The endocannabinoid system in canine Steroid-Responsive Meningitis-Arteritis and Intraspinal Spirocercosis

Freundt-Revilla, Jessica; Heinrich, Franciska; Zoerner, Alexander A.; Gesell, Felix K; Beyerbach, Martin; Shamir, Merav H.; Oevermann, Anna; Baumgärtner, Wolfgang; Tipold, Andrea

doi:10.1371/journal.pone.0187197

Cited by 21 publications

(20 citation statements)

References 95 publications

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“…Given the interest to evaluate whether this phytocannabinoid-based medicine has beneficial effects on different central and peripheral canine disorders, the pharmacokinetic profile of Sativex, when administered via sublingual delivery to naïve dogs, has been determined. This may help to determine the best dosage and timing for the future evaluation of Sativex in dogs affected by different pathologies (e.g., osteoarthritis [19], atopic dermatitis [20], epilepsy [21], degenerative myelopathy [22], some neuroinflammatory diseases (meningitis-asteritis and intraspinal spirocercosis) [23], and others [24]), although the effect that different pathologies may have on Sativex pharmacokinetics remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathological conditions. This may include pathologies as osteoarthritis [19], atopic dermatitis [20], epilepsy [21], degenerative myelopathy [22], some neuroinflammatory diseases (meningitis-asteritis and intraspinal spirocercosis) [23], and others [24]. It is important to remark that the information collected in studies with dogs with these pathologies is not only important for the development of Sativex in Veterinary Medicine but also for their equivalents in the human pathologies, thus representing suitable translational models for studying specific human pathologies.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders

et al. 2020

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The phytocannabinoid-based medicine Sativex ® is currently marketed for the treatment of spasticity and pain in multiple sclerosis patients and is being investigated for other central and peripheral pathological conditions. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathologies, including human-like pathological conditions. With the purpose of assessing different dosing paradigms for using Sativex in Veterinary Medicine, we investigated its pharmacokinetics when administered to naïve dogs via sublingual delivery. In the single dose arm of the study, adult Beagle dogs were treated with 3 consecutive sprays of Sativex, and blood samples were collected at 12 intervals up to 24 h later. In the multiple dose arm of the study, Beagle dogs received 3 sprays daily for 14 days, and blood samples were collected for 24 h post final dose. Blood was used to obtain plasma samples and to determine the levels of cannabidiol (CBD), ∆ 9 -tetrahydrocannabinol (∆ 9 -THC) and its metabolite 11-hydroxy-∆ 9 -THC. Maximal plasma concentrations of both ∆ 9 -THC (C max = 18.5 ng/mL) and CBD (C max = 10.5 ng/mL) were achieved 2 h after administration in the single dose condition and at 1 h in the multiple dose treatment (∆ 9 -THC: C max = 24.5 ng/mL; CBD: C max = 15.2 ng/mL). 11-hydroxy-∆ 9 -THC, which is mainly formed in the liver from ∆ 9 -THC, was almost undetected, which is consistent with the use of sublingual delivery. A potential progressive accumulation of both CBD and ∆ 9 -THC was detected following repeated exposure, with maximum plasma concentrations for both cannabinoids being achieved following multiple dose. Neurological status, body temperature, respiratory rate and some hemodynamic parameters were also recorded in both conditions, but in general, no changes were observed. In conclusion, this study demonstrates that single or multiple dose sublingual administration of Sativex to naïve dogs results in the expected pharmacokinetic profile, with maximal levels of phytocannabinoids detected at 1-2 h and suggested progressive accumulation after the multiple dose treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders

et al. 2020

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“…It is now clear that PEA is an endocannabinoid-related compound, sharing metabolic pathways and targets with the endocannabinoid system, which is now considered to play an integral role in maintaining body homeostasis [ 94 ]. Most notably, the heterogeneous family of canonical and putative cannabinoid receptors, i.e., PEA targets, are being extensively studied in companion animals and their distribution has been found in several body tissues [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 ]. Table 2 provides a summary of the main results.…”

Section: Pea Mechanism Of Action: a Multitarget Redundancymentioning

confidence: 99%

“…A glance over cannabinoid receptor distribution in dogs and cats[95][96][97][98][99][100][101][102][103][104][105][106][107][108][109].…”

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confidence: 99%

Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing

Gugliandolo

Peritore

Piras

et al. 2020

Veterinary Sciences

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Virtually every cellular process is affected by diet and this represents the foundation of dietary management to a variety of small animal disorders. Special attention is currently being paid to a family of naturally occurring lipid amides acting through the so-called autacoid local injury antagonism, i.e., the ALIA mechanism. The parent molecule of ALIAmides, palmitoyl ethanolamide (PEA), has being known since the 1950s as a nutritional factor with protective properties. Since then, PEA has been isolated from a variety of plant and animal food sources and its proresolving function in the mammalian body has been increasingly investigated. The discovery of the close interconnection between ALIAmides and the endocannabinoid system has greatly stimulated research efforts in this field. The multitarget and highly redundant mechanisms through which PEA exerts prohomeostatic functions fully breaks with the classical pharmacology view of “one drug, one target, one disease”, opening a new era in the management of animals’ health, i.e., an according-to-nature biomodulation of body responses to different stimuli and injury. The present review focuses on the direct and indirect endocannabinoid receptor agonism by PEA and its analogues and also targets the main findings from experimental and clinical studies on ALIAmides in animal health and wellbeing.

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“…During the analysis of low interleukin 2 (IL-2) and interferon-γ (INF-γ) concentrations, elevated interleukin 4 (IL-4) concentrations in CSF leucocytes and in mononuclear cells of the peripheral blood were found indicative for the presence of a Th2-dominant immune response [28]. Furthermore, current studies indicate that other cytokines such as the vascular endothelial growth factor (VEGF), the transforming growth factor 1 (TFG1), interleukin 6 (IL-6) and interleukin 17 (IL-7) played a crucial role in the pathogenesis of SRMA [10] [19]. Until now no final trigger has been identified in this pathogenesis.…”

mentioning

confidence: 84%

Steroid-responsive meningitis-arteritis in dogs in Germany: Are there epidemiological or clinical factors influencing recurrence rate?

Hilpert

Tipold

Meyerhoff

et al. 2020

Tierarztl Prax Ausg K

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Objective Steroid-responsive meningitis arteritis (SRMA) is one of the most common inflammatory diseases of the central nervous system in dogs. The present study examined breed and sex predisposition factors based on the population of dogs in Germany as well as epidemiological and clinical factors regarding the relapse rate of SRMA. Material and methods Data of 153 dogs with SRMA (SRMA) were analysed retrospectively in this multicentre study. It was investigated whether some dog breeds that suffer from SRMA were disproportionately more often (n ≥ 5) represented when compared to the total population of dogs in Germany. Furthermore it was examined which sex is affected more often. Data provided by “Verband für das deutsche Hundewesen“ (VDH) and „Tasso e. V.“ was used as reference data of the total population. The following factors were investigated with regard to the occurrence of one or more relapses: signalment; body weight; age at first presentation; time period between last vaccination and onset of clinical signs; clinical signs and timepoint of the first SRMA manifestation; results of cerebrospinal fluid (CSF) analysis at first presentation (nucleated cell count and differentiation, protein concentration); immunglobulin A and C-reactive protein (CRP) concentrations in serum and CSF; immunosuppressive medication; follow-up data including response to therapy, occurrence of relapses and mortality including reasons, i. e. due to the disease, therapy or euthanasia. Results The breed had a statistically significant influence on the development of SRMA (p < 0.05). Beagles and Boxers were affected more often by SRMA than other breeds in relation to the total population in Germany. Relapses occurred in 29.4 % of the 153 dogs of this study. In contrast to the development of SRMA, in which male dogs have a significantly increased risk of developing SRMA (p < 0.05), female dogs are more likely to relapse (p = 0.02). Patients on prednisolone monotherapy had fewer relapses than those with prednisolone and azathioprine in combination (p < 0.05). Younger age (p = 0.071) und lower CRP concentrations (p = 0.081) at first presentation were tentatively associated with a higher incidence of relapses. Conclusion The determined breed and sex predispositions support the diagnosis of SRMA arteritis and confirm previous observations. This study allows a more accurate explanation to owners about the risk of relapse.

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The endocannabinoid system in canine Steroid-Responsive Meningitis-Arteritis and Intraspinal Spirocercosis

Cited by 21 publications

References 95 publications

Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders

Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders

Palmitoylethanolamide and Related ALIAmides: Prohomeostatic Lipid Compounds for Animal Health and Wellbeing

Steroid-responsive meningitis-arteritis in dogs in Germany: Are there epidemiological or clinical factors influencing recurrence rate?

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