Within-person analysis suggests cannabis causally impacts psychosis risk, but not the reverse | Research

The takeaway

Using a within-person design that removes confounding from fixed characteristics, prior cannabis use was associated with a sevenfold increase in odds of psychotic experiences, while prior psychotic experiences did not predict cannabis use.

Psychiatrists, psychosis researchers, public health officials, and anyone interested in the cannabis-psychosis relationship.

7x increased odds of psychotic experiences after cannabis use

What the researchers found

In the fixed-effects model, prior cannabis use predicted subsequent psychotic experiences (adjusted OR = 7.03, 95% CI: 2.39-20.69), but prior psychotic experiences did not predict subsequent cannabis use (adjusted OR = 0.59, 95% CI: 0.21-1.71).

Why it matters

Most cannabis-psychosis research uses between-person comparisons, which cannot fully control for genetic and environmental confounders. This within-person design substantially strengthens the causal inference that cannabis impacts psychosis.

The numbers in context

Combined cohort: 7,998 at baseline. Follow-up: approximately 10 years across 4 time points. Cannabis to psychosis OR: 7.03 (95% CI: 2.39-20.69). Psychosis to cannabis OR: 0.59 (95% CI: 0.21-1.71).

How the study worked

Combined two general population cohorts (n = 7,998 at baseline) with repeated interviews over approximately 10 years (4 time points). Used fixed-effects within-person models where each individual serves as their own control, removing confounding by any stable characteristic. Adjusted for time-varying confounders.

What this study cannot tell us

Self-reported measures of both cannabis use and attenuated psychotic experiences. Attenuated psychotic experiences are not the same as clinical psychosis diagnoses. Time-varying confounders may not be fully captured.

How to read the evidence

Within-person design across two population cohorts with 10-year follow-up provides strong causal inference, though based on self-report.

When this study was published

Published in 2021.

The bigger picture

The debate about whether cannabis causes psychosis or whether people predisposed to psychosis seek out cannabis has persisted for decades. This within-person approach provides some of the strongest evidence yet for a directional effect from cannabis to psychosis.

Questions still open

Does the strength of this causal relationship vary by cannabis potency or frequency of use? At what threshold of use does the risk become meaningful?

Common questions

What makes within-person analysis stronger than typical studies?

Each person serves as their own control, automatically removing confounding from all stable characteristics like genetics, childhood environment, and personality traits.

Does this prove cannabis causes psychosis?

It provides strong evidence for a causal direction from cannabis to psychotic experiences, but the study measured attenuated psychotic experiences in the general population, not clinical psychosis diagnoses.

Read the original research

Schizophrenia and the Environment: Within-Person Analyses May be Required to Yield Evidence of Unconfounded and Causal Association-The Example of Cannabis and Psychosis.

Schizophrenia bulletin, 47(3), 594-603

View on PubMed ↗Publisher’s paper ↗

Citation

van Os, Jim; Pries, Lotta-Katrin; Ten Have, Margreet; de Graaf, Ron; van Dorsselaer, Saskia; Bak, Maarten; Wittchen, Hans-Ulrich; Rutten, Bart P F; Guloksuz, Sinan. (2021). Schizophrenia and the Environment: Within-Person Analyses May be Required to Yield Evidence of Unconfounded and Causal Association-The Example of Cannabis and Psychosis.. Schizophrenia bulletin, 47(3), 594-603. https://doi.org/10.1093/schbul/sbab019