Exploring the Anti-inflammatory Properties of Cannabis and Their Relevance to Insulin Sensitivity

Study Overview
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Brief Summary
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This study tests the effects of cannabinoid levels in blood on inflammation and insulin sensitivity both acutely and chronically in individuals across the weight spectrum. To that end, the study employs two observational designs: 1) A study of acute effects with intermittent cannabis users and 2) A study in which current cannabis users will select one of three cannabis strains for four weeks and are compared to a matched control group who do not use cannabis to study chronic effects. Blood levels of THC and CBD, inflammatory biomarkers, and insulin resistance will be measured in both studies.

Detailed Description
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According to the National Institute of Diabetes and Digestive and Kidney Diseases, over 30 million people in the US have diabetes, and just over 84 million people have pre-diabetes. Concurrently, 30 states and the District of Columbia have legalized cannabis for medical and/or recreational use and over the past decade, cannabis use among adults has more than doubled. Public perception and some scientific data suggest that cannabis causes acute over-eating, creating concern that public and legal acceptance of cannabis use will worsen the obesity epidemic in the United States, where more than two-thirds of US adults (68.8%) are currently overweight or obese. Paradoxically, cross sectional data demonstrate associations between chronic cannabis use and lower body mass index (BMI), prevalence of obesity, insulin resistance, waist circumference, and actual rates of type 2 diabetes despite data supporting higher caloric intake acutely. This study examines the effects of cannabinoid levels in blood on inflammation and insulin sensitivity both acutely and chronically in individuals across the weight spectrum. To that end, the study employs two observational designs: 1) A study of acute effects with intermittent cannabis users and 2) A study in which current cannabis users will select one of three cannabis strains for four weeks and are compared to a matched control group who do not use cannabis to study chronic effects.

Official Title
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Exploring the Anti-inflammatory Properties of Cannabis and Their Relevance to Insulin Sensitivity

Conditions
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Type 2 Diabetes, Obesity, Cannabis Use, Insulin Sensitivity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide informed consent Cannabis users in Study A must have smoked or vaped cannabis at least once since January 1st 2014 with no negative effects but NOT used in the past three months Cannabis users in Study B must have been a regular (at least weekly) user for at least a year Non-users in Study B cannot have used any cannabis in the previous year Weight stable (<5 pound fluctuation in the past six months) Planning to remain in the Boulder-Denver area for the next month Fasting blood glucose greater than or equal to 55 mg/dl and less than or equal to 126 mg/dl Cannabis users in Study A must endorse knowledge of the procedure(s) for smoking or vaping cannabis Exclusion Criteria: Known auto-immune disease Report of other drug use (cocaine, opiates, methamphetamine) in the past 90 days or fail urine screen for any of these drugs Daily tobacco (cigarette, E-cigs, smokeless) user, given the impact of tobacco smoking on insulin function Blood alcohol level greater than 0 at screening Current use of medications for glucose lowering, immunosuppression, or anti-inflammation Acute illness Current use of psychotropic medications Current diagnosis of diabetes Heavy drinking as defined by an Alcohol Use Disorders Test (AUDIT) Females can not be pregnant or trying to become pregnant Females can not be nursing mothers Have donated blood in the 8 weeks before the study or intend to donate blood in the 8 weeks after the study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study A<br>Adults balanced across the weight spectrum who have tried cannabis at least once with no negative reaction but are not regular users. | |
| Study B<br>Sample of current cannabis users and non-users balanced across the weight spectrum who are matched on age, gender, BMI and physical activity. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Markers of Inflammation | Change in Circulating Levels of Cytokines (TNF-α, IL-1B, IL-4, IL-6, IL-10, IL-13, MCP-1) | Study A: Difference between cytokines at baseline and cytokines one week later after acute use of cannabis product. Study B: Change from baseline to four weeks | 
| Change in Matsuda Index of Insulin Sensitivity | Calculation of Insulin Sensitivity using changes in fasting plasma glucose (FPG) and fasting plasma insulin (FPI). Measurements are collected on venous blood samples at 0, 30, 60, 90, and 120 minutes after ingestion of 75 grams oral glucose during oral glucose tolerance test (OGTT) Matsuda Index is calculated as follows: 10000/sqrt ((FPG X FPI) X (Mean OGTT glucose concentration X Mean OGTT insulin concentration)) | Study A: Baseline versus after acute use one week later of cannabis product. Study B: The two tests will be separated by four weeks | 
| Change in Plasma Glucose | Change in glucose over time after ingestion of 75 grams oral glucose measured during during oral glucose tolerance test (OGTT). Measurements are collected on venous blood samples at 0, 30, 60, 90, and 120 minutes. | Study A: Baseline versus one week later after acute use of cannabis product. Study B: The two tests will be separated by four weeks | 
| Change in Plasma Insulin | Change in insulin over time after ingestion of 75 grams oral glucose measured during OGTT. Measurements are collected on venous blood samples at 0, 30, 60, 90, and 120 minutes. | Study A: Baseline versus one week later after acute use of cannabis product. Study B: The two tests will be separated by four weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stanford Seven-Day Physical Activity Recall (PAR) | Interviewer administered assessment of number of minutes of mild, moderate, and vigorous physical activity over the previous seven days. | Study A: Baseline and one week following baseline Study B: Baseline and four weeks following baseline | 
| Sleep Quality | Pittsburgh Sleep Quality Index: Measurement of the quality and patterns of sleep from poor to good measuring seven domains (e.g., latency, duration, disturbances) over the last 2 weeks. | Study A: Baseline to one week following baseline Study B: Baseline to four weeks following baseline | 
| Marijuana Consumption Questionnaire | Frequency and quantity of cannabis use, age of first use, peer use, perceived risk from cannabis, and perceived availability of cannabis | Study A: Baseline and one week following baseline Study B: Baseline and four weeks following baseline | 
| Marijuana Dependence Scale | Based on DSM V criteria that were converted to a self-report to assess dependence and other problems related to the use of cannabis | Study A: Baseline and one week following baseline Study B: Baseline and four weeks following baseline | 
| Marijuana Withdrawal Checklist | A 15-item scale used to collect information on withdrawal symptoms participants may be experiencing due to lack of use of marijuana | Study A: Baseline and one week following baseline Study B: Baseline and four weeks following baseline | 
| The Alcohol Use Disorder Identification Test (AUDIT) | Standardized assessment of the extent of alcohol use and problems related to alcohol use | Study A: Baseline and one week following baseline Study B: Baseline and four weeks following baseline | 
| Timeline Follow-Back of Substance Use | Calendar-based assessment of daily substance use for the 30 days prior to the baseline session only for both studies | Study A: Baseline and one week following baseline Study B: Baseline and four weeks following baseline | 
| SF-12 Health Survey | The SF-12 Health Survey is a 12-item questionnaire used to assess general health and well-being and includes domains of physical functioning, role-physical, pain, general health, vitality, social functioning, role-emotional and mental health | Study A: Baseline and one week following baseline Study B: Baseline and four weeks following baseline | 
| Nutrition Data System for Research 24-Hour Dietary Recall | Interviewer administered recall measure developed by the University of Minnesota Nutrition Coordinating Center (NCC), that facilitates the standardized collection of 24-hour dietary recall data | Study A: Baseline and one week following baseline Study B: Baseline and four weeks following baseline | 
| Stanford Leisure-Time Activity Categorical Item (L-Cat) | Self-report measure of a single item comprising six descriptive categories ranging from inactive to very active | Study A: Baseline and one week following baseline Study B: Baseline and four weeks following baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Obesity, Cannabis, Insulin Sensitivity