Impact of prenatal cannabis exposure on offspring brain structure and function: a systematic review of MRI studies.

Karimi E.; Sabet A.; Terplan M.; Parsaei M. · Neurotoxicology and teratology · 2026

**Background & Methods** This systematic review following PRISMA guidelines evaluated MRI-based evidence on prenatal cannabis exposure (PCE) and offspring brain development. The authors searched PubMed, Web of Science, and Embase through September 2026, identifying 18 studies (2004-2026) comparing prenatally exposed offspring with non-exposed controls across structural, diffusion, resting-state functional, and task-based functional MRI modalities, with participants ranging from the fetal period to young adulthood. **Key Findings** - Structural MRI demonstrated no consistent global brain-volume reductions; however, region-specific differences were noted in frontal regions and intracranial-volume trajectories in some studies. - Diffusion MRI identified inconsistent alterations in selected white-matter pathways, particularly frontolimbic and corticostriatal tracts, with findings not uniformly replicated across studies. - Resting-state and task-based functional MRI studies showed heterogeneous results, with variable connectivity differences across hippocampal, salience, thalamic, and auditory networks, and inconsistent reward and executive-control activation patterns, including some null findings. **Dosage & Administration** Not reported. The review did not provide standardized cannabis dose metrics or exposure assessment protocols across included studies. **Safety & Adverse Effects** Not reported. The abstract does not specify adverse effects or clinical outcomes beyond brain imaging findings. The review focused on structural and functional brain changes rather than clinical symptomatology. **Evidence Quality** Overall certainty of evidence was rated as low to very low according to the GRADE framework due to multiple limitations: risk of bias, inconsistency between studies, imprecision, residual confounding, methodological heterogeneity, and cohort overlap across studies. The authors concluded that while PCE may be associated with subtle, regionally specific differences in brain structure, microstructure, and function, causal interpretation remains substantially limited. Significant gaps include incomplete exposure assessment characterization, inadequate control for maternal and environmental confounders, and lack of standardized MRI protocols across studies. The heterogeneous findings across all imaging modalities suggest either truly variable effects across populations or methodological limitations preventing consistent detection of genuine associations. The authors emphasize the need for prospective, well-controlled studies with standardized exposure assessment and harmonized neuroimaging protocols to establish causal relationships.

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