Tolerability of long-term cannabidiol supplementation to healthy adult dogs.

BACKGROUND: Cannabidiol (CBD) has therapeutic potential in companion animals. Shorter-term studies have determined that CBD is well tolerated in dogs with mild adverse effects and an increase in alkaline phosphatase (ALP) activity. There is need to assess CBD's long-term tolerability. HYPOTHESIS: Determine the long-term tolerability of CBD administered PO to healthy dogs for 36 weeks at dosages of 5 and 10 mg/kg body weight (BW)/day. Our hypothesis was that CBD would be well tolerated by dogs. METHODS: Eighteen healthy adult beagle dogs were randomly assigned to 3 groups of 6 each that received 0, 5, or 10 mg/kg BW/day CBD PO. Dogs were adapted to their housing for 3 weeks and received treatment for 36 weeks once daily with food. Adverse events (AEs) were recorded daily. Blood biochemistry profiles were monitored every 4 weeks. Data were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05. RESULTS: The 0 and 5 mg/kg treatment groups had similar fecal scores, and the 10 mg/kg treatment group had higher frequency of soft feces. No other significant AEs were noted. An increase (P < .0001) in ALP activity occurred in groups that received CBD. Remaining blood variables were within reference range. CONCLUSIONS AND CLINICAL IMPORTANCE: Chronic administration of CBD in healthy dogs at 5 mg/kg was better tolerated than 10 mg/kg, and both dosages caused an increase in ALP activity. Although our data does not indicate hepatic damage, it is recommended to monitor liver function in dogs receiving CBD chronically.

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.

Substrate degradation and postbiotic analysis of alternative fiber ingredients fermented using an in vitro canine fecal inoculum model.

Many fiber ingredients are used by the pet food industry; however, little data are available regarding the fermentation characteristics of alternative fibers currently being used. The objectives of this study were to determine organic matter disappearance (OMD) and postbiotic production from various fruit and vegetable fiber sources using an in vitro dog fecal inoculum model. Apple pomace (AP), blueberry pomace (BP), cranberry pomace (CP), tomato pomace (TP), and pea fiber (PF) were used as experimental treatments. Inoculum was prepared using freshly voided feces under anaerobic conditions. Predigested fibers were inoculated and incubated for 1, 3, 6, and 12 h at 39 °C. Short-chain fatty acids (SCFA), branched-chain fatty acids (BCFA), total volatile fatty acids (VFA), and OMD were determined for each fiber source and time point in triplicate. After 12 h of incubation, OMD was similar (P > 0.05; average of 18.5%) among treatments. Proportionally, acetate was greater for BP and AP (P < 0.05; average of 80.1%) than for the other treatments (68.3% to 71.2%). Molar proportions of propionate was greatest (P < 0.05) for CP (26.8%) compared to the remaining treatments (13.6 to 20.7%). Butyrate was proportionally greater for PF (7.7%; P < 0.05) than for BP and CP (average of 4.8%) and was lowest for AP (3.8%); however, TP was not different from PF (P > 0.05; average of 7.25%). Total VFA concentration was highest for AP (P < 0.05) followed by TP (1.17 and 0.75 mmol*g-1 of substrate, respectively). Both BP and PF were similar (average of 0.48 mmol*g-1 of substrate) and lower than for TP, with CP having the lowest VFA concentration (0.21 mmol*g-1 of substrate) among all treatments. Additionally, when comparing molar concentrations, AP and TP (average of 0.0476 mmol*g-1 of substrate) had greater butyrate concentrations than did PF (0.0344 mmol*g-1 of substrate). The AP, BP, and TP treatments had both linear and quadratic relationships (Table 7; P < 0.05) for acetate, propionate, and butyrate concentrations across time. CP only demonstrated a linear relationship for propionate (P < 0.05), whereas acetate and butyrate had quadratic relationships with time. PF only demonstrated quadratic relationships between acetate, propionate, and butyrate concentrations and time (P < 0.05). Overall, the fiber substrates evaluated were marginally to moderately fermentable when incubated for up to 12 h with canine fecal inoculum.

Fibers fermented in the gut result in the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate. These postbiotic compounds, particularly butyrate, play an important role in colonic and host health. Fibers not degraded by the microbiota aid in stool formation and promote laxation. Many fiber ingredients are used in pet diets; however, data regarding the fermentation characteristics of alternative fiber ingredients are scarce. In this work, substrate degradation and postbiotic analysis were evaluated for apple pomace (AP), blueberry pomace (BP), cranberry pomace (CP), pea fiber (PF), and tomato pomace (TP) incubated for 1, 3, 6, and 12 h at 39 °C using canine fecal inoculum. After 12 h, substrate degradation was not different among treatments due to high variability. AP had the highest concentration of total SCFA, followed by TP, BP, PF, and CP. The molar proportion of acetate was greatest for AP and BP. CP had the highest molar proportion of propionate. PF had greater molar proportions of butyrate than did AP, BP, and CP, but had similar molar proportions as TP. Additionally, the molar concentrations of butyrate were greatest for AP and TP. Overall, fiber substrates were marginally to moderately fermentable when incubated for up to 12 h with canine fecal inoculum.

The effect of sorghum fractions on apparent total tract digestibility and antioxidant capacity by dogs.

Sorghum is an abundant starch source that has many potential health benefits. Some pet food companies have adopted whole sorghum in their formulations, however sorghum flour and (or) its phenolic rich seed coat might provide added benefit to companion animal diets. The objective of this experiment was to evaluate diets utilizing sorghum flour (FLD), and sorghum mill feed (MFD) relative to whole sorghum (WSD), and conventional grains (rice, corn and wheat; CON) in a typical dog diet. Adult (1-3 yr) Beagle dogs (n = 12; 10.6 kg ± 1.4) were randomly assigned to individual pens with ad libitum access to water. Dogs were fed twice daily and adapted to diet (9 d), and then total feces were collected for 5 d over 4 periods in a 4x4 replicated Latin square design. Fecal output for determination of digestibility was estimated using Cr2O3 as a marker. Number of defecations were quantified, and feces were scored. Approximately 3 mL of blood from each dog was collected at the end of each period and stored at -80° until further analyses. Means were separated using multivariate analysis of variance (MANOVA). Intake did not differ among treatments (average 187 g/d), but dogs fed the MFD excreted a larger (P<0.05) amount of feces, had more defecations per day, and lower (P<0.05) overall nutrient digestibility compared to the other treatments. The FLD had the highest (P<0.05) dry matter (DM), organic matter (OM), crude protein (CP) and gross energy (GE) digestibility, suggesting a possible application in "easy-to-digest" pet foods. Dogs fed the MFD had the highest (P < 0.05) plasma oxygen radical absorbance capacity (ORAC) value, but plasma ferulic and p-coumaric acids did not differ among treatments. Sorghum fractions have potential application in pet food; wherein, a bran rich fraction may promote antioxidant capacity, and flour increased digestibility.