Psychiatry and Behavioral Sciences, School of Medicine
Neurodevelopmental impact of prenatal tetrahydrocannabinol (THC) exposure
The prevalence of marijuana (Cannabis sativa) use among pregnant women is already high and is likely to increase as more states adopt legalization of medical and recreational marijuana. The long term effects of prenatal cannabis exposure on the developing brain are not well understood. Epidemiological studies of children prenatally exposed to cannabis have yielded mixed results, though a general pattern emerging from these studies indicates that these children exhibit long-term impairments in cognitive/behavioral development and alterations in brain structure/function. There is a critical need to understand the impact of cannabis, and its active ingredient, Δ9-tetra-hydrocannabinol (THC), on the developing fetal brain. Most of our knowledge on the effects of prenatal cannabis exposure stems from rodent studies documenting adverse neurodevelopmental outcomes in offspring prenatally exposed to THC. Although animal model experiments provide an opportunity to evaluate the effects of prenatal cannabis exposure in a controlled environment, differences in route of administration, dose, gestational timing and choice of species have contributed to inconsistent findings. Moreover, the vast majority of animal models have utilized oral or subcutaneous routes of prenatal THC exposure rather than inhalation, which more closely replicates real world exposure. In humans, marijuana is commonly used to self-administer THC via inhalation of combusted plant material, though non-combusting devices have been recently adapted for use with cannabis extracts. Alternative routes of exposure, such as vaping, are becoming increasingly popular but have been unexplored in prenatal animal models. Here we propose to develop a novel rat model to evaluate the effects of in utero exposure to THC via e-cigarette on offspring brain and behavioral development. The long term goal of this highly-translational research is to generate critical data necessary to understand the impact of prenatal THC exposure on offspring brain and behavioral development and to inform pregnancy safety recommendations and therapeutic interventions.
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