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The cause for this sort of disparity in products can be from a range of issues, including batch to batch variation, intentional improper labeling, degradation over time, poor extraction techniques, and lack of certification of the laboratories being used to measure cannabinoids. That said, in the veterinary literature, there has been some initial pilot pharmacokinetic, safety, and clinical trials that provide some insights for veterinarians regarding dosing regimens.<ref name="Łebkowska-WieruszewskaPharma19">{{cite journal |title=Pharmacokinetics of Bedrocan, a cannabis oil extract, in fasting and fed dogs: An explorative study |journal=Research in Veterinary Science |author=Łebkowska-Wieruszewska, B.; Stefanelli, F.; Chericoni, S. et al. |volume=123 |pages=26–8 |year=2019 |doi=10.1016/j.rvsc.2018.12.003 |pmid=30580232}}</ref><ref name="GamblePharma18">{{cite journal |title=Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs |journal=Frontiers in Veterinary Science |author=Gamble, L.-J.; Boesch, J.M.; Frye, C.W. et al. |volume=5 |at=165 |year=2018 |doi=10.3389/fvets.2018.00165 |pmid=30083539 |pmc=PMC6065210}}</ref><ref name="BartnerPharma18">{{cite journal |title=Pharmacokinetics of cannabidiol administered by 3 delivery methods at 2 different dosages to healthy dogs |journal=Canadian Journal of Veterinary Research |author=Bartner, L.R.; McGrath, S.; Rao, S. et al. |volume=82 |issue=3 |pages=178–83 |year=2018 |pmid=30026641 |pmc=PMC6038832}}</ref><ref name="McGrathRandom19">{{cite journal |title=Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy |journal=Journal of the American Veterinary Medical Association |author=McGrath, S.; Bartner, L.R.; Rao, S. et al. |volume=254 |issue=11 |pages=1301–8 |year=2019 |doi=10.2460/javma.254.11.1301 |pmid=31067185}}</ref><ref name="DeaboldSingle19">{{cite journal |title=Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats |journal=Animals |author=Deabold, K.A.; Schwark, W.S.; Wolf, L. et al. |volume=9 |issue=10 |at=832 |year=2019 |doi=10.3390/ani9100832 |pmid=31635105 |pmc=PMC6826847}}</ref>
The cause for this sort of disparity in products can be from a range of issues, including batch to batch variation, intentional improper labeling, degradation over time, poor extraction techniques, and lack of certification of the laboratories being used to measure cannabinoids. That said, in the veterinary literature, there has been some initial pilot pharmacokinetic, safety, and clinical trials that provide some insights for veterinarians regarding dosing regimens.<ref name="Łebkowska-WieruszewskaPharma19">{{cite journal |title=Pharmacokinetics of Bedrocan, a cannabis oil extract, in fasting and fed dogs: An explorative study |journal=Research in Veterinary Science |author=Łebkowska-Wieruszewska, B.; Stefanelli, F.; Chericoni, S. et al. |volume=123 |pages=26–8 |year=2019 |doi=10.1016/j.rvsc.2018.12.003 |pmid=30580232}}</ref><ref name="GamblePharma18">{{cite journal |title=Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs |journal=Frontiers in Veterinary Science |author=Gamble, L.-J.; Boesch, J.M.; Frye, C.W. et al. |volume=5 |at=165 |year=2018 |doi=10.3389/fvets.2018.00165 |pmid=30083539 |pmc=PMC6065210}}</ref><ref name="BartnerPharma18">{{cite journal |title=Pharmacokinetics of cannabidiol administered by 3 delivery methods at 2 different dosages to healthy dogs |journal=Canadian Journal of Veterinary Research |author=Bartner, L.R.; McGrath, S.; Rao, S. et al. |volume=82 |issue=3 |pages=178–83 |year=2018 |pmid=30026641 |pmc=PMC6038832}}</ref><ref name="McGrathRandom19">{{cite journal |title=Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy |journal=Journal of the American Veterinary Medical Association |author=McGrath, S.; Bartner, L.R.; Rao, S. et al. |volume=254 |issue=11 |pages=1301–8 |year=2019 |doi=10.2460/javma.254.11.1301 |pmid=31067185}}</ref><ref name="DeaboldSingle19">{{cite journal |title=Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats |journal=Animals |author=Deabold, K.A.; Schwark, W.S.; Wolf, L. et al. |volume=9 |issue=10 |at=832 |year=2019 |doi=10.3390/ani9100832 |pmid=31635105 |pmc=PMC6826847}}</ref>


The primary objective of this study were to provide information regarding the important plant constituents—including cannabinoids, terpenes, and [[heavy metals]] contamination ([[lead]], [[arsenic]], [[Mercury (element)|mercury]], and [[cadmium]])—in commercial products obtained through internet commerce, using [[liquid chromatography]] with [[Chromatography detector|diode array detection]] and [[mass spectroscopy]] (LC-DAD/MS), [[Headspace gas chromatography for dissolved gas measurement|headspace gas chromatography]] with flame ionization detection (HS-GC-FID), and [[inductively coupled plasma mass spectrometry]] (ICP-MS), respectively. The cannabinoids analyzed included CBD, THC, ∆8-THC, CBG, CBN, CBC, THCV, CBDV, and the derived acids CBDA, THCA, and CBGA. Major terpenes in the analysis included [[Myrcene|β-myrcene]], [[linalool]], [[limonene]], [[Caryophyllene|β-caryophyllene]], [[pinene]]s, and other lesser terpenes. Secondary objectives were to examine labels to determine if manufacturers complied with current FDA supplement guidelines, examine the relative consistency between analyzed concentrations versus labeled CBD or total cannabinoids, and examine the manufacturer’s ability to produce a certificate of analysis regarding cannabinoid analysis for the lot purchased.
The primary objective of this study were to provide information regarding the important plant constituents—including cannabinoids, terpenes, and [[heavy metals]] contamination ([[arsenic]], [[cadmium]], [[lead]] and [[Mercury (element)|mercury]])—in commercial products obtained through internet commerce, using liquid [[chromatography]] with [[Chromatography detector|diode array detection]] and [[mass spectrometry]] (LC-DAD/MS), [[Headspace gas chromatography for dissolved gas measurement|headspace gas chromatography]] with flame ionization detection (HS-GC-FID), and [[inductively coupled plasma mass spectrometry]] (ICP-MS), respectively. The cannabinoids analyzed included CBD, THC, ∆8-THC, CBG, CBN, CBC, THCV, CBDV, and the derived acids CBDA, THCA, and CBGA. Major terpenes in the analysis included [[Myrcene|β-myrcene]], [[linalool]], [[limonene]], [[Caryophyllene|β-caryophyllene]], [[pinene]]s, and other lesser terpenes. Secondary objectives were to examine labels to determine if manufacturers complied with current FDA supplement guidelines, examine the relative consistency between analyzed concentrations versus labeled CBD or total cannabinoids, and examine the manufacturer’s ability to produce a certificate of analysis regarding cannabinoid analysis for the lot purchased.


==Materials and methods==
==Materials and methods==
===Product selection and preparation===
Pet-specific products were obtained from an internet search, which included the Google search engine input of “hemp extract and dog” or “CBD product and dog.” The first 30 products out of 65 products specifically for dog use were identified and often came in multiple forms (dry capsule, oil tincture, soft chew, or powder). Products were not purchased if the advertisements were from hemp seed rather than whole plant extract. If multiple forms were identified, then an oil product was chosen for analysis. If an oil was not available, then a powdered capsule form was chosen, and if a chew was the only form available, then it was chosen for analysis. All products were paid for in U.S. dollars, and the retail price was recorded minus the shipping and handling costs.


After purchase all companies were contacted to provide a certificate of analysis (COA) related to the product purchased based on lot number. If an original third-party COA was not provided, then marketing material or label concentrations were used to assess against laboratory analysis by a certified third-party laboratory. After mixing well, three separate 2 mL or 2 g aliquots were prepared for analysis within a month of receipt (ensuring they were within the labeled expiratory date) and were then sent to an [[ISO/IEC 17025]]-certified laboratory (ProVerde, Milford, MA, USA) for analysis of products for common cannabinoids, including CBD, CBDA, CBDV, THC, THCA, ∆8-THC, exo-THC, THCV, CBC, CBG, CBGA, and CBN. Products were also tested for a range of common terpenes found in ''Cannabis'', including [[camphene]], β-pinene, [[3-Carene|3-carene]], [[Terpinene|α-terpinene]], α-pinene, [[ocimene]], limonene, [[P-Cymene|P-cymene]], [[eucalyptol]], γ-terpinene, terpinolene, linalool, β-myrcene, β-caryophyllene, [[humulene]], caryophyllene oxide, and [[Bisabolol|α-bisabolol]]. Lastly, one aliquot from each product was tested for four major heavy metals found in cannabis, including arsenic, cadmium, lead, and mercury.


==References==
==References==

Revision as of 19:16, 3 December 2020

Full article title Cannabinoid, terpene, and heavy metal analysis of 29 over-the-counter commercial veterinary hemp supplements
Journal Veterinary Medicine: Research and Reports
Author(s) Wakshlag, Joseph J.; Cital, Stephen; Eaton, Scott J.; Prussin, Reece; Hudalla, Christopher
Author affiliation(s) Cornell University College of Veterinary Medicine, ElleVet Sciences, ProVerde Laboratories
Primary contact Email: Dr dot joesh at gmail dot com
Year published 2020
Volume and issue 11
Page(s) 45–55
DOI 10.2147/VMRR.S248712
ISSN 2230-2034
Distribution license Creative Commons Attribution-NonCommercial 3.0 Unported
Website https://www.dovepress.com/cannabinoid-terpene-and-heavy-metal-analysis-of-29-over-the-counter-co
Download https://www.dovepress.com/getfile.php?fileID=57398 (PDF)
Emblem-important-yellow.svg This article should be considered a work in progress and incomplete. Consider this article incomplete until this notice is removed.

Abstract

Purpose: The use of veterinary low-tetrahydrocannabinol (THC) Cannabis sativa (i.e., hemp) products has increased in popularity for a variety of pet ailments. Low-THC Cannabis sativa is federally legal for sale and distribution in the United States, and the rise in internet commerce has provided access to interested consumers, with minimal quality control.

Materials and methods: We performed an internet word search of “hemp extract and dog” or “CBD product and dog” and analyzed 29 products that were using low-THC Cannabis sativa extracts in their production of supplements. All products were tested for major cannabinoids, including ∆9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and other minor cannabinoids, as well as their respective carboxylic acid derivatives tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), and cannabigerolic acid (CBGA) using an ISO/IEC 17025-certified laboratory. Products were also tested for major terpenes and heavy metals to understand constituents in the hemp plants being extracted and distributed.

Results: All products were below the federal limit of 0.3% THC, with variable amounts of CBD (0– 88 mg/mL or g). Only two products did not supply a CBD or total cannabinoid concentration on their packaging or website, while 22 of 29 had an associated certificate of analysis (COA) from a third-party laboratory. Ten of the 27 products were within 10% of the total cannabinoid concentrations of their label claim, with a median concentration of 93% of claims (0– 154%). Heavy metal contamination was found in four of 29 products, with lead being the most prevalent contaminant (three of 29).

Conclusion: The products analyzed had highly variable concentrations of CBD or total cannabinoids, with only 18 of 29 being appropriately labeled according to current Food and Drug Administration (FDA) non-medication, non-dietary supplement, or non-food guidelines. Owners and veterinarians wanting to utilize CBD-rich Cannabis sativa products should be aware of low-concentration products and should obtain a COA enabling them to fully discuss the implications of use and calculated dosing before administering to pets.

Keywords: cannabinoid, hemp, supplement, cannabidiol, pet, terpene, oral

Introduction

The recent federal legalization and deregulation of low-tetrahydrocannabinol (THC) Cannabis sativa, otherwise known as hemp, as a commercial crop in the United States has created a new supplement market for humans and pets alike that is largely unregulated.[1] The de-scheduling of low-THC Cannabis sativa-derived extracts forced any oversight of products containing hemp-derived cannabidiol (CBD), and other cannabinoids, to the Food and Drug Administration (FDA).[2] The lack of clear FDA regulations and inconsistent state regulations being implemented leaves many practitioners contemplating the legality of low-THC Cannabis sativa distribution in each state, even though federally legal. Some associations and organizations refer to the Dietary Supplement Health and Education Act of 1994 (DSHEA) for guidelines regarding marketing and labeling of Cannabis sativa-derived CBD products, when in fact the U.S. Congress clarified the intent of DSHEA as not relevant to animals.[3] Instead, this lack of oversight responsibility has left a legal gray zone where animal supplements are not illegal, but are self-regulated with enforcement discretion maintained by the FDA. The FDA currently only oversees three defined categories when it comes to animal products: medicines, medical devices, and food.

Currently, at the time of writing, compliant labeling and marketing of low-THC CBD products must not state or imply the prevention, mitigation, or curing of disease. This mandate mirrors all other human or animal supplements and nutraceuticals on the market today. Until the FDA resolves the issue regarding guidelines of “hemp” CBD products, many manufacturers will likely continue illegal and dishonest marketing and labeling, possibly weighing the earning potential against the unlikely event of FDA enforcement in a saturated market.

The use of CBD-rich extracts on pets is commonplace, as identified by Kogan et al. in a range of survey work, leaving veterinarians in a tenuous place as health professionals, particularly due to the paucity of clinical or safety studies. Client survey work suggests that CBD-rich Cannabis extracts are currently being used to treat a variety of disorders, including anxiety, cancer and cancer chemotherapy side effects, inflammatory bowel disease, osteoarthritis, and seizures.[4][5] CBD is the primary cannabinoid of interest due to the tremendous amount of pre-clinical and human clinical research suggesting it may have utility in a range of inflammatory and neurologic disease processes.[6][7][8][9][10] Other cannabinoids can also be found in many of these preparations, including ∆9-tetrahydrocannabinol (THC), ∆8-tetrahydrocannabinol (∆8-THC), cannabichromene (CBC), cannabinol (CBN), cannabigerol (CBG), cannabidivarin (CBDV), exo-THC, tetrahydrocannabivarin (THCV), and all their derived acids, such as tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA), and cannabigerolic acid (CBGA), as well as terpenes. Terpenes are a class of mono- and dicyclical volatile compounds that lead to the aroma of the extract and may also have modest medicinal properties, but they are typically found at lower concentrations than cannabinoids (less than 1% dry weight of plant material).[11]

Unfortunately, due to a lack of regulation, quality control is suspect in all human and animal supplements, Cannabis and non-Cannabis supplements alike. Two recent publications examining selected cannabinoid concentrations in human over-the-counter products showed a tremendous disparity between labeling claims and analysis of the products, with over 40% having less than the labeled amount and over 40% having more than the labeled amount.[12][13] The THC concentrations in a Canadian study were less than 0.01% for all products showing compliance with the Canadian standard for Cannabis-derived CBD products.[12] In a study examining 14 European products, all with THC concentrations being below the 0.2% allowable limit, CBD concentrations varied from the labeled amount of total cannabinoids or CBD concentrations.[14]

The cause for this sort of disparity in products can be from a range of issues, including batch to batch variation, intentional improper labeling, degradation over time, poor extraction techniques, and lack of certification of the laboratories being used to measure cannabinoids. That said, in the veterinary literature, there has been some initial pilot pharmacokinetic, safety, and clinical trials that provide some insights for veterinarians regarding dosing regimens.[15][16][17][18][19]

The primary objective of this study were to provide information regarding the important plant constituents—including cannabinoids, terpenes, and heavy metals contamination (arsenic, cadmium, lead and mercury)—in commercial products obtained through internet commerce, using liquid chromatography with diode array detection and mass spectrometry (LC-DAD/MS), headspace gas chromatography with flame ionization detection (HS-GC-FID), and inductively coupled plasma mass spectrometry (ICP-MS), respectively. The cannabinoids analyzed included CBD, THC, ∆8-THC, CBG, CBN, CBC, THCV, CBDV, and the derived acids CBDA, THCA, and CBGA. Major terpenes in the analysis included β-myrcene, linalool, limonene, β-caryophyllene, pinenes, and other lesser terpenes. Secondary objectives were to examine labels to determine if manufacturers complied with current FDA supplement guidelines, examine the relative consistency between analyzed concentrations versus labeled CBD or total cannabinoids, and examine the manufacturer’s ability to produce a certificate of analysis regarding cannabinoid analysis for the lot purchased.

Materials and methods

Product selection and preparation

Pet-specific products were obtained from an internet search, which included the Google search engine input of “hemp extract and dog” or “CBD product and dog.” The first 30 products out of 65 products specifically for dog use were identified and often came in multiple forms (dry capsule, oil tincture, soft chew, or powder). Products were not purchased if the advertisements were from hemp seed rather than whole plant extract. If multiple forms were identified, then an oil product was chosen for analysis. If an oil was not available, then a powdered capsule form was chosen, and if a chew was the only form available, then it was chosen for analysis. All products were paid for in U.S. dollars, and the retail price was recorded minus the shipping and handling costs.

After purchase all companies were contacted to provide a certificate of analysis (COA) related to the product purchased based on lot number. If an original third-party COA was not provided, then marketing material or label concentrations were used to assess against laboratory analysis by a certified third-party laboratory. After mixing well, three separate 2 mL or 2 g aliquots were prepared for analysis within a month of receipt (ensuring they were within the labeled expiratory date) and were then sent to an ISO/IEC 17025-certified laboratory (ProVerde, Milford, MA, USA) for analysis of products for common cannabinoids, including CBD, CBDA, CBDV, THC, THCA, ∆8-THC, exo-THC, THCV, CBC, CBG, CBGA, and CBN. Products were also tested for a range of common terpenes found in Cannabis, including camphene, β-pinene, 3-carene, α-terpinene, α-pinene, ocimene, limonene, P-cymene, eucalyptol, γ-terpinene, terpinolene, linalool, β-myrcene, β-caryophyllene, humulene, caryophyllene oxide, and α-bisabolol. Lastly, one aliquot from each product was tested for four major heavy metals found in cannabis, including arsenic, cadmium, lead, and mercury.

References

  1. ↑ "Public Law 115 - 334 - Agriculture Improvement Act of 2018". govinfo. United States Government Publishing Office. 20 December 2018. https://www.govinfo.gov/app/details/PLAW-115publ334. 
  2. ↑ Food and Drug Administration (2020). "FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)". Food and Drug Administration. https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd. Retrieved 27 March 2020. 
  3. ↑ "S.784 - Dietary Supplement Health and Education Act of 1994". Congress.gov. 25 October 1994. https://www.congress.gov/bill/103rd-congress/senate-bill/784. 
  4. ↑ Kogan, L.R.; Hellyer, P.W.; Robinson, N.G. (2016). "Consumers' Perceptions of Hemp Products for Animals" (PDF). Journal of the American Holistic Veterinary Medical Association 42 (Spring): 40–48. https://www.ahvma.org/wp-content/uploads/AHVMA-2016-V42-Hemp-Article.pdf. 
  5. ↑ Kogan, L.R.; Hellyer, P.W.; Silcox, S. et al. (2019). "Canadian dog owners' use and perceptions of cannabis products". Canadian Veterinary Journal 60 (7): 749–55. PMC PMC6563876. PMID 31281193. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC6563876. 
  6. ↑ Izzo, A.A.; Borrelli, F.; Capasso, R. et al. (2009). "Non-psychotropic plant cannabinoids: New therapeutic opportunities from an ancient herbs". Trends in Pharmacological Sciences 30 (10): 515–27. doi:10.1016/j.tips.2009.07.006. PMID 19729208. 
  7. ↑ White, C.M. (2019). "A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential". Journal of Clinical Pharmacology 59 (7): 923–34. doi:10.1002/jcph.1387. PMID 30730563. 
  8. ↑ Landa, L.; Sulcova, A.; Gbelec, P. (2016). "The use of cannabinoids in animals and therapeutic implications for veterinary medicine: A review". Veterinarni Medicina 61: 111–22. doi:10.17221/8762-VETMED. 
  9. ↑ Mastinu, A.; Ribaudo, G.; Ongaro, A. et al. (2020). "Critical Review on the Chemical Aspects of Cannabidiol (CBD) and Harmonization of Computational Bioactivity Data". Current Medicinal Chemistry. doi:10.2174/0929867327666200210144847. PMID 32039672. 
  10. ↑ Premoli, M.; Aria, F.; Bonini, S.A. et al. (2019). "Cannabidiol: Recent advances and new insights for neuropsychiatric disorders treatment". Life Sciences 224: 120–7. doi:10.1016/j.lfs.2019.03.053. PMID 30910646. 
  11. ↑ Pavlovic, R.; Nenna, G.; Calvi, L. et al. (2018). "Quality Traits of "Cannabidiol Oils": Cannabinoids Content, Terpene Fingerprint and Oxidation Stability of European Commercially Available Preparations". Molecules 23 (5): 1230. doi:10.3390/molecules23051230. PMC PMC6100014. PMID 29783790. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC6100014. 
  12. ↑ 12.0 12.1 Meng, Q.; Buchanan, B.; Zuccolo, J. et al. (2018). "A reliable and validated LC-MS/MS method for the simultaneous quantification of 4 cannabinoids in 40 consumer products". PLoS One 13 (5): e0196396. doi:10.1371/journal.pone.0196396. PMC PMC5931681. PMID 29718956. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC5931681. 
  13. ↑ Bonn-Miller, M.O.; Liflin, M.J.E.; Thomas, B.F. et al. (2017). "Labeling Accuracy of Cannabidiol Extracts Sold Online". JAMA 318 (17): 1708–9. doi:10.1001/jama.2017.11909. PMC PMC5818782. PMID 29114823. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC5818782. 
  14. ↑ Hazekamp, A. (2018). "The Trouble with CBD Oil". Medical Cannabis and Cannabinoids 1: 65–72. doi:10.1159/000489287. 
  15. ↑ Łebkowska-Wieruszewska, B.; Stefanelli, F.; Chericoni, S. et al. (2019). "Pharmacokinetics of Bedrocan, a cannabis oil extract, in fasting and fed dogs: An explorative study". Research in Veterinary Science 123: 26–8. doi:10.1016/j.rvsc.2018.12.003. PMID 30580232. 
  16. ↑ Gamble, L.-J.; Boesch, J.M.; Frye, C.W. et al. (2018). "Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs". Frontiers in Veterinary Science 5: 165. doi:10.3389/fvets.2018.00165. PMC PMC6065210. PMID 30083539. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC6065210. 
  17. ↑ Bartner, L.R.; McGrath, S.; Rao, S. et al. (2018). "Pharmacokinetics of cannabidiol administered by 3 delivery methods at 2 different dosages to healthy dogs". Canadian Journal of Veterinary Research 82 (3): 178–83. PMC PMC6038832. PMID 30026641. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC6038832. 
  18. ↑ McGrath, S.; Bartner, L.R.; Rao, S. et al. (2019). "Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy". Journal of the American Veterinary Medical Association 254 (11): 1301–8. doi:10.2460/javma.254.11.1301. PMID 31067185. 
  19. ↑ Deabold, K.A.; Schwark, W.S.; Wolf, L. et al. (2019). "Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats". Animals 9 (10): 832. doi:10.3390/ani9100832. PMC PMC6826847. PMID 31635105. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=PMC6826847. 

Notes

This presentation is faithful to the original, with only a few minor changes to presentation. Some grammar and punctuation was cleaned up to improve readability. In some cases important information was missing from the references, and that information was added.

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