Interaction Between Cannabidiol, Meal Ingestion, and Liver Function
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Pharmacokinetic Time to Maximum Concentration- (Tmax) for Different Formulations of CBD
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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
- •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.
研究组 & 干预措施
Two Visits Including A Test Meal
Separated by a minimum of 4 days.
干预措施: Cannabidiol (CBD) powder formulation (Dietary Supplement)
Two Visits Including A Test Meal
Separated by a minimum of 4 days.
干预措施: CBD matching Placebo (Dietary Supplement)
Five Visits Not Involving A Test Meal
Separated by a minimum of 14 days.
干预措施: Cannabidiol (CBD) powder formulation (Dietary Supplement)
Five Visits Not Involving A Test Meal
Separated by a minimum of 14 days.
干预措施: Cannabidiol (CBD) Oil based tincture formulation (Dietary Supplement)
Five Visits Not Involving A Test Meal
Separated by a minimum of 14 days.
干预措施: Cannabidiol (CBD) Gum Arabic, maltodextrin base formulation (Dietary Supplement)
Five Visits Not Involving A Test Meal
Separated by a minimum of 14 days.
干预措施: Cannabidiol (CBD) Gum Arabic, sorbitol base formulation (Dietary Supplement)
Five Visits Not Involving A Test Meal
Separated by a minimum of 14 days.
干预措施: Cannabidiol (CBD) Isolate in water formulation (Dietary Supplement)
结局指标
主要结局
Pharmacokinetic Time to Maximum Concentration- (Tmax) for Different Formulations of CBD
时间窗: 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.
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).
Pharmacokinetic Maximum Concentration-(Cmax) for Different Formulations of CBD
时间窗: 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).
Pharmacokinetic Area Under the Curve Representing Total Cannabidiol Exposure Between 0 and 4 h (AUC 0-4) for Different Formulations of CBD
时间窗: 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 (min x ng/mL).
Pharmacokinetic Area Under the Curve an Estimate of Total Exposure to CBD Over Time (AUC 0-inf) for Different Formulations of CBD
时间窗: 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 (mins x ng/mL).
Pharmacokinetic Amount of Time it Takes to Decrease the Circulating Concentration to Half of Its Initial Value (t1/2) for Different Formulations of CBD
时间窗: 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 (mins).
Pharmacokinetic Rate at Which CBD is Absorbed Into the Body (Ka) for Different Formulations of CBD
时间窗: 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).
Pharmacokinetic Rate at Which CBD is Removed From the Body (Ke) for Different Formulations of CBD
时间窗: 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).
CBD Pharmacokinetic Volume of Distribution- (Vd) for Different Formulations of CBD
时间窗: 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).
Pharmacokinetic Parameter Tmax of a Formulation 725 After a Standardized Meal
时间窗: 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 (mins).
Pharmacokinetic Parameter Cmax of a Formulation 725 After a Standardized Meal
时间窗: 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.
At the 2 randomized visits Including a Test Meal, determine if a high-fat meal impacts maximal concentration of circulating CBD Cmax (ng/L).
Pharmacokinetic Parameter AUC 0-4 of Formulation 725 After a Standardized Meal
时间窗: 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 (min x ng/mL).
Pharmacokinetic Parameter AUC 0-inf of Formulation 725 After a Standardized Meal
时间窗: 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.
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).
Pharmacokinetic Parameter t1/2 of Formulation 725 After a Standardized Meal
时间窗: 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).
Pharmacokinetic Parameter Ka of Formulation 725 After a Standardized Meal
时间窗: 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).
Pharmacokinetic Parameter Ke of Formulation 725 After a Standardized Meal
时间窗: 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).
Pharmacokinetic Parameter Vd of Formulation 725 After a Standardized Meal
时间窗: 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).
Ingested CBD on Postprandial Metabolism Via Indirect Calorimetry
时间窗: Randomized visit Including a test meal collected during 235 minutes of TEF
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.
Ingested CBD on Postprandial Metabolism Via Measurements of Glucose
时间窗: Compare 2 randomized visits Including a test meal collected at baseline,10,20,30,45,60,90,120,150,180,210, and 240 minutes.
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.
Ingested CBD on Postprandial Metabolism Via Measurements of Insulin
时间窗: Compare 2 randomized visits Including a test meal collected at baseline,10,20,30,45,60,90,120,150,180,210, and 240 minutes.
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.
Ingested CBD on Postprandial Metabolism Via Measurements of Triglycerides
时间窗: Compare 2 randomized visits Including a test meal collected at baseline,10,20,30,45,60,90,120,150,180,210, and 240 minutes.
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.
Acute Influence of Liver Function, Alanine Aminotransferase (ALT), With the Different Formulations of CBD.
时间窗: Change from baseline at time 0, 60, 240 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).
Acute Influence of Liver Function, Albumin, for Different Formulations of CBD.
时间窗: Change from baseline at time 0, 60, 240 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.
Acute Influence of Liver Function, Alkaline Phosphatase, With the Different Formulations of CBD.
时间窗: Change from baseline at time 0, 60, 240 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.
Acute Influence of Liver Function, Aspartate Aminotransferase, With the Different Formulations of CBD.
时间窗: Change from baseline at time 0, 60, 240 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.
Acute Influence of Liver Function, Total Bilirubin, With the Different Formulations of CBD.
时间窗: Change from baseline at time 0, 60, 240 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.
Acute Influence of Kidney Function, Blood Urea, With the Different Formulations of CBD.
时间窗: Change from baseline at time 0, 60, 240 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.
CBD on Postprandial Metabolism Via Indirect Calorimetry
时间窗: Compare 2 randomized visits Including a test meal collected during 45 minutes of resting metabolic rate
At the 2 randomized visits including a Resting Metabolic Rate prior to and after ingestion of a single dose of Formulation 725 or placebo.
次要结局
未报告次要终点
研究者
Christopher Bell
Associate Professor
Colorado State University