of cannabis use and psychotic symptoms are needed to clarify this issue. The EDSP study,12 13 which completed its recent 10 year follow-up representing the fourth assessment (assessments at baseline, T1, T2, and T3, see also fig 1⇓), is uniquely suitable for the investigation of the temporal association between cannabis and psychosis.

Another issue is the mechanism by which cannabis might increase the risk of psychotic symptoms, particularly whether it might increase the risk by causing persistence of normally transitory developmental expression of psychotic experiences. For most individuals, subclinical expression of psychotic phenomena (that is, expression of psychosis below the level required for a clinical diagnosis) is transitory and never progresses to psychotic illness.15 Subthreshold psychotic experiences could, however, become abnormally persistent, depending on the degree of additional exposure to environmental risk factors,16 17 18 and progressively greater levels of persistence might be associated with a greater risk for transition to clinical psychotic disorder.19 Spauwen and colleagues showed that the persistence rate of psychotic experiences was much higher for individuals growing up in an urban rather than a rural environment.16 Similarly, Cougnard and co-workers provided evidence that childhood trauma, urban environment, and cannabis act additively in increasing the risk of persistence of psychotic experiences.17 The fact that cannabis use increases risk of psychosis in a dose-response fashion6 14 20 and that patients with psychosis who continue to use cannabis show more severe and persistent symptoms21 suggests that cannabis use might increase the risk for psychotic illness by impacting on the persistence rate of psychotic experiences that under normal circumstances (that is, without exposure to cannabis) would have remained transitory phenomena for most people. In a population based 10 year follow-up cohort study of adolescents and young adults, we investigated the association between incident cannabis use and true incidence of psychotic experiences (that is, after exclusion of individuals with lifetime pre-existing psychotic experiences) and risk of persistence of psychotic experiences.