Evidence mapPaperPMID 39090371Full record

SynthesisMolecular psychiatry2025

Systematic review and meta-analysis on the effects of chronic peri-adolescent cannabinoid exposure on schizophrenia-like behaviour in rodents.

Zhikun Li, Diptendu Mukherjee, Bea Duric, Isabelle Austin-Zimmerman, Giulia Trotta, Edoardo Spinazzola, Diego Quattrone, Robin M Murray, Marta Di Forti

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis in Molecular psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Zhikun Li *Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.ORCID 0009-0005-4577-1794
Diptendu Mukherjee *MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, London, SE1 1UL, UK.ORCID 0000-0002-9752-1026
Bea DuricGKT School of Medical Education, King's College London, London, SE1 1UL, UK.ORCID 0000-0002-9409-0099
Isabelle Austin-ZimmermanSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.
Giulia TrottaSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.
Edoardo SpinazzolaSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.ORCID 0000-0002-8070-0618
Diego QuattroneSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.ORCID 0000-0002-6051-8309
Robin M MurraySouth London and Maudsley NHS Mental Health Foundation Trust, London, UK.ORCID 0000-0003-0829-0519
Marta Di FortiSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK. Marta.diforti@kcl.ac.uk.ORCID 0000-0002-3218-6925

Funding

Medical Research Council MR/T007818/1RCUK | Medical Research Council (MRC) MR/T007818/1
6 · The paper itself

Abstract

backgroundThe link between cannabis use and schizophrenia is well-established in epidemiological studies, especially among adolescents with early-onset use. However, this association in rodent models is less clear. This meta-analysis examined the effects of adolescent cannabinoid exposure on distinct schizophrenia-like behaviours in rodents and how experimental variations influence outcomes.

methodsFollowing a pre-registered protocol (CRD42022338761), we searched PubMed, Ovid Medline, Embse and APA PsychInfo for English-language original studies until May 2024. We synthesised data from experiments on schizophrenia-like behaviour in rats and mice after repeated peri-pubertal (onset between P23-P45) cannabinoid exposure. Risk of bias was assessed using the SYRCLE's tool.

resultsWe included 359 experiments from 108 articles across 9 behavioural tests. We found meta-analytic evidence supporting that CB1R agonists, both natural and synthetic, elicited broad schizophrenia-like behavioural alterations, including impaired working memory [g  = -0.56; (CI: -0.93, -0.18)], novel object recognition [g = -0.66; (CI: -0.97, -0.35)], novel object location recognition [g = -0.70; (CI: -1.07, -0.33]), social novelty preference [g = -0.52; (CI: -0.93, -0.11)], social motivation [g = -0.21; (CI: -0.42, -0.00)], pre-pulse inhibition [g = -0.43; (CI: -0.76, -0.10)], and sucrose preference [g = -0.87; (CI: -1.46, -0.27)]. By contrast, effects on novelty-induced locomotion were negligible. Subgroup analyses revealed similar effects across sexes and species. Substantial variance in the protocols and moderate-to-high heterogeneity in behavioural outcomes were observed. We found CBD may enhance fear memory recall, but data was limited. DISCUSSION: This is the first meta-analysis to comprehensively assess the link between cannabinoids and schizophrenia-like behaviours in rodents. Our results support epidemiological links between early cannabis use and schizophrenia-like phenotypes, confirming the utility of animal models. Standardising protocols will optimise models to strengthen reproducibility and comparisons, our work provides a framework for refining rodent models to elucidate biological pathways linking cannabis and schizophrenia.

Indexed as

CannabinoidsDisease Models, AnimalSchizophreniaAdolescentAnimalsBehavior, AnimalHumansMaleMemory, Short-TermMiceRatsRodentiaCannabinoids

Identifiers

PMID39090371
PMCPMC11649573

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.