A meta-analysis of studies examining the association between the use of cannabis and earlier age of psychosis onset appears to confirm the association and could support a hypothesis of a causal link between cannabis use and development of psychosis in some patients.

An analysis of 83 studies showed that the age of psychosis onset for cannabis users was 2.7 years earlier than for nonusers. For those with unspecified substance use, the age at onset of psychosis was two years earlier than for nonusers, but there was no association between alcohol use and earlier psychosis onset.

The study, "Cannabis Use and Earlier Onset of Psychosis: A Systematic Meta-Analysis," was conducted by Matthew Large, B.Sc.(Med.), of the Euroa Centre, Prince of Wales Hospital, New South Wales, Australia, and colleagues. It was published online in the Archives of General Psychiatry on February 7.

A substantial body of research has pointed to a link between cannabis use and earlier onset of psychosis, as well as an association with more severe psychosis symptoms over time. One recent prospective study found that a longer duration since first use of cannabis—implying earlier first use—is associated with increased risk for psychosis at age 21. That study was published in the March 2010 Archives of General Psychiatry (Psychiatric News, April 2, 2010).

Another study, this one a 10-year longitudinal study posted online May 15, 2010, in AJP in Advance, showed that marijuana use among individuals with schizophrenia is associated with more severe positive psychotic symptoms over time (Psychiatric News, May 21, 2010).

The results of the systematic review and meta-analysis in the Archives appear to confirm an association between substance use, particularly the use of cannabis, and an earlier age at onset of psychotic illnesses.

In the meta-analysis, researchers searched the Cumulative Index to Nursing and Allied Health Literature, EMBASE, MEDLINE, PsycINFO, and ISI Web of Science for peer-reviewed publications in English reporting age at onset of psychotic illness in substance-using and non–substance-using subjects. The search yielded 443 articles, of which 83 met inclusion criteria.

A higher proportion of cannabis users among the substance-using groups in the 83 studies was associated with a greater negative effect size, indicating an earlier mean age at onset of psychosis for cannabis use; this was seen in the group of studies that specifically examined cannabis use and was also demonstrated through statistical analysis of studies that included use of multiple substances of abuse, according to the report.

The authors noted that several hypotheses have been proposed to explain the association between cannabis use and schizophrenia: that cannabis use is a causal factor for schizophrenia, that it precipitates psychosis in vulnerable people, that it exacerbates symptoms of schizophrenia, and that people with schizophrenia are more likely to use cannabis.

"The association between the extent of cannabis use in the substance-using group and the effect size, as well as the weaker association between earlier age at onset and alcohol use, support the hypothesis that cannabis use is a causal factor in psychotic disorders," the authors said.

They added that the study lends weight to the view that cannabis use precipitates schizophrenia and other psychotic disorders, most likely via an interaction between genetic and environmental factors or by disrupting brain development during the important neurological maturation that takes place during adolescence.

"The finding raises the important questions of whether cannabis and other substances can trigger psychosis by direct neurotoxic effects, by alterations in dopamine activity, or by other changes in neurotransmission and the extent to which any adverse effects on the brain are reversible," the researchers stated.

"Cannabis Use and Earlier Onset of Psychosis: A Systematic Meta-analysis," is posted at <http://archpsyc.ama-assn.org/cgi/content/full/archgenpsychiatry.2011.5v1>.