Early Cannabis Use May Contribute to Psychosis-Related Outcomes in Young Adults

Jill Stein

May 07, 2010

May 7, 2010 — Early-onset cannabis use appears to heighten the risk for psychosis-related outcomes in young adults, according to a study that used a sibling pair analysis.

Sibling pair analysis reduces the effect of unmeasured confounding variables that has cast doubt on prior research purporting to show an association between early-onset cannabis use and an increased risk for psychosis-related outcomes.

The new results, reported by an Australian group, demonstrated that a longer time interval since first cannabis use was associated with multiple psychosis-related outcomes in young adults. What's more, this association remained significant when examined in sibling pairs.

"The quality of the evidence linking early cannabis use and risk of psychosis is now even stronger with our recent study, as the use of the sibling pairs is a very stringent test," principal investigator John McGrath, MD, PhD, FRANZCP, director of the Queensland Centre for Mental Health Research, Australia, told Medscape Psychiatry.

"The clinical implications are from a public health perspective," he added. "We need to warn young people about the risks they take when using cannabis. For clinicians treating young people for mental health disorders, they should counsel them about the risks associated with cannabis use."

The study was published in the May issue of the Archives of General Psychiatry.

Exaggerated Association?

Prospective cohort studies have reported a direct association between cannabis use and later psychosis-related outcomes. Reviews of these studies, coupled with additional research in this area, have usually concluded that cannabis use is a "risk-modifying" factor for these outcomes.

However, there has been a longstanding concern among researchers that the purported association is exaggerated and may actually be the result of residual confounding.

Sibling pair studies should, in theory, provide stronger evidence on the true nature of the association between cannabis use and psychosis-related outcomes.

In short, sibling pair studies exploit differences between siblings while decreasing the odds of residual confounding, as differences are less likely, because of shared genetic and environmental exposures.

The authors say that, to their knowledge, their study is the first to use a sibling pair design to examine the association between cannabis use and psychosis-related outcomes.

If the study were to fail to identify a significant association between cannabis use and psychosis-related outcomes in sibling pairs, the claim that cannabis use is a risk-modifying factor for psychosis-related outcomes would be strongly undermined.

Sibling Pair Analysis

Dr. McGrath and colleagues examined the association between cannabis use and multiple psychosis-related outcomes in 228 pairs of siblings. The siblings were drawn from a birth cohort of 3801 adults who were being prospectively followed-up, along with their mothers, in the Mater-University Study of Pregnancy (MUSP), conducted at the University of Queensland.

The MUSP, which is ongoing, examines medical and social outcomes for the mother and child. As part of the study, cohort members and their mothers are followed-up at 5, 14, and 21 years.

In the present investigation, cannabis use was retrospectively determined using a self-report questionnaire at the 21-year follow-up.

The presence of nonaffective psychosis, hallucinations, and Peters et al Delusions Inventory (PDI) score was also assessed at this time. The PDI is a validated tool for measuring delusional ideation.

Associations between the amount of time that had elapsed since first cannabis use and psychosis-related outcomes were examined at the 14-year follow-up.

Results showed that duration since first cannabis use was associated in a dose-response manner with all 3 psychosis-related outcomes. Compared with those who had never used cannabis, young adults who had first used cannabis at least 6 years earlier when they were approximately 15 years of age or younger were:

  • twice as likely to develop a nonaffective psychosis,

  • 4 times as likely to have high scores on the PDI, and

  • 3 times as likely to develop hallucinations.

Importantly, the data showed that these findings persisted within sibling pairs, thus limiting the possibility that these associations are the result of unmeasured residual confounding.

"To me, a big surprise was that the association between cannabis use and later psychosis-related outcomes was so stubborn," said Dr. McGrath "Every way we looked at it (different types of psychosis outcomes, sibling pairs, only siblings that BOTH used cannabis, etc.), the effect persisted."

He added that future studies need to explore genetic contributions to this risk.

Mounting Evidence

"This study adds to the body of emerging literature identifying early cannabis use as a risk factor for schizophrenia," Subroto Ghose, MD, assistant professor of psychiatry at the University of Texas Southwestern Medical Center at Dallas, told Medscape Psychiatry. "The concordance between this study and previous epidemiologic studies strengthens the argument that adolescent cannabis use is a risk factor for the development of psychosis," he added.

When asked whether he believes that the results of the Australian study are clinically relevant, he said: "The general perception that cannabis is a 'soft' drug may not be true. There is now evidence that cannabis may affect the adolescent brain[, permanently altering] its developmental trajectory. While this may not occur in everyone, some people may be particularly vulnerable. Until we can identify who is particularly vulnerable, using cannabis during adolescence may be like playing Russian roulette."

He also emphasized that it is critical that medical professionals convey this information about the association between cannabis use and later psychosis to their patients.

"This is probably especially important in children and adolescents who have family members diagnosed with schizophrenia or other psychotic illnesses," he said.

"These individuals probably have a higher genetic predisposition for schizophrenia, and using cannabis during childhood and adolescence could be the proverbial straw that breaks the camel's back."

The study was funded by the National Health and Medical Research Council of Australia. Dr. McGrath and Dr. Ghose have disclosed no relevant financial relationships.

Arch Gen Psychiatry. 2010:67:440-447. Abstract

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