The first comprehensive meta-analysis of rodent studies found that adolescent exposure to cannabinoids consistently produced schizophrenia-like behavioral changes including impaired memory, reduced social behavior, and disrupted sensory gating.
Anyone concerned about adolescent cannabis use and mental health risk, researchers studying cannabis-psychosis links.
359 experiments across 108 studies consistently showed schizophrenia-like behavior after adolescent cannabinoid exposure
What the researchers found
Across 359 experiments from 108 articles, CB1 receptor agonists (both natural and synthetic cannabinoids) during adolescence impaired working memory (g=-0.56), novel object recognition (g=-0.66), novel object location recognition (g=-0.70), social novelty preference (g=-0.52), social motivation (g=-0.21), pre-pulse inhibition (g=-0.43), and sucrose preference (g=-0.87). Effects were similar across sexes and species. Locomotion effects were negligible.
Why it matters
This is the first meta-analysis to comprehensively test whether epidemiological links between adolescent cannabis use and schizophrenia are supported by controlled animal experiments. The consistent findings across hundreds of experiments strengthen the biological plausibility of this association.
The numbers in context
359 experiments from 108 articles across 9 behavioral tests. Effect sizes ranged from g=-0.21 (social motivation) to g=-0.87 (sucrose preference). Working memory: g=-0.56. Pre-pulse inhibition: g=-0.43. Novel object recognition: g=-0.66. Effects were consistent across sexes and species.
How the study worked
Pre-registered systematic review and meta-analysis (CRD42022338761) searching four databases through May 2024. Included studies on schizophrenia-like behavior in rats and mice after repeated cannabinoid exposure during the peri-pubertal period (postnatal day 23-45). Risk of bias assessed using SYRCLE tool.
What this study cannot tell us
Animal models cannot fully replicate human schizophrenia. Substantial protocol variability and moderate-to-high heterogeneity across studies. Synthetic cannabinoids used in many studies may not reflect typical cannabis exposure. CBD may have different effects (limited data suggested enhanced fear memory recall).
How to read the evidence
Strong: pre-registered meta-analysis with large number of experiments, consistent effects across species and sexes, and rigorous methodology, though limited to animal models.
When this study was published
2025 study analyzing literature through May 2024.
The bigger picture
Epidemiological studies have long linked adolescent cannabis use to increased schizophrenia risk, but critics note that observational data cannot prove causation. This meta-analysis of controlled animal experiments provides the experimental evidence that was missing from the debate.
Questions still open
- Do these behavioral changes reflect permanent brain alterations or temporary effects? What is the minimum exposure needed to produce these changes? Could CBD counteract the schizophrenia-like effects of THC during adolescence?
Common questions
Did male and female animals respond differently?
Does this prove cannabis causes schizophrenia in humans?
Read the original research
Systematic review and meta-analysis on the effects of chronic peri-adolescent cannabinoid exposure on schizophrenia-like behaviour in rodents.
Molecular psychiatry, 30(1), 285-295
Citation
Li, Zhikun; Mukherjee, Diptendu; Duric, Bea; Austin-Zimmerman, Isabelle; Trotta, Giulia; Spinazzola, Edoardo; Quattrone, Diego; Murray, Robin M; Di Forti, Marta. (2025). Systematic review and meta-analysis on the effects of chronic peri-adolescent cannabinoid exposure on schizophrenia-like behaviour in rodents.. Molecular psychiatry, 30(1), 285-295. https://doi.org/10.1038/s41380-024-02668-5
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