Original Research

Exp. Biol. Med.

Sec. Anatomy/Pathology

Volume 250 - 2025 | doi: 10.3389/ebm.2025.10608

This article is part of the Issue2024 International Conference on Neuroprotective Agents Conference ProceedingsView all 12 articles

The effects of cannabidiol and its main metabolites on human neural stem cells

Leah  E LathamLeah E LathamQiang  GuQiang GuShuliang  LiuShuliang LiuCheng  WangCheng WangFang  LiuFang Liu*
  • Division of Neurotoxicology, National Center for Toxicological Research (FDA), Jefferson, United States

The final, formatted version of the article will be published soon.

Cannabidiol (CBD) has been used for different purposes by different populations in recent years. When consumed by pregnant women, CBD can pass through the placenta and enter the fetal blood stream.There is concern over adverse effects of fetal exposure to CBD and its major metabolites (7-OH-CBD and 7-COOH-CBD). In the present study, human neural stem cells (NSCs) were treated with CBD and its metabolites at different concentrations for various durations to understand how the drug may affect fetal brain development. NSCs were also treated with delta-9 tetrahydrocannabinol (THC) for comparison purposes. CBD, 7-OH-CBD and 7-COOH-CBD dose-dependently reduced NSC viability. CBD and 7-OH-CBD reduced NSC number at the G1 phase. A 24h exposure did not cause significant change in NSC proliferation. At concentrations comparable to those detected in human blood, longer exposures to CBD, 7-OH-CBD and 7-COOH-CBD caused more obvious cell death. After NSCs differentiation, CBD treatment reduced GFAP and cannabinoid receptor 2 (CB2) expression. THC treatment reduced the GFAP expression, but the change in CB2 expression did not reach statistical significance. The expression of cannabinoid receptor 1 (CB1) and beta-tubulin III were not significantly altered by drug exposures.The study demonstrated that clinically relevant concentrations of CBD, 7-OH-CBD and 7-COOH-CBD affect basic physiological features of human NSCs. After NSC differentiation, the reduced expression of CB2 receptors and GFAP on differentiated cells further indicated the vulnerability of developing central nervous system to CBD and THC. These data will help to contextualize in vivo neurodevelopmental studies that may not accurately model human metabolite profiles of CBD.

Keywords: CBD, 7-OH-CBD, 7-COOH-CBD, THC, and neural stem cells

Received: 28 Mar 2025; Accepted: 06 May 2025.

Copyright: © 2025 Latham, Gu, Liu, Wang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Fang Liu, Division of Neurotoxicology, National Center for Toxicological Research (FDA), Jefferson, United States

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