THC Effects on Glucose in Type 2 Diabetes

A single-center, double-blind, placebo-controlled, cross-over study designed to evaluate the effects of THC on glucose metabolism and endothelial functioning in individuals with type 2 diabetes. To accomplish the specific AIMS proposed, a single clinical trial will be conducted in which a maximum of 30 subjects with T2D, who are otherwise healthy, will be treated with THC and matching placebo in a cross-over study design. Each treatment period will be 2 weeks in duration with metabolic and endothelial assessments done post-therapy. Subjects will be randomized on a 1:1 basis to either receive either THC or placebo for the first 2 weeks of therapy. Then following a 4-week washout, they will receive the opposite investigational product for the second 2 weeks of therapy. Subjects will remain on their standard treatment for T2D throughout the entire course of the study. There will be a total of 10 study visits and subjects will be enrolled for approximately 16 weeks.

• Screening - Complete consenting process, complete medical history and physical exam, review of current medications, collect height/weight, vital signs, ECG and fasting laboratory (blood and urine) tests.
• Visit 2 - Treatment Session 1 Start - Collect weight, vital signs and fasting laboratory tests. Receive investigational product and training on its use.
• Visit 3 - Monitory investigational product compliance and adjust dosing.
• Visit 4 - Complete endothelial function tests including flow mediated dilation and EndoPat, complete vital signs, weight and laboratory tests for safety.
• Visit 5 - Complete a 2-Step Hyperinsulinemic/Euglycemic clamp and Indirect Calorimetry. Begin 4-week washout.
• Visit 6 - Treatment Session 2 Start - Collect weight, vital signs and receive investigational product and training on its use.
• Visit 7 - Monitory investigational product compliance and adjust dosing.
• Visit 8 - Complete endothelial function tests including flow mediated dilation and EndoPat, complete vital signs, weight and laboratory tests for safety.
• Visit 9 - Complete a 2-Step Hyperinsulinemic/Euglycemic clamp and Indirect Calorimetry. Discontinue use of investigational product.
• Safety Follow-up - Collect weight, vital signs, ECG and fasting laboratory tests. Receive investigational product and training on its use.

Inclusion criteria

• Males and Females 21-70 years old at the time of screening.
• Females of non-child bearing potential must be ≥ 1 year post-menopausal or documented as being surgically sterile. Females of child bearing potential must agree to use two methods of contraception during the entire study.
• Male subjects must be willing to use clinically acceptable method of contraception during the entire study.
• Have a clinical diagnosis of Type 2 Diabetes on a stable medication regimen for at least 3 months.
• BMI > 25 kg/m2).
• HbA1c < 10%).
• Negative urine toxicology result at screening visit.
• Able to provide written informed consent approved by an Institutional Review Board (IRB).

Exclusion criteria

• History or presence of any clinically significant illness, as detected by history, physical examination, and/or laboratory tests, that might put the participant at increased risk of adverse events (e.g., history of psychotic disorder, clinically significant mood and/or anxiety disorder, liver, or renal disease).
• No prior history of myocardial infarction, stroke or heart failure.
• Whole blood donation of 1 pint (500 mL) within 8 weeks prior to Screening. Donations of plasma, packed RBCs, platelets or quantities less than 500 mL are allowed at investigator discretion.
• Hemoglobin < 9g/dL.
• Liver enzymes ≥ 2 times upper normal limit and/or clinical signs/symptoms consistent with liver disease, including but not limited to nausea, vomiting, jaundice, itching, abdominal pain, or edema.
• History of clinically significant adverse events associated with cannabis intoxication (e.g., severe anxiety and panic, paranoia and psychosis, sustained tachycardia, or severe hypotension).
• History of seizures, head trauma, or other history of CNS insult that could predispose the participant to seizures.
• Use of any THC containing products within 30 days prior to the screening visit.
• Current use of tobacco products.
• Individuals who are pregnant or lactating/breastfeeding.
• Current use of insulin to treat Type 2 Diabetes.
• Unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits.
• Any other condition(s) that might reduce the chance of obtaining study data, or that might cause safety concerns, or that might compromise the ability to give truly informed consent.