Clinical trial NCT04971837: Interaction Between Cannabidiol, Meal Ingestion, and Liver Function
Official title: Interaction Between Cannabidiol, Meal Ingestion, and Liver Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolism
Liver Function
Pharmacokinetics
Lead sponsor: Colorado State University
Sponsor class: OTHER
First posted: 2021-07-22
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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.

Primary outcomes:
measure: Pharmacokinetic Time to Maximum Concentration- (Tmax) for Different Formulations of CBD
timeFrame: 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.
measure: Pharmacokinetic Maximum Concentration-(Cmax) for Different Formulations of CBD
timeFrame: 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.
measure: Pharmacokinetic Area Under the Curve Representing Total Cannabidiol Exposure Between 0 and 4 h (AUC 0-4) for Different Formulations of CBD
timeFrame: 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.
measure: Pharmacokinetic Area Under the Curve an Estimate of Total Exposure to CBD Over Time (AUC 0-inf) for Different Formulations of CBD
timeFrame: 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.
measure: Pharmacokinetic Amount of Time it Takes to Decrease the Circulating Concentration to Half of Its Initial Value (t1/2) for Different Formulations of CBD
timeFrame: 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.
measure: Pharmacokinetic Rate at Which CBD is Absorbed Into the Body (Ka) for Different Formulations of CBD
timeFrame: 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.
measure: Pharmacokinetic Rate at Which CBD is Removed From the Body (Ke) for Different Formulations of CBD
timeFrame: 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.
measure: CBD Pharmacokinetic Volume of Distribution- (Vd) for Different Formulations of CBD
timeFrame: 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.
measure: Pharmacokinetic Parameter Tmax of a Formulation 725 After a Standardized Meal
timeFrame: 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.
measure: Pharmacokinetic Parameter Cmax of a Formulation 725 After a Standardized Meal
timeFrame: 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.
measure: Pharmacokinetic Parameter AUC 0-4 of Formulation 725 After a Standardized Meal
timeFrame: 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.
measure: Pharmacokinetic Parameter AUC 0-inf of Formulation 725 After a Standardized Meal
timeFrame: 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.
measure: Pharmacokinetic Parameter t1/2 of Formulation 725 After a Standardized Meal
timeFrame: 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.
measure: Pharmacokinetic Parameter Ka of Formulation 725 After a Standardized Meal
timeFrame: 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.
measure: Pharmacokinetic Parameter Ke of Formulation 725 After a Standardized Meal
timeFrame: 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.
measure: Pharmacokinetic Parameter Vd of Formulation 725 After a Standardized Meal
timeFrame: 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.
measure: Ingested CBD on Postprandial Metabolism Via Indirect Calorimetry
timeFrame: Randomized visit Including a test meal collected during 235 minutes of TEF
measure: Ingested CBD on Postprandial Metabolism Via Measurements of Glucose
timeFrame: Compare 2 randomized visits Including a test meal collected at baseline,10,20,30,45,60,90,120,150,180,210, and 240 minutes.
measure: Ingested CBD on Postprandial Metabolism Via Measurements of Insulin
timeFrame: Compare 2 randomized visits Including a test meal collected at baseline,10,20,30,45,60,90,120,150,180,210, and 240 minutes.
measure: Ingested CBD on Postprandial Metabolism Via Measurements of Triglycerides
timeFrame: Compare 2 randomized visits Including a test meal collected at baseline,10,20,30,45,60,90,120,150,180,210, and 240 minutes.
measure: Acute Influence of Liver Function, Alanine Aminotransferase (ALT), With the Different Formulations of CBD.
timeFrame: Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days
measure: Acute Influence of Liver Function, Albumin, for Different Formulations of CBD.
timeFrame: Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days
measure: Acute Influence of Liver Function, Alkaline Phosphatase, With the Different Formulations of CBD.
timeFrame: Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days
measure: Acute Influence of Liver Function, Aspartate Aminotransferase, With the Different Formulations of CBD.
timeFrame: Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days
measure: Acute Influence of Liver Function, Total Bilirubin, With the Different Formulations of CBD.
timeFrame: Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days
measure: Acute Influence of Kidney Function, Blood Urea, With the Different Formulations of CBD.
timeFrame: Change from baseline at time 0, 60, 240 minutes for each formulation, visits separated by 14 days
measure: CBD on Postprandial Metabolism Via Indirect Calorimetry
timeFrame: Compare 2 randomized visits Including a test meal collected during 45 minutes of resting metabolic rate
Secondary outcomes:
Other outcomes:
Locations:
city: Fort Collins
country: United States
facility: Colorado State University, Dept. of Health and Exercise Science
state: Colorado
Study officials:
References:
citation: 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.