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.

Inclusion Criteria:

• 18 years of age and older
• Weight more than 110 pounds
• Have a Body Mass Index greater than or equal to 25 kilograms/squared meters
• Free of gastrointestinal or metabolic diseases
• Sedentary (less than 150 minutes of moderate-intensity exercise per week during the previous 3 months)

Exclusion Criteria:

• Less than 18 years of age
• Pregnant or breastfeeding
• Have known food allergies
• Have been diagnosed with any autoimmune disorders or with compromised immune function
• Celiac disease
• Inflammatory bowel diseases
• Gastrointestinal cancers
• Diabetes
• Human Immunodeficiency Virus
• Adverse reaction to ingesting CBD oils, or CBD containing food products
• Taking any of the following medications will be excluded as these may have negative interactions with CBD:
• steroids,
• 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors,
• calcium channel blockers,
• antihistamines,
• human immunodeficiency virus antivirals
• immune modulators,
• benzodiazepines,
• antiarrythmics,
• antibiotics,
• anesthetics,
• antipsychotics,
• antidepressants,
• anti-epileptics,
• beta blockers,
• coumadin (warfarin),
• proton pump inhibitors,
• non-steroidal anti-inflammatory drugs,
• angiotension II blockers,
• oral hypoglycemic agents,
• sulfonylureas.

The CBD and placebo formulations are prepared, bottled, and coded by Caliper Foods. The participants will receive a coded bottle to consume of the different formulations of CBD and placebo.