Maternal cannabis use during pregnancy associates with alterations in placental endocannabinoid- and steroid-homeostasis and morphology.

Harhangi M.; Meier P.; Bijma H.; van der Meeren L.; Rousian M.; Mulders A.; Steegers-Theunissen R.; Simons S.; Reiss I.; Danser A. et al. · Toxicology and applied pharmacology · 2026

**Background & Methods** This study examined placentas from pregnant women with frequent cannabis use throughout pregnancy compared to non-exposed controls. Researchers used ex vivo dual-sided cotyledon perfusion to measure maternal and fetal release of cannabinoids, endocannabinoid system (ECS)-related lipid mediators, prostaglandins, and steroids via LC-ESI-MS/MS, supplemented by RT-qPCR gene expression analysis and comparative placental histopathology across cannabis users, non-smoking controls, and tobacco-exposed pregnancies. **Key Findings** • Delta-9-tetrahydrocannabinol (THC) accumulated in placental tissue with detectable release to both maternal and fetal compartments; cannabis exposure altered ECS-related lipid release patterns, including enhanced fetal release of N-acylethanolamines and disrupted normal maternal-fetal release polarity for multiple lipid mediators. • Cannabis-exposed placentas demonstrated reduced tissue concentrations of cortisone, membrane phospholipids, and selected mono- and diglycerides, with increased maternal cortisol release and upregulated HSD3B1 gene expression despite unchanged progesterone levels, indicating dysregulation of steroid homeostasis. • Histopathological examination revealed reduced placental weight, umbilical cord length, and maximal placental diameter; increased marginal/peripheral cord insertion; accelerated maturation; ischemia; and chorioamnionitis in cannabis-exposed pregnancies compared to controls. **Dosage & Administration** Not reported. Study characterized "frequent cannabis use throughout pregnancy" without specifying quantitative dose, frequency, or route of administration. **Safety & Adverse Effects** Cannabis use during pregnancy associated with placental dysfunction markers including structural abnormalities, ischemia, and inflammatory changes (chorioamnionitis). Findings are consistent with previously reported adverse pregnancy outcomes including preeclampsia. Specific fetal or neonatal adverse effects were not directly assessed in this placental tissue study. **Evidence Quality** This is a human observational study with ex vivo experimental methodology, providing mechanistic insights into cannabis-associated placental pathology. Limitations include lack of quantified cannabis exposure metrics, absence of dose-response analysis, and inability to control for confounding variables inherent to observational design. The ex vivo perfusion system provides controlled experimental conditions but may not fully represent in vivo placental physiology. No randomized controlled trials are ethically feasible for this exposure, limiting evidence hierarchy. Findings support biologically plausible mechanisms linking prenatal cannabis exposure to placental dysfunction and adverse outcomes.

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