Female rats exposed to high-THC cannabis smoke during pregnancy produced litters with a skewed male-to-female ratio, and adult offspring showed increased anxiety-like behavior and altered amygdala gene expression, though they performed better on some cognitive tasks.
Reproductive toxicologists, developmental neuroscientists, obstetricians, pregnancy researchers.
Prenatal cannabis smoke shifted litter sex ratio toward more males
What the researchers found
Cannabis smoke exposure during pregnancy caused a significant increase in male-to-female ratio in litters. Adult offspring of both sexes explored the inner zone of an open field less (anxiety-like behavior). Cannabis-exposed offspring performed better at visual discrimination and reversal learning. RNA sequencing of adult amygdala revealed changes in genes related to development, cellular function, and nervous system disease in male offspring. Maternal weight, litter size, and gestational length were unaffected.
Why it matters
This is one of few studies using actual cannabis smoke rather than injected THC, making it more relevant to real-world prenatal exposure. The sex ratio shift is a particularly striking and novel finding that raises questions about cannabinoid effects on sexual differentiation.
The numbers in context
Gestational day 6-20 exposure. Significant male-biased sex ratio in cannabis litters. Decreased inner zone exploration in open field. Improved visual discrimination and reversal learning. Subtle amygdala gene expression changes in males.
How the study worked
Female Sprague Dawley rats exposed to cannabis smoke daily from gestational day 6-20 or room air. Offspring assessed in adulthood for open field, elevated plus maze, social interaction, and touchscreen operant conditioning tasks. Amygdala RNA sequencing in male offspring.
What this study cannot tell us
Rat model with smoke exposure may not perfectly replicate human smoking patterns. Gene expression changes were subtle and only examined in males. Touchscreen tasks may not translate to human cognitive function. Sample sizes not specified in abstract. Single cannabis variety tested.
How to read the evidence
Well-controlled rat study using actual cannabis smoke, but findings are preliminary and specific to this strain and exposure protocol.
When this study was published
Published in 2023.
The bigger picture
The finding that cannabis-exposed offspring showed better cognitive task performance alongside increased anxiety challenges simple narratives about prenatal cannabis being purely harmful. Biology is more nuanced, with some domains affected negatively and others potentially enhanced.
Questions still open
- What mechanism causes the sex ratio shift in cannabis-exposed litters?
- Does improved reversal learning in cannabis-exposed offspring reflect a genuine cognitive advantage or a different underlying process?
Common questions
Does smoking cannabis during pregnancy affect the baby?
Can cannabis change the sex ratio of offspring?
Read the original research
Repeated Exposure to High-THC Cannabis Smoke during Gestation Alters Sex Ratio, Behavior, and Amygdala Gene Expression of Sprague Dawley Rat Offspring.
eNeuro, 10(11)
Citation
Sandini, Thaisa M; Onofrychuk, Timothy J; Roebuck, Andrew J; Hammond, S Austin; Udenze, Daniel; Hayat, Shahina; Herdzik, Melissa A; McElroy, Dan L; Orvold, Spencer N; Greba, Quentin; Laprairie, Robert B; Howland, John G. (2023). Repeated Exposure to High-THC Cannabis Smoke during Gestation Alters Sex Ratio, Behavior, and Amygdala Gene Expression of Sprague Dawley Rat Offspring.. eNeuro, 10(11). https://doi.org/10.1523/ENEURO.0100-23.2023
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