Prenatal Cannabis Exposure Disrupted Breathing Regulation in Offspring With Sex-Specific Effects Lasting Into Adolescence

Prenatal WIN55,212-2 caused greater CO2 sensitivity at most ages in males and juvenile females. Males showed altered hypoxic chemoreflex at birth (hyperventilation) and P6-7 (hypoventilation), absent in females. Males had increased catecholaminergic neurons, more CB1 expression, and altered tissue respiration in brainstem. Reduced pulmonary compliance was seen in juvenile males. Females at birth showed enhanced spontaneous apnea and reduced serotonin neurons in raphe magnus.

Prenatal WIN55,212-2 (0.5 mg/kg/day) administered to pregnant rats. Respiratory function assessed in male and female offspring at four developmental timepoints (P0, P6-7, P12-13, P27-28). Brainstem neurochemistry and pulmonary mechanics also examined.

This is one of the first studies to examine how prenatal cannabinoid exposure affects the developing respiratory system. The sex-specific effects are striking: males show widespread breathing dysregulation while females show a potentially dangerous pattern of spontaneous apnea at birth with reduced serotonin neurons, relevant to SIDS risk.

The female finding of increased apnea with reduced serotonin neurons is particularly concerning because serotonergic dysfunction in the brainstem is one of the leading hypotheses for SIDS. If prenatal cannabis exposure impairs this system, it could contribute to sudden infant death risk.

Animal study with synthetic cannabinoid at a single dose, which may not reflect human cannabis use patterns. Rat respiratory development differs from humans. Cannot directly extrapolate to SIDS risk.