Detrimental effects of prenatal combined delta-9 tetrahydrocannabinol and cannabidiol exposure on placental morphometry and neurodevelopment

(CBD) on the prefrontal cortex, neurodevelopmental indices, placental morphology, and fetal growth in Wistar rats. Pregnant rats received 150 mg/kg of ?9-THC and CBD from gestational day 6 to day 19 or until delivery. Placental morphometry was assessed using Vernier calipers, while the prefrontal cortex morphology was evaluated histologically using Hematoxylin & Eosin staining. Neurodevelopmental indices were measured using reflex tests. Placental morphometric analysis at gestational day 19 revealed a significant increase in placental length (control: 1.40 ± 0.04 cm; experimental: 1.45 ± 0.22 cm, P < 0.05) and a significant reduction in placental area (control: 2.39 ± 0.0153 m²; experimental: 2.23 ± 0.07 m², P < 0.01). Fetal weight at gestational day 19 (control: 3.78 ± 0.043 g; experimental: 3.51 ± 0.064 g, P < 0.001) and pup weight at postnatal day 1 (control: 5.742 ± 0.081 g; experimental: 3.72 ± 0.039 g, P < 0.001) were significantly reduced. Reflex assessment in neonates showed reduction in righting (control: 1.78 ± 0.07; experimental: 1.08 ± 0.15, P < 0.001), forelimb grasp (control: 1.88 ± 0.06; experimental: 1.24 ± 0.13, P < 0.01), and cliff avoidance tests (control: 1.84 ± 0.06; experimental: 1.15 ± 0.14, p < 0.05). Morphology revealed disrupted blood spaces, trophoblast abnormalities, cortical disorganization, and neuronal vacuolation, indicating structural damage and stress. These results suggest that prenatal exposure to combined ?9-THC and CBD adversely affects placental integrity and neurodevelopmental outcomes, posing potential risks to fetal health.

Key Words: Delta-9-tetrahydrocannabinol, cannabidiol, neurodevelopment, placental morphometry, prefrontal cortex