2023 FDA Science Forum
The effects of cannabidiol and its main metabolites on human neural stem cells
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Abstract
Cannabidiol (CBD) is used for a variety of purposes by different groups of people, including to reduce nausea in pregnancy. In recent years, demand for CBD or CBD containing products has increased at an alarming rate. When consumed during pregnancy, CBD can pass through the placenta and enter the fetal blood stream. There are concerns about the effects of CBD and its major metabolites (7-OH-CBD and 7-COOH-CBD) on fetal development. In the present study, human neural stem cells (NSCs) were treated with CBD and its metabolites at different concentrations and durations to understand how the drug may affect fetal brain development. Drug effects on NSC viability and proliferation rate were assessed using MTT reduction, LDH release and EdU incorporation assays. Cell cycle analysis was performed using flow cytometry after cellular DNA was stained with propidium iodide. CBD, 7-OH-CBD and 7-COOH-CBD dose-dependently reduced NSC viability. At clinically relevant concentrations (i.e. human plasma concentrations), CBD, 7-OH-CBD and 7-COOH-CBD caused more obvious cell death when exposure duration increased. CBD and 7-OH-CBD reduced NSC numbers in the G1 phase after 24h exposure. However, 24h exposure did not cause significant change in NSC proliferation. This study demonstrates that clinically relevant concentrations of CBD, 7-OH-CBD and 7-COOH-CBD affect basic physiological features of human NSCs, suggesting the drug may have adverse effects on the developing human brain in vivo.
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