Prenatal Cannabis Exposure Had Opposite Metabolic Effects in Male and Female Mouse Offspring

Pregnant mice consumed cannabis extract (5 mg/kg THC daily) from early gestation through postnatal day 10. Pup weight was initially reduced but recovered by day 16. On a high-fat diet, exposed females had reduced fat accumulation and lower insulin, leptin, and resistin, independent of body weight. On a normal diet, exposed females showed altered insulin sensitivity with increased glucagon levels and reduced pancreatic islet size. Male offspring showed no metabolic effects from exposure.

Pregnant mice voluntarily consumed cannabis extract (5 mg/kg/day THC) from gestational day 1.5 through postnatal day 10. Male and female offspring were placed on high-fat or control diet at postnatal day 49 for 12 weeks. Measured weight gain, adiposity, glucose tolerance, insulin sensitivity, hormones, and pancreatic structure.

Cannabis use during pregnancy is increasing with legalization. This study reveals sex-specific metabolic programming effects that may not be apparent until later in life, particularly under metabolic challenge (high-fat diet). The finding that effects appear only in females highlights the importance of studying both sexes.

The paradox of prenatal cannabis exposure being metabolically harmful on a normal diet but seemingly protective on a high-fat diet raises complex questions. It suggests the exposure alters fundamental metabolic programming in sex-specific ways that interact with later dietary environment.

Animal study; mouse metabolism differs from human. Voluntary cannabis consumption model, though ecological, makes precise dosing difficult. Small group sizes typical of animal studies. Cannot separate prenatal from postnatal exposure effects (exposure continued to PD10).