Shared mechanisms of alcohol use disorder and Anxiety and effects of the endocannabinoid system

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Project Summary Anxiety disorders and alcohol related disorders (ARD) are both physiologically inflammatory and psychologically debilitating illnesses with high individual and societal costs. In addition, the presence of alcohol use related disorder (ARD) can double the odds of having an anxiety-related disorder. Current treatment options for anxiety disorders or ARDs may be effective in alleviating symptoms for one disorder, but may exacerbate symptoms for the other. Available treatments generally do not target their shared neurobiological mechanisms, in turn highlighting the lack of an objective marker of systemic and neurobiological change associated with both conditions, and limiting the effectiveness of unifocal diagnostic tools and therapeutic targets. Furthermore, there are additional challenges for sexual and ethnic minorities with ARDs or anxiety disorders, including increased stigma, problems accessing care, and exposure to discrimination, all of which are sorely understudied. There is a need for new therapeutic targets that are studied more equitably across diverse groups that account for both physiological effects of anxiety symptomology and comorbidity with ARDs. One such potential target may be the endocannabinoid system (ECS) and its relationship with inflammatory processes. Promisingly, exogenous cannabinoids such as cannabidiol (CBD) have been shown to differentially act on inflammatory mechanisms of the ECS, and CBD alone or with THC may also dose-dependently decrease reward response to alcohol, have anxiolytic properties, be assistive to extinction learning, and possibly stimulate neurosteroidogenesis, which is thought to support fear extinction and limit hyperarousal. Thus, this study will investigate the effects of exogenous cannabinoids among anxiety-symptomatic participants on alcohol consumption, subjective anxiety symptoms, and a shared biomarker summary risk score for anxiety and ARDs. Furthermore, given the current underrepresentation of sexual and ethnic minorities in research on anxiety and ARDs, this study will focus on these populations as well as investigate the effects of discrimination-related stress on the same outcomes. The long-term goal of this proposal is to expand upon the applicant’s background in conducting inclusive research among underrepresented groups while building expertise in the neurobiology and psychopharmacology of co-occurring psychological and substance use disorders. The eventual development of an integrated, evidence-based treatment model that is inclusive of equitable and diverse samples and is broadly applicable across patients is a distant, yet wholly worthwhile goal which this project supports.