Omega-3 Supplements Reversed Prenatal THC Brain Effects in Male Rats Only
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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).
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?Why omega-3 supplementation protected male but not female offspring
- ?Whether the persistent lipidomic changes predict later-life vulnerability despite behavioral improvement
Trust & Context
- Key Stat:
- Evidence Grade:
- Comprehensive preclinical study with behavioral and lipidomic data across multiple brain regions, but animal model results cannot be directly applied to human pregnancy.
- Study Age:
- Published 2025.
- Original Title:
- Perinatal omega-3 sex-selectively mitigates neuropsychiatric impacts of prenatal THC in the cortico-striatal-hippocampal circuit.
- Published In:
- Molecular psychiatry, 30(11), 5264-5282 (2025)
- Authors:
- Sarikahya, Mohammed H(8), Cousineau, Samantha L(3), De Felice, Marta(6), 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
- Database ID:
- RTHC-07576
Evidence Hierarchy
Frequently Asked Questions
Could pregnant people who used cannabis take omega-3s to protect their baby?
This study was in rats, so direct translation to human pregnancy is not possible. The finding that omega-3s helped male offspring is interesting but preliminary, and the persistent brain lipid changes in both sexes suggest protection may be incomplete.
Why did omega-3s help males but not females?
The researchers found sex-specific patterns in how prenatal THC disrupted brain lipid pathways. Male and female brains develop on different timelines and have different endocannabinoid system dynamics, which likely explains the different responses to supplementation.
Read More on RethinkTHC
Cite This Study
https://rethinkthc.com/research/RTHC-07576APA
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
MLA
Sarikahya, Mohammed H, et al. "Perinatal omega-3 sex-selectively mitigates neuropsychiatric impacts of prenatal THC in the cortico-striatal-hippocampal circuit.." Molecular psychiatry, 2025. https://doi.org/10.1038/s41380-025-03113-x
RethinkTHC
RethinkTHC Research Database. "Perinatal omega-3 sex-selectively mitigates neuropsychiatric..." RTHC-07576. Retrieved from https://rethinkthc.com/research/sarikahya-2025-perinatal-omega3-sexselectively-mitigates
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.