Adolescent THC exposure causes lasting brain changes in male rats, but different from females

Researchers treated adolescent male rats with escalating doses of THC twice daily from postnatal day 35 to 45 (roughly equivalent to human mid-adolescence). At adulthood, they ran behavioral tests for psychotic-like symptoms, emotional reactivity, and cognition. They then examined hippocampal and prefrontal cortex tissue for glutamate receptor expression, synaptic markers, neurotransmitter release, and inflammatory markers.

This study adds to growing evidence that adolescent cannabis exposure can permanently reshape brain development, and that the effects differ by sex. The finding that males show hippocampal-centered damage while females show prefrontal-centered damage suggests the adolescent brain has region-specific windows of vulnerability to THC.

The sex-dependent pattern revealed here and in the companion female study creates a more nuanced picture of adolescent THC risk. Rather than a single uniform harm, THC appears to exploit whichever brain regions are most actively developing at the time of exposure, and this differs between sexes. This has implications for understanding why cannabis-related outcomes vary so widely across populations.

This is an animal study using injected THC at controlled doses, which differs from how humans consume cannabis. The doses and timing may not directly translate to human adolescent use patterns. The study examined only one timepoint in adulthood, so it is unclear whether these changes persist lifelong or eventually resolve.