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Veterinary research communications2024; doi: 10.1007/s11259-024-10509-7

Endocannabinoid system and phytocannabinoids in the main species of veterinary interest: a comparative review.

Abstract: Since the discovery of the endocannabinoid system and due to the empirical evidence of the therapeutic effects on several illnesses both in humans and animals that follow the administration of exogenous cannabinoids (i.e., phytocannabinoids), numerous studies have been conducted. These investigations aimed to identify the expression and distribution of cannabinoid receptors in healthy and pathologic organs and tissues of different animal species and to define the interactions of phytocannabinoids with these receptors. In the last decade, pharmacokinetics, efficacy and tolerability of many Cannabis derivatives formulations, mainly containing cannabidiol, in the main species of veterinary interest, have been also investigated. This manuscript summarizes the findings reported by the scientific studies published so far on the molecular mode of action of the main phytocannabinoids, the localization of cannabinoid receptors in organs and tissues, as well as the pharmacokinetics, efficacy and tolerability of Cannabis derivatives in dogs, cats, horses and other species of veterinary interest. A deep knowledge of these issues is crucial for the use of phytocannabinoids for therapeutic purposes in animal species.
© 2024. The Author(s).
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Publication Date: 2024-08-20 PubMed ID: 39162768PubMed Central: 8298633DOI: 10.1007/s11259-024-10509-7Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article discusses the studies conducted on the effects and interactions of cannabinoids (particularly the plant-derived variety known as phytocannabinoids) with the endocannabinoid system in animals. It provides an overview of the identified expression and distribution of cannabinoid receptors in healthy and pathological organs and tissues across several animal species, and presents data on the efficacy, tolerability, and pharmacokinetics of cannabis derivatives, primarily cannabidiol, within the main species of interest in veterinary medicine.

Endocannabinoid System and Phytocannabinoids

  • The endocannabinoid system (ECS) consists of cannabinoid receptors, endocannabinoids (naturally occurring cannabinoids in the body), and enzymes that regulate the synthesis and degradation of these endocannabinoids. This system has crucial roles in various physiological processes, such as pain sensation, mood, appetite, sleep, among others.
  • Phytocannabinoids are plant-derived cannabinoids, primarily sourced from Cannabis. This research focuses on the interaction of these exogenous cannabinoids with the endocannabinoid system within different animal species.

Expression and Distribution of Cannabinoid Receptors

  • The focus of many studies is to understand the presence (“expression”) and location (“distribution”) of cannabinoid receptors in both normal and transformed (pathogenic) animal organs and tissues. This helps researchers investigate how cannabinoids, both natural and plant-derived, can influence health and disease in animal models.

Pharmacokinetics, Efficacy, and Tolerability of Cannabis Derivatives

  • Pharmacokinetics deal with how drugs are absorbed, distributed, metabolized, and excreted by the body. The research discusses these aspects for cannabis derivatives, especially cannabidiol (CBD), in veterinary contexts. It is crucial to understand these parameters to optimize drug dosages and minimize the risk of adverse effects.
  • The efficacy of these exogenous cannabinoids in treating various illnesses in animals is also considered in these studies. Exploring this potentially therapeutic aspect is vital for developing and recommending effective veterinary treatments.
  • Tolerability pertains to the degree to which side effects can be tolerated by patients. If a veterinary drug is not well-tolerated, it will not be effective, regardless of its potential benefits. Therefore, it is equally important to investigate the effects of cannabis derivatives in terms of tolerability.

Conclusions and Future Directions

  • The article concludes by emphasizing the importance of this deep understanding of the endocannabinoid system and the interaction of phytocannabinoids with it for possible medical usage in animals. This knowledge can potentially lead to new, effective treatments for various ailments in animals.

Cite This Article

APA
Di Salvo A, Chiaradia E, Sforna M, Della Rocca G. (2024). Endocannabinoid system and phytocannabinoids in the main species of veterinary interest: a comparative review. Vet Res Commun. https://doi.org/10.1007/s11259-024-10509-7

Publication

Veterinary research communications
ISSN: 1573-7446
NlmUniqueID: 8100520
Country: Switzerland
Language: English

Researcher Affiliations

Di Salvo, Alessandra
  • Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
  • Research Center on Animal Pain (CeRiDA), University of Perugia, Perugia, Italy.
Chiaradia, Elisabetta
  • Department of Veterinary Medicine, University of Perugia, Perugia, Italy. elisabetta.chiaradia@unipg.it.
Sforna, Monica
  • Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
Della Rocca, Giorgia
  • Department of Veterinary Medicine, University of Perugia, Perugia, Italy.
  • Research Center on Animal Pain (CeRiDA), University of Perugia, Perugia, Italy.

References

This article includes 190 references
  1. Alonso-Ferrero ME, Paniagua MA, Mostany R, Pilar-Cuéllar F, Díez-Alarcia R, Pazos A, Fernández-López A. Cannabinoid system in the budgerigar brain. Brain Res 1087:105–113.
    doi: 10.1016/j.brainres.2006.02.119pubmed: 16626655google scholar: lookup
  2. Amstutz K, Schwark WS, Zakharov A, Gomez B, Lyubimov A, Ellis K, Venator KP, Wakshlag JJ. Single dose and chronic oral administration of cannabigerol and cannabigerolic acid-rich hemp extract in fed and fasted dogs: physiological effect and pharmacokinetic evaluation. J Vet Pharmacol Ther 45:245–254.
    doi: 10.1111/jvp.13048pubmed: 35246858google scholar: lookup
  3. Anderson LL, Low IK, Banister SD, McGregor IS, Arnold JC. Pharmacokinetics of phytocannabinoid acids and anticonvulsant effect of cannabidiolic acid in a mouse model of Dravet syndrome. J Nat Prod 82:3047–3055.
    doi: 10.1021/acs.jnatprod.9b00600pubmed: 31686510google scholar: lookup
  4. Anderson LL, Etchart MG, Bahceci D, Golembiewski TA, Arnold JC. Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations. Sci Rep 11:14948.
    doi: 10.1038/s41598-021-94212-6pubmed: 34294753pmc: 8298633google scholar: lookup
  5. Ang SP, Sidharthan S, Lai W, Hussain N, Patel KV, Gulati A, Henry O, Kaye AD, Orhurhu V. Cannabinoids as a potential alternative to opioids in the management of various pain subtypes: benefits, limitations, and risks. Pain Ther 12:355–375.
    doi: 10.1007/S40122-022-00465-Ypubmed: 36639601pmc: 10036719google scholar: lookup
  6. Atalay Ekiner S, Gęgotek A, Skrzydlewska E. The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress. Redox Biol 57:102489.
    doi: 10.1016/j.redox.2022.102489pubmed: 36198205pmc: 9535304google scholar: lookup
  7. Bartner LR, McGrath S, Rao S, Hyatt LK, Wittenburg LA. Pharmacokinetics of cannabidiol administered by 3 delivery methods at 2 different dosages to healthy dogs. Can J Vet Res 82:178–183.
    pubmed: 30026641pmc: 6038832
  8. Berthold EC, Kamble SH, Kanumuri SRR, Kuntz MA, Senetra AS, Chiang Y-H, McMahon LR, McCurdy CR, Sharma A. Comparative pharmacokinetics of commercially available cannabidiol isolate, broad-spectrum, and full-spectrum products. Eur J Drug Metab Pharmacokinet 48:427–435.
    doi: 10.1007/s13318-023-00839-3pubmed: 37337087google scholar: lookup
  9. Bie B, Wu J, Foss JF, Naguib M. An overview of the cannabinoid type 2 receptor system and its therapeutic potential. Curr Opin Anaesthesiol 31:407–414.
    doi: 10.1097/ACO.0000000000000616pubmed: 29794855pmc: 6035094google scholar: lookup
  10. Blebea NM, Pricopie AI, Vlad RA, Hancu G. Phytocannabinoids: exploring pharmacological profiles and their impact on therapeutical use. Int J Mol Sci 25.
    doi: 10.3390/ijms25084204google scholar: lookup
  11. Bookout W, Dziwenka M, Valm K, Kovacs-Nolan J. Safety study of cannabidiol products in healthy dogs. Front Vet Sci 11:1349590.
    doi: 10.3389/fvets.2024.1349590pubmed: 38496308pmc: 10940325google scholar: lookup
  12. Bradley S, Young S, Bakke AM, Holcombe L, Waller D, Hunt A, Pinfold K, Watson P, Logan DW. Long-term daily feeding of cannabidiol is well-tolerated by healthy dogs. Front Vet Sci 9:977457.
    doi: 10.3389/fvets.2022.977457google scholar: lookup
  13. Brioschi FA, Di Cesare F, Gioeni D, Rabbogliatti V, Ferrari F, D’Urso ES, Amari M, Ravasio G. Oral transmucosal cannabidiol oil formulation as part of a multimodal analgesic regimen: effects on pain relief and quality of life improvement in dogs affected by spontaneous osteoarthritis. Animals 10:1505.
    doi: 10.3390/ani10091505pubmed: 32858828pmc: 7552307google scholar: lookup
  14. Brown C, Mitsch M, Blankenship K, Campbell C, Pelanne M, Sears J, Bell A, Olivier AK, Ross MK, Archer T, Kaplan BLF. Canine immune cells express high levels of CB1 and CB2 cannabinoid receptors and cannabinoid-mediated alteration of canine cytokine production is vehicle-dependent. Vet Immunol Immunopathol 265:110667.
    doi: 10.1016/j.vetimm.2023.110667pubmed: 37931433google scholar: lookup
  15. Campora L, Miragliotta V, Ricci E, Cristino L, Di Marzo V, Albanese F, Federica Della Valle M, Abramo F. Cannabinoid receptor type 1 and 2 expression in the skin of healthy dogs and dogs with atopic dermatitis. Am J Vet Res 73:988–995.
    doi: 10.2460/ajvr.73.7.988pubmed: 22738050google scholar: lookup
  16. Carlisle SJ, Marciano-Cabral F, Staab A, Ludwick C, Cabral GA. Differential expression of the CB2 cannabinoid receptor by rodent macrophages and macrophage-like cells in relation to cell activation. Int Immunopharmacol 2:69–82.
    doi: 10.1016/S1567-5769(01)00147-3pubmed: 11789671google scholar: lookup
  17. Chicoine A, Illing K, Vuong S, Pinto KR, Alcorn J, Cosford K. Pharmacokinetic and safety evaluation of various oral doses of a novel 1:20 THC:CBD cannabis herbal extract in dogs. Front Vet Sci 7.
    doi: 10.3389/fvets.2020.583404google scholar: lookup
  18. Chiocchetti R, Galiazzo G, Tagliavia C, Stanzani A, Giancola F, Menchetti M, Militerno G, Bernardini C, Forni M, Mandrioli L. Cellular distribution of canonical and putative cannabinoid receptors in canine cervical dorsal root ganglia. Front Vet Sci 6:313.
    doi: 10.3389/fvets.2019.00313google scholar: lookup
  19. Chiocchetti R, Rinnovati R, Tagliavia C, Stanzani A, Galiazzo G, Giancola F, Silva M De, Capodanno Y, Spadari A. Localisation of cannabinoid and cannabinoid-related receptors in the equine dorsal root ganglia. Equine Vet J 53:549–557.
    doi: 10.1111/evj.13305pubmed: 32524649google scholar: lookup
  20. Chiocchetti R, De Silva M, Aspidi F, Cunha RZ, Gobbo F, Tagliavia C, Sarli G, Morini M. Distribution of cannabinoid receptors in keratinocytes of healthy dogs and dogs with atopic dermatitis. Front Vet Sci 9:915896.
    doi: 10.3389/fvets.2022.915896google scholar: lookup
  21. Chiocchetti R, Salamanca G, De Silva M, Gobbo F, Aspidi F, Cunha RZ, Galiazzo G, Tagliavia C, Sarli G, Morini M. Cannabinoid receptors in the inflammatory cells of canine atopic dermatitis. Front Vet Sci 9:987132.
    doi: 10.3389/fvets.2022.987132pubmed: 36187821pmc: 9521433google scholar: lookup
  22. Coelho RCMP, De OP, Leme F, Moreira A, Branco FEMT, Melo SM, De Melo MG, E. Current review of hemp-based medicines in dogs. J Vet Pharmacol Ther 44:870–882.
    doi: 10.1111/jvp.13016google scholar: lookup
  23. Coelho JC, Duarte N, Da Silva B, Bronze A, Mestrinho MDR, L.A. Placebo-controlled trial of daily oral cannabidiol as adjunctive treatment for cats with chronic gingivostomatitis. Animals 13:2716.
    doi: 10.3390/ani13172716pubmed: 37684980pmc: 10487179google scholar: lookup
  24. Coltherd JC, Bednall R, Bakke AM, Ellerby Z, Newman C, Watson P, Logan DW, Holcombe LJ. Healthy cats tolerate long-term daily feeding of Cannabidiol. Front Vet Sci 10:1324622.
    doi: 10.3389/fvets.2023.1324622pubmed: 38327816pmc: 10847353google scholar: lookup
  25. Console-Bram L, Brailoiu E, Brailoiu GC, Sharir H, Abood ME. Activation of GPR18 by cannabinoid compounds: a tale of biased agonism. Br J Pharmacol 171:3908–3917.
    doi: 10.1111/bph.12746pubmed: 24762058pmc: 4128052google scholar: lookup
  26. Corsato Alvarenga I, Gustafson D, Banks K, Wilson K, McGrath S. 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. Front Vet Sci 10:1279926.
    doi: 10.3389/fvets.2023.1279926pubmed: 37841465pmc: 10571049google scholar: lookup
  27. Corsato Alvarenga I, Wilson KM, McGrath S. Tolerability of long-term cannabidiol supplementation to healthy adult dogs. J Vet Intern Med 38:326–335.
    doi: 10.1111/jvim.16949pubmed: 38009749google scholar: lookup
  28. Corsetti S, Borruso S, Malandrucco L, Spallucci V, Maragliano L, Perino R, DAgostino P, Natoli E. Cannabis sativa L. may reduce aggressive behaviour towards humans in shelter dogs. Sci Rep 11:2773.
    doi: 10.1038/s41598-021-82439-2pubmed: 33531559pmc: 7854708google scholar: lookup
  29. Costa B, Giagnoni G, Franke C, Trovato AE, Colleoni M. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. Br J Pharmacol 143:247–250.
    doi: 10.1038/sj.bjp.0705920pubmed: 15313881google scholar: lookup
  30. Court MH, Mealey KL, Burke NS, Jimenez TP, Zhu Z, Wakshlag JJ. Cannabidiol and cannabidiolic acid: preliminary in vitro evaluation of metabolism and drugdrug interactions involving canine cytochrome P-450, UDP-glucuronosyltransferase, and P-glycoprotein. J Vet Pharmacol Ther 47:1–13.
    doi: 10.1111/jvp.13403pubmed: 37469115google scholar: lookup
  31. Cui Sun M, Otálora-Alcaraz A, Prenderville JA, Downer EJ. Toll-like receptor signalling as a cannabinoid target. Biochem Pharmacol 222:116082.
    doi: 10.1016/j.bcp.2024.116082pubmed: 38438052google scholar: lookup
  32. Cunha RZ, Felisardo LL, Salamanca G, Marchioni GG, Neto OI, Chiocchetti R. The use of cannabidiol as a novel treatment for oral stereotypic behaviour (crib-biting) in a horse. Vet Anim Sci 19:100289.
    doi: 10.1016/j.vas.2023.100289pubmed: 36824298pmc: 9941357google scholar: lookup
  33. Da Silva MES, Christianetti B, Amazonas E, Pereira ML. Case report: cannabinoid therapy for discoid lupus erythematosus in a dog. Front Vet Sci 11:1309167.
    doi: 10.3389/fvets.2024.1309167pubmed: 38406630pmc: 10884172google scholar: lookup
  34. Dall’Aglio C, Mercati F, Pascucci L, Boiti C, Pedini V, Ceccarelli P. Immunohistochemical localization of CB1 receptor in canine salivary glands. Vet Res Commun 34:9–12.
    doi: 10.1007/s11259-010-9379-0google scholar: lookup
  35. Dall’Aglio C, Polisca A, Cappai MG, Mercati F, Troisi A, Pirino C, Scocco P, Maranesi M. Immunohistochemistry detected and localized cannabinoid receptor type 2 in bovine fetal pancreas at late gestation. Eur J Histochem .
    doi: 10.4081/ejh.2017.2761pubmed: 28348424pmc: 5364978google scholar: lookup
  36. Dawidowicz AL, Olszowy-Tomczyk M, Typek R. ∆9-THC CBGCBD CBN, CBGA, CBDA and ∆9-THCA as antioxidant agents and their intervention abilities in antioxidant action. Fitoterapia 152:104915.
    doi: 10.1016/j.fitote.2021.104915google scholar: lookup
  37. Deabold KA, Schwark WS, Wolf L, Wakshlag JJ. Single-dose pharmacokinetics and preliminary safety assessment with use of CBD-Rich hemp nutraceutical in healthy dogs and cats. Animals 9:832.
    doi: 10.3390/ani9100832pubmed: 31635105pmc: 6826847google scholar: lookup
  38. Deiana S, Watanabe A, Yamasaki Y, Amada N, Arthur M, Fleming S, Woodcock H, Dorward P, Pigliacampo B, Close S, Platt B, Riedel G. Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), ∆9-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessivecompulsive behaviour. Psychopharmacology 219:859–873.
    doi: 10.1007/s00213-011-2415-0pubmed: 21796370google scholar: lookup
  39. Della Rocca G, Di Salvo A. Hemp in veterinary medicine: from feed to drug. Front Vet Sci 7:387.
    doi: 10.3389/fvets.2020.00387pubmed: 32850997pmc: 7399642google scholar: lookup
  40. Della Rocca G, Paoletti F, Conti MB, Galarini R, Chiaradia E, Sforna M, Dall’Aglio C, Polisca A, Di Salvo A. Pharmacokinetics of cannabidiol following single oral and oral transmucosal administration in dogs. Front Vet Sci 9:1104152.
    doi: 10.3389/fvets.2022.1104152pubmed: 36686155pmc: 9859632google scholar: lookup
  41. Denapoli A, Denapoli C. Method of reducing stress and anxiety in equines. United States Patent 2020 Apr; Patent No.: US 10,624,936 B2.
  42. Deng J, Zhu X, Chen Z, Fan CH, Kwan HS, Wong CH, Shek KY, Zuo Z, Lam TN. A review of fooddrug interactions on oral drug absorption. Drugs 77:1833–1855.
    doi: 10.1007/s40265-017-0832-zpubmed: 29076109google scholar: lookup
  43. Di Salvo A, Conti MB, della Rocca G. Pharmacokinetics, efficacy, and safety of cannabidiol in dogs: an update of current knowledge. Front Vet Sci 10.
    doi: 10.3389/fvets.2023.1204526google scholar: lookup
  44. Di Wang MV J. The endocannabinoidome: the world of endocannabinoids and related mediators. Academic Press .
  45. Divín D, Goméz Samblas M, Kuttiyarthu Veetil N, Voukali E, Świderská Z, Krajzingrová T, Těšický M, Beneš V, Elleder D, Bartoš O, Vinkler M. Cannabinoid receptor 2 evolutionary gene loss makes parrots more susceptible to neuroinflammation. Proc R Soc B Biol Sci 289:20221941.
    doi: 10.1098/rspb.2022.1941google scholar: lookup
  46. Doran CE, McGrath S, Bartner LR, Thomas B, Cribb AE, Gustafson DL. Drug-drug interaction between cannabidiol and phenobarbital in healthy dogs. Am J Vet Res 83:86–94.
    doi: 10.2460/ajvr.21.08.0120google scholar: lookup
  47. Draeger AL, Thomas EP, Jones KA, Davis AJ, Porr CAS. The effects of pelleted cannabidiol supplementation on heart rate and reaction scores in horses. J Veterinary Behav 46:97–100.
    doi: 10.1016/j.jveb.2021.09.003google scholar: lookup
  48. Draeger AL, Hoffman LK, Godwin PR, Davis AJ. Pharmacokinetics of a single feeding of pelleted cannabidiol in horses. Steeplechase: an ORCA Student Journal 4.
  49. Eichler F, Ehrle A, Jensen KC, Baudisch N, Petersen H, Bäumer W, Lischer C, Wiegard M. Behavioral observations, heart rate and heart rate variability in horses following oral administration of a cannabidiol containing paste in three escalating doses (part 1/2). Front Vet Sci 10:1305868.
    doi: 10.3389/fvets.2023.1305868google scholar: lookup
  50. Eichler F, Poźniak B, Machnik M, Schenk I, Wingender A, Baudisch N, Thevis M, Bäumer W, Lischer C, Ehrle A. Pharmacokinetic modelling of orally administered cannabidiol and implications for medication control in horses. Front Vet Sci 10:1234551.
    doi: 10.3389/fvets.2023.1234551google scholar: lookup
  51. Eichler F, Ehrle A, Machnik M, Jensen KC, Wagner S, Baudisch N, Bolk J, Pötzsch M, Thevis M, Bäumer W, Lischer C, Wiegard M. Behavioral observations, heart rate and cortisol monitoring in horses following multiple oral administrations of a cannabidiol containing paste (part 2/2). Front Vet Sci 10:1305873.
    doi: 10.3389/fvets.2023.1305873google scholar: lookup
  52. Ellis KL, Contino EK. Treatment using cannabidiol in a horse with mechanical allodynia. Equine Vet Educ 33.
    doi: 10.1111/eve.13168google scholar: lookup
  53. Etemad L, Karimi G, Alavi MS, Roohbakhsh A. Pharmacological effects of cannabidiol by transient receptor potential channels. Life Sci 300.
    doi: 10.1016/j.lfs.2022.120582google scholar: lookup
  54. Fernández-Trapero M, Pérez-Díaz C, Espejo-Porras F, De Lago E, Fernández-Ruiz J. Pharmacokinetics of Sativex in dogs: towards a potential cannabinoid-based therapy for canine disorders. Biomolecules 10:279.
    doi: 10.3390/biom10020279pubmed: 32054131pmc: 7072526google scholar: lookup
  55. Flint HE, Hunt ABG, Logan DW, King T. Daily dosing of cannabidiol (CBD) demonstrates a positive effect on measures of stress in dogs during repeated exposure to car travel. J Anim Sci 102:skad414.
    doi: 10.1093/jas/skad414google scholar: lookup
  56. . GW Pharmaceuticals. Food and Drug Administration application 210365Orig1s000 2018.
  57. Fraguas-Sánchez AI, Martín‐Sabroso C, Torres‐Suárez AI. Insights into the effects of the endocannabinoid system in cancer: a review. Br J Pharmacol 175:2566–2580.
    doi: 10.1111/bph.14331google scholar: lookup
  58. Freundt-Revilla J, Kegler K, Baumgärtner W, Tipold A. Spatial distribution of cannabinoid receptor type 1 (CB1) in normal canine central and peripheral nervous system. PLoS ONE 12:e0181064.
    doi: 10.1371/journal.pone.0181064google scholar: lookup
  59. Galiazzo G, Giancola F, Stanzani A, Fracassi F, Bernardini C, Forni M, Pietra M, Chiocchetti R. Localization of cannabinoid receptors CB1, CB2, GPR55, and PPARα in the canine gastrointestinal tract. Histochem Cell Biol 150:187–205.
    doi: 10.1007/s00418-018-1684-7google scholar: lookup
  60. Galiazzo G, Tagliavia C, Giancola F, Rinnovati R, Sadeghinezhad J, Bombardi C, Grandis A, Pietra M, Chiocchetti R. Localisation of cannabinoid and cannabinoid-related receptors in the horse ileum. J Equine Vet Sci 104:103688.
    doi: 10.1016/j.jevs.2021.103688google scholar: lookup
  61. Galiazzo G, De Silva M, Giancola F, Rinnovati R, Peli A, Chiocchetti R. Cellular distribution of cannabinoid-related receptors TRPV1, PPAR-gamma, GPR55 and GPR3 in the equine cervical dorsal root ganglia. Equine Vet J 54:788–798.
    doi: 10.1111/evj.13499google scholar: lookup
  62. Gamble L-J, Boesch JM, Frye CW, Schwark WS, Mann S, Wolfe L, Brown H, Berthelsen ES, Wakshlag JJ. Pharmacokinetics, safety, and clinical efficacy of cannabidiol treatment in osteoarthritic dogs. Front Vet Sci 5:165.
    doi: 10.3389/fvets.2018.00165pubmed: 30083539pmc: 6065210google scholar: lookup
  63. Garcia GA, Kube S, Carrera-Justiz S, Tittle D, Wakshlag JJ. Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs. Front Vet Sci 9:939966.
    doi: 10.3389/fvets.2022.939966pubmed: 35967998pmc: 9372618google scholar: lookup
  64. Gebremedhin D, Lange AR, Campbell WB, Hillard CJ, Harder DR. Cannabinoid CB1 receptor of cat cerebral arterial muscle functions to inhibit L-type ca ^2 + channel current. Am J Physiol Heart Circ Physiol 276:H2085–H2093.
    doi: 10.1152/ajpheart.1999.276.6.H2085google scholar: lookup
  65. Gomez-Canas M, Rodrıguez-Cueto C, Satta V, Hernandez-Fisac I, Navarro E, Fernandez-Ruiz J. Endocannabinoid-binding receptors as drug targets. Methods Mol Biol 2576:67–94.
    doi: 10.1007/978-1-0716-2728-0_6google scholar: lookup
  66. Gutierre E, Crosignani N, García-Carnelli C, Di Mateo A, Recchi L. A case report of CBD and THC as analgesic therapy in a cat with chronic osteoarthritic pain. Vet Med Sci 9:1021–1025.
    doi: 10.1002/vms3.1057google scholar: lookup
  67. Hannon MB, Deabold KA, Talsma BN, Lyubimov A, Iqbal A, Zakharov A, Gamble LJ, Wakshlag JJ. Serum cannabidiol, tetrahydrocannabinol (THC), and their native acid derivatives after transdermal application of a low-THC Cannabis sativa extract in beagles. J Vet Pharmacol Ther 43:508–511.
    doi: 10.1111/jvp.12896pubmed: 32735381google scholar: lookup
  68. Hasckel Gewehr JL, Enzele ML, Freiria LM, Nunes MM, Spengler J, Dondoerfer Teixeira AP, Amazonas E, Padilha S, V. Full spectrum cannabidiol-rich extract reduced propofol dosage required for anesthetic induction in dogsa pilot study. Front Vet Sci 11:1352314.
    doi: 10.3389/fvets.2024.1352314pubmed: 38645644pmc: 11026717google scholar: lookup
  69. Hegde VL, Singh UP, Nagarkatti PS, Nagarkatti M. Critical role of mast cells and peroxisome proliferator-activated receptor γ in the induction of myeloid-derived suppressor cells by marijuana cannabidiol in vivo. J Immunol 194:5211–5222.
    doi: 10.4049/JIMMUNOL.1401844pubmed: 25917103google scholar: lookup
  70. Huang J, Korsunsky A, Yazdani M, Chen J. Targeting TRP channels: recent advances in structure, ligand binding, and molecular mechanisms. Front Mol Neurosci 16.
    doi: 10.3389/fnmol.2023.1334370google scholar: lookup
  71. Hunt ABG, Flint HE, Logan DW, King T. A single dose of cannabidiol (CBD) positively influences measures of stress in dogs during separation and car travel. Front Vet Sci 10:1112604.
    doi: 10.3389/fvets.2023.1112604google scholar: lookup
  72. Interlandi C, Tabbì M, Di Pietro S, DAngelo F, Costa GL, Arfuso F, Giudice E, Licata P, Macrì D, Crupi R, Gugliandolo E. Improved quality of life and pain relief in mature horses with osteoarthritis after oral transmucosal cannabidiol oil administration as part of an analgesic regimen. Front Vet Sci 11:1341396.
    doi: 10.3389/fvets.2024.1341396google scholar: lookup
  73. Irving A, Abdulrazzaq G, Chan SLF, Penman J, Harvey J, Alexander SPH. Cannabinoid receptor-related orphan G protein-coupled receptors. Adv Pharmacol 80:223–247.
    doi: 10.1016/bs.apha.2017.04.004google scholar: lookup
  74. Jukier T, Cruz-Espindola C, Martin D, Boothe DM. Disposition of a single oral dose of a cannabidiol medication in healthy cats. Front Vet Sci 10:1181517.
    doi: 10.3389/fvets.2023.1181517google scholar: lookup
  75. Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn Schmiedebergs Arch Pharmacol 372:354–361.
    doi: 10.1007/s00210-006-0033-xpubmed: 16489449google scholar: lookup
  76. Khosropoor S, Alavi MS, Etemad L, Roohbakhsh A. Cannabidiol goes nuclear: the role of PPARγ. Phytomedicine 114:154771.
    doi: 10.1016/j.phymed.2023.154771pubmed: 36965374google scholar: lookup
  77. Kibret BG, Canseco-Alba A, Onaivi ES, Engidawork E. Crosstalk between the endocannabinoid and mid-brain dopaminergic systems: implication in dopamine dysregulation. Front Behav Neurosci 17.
    doi: 10.3389/fnbeh.2023.1137957google scholar: lookup
  78. Klatzkow S, Davis G, Shmalberg J, Gallastegui A, Miscioscia E, Tarricone J, Elam L, Johnson MD, Leonard KM, Wakshlag JJ. Evaluation of the efficacy of a cannabidiol and cannabidiolic acid rich hemp extract for pain in dogs following a tibial plateau leveling osteotomy. Front Vet Sci 9:1036056.
    doi: 10.3389/fvets.2022.1036056google scholar: lookup
  79. Kleinhenz MD, Magnin G, Lin Z, Griffin J, Kleinhenz KE, Montgomery S, Curtis A, Martin M, Coetzee JF. Plasma concentrations of eleven cannabinoids in cattle following oral administration of industrial hemp (Cannabis sativa). Sci Rep 10:12753.
    doi: 10.1038/s41598-020-69768-4google scholar: lookup
  80. Kleinhenz MD, Weeder M, Montgomery S, Martin M, Curtis A, Magnin G, Lin Z, Griffin J, Coetzee JF. Short term feeding of industrial hemp with a high cannabidiolic acid (CBDA) content increases lying behavior and reduces biomarkers of stress and inflammation in Holstein steers. Sci Rep 12:3683.
    doi: 10.1038/s41598-022-07795-zgoogle scholar: lookup
  81. Kogan LR, Hellyer PW, Silcox S-, Schoenfeld-Tacher R. Canadian dog owners’ use and perceptions of cannabis products. Can Vet J 60:749–755.
  82. Kogan L, Schoenfeld-Tacher R, Hellyer P, Rishniw M. US veterinarians’ knowledge, experience, and perception regarding the use of cannabidiol for canine medical conditions. Front Vet Sci 5:338.
    doi: 10.3389/fvets.2018.00338google scholar: lookup
  83. Kogan L, Hellyer P, Downing R. The use of cannabidiol-rich hemp oil extract to treat canine osteoarthritis-related pain: a pilot study. AHVMA J 58:35–42.
  84. Kostic D, Nowakowska M, Freundt Revilla J, Attig F, Rohn K, Gualtieri F, Baumgärtner W, Potschka H, Tipold A. Hippocampal expression of the cannabinoid receptor type 1 in canine epilepsy. Sci Rep 13:3138.
    doi: 10.1038/s41598-023-29868-3google scholar: lookup
  85. Krebs GL, De Rosa DW, White DM, Blake BL, Dods KC, May CD, Tai ZX, Clayton EH, Lynch EE. Intake, nutrient digestibility, rumen parameters, growth rate, carcase characteristics and cannabinoid residues of sheep fed pelleted rations containing hemp (Cannabis sativa L.) Stubble. Transl Anim Sci 5:txab213.
    doi: 10.1093/tas/txab213google scholar: lookup
  86. Kulpa JE, Paulionis LJ, Eglit GM, Vaughn DM. Safety and tolerability of escalating cannabinoid doses in healthy cats. J Feline Med Surg 23:1162–1175.
    doi: 10.1177/1098612x211004215google scholar: lookup
  87. Kumar V, Kumaresan A, Nag P, Kumar P, Datta TK, Baithalu RK, Mohanty TK. Transcriptional abundance of type-1 endocannabinoid receptor (CB1) and fatty acid amide hydrolase (FAAH) in bull spermatozoa: relationship with field fertility. Theriogenology 114:252–257.
    doi: 10.1016/j.theriogenology.2018.04.001google scholar: lookup
  88. Kupczyk P, Rykala M, Serek P, Pawlak A, Slowikowski B, Holysz M, Chodaczek G, Madej JP, Ziolkowski P, Niedzwiedz A. The cannabinoid receptors system in horses: tissue distribution and cellular identification in skin. J Vet Intern Med 36:1508–1524.
    doi: 10.1111/jvim.16467google scholar: lookup
  89. Lachowicz J, Szopa A, Ignatiuk K, Świ ader K, Serefko A. Zebrafish as an animal model in cannabinoid research. Int J Mol Sci 24:10455.
    doi: 10.3390/ijms241310455google scholar: lookup
  90. Łebkowska-Wieruszewska B, Stefanelli F, Chericoni S, Owen H, Poapolathep A, Lisowski A, Giorgi M. Pharmacokinetics of Bedrocan, a cannabis oil extract, in fasting and fed dogs: an explorative study. Res Vet Sci 123:26–28.
    doi: 10.1016/j.rvsc.2018.12.003google scholar: lookup
  91. Leise JM, Leatherwood JL, Paris BL, Walter KW, George JM, Martinez RE, Glass KP, Lo C-P, Mays TP, Wickersham TA. Evaluation of an oral supplemental cannabidiol product for acceptability and performance in mature horses. Animals 13:245.
    doi: 10.3390/ani13020245google scholar: lookup
  92. Lile JA, Kelly TH, Hays LR. Separate and combined effects of the GABAA positive allosteric modulator diazepam and ∆9-THC in humans discriminating ∆9-THC. Drug Alcohol Depend 143:141–148.
    doi: 10.1016/j.drugalcdep.2014.07.016pubmed: 25124305pmc: 4167716google scholar: lookup
  93. Lim J, Squire E, Jung K-M. Phytocannabinoids, the endocannabinoid system and male reproduction. World J Mens Health 41:1.
    doi: 10.5534/wjmh.220132pubmed: 36578200pmc: 9826913google scholar: lookup
  94. Lima TdeM, Santiago NR, Alves ECR, Chaves DS, de Visacri A, M.B. Use of cannabis in the treatment of animals: a systematic review of randomized clinical trials. Anim Health Res Rev 23:25–38.
    doi: 10.1017/S1466252321000189pubmed: 35703023google scholar: lookup
  95. Limsuwan S, Phonsatta N, Panya A, Asasutjarit R, Tansakul N. Pharmacokinetics behavior of four cannabidiol preparations following single oral administration in dogs. Front Vet Sci 11:1389810.
    doi: 10.3389/fvets.2024.1389810pubmed: 38725584pmc: 11080651google scholar: lookup
  96. Loewinger M, Wakshlag JJ, Bowden D, Peters-Kennedy J, Rosenberg A. The effect of a mixed cannabidiol and cannabidiolic acid based oil on client‐owned dogs with atopic dermatitis. Vet Dermatol 33:329.
    doi: 10.1111/vde.13077pubmed: 35644533pmc: 9543248google scholar: lookup
  97. Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol 84:2477–2482.
    doi: 10.1111/bcp.13710pubmed: 30001569pmc: 6177698google scholar: lookup
  98. Lutz B. Neurobiology of cannabinoid receptor signaling. Dialogues Clin Neurosci 22:207–222.
    doi: 10.31887/DCNS.2020.22.3/blutzpubmed: 33162764pmc: 7605026google scholar: lookup
  99. Lyons C, McEwan K, Munn-Patterson M, Vuong S, Alcorn J, Chicoine A. Pharmacokinetic of two oral doses of a 1:20 THC:CBD cannabis herbal extract in cats. Front Vet Sci 11:1352495.
    doi: 10.3389/fvets.2024.1352495pubmed: 38585296pmc: 10996858google scholar: lookup
  100. Maccarrone M, Marzo V Di, Gertsch J, Grether U, Howlett AC, Hua T, Makriyannis A, Piomelli D, Ueda N, van der Stelt M. Goods and bads of the endocannabinoid system as a therapeutic target: lessons learned after 30 years. Pharmacol Rev 75:885–958.
    doi: 10.1124/PHARMREV.122.000600pubmed: 37164640google scholar: lookup
  101. Mariga C, Souza Silva Mateus AL, dos Santos Dullius ÂI, da Silva AP, Martins Flores M, Soares V, Amazonas A, Filho ETLP, S. Dermatological evaluation in dogs with atopic dermatitis treated with full-spectrum high cannabidiol oil: a pre study part 1. Front Vet Sci 10.
    doi: 10.3389/fvets.2023.1285384google scholar: lookup
  102. Martello E, Bigliati M, Bisanzio D, Biasibetti E, Dosio F, Pastorino D, Nardi M, De, Bruni N. Effects on pain and mobility of a new diet supplement in dogs with osteoarthritis: a pilot study. Ann Clin Lab Res 7:304.
  103. Martinez Naya N, Kelly J, Corna G, Golino M, Abbate A, Toldo S. Molecular and cellular mechanisms of action of cannabidiol. Molecules 28:5980.
    doi: 10.3390/molecules28165980pubmed: 37630232pmc: 10458707google scholar: lookup
  104. Martins AM, Gomes AL, Vilas Boas I, Marto J, Ribeiro HM. Cannabis-based products for the treatment of skin inflammatory diseases: a timely review. Pharmaceuticals (Basel) 15:210.
    doi: 10.3390/ph15020210google scholar: lookup
  105. Masataka N. Possible effects of cannabidiol (CBD) administration on the vocal activity of healthy domestic dogs upon their temporary separation from caregivers. Heliyon 10:e25548.
    doi: 10.1016/j.heliyon.2024.e25548google scholar: lookup
  106. McGrath S, Bartner LR, Rao S, Kogan LR, Hellyer PW. A report of adverse effects associated with the administration of cannabidiol in healthy dogs. AHVMA J 52:34–38.
  107. McGrath S, Bartner LR, Rao S, Packer RA, Gustafson DL. 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. J Am Vet Med Assoc 254:1301–1308.
    doi: 10.2460/javma.254.11.1301google scholar: lookup
  108. McIver V, Tsang A, Symonds N, Perkins N, Uquillas E, Dart C, Jeffcott L, Dart A. Effects of topical treatment of cannabidiol extract in a unique manuka factor 5 manuka honey carrier on second intention wound healing on equine distal limb wounds: a preliminary study. Aust Vet J 98:250–255.
    doi: 10.1111/avj.12932google scholar: lookup
  109. McPartland JM, Duncan M, Di Marzo V, Pertwee RG. Are cannabidiol and ∆(9) -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. Br J Pharmacol 172:737–753.
    doi: 10.1111/bph.12944pubmed: 25257544pmc: 4301686google scholar: lookup
  110. Mechoulam R. A delightful trip along the pathway of cannabinoid and endocannabinoid chemistry and pharmacology. Annu Rev Pharmacol Toxicol 63:1–13.
    doi: 10.1146/annurev-pharmtox-051921-083709google scholar: lookup
  111. Mechoulam R, Hanuš L. Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects. Chem Phys Lipids 121:35–43.
    doi: 10.1016/S0009-3084(02)00144-5pubmed: 12505688google scholar: lookup
  112. Mejia S, Duerr FM, Griffenhagen G, McGrath S. Evaluation of the effect of cannabidiol on naturally occurring osteoarthritis-associated pain: a pilot study in dogs. J Am Anim Hosp Assoc 57:81–90.
    doi: 10.5326/jaaha-ms-7119google scholar: lookup
  113. Mercati F, DallAglio C, Pascucci L, Boiti C, Ceccarelli P. Identification of cannabinoid type 1 receptor in dog hair follicles. Acta Histochem 114:68–71.
    doi: 10.1016/j.acthis.2011.01.003pubmed: 21414652google scholar: lookup
  114. Meyer K, Hayman K, Baumgartner J, Gorden PJ. Plasma pharmacokinetics of cannabidiol following oral administration of cannabidiol oil to dairy calves. Front Vet Sci 9:789495.
    doi: 10.3389/fvets.2022.789495pubmed: 35141311pmc: 8818876google scholar: lookup
  115. Miagkoff L, Girard CA, St-Jean G, Richard H, Beauchamp G, Laverty S. Cannabinoid receptors are expressed in equine synovium and upregulated with synovitis. Equine Vet J 55:681–695.
    doi: 10.1111/evj.13860pubmed: 35836386google scholar: lookup
  116. Migliaro M, Ruiz-Contreras AE, Herrera-Solís A, Méndez-Díaz M, Prospéro-García OE. Endocannabinoid system and aggression across animal species. Neurosci Biobehav Rev 153:105375.
    doi: 10.1016/j.neubiorev.2023.105375pubmed: 37643683google scholar: lookup
  117. Millar SA, Maguire RF, Yates AS, OSullivan SE. Towards better delivery of cannabidiol (CBD). Pharmaceuticals 13:219.
    doi: 10.3390/ph13090219pubmed: 32872355pmc: 7558665google scholar: lookup
  118. Miragliotta V, Ricci PL, Albanese F, Pirone A, Tognotti D, Abramo F. Cannabinoid receptor types 1 and 2 and peroxisome proliferator-activated receptor‐α: distribution in the skin of clinically healthy cats and cats with hypersensitivity dermatitis. Vet Dermatol 29:316.
    doi: 10.1111/vde.12658google scholar: lookup
  119. Miranda-Cortés A, Mota-Rojas D, Crosignani-Outeda N, Casas-Alvarado A, Martínez-Burnes J, Olmos-Hernández A, Mora-Medina P, Verduzco-Mendoza A, Hernández-Ávalos I. The role of cannabinoids in pain modulation in companion animals. Front Vet Sci 9:1050884.
    doi: 10.3389/fvets.2022.1050884google scholar: lookup
  120. Mogi C, Fukuyama T. Cannabidiol as a potential anti-epileptic dietary supplement in dogs with suspected epilepsy: three case reports. Pet Behav Sci 11–16.
    doi: 10.21071/pbs.v0i7.11800google scholar: lookup
  121. Mogi C, Yoshida M, Kawano K, Fukuyama T, Arai T. Effects of cannabidiol without delta-9-tetrahydrocannabinol on canine atopic dermatitis: a retrospective assessment of 8 cases. Can Veterinary J 63:423.
  122. Morales P, Reggio PH. An update on non-CB1, Non-CB2 cannabinoid related g-protein-coupled receptors. Cannabis Cannabinoid Res 2:265–273.
    doi: 10.1089/can.2017.0036pubmed: 29098189pmc: 5665501google scholar: lookup
  123. Morales P, Lago-Fernandez A, Hurst DP, Sotudeh N, Brailoiu E, Reggio PH, Abood ME, Jagerovic N. Therapeutic exploitation of GPR18: beyond the cannabinoids?. J Med Chem 63:14216–14227.
    doi: 10.1021/acs.jmedchem.0c00926google scholar: lookup
  124. Morris EM, Kitts-Morgan SE, Spangler DM, McLeod KR, Costa JHC, Harmon DL. The impact of feeding Cannabidiol (CBD) containing treats on canine response to a noise-induced fear response test. Front Vet Sci 7:569565.
    doi: 10.3389/fvets.2020.569565google scholar: lookup
  125. Morris EM, Kitts-Morgan SE, Spangler DM, Gebert J, Vanzant ES, McLeod KR, Harmon DL. Feeding cannabidiol (CBD)-containing treats did not affect canine daily voluntary activity. Front Vet Sci 8:645667.
    doi: 10.3389/fvets.2021.645667google scholar: lookup
  126. Nabissi M, Morelli MB, Amantini C, Liberati S, Santoni M, Ricci-Vitiani L, Pallini R, Santoni G. Cannabidiol stimulates Aml-1a-dependent glial differentiation and inhibits glioma stem-like cells proliferation by inducing autophagy in a TRPV2-dependent manner. Int J Cancer 137:1855–1869.
    doi: 10.1002/ijc.29573google scholar: lookup
  127. O’Sullivan SE. An update on PPAR activation by cannabinoids. Br J Pharmacol 173:1899–1910.
    doi: 10.1111/bph.13497pubmed: 27077495pmc: 4882496google scholar: lookup
  128. Panda C, Rathinasabapathy T, Metzger B, Dodson S, Hanson D, Griffiths J, Komarnytsky S. Efficacy and tolerability of full spectrum hemp oil in dogs living with pain in common household settings. Front Vet Sci 11:1384168.
    doi: 10.3389/fvets.2024.1384168google scholar: lookup
  129. Patikorn C, Nerapusee O, Soontornvipart K, Lawonyawut K, Musikpodok K, Waleethanaphan K, Anantachoti P. Efficacy and safety of cannabidiol for the treatment of canine osteoarthritis: a systematic review and meta-analysis of animal intervention studies. Front Vet Sci 10.
    doi: 10.3389/fvets.2023.1248417google scholar: lookup
  130. Pérez-Acevedo A, Busardò F, Pacifici R, Mannocchi G, Gottardi M, Poyatos L, Papaseit E, Pérez-Mañá C, Martin S, Di Trana A, Pichini S, Farré M. Disposition of cannabidiol metabolites in serum and urine from healthy individuals treated with pharmaceutical preparations of medical cannabis. Pharmaceuticals 13:459.
    doi: 10.3390/ph13120459google scholar: lookup
  131. Perucca E, Bialer M. Critical aspects affecting cannabidiol oral bioavailability and metabolic elimination, and related clinical implications. CNS Drugs 34:795–800.
    doi: 10.1007/s40263-020-00741-5pubmed: 32504461google scholar: lookup
  132. Peyravian N, Deo S, Daunert S, Jimenez JJ. Cannabidiol as a novel therapeutic for immune modulation. Immunotargets Ther 9:131–140.
    doi: 10.2147/itt.s263690google scholar: lookup
  133. Pirone A, Lenzi C, Coli A, Giannessi E, Stornelli MR, Miragliotta V. Preferential epithelial expression of type-1 cannabinoid receptor (CB1R) in the developing canine embryo. Springerplus 4:804.
    doi: 10.1186/s40064-015-1616-0google scholar: lookup
  134. Pirone A, Cantile C, Miragliotta V, Lenzi C, Giannessi E, Cozzi B. Immunohistochemical distribution of the cannabinoid receptor 1 and fatty acid amide hydrolase in the dog claustrum. J Chem Neuroanat 74:21–27.
    doi: 10.1016/j.jchemneu.2016.02.002google scholar: lookup
  135. Pirone A, Lenzi C, Briganti A, Abbate F, Levanti M, Abramo F, Miragliotta V. Spatial distribution of cannabinoid receptor 1 and fatty acid amide hydrolase in the cat ovary and oviduct. Acta Histochem 119:417–422.
    doi: 10.1016/j.acthis.2017.04.007google scholar: lookup
  136. Pirone A, Lazzarini G, Lenzi C, Giannessi E, Miragliotta V. Immunolocalization of cannabinoid receptor 1 (CB1), monoglyceride lipase (MGL) and fatty-acid amide hydrolase 1 (FAAH) in the pig claustrum. J Chem Neuroanat 109:101843.
    doi: 10.1016/j.jchemneu.2020.101843google scholar: lookup
  137. Polidoro G, Galiazzo G, Giancola F, Papadimitriou S, Kouki M, Sabattini S, Rigillo A, Chiocchetti R. Expression of cannabinoid and cannabinoid-related receptors in the oral mucosa of healthy cats and cats with chronic gingivostomatitis. J Feline Med Surg 23:679–691.
    doi: 10.1177/1098612x20970510google scholar: lookup
  138. Polidoro D, Temmerman R, Devreese M, Charalambous M, Ham L, Van Cornelis I, Broeckx BJG, Mandigers PJJ, Fischer A, Storch J, Bhatti SFM. Pharmacokinetics of cannabidiol following intranasal, intrarectal, and oral administration in healthy dogs. Front Vet Sci 9:899940.
    doi: 10.3389/fvets.2022.899940google scholar: lookup
  139. Rajan TS, Giacoppo S, Iori R, De Nicola GR, Grassi G, Pollastro F, Bramanti P, Mazzon E. Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages. Fitoterapia 112:104–115.
    doi: 10.1016/j.fitote.2016.05.008google scholar: lookup
  140. Rinaldi V, Boari A, Ressel L, Bongiovanni L, Crisi PE, Cabibbo E, Finotello R. Expression of cannabinoid receptors CB1 and CB2 in canine cutaneous mast cell tumours. Res Vet Sci 152:530–536.
    doi: 10.1016/j.rvsc.2022.09.013google scholar: lookup
  141. Rodríguez-Muñoz M, Onetti Y, Cortés-Montero E, Garzón J, Sánchez-Blázquez P. Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor. Mol Brain 11:51.
    doi: 10.1186/s13041-018-0395-2google scholar: lookup
  142. Rooney TA, Carpenter JW, KuKanich B, Gardhouse SM, Magnin GC, Tully TN. Feeding decreases the oral bioavailability of cannabidiol and cannabidiolic acid in hemp oil in New Zealand White rabbits (Oryctolagus cuniculus). Am J Vet Res 83.
  143. Rozental AJ, Gustafson DL, Kusick BR, Bartner LR, Castro SC, McGrath S. Pharmacokinetics of escalating single-dose administration of cannabidiol to cats. J Vet Pharmacol Ther 46:25–33.
    doi: 10.1111/jvp.13100google scholar: lookup
  144. Rozental AJ, Weisbeck BG, Corsato Alvarenga I, Gustafson DL, Kusick BR, Rao S, Bartner LR, McGrath S. The efficacy and safety of cannabidiol as adjunct treatment for drug-resistant idiopathic epilepsy in 51 dogs: a double‐blinded crossover study. J Vet Intern Med 37:2291–2300.
    doi: 10.1111/jvim.16912google scholar: lookup
  145. Ruel HLM, Monteiro BP, Blais E, Richard H, St-Jean G, Laverty S, Steagall PV. Immunohistochemical localization of cannabinoid receptor type I in the feline synovial membrane with and without degenerative lesions. in Proceedings of the AVA Spring Meeting 2022 pp. 116, Association of Veterinary Anaesthetists (AVA) Spring Meeting (2022), Nafplio, Greece, 18/05/22.
  146. Ruffolo G, Gaeta A, Cannata B, Pinzaglia C, Aronica E, Morano A, Cifelli P, Palma E. GABAergic neurotransmission in human tissues is modulated by cannabidiol. Life 12:2042.
    doi: 10.3390/life12122042google scholar: lookup
  147. Ryan D, McKemie DS, Kass PH, Puschner B, Knych HK. Pharmacokinetics and effects on arachidonic acid metabolism of low doses of cannabidiol following oral administration to horses. Drug Test Anal 13:1305–1317.
    doi: 10.1002/dta.3028google scholar: lookup
  148. Rybarczyk A, Majchrzak-Celińska A, Krajka-Kuźniak V. Targeting Nrf2 signaling pathway in cancer prevention and treatment: the role of cannabis compounds. Antioxid (Basel) 12.
    doi: 10.3390/antiox12122052google scholar: lookup
  149. Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson N-O, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101.
    doi: 10.1038/sj.bjp.0707460google scholar: lookup
  150. Samara E, Bialer M, Mechoulam R. Pharmacokinetics of cannabidiol in dogs. Drug Metab Dispos 16:469–472.
  151. Samara E, Bialer M, Harvey DJ. Pharmacokinetics of urinary metabolites of cannabidiol in the dog. Biopharm Drug Dispos 11:785–795.
    doi: 10.1002/bdd.2510110906google scholar: lookup
  152. Sánchez De Medina A, Serrano-Rodríguez JM, Díez De Castro E, García-Valverde MT, Saitua A, Becero M, Muñoz A, Ferreiro-Vera C, Sánchez De Medina V. Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations. Equine Vet J 55:1094–1103.
    doi: 10.1111/evj.13923google scholar: lookup
  153. Schaefer N, Wojtyniak J-G, Kettner M, Schlote J, Laschke MW, Ewald AH, Lehr T, Menger MD, Maurer HH, Schmidt PH. Pharmacokinetics of (synthetic) cannabinoids in pigs and their relevance for clinical and forensic toxicology. Toxicol Lett 253:7–16.
    doi: 10.1016/j.toxlet.2016.04.021google scholar: lookup
  154. Schaefer N, Kettner M, Laschke MW, Schlote J, Ewald AH, Menger MD, Maurer HH, Schmidt PH. Distribution of synthetic cannabinoids JWH-210, RCS-4 and ∆ 9-Tetrahydrocannabinol after intravenous administration to pigs. Curr Neuropharmacol 15.
    doi: 10.2174/1570159x15666161111114214google scholar: lookup
  155. Senn L, Cannazza G, Biagini G. Receptors and channels possibly mediating the effects of phytocannabinoids on seizures and epilepsy. Pharmaceuticals (Basel Switzerland) 13:174.
    doi: 10.3390/ph13080174google scholar: lookup
  156. Sermet S, Li J, Bach A, Crawford RB, Kaminski NE. Cannabidiol selectively modulates interleukin (IL)-1β and IL-6 production in toll-like receptor activated human peripheral blood monocytes. Toxicology 464.
    doi: 10.1016/j.tox.2021.153016google scholar: lookup
  157. Shilo-Benjamini Y, Cern A, Zilbersheid D, Hod A, Lavy E, Barasch D, Barenholz Y. A case report of subcutaneously injected liposomal cannabidiol formulation used as a compassion therapy for pain management in a dog. Front Vet Sci 9:892306.
    doi: 10.3389/fvets.2022.892306google scholar: lookup
  158. Shilo-Benjamini Y, Lavy E, Yair N, Milgram J, Zilbersheid D, Hod A, Barasch D, Abu Ahmad W, Cern A, Barenholz Y. Therapeutic efficacy and pharmacokinetics of liposomal-cannabidiol injection: a pilot clinical study in dogs with naturally-occurring osteoarthritis. Front Vet Sci 10.
    doi: 10.3389/fvets.2023.1224452google scholar: lookup
  159. Silver RJ. The endocannabinoid system of animals. Animals 9:686.
    doi: 10.3390/ani9090686google scholar: lookup
  160. Simpson AC, Bradley CW, Schissler JR. Probable cutaneous adverse drug reaction due to a cannabidiol-containing hemp oil product in a dog. Vet Dermatol 31:404.
    doi: 10.1111/vde.12876google scholar: lookup
  161. Sitovs A, Logviss K, Lauberte L, Mohylyuk V. Oral delivery of cannabidiol: revealing the formulation and absorption challenges. J Drug Deliv Sci Technol 92:105316.
    doi: 10.1016/j.jddst.2023.105316google scholar: lookup
  162. Soga T, Ohishi T, Matsui T, Saito T, Matsumoto M, Takasaki J, Matsumoto SI, Kamohara M, Hiyama H, Yoshida S, Momose K, Ueda Y, Matsushime H, Kobori M, Furuichi K. Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor. Biochem Biophys Res Commun 326:744–751.
    doi: 10.1016/j.bbrc.2004.11.120google scholar: lookup
  163. Sosa-Higareda M, Guzman DS-M, Knych H, Lyubimov A, Zakharov A, Gomez B, Beaufrère H. Twice-daily oral administration of a cannabidiol and cannabidiolic acidrich hemp extract was well tolerated in orange-winged Amazon parrots (Amazona amazonica) and has a favorable pharmacokinetic profile. Am J Vet Res 1–11.
    doi: 10.2460/ajvr.22.11.0197google scholar: lookup
  164. St. Blanc MP, Chapman AM, Keowen ML, Garza F, Liu C-C, Gray L, Andrews FM. Effects of a supplement containing cannabidiol (CBD) on sedation and ataxia scores and health. J Equine Vet Sci 117:104085.
    doi: 10.1016/j.jevs.2022.104085google scholar: lookup
  165. Stanzani A, Galiazzo G, Giancola F, Tagliavia C, De Silva M, Pietra M, Fracassi F, Chiocchetti R. Localization of cannabinoid and cannabinoid related receptors in the cat gastrointestinal tract. Histochem Cell Biol 153:339–356.
    doi: 10.1007/s00418-020-01854-0google scholar: lookup
  166. Starkus J, Jansen C, Shimoda LMN, Stokes AJ, Small-Howard AL, Turner H. Diverse TRPV1 responses to cannabinoids. Channels (Austin) 13:172–191.
    doi: 10.1080/19336950.2019.1619436pubmed: 31096838google scholar: lookup
  167. Stevens SA, Krebs GL, Scrivener CJ, Noble GK, Blake BL, Dods KC, May CD, Tai ZX, Clayton EH, Lynch EE, Johnson KN. Nutrient digestibility, rumen parameters, and (cannabinoid) residues in sheep fed a pelleted diet containing green hemp (Cannabis sativa L.) biomass. Transl Anim Sci 6:txac141.
    doi: 10.1093/tas/txac141google scholar: lookup
  168. Stincic TL, Hyson RL. Localization of CB1 cannabinoid receptor mRNA in the brain of the chick (Gallus Domesticus). Brain Res 1245:61–73.
    doi: 10.1016/j.brainres.2008.09.037google scholar: lookup
  169. Taylor L, Gidal B, Blakey G, Tayo B, Morrison G. A phase I, randomized, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect trial of the safety, tolerability and pharmacokinetics of highly purified cannabidiol in healthy subjects. CNS Drugs 32:1053–1067.
    doi: 10.1007/s40263-018-0578-5google scholar: lookup
  170. Thomson ACS, McCarrel TM, Zakharov A, Gomez B, Lyubimov A, Schwark WS, Mallicote MF, Portela DA, Bisiau AL, Wakshlag JJ. Pharmacokinetics and tolerability of single-dose enteral cannabidiol and cannabidiolic acid rich hemp in horses (Equus caballus). Front Vet Sci 11:1356463.
    doi: 10.3389/fvets.2024.1356463pubmed: 38681854pmc: 11047043google scholar: lookup
  171. Tittle D, Wakshlag J, Schwark W, Lyubimov A, Zakharov A, Gomez B. Twenty-four hour and one-week steady state pharmacokinetics of cannabinoids in two formulations of cannabidiol and cannabidiolic acid rich hemp in dogs. Med Res Arch 10.
    doi: 10.18103/mra.v10i7.2907google scholar: lookup
  172. Toschi A, Galiazzo G, Piva A, Tagliavia C, Mazzuoli-Weber G, Chiocchetti R, Grilli E. Cannabinoid and cannabinoid-related receptors in the myenteric plexus of the porcine ileum. Animals 11:263.
    doi: 10.3390/ani11020263google scholar: lookup
  173. Turner SE, Knych HK, Adams AA. Pharmacokinetics of cannabidiol in a randomized crossover trial in senior horses. Am J Vet Res 83.
    doi: 10.2460/ajvr.22.02.0028google scholar: lookup
  174. Turner S, Knych HK, Adams AA. The effects of cannabidiol on immune function and health parameters in senior horses. Vet Immunol Immunopathol 257:110549.
    doi: 10.1016/j.vetimm.2023.110549google scholar: lookup
  175. Vaughn D, Kulpa J, Paulionis L. Preliminary investigation of the safety of escalating cannabinoid doses in healthy dogs. Front Vet Sci 7:51.
    doi: 10.3389/fvets.2020.00051pubmed: 32118071pmc: 7029731google scholar: lookup
  176. Vaughn DM, Paulionis LJ, Kulpa JE. Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs. Am J Vet Res 82:405–416.
    doi: 10.2460/ajvr.82.5.405pubmed: 33904801google scholar: lookup
  177. Verrico CD, Wesson S, Konduri V, Hofferek CJ, Vazquez-Perez J, Blair E, Dunner K, Salimpour P, Decker WK, Halpert MM. A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain. Pain 161:2191–2202.
    doi: 10.1097/j.pain.0000000000001896pubmed: 32345916pmc: 7584779google scholar: lookup
  178. Vrechi TAM, Leão AHFF, Morais IBM, Abílio VC, Zuardi AW, Hallak JEC, Crippa JA, Bincoletto C, Ureshino RP, Smaili SS, Pereira GJS. Cannabidiol induces autophagy via ERK1/2 activation in neural cells. Sci Rep 11:5434.
    doi: 10.1038/s41598-021-84879-2google scholar: lookup
  179. Wagner B, Gerletti P, Fürst P, Keuth O, Bernsmann T, Martin A, Schäfer B, Numata J, Lorenzen MC, Pieper R. Transfer of cannabinoids into the milk of dairy cows fed with industrial hemp could lead to ∆9-THC exposure that exceeds acute reference dose. Nat Food 3:921–932.
    doi: 10.1038/s43016-022-00623-7google scholar: lookup
  180. Wakshlag JJ, Schwark WS, Deabold KA, Talsma BN, Cital S, Lyubimov A, Iqbal A, Zakharov A. Pharmacokinetics of cannabidiol, cannabidiolic acid, ∆9-Tetrahydrocannabinol, tetrahydrocannabinolic acid and related metabolites in canine serum after dosing with three oral forms of hemp extract. Front Vet Sci 7:505.
    doi: 10.3389/fvets.2020.00505google scholar: lookup
  181. Wang T, Zakharov A, Gomez B, Lyubimov A, Trottier NL, Schwark WS, Wakshlag JJ. Serum cannabinoid 24 h and 1 week steady state pharmacokinetic assessment in cats using a CBD/CBDA rich hemp paste. Front Vet Sci 9:895368.
    doi: 10.3389/fvets.2022.895368google scholar: lookup
  182. Whyte LS, Ryberg E, Sims NA, Ridge SA, Mackie K, Greasley PJ, Ross RA, Rogers MJ. The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc Natl Acad Sci 106:16511–16516.
    doi: 10.1073/pnas.0902743106google scholar: lookup
  183. Williams MR, Holbrook TC, Maxwell L, Croft CH, Ientile MM, Cliburn K. Pharmacokinetic evaluation of a cannabidiol supplement in horses. J Equine Vet Sci 110:103842.
    doi: 10.1016/j.jevs.2021.103842google scholar: lookup
  184. Wright J. Evaluating the benefits of cannabidiol for analgesia following surgery for intervertebral disc herniation in dogs. Proceedings of the American College of Veterinary Internal Medicine Forum 2022.
  185. Ye L, Cao Z, Wang W, Zhou N. New insights in cannabinoid receptor structure and signaling. Curr Mol Pharmacol 12:239–248.
    doi: 10.2174/1874467212666190215112036google scholar: lookup
  186. Yocom AF, O’Fallon ES, Gustafson DL, Contino EK. Pharmacokinetics, safety, and synovial fluid concentrations of single- and multiple-dose oral administration of 1 and 3 mg/kg cannabidiol in horses. J Equine Vet Sci 113:103933.
    doi: 10.1016/j.jevs.2022.103933google scholar: lookup
  187. Zamith Cunha R, Salamanca G, Mille F, Delprete C, Franciosi C, Piva G, Gramenzi A, Chiocchetti R. Endocannabinoid system receptors at the hip and stifle joints of middle-aged dogs: a novel target for the therapeutic use of cannabis sativa extract in canine arthropathies. Animals 13:2833.
    doi: 10.3390/ani13182833google scholar: lookup
  188. Zamith Cunha R, Semprini A, Salamanca G, Gobbo F, Morini M, Pickles KJ, Roberts V, Chiocchetti R. Expression of cannabinoid receptors in the trigeminal ganglion of the horse. Int J Mol Sci 24:15949.
    doi: 10.3390/ijms242115949google scholar: lookup
  189. Zamith Cunha R, Zannoni A, Salamanca G, De Silva M, Rinnovati R, Gramenzi A, Forni M, Chiocchetti R. Expression of cannabinoid (CB1 and CB2) and cannabinoid-related receptors (TRPV1, GPR55, and PPARα) in the synovial membrane of the horse metacarpophalangeal joint. Front Vet Sci 10:1045030.
    doi: 10.3389/fvets.2023.1045030google scholar: lookup
  190. Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci 19:833.
    doi: 10.3390/ijms19030833google scholar: lookup

Citations

This article has been cited 7 times.
  1. Zamith Cunha R, Gobbo F, Morini M, Salamanca G, Zanoni A, Bernardini C, Gramenzi A, Chiocchetti R. Cannabinoid and cannabinoid related receptors in fibroblasts, inflammatory and endothelial cells of the equine hoof with and without laminitis: novel pharmacological target. Front Vet Sci 2025;12:1723160.
    doi: 10.3389/fvets.2025.1723160pubmed: 41394912google scholar: lookup
  2. Serrano-Rodríguez JM, Miraz R, Saitua A, Díez de Castro E, Ledesma-Escobar C, Ferreiro-Vera C, Priego-Capote F, Sánchez de Medina V, Sánchez de Medina A. Metabolism, pharmacokinetics, and bioavailability of cannabigerol in horses following intravenous and oral administration with micellar and oil formulations. Front Vet Sci 2025;12:1688214.
    doi: 10.3389/fvets.2025.1688214pubmed: 41234397google scholar: lookup
  3. Kongkeaw A, Tartrakoon W, Numthuam S, Incharoen T, Hwanhlem N, Loor JJ, Charoensook R. Medium-Chain Triglyceride Emulsion with Phytocannabinoids and Monolaurin Improves Growth and Survival in Suckling Piglets. Animals (Basel) 2025 Oct 1;15(19).
    doi: 10.3390/ani15192881pubmed: 41096476google scholar: lookup
  4. Della Rocca G, Di Salvo A, Salucci E, Amadori M, Re G, Vercelli C. The Role of the Endocannabinoid System in Oncology and the Potential Use of Cannabis Derivatives for Cancer Management in Companion Animals. Animals (Basel) 2025 Jul 24;15(15).
    doi: 10.3390/ani15152185pubmed: 40804975google scholar: lookup
  5. Bazzano M, Laus F, Cerquetella M, Spaterna A, Marchegiani A. Effect of orally administered cannabidiol oil on daily tonometric curve in healthy Italian Saddle horses. PLoS One 2025;20(5):e0325191.
    doi: 10.1371/journal.pone.0325191pubmed: 40435047google scholar: lookup
  6. Temmerman R. Editorial: Use of cannabis derivatives in veterinary medicine. Front Vet Sci 2025;12:1539422.
    doi: 10.3389/fvets.2025.1539422pubmed: 40125319google scholar: lookup
  7. Di Salvo A, Bazzano M, Rocca GD, Galarini R, Marchegiani A, Paoletti F, Giusepponi D, Mantovani M, Laus F. Pharmacokinetics of a single oral administration of two cannabidiol formulations in fed and fasted horses. Front Vet Sci 2025;12:1515833.
    doi: 10.3389/fvets.2025.1515833pubmed: 40046423google scholar: lookup
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