Prenatal Cannabis Smoke Exposure Altered Sex Ratio, Increased Anxiety, and Changed Gene Expression in Rat Offspring

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.

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.

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 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.

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.