GRANT NUMBER: R01 DA020129-07S1

ABSTRACT: Alcohol and cannabis are frequently used concomitantly and this polysubstance use is associated with heightened adverse consequences compared with usage of either substance alone. Chronic exposure to either alcohol or cannabinoids results in significant dysregulation of the brain noradrenergic system. However, gaps exist in our knowledge regarding how combined alcohol and cannabinoid exposure impacts the noradrenergic system. In the administrative supplement, we will test the hypothesis that concomitant exposure to alcohol further intensifies cannabinoid-induced dysregulation of brain noradrenergic activity. In addition, there is increasing evidence to support that alcohol exposure has a greater impact on females as compared to males, adding to the view that the prevalence and/or severity of polysubstance abuse may have greater negative consequences in females. We will build on preliminary data showing a sex dependent effect of chronic alcohol exposure on components of the endocannabinoid system regulating the noradrenergic system providing a potential mechanism for overactivation of noradrenergic circuitry following combined alcohol and cannabinoid use that may be particularly exaggerated in females. Taken together, the proposed studies will provide an in-depth understanding of the interaction between alcohol and cannabinoids on stress-integrative neural circuits across the sexes. This work has significant public health relevance and could potentially guide individualized therapies for the clinical management of polysubstance abuse.


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