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People use cannabidiol (CBD), the primary non-psychoactive cannabinoid of cannabis, as a treatment for symptoms that are commonly associated with pregnancy including nausea, pain, and anxiety. Many people believe CBD is safe to take during pregnancy. However, CBD crosses the placenta and affects the activity of protein targets that are expressed in the fetal brain. Cannabidiol alters the activity of ion channels including voltage- gated sodium, potassium, and calcium channels that control the electrical activity of neurons. Abnormal electrical activity could disrupt brain function via changes in axon growth and synapse structure and function. Furthermore, CBD alters the activity of G- protein coupled receptors that are expressed in the fetal brain and are important for axon growth and guidance suggesting that fetal exposure could prevent axons from reaching their correct targets. Indeed, cannabidiol exposure reduces axon growth in vitro and in vivo. This raises the possibility that CBD consumption during pregnancy could disrupt fetal brain development. Recent studies show that oral cannabidiol consumption during pregnancy alters the excitability of the pyramidal neurons of the prefrontal cortex and affects postnatal cognitive function in mouse offspring. Furthermore, fetal CBD exposure increases thermal pain sensitivity in offspring. Gestational cannabidiol exposure affects compulsivity and memory in a different rodent model. Here, we discuss how CBD affects various ion channels and G-protein coupled receptors, the roles of these proteins in neurodevelopment, and evidence that CBD affects brain development.
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Fetal cannabidiol (CBD) exposure alters thermal pain sensitivity, problem-solving, and prefrontal cortex excitability
Abstract Thousands of people suffer from nausea with pregnancy each year. Nausea can be alleviated with cannabidiol (CBD), a primary component of cannabis that is widely available. However, it is unknown how fetal CBD exposure affects embryonic development and postnatal outcomes. CBD binds and activates receptors that are expressed in the fetal brain and are important for brain development, including serotonin receptors (5HT1A), voltage-gated potassium (Kv)7 receptors, and the transient potential vanilloid 1 receptor (TRPV1). Excessive activation of each of these receptors can disrupt neurodevelopment. Here, we test the hypothesis that fetal CBD exposure in mice alters offspring neurodevelopment and postnatal behavior. We administered 50 mg/kg CBD in sunflower oil or sunflower oil alone to pregnant mice from embryonic day 5 through birth. We show that fetal CBD exposure sensitizes adult male offspring to thermal pain through TRPV1. We show that fetal CBD exposure decreases problem-solving behaviors in female CBD-exposed offspring. We demonstrate that fetal CBD exposure increases the minimum current required to elicit action potentials and decreases the number of action potentials in female offspring layer 2/3 prefrontal cortex (PFC) pyramidal neurons. Fetal CBD exposure reduces the amplitude of glutamate uncaging-evoked excitatory post-synaptic currents, consistent with CBD-exposed female problem-solving behavior deficits. Combined, these data show that fetal CBD exposure disrupts neurodevelopment and postnatal behavior in a sex specific manner.
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- Award ID(s):
- 1945916
- PAR ID:
- 10574881
- Publisher / Repository:
- Springer Nature
- Date Published:
- Journal Name:
- Molecular Psychiatry
- Volume:
- 28
- Issue:
- 8
- ISSN:
- 1359-4184
- Page Range / eLocation ID:
- 3397 to 3413
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1038/s41380-023-02130-y
