Cannabidiol regulation of fear memory processing and associated brain function

Abstract

Anxiety disorders such as phobias and post-traumatic stress are common and often debilitating diseases linked to abnormally persistent memories of fearful events. Although psychological and drug therapies are available, these treatments show limited effectiveness and can cause adverse side effects, highlighting the urgent need for better therapies to treat these disorders. Cannabidiol, the main non-psychotropic phytocannabinoid present in the Cannabis sativa plant, is a drug that has shown great promise for treating anxiety disorders. We have shown that cannabidiol reduces fear in various animal models of anxiety and have recently extended these findings to show that it also reduces fear memory expression. Interestingly, cannabidiol has also been shown to enhance fear memory extinction, the process by which psychological therapy can reduce fear memory persistence. However, the pharmacological mechanisms and brain sites involved in mediating these effects remain unclear or unknown. In this multi-disciplinary project we will combine behavioral, pharmacological, electrophysiological and molecular biology techniques to determine the neurochemical and neural circuit mechanisms underlying the effects of cannabidiol on fear memory processing. Specifically, we will examine the roles of endocannabinoid transmission and prefrontal cortex-hippocampus circuit function in mediating the effects of cannabidiol on the expression and extinction of contextual fear memory in rats. Understanding the basic mechanisms underlying cannabidiol's effects on behaviour and brain function has important translational implications for its potential use in treating anxiety. (AU)