The sex hormones that bathe a fetus in the womb are some of the earliest and most potent determinates of gender differences in brain structure and social behavior. But other chemicals produced by the human body more subtly tweak the neural pathways underlying these distinctions. Endocannabinoids, natural compounds in the brain that excite the same receptors as marijuana, influence gender-specific behaviors, according to a study published in November in the Proceedings of the National Academy of Sciences USA.

Desiree Krebs-Kraft of the University of Maryland School of Medicine, Baltimore, counted the number of actively dividing glia (nonneuron brain cells) in the medial amygdala (MeA) of four-day-old rats. The MeA controls gender-specific differences in youthful play and regulates mating, parenting, aggression and territoriality in adults.

Krebs-Kraft found that females had more dividing MeA glia than males did. But when the researchers gave newborn rats a drug that mimics the effect of endocannabinoids on brain cells, the rate of cell division in females slowed to the same pace observed in male brains. The drug also changed behavior. Juvenile male rats usually engage in more social play than females, but female rats that received the drug frolicked just as much as the males.

Marijuana affects the mind because substances in the plant called cannabinoids imitate the naturally occurring endocannabinoids found in the brain. “Our results show that endocannabinoids are part of a natural signaling system that underlies the establishment of sex differences in the brain that are an important part of social behavior,” explains Margaret McCarthy, one of the study’s co-authors. “This would suggest that the use of cannabis during pregnancy could alter those systems and have unintended conse­quences,” she says, though cautioning that much more research is needed to say for sure. Studies have shown that the cannabinoids in marijuana can in fact breach the placenta, so an indulgent mother is smoking for two.

Curiously, the cannabinoid treatment had no effect on cell division or play behavior in males. The researchers found that male rats have inherently higher levels of endo­can­nabinoids in their brains than females, so trying to give the males a little boost did not cause any measurable changes.