Pregnant mice exposed to both THC and chronic stress had the worst maternal behavior and offspring outcomes, with adolescent offspring showing sex-specific anxiety, reduced motivation, and altered gene expression in brain reward circuits.
Prenatal care providers, developmental neuroscientists, researchers studying cannabis-stress interactions in pregnancy.
Prenatal THC + stress produced additive harm: worse than either exposure alone
What the researchers found
All exposure groups (THC alone, stress alone, combined) showed impaired maternal behavior, with additive effects in the combined group. Adolescent offspring showed sex-specific behavioral changes: stress and combined exposures increased anxiety and reduced motivation in both sexes; THC alone primarily affected female self-care and social behavior. Brain transcriptomics revealed sex- and region-specific gene expression changes affecting mitochondrial function, synaptic organization, and glial signaling.
Why it matters
Many pregnant women use cannabis specifically to manage stress and anxiety, making the combined exposure scenario highly relevant. The finding that THC plus stress produces additive harm to both maternal behavior and offspring brain development challenges the assumption that cannabis alleviates prenatal stress.
The numbers in context
THC 2 mg/kg daily; stress GD3-12; combined group showed additive maternal impairment; sex-specific offspring behavioral changes; PFC and NAc transcriptomics showed distinct molecular pathway alterations for each exposure.
How the study worked
Translational mouse model combining prenatal THC (2 mg/kg daily) from GD3 to birth with maternal witness defeat stress from GD3-12. Assessed maternal behavior, adolescent offspring behavior, and transcriptomic profiling of prefrontal cortex and nucleus accumbens.
What this study cannot tell us
Mouse model may not fully translate to humans. Single THC dose and stress paradigm tested. Transcriptomic changes do not necessarily predict functional outcomes. Cannot separate direct THC effects from indirect effects through altered maternal behavior.
How to read the evidence
Preliminary: Well-designed translational mouse model combining THC and stress, but animal results require human validation.
When this study was published
Published in 2025 (preprint).
The bigger picture
This study is the first to model the real-world scenario of pregnant women using cannabis for stress relief. The finding that THC does not mitigate stress effects and may add to them has direct implications for prenatal counseling.
Questions still open
- Do the combined effects of THC and stress in human pregnancies mirror these animal findings? Which specific offspring brain changes are most clinically relevant? Would CBD or other cannabinoids produce different results?
Common questions
Why is the combined THC + stress finding important?
How were male and female offspring affected differently?
Read the original research
Concurrent maternal stress and THC exposure during pregnancy alters adolescent behavioral outcomes and corticolimbic molecular programs.
bioRxiv : the preprint server for biology
Citation
Olusakin, Jimmy; Dewan, Mahima; Kashyap, Atul; Franco, Daniela; Kumar, Gautam; Lujan, Miguel A; Mark, Katrina S; Cheer, Joseph; Lobo, Mary Kay. (2025). Concurrent maternal stress and THC exposure during pregnancy alters adolescent behavioral outcomes and corticolimbic molecular programs.. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2025.06.26.661775
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