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.

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.

Reprogramming the Canine Glioma Microenvironment with Tumor Vaccination plus Oral Losartan and Propranolol Induces Objective Responses.

Purpose: Malignant gliomas have a highly immune suppressive tumor microenvironment (TME) which renders them largely unresponsive to conventional therapeutics. Therefore, the present study evaluated a therapeutic protocol designed overcome the immune barrier by combining myeloid cell targeted immunotherapy with tumor vaccination. Experimental Design: We utilized a spontaneously occurring canine glioma model to investigate an oral TME modifying immunotherapy in conjunction with cancer stem cell (CSC) vaccination. Dogs were treated daily with losartan (monocyte migration inhibitor) and propranolol (myeloid-derived suppressor cell depleting agent) plus anti-CSC vaccination on a bi-weekly then monthly schedule. Tumor volume was monitored by MRI and correlated with patient immune responses. Results: Ten dogs with histologically confirmed gliomas were enrolled into a prospective, open-label clinical trial to evaluate the immunotherapy protocol. Partial tumor regression was observed in 2 dogs, while 6 dogs experienced stable disease, for an overall clinical benefit rate of 80%. Overall survival times (median = 351 days) and progression-free intervals (median = 163 days) were comparable to prior studies evaluating surgical debulking followed by immunotherapy. Dogs with detectable anti-CSC antibody responses had an increased overall survival time relative to dogs that did not generate antibody responses (vaccine responder MST = 500 days; vaccine non-responder MST = 218 days; p = 0.02). Conclusions: These findings suggest that combining myeloid cell targeted oral immunotherapy with tumor vaccination can generate objective tumor responses, even in the absence of conventional therapy. Overall, this approach has promise as a readily implemented therapeutic strategy for use in brain cancer patients.

Evaluation of cell-based and tissue-based immunofluorescent assays for detection of glial fibrillary acidic protein autoantibodies in the cerebrospinal fluid of dogs with meningoencephalitis of unknown origin and other central nervous system disorders.

OBJECTIVE: To evaluate whether cell-based and tissue-based immunofluorescent assays (IFAs) run in parallel could be used to detect glial fibrillary acidic protein (GFAP) autoantibodies in the CSF of dogs with meningoencephalitis of unknown origin (MUO) and other CNS disorders. ANIMALS: 15 CSF samples obtained from dogs with presumed MUO (n = 5), CNS disease other than MUO (5), and idiopathic epilepsy (5). PROCEDURES: All CSF samples underwent parallel analysis with a cell-based IFA that targeted the α isoform of human GFAP and a tissue-based IFA that involved mouse brain cryosections. Descriptive data were generated. RESULTS: Only 1 CSF sample yielded mildly positive results on the cell-based IFA; that sample was from 1 of the dogs with presumed MUO. The remaining 14 CSF samples tested negative on the cell-based IFA. All 15 CSF samples yielded negative results on the tissue-based IFA. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that concurrent use of a cell-based IFA designed to target the human GFAP-α isoform and a tissue-based IFA that involved mouse tissue cryosections was inadequate for detection of GFAP autoantibodies in canine CSF samples. Given that GFAP autoantibodies were likely present in the CSF samples analyzed, these findings suggested that epitopes differ substantially between canine and human GFAP and that canine GFAP autoantibody does not bind to mouse GFAP. Without a positive control, absence of GFAP autoantibody in this cohort cannot be ruled out. Further research is necessary to develop a noninvasive and sensitive method for diagnosis of MUO in dogs.