The Neurobehavioral and Psychophysiological Mechanisms of Cannabidiol for Alcohol Use Disorder

Abstract

Alcohol use disorder (AUD) is characterised by compulsive alcohol seeking despite negative consequences. Although AUD is associated with a large proportion of the total global disease burden, there remains a paucity of effective medications available for this indication. Cannabidiol (CBD) has emerged as a promising novel pharmacotherapeutic agent, however, relatively little research has been conducted in human samples with AUD. This thesis addresses this gap with a cross-over double-blind randomized controlled trial of 800 mg/day CBD versus placebo in individuals with AUD. The data from this research is then considered in three separate empirical chapters in which CBD-mediated effects on psychophysiology, regional brain activity, and neurometabolites are detailed.

Results from this thesis suggest that CBD administration is associated with elevated parasympathetic nervous system activity, reductions in self-reported anxiety during cue exposure stages, and improved self-reported craving recovery following cue exposure, relative to placebo sessions (Chapter 4). Additionally, CBD is linked to hypoactivation of the precuneus during both control and alcohol cue exposure (Chapter 5). Moreover, CBD administration is associated with the restoration of glutamate (Glu) and γ-aminobutyric acid (GABA), and significant increases in glutamine + glutamate (Glx) concentrations in the dorsal anterior cingulate cortex, particularly in individuals who consumed alcohol the previous day compared to those who did not (Chapter 6). Together, these findings provide sufficient evidence to discuss the potential therapeutic mechanisms and preliminary signs of efficacy for the use of CBD in the treatment of AUD (Chapter 7).

In conclusion, this body of work contributes to the literature that considers the potential role of CBD in the treatment of AUD and suggests the need for a large parallel randomised controlled trial to further understand CBD-associated therapeutic mechanisms for AUD.