In this study, we tested how prenatal THC exposure affects offspring with different inherited stress-coping traits. We selectively bred Dominant and Submissive mice, representing stress-resilient and stress-vulnerable phenotypes. Pregnant mothers were exposed to THC during late gestation, and we evaluated offspring body weight, anxiety-like behavior, sociability, and brain gene expression related to the endocannabinoid and dopaminergic systems.

We found that prenatal THC exposure reduced offspring body weight and produced phenotype-specific behavioral effects. Dominant offspring showed increased anxiety-like behavior, while Submissive offspring showed reduced anxiety-like behavior and increased sociability. We also checked molecular changes in the brain and found altered expressions of genes related to cannabinoid and dopamine signaling, including changes in FAAH, CB1, CB2, and dopamine receptors.

Overall, our findings suggest that the effects of prenatal THC exposure depend on inherited stress-coping phenotype. This highlights the importance of individual biological background when evaluating the risks of cannabis exposure during pregnancy.