Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs

Abstract

The use of cannabidiol (CBD) in childhood refractory seizures has become a common therapeutic approach for specific seizure disorders in human medicine. Similarly, there is an interest in using CBD, cannabidiolic acid (CBDA) or cannabinoid-rich hemp products in the treatment of idiopathic epilepsy in dogs. We aimed to examine a small cohort in a pilot investigation using a CBD and CBDA-rich hemp product for the treatment of refractory epileptic seizures in dogs. Fourteen dogs were examined in a 24-week randomized cross-over study being provided placebo or CBD/CBDA-rich hemp extract treatment at 2 mg/kg orally every 12 h for each 12-week arm of the study. Serum chemistry, complete blood counts, serum anti-seizure medication (ASM) concentrations and epileptic seizure frequency were followed over both arms of the cross-over trial. Results demonstrated that besides a mild increase in alkaline phosphatase, there were no alterations observed on routine bloodwork at 2, 6, and 12 weeks during either arm of the study. Epileptic seizure frequency decreased across the population from a mean of 8.0 ± 4.8 during placebo treatment to 5.0 ± 3.6 with CBD/CBDA-rich hemp extract (P = 0.02). In addition, epileptic seizure event days over the 12 weeks of CBD/CBDA-rich hemp treatment were 4.1 ± 3.4, which was significantly different than during the 12 weeks of placebo treatment (5.8 ± 3.1; P =0.02). The number of dogs with a 50% reduction in epileptic activity while on treatment were 6/14, whereas 0/14 had reductions of 50% or greater while on the placebo (P = 0.02). No differences were observed in serum zonisamide, phenobarbital or bromide concentrations while on the treatment across groups. Adverse events were minimal, but included somnolence (3/14) and transient increases in ataxia (4/14) during CBD/CBDA-rich hemp extract treatment; this was not significantly different from placebo. This further indicates that providing CBD/CBDA-rich hemp extract during refractory epilepsy (only partially responsive to ASM), in conjunction with other ASM appears safe. Based on this information, the use of 2 mg/kg every 12 h of a CBD/CBDA-rich hemp extract can have benefits in reducing the incidence of epileptic seizures, when used concurrently with other ASMs.

Keywords: cannabidiol; cannabidiolic acid; dog; phenobarbital; seizure; zonisamide.

Figure 1

Log serum ALP activity shown over 12 weeks in both CBD/CBDA-rich hemp oil and placebo treatment phases of the study. No differences were observed across time or between groups at any time point, however there is a global treatment effect with slightly elevated ALP concentrations (P < 0.01).

Figure 2

Mean seizure activity over 12-weeks of CBD/CBDA-rich hemp oil vs. placebo compared to placebo. (A) Epileptic seizure numbers recorded by owners during treatment using an encapsulated CBD/CBDA-rich hemp oil (2 mg/kg every 12 h) vs. placebo treatment. Asterisk indicates a significant difference (P = 0.02). (B) Total days of seizure activity over the 12 week period using an encapsulated CBD/CBDA-rich hemp oil vs. placebo treatment. Asterisk indicates a significant difference (P = 0.02).