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- Rudy Ortiz, PhD - Effects of CBD on blood pressure and substrate metabolism during metabolic syndrome

INVESTIGATOR: Rudy Ortiz, PhD

STUDY LOCATION: University of California, Merced

PROJECT TITLE: Effects of CBD on blood pressure and substrate metabolism during metabolic syndrome

FUNDING SOURCE: Center for Medicinal Cannabis Research

PROJECT TYPE: Pre-Clinical Study

STATUS:  COMPLETED

ABSTRACT:

Cardiovascular disease (CVD) is the leading cause of death in the US (1), and is a primary outcome of metabolic syndrome (MetS). Metabolic syndrome is defined by the simultaneous presence of multiple maladies that include hypertension and glucose intolerance. MetS is also a leading cause of the development of type 2 diabetes mellitus (T2DM), an additional metabolic disorder associated with CVD, with 1.4 million new cases of diabetes diagnosed in the US yearly. MetS is a link to both CVD and T2D as it develops earlier than both of the other conditions, thus, targeting MetS in its early stages may help avoid the later onset of either frank CVD and T2D. However, because MetS is a cluster of conditions present simultaneously, elucidating the mechanisms of each factor individually is complex. Urgency exists to identify novel therapeutics for addressing the growing prevalence of metabolic disorders. The medicinal use of marijuana has recently been realized for metabolic disorders. Cannabidiol (CBD) has therapeutic potential because of its anti-inflammatory and antioxidant effects. Because pro-inflammatory and oxidant pathways contribute to the manifestation of some aspects of MetS, CVD, and T2D, CBD has the potential to ameliorate CVD-associated hypertension and T2D-associated glucose intolerance (both of which are factors in MetS) by attenuating inflammation and oxidative stress. However, the potential benefits of CBD on MetS-associated hypertension and glucose intolerance have not been examined.

We propose to use a rat model of MetS that develops the hallmarks of the syndrome early, ultimately developing profound CVD and frank T2D. We propose to address the central hypothesis that chronic CBD treatment ameliorates the hypertension and glucose intolerance associated with MetS. We propose the following specific aims: (1) to determine the benefits of CBD on the development of elevated arterial blood pressure associated with MetS, and (2) to examine the benefits of CBD on ameliorating the glucose intolerance and insulin resistance associated with the model of MetS. Two sub-aims include examining the benefits on (a) lipid metabolism as dyslipidemia is a cluster factor in MetS and (b) the mitochondria as a principal regulator of substrate metabolism. The outcomes of these aims will be unique, novel contributions to the growing body of evidence that suggests that chronic CBD use alleviates the detriments associated with the manifestation of CVD and T2D.

PUBLICATIONS:

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Journal Article Wilson JN, Mendez DA, Dhoro F, Shevchenko N, Mescal M, Lund K, Fitzgerald R, DiPatrizio NV, Ortiz RM. (2024). Pseudocannabinoid H4CBD improves glucose response during advanced metabolic syndrome in OLETF rats independent of increase in insulin signaling proteins. American Journal of Physiol Intgr Comp Physiol, 326(2), R100-R109.