Perinatal omega-3 sex-selectively mitigates neuropsychiatric impacts of prenatal THC in the cortico-striatal-hippocampal circuit.
Mohammed H Sarikahya, Samantha L Cousineau, Marta De Felice, Hanna J Szkudlarek, Kendrick Lee, Aleksandra Doktor, Amanda Alcaide, Marieka V DeVuono, Anubha Dembla, Karen Wong, Mathanke Balarajah, Sebastian Vanin, Miray Youssef, Kuralay Zhaksylyk, Madeline Machado, Haseeb Mahmood, Susanne Schmid, Ken K-C Yeung, Daniel B Hardy, Walter J Rushlow, Steven R Laviolette
Molecular Psychiatry November 2025 DOI: 10.1038/s41380-025-03113-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Wistar rat offspring prenatally exposed to Δ9-tetrahydrocannabinol |
| Interventions | Omega-3 fatty acid supplementation Prenatal Δ9-tetrahydrocannabinol exposure |
| Topics | Cannabis |
| Key points | Omega-3 supplementation sex-selectively reduced cognitive and emotional disturbances in male offspring and normalized many neuronal and neurochemical abnormalities in prefrontal cortex, nucleus accumbens, and ventral hippocampus. Lipidomic analyses revealed pronounced, sex-specific prenatal THC-induced disruptions in pathways critical for synaptic integrity and neurodevelopment, including endocannabinoid-related pathways, regardless of omega-3 supplementation. |
Abstract
Prenatal Δ9-tetrahydrocannabinol exposure (PTE) poses long-lasting neuropsychiatric risks, as evidenced by clinical and preclinical studies, yet the neurobiological mechanisms remain poorly defined. Emerging evidence implicates the neurolipidome, a critical mediator of neurodevelopment and endocannabinoid signaling, as a potential contributor. Here, we demonstrate that dietary omega-3 fatty acid supplementation sex-selectively ameliorates neurodevelopmental deficits induced by PTE in a Wistar rat model. Omega-3 supplementation reduced cognitive and emotional disturbances in male offspring and normalized many neuronal and neurochemical abnormalities in the prefrontal cortex, nucleus accumbens, and ventral hippocampus. However, lipidomic analyses, regardless of omega-3 supplementation, uncovered pronounced, sex-specific PTE-induced disruptions in pathways critical for synaptic integrity and neurodevelopment, including those related to the endocannabinoid system. These findings provide new insights into the interplay between lipid metabolism and the endocannabinoid system in the context of PTE.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 2
- Adult Rat Offspring Exposed to THC during Gestation Exhibit Distinct Biomolecular Changes Identified by X-ray Fluorescence Imaging and Fourier Transform Infrared Spectroscopy in Cortico-Limbic Circuits. ACS Chemical Neuroscience February 18, 2026
- Perinatal LC-ω-3-PUFA supplementation offsets prenatal THC-induced cognitive deficit via sex-specific modulation of hippocampal neuroplasticity. European Journal of Pharmacology June 1, 2026
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and 11 more in the library