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Article ; Online: Nutrition and Theriogenology: A Glimpse Into Nutrition and Nutritional Supplementation During Gestation, Lactation, Weaning and Breeding Dogs and Cats.

Kim, Hyun-Tae / Wakshlag, Joseph J

The Veterinary clinics of North America. Small animal practice

2023 Volume 53, Issue 5, Page(s) 1083–1098

Abstract: Feeding during normal reproduction is often not thought of until there is a problem with conception or gestational losses. Energy demands of lactation and early puppy/kitten are of concern, particularly in large and giant breed dogs where mineral balance ...

Abstract	Feeding during normal reproduction is often not thought of until there is a problem with conception or gestational losses. Energy demands of lactation and early puppy/kitten are of concern, particularly in large and giant breed dogs where mineral balance is crucial to normal development. There is a paucity of information around optimizing feeding during conception and gestation with many myths around ingredients which will be explored in this article along with supplements that may be able to support spermatogenesis and conception which primarily comes from the human literature and may have validity in times of difficult conception.
MeSH term(s)	Male ; Cats ; Pregnancy ; Dogs ; Animals ; Female ; Humans ; Weaning ; Cat Diseases ; Diet/veterinary ; Dog Diseases ; Lactation ; Dietary Supplements ; Breeding ; Animal Feed/analysis
Language	English
Publishing date	2023-06-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	757662-6
ISSN	1878-1306 ; 0195-5616
ISSN (online)	1878-1306
ISSN	0195-5616
DOI	10.1016/j.cvsm.2023.05.003
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Article ; Online: A One Health perspective on comparative cannabidiol and cannabidiolic acid pharmacokinetics and biotransformation in humans and domestic animals.

Schwark, Wayne S / Wakshlag, Joseph J

American journal of veterinary research

2023 Volume 84, Issue 5

Abstract: The goal of pharmacokinetic (PK) studies is to provide a basis for appropriate dosing regimens with novel therapeutic agents. With a knowledge of the desired serum concentration for optimum pharmacological effect, the amount and rate of drug ... ...

Abstract	The goal of pharmacokinetic (PK) studies is to provide a basis for appropriate dosing regimens with novel therapeutic agents. With a knowledge of the desired serum concentration for optimum pharmacological effect, the amount and rate of drug administration can be tailored to maintain that concentration based on the 24-hour PK modeling (eg, every 24 hours, every 12 hours) to achieve therapeutic ranges. This dosing and PK information are tailored to maintain that concentration. Typically, these optimum serum concentrations pertain across species. Single-dose PK modeling provides fundamental parameters to suggest dosing regimes. Multiple-dose PK studies provide information on steady-state serum levels to assure that desired therapeutic levels are maintained during chronic administration. Clinical trials using dosing suggested by these PK determinations provide proof that the compound is producing the desired therapeutic effect. A number of PK studies with cannabinoids in humans and domestic animals have been conducted with the goal of determining appropriate clinical use with these plant-derived products. The following review will focus on the PK of cannabidiol (CBD) and the lesser-known precursor of CBD, cannabidiolic acid (CBDA). Although Δ9-tetrahydrocannabinol (THC) has profound pharmacological effects and may be present at variable and potentially violative concentrations in hemp products, PK studies with THC will not be a major consideration. Because, in domestic animals, hemp-CBD products are usually administered orally, that route will be a focus. When available, PK results with CBD administered by other routes will be summarized. In addition, the metabolism of CBD across species appears to be different in carnivorous species compared with omnivorous/herbivorous species (including humans) based on current information, and the preliminary information related to this will be explained with the therapeutic implication being addressed in Currents in One Health by Ukai et al, JAVMA, May 2023.
MeSH term(s)	Humans ; Animals ; Cannabidiol/pharmacokinetics ; Dronabinol/pharmacokinetics ; Animals, Domestic ; One Health ; Cannabinoids/pharmacokinetics ; Biotransformation
Chemical Substances	cannabidiolic acid (FJX8O3OJCD) ; Cannabidiol (19GBJ60SN5) ; Dronabinol (7J8897W37S) ; Cannabinoids
Language	English
Publishing date	2023-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	390796-x
ISSN	1943-5681 ; 0002-9645
ISSN (online)	1943-5681
ISSN	0002-9645
DOI	10.2460/ajvr.23.02.0031
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Article ; Online: Key quality control aspects about cannabinoid-rich hemp products that a veterinarian needs to know: a practitioner's guide.

Henion, Jack / Evans, Stacey / Wakshlag, Joseph J

Journal of the American Veterinary Medical Association

2023 Volume 261, Issue 7, Page(s) 1054–1060

Abstract: There is considerable confusion in the veterinary profession surrounding the rise in hemp cannabidiol-based animal products and what veterinarians should know before discussing these products with clients. There is emerging evidence for the potential use ...

Abstract	There is considerable confusion in the veterinary profession surrounding the rise in hemp cannabidiol-based animal products and what veterinarians should know before discussing these products with clients. There is emerging evidence for the potential use in case management across many veterinary indications; however, the cannabinoid concentrations and whether these are isolated cannabinoids or whole hemp extracts is difficult to elucidate, even from the published papers. Much like any extract from a plant, there are multiple considerations including quality control, pharmacokinetics in the intended species, microbiological and chemical contamination, and product consistency-all aspects that should be considered before a conversation can begin with a client. The aim of this review is to help practitioners make informed decisions and better facilitate discussions with clients for companion animals kept as pets. This review will not address food animal issues, as established withholding times have yet to be fully researched.
MeSH term(s)	Animals ; Humans ; Cannabis ; Cannabinoids ; Veterinarians ; Pets ; Quality Control
Chemical Substances	Cannabinoids
Language	English
Publishing date	2023-04-18
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	390811-2
ISSN	1943-569X ; 0003-1488
ISSN (online)	1943-569X
ISSN	0003-1488
DOI	10.2460/javma.22.10.0470
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Article ; Online: Cannabidiol and cannabidiolic acid: Preliminary in vitro evaluation of metabolism and drug–drug interactions involving canine cytochrome P‐450, UDP‐glucuronosyltransferase, and P‐glycoprotein

Court, Michael H. / Mealey, Katrina L. / Burke, Neal S. / Jimenez, Tania Perez / Zhu, Zhaohui / Wakshlag, Joseph J.

Journal of Veterinary Pharmacology and Therapeutics. 2024 Jan., v. 47, no. 1 p.1-13

2024

Abstract: Phytocannabinoid‐rich hemp extracts containing cannabidiol (CBD) and cannabidiolic acid (CBDA) are increasingly being used to treat various disorders in dogs. The objectives of this study were to obtain preliminary information regarding the in vitro ... ...

Abstract	Phytocannabinoid‐rich hemp extracts containing cannabidiol (CBD) and cannabidiolic acid (CBDA) are increasingly being used to treat various disorders in dogs. The objectives of this study were to obtain preliminary information regarding the in vitro metabolism of these compounds and their capacity to inhibit canine cytochrome P450 (CYP)‐mediated drug metabolism and canine P‐glycoprotein‐mediated transport. Pure CBD and CBDA, and hemp extracts enriched for CBD and for CBDA were evaluated. Substrate depletion assays using pooled dog liver microsomes showed CYP cofactor‐dependent depletion of CBD (but not CBDA) and UDP‐glucuronosytransferase cofactor‐dependent depletion of CBDA (but not CBD) indicating major roles for CYP and UDP‐glucuronosytransferase in the metabolism of these phytocannabinoids, respectively. Further studies using recombinant canine CYPs demonstrated substantial CBD depletion by the major hepatic P450 enzymes CYP1A2 and CYP2C21. These results were confirmed by showing increased CBD depletion by liver microsomes from dogs treated with a known CYP1A2 inducer (β‐naphthoflavone) and with a known CYP2C21 inducer (phenobarbital). Cannabinoid‐drug inhibition experiments showed inhibition (IC₅₀ = 4.6–8.1 μM) of tramadol metabolism via CYP2B11‐mediated N‐demethylation (CBD and CBDA) and CYP2D15‐mediated O‐demethylation (CBDA only) by dog liver microsomes. CBD and CBDA did not inhibit CYP3A12‐mediated midazolam 1′‐hydroxylation (IC₅₀ > 10 μM). CBD and CBDA were not substrates or competitive inhibitors of canine P‐glycoprotein. Results for cannabinoid‐enriched hemp extracts were identical to those for pure cannabinoids. These in vitro studies indicate the potential for cannabinoid–drug interactions involving certain CYPs (but not P‐glycoprotein). Confirmatory in vivo studies are warranted.
Keywords	P-glycoproteins ; cannabidiol ; cytochrome P-450 ; dogs ; glucuronosyltransferases ; hemp ; liver microsomes ; pharmacokinetics ; phenobarbital ; therapeutics
Language	English
Dates of publication	2024-01
Size	p. 1-13.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	435216-6
ISSN	1365-2885 ; 0140-7783
ISSN (online)	1365-2885
ISSN	0140-7783
DOI	10.1111/jvp.13403
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Clinical Guide to Obesity and Nonherbal Nutraceuticals in Canine Orthopedic Conditions.

Ratsch, Barbara Esteve / Levine, David / Wakshlag, Joseph J

The Veterinary clinics of North America. Small animal practice

2022 Volume 52, Issue 4, Page(s) 939–958

Abstract: The typical canine rehabilitation patient with orthopedic disease may differ in its nutritional needs, with the assumption that most patients will be on a complete and balanced commercial dog food that is not enriched with agents for ameliorating their ... ...

Abstract	The typical canine rehabilitation patient with orthopedic disease may differ in its nutritional needs, with the assumption that most patients will be on a complete and balanced commercial dog food that is not enriched with agents for ameliorating their condition. For a significant number of rehabilitation patients, obesity is a major issue where hypocaloric diet plans are often implemented and are covered extensively elsewhere (VCNA Small Animal Practice May 2021). The focus of this article will be implementation of physical activity or structured physical exercise protocols and how they might be used in combination with a typical hypocaloric diet plan, a diet low in calories. Considering the limited information regarding physical activity or structured exercise programs in dogs, a human comparative assessment of efficacy is fundamental as a baseline of information regarding typical interventions. In addition, many of these long-term rehabilitation cases typically exhibit osteoarthritis (OA) and as part of case management, there is a need to implement nutrient or nutraceutical intervention to either diminish the progression of OA or help with pain control measures, particularly for the nonsteroidal anti-inflammatory intolerant patient. Nutraceutical intervention comes in many forms from botanicals to nutritional enhancement; botanicals will be covered elsewhere in this issue. This overview of nutraceuticals will cover nonbotanical interventions including fish oil, glucosamine/chondroitin, avocado/soybean unsaponifiables, undenatured collagen, green lipped mussel, and egg shell membrane supplementation.
MeSH term(s)	Animals ; Diet, Reducing/veterinary ; Dietary Supplements/classification ; Dog Diseases/drug therapy ; Dog Diseases/therapy ; Dogs ; Humans ; Obesity/drug therapy ; Obesity/therapy ; Obesity/veterinary ; Osteoarthritis/drug therapy ; Osteoarthritis/therapy ; Osteoarthritis/veterinary
Language	English
Publishing date	2022-05-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	757662-6
ISSN	1878-1306 ; 0195-5616
ISSN (online)	1878-1306
ISSN	0195-5616
DOI	10.1016/j.cvsm.2022.03.002
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Article: EXPERIMENTAL CHOLECALCIFEROL SUPPLEMENTATION IN A HERD OF MANAGED ASIAN ELEPHANTS (

Childs-Sanford, Sara E / Makowski, Andrew J / Hilliard, Rachel L / Wakshlag, Joseph J

Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians

2023 Volume 54, Issue 2, Page(s) 219–230

Abstract: Vitamin D supplementation may pose a significant health risk in species where levels of deficiency, sufficiency, and toxicity have not been clearly established, and species-specific research on vitamin D supplementation should be performed. This study ... ...

Abstract	Vitamin D supplementation may pose a significant health risk in species where levels of deficiency, sufficiency, and toxicity have not been clearly established, and species-specific research on vitamin D supplementation should be performed. This study documented the effect of vitamin D supplementation on serum vitamin D metabolites and other analytes of Ca homeostasis in Asian elephants (
MeSH term(s)	Animals ; Cholecalciferol ; Elephants/metabolism ; Vitamin D ; Ergocalciferols ; Parathyroid Hormone ; Dietary Supplements
Chemical Substances	Cholecalciferol (1C6V77QF41) ; Vitamin D (1406-16-2) ; Ergocalciferols ; Parathyroid Hormone
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2174930-9
ISSN	1937-2825 ; 1042-7260
ISSN (online)	1937-2825
ISSN	1042-7260
DOI	10.1638/2022-0024
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Article: Pharmacokinetics of cannabidiol-/cannabidiolic acid-rich hemp oil in juvenile cynomolgus macaques (

Johns, Tinika N / Wakshlag, Joseph J / Lyubimov, Alexander V / Zakharov, Alexander / Burnside, Wesley M

Frontiers in veterinary science

2023 Volume 10, Page(s) 1286158

Abstract: Introduction: Cannabinoids are increasingly popular in human and veterinary medicine and have been studied as an alternative treatment for a wide range of disorders. The goal of this study was to perform a pharmacokinetic analysis of oral cannabidiol ( ... ...

Abstract	Introduction: Cannabinoids are increasingly popular in human and veterinary medicine and have been studied as an alternative treatment for a wide range of disorders. The goal of this study was to perform a pharmacokinetic analysis of oral cannabidiol (CBD)-/cannabidiolic acid (CBDA)-rich hemp oil (CBD/ArHO) in juvenile cynomolgus macaques ( Methods: After a 2 mg/kg CBD/ArHO pilot study, 4 and 8 mg/kg direct-to-mouth CBD/ArHO were administered ( Results: The maximum mean serum concentration (C Discussion: Given the low serum CBD concentrations, the doses and frequency used in this study may be insufficient for a therapeutic effect of CBD in particular; therefore, clinical studies are needed to determine the therapeutic dose of CBD and CBDA for macaques, which may differ based on the disorder targeted.
Language	English
Publishing date	2023-11-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2023.1286158
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Article: The effect of a mixed cannabidiol and cannabidiolic acid based oil on client‐owned dogs with atopic dermatitis

Loewinger, Melissa / Wakshlag, Joseph J. / Bowden, Daniel / Peters‐Kennedy, Jeanine / Rosenberg, Andrew

Veterinary dermatology. 2022 Aug., v. 33, no. 4

2022

Abstract: BACKGROUND: Cannabidiol (CBD) and cannabidiolic acid (CBDA) are reported to have antinociceptive, immunomodulatory and anti‐inflammatory actions. OBJECTIVES: To determine if CBD/CBDA is an effective therapy for canine atopic dermatitis (cAD). ANIMALS: ... ...

Abstract	BACKGROUND: Cannabidiol (CBD) and cannabidiolic acid (CBDA) are reported to have antinociceptive, immunomodulatory and anti‐inflammatory actions. OBJECTIVES: To determine if CBD/CBDA is an effective therapy for canine atopic dermatitis (cAD). ANIMALS: Thirty‐two privately owned dogs with cAD. MATERIALS AND METHODS: Prospective, randomised, double‐blinded, placebo‐controlled study. Concurrent therapies were allowed if remained unchanged. Dogs were randomly assigned to receive either 2 mg/kg of an equal mix of CBD/CBDA (n = 17) or placebo for 4 weeks. On Day (D)0, D14 and D28, Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI‐04) and pruritus Visual Analog Scale (pVAS) scores were determined by investigators and owners, respectively. Complete blood count, serum biochemistry profiles and cytokine bioassays were performed on serum collected on D0 and D28. RESULTS: There was no significant difference in CADESI‐04 from D0 to D14 (p = 0.42) or D28 (p = 0.51) in either group. pVAS scores were significantly lower for the treatment group at D14 (p = 0.04) and D28 (p = 0.01) and a significant change in pVAS from baseline was seen at D14 (p = 0.04) and not D28 (p = 0.054) between groups. There was no significant difference in serum levels of interleukin (IL)‐6, IL‐8, monocyte chemoattractant protein ‐ 1, IL‐31 or IL‐34 between groups at D0 or D28. Elevated alkaline phosphatase was observed in four of 17 treatment group dogs. CONCLUSIONS AND CLINICAL RELEVANCE: CBD/CBDA as an adjunct therapy decreased pruritus, and not skin lesions associated with cAD in dogs.
Keywords	alkaline phosphatase ; atopic dermatitis ; blood chemistry ; blood serum ; cannabidiol ; chemoattractants ; dogs ; interleukin-8 ; monocytes ; oils ; placebos ; pruritus ; therapeutics ; veterinary medicine
Language	English
Dates of publication	2022-08
Size	p. 329-e77.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2011122-8
ISSN	1365-3164 ; 0959-4493
ISSN (online)	1365-3164
ISSN	0959-4493
DOI	10.1111/vde.13077
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Article: Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs.

Garcia, Gabriel A / Kube, Stephanie / Carrera-Justiz, Sheila / Tittle, David / Wakshlag, Joseph J

Frontiers in veterinary science

2022 Volume 9, Page(s) 939966

Abstract: The use of cannabidiol (CBD) in childhood refractory seizures has become a common therapeutic approach for specific seizure disorders in human medicine. Similarly, there is an interest in using CBD, cannabidiolic acid (CBDA) or cannabinoid-rich hemp ... ...

Abstract	The use of cannabidiol (CBD) in childhood refractory seizures has become a common therapeutic approach for specific seizure disorders in human medicine. Similarly, there is an interest in using CBD, cannabidiolic acid (CBDA) or cannabinoid-rich hemp products in the treatment of idiopathic epilepsy in dogs. We aimed to examine a small cohort in a pilot investigation using a CBD and CBDA-rich hemp product for the treatment of refractory epileptic seizures in dogs. Fourteen dogs were examined in a 24-week randomized cross-over study being provided placebo or CBD/CBDA-rich hemp extract treatment at 2 mg/kg orally every 12 h for each 12-week arm of the study. Serum chemistry, complete blood counts, serum anti-seizure medication (ASM) concentrations and epileptic seizure frequency were followed over both arms of the cross-over trial. Results demonstrated that besides a mild increase in alkaline phosphatase, there were no alterations observed on routine bloodwork at 2, 6, and 12 weeks during either arm of the study. Epileptic seizure frequency decreased across the population from a mean of 8.0 ± 4.8 during placebo treatment to 5.0 ± 3.6 with CBD/CBDA-rich hemp extract (
Language	English
Publishing date	2022-07-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2022.939966
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Article ; Online: Serum myostatin decreases in exercising and aging Alaskan sled dogs, while growth and differentiation factor 15 remains unaltered.

Shiomitsu, Sayaka / Hansen, Cristina M / Lenfest, Margret I / Frye, Christopher W / Wakshlag, Joseph J

Journal of the American Veterinary Medical Association

2022 Volume 260, Issue S3, Page(s) S77–S82

Abstract: Objectives: To evaluate the serum concentrations of myostatin and growth and differentiation factor 15 (GDF-15) in Alaskan Husky sled dogs participating in a 350-mile (560-km) race and in an older population, and to examine correlations between changes ... ...

Abstract	Objectives: To evaluate the serum concentrations of myostatin and growth and differentiation factor 15 (GDF-15) in Alaskan Husky sled dogs participating in a 350-mile (560-km) race and in an older population, and to examine correlations between changes in serum concentrations and body condition scores (BCSs). Animals: Dogs were recruited from 3 teams of Alaskan Huskies participating in the Alaskan-Yukon Quest sled-dog race and retirees from a research sled-dog colony. Procedures: Serum samples and BCSs were collected prior to racing, midway, and postrace; and in an older cohort (13 to 14 years). Myostatin and GDF-15 concentrations were assessed using commercially available ELISA kits. Results: The median myostatin prerace concentration (9,519 pg/mL) was significantly greater than the mid- and postrace concentrations (7,709 pg/mL and 3,247 pg/mL, respectively). The prerace concentration was also significantly greater than that of the retired sled group dogs at 6,134 pg/mL. GDF-15 median serum concentrations did not change significantly across any racing time point (approx 350 pg/mL) or in the older cohort. No significant correlations were observed between changes in BCS and myostatin or GDF-15 concentrations. Clinical relevance: Serum myostatin decreases dramatically, yet no correlations to loss of BCS could be found. Myostatin signaling may be involved in maintaining hypertrophic signaling during intense exercise. Neither racing distance nor geriatric/retirement status appears to have an effect on serum GDF-15 concentration. Myostatin was less in the older, retired sled dogs compared to the younger racing cohort. Such differences highlight the roles that fitness level and age play regarding myostatin levels.
MeSH term(s)	Dogs ; Animals ; Myostatin ; Physical Conditioning, Animal ; Growth Differentiation Factor 15 ; Running ; Aging
Chemical Substances	Myostatin ; Growth Differentiation Factor 15
Language	English
Publishing date	2022-10-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	390811-2
ISSN	1943-569X ; 0003-1488
ISSN (online)	1943-569X
ISSN	0003-1488
DOI	10.2460/javma.22.07.0323
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