Rats exposed to THC in the womb developed anxiety-like and depression-like behaviors in adulthood, with males showing more persistent brain lipid disruptions than females.
People interested in how cannabis use during pregnancy may affect fetal brain development differently in males and females.
Males showed persistent fatty acid deficits into adulthood; females recovered
What the researchers found
Prenatal THC exposure induced lasting behavioral and neuronal changes in male and female rat offspring resembling neuropsychiatric conditions, with profound disruption of fatty acid pathways in the developing brain.
Why it matters
This study identifies specific biological mechanisms through which prenatal cannabis exposure may alter brain development, showing that THC disrupts the brain's fatty acid landscape in ways that differ between males and females.
The numbers in context
THC dose was 3 mg/kg daily from GD7 to GD22. Females showed significant fatty acid alterations at prepubescence but recovered by adulthood. Males had persistent fatty acid deficits into adulthood. Both sexes showed enduring glutamatergic/GABAergic dysfunction in the nucleus accumbens.
How the study worked
Pregnant Wistar rats received THC (3 mg/kg) or vehicle from gestational day 7 to 22. Adult offspring underwent behavioral testing, electrophysiology, molecular assays, and MALDI imaging mass spectrometry of brain fatty acids at prepubescence and adulthood.
What this study cannot tell us
This is an animal study, so results may not directly translate to humans. The THC dose and route of administration differ from typical human consumption patterns. The study used only THC, not whole cannabis with its many other compounds.
How to read the evidence
Preliminary: single animal study with controlled conditions but no human data.
When this study was published
Published in 2022.
The bigger picture
With maternal cannabis use rising, understanding exactly how THC affects fetal brain development is critical. This study points to fatty acid pathways and sex-specific vulnerability as key pieces of that puzzle.
Questions still open
- Do similar fatty acid disruptions occur in human fetuses exposed to cannabis? Why do females recover from lipid changes while males do not? Could omega-3 supplementation during pregnancy offset any THC-related fatty acid deficits?
Common questions
What did THC do to the developing brain in this study?
Why were males and females affected differently?
Can these findings be applied to humans?
Read the original research
Prenatal THC Exposure Induces Sex-Dependent Neuropsychiatric Endophenotypes in Offspring and Long-Term Disruptions in Fatty-Acid Signaling Pathways Directly in the Mesolimbic Circuitry.
eNeuro, 9(5)
Citation
Sarikahya, Mohammed H; Cousineau, Samantha; De Felice, Marta; Lee, Kendrick; Wong, Karen Kw; DeVuono, Marieka V; Jung, Tony; Rodríguez-Ruiz, Mar; Ng, Tsun Hay Jason; Gummerson, Dana; Proud, Emma; Hardy, Daniel B; Yeung, Ken K-C; Rushlow, Walter; Laviolette, Steven R. (2022). Prenatal THC Exposure Induces Sex-Dependent Neuropsychiatric Endophenotypes in Offspring and Long-Term Disruptions in Fatty-Acid Signaling Pathways Directly in the Mesolimbic Circuitry.. eNeuro, 9(5). https://doi.org/10.1523/ENEURO.0253-22.2022
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