The Repository @ St. Cloud State

Open Access Knowledge and Scholarship

Date of Award

5-2024

Culminating Project Type

Thesis

Styleguide

apa

Degree Name

Biological Sciences - Cell and Molecular: M.S.

Department

Biology

College

College of Science and Engineering

First Advisor

Marina Cetkovic-Cvrlje

Second Advisor

Mark Mechelke

Third Advisor

Timothy Schuh

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Keywords and Subject Headings

CBD, Type 1 Diabetes, Autoimmunity, Mouse Models

Abstract

Type 1 Diabetes (T1D) is an autoimmune disease in which immune cells called T cells initiate an attack on the insulin-producing beta cells of the pancreas, resulting in chronic hyperglycemia. Oil-based cannabidiol (CBD) has been used in previous research of T1D, showing beneficial effects in lowering diabetes incidence, glycemia, and pro-inflammatory cytokines. However, recently emerging water-soluble CBD products claiming an increased bioavailability, have never been tested in T1D. Therefore, the goal of this study was to evaluate the effects of water-soluble CBD on the development and severity of T1D in two mouse models: the non-obese diabetic (NOD) and low-dose streptozotocin-induced C57BL/6 (STZ-B6) mice. We expected to see a reduction in disease incidence, glycemia levels, along with altering T cell composition, function, and cytokine profiles of CBD-treated mice. For the NOD model, 5-6-week-old female mice were injected intraperitoneally (IP) for 6 weeks with 5 or 10 mg/kg of commercially available water-soluble CBD. They were then monitored weekly for glucose and body weight measurements up to 24 weeks of age. Mice were sacrificed at an early (11 weeks of age) and late (24 weeks of age or when confirmed hyperglycemic) timepoint in disease development, when immune parameters, such as spleen weights, cell counts, viability, immunophenotypes, and cytokine profiles were assessed. For the B6 model, 5-7-week-old male mice were injected with 5 mg/kg water-soluble CBD IP, for 4 weeks. While one cohort of B6 mice received IP injections of low-dose-streptozotocin (STZ) post CBD administration, another cohort received STZ and CBD simultaneously during the fourth week of CBD treatment. Following STZ administration, the mice were followed up to 33 days post first STZ injection for glucose and body weights measurements. An early and late time point was also assessed, day 11 and day 33 post first STZ injection. In the NOD model, dosage of 5 mg/kg of water-soluble CBD did not exhibit a beneficial effect of delaying disease development or reducing hyperglycemia. However, 10 mg/kg CBD treatment appeared to exhibit detrimental effects on T1D development, with significantly increased glycemic levels. In the STZ-B6 mouse model, a dosage of 5 mg/kg CBD was used both before and during STZ administration. When CBD was given before STZ, a non-significant lowering of hyperglycemia and a significant reduction in pro-inflammatory cytokines at an early time point was seen. However, when mice received CBD during STZ administration, we noted that CBD-treated mice exhibited significantly increased T1D incidence, along with a trend of higher glycemia. In conclusion, our findings highlight the need for further investigation of long-term water-soluble CBD usage and its effective dosages, as well as necessity for overall standardization of commercially available CBD formulations.

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