Association between cannabis use disorder and schizophrenia stronger in young males than in females

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Paper Summary

Conflicts of Interest

Identified Weaknesses

Rating Explanation

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Paper Summary

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Young Men: Cannabis Use Disorder & Schizophrenia - A Stronger Link?

This nationwide Danish study found a stronger association between cannabis use disorder (CUD) and schizophrenia in young males compared to females. Using register data, researchers found that in 2021, approximately 15% of recent schizophrenia cases in males (vs. 4% in females) might have been preventable without CUD. The study is observational so causality cannot be determined, and other unmeasured factors (like tobacco use or THC potency of used cannabis) could influence the results.

Possible Conflicts of Interest

None identified.

Identified Weaknesses

Reliance on Diagnostic Codes

The study relies on diagnostic codes for CUD and schizophrenia, which may not fully capture the complexity of these conditions. Individuals with subthreshold symptoms or those who have not sought treatment would be missed, potentially leading to an underestimation of the true association.

Unmeasured Confounders

While the study controls for several factors, it does not account for all potential confounders, such as tobacco use (which has been linked to psychosis), frequency and amount of cannabis use, age of first use, or specific THC content of cannabis products. These unmeasured confounders could influence the observed association.

Observational Design

While the study utilizes national registers and a large sample size, it is observational and thus cannot establish causality. It remains possible that the association between CUD and schizophrenia is influenced by unmeasured factors or that the relationship is bidirectional (i.e. schizophrenia increases risk of cannabis use).

Potential Over-adjustment

Although unlikely, there is a possibility of over-adjustment in the model by including other psychiatric disorders as covariates. Some of these other disorders could potentially be mediators (intermediate steps) in the causal pathway between CUD and schizophrenia, thus somewhat attenuating the true direct effect of CUD.

Rating Explanation

This is a strong study using a robust nationwide dataset with longitudinal follow-up, providing compelling evidence for a stronger association between cannabis use disorder and schizophrenia in young males. While the study acknowledges limitations (reliance on diagnostic codes, unmeasured confounding, observational design), it controls for many relevant factors and explores age and sex differences in a detailed way. The large sample size and comprehensive data minimize selection bias and provide solid statistical power. The findings are relevant to public health and policy discussions regarding cannabis use and schizophrenia.

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