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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Type 2 Diabetes; Cannabis Use; Insulin Sensitivity
• Intervention / Treatment: Other: Study A: Single use of cannabis flower product; Other: Study B: Ad libitum cannabis use for four weeks or no cannabis use

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 233

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Center for Innovation and Creativity

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 40 years (Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Community Sample

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study A; Adults balanced across the weight spectrum who have tried cannabis at least once with no negative reaction but are not regular users.	Other: Study A: Single use of cannabis flower product; Participants are asked to purchase and use one of three cannabis flower strains with differing levels of THC and CBD: 1) CBD (~14% CBD/0% THC), 2) THC (~14% THC/0% CBD), or 3) THC+CBD (~7% THC/7% CBD).
Study B; Sample of current cannabis users and non-users balanced across the weight spectrum who are matched on age, gender, BMI and physical activity.	Other: Study B: Ad libitum cannabis use for four weeks or no cannabis use; Participants choose whether to use a cannabis flower product ad libitum for four weeks or to not use cannabis for four weeks. Participants who choose to use cannabis are asked to purchase and use one of three cannabis flower strains with differing levels of THC and CBD: 1) CBD (~14% CBD/0% THC), 2) THC (~14% THC/0% CBD), or 3) THC+CBD (~7% THC/7% CBD).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Markers of Inflammation	Change in Circulating Levels of Cytokines (TNF-α, IL-6, IL-1β, IL-12, IFNG, and IL-4). Results are reported as a composite score of TNF-α, IL-6, IL-1β, IL-12, IFNG, and IL-4	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). Values across the timepoints were combined to create a Matsuda Index score as follows: 10000/sqrt ((FPG X FPI) X (Mean OGTT glucose concentration X Mean OGTT insulin concentration)). Higher scores mean higher sensitive to insulin and that your body more efficiently clears glucose from your bloodstream, thus higher scores are better.	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 and averaged across these timepoints for a mean score.	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 and averaged across these timepoints for a mean score.	Study A: Baseline versus one week later after acute use of cannabis product. Study B: Baseline versus four weeks later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stanford Seven-Day Physical Activity Recall (PAR)	Interviewer administered assessment of number of minutes of moderate to vigorous physical activity over the previous seven days. Scores are reported as total minutes in the last week summed across moderate, hard, and very hard activity levels.	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. Participants' scores are reported as a global score of the summed seven component scores together ranging from 0 to 21, where higher scores indicate worse sleep and a global score of 5 or above indicates poor sleep quality.	Study A: Baseline only Study B: Baseline to four weeks following baseline
Marijuana Consumption Questionnaire	Times per day of cannabis flower use from 0 to 6. Includes all participants in Study A and only cannabis users in Study B.	Study A: Baseline only. Study B: Baseline and four weeks following baseline
Marijuana Dependence Scale	This is a self-report scale based on DSM-5 criteria to assess dependence and other problems related to the use of cannabis. Scores are reported as a sum across the 11 items with yes/no options, ranging from 0 to 11, with higher scores indicating more dependence symptoms. Includes all participants in Study A and only cannabis users in Study B.	Study A: Baseline only. Study B: Baseline and four weeks following baseline
Marijuana Withdrawal Checklist	A 15-item scale used to collect information on withdrawal symptoms that participants may be experiencing due to the lack of use of marijuana. Options range from 0 (none) to 3 (severe) for each question and are summed to create a final score ranging from 0 to 45. Includes all participants in Study A and only cannabis users in Study B.	Study A: Assessed at follow-up, one week following baseline. Study B: Assessed at follow-up, 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. Scores are summed and range from 0 to 40 with higher scores indicating more hazardous alcohol use.	Study A: Baseline only. 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 for both studies. The average days of smoked cannabis use in the last 30 days are reported.	Study A: Baseline only. 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. Only the mental component was analyzed. Scores are calculated using a weighted algorithm with scores ranging from 0 to 100; scores greater than 50 meaning better than average health and scores worse than 50 meaning worse than average health.	Study A: Baseline only. 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. Healthy Eating Index (HEI) total scores are reported for each participant, which is a measure of healthy eating on a scale of 0 (poor eating) to 100 (very healthy eating). Scores above 80 indicate a good diet, and scores below 80 indicate a diet in need of improvement.	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 (1) to very active (6).	Study A: Baseline and one week following baseline Study B: Baseline and four weeks following baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily Online Survey of Alcohol Use	Daily surveys sent to Study B participants during the four-week period between study visits querying alcohol use. This is reported as average number of drinks/day of alcohol use.	Study B only: Daily for four weeks between baseline and second study visit
Daily Only Survey of Exercise	Daily surveys sent to Study B participants during the four-week period between study visits querying minutes of exercise. This is reported as average minutes/day on exercise days.	Study B only: Daily for four weeks between baseline and second study visit
Daily Only Survey of Fruit/Vegetable Consumption	Daily surveys sent to Study B participants during the four-week period between study visits querying consumption of fruits and vegetables. This is reported as average servings/day on fruit/vegetable consumption days.	Study B only: Daily for four weeks between baseline and second study visit
Daily Online Survey on Cannabis Use	Daily surveys sent to Study B participants during the four-week period between study visits querying amount of cannabis used. This is reported as average grams/cannabis use day.	Study B only: Daily for four weeks between baseline and second study visit

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder
• Collaborators: University of Colorado, Denver

Publications and helpful links

General Publications

• Bryan AD, Skrzynski CJ, Yang J, Chrystal KA, Bidwell LC, Hutchison KE, Perreault L. Inhaling high THC cannabis acutely increases inflammation but not insulin sensitivity: a quasi-randomized trial. Sci Rep. 2026 Jul 16. doi: 10.1038/s41598-026-62837-0. Online ahead of print.
• Skrzynski CJ, Bryan AD, Schmiege SJ. Quasi-randomization to Cannabinoid Condition in Studies of US Legal Market Cannabis: Characteristics of Accepters Versus Decliners of Condition Assignment. Prev Sci. 2026 Mar;27(3):441-450. doi: 10.1007/s11121-026-01893-4. Epub 2026 Mar 13.

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2019
• Primary Completion (Actual): December 1, 2024
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: September 6, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (Actual): October 3, 2019

Study Record Updates

• Last Update Posted (Actual): August 6, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Diabetes; Obesity; Insulin Sensitivity; Cannabis
• Additional Relevant MeSH Terms: Endocrine System Diseases; Mental Disorders; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Hyperinsulinism; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Diabetes Mellitus, Type 2; Diabetes Mellitus; Marijuana Abuse; Insulin Resistance
• Other Study ID Numbers: 1R01DA050515 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No