Differential Cannabidiol Pharmacology Across Amygdala Subnuclei

Abstract

Cannabidiol (CBD) is one of the primary phytocannabinoid constituents of Cannabis and is increasingly utilized to treat a variety of conditions, such as anxiety and epilepsy. Despite the growing use of CBD, the clinical and off‐label applications of CBD and related products have greatly preceded the state of pre‐clinical and clinical research regarding the pharmacological properties of CBD. As such, an empirical and mechanistic understanding of the physiological and therapeutic effects of CBD remains poorly lacking. CBD exhibits remarkably complex polypharmacology and engages a variety of targets in the central nervous system, rendering it a challenge to discern the precise molecular mechanisms by which CBD exerts its purported effects. Here, we explore the effects of CBD on the physiology of distinct cell types in the amygdala, a subcortical brain structure critical for the processing of fear and anxiety, and in some cases linked to epilepsy. Preliminary data shows that CBD decreases passive membrane excitability of pyramidal neurons in the basolateral nucleus, exhibited as a decrease in action potential firing in response to square wave depolarizing steps. Additionally, CBD decreases spontaneous release of GABA onto a population of cells in the central nucleus, without affecting the frequency of spontaneous glutamate release, resulting in a shift in the excitation/inhibition ratio. Ongoing studies are aimed at further characterizing these findings in distinct amygdala cell types, identifying the molecular targets of CBD that mediate these effects, and determining the behavioral relevance of CBD effects on amygdala physiology.