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Randomized Controlled Trial
. 2022 May 21;14(10):2152.
doi: 10.3390/nu14102152.

Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function

Kieran Shay Struebin Abbotts  1 , Taylor Russell Ewell  1 , Hannah Michelle Butterklee  1 , Matthew Charles Bomar  1 , Natalie Akagi  2 , Gregory P Dooley  2 , Christopher Bell  1
Affiliations
Randomized Controlled Trial

Cannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function

Kieran Shay Struebin Abbotts et al. Nutrients. .

Abstract

Cannabidiol (CBD) is widely available and marketed as having therapeutic properties. Over-the-counter CBD is unregulated, many of the therapeutic claims lack scientific support, and controversy exists as to the safety of CBD-liver interaction. The study aims were to compare the pharmacokinetics of commercial CBD and CBD metabolites following the ingestion of five different CBD formulations, determine the influence of CBD on food induced thermogenesis, determine the influence of food on CBD pharmacokinetics, and determine the influence of CBD on markers of liver function. Fourteen males (body mass index ≥ 25 kg/m2) were studied in a placebo-controlled, randomized, crossover design. On five occasions, different CBD formulations were ingested (one per visit). On two additional occasions, CBD or placebo was ingested following a meal. CBD servings were standardized to 30 mg. Considerable pharmacokinetic variability existed between formulations; this pharmacokinetic variability transferred to several of the metabolites. CBD did not influence food induced thermogenesis but did favorably modify early insulin and triglyceride responses. Food appreciably altered the pharmacokinetics of CBD. Finally, CBD did not evoke physiologically relevant changes in markers of liver function. Collectively, these data suggest that consumers should be aware of the appreciable pharmacokinetic differences between commercial CBD formulations, CBD is unlikely to influence the caloric cost of eating but may prove to be of some benefit to initial metabolic responses, consuming CBD with food alters the dynamics of CBD metabolism and increases systemic availability, and low-dose CBD probably does not represent a risk to normal liver function.

Keywords: cannabinoid; cannabis; energy expenditure; insulin; metabolism; pharmacodynamics; thermogenesis; triglyceride.

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Conflict of interest statement

The authors declare no conflict of interest. The funder, Caliper Foods, had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Consolidated Standards of Reporting Trials (CONSORT) flow diagram. Abbreviation: BMI body mass index.
Figure 2
Figure 2
Circulating cannabidiol (CBD) concentration following ingestion of each of the CBD formulations. LOQ: Limit of Quantitation. Data: Mean and standard error.
Figure 3
Figure 3
Circulating 6-OH-CBD concentration following ingestion of each of the cannabidiol formulations. Each CBD serving was standardized to 30 mg. LOQ: Limit of Quantitation. Data are mean and standard error.
Figure 4
Figure 4
Circulating 7-OH-CBD concentration following ingestion of each of the cannabidiol formulations. Each CBD serving was standardized to 30 mg. LOQ: Limit of Quantitation. Data are mean and standard error.
Figure 5
Figure 5
Circulating CBD-COOH concentration following ingestion of each of the cannabidiol formulations. Each CBD serving was standardized to 30 mg. LOQ: Limit of Quantitation. Data are mean and standard error.
Figure 6
Figure 6
Energy expenditure prior to and following consumption of a mixed macronutrient meal and placebo or 30 mg of cannabidiol (CBD). Food ingestion increased energy expenditure (main effect of time; p < 0.001); CBD did not alter the response (placebo vs. CBD × time interaction; p = 0.32). Data are mean and standard error.
Figure 7
Figure 7
Respiratory exchange ratio prior to and following consumption of a mixed macronutrient meal and placebo or 30 mg of cannabidiol (CBD). Respiratory exchange ratio was increased after food (main effect of time: p < 0.001); CBD did not alter this response (placebo vs. CBD × time interaction; p = 0.13). Data are mean and standard error.
Figure 8
Figure 8
Circulating glucose concentration prior to and following consumption of a mixed macronutrient meal and placebo or 30 mg of cannabidiol (CBD). CBD did not influence the glucose response to food (placebo vs. CBD × time interaction; p = 0.31). Data are mean and standard error.
Figure 9
Figure 9
Circulating insulin concentration prior to and following consumption of a mixed macronutrient meal and placebo or 30 mg of cannabidiol (CBD). CBD evoked lower insulin concentrations at minutes 10 and 20 (placebo vs. CBD × time interaction; p = 0.013 indicated as *). Data are mean and standard error.
Figure 10
Figure 10
Circulating triglyceride concentration prior to and following consumption of a mixed macronutrient meal and placebo or 30 mg of cannabidiol (CBD). CBD evoked lower triglyceride concentrations at minute 30 (placebo vs. CBD × time interaction; p = 0.010 indicated as *). Data are mean and standard error.
Figure 11
Figure 11
Circulating cannabidiol (CBD) concentration following ingestion of 30 mg of CBD with or without immediate prior ingestion of a mixed macronutrient meal. Abbreviation: LOQ Limit of Quantitation. Data are mean and standard error.
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