Prenatal THC Exposure Affected Brain Development and Social Behavior Differently Depending on Timing

Postnatal THC exposure (modeling late pregnancy) produced sex-specific changes in microglial phagocytosis during brain development and altered social behavior during the juvenile period. Prenatal THC exposure (modeling early pregnancy) produced inverse changes to both phagocytosis and social behavior compared to postnatal exposure. The effects were mediated through microglia, the brain's immune cells, which express both cannabinoid receptors.

Animal study exposing rats to THC either prenatally (via dam injection, modeling early human pregnancy) or postnatally (via direct injection in early postnatal period, modeling late human pregnancy). Microglial phagocytosis in the amygdala and social behavior were measured.

Cannabis use during pregnancy is increasing, and many users assume earlier use is less harmful. This study suggests the timing of exposure during pregnancy matters enormously, with early and late exposure producing opposite developmental effects. This complicates any simple guidance about cannabis use during pregnancy.

The endocannabinoid system guides normal brain development, and disrupting it with exogenous THC can alter the trajectory of neural circuit formation. The finding that timing produces opposite effects highlights the complexity of prenatal drug exposure and explains why epidemiological studies may find inconsistent results when they don't account for trimester of exposure.

Animal model using direct THC injection, which differs from human cannabis use. Cannot directly translate rat developmental periods to human trimesters. Focused on amygdala and social behavior; other brain regions and behaviors were not assessed. Preprint, not yet peer-reviewed.