Cannabis use, schizophrenia genetic predisposition both independently raise psychosis risk

Key takeaways:

• Lifetime cannabis use associated with psychosis risk in both study samples.
• Meanwhile, schizophrenia polygenic risk score could help identify psychosis risk among cannabis users in the future.

Genetic predisposition for schizophrenia and frequent use of cannabis both independently corresponded with an increased likelihood of developing psychosis, results of a case-control study showed.

However, researchers found no evidence of an interaction between genetic predisposition and cannabis use.

Such a result “[suggests] they influence the risk of psychosis through separate pathways and could potentially have an additive effect [whereas] those with increased genetic risk who use cannabis are highly likely to develop psychosis,” Edoardo Spinazzola, PhD, a research assistant at King’s College London, said in a press release. “We have shown that highest risk for psychosis is in those with greater genetic predisposition to schizophrenia who use high potency cannabis daily.”

Multiple studies have previously examined the relationship between cannabis use and psychosis, particularly in youth. One analysis showed that adolescents who used cannabis had much greater odds of developing a psychosis disorder vs. their nonusing peers, whereas another suggested that self-medication may explain such links.

In the current analysis, published in Psychological Medicine, Spinazzola and colleagues assessed the effects of cannabis use disorder and schizophrenia polygenic risk scores (PRSs) and different frequencies and potency of cannabis use on psychosis odds in cohorts taken from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions, or EU-GEI (n = 1,592), and U.K. Biobank (n = 145,244).

Participants were aged 40 to 70 years.

The result showed an association between lifetime cannabis use and a greater likelihood for psychosis in both the EU-GEI (OR = 1.67; 95% CI 1.3-2.15) and U.K. Biobank (OR = 1.08; 95% CI, 1.07-1.09) samples.

These links remained the same when researchers accounted for PRSs for schizophrenia, “demonstrating that genetic risk is independent of the environmental risk factor that is cannabis use,” they wrote.

Spinazzola and colleagues found effects of the association were greater among daily vs. weekly users and greatest among daily users of high potency cannabis, defined as cannabis with delta-9 tetrahydrocannabinol content of 10% or more (OR = 5.09; 95% CI, 3.08-8.43).

In the EU-GEI cohort, schizophrenia PRSs did not correspond with a person’s propensity to try cannabis or frequency of cannabis use, nor did the analysis show an association between cannabis use and schizophrenia PRSs among people with psychosis.

Schizophrenia PRSs corresponded with patterns of cannabis use among those without psychosis in the U.K. Biobank sample, explaining less than 1% of the variance between lifetime and daily use.

However, this effect decreased by 39% and 82% for lifetime and daily use, respectively, when the model included PRSs for cannabis use disorder.

“Nonetheless, there does seem to be some independent effects of schizophrenia genetic risk on cannabis use, which should be interrogated in other population-based cohorts,” the researchers wrote.

Marta di Forti, MD, MRCPsych, PhD, a professor of drug use, genetics and psychosis at King’s College London and study co-author, said in the release that the findings are important “at a time of increasing use and potency of cannabis worldwide.”

“The [PRSs] for schizophrenia might, in the near future, become useful to identify those at risk for psychosis among less frequent users to enable early preventive measures to be put in place,” she said.

References:

• Austin-Zimmerman I, et al. Psychol Med. 2024;doi:10.1017/S0033291724002058.
• Cannabis use increases risk of psychosis independently from genetic predisposition. Available at: https://www.eurekalert.org/news-releases/1067331. Published Dec. 5, 2024. Accessed Dec. 17, 2024.