Pharmacokinetics of escalating single-dose administration of cannabidiol to cats.

This study aimed to assess the single-dose pharmacokinetics and tolerability of a cannabidiol (CBD) isolate in sunflower oil with escalating oral doses in eight healthy, purpose-bred cats. Eight cats were randomized into six dosing groups of four cats each. Cats were administered a single 2.5, 5, 10, 20, 40, or 80 mg/kg dose orally with at least a two-week washout in between doses. Behavior scoring, complete blood count, serum biochemistry analysis, physical examination, and CBD plasma levels were evaluated before and after dosing. All cats successfully completed the study. CBD was measured in the plasma of all cats dosed with CBD oil. The Cmax and AUC increased in a dose-proportional fashion across all dosing groups. There were no major bloodwork or behavioral changes although the BUN and creatinine values decreased after treatment across all doses. No adverse effects were observed, and behavioral changes were limited to head shaking, lip smacking, and hypersalivation immediately following dose administration. Single orally administered CBD doses up to 80 mg/kg were safe and well tolerated in this cohort of cats and display dose-proportional pharmacokinetics across a broad concentration.

Thoracolumbar myelopathies in pug dogs.

BACKGROUND: Constrictive myelopathy (CM) involving a fibrous band around the spinal cord is a newly recognized disease in pug dogs. OBJECTIVES: To identify the frequency of CM based on diagnostic imaging supplemented with necropsy; to determine whether a relationship exists between the sites of CM and other described T3-L3 myelopathies; and to determine the frequency of caudal articular process dysplasia (CAPD). ANIMALS: Thirty-two client-owned pug dogs diagnosed with a chronic, progressive T3-L3 myelopathy based on neurological examination performed by a board-certified neurologist. METHODS: This is a prospective study. All dogs underwent computed tomography (CT) and magnetic resonance imaging (MRI) reviewed by a board-certified radiologist. Magnetic resonance imaging abnormalities were categorized into diseases; CM only, CM plus other non-CM condition(s), or non-CM condition. Sites of CAPD were reported on CT. Nineteen dogs underwent necropsy. RESULTS: Magnetic resonance imaging revealed 3 dogs with CM only, 17 with CM plus at least 1 other myelopathy, 11 dogs with non-CM myelopathies only, and 1 with no MRI abnormalities. Nineteen of 32 dogs had >1 myelopathy diagnosis on MRI whereas 15/32 had >1 site of spinal cord compression. All dogs had CAPD at >1 site in the T3-L3 vertebral column on CT. CONCLUSIONS AND CLINICAL IMPORTANCE: Constrictive myelopathy affected more than half of pug dogs presenting with chronic thoracolumbar myelopathies. Most had multilevel disease, concurrent myelopathies, or both. There was no apparent relationship between anatomic locations of CAPD and most severe myelopathy or myelopathy type.

The efficacy and safety of cannabidiol as adjunct treatment for drug-resistant idiopathic epilepsy in 51 dogs: A double-blinded crossover study.

BACKGROUND: Approximately 30% of dogs with idiopathic epilepsy (IE) are drug-resistant. Recent studies have suggested cannabidiol (CBD) may be an effective anticonvulsant in dogs with IE. OBJECTIVE: To evaluate the addition of CBD to antiseizure drugs (ASDs) on seizure frequency and to report adverse events in dogs with drug-resistant IE. ANIMALS: Fifty-one dogs. Dogs having at least 2 seizures per month while receiving at least 1 ASD were included in the trial. METHODS: Double-blinded placebo-controlled crossover study. The 5 mg/kg/day dosage met futility requirements after 12 dogs, and a dosage of 9 mg/kg/day was used in the next 39 dogs. Dogs were randomly assigned to receive CBD or placebo for 3 months, with a 1-month washout period between oils. Total numbers of seizures and seizure days were recorded. Diagnostic testing was performed periodically throughout the trial. RESULTS: At the 9 mg/kg/day dose, the decrease in total seizure frequency was significant compared with placebo. A 24.1% decrease in seizure days occurred in dogs receiving CBD and a 5.8% increase occurred in dogs receiving placebo (P ≤ .05). No significant difference was found in the number of responders (≥50% decrease in total seizures or seizure days). Liver enzyme activities increased at both dosages. Decreased appetite and vomiting were more common in the CBD phase (P ≤ .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Cannabidiol decreased total seizures and seizure days compared to placebo when administered to dogs PO at 9 mg/kg/day. Liver enzymes should be monitored with administration of CBD in dogs.

What Is Your Diagnosis?

In collaboration with the American College of Veterinary Radiology.

Drug-drug interaction between cannabidiol and phenobarbital in healthy dogs.

OBJECTIVE: To assess drug-drug interactions between cannabidiol (CBD) and phenobarbital (PB) when simultaneously administered to healthy dogs. ANIMALS: 9 healthy, purpose bred Beagles. PROCEDURES: A 3-phase prospective, randomized pharmacokinetic (PK) interaction study of CBD and PB was performed as follows: phase 1, CBD PK determination and evaluation of CBD tolerability by 3 single-dose CBD (5 mg/kg, 10 mg/kg, and 20 mg/kg) protocols followed by 2-week CBD dosing; phase 2, a single-dose, 3-way, crossover PK study of CBD (10 mg/kg), PB (4 mg/kg), or CBD (10 mg/kg) administration plus PB (4 mg/kg); and phase 3, evaluation of chronic PB (4 mg/kg, q 30 d) administration followed by single-dose CBD (10 mg/kg) PK study. RESULTS: Although there were variations in CBD PK variables in dogs receiving CBD alone or in conjunction with PB, significance differences in CBD PK variables were not found. No significant difference was observed in PB PK variables of dogs receiving PB alone or with CBD. During chronic CBD administration, mild gastrointestinal signs were observed in 5 dogs. At daily CBD doses of 10 to 20 mg/kg/d, hypoxia was observed in 5 dogs and increased serum alkaline phosphatase (ALP) activities (range, 301 to 978 U/L) was observed in 4 dogs. A significant increase in ALP activity was observed with chronic administration of CBD during phase 1 between day 0 and day 14. CONCLUSIONS AND CLINICAL RELEVANCE: No significant PK interactions were found between CBD and PB. Dose escalation of CBD or adjustment of PB in dogs is not recommended on the basis of findings of this study.

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.

OBJECTIVE: To assess the effect of oral cannabidiol (CBD) administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with idiopathic epilepsy. DESIGN: Randomized blinded controlled clinical trial. ANIMALS: 26 client-owned dogs with intractable idiopathic epilepsy. PROCEDURES: Dogs were randomly assigned to a CBD (n = 12) or placebo (14) group. The CBD group received CBD-infused oil (2.5 mg/kg [1.1 mg/lb], PO) twice daily for 12 weeks in addition to existing antiepileptic treatments, and the placebo group received noninfused oil under the same conditions. Seizure activity, adverse effects, and plasma CBD concentrations were compared between groups. RESULTS: 2 dogs in the CBD group developed ataxia and were withdrawn from the study. After other exclusions, 9 dogs in the CBD group and 7 in the placebo group were included in the analysis. Dogs in the CBD group had a significant (median change, 33%) reduction in seizure frequency, compared with the placebo group. However, the proportion of dogs considered responders to treatment (≥ 50% decrease in seizure activity) was similar between groups. Plasma CBD concentrations were correlated with reduction in seizure frequency. Dogs in the CBD group had a significant increase in serum alkaline phosphatase activity. No adverse behavioral effects were reported by owners. CONCLUSIONS AND CLINICAL RELEVANCE: Although a significant reduction in seizure frequency was achieved for dogs in the CBD group, the proportion of responders was similar between groups. Given the correlation between plasma CBD concentration and seizure frequency, additional research is warranted to determine whether a higher dosage of CBD would be effective in reducing seizure activity by ≥ 50%.

Pharmacokinetics of cannabidiol administered by 3 delivery methods at 2 different dosages to healthy dogs.

The purpose of this study was to determine the pharmacokinetics of cannabidiol (CBD) in healthy dogs. Thirty, healthy research dogs were assigned to receive 1 of 3 formulations (oral microencapsulated oil beads, oral CBD-infused oil, or CBD-infused transdermal cream), at a dose of 75 mg or 150 mg q12h for 6 wk. Serial cannabidiol plasma concentrations were measured over the first 12 h and repeated at 2, 4, and 6 wk. Higher systemic exposures were observed with the oral CBD-infused oil formulation and the half-life after a 75-mg and 150-mg dose was 199.7 ± 55.9 and 127.5 ± 32.2 min, respectively. Exposure is dose-proportional and the oral CBD-infused oil provides the most favorable pharmacokinetic profile.

Le but de la présente étude était de déterminer la pharmacocinétique du cannbidiol (CBD) chez des chiens en santé. Trente chiens de recherche en santé ont été assignés à recevoir une des trois formulations (de l'huile micro-encapsulé dans des billes par voie orale, de l'huile infusé de CBD par voie orale, ou une crème infusée de CBD par voie transdermique), à une dose de 75 mg ou 150 mg q12h pendant 6 semaines. Les concentrations plasmatiques de cannabidiol ont été mesurées pendant les 12 premières heures et répétées après 2, 4 et 6 semaines. Les expositions systémiques les plus élevées ont été observées avec la formulation d'huile infusé de CBD administrée par voie orale et la demi-vie après une dose de 75 mg et de 150 mg était de 199,7 ± 55,9 et 127,5 ± 32,2 min, respectivement. L'exposition est proportionnelle à la dose et l'huile infusée de CBD par voie orale fournie le profile pharmacocinétique le plus favorable.(Traduit par Docteur Serge Messier).

Testing for Bartonella ssp. DNA in cerebrospinal fluid of dogs with inflammatory central nervous system disease.

BACKGROUND: Neurobartonellosis occurs in people. The role these organisms might play in inflammatory brain disease of dogs is unclear. HYPOTHESIS/OBJECTIVES: That Bartonella spp. DNA would be amplified more commonly from the CSF of dogs with inflammatory disease compared to those with noninflammatory disease. To report the prevalence of Bartonella spp. in dogs with and without inflammatory CNS disease with a commercially available PCR assay. ANIMALS: Cerebrospinal fluid (CSF) samples from 172 dogs from either Washington State University or Colorado State University. METHODS: Retrospective study. A search was performed of all medical records from dogs with CSF samples submitted to CSU's Center for Companion Animal Studies or Veterinary Diagnostic Laboratory from CSU or WSU for Toxoplasma or Neospora PCR assay. Increased CSF nucleated cell counts and an adequate volume of CSF must have been present to evaluate Bartonella spp. by PCR assay. RESULTS: Inflammatory CNS disease was confirmed in 65 dogs, none of which were positive for Bartonella spp. DNA. Of the other 107 dogs, one was positive for B. henselae DNA. The CSF from this dog contained red blood cells. CONCLUSIONS AND CLINICAL IMPORTANCE: Failure to amplify Bartonella spp. DNA from the CSF of the dogs with inflammatory disease suggests the organism was not involved in the etiology of the disease, the organism was in the CNS tissues but not in the CSF, or the organism was present but in quantities undetectable by this PCR assay. The combination of PCR and culture is the most sensitive way to detect Bartonella spp. and the use of that technique should be considered in future studies.

Persistent mucus accumulation: a consequence of delayed bronchial mucous cell apoptosis in RAO-affected horses?

This study examined the contribution of delayed apoptosis of bronchial mucous cells to mucus accumulation in equine recurrent airway obstruction (RAO). In pilot studies, Bcl-2, an apoptosis inhibitor, was detected in airway mucous cells of RAO-affected horses in remission and during acute disease, when most mucus was secreted. To study whether delayed apoptosis results in an increase in the number of mucous cells during disease recovery, six RAO-affected and six control horses were fed hay for 5 days to induce inflammation and then pellets for 7 days to partially resolve RAO before euthanasia. RAO-affected horses had more airway obstruction and luminal mucus than control horses under both management systems. At the time of euthanasia, RAO-affected horses had more inflammation and Bcl-2-positive bronchial mucous cells than control animals. In horses with >10 and <10 neutrophils per microliter of bronchoalveolar lavage fluid, >50% and <10% of mucous cells stained positive for Bcl-2, respectively. No differences in mucous cell number or amount of stored mucosubstance were observed between RAO-affected and control horses, but in RAO-affected animals, the amount of stored mucosubstance decreased as the number of neutrophils in bronchoalveolar lavage fluid increased. Because the number of mucous cells was similar in both groups of horses but only mucous cells of RAO-affected horses expressed Bcl-2 during recovery from acute disease, a conclusive role for Bcl-2 in prolonging bronchial mucous cell life could not be determined. Future studies are needed to compare horses that are kept in remission for prolonged periods when all mucous cells are fully developed.