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Impact of Chronic Cannabis Exposure on Metabolic Health and Disease

Institution: University of California, Riverside
Investigator(s): Nicholas DiPatrizio,
Award Cycle: 2019 (Cycle 29) Grant #: T29KT0232 Award: $743,386
Subject Area: Cardiovascular and Cerebrovascular Disease
Award Type: New Investigator Awards
Abstracts

Initial Award Abstract
Scientific and clinical evidence indicates that tobacco smoking is associated with a significantly increased risk of developing type-2 diabetes. The 2014 Surgeon General's report states that “The risk of developing diabetes is 30-40% higher for active smokers” and “There is a positive dose-response relationship between the number of cigarettes smoked and the risk of developing diabetes”. In light of this shocking data, we ask: Is cannabis exposure associated with a similar dysregulation of glucose homeostasis and promotion of type-2 diabetes? Indeed, California recently legalized recreational use of cannabis; however, the impact of chronic activation of the cannabinoid system in health and a variety of tobacco-related pathologies – including type-2 diabetes and other metabolic diseases – is largely unknown and the focus of our project. Chemical constituents of cannabis (i.e., delta-9 THC) activate cannabinoid receptors on cells throughout the body and control energy homeostasis. Studies from our lab and others suggest that cannabinoid receptor signaling becomes dysregulated in diet-induced metabolic dysfunction (e.g., hyperglycemia associated with type-2 diabetes). We will investigate the impact of chronic cannabis exposure on metabolic health and disease, and the role for cannabinoid receptor signaling along the intestinal-pancreatic glucose regulatory axis in these processes. First, we will examine the impact of THC or whole cannabis oil extract exposure daily for up to 60 days on glucose homeostasis, inflammation, and feeding behavior in hyperglycemic obese mice or lean mice. Second, we will assess the impact of these cannabinoids on expression and function of the endocannabinoid system in the intestine and pancreas using novel biochemical and analytical tools. Third, we will assess the impact of THC exposure on nutrient-induced release of incretins from small intestine – which control glucose homeostasis and insulin secretion from the pancreas – in lean and obese mutant mice that conditionally lack CB1Rs in small-intestinal epithelial cells that secrete incretins. The knowledge gained will aid in guiding science-based public policy associated with the impact of acute and chronic cannabis use in health and disease.