Perinatal exposure to cannabinoids alters neurochemical development in rat brain

Adult female rats received daily oral doses of delta 9-tetrahydrocannabinol (delta 9-THC), delta 8-THC and cannabidiol (CBD) throughout gestation and lactation. The offspring were sacrificed at various ages and tissue samples of cerebral cortex and striatum were assayed for alpha 1-adrenergic and D2-dopaminergic receptors, respectively. In addition, tyrosine hydroxylase activity was determined in the striatum. The Kd for ligand binding to alpha 1 receptors in the cerebral cortex was significantly increased in 10-day-old offspring exposed to CBD. Significant increases in the Bmax of these receptors occurred at 20 days of age following perinatal exposure to delta 9-THC or delta 8-THC. Exposure to CBD increased the Kd of D2 receptors in the striatum of 10 and 20-day-old offspring compared to control. There were no significant treatment effects on the Bmax of D2 receptors in the striatum at any age. Tyrosine hydroxylase activity was significantly decreased only at 60 days of age in offspring exposed to delta 8-THC or CBD. These results differ from those previously reported with a crude marihuana extract, suggesting that changes in the development of brain catecholamine mechanisms resulting from perinatal exposure to marihuana extracts may be due to an additional constituent of the extract, interactions between specific cannabinoids or other unknown factors.