While many empirical projects have described multiple potential health benefits of CBD, the potential for CBD to provide protection against the development of diabetes via favorable modification of the gut microbiota has received relatively less attention. We hope to learn if CBD can improve glucose tolerance and the gut microbiota, and if these two improvements might be related.
More than 122 million Americans have diabetes, or its precursor, pre-diabetes. The clinical and public health implications are not trivial as diabetes is the leading cause of blindness and non-traumatic amputation; it is closely associated with vascular disease and premature death, and people with diabetes are at greater risk of serious and fatal complications associated with Covid-19. The defining feature of diabetes is dysfunctional regulation of blood glucose (blood sugar). Although numerous factors contribute to the development of type 2 diabetes, the gut microbiota has recently emerged as an important regulator of glucose homeostasis. Imbalances in the microbiota can lead to intestinal inflammation and loss of gut barrier integrity, which in turn activates inflammatory cascades outside of the gut that can precipitate development of metabolic dysfunction. Changes in the gut microbiota can also alter proportions of microbial metabolites such as secondary bile acids and short chain fatty acids, which have been shown to influence host metabolism. Diet is one of the most important modifiers of the gut microbiota and several plant-based chemicals have been shown to exert beneficial effects on its composition and function. Cannabis sativa L., which produces a suite of phytochemicals, referred to collectively as cannabinoids, has also been shown in epidemiologic studies to exert beneficial effects on glucose regulation. These effects may be, in part, due to interactions with the gut microbiota. The focus of this project is cannabidiol (often abbreviated as CBD). CBD is not marijuana. CBD is not cannabis. CBD is a bioactive phytochemical that is present in the plant Cannabis sativa; it has no psychoactive properties. Over recent years CBD has garnered considerable attention on account of its potential medicinal properties. There is increasing evidence that CBD may have therapeutic and/or preventative effects pertinent to cancer, cardiovascular disease, anxiety, and most relevant to the current proposal, diabetes and the gut microbiota. The aim of the proposed study is to evaluate the influence of short-term CBD on glucose tolerance and the gut microbiota. Hypothesis: compared with daily ingestion of a placebo, 4-weeks daily ingestion of CBD will improve glucose tolerance and favorably modify the gut microbiota towards a more anti-inflammatory profile.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
30
30 mg CBD in the form of 300 mg of 10% CBD isolate
Matching Placebo
Colorado State University, Dept. of Health and Exercise Science
Fort Collins, Colorado, United States
Circulating blood glucose
Measurements of circulating blood glucose during an Oral Glucose Tolerance Tests via a blood analyzer
Time frame: Compared to baseline after 4 weeks of the intervention
Circulating blood insulin
Measurements of circulating insulin during an Oral Glucose Tolerance Tests via a blood analyzer
Time frame: Compared to baseline after 4 weeks of the intervention
Hepatic Insulin Extraction
Measurements of C-Peptide concentration via ELISA Assays
Time frame: Compared to baseline after 4 weeks of the intervention
Tissue oxygenation
Measurement of tissue oxygenation via Near-Infrared Spectroscopy (NIRS)
Time frame: Compared to baseline after 4 weeks of the intervention
Reactive hyperemia
Measurement of reactive hyperemia via doppler ultrasound
Time frame: Compared to baseline after 4 weeks of the intervention
Shannon and Faith's microbiota diversity scores in feces
Assessed via 16s ribosomal ribonucleic acid microbial profiling
Time frame: Compared to baseline after 4 weeks of the intervention
B-diversity scores for all fecal samples to assess clustering
Assessed via 16s ribosomal ribonucleic acid microbial profiling
Time frame: Compared to baseline after 4 weeks of the intervention
Differentially abundant microbiota in feces of collected during treatment
Assessed via 16s ribosomal ribonucleic acid microbial profiling
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Time frame: Compared to baseline after 4 weeks of the intervention
Abundant microbiota to markers in feces
Assessed via Linear discriminant analysis Effect Size algorithm
Time frame: Compared to baseline after 4 weeks of the intervention
Human Granulocyte Macrophage Colony-Stimulating Factor
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interferon gamma
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interleukin 1 beta
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interleukin 2
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interleukin 4
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interleukin 5
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interleukin 6
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interleukin 7
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interleukin 8
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interleukin 10
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interleukin 12 (p70)
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Interleukin 13
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
Tumor Necrosis Factor alpha
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention
High-sensitivity C-reactive protein
Assessed via 13-plex human T-cell cytokine panel
Time frame: Compared to baseline after 4 weeks of the intervention