Dietary omega-3 supplementation reduced cognitive and emotional problems caused by prenatal THC exposure in male rat offspring but not females, while revealing widespread sex-specific disruptions in brain lipid metabolism.
Neuroscientists, reproductive health researchers, and those interested in how prenatal cannabis exposure affects brain development.
What the researchers found
Omega-3 supplementation normalized many neuronal and neurochemical abnormalities in male offspring's prefrontal cortex, nucleus accumbens, and ventral hippocampus. However, lipidomic analyses revealed pronounced, sex-specific disruptions in endocannabinoid-related pathways regardless of omega-3 treatment.
Why it matters
Cannabis use during pregnancy is increasing, and understanding both the risks and potential protective factors matters. This study suggests omega-3s could mitigate some effects but also reveals that prenatal THC causes deep lipid metabolism changes in the brain that persist regardless of supplementation.
The numbers in context
Three brain regions analyzed (prefrontal cortex, nucleus accumbens, ventral hippocampus). Omega-3 reduced cognitive and emotional disturbances in male offspring. Lipidomic disruptions persisted in both sexes despite supplementation. Sex-specific effects were observed across endocannabinoid system pathways.
How the study worked
Wistar rat model with prenatal THC exposure followed by perinatal omega-3 supplementation. Offspring underwent behavioral assessments and lipidomic analyses of three brain regions (prefrontal cortex, nucleus accumbens, ventral hippocampus).
What this study cannot tell us
Rat model with synthetic THC does not fully replicate human prenatal cannabis exposure. Omega-3 doses and timing may not translate directly to human supplementation. Behavioral improvements in males without corresponding lipidomic normalization raise questions about long-term durability of protective effects.
How to read the evidence
Comprehensive preclinical study with behavioral and lipidomic data across multiple brain regions, but animal model results cannot be directly applied to human pregnancy.
When this study was published
Published 2025.
The bigger picture
The sex-selective response to omega-3 supplementation adds to growing evidence that males and females respond differently to both prenatal cannabis exposure and potential interventions. The persistent lipidomic changes, even when behavior improves, suggest underlying vulnerability may remain.
Questions still open
- Why omega-3 supplementation protected male but not female offspring
- Whether the persistent lipidomic changes predict later-life vulnerability despite behavioral improvement
Common questions
Could pregnant people who used cannabis take omega-3s to protect their baby?
Why did omega-3s help males but not females?
Read the original research
Perinatal omega-3 sex-selectively mitigates neuropsychiatric impacts of prenatal THC in the cortico-striatal-hippocampal circuit.
Molecular psychiatry, 30(11), 5264-5282
Citation
Sarikahya, Mohammed H; Cousineau, Samantha L; De Felice, Marta; Szkudlarek, Hanna J; Lee, Kendrick; Doktor, Aleksandra; Alcaide, Amanda; DeVuono, Marieka V; Dembla, Anubha; Wong, Karen; Balarajah, Mathanke; Vanin, Sebastian; Youssef, Miray; Zhaksylyk, Kuralay; Machado, Madeline; Mahmood, Haseeb; Schmid, Susanne; Yeung, Ken K-C; Hardy, Daniel B; Rushlow, Walter; Laviolette, Steven R. (2025). Perinatal omega-3 sex-selectively mitigates neuropsychiatric impacts of prenatal THC in the cortico-striatal-hippocampal circuit.. Molecular psychiatry, 30(11), 5264-5282. https://doi.org/10.1038/s41380-025-03113-x
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