Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs
IntroductionVeterinary hemp products containing cannabidiol (CBD) and negligible psychoactive (THC) have increased popularity since hemp (with <0.3% THC) was removed from schedule 1 substances under the Controlled Substances Act in 2018. This was accompanied by increased CBD research, mostly...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Veterinary Science |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2023.1279926/full |
| _version_ | 1797262523551973376 |
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| author | Isabella Corsato Alvarenga Daniel Gustafson Krista Banks Kim Wilson Stephanie McGrath |
| author_facet | Isabella Corsato Alvarenga Daniel Gustafson Krista Banks Kim Wilson Stephanie McGrath |
| author_sort | Isabella Corsato Alvarenga |
| collection | DOAJ |
| description | IntroductionVeterinary hemp products containing cannabidiol (CBD) and negligible psychoactive (THC) have increased popularity since hemp (with <0.3% THC) was removed from schedule 1 substances under the Controlled Substances Act in 2018. This was accompanied by increased CBD research, mostly on the short-term safety and efficacy for inflammatory and neurological conditions. It is imperative to understand how CBD is metabolized or accumulated in the body long-term, thus the goal of the present work was to determine monthly plasma CBD concentrations, as well as changes in pharmacokinetic (PK) parameters in chronically dosed dogs.MethodsThe study was a masked, placebo-controlled, randomized design. Six adult beagles were assigned to placebo, 5 and 10 mg/kg/day CBD treatment groups. Dogs received oral oil treatment once daily for 36 weeks. Blood was collected once every 4 weeks pre- and postprandially for CBD plasma determination (at 0 and 2 h). Pharmacokinetics were conducted at 0, 18 and 36 weeks. Pharmacokinetics and monthly CBD plasma data of dogs who received CBD were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05.ResultsAverage plasma CBD at 5 and 10 mg/kg were 97.3 ng/mL and 236.8 ng/mL pre-prandial, 341 ng/mL and 1,068 ng/mL postprandial, respectively. PK parameters suggested CBD accumulation over time, with significant increases in Cmax and AUC at both the 18 and 36-week timepoints. Cmax and AUC were dose proportional. Half-life demonstrated large inter-individual variations and increased (p < 0.05) at weeks 18 and 36 compared to baseline. Volume of distribution was not affected by time or treatment, while MRT increased, and clearance decreased over time (p < 0.05).Conclusions and clinical importanceChronic administration of CBD to healthy adult dogs led to a dose-proportional accumulation in the body for 36 weeks, which was confirmed by an increased half-life, total exposure, mean residence time and plasma peak. Our data also suggests that CBD plasma levels may have less daily variation if administered twice daily. |
| first_indexed | 2024-04-24T23:58:28Z |
| format | Article |
| id | doaj.art-8d15f98ffb5742029dc32b087c2477fe |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-04-24T23:58:28Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-8d15f98ffb5742029dc32b087c2477fe2024-03-14T10:51:14ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692023-09-011010.3389/fvets.2023.12799261279926Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogsIsabella Corsato Alvarenga0Daniel Gustafson1Krista Banks2Kim Wilson3Stephanie McGrath4Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesHill’s Pet Nutrition, Topeka, KS, United StatesDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United StatesIntroductionVeterinary hemp products containing cannabidiol (CBD) and negligible psychoactive (THC) have increased popularity since hemp (with <0.3% THC) was removed from schedule 1 substances under the Controlled Substances Act in 2018. This was accompanied by increased CBD research, mostly on the short-term safety and efficacy for inflammatory and neurological conditions. It is imperative to understand how CBD is metabolized or accumulated in the body long-term, thus the goal of the present work was to determine monthly plasma CBD concentrations, as well as changes in pharmacokinetic (PK) parameters in chronically dosed dogs.MethodsThe study was a masked, placebo-controlled, randomized design. Six adult beagles were assigned to placebo, 5 and 10 mg/kg/day CBD treatment groups. Dogs received oral oil treatment once daily for 36 weeks. Blood was collected once every 4 weeks pre- and postprandially for CBD plasma determination (at 0 and 2 h). Pharmacokinetics were conducted at 0, 18 and 36 weeks. Pharmacokinetics and monthly CBD plasma data of dogs who received CBD were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05.ResultsAverage plasma CBD at 5 and 10 mg/kg were 97.3 ng/mL and 236.8 ng/mL pre-prandial, 341 ng/mL and 1,068 ng/mL postprandial, respectively. PK parameters suggested CBD accumulation over time, with significant increases in Cmax and AUC at both the 18 and 36-week timepoints. Cmax and AUC were dose proportional. Half-life demonstrated large inter-individual variations and increased (p < 0.05) at weeks 18 and 36 compared to baseline. Volume of distribution was not affected by time or treatment, while MRT increased, and clearance decreased over time (p < 0.05).Conclusions and clinical importanceChronic administration of CBD to healthy adult dogs led to a dose-proportional accumulation in the body for 36 weeks, which was confirmed by an increased half-life, total exposure, mean residence time and plasma peak. Our data also suggests that CBD plasma levels may have less daily variation if administered twice daily.https://www.frontiersin.org/articles/10.3389/fvets.2023.1279926/fullCBDhempPKcaninelong-termhealth |
| spellingShingle | Isabella Corsato Alvarenga Daniel Gustafson Krista Banks Kim Wilson Stephanie McGrath Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs Frontiers in Veterinary Science CBD hemp PK canine long-term health |
| title | Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs |
| title_full | Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs |
| title_fullStr | Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs |
| title_full_unstemmed | Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs |
| title_short | Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs |
| title_sort | cannabidiol plasma determination and pharmacokinetics conducted at beginning middle and end of long term supplementation of a broad spectrum hemp oil to healthy adult dogs |
| topic | CBD hemp PK canine long-term health |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2023.1279926/full |
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