2023 FDA Science Forum
Assessing the Developmental Neurotoxicity of Perinatal Exposure to Cannabidiol in Sprague Dawley Rats
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Contributing OfficeNational Center for Toxicological Research
Abstract
Cannabidiol (CBD) is a non-intoxicating chemical component of the cannabis plant, and it is the active ingredient in Epidiolex, which is FDA-approved to treat seizures in rare childhood disorders. Recently, non-drug CBD usage has increased across the US, as CBD is often perceived as a safe and natural product that purportedly relieves anxiety, pain, and sleeplessness, among others. This is concerning because these issues are often associated with pregnancy, and pregnant women may use CBD because of its perceived safety. However, cannabis use during pregnancy has been linked to poor developmental outcomes, and CBD cannot currently be excluded as a contributing factor. The endocannabinoid system influences neurodevelopment and immune function, and the effects of developmental exposure to CBD on those systems is currently unclear. The current study investigated the developmental neurotoxicity of purified CBD in Sprague Dawley rats. Pregnant dams were orally gavaged with vehicle, 15, 30, 100, 250, 300 or 350 mg/kg/day CBD from gestational day 6 to the day prior to parturition. Pups were orally gavaged with the same dose as their respective dam from postnatal day (PND) 1 to 21. Offspring underwent a series of neurobehavioral tests from PND 21-180, which included tests of motor function, anxiety-like behavior, and cognition. Neurochemistry assays and IHC analysis of PND21 and PND180 tissue were conducted with a particular focus on the dopamine system. Neurobehavioral tests showed that CBD had no dose-dependent effect on motor function, anxiety-like behavior, sensorimotor gaiting, or cognition. There were no observed differences in measured neurotransmitter levels and brain protein concentrations within dopamine systems, and this was also true of select markers within serotonin and acetylcholine systems. Results from this study indicate no dose-dependent behavioral or neurochemical effects of perinatal CBD exposure. Additional behavioral and neurochemical tests are ongoing and will be analyzed to further investigate the effects of CBD on neurodevelopment.