Marijuana use at a young age significantly increased the risk of psychosis in young adulthood, Australian investigators reported.
Young adults who reported a longer duration since first exposure to marijuana had a two- to fourfold greater prevalence of three different psychosis-related outcomes, John McGrath, MD, PhD, of the Queensland Center for Mental Health Research in Wacol, and colleagues concluded in an article published online in Archives of General Psychiatry.
Apart from the implications for policy makers and health planners, we hope our findings will encourage further clinical and animal model-based research to unravel the mechanisms linking cannabis use and psychosis, the researchers concluded.
Several prospective-cohort studies have demonstrated an association between early marijuana use and an increased risk of psychosis. On the basis of such studies, reviews of the issue have generally concluded that early use of marijuana, or cannabis, is a modifiable risk factor for psychosis-related outcomes, the authors wrote.
However, some concern has persisted about potential methodologic biases and unmeasured confounders in the cohort studies. In an effort to address the concern, McGrath and colleagues examined the association between cannabis use and psychosis in 3,800 participants in a long-term evaluation of pregnancy and outcomes. In contrast to prior cohort studies, the authors incorporated a subset analysis involving 228 sibling pairs.
“If a significant association between cannabis use and psychosis-related outcomes was not detected in sibling pairs, it would seriously weaken the argument that cannabis use was a risk-modifying factor for psychosis-related outcomes,” they wrote.
Participants were born between 1981 and 1984 at a single hospital in Brisbane. Mothers and their offspring were followed up at five, 14, and 21 years after birth. At the 21-year follow-up, McGrath and colleagues retrospectively assessed cannabis use among the offspring, whose age averaged 20 and ranged from 18 to 23.
Cannabis use was assessed by means of the young adults’ responses to two questions: In the last month, how often did you use cannabis, marijuana, pot, etc.? At what age did you first use cannabis?
Possible responses to the first question were never, every day, every few days, once or so, and not in the past month.
Investigators separated the cohort into four groups on the basis of self-reported cannabis use. One group included never-users, and the remaining three groups were categorized by duration since first use of cannabis: three years or less, four to five years, six years or more.
Investigators compared participants’ history of cannabis use with three psychosis-related outcomes: non-affective psychosis, hallucinations (assessed by the Computerized International Diagnostic Interview), and the Peters et al Delusions Inventory (PDI) score (Schizophr Bull 2004; 30: 1005-1022).
The authors found that 65 participants met criteria for a diagnosis of non-affective psychosis, and 233 reported at least one hallucination-related incident. The PDI has a score range of 0-21, and participants were grouped into PDI quartiles representing scores of =2, 3 or 4, 5 to 7, and =8.
The authors analyzed the results by means of two statistical models, one adjusted for participant sex and age at testing and the other adjusted for sex, age at testing, presence of hallucinations at the 14-year follow-up, and parental history of mental illness.
Using never-users as the reference, the odds ratio for non-affective psychosis increased from 1.5 to 2.1 or 2.2 in the two models as duration of first cannabis use increased. The odds for hallucinations increased from 1.4 to 2.5 and 1.5 to 2.8.
Comparing the lowest and highest quartiles of PDI scores, the authors found that the odds of a higher score increased from 1.6 to 4.0 or 4.3 as duration since first cannabis use increased. Associations for all three psychosis-related outcomes were statistically significant in both models (P=0.001 to P<0.001).
The sibling analysis was limited to the PDI scores. For each pair, the authors calculated difference scores for duration since first cannabis use and PDI total score. The association between time since first cannabis use and PDI score remained statistically significant in the sibling subset analysis.
Limitations of the study included: retrospective self-reporting of time since first cannabis use, lack of data on cumulative exposure to cannabis, no clinical validation of non-affective psychosis diagnosis and lack of use of the instrument at the 14-year follow up, and loss of participants at the 21-year mark with significant differences in the group lost to follow up compared with those retained.
Source:. “Association between cannabis use and psychosis-related outcomes using sibling pair analysis in a cohort of young adults” Arch Gen Psychiatry 2010; DOI: 10.1001/archgenpsychiatry.2010.6.