There have been claims for many years that cannabis use can induce a psychotic illness,1
termed cannabis psychosis by some psychiatrists.2,3
Recent studies show that the use of cannabis in the general population is associated with increased levels of psychotic symptoms.4
Furthermore, a number of studies have shown that patients with diagnosed psychosis, use more cannabis than the general population.5,6
All the above are compatible with the idea that use of cannabis may increase the risk of psychotic illnesses like schizophrenia. In patients with an established psychotic disorder, cannabis use is associated with more and earlier relapses7
and poorer psychosocial functioning8
but perhaps surprisingly also with less negative9,10
and affective symptoms.11
These latter findings, together with data from studies asking patients to complete self-report questionnaires, identified enhancement of positive affect, social acceptance, and coping with negative affect12,13
as the main motives for patients to use cannabis. This led to the notion that cannabis use might be secondary to psychosis (or liability to psychosis).
Several meta-analyses on this issue of whether cannabis use is a cause or consequence of psychosis have now been published, consistently showing that use of cannabis (analyzed as lifetime use in most studies and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
) cannabis dependence in some) increases the risk to develop later psychotic symptoms or psychotic illness with a factor 2.14,15
This effect size held regardless of whether only studies using DSM-IV
diagnoses of psychotic disorder were included or whether, in addition, studies using the broader psychosis phenotype as the outcome measure were also considered. The association between cannabis and subsequent psychosis in these population-based studies cannot be explained entirely by confounding because in these studies the effect of cannabis on psychosis outcome remained significant after adjustment for factors such as age, sex, social class, ethnicity, urbanicity, and use of other drugs. Thus, cannabis use is now widely accepted as a modest contributory cause of schizophrenia and similar illnesses.16
However, it is manifestly obvious that only a small proportion of cannabis users develop psychosis. This can partly be explained on the basis of the amount and duration of consumption because there is a dose-response effect.4,17,18
In addition, some studies suggest that adolescence is a particularly vulnerable period for a person to be exposed to cannabis. In the Dunedin birth cohort, Arseneault et al19
showed that the onset of cannabis use before the age of 15 years was associated with a greater risk of developing schizophreniform disorder at age 26 years than the onset of cannabis use at an older age. This finding was replicated by Stefanis et al20
and recently by Konings et al21
, who both investigated the association between age of first cannabis use and lifetime subclinical psychotic symptoms in a general population sample. In this last study, the association between cannabis use and psychosis was studied for the first time in a non-Western society, showing once more that early exposure to cannabis (before the age of 14 years in this sample) was associated with a greater risk to develop psychotic symptoms than first exposure during later adolescence.
Another possible explanation as to why only a minority of individuals develop psychosis is that certain individuals may be especially genetically vulnerable. This review will therefore consider the interplay between genes and exposure to cannabis in the development of psychotic symptoms and schizophrenia. Genetic, epidemiological, observational, and experimental findings will be discussed to investigate mechanisms of both gene-environment interaction (GEI) and gene-environment correlation (rGE) within the cannabis-psychosis association.