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Interaction Between Cannabidiol, Meal Ingestion, and Liver Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04971837
Recruitment Status : Completed
First Posted : July 22, 2021
Last Update Posted : June 30, 2022
Sponsor:
Information provided by (Responsible Party):
Christopher Bell, Colorado State University

Brief Summary:

According to a recent consumer poll, over 20 million Americans regularly use cannabidiol (CBD). Moreover, 64 million Americans (over 25% of the population) report trying CBD at least once within the previous 2 years. Since the passing of the 2018 Agriculture Improvement Act, the use of hemp-derived products, such as CBD, is highly prevalent across North America. The acceleration of the use of CBD has outpaced our understanding of the associated potential risks and benefits, and the way it is processed within the body.

In the current proposed project, investigators wish to continue our ongoing collaboration with Caliper Foods, a Colorado-based manufacturer of CBD products. The focus of this project is three-fold: (1) investigators will compare the pharmacokinetics of different formulations of ingestible CBD; (2) investigators will examine the potential two-way interaction between a meal and one formulation of ingestible CBD; and, (3) investigators will examine the influence of different formulations of CBD on markers of liver function.


Condition or disease Intervention/treatment Phase
Metabolism Liver Function Pharmacokinetics Dietary Supplement: Cannabidiol (CBD) powder formulation Dietary Supplement: Cannabidiol (CBD) Oil based tincture formulation Dietary Supplement: Cannabidiol (CBD) Gum Arabic, maltodextrin base formulation Dietary Supplement: Cannabidiol (CBD) Gum Arabic, sorbitol base formulation Dietary Supplement: Cannabidiol (CBD) Isolate in water formulation Dietary Supplement: CBD matching Placebo Not Applicable

Detailed Description:

Pharmacokinetics describes the speed in which something that is ingested is made available within the body (i.e. bioavailability).There are many different preparations/formulations of CBD and they may differ from one another with regards to their pharmacokinetics. One important consideration when evaluating CBD formulations is the pharmacokinetic goal and intended use. For example, if the indication for the CBD is to treat acute pain, then a faster time to peak concentration (Tmax) and higher maximal concentration (Cmax) may be desirable, and also may help to decrease the risk of overdose due to premature repeat self administration. Alternatively, as a chronic treatment for anxiety, a larger area under the curve (AUC) may be preferable if a user follows a regular dosing schedule.

One purpose of the proposed project is to compare the pharmacokinetics of different formulations of CBD. The formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble).

Several previous studies have demonstrated an influence of eating on the pharmacokinetics of ingested CBD. The general consensus appears to be that prior ingestion of a high-fat meal increases the maximal concentration of circulating CBD (Cmax) and lowers the time to attain peak circulating concentration (Tmax).

One purpose of the proposed project is to study the influence of a standardized meal on the pharmacokinetics of a CBD formulation.

Little is known about the influence of ingested CBD on postprandial metabolism. The thermic effect of feeding (i.e. the increase in metabolic rate above resting metabolism) is considered an important physiological determinant of energy balance, and therefore also of weight gain or loss. Further, the dynamics of circulating glucose and triglycerides following a meal are reflective of metabolic health and predictive of future cardiometabolic disease risk. CBD has been purported to have a variety of beneficial physiological properties, including anti-inflammatory and antioxidant actions. Either of these individual properties alone could favorably modify postprandial metabolism, given that CBD potentially does both, it appears likely that CBD might improve the physiological regulation of postprandial metabolism.

One purpose of the proposed project is to determine the influence of CBD on postprandial metabolism.

The liver plays a critical regulatory role in postprandial metabolism, and also with the physiological processing of cannabinoids. The relationship between the use of cannabinoids and liver health is unclear. While early studies implied that exposure of the liver to very high daily dosing of cannabinoids may be detrimental, more recent studies are suggesting that some cannabinoids, including CBD, may have therapeutic potential for the treatment of non-alcoholic fatty liver disease. The acute effects of low dose CBD (e.g. 30 mg) on liver function in healthy adults have not been well described, and may be influenced by the formulation of the CBD product (i.e. whether it is water or lipid soluble).

One purpose of the proposed project is to determine the acute influence of different formulations of CBD on circulating markers of liver function.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Basic Science
Official Title: Interaction Between Cannabidiol, Meal Ingestion, and Liver Function
Actual Study Start Date : May 20, 2021
Actual Primary Completion Date : December 9, 2021
Actual Study Completion Date : December 9, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions
Drug Information available for: Cannabidiol

Arm Intervention/treatment
Experimental: Two Visits Including A Test Meal
Separated by a minimum of 4 days.
Dietary Supplement: Cannabidiol (CBD) powder formulation
T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate

Dietary Supplement: CBD matching Placebo
Matching Placebo

Experimental: Five Visits Not Involving A Test Meal
Separated by a minimum of 14 days.
Dietary Supplement: Cannabidiol (CBD) powder formulation
T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate

Dietary Supplement: Cannabidiol (CBD) Oil based tincture formulation
30 mg CBD isolate in MCT oil (1:1 ratio of CBD to Medium Chain Triglycerides oil)

Dietary Supplement: Cannabidiol (CBD) Gum Arabic, maltodextrin base formulation
10% CBD Gum Arabic, maltodextrin base

Dietary Supplement: Cannabidiol (CBD) Gum Arabic, sorbitol base formulation
10% CBD Gum Arabic, sorbitol base

Dietary Supplement: Cannabidiol (CBD) Isolate in water formulation
formulation




Primary Outcome Measures :
  1. Compare different formulations of CBD Pharmacokinetic Time to Maximum Concentration- (Tmax) [ Time Frame: Venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be sampled at standardized intervals over 4-hours to calculate Tmax (hours).

  2. Compare different formulations of CBD Pharmacokinetic maximum concentration-(Cmax). [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be sampled at standardized intervals over 4-hours to calculate Cmax (ng/mL).

  3. Compare different formulations of CBD Pharmacokinetic area under the curve representing total cannabidiol exposure between 0 and 4 h (AUC 0-4) [ Time Frame: Venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be sampled at standardized intervals over 4-hours to calculate AUC 0-4 (h x ng/mL).

  4. Compare different formulations of CBD Pharmacokinetic area under the curve an estimate of total exposure to CBD over time (AUC 0-inf). [ Time Frame: Venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be sampled at standardized intervals over 4-hours to calculate AUC 0-inf (h x ng/mL).

  5. Compare different formulations of CBD Pharmacokinetic amount of time it takes to decrease the circulating concentration to half of its initial value (t1/2). [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be sampled at standardized intervals over 4-hours to calculate t1/2 (h).

  6. Compare different formulations of CBD Pharmacokinetic rate at which CBD is absorbed into the body (Ka). [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be sampled at standardized intervals over 4-hours to calculate Ka(1/h).

  7. Compare different formulations of CBD Pharmacokinetic rate at which CBD is removed from the body (Ke). [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be sampled at standardized intervals over 4-hours to calculate Ke (1/h).

  8. Compare different formulations of CBD Pharmacokinetic volume of distribution- (Vd) [ Time Frame: Venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be sampled at standardized intervals over 4-hours to calculate Vd (L).

  9. Determine the Pharmacokinetic parameter Tmax of a T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate after standardized meal [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts the time to attain peak circulating concentration Tmax (h).

  10. Determine the Pharmacokinetic parameter Cmax of a T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate after standardized meal [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD Cmax (ng/L).

  11. Determine the Pharmacokinetic parameter AUC 0-4 of a T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate after standardized meal [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD AUC 0-4 (hxng/mL).

  12. Determine the Pharmacokinetic parameter AUC 0-inf of a T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate after standardized meal [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD AUC 0-inf (hxng/mL).

  13. Determine the Pharmacokinetic parameter t1/2 of a T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate after standardized meal [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD t1/2 (h).

  14. Determine the Pharmacokinetic parameter Ka of a T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate after standardized meal [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD Ka (1/h).

  15. Determine the Pharmacokinetic parameter Ke of a T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate after standardized meal [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD Ke (1/h).

  16. Determine the Pharmacokinetic parameter Vd of a T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate after standardized meal [ Time Frame: venous blood will be sampled at standardized intervals over 4-hours: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration. ]
    At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD Vd (L).

  17. Determine ingested CBD on postprandial metabolism via indirect calorimetry [ Time Frame: Change from the 2 randomized visits Including a test meal separated by 4 days ]
    At the 2 randomized visits Including a Test Meal measure resting metabolic rate (RMR- kcal/day) followed immediately by ingestion of a liquid meal and a single 30 mg dose of Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate or a placebo.

  18. Determine ingested CBD on postprandial metabolism via measurements of glucose [ Time Frame: Compare 2 randomized visits Including a test meal collected at 90,150,210,725 minutes. ]
    At the 2 randomized visits Including a Test Meal measure blood glucose at standardized intervals after ingestion of a liquid meal and a single dose of Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate or a placebo.

  19. Determine ingested CBD on postprandial metabolism via measurements of insulin [ Time Frame: Compare 2 randomized visits Including a test meal collected at 90,150,210,725 minutes. ]
    At the 2 randomized visits Including a Test Meal measure insulin at standardized intervals after ingestion of a liquid meal and a single dose of Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate or a placebo.

  20. Determine ingested CBD on postprandial metabolism via measurements of triglycerides [ Time Frame: Compare 2 randomized visits Including a test meal collected at 90,150,210,725 minutes. ]
    At the 2 randomized visits Including a Test Meal measure triglycerides at standardized intervals after ingestion of a liquid meal and a single dose of Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate or a placebo.

  21. Determine the change in the acute influence of liver function, alanine aminotransferase (ALT), with the different formulations of CBD. [ Time Frame: Change from baseline at time 0, 60, 120 minutes for each formulation, visits separated by 14 days ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be collected at standardized intervals and analyzed for alanine aminotransferase (ALT).

  22. Determine the change in the acute influence of liver function, albumin, with the different formulations of CBD. [ Time Frame: Change from baseline at time 0, 60, 120 minutes for each formulation, visits separated by 14 days ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be collected at standardized intervals and analyzed for albumin.

  23. Determine the change in the acute influence of liver function, alkaline phosphatase, with the different formulations of CBD. [ Time Frame: Change from baseline at time 0, 60, 120 minutes for each formulation, visits separated by 14 days ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be collected at standardized intervals and analyzed for alkaline phosphatase.

  24. Determine the change in the acute influence of liver function, aspartate aminotransferase, with the different formulations of CBD. [ Time Frame: Change from baseline at time 0, 60, 120 minutes for each formulation, visits separated by 14 days ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be collected at standardized intervals and analyzed for aspartate aminotransferase.

  25. Determine the change in the acute influence of liver function, total bilirubin, with the different formulations of CBD. [ Time Frame: Change from baseline at time 0, 60, 120 minutes for each formulation, visits separated by 14 days ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be collected at standardized intervals and analyzed for total bilirubin.

  26. Determine the change in the acute influence of kidney function, blood urea, with the different formulations of CBD. [ Time Frame: Change from baseline at time 0, 60, 120 minutes for each formulation, visits separated by 14 days ]
    The different formulations will be standardized for CBD dose (30 mg) but will differ in their preparation (e.g. water vs. fat-soluble). At the 5 randomized Visits Not Including A Test Meal venous blood will be collected at standardized intervals and analyzed for blood urea.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Participants must be greater than 18 years of age
  • Weigh more than 110 pounds
  • Have a body mass index greater than 25kg/m^2
  • Be free of any gastrointestinal or metabolic diseases
  • Be able to refrain from use of any Cannabis or cannabis containing products for three days prior to participating in the study.

Exclusion Criteria:

  • Less than 18 years of age
  • Pregnant or breastfeeding
  • Food allergies
  • Autoimmune disorders or with compromised immune function,
  • Celiac disease
  • Inflammatory bowel Diseases
  • Gastrointestinal cancers
  • Diabetes
  • HIV
  • Adverse reactions to ingesting Cannabis spp. or cannabis-containing products (including, but not limited to, marijuana, CBD oils, or CBD/THC containing food products)
  • Taking any of the follow medications: steroids, HMG-CoA reductase inhibitors, calcium channel blockers, antihistamines, HIV antivirals, immune modulators, benzodiazepines, antiarrythmics, antibiotics, anesthetics, antipsychotics, antidepressants, anti-epileptics, beta blockers, proton pump inhibitors, NSAIDs, angiotension II blockers, oral hypoglycemic agents, and sulfonylureas.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04971837


Locations
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United States, Colorado
Colorado State University, Dept. of Health and Exercise Science
Fort Collins, Colorado, United States, 80523-1582
Sponsors and Collaborators
Colorado State University
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Responsible Party: Christopher Bell, Associate Professor, Colorado State University
ClinicalTrials.gov Identifier: NCT04971837    
Other Study ID Numbers: 21-10634H
First Posted: July 22, 2021    Key Record Dates
Last Update Posted: June 30, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cannabidiol
Sorbitol
Anticonvulsants
Cathartics
Gastrointestinal Agents