Interaction Between Cannabidiol, Meal Ingestion, and Liver Function

NCT04971837 | Completed Results

• 1 other identifier: 21-10634H
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolism; Liver Function; Pharmacokinetics

Outcome Measures

Primary Outcomes (27)

• Pharmacokinetic Time to Maximum Concentration- (Tmax) for Different Formulations of CBD

  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 (minutes).

  Venous blood will be sampled at standardized intervals: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration.

• Pharmacokinetic Maximum Concentration-(Cmax) for Different Formulations of CBD

  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).

  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.

• Pharmacokinetic Area Under the Curve Representing Total Cannabidiol Exposure Between 0 and 4 h (AUC 0-4) for Different Formulations of CBD

  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 (min x ng/mL).

  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.

• Pharmacokinetic Area Under the Curve an Estimate of Total Exposure to CBD Over Time (AUC 0-inf) for Different Formulations of CBD

  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 (mins x ng/mL).

  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.

• Pharmacokinetic Amount of Time it Takes to Decrease the Circulating Concentration to Half of Its Initial Value (t1/2) for Different Formulations of CBD

  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 (mins).

  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.

• Pharmacokinetic Rate at Which CBD is Absorbed Into the Body (Ka) for Different Formulations of CBD

  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).

  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.

• Pharmacokinetic Rate at Which CBD is Removed From the Body (Ke) for Different Formulations of CBD

  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).

  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.

• CBD Pharmacokinetic Volume of Distribution- (Vd) for Different Formulations of CBD

  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).

  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.

• Pharmacokinetic Parameter Tmax of a Formulation 725 After a Standardized Meal

  At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts the time to attain peak circulating concentration Tmax (mins).

  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.

• Pharmacokinetic Parameter Cmax of a Formulation 725 After a Standardized Meal

  At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD Cmax (ng/L).

  venous blood will be sampled at standardized intervals over: 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration.

• Pharmacokinetic Parameter AUC 0-4 of Formulation 725 After a Standardized Meal

  At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD AUC 0-4 (min x ng/mL).

  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.

• Pharmacokinetic Parameter AUC 0-inf of Formulation 725 After a Standardized Meal

  At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD AUC 0-inf (min x ng/mL).

  venous blood will be sampled at standardized intervals 0, 10, 20, 30, 45, 60, 120, 180, and 240 minutes and will be analyzed to compare circulating CBD concentration.

• Pharmacokinetic Parameter t1/2 of Formulation 725 After a Standardized Meal

  At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD t1/2 (h).

  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.

• Pharmacokinetic Parameter Ka of Formulation 725 After a Standardized Meal

  At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD Ka (1/h).

  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.

• Pharmacokinetic Parameter Ke of Formulation 725 After a Standardized Meal

  At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD Ke (1/h).

  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.

• Pharmacokinetic Parameter Vd of Formulation 725 After a Standardized Meal

  At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD Vd (L).

  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.

• Ingested CBD on Postprandial Metabolism Via Indirect Calorimetry

  At the 2 randomized visits Including a Test Meal Thermic Effect of Feeding (TEF) Under the Curve was calculated from standardized intervals prior to and after ingestion of a liquid meal and a single dose of Formulation 725.

  Randomized visit Including a test meal collected during 235 minutes of TEF

• Ingested CBD on Postprandial Metabolism Via Measurements of Glucose

  At the 2 randomized visits Including a Test Meal, glucose Area Under the Curve was calculated from standardized intervals after ingestion of a liquid meal and a single dose of Formulation 725.

  Compare 2 randomized visits Including a test meal collected at baseline,10,20,30,45,60,90,120,150,180,210, and 240 minutes.

• Ingested CBD on Postprandial Metabolism Via Measurements of Insulin

  At the 2 randomized visits Including a Test Meal insulin Area Under the Curve was calculated from standardized intervals after ingestion of a liquid meal and a single dose of Formulation 725.

  Compare 2 randomized visits Including a test meal collected at baseline,10,20,30,45,60,90,120,150,180,210, and 240 minutes.

• Ingested CBD on Postprandial Metabolism Via Measurements of Triglycerides

  At the 2 randomized visits Including a Test Meal triglyceride Area Under the Curve was calculated from standardized intervals after ingestion of a liquid meal and a single dose of Formulation 725.

  Compare 2 randomized visits Including a test meal collected at baseline,10,20,30,45,60,90,120,150,180,210, and 240 minutes.

• Acute Influence of Liver Function, Alanine Aminotransferase (ALT), With the Different Formulations of CBD.

  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).

  Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days

• Acute Influence of Liver Function, Albumin, for Different Formulations of CBD.

  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.

  Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days

• Acute Influence of Liver Function, Alkaline Phosphatase, With the Different Formulations of CBD.

  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.

  Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days

• Acute Influence of Liver Function, Aspartate Aminotransferase, With the Different Formulations of CBD.

  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.

  Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days

• Acute Influence of Liver Function, Total Bilirubin, With the Different Formulations of CBD.

  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.

  Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days

• Acute Influence of Kidney Function, Blood Urea, With the Different Formulations of CBD.

  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.

  Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days

• CBD on Postprandial Metabolism Via Indirect Calorimetry

  At the 2 randomized visits including a Resting Metabolic Rate prior to and after ingestion of a single dose of Formulation 725 or placebo.

  Compare 2 randomized visits Including a test meal collected during 45 minutes of resting metabolic rate

Study Arms (2)

Two Visits Including A Test Meal

EXPERIMENTAL

Separated by a minimum of 4 days.

Dietary Supplement: Cannabidiol (CBD) powder formulation; Dietary Supplement: CBD matching Placebo

Five Visits Not Involving A Test Meal

EXPERIMENTAL

Separated by a minimum of 14 days.

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

Interventions

Cannabidiol (CBD) powder formulation DIETARY_SUPPLEMENT

T-P-S-10 Caliper powder - 30 mg CBD in the form of 300 mg of 10% CBD isolate (Formulation 725: Water soluble.Contains sorbitol)

Five Visits Not Involving A Test Meal; Two Visits Including A Test Meal

Cannabidiol (CBD) Oil based tincture formulation DIETARY_SUPPLEMENT

30 mg CBD isolate in MCT oil,1:1 ratio of CBD to Medium Chain Triglycerides oil. (Formulation 088: Not water soluble. Contains medium chain triglyceride coconut oil.)

Five Visits Not Involving A Test Meal

Cannabidiol (CBD) Gum Arabic, maltodextrin base formulation DIETARY_SUPPLEMENT

10% CBD Gum Arabic, maltodextrin base(Formulation 126: Water soluble. Contains gum arabic and maltodextrin)

Five Visits Not Involving A Test Meal

Cannabidiol (CBD) Gum Arabic, sorbitol base formulation DIETARY_SUPPLEMENT

10% CBD Gum Arabic, sorbitol base (Formulation 213: Water soluble. Contains gum arabic and sorbitol)

Five Visits Not Involving A Test Meal

Cannabidiol (CBD) Isolate in water formulation DIETARY_SUPPLEMENT

Pure CBD as crystalline powder (\>99% purity) (Formulation 625 Not water soluble)

Five Visits Not Involving A Test Meal

CBD matching Placebo DIETARY_SUPPLEMENT

Matching Placebo

Two Visits Including A Test Meal

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Colorado State University: lead

Study Sites (1)

Colorado State University, Dept. of Health and Exercise Science

Fort Collins, Colorado, 80523-1582, United States

Location

Related Publications (1)

• Abbotts KSS, Ewell TR, Butterklee HM, Bomar MC, Akagi N, Dooley GP, Bell C. Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function. Nutrients. 2022 May 21;14(10):2152. doi: 10.3390/nu14102152.

  PMID: 35631293 RESULT

MeSH Terms

Interventions

Cannabidiol; Gum Arabic

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Plant Gums; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Plant Exudates; Biological Products; Complex Mixtures

Limitations and Caveats

1. Protocol was only competed by males, even though both men and women were invited to participate in the study. 2. Commercially available meal replacements were used but are not representative of the average person's meals (i.e. solid foods). 3. A relatively small dose of CBD was administered (30mg) and does not reflect the average dose of CBD individual are self-administering. The dose is also significantly smaller than FDA approved, Epidiolex, a seizure medication.

Results Point of Contact

• Title: Dr. Christopher Bell, Director, Laboratory of Integrative Physiology
• Organization: Colorado State University

Christopher.Bell@colostate.edu

(970) 491-7522

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 4, 2021
• First Posted: July 22, 2021
• Study Start: May 20, 2021
• Primary Completion: December 9, 2021
• Study Completion: December 9, 2021
• Last Updated: November 15, 2024
• Results First Posted: November 15, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)