Cannabidiol Differentially Modulates Synaptic Release and Cellular Excitability in Amygdala Subnuclei.

Cannabidiol (CBD) is a non-psychoactive constituent of the Cannabis plant that has purported effectiveness in treating an array of stress-related neuropsychiatric disorders. The amygdala is a subcortical brain structure that regulates emotional behavior, and its dysfunction has been linked to numerous disorders including anxiety and posttraumatic stress disorder. Despite this, the direct effects of CBD on synaptic and cellular function in the amygdala are not known. Using electrophysiology and pharmacology, we report that CBD reduces presynaptic neurotransmitter release in the amygdala, and these effects are dependent on subnucleus and cell type. Furthermore, CBD broadly decreases cellular excitability across amygdala subnuclei. These data reveal physiological mechanisms by which CBD modulates amygdala activity and could provide insights into how CBD could affect emotional and stress-related behavioral responses.