Despite the increased interest and widespread use of cannabidiol (CBD) in humans and companion animals, much remains to be learned about its effects on health and physiology. Metabolomics is a useful tool to evaluate changes in the health status of animals and to analyze metabolic alterations caused by diet, disease, or other factors. Thus, the purpose of this investigation was to evaluate the impact of CBD supplementation on the canine plasma metabolome. Sixteen dogs (18.2 ± 3.4 kg BW) were utilized in a completely randomized design with treatments consisting of control and 4.5 mg CBD/kg BW/d. After 21 d of treatment, blood was collected ~2 h after treat consumption. Plasma collected from samples was analyzed using CIL/LC-MS-based untargeted metabolomics to analyze amine/phenol- and carbonyl-containing metabolites. Metabolites that differed — fold change (FC) ≥ 1.2 or ≤ 0.83 and false discovery ratio (FDR) ≤ 0.05 — between the two treatments were identified using a volcano plot. Biomarker analysis based on receiver operating characteristic (ROC) curves was performed to identify biomarker candidates (area under ROC ≥ 0.90) of the effects of CBD supplementation. Volcano plot analysis revealed that 32 amine/phenol-containing metabolites and five carbonyl-containing metabolites were differentially altered (FC ≥ 1.2 or ≤ 0.83, FDR ≤ 0.05) by CBD; these metabolites are involved in the metabolism of amino acids, glucose, vitamins, nucleotides, and hydroxycinnamic acid derivatives. Biomarker analysis identified 24 amine/phenol-containing metabolites and 1 carbonyl-containing metabolite as candidate biomarkers of the effects of CBD (area under ROC ≥ 0.90; P < 0.01). Results of this study indicate that 3 weeks of 4.5 mg CBD/kg BW/d supplementation altered the canine metabolome. Additional work is warranted to investigate the physiological relevance of these changes.
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The authors declare that this study received funding from AgTech Scientific, Paris, KY.
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.
Morris, Elizabeth M.; Kitts-Morgan, Susanna E.; Spangler, Dawn M.; Ogunade, Ibukun M.; McLeod, Kyle R.; and Harmon, David L., "Alteration of the Canine Metabolome After a 3-Week Supplementation of Cannabidiol (CBD) Containing Treats: An Exploratory Study of Healthy Animals" (2021). Animal and Food Sciences Faculty Publications. 46.
Supplementary Table 1. Amine/phenol- and carbonyl-containing metabolites identified in the tier 1 chemical isotope labeling (CIL) library.
Image_2_Alteration of the Canine Metabolome After a 3-Week Supplementation of Cannabidiol (CBD) Containing Treats An Exploratory Study of Healthy Ani.TIFF (188 kB)
Supplementary Table 2. Amine/phenol- and carbonyl-containing metabolites identified in the tier 2 linked identity (LI) library.
Table_1_Alteration of the Canine Metabolome After a 3-Week Supplementation of Cannabidiol (CBD) Containing Treats An Exploratory Study of Healthy Ani.XLSX (12 kB)
Supplementary Figure 1. Partial least squares discriminant analysis (PLS-DA) model permutation for amine/phenol-containing metabolites.
Table_2_Alteration of the Canine Metabolome After a 3-Week Supplementation of Cannabidiol (CBD) Containing Treats An Exploratory Study of Healthy Ani.XLSX (12 kB)
Supplementary Figure 2. Partial least squares discriminant analysis (PLS-DA) model permutation for carbonyl-containing metabolites.