A Single THC Dose in Newborn Rats Caused Memory Problems in Females But Not Males

Male and female Sprague-Dawley rat pups received a single IP injection of THC (5 mg/kg) or vehicle (sesame oil) at postnatal day 3. Behavioral testing at postnatal weeks 6–8: Barnes maze (spatial memory), open field (anxiety), elevated plus maze (anxiety). Golgi-Cox staining for dendritic morphology and spine density in frontal cortex and hippocampus.

This study is remarkable for two reasons: first, a single dose of THC was sufficient to produce lasting cognitive effects; second, only females were affected. This sex-specific vulnerability suggests that the developing female brain may be more sensitive to endocannabinoid system disruption — a finding with implications for prenatal cannabis exposure, since THC crosses the placenta.

The sex difference here echoes the prenatal THC mouse MRI study (RTHC-00236), which also found females more affected. The BDNF study (RTHC-00284) provides a potential molecular mechanism — if BDNF changes are also sex-specific, they could explain why females are more vulnerable. The human ABCD data (RTHC-00241, RTHC-00285) can be re-examined for sex differences in prenatal exposure effects. Together, these studies build a consistent picture of female-specific vulnerability to early cannabinoid exposure.

Single dose at a single timepoint — doesn't model chronic exposure. Neonatal injection is a different route than prenatal placental transfer. Rat brain development timing doesn't perfectly map to human development. Only one THC dose tested. The mechanism connecting structural changes (both sexes) to behavioral effects (females only) needs further investigation.