Fetal cannabidiol (CBD) exposure alters thermal pain sensitivity, cognition, and prefrontal cortex excitability

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, is it unknown how fetal CBD exposure affects embryonic development and postnatal outcomes. CBD binds and activates receptors that are important for fetal development and are expressed in the fetal brain, 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 during fetal development can disrupt neurodevelopment. Here, we test the hypothesis that intrauterine CBD exposure alters offspring neurodevelopment and postnatal behavior. We show that fetal CBD exposure sensitizes male offspring to thermal pain in a TRPV1 dependent manner. We show that fetal CBD exposure decreases cognitive function 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. Combined, these data show that fetal CBD exposure disrupts neurodevelopment and postnatal behavior in a sex-dependent manner. One Sentence Summary Cannabidiol (CBD) consumption during pregnancy alters offspring behavior and neuronal excitability in a sex dependent manner in mice.