March 4, 2010 (Updated with comment March 10, 2010) — Experimenting with marijuana at a young age increases the risk for hallucinations or delusions later in life, a new study shows.

"Early cannabis use increases the risk of psychosis in young adults," lead investigator John McGrath, MD, from the Queensland Centre for Mental Health Research in Brisbane, Australia, told Medscape Psychiatry.

"Apart from having an increased risk of having a disorder like schizophrenia, the longer the young adults reported since their first cannabis use, the more likely they were to report isolated symptoms of psychosis."

Cannabis is a risk factor for psychosis, and we need to let the general community know about these risks.

Psychotic disorders are common and typically affect 1 or 2 people of every 100. "Despite our best efforts with treatment, not everyone makes a full recovery," Dr. McGrath said. "We need to think about prevention. Cannabis is a risk factor for psychosis, and we need to let the general community know about these risks."

Dr. McGrath says he was surprised that the results were so strong and so consistent.

The study was published online March 1 in Archives of General Psychiatry.

Investigators studied 3800 young adults born at an Australian hospital taking part in the Mater-University Study of Pregnancy.

Prospective studies have already identified an association between marijuana use and later psychosis-related outcomes, but concerns remain about unmeasured confounding variables.

Dr. McGrath and his team focused instead on 228 sibling pairs in the prospective birth cohort to reduce the influence of unmeasured residual confounding.

Investigators followed up study participants at ages 5, 14, and 21 years. The researchers assessed first marijuana use and 3 psychosis-related outcomes. These outcomes included nonaffective disease, hallucinations, and the Peters et al delusions inventory score.

Table. Odds Ratio of Psychosis-Related Outcomes With Marijuana Use

Marijuana Use Nonaffective Psychosis Hallucinations Peters Delusion Inventory Never 1 (reference) 1 (reference) 1 (reference) ≤3 years 1.5 1.4 1.6 4-5 years 1.6 1.5 2.5 ≥6 years 2.1 2.5 4.0

Investigators evaluated all associations between duration of marijuana use and psychosis-related outcomes using logistic regression adjusted for sex, age, parental mental illness, and hallucinations at the 14-year follow-up.

The results mirror those of another study published in the November issue of the American Journal of Psychiatry (2009;166:1251–1257). That work suggests a link between daily cannabis or tobacco use and early-onset psychosis.

In that study, investigators looked at 109 patients in a psychiatric unit and found that daily marijuana and tobacco use was common. More than 40% of patients used one or both substances.

Of those who abused cannabis, almost 88% were classified as weekly or daily users before the onset of psychosis.

Escalating Marijuana Use Hastened Psychosis

It is not clear why escalating marijuana use may hasten psychosis, lead investigator Michael Compton, MD, from the Emory University School of Medicine in Atlanta, Georgia, noted in November. However, studies have shown increased cannabinoid receptor density in areas of the brain and elevated levels of endogenous cannabinoids in the blood of some patients with psychosis.

This new study, Dr. McGrath points out, provides additional evidence that early cannabis use is a risk-modifying factor for psychosis-related outcomes in young adults.

Asked by Medscape Psychiatry to comment, Emma Barkus, PhD, from the University of Wollongong in New South Wales, Australia, says the findings are consistent with the substance literature, which suggests that those who are engaging in risk behaviors at the age of 14 years are more likely to persist as they get older.

"Despite the restrictions of the methodologies," she noted, "such as use of retrospective recall and the pseudoquantification of cannabis exposure, the sample size and the persistence of the findings in the face of controlling for confounding variables and analyses on subsets of participants lend strength to an area of literature which is still fraught with controversy."

Dr. Barkus says the findings add further support to the role of cannabis use in psychoses in outcomes.

This study was funded by the National Health and Medical Research Council of Australia. Coauthor Dr. Rosa Alati is supported by a National Health and Medical Research Council Career Development Award in Population Health.

Arch Gen Psychiatry. Published online March 1, 2010.