Cannabidiol, the primary non-psychoactive phytocannabinoid found in cannabis, has generated significant research interest due to its potential for biological effects, such as anti-inflammatory, analgesic, immunomodulatory, and anticonvulsant properties. Several studies have demonstrated the potential of CBD to alter inflammatory cytokines; however, data on CBD’s effects on cell viability and pro-inflammatory cytokines in target animals, such as dogs, are limited. Therefore, in this study, we investigated the effects of CBD on the cell viability and modulation of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), in canine PBMCs stimulated with LPS. To evaluate the effect of CBD on neuroinflammation in epilepsy pathology, an independent study of five refractory epileptic dogs co-treated with CBD for 30 days was conducted. The current findings revealed that CBD concentrations of 16 µg/mL had a statistically significant effect on the viability of canine PBMCs with a calculated IC50 of 15.54 µg/mL. The effect of CBD on inflammatory cytokines in LPS-stimulated PBMCs tended to be dose-dependent, with CBD concentrations of 5–30 μg/mL resulting in decreased production of the tested pro-inflammatory cytokines. Considering the effect of CBD on cytokine production by PBMCs from epileptic dogs, CBD has the potential to modulate immune responses and provide benefits when used in combination with antiepileptic drugs. The findings provided evidence of CBD cytotoxicity and its effect on the alteration of pro-inflammatory cytokines in canine PBMCs.
Canine epilepsy often resists conventional antiepileptic drugs (AEDs), which affects their quality of life. Cannabidiol (CBD) has anticonvulsant properties; however, evidence of its use in canine epilepsy is limited and contradictory. This prospective pilot study aimed to investigate the potential advantages, safety profile, and effects of CBD on quality of life when used as an adjunctive therapy in cases of drug-resistant epilepsy in canines. Thirteen dogs with refractory epilepsy, all on 2–6 concurrent AEDs, were enrolled. A single-arm pretest–post-test design was used. CBD was titrated from 0.5 mg/kg BID 2.5 mg/kg q12h. The primary outcome was the change in seizure frequency. Secondary outcomes included changes in seizure severity, seizure cluster, hematological and biochemical parameters, and owner-reported quality of life (QoL). Significant overall seizure frequency reduction (p = 0.02) with the median decreased from 11 (IQR 9–22) during the pre-intervention period to 5 (IQR 2–13) at the post-intervention follow-up. Notably, 61.5% of the dogs achieved a ≥50% reduction in seizure frequency. The number of seizure clusters was significantly decreased (p = 0.001). Most hematological/renal parameters remained stable; however, Alkaline Phosphatase (ALP) levels significantly increased (p < 0.001). The owners reported positive CBD perceptions and an improved quality of life. CBD shows the potential for refractory canine epilepsy, especially in clusters. Increased hepatic enzyme levels necessitate rigorous monitoring, particularly with the concurrent use of AEDs. This groundbreaking study explored the application of CBD in managing canine epilepsy, utilizing a “start-low, go-slow” strategy to minimize adverse effects while effectively controlling seizures. Our findings underscore the necessity of customizing CBD dosages for individual needs and highlight the critical importance of monitoring liver function. This study challenged the traditional one-size-fits-all dosing approach. It provides the first evidence and practical framework for the use of CBD to treat canine epilepsy in Asia, detailing the pioneering approach and the initial findings from this cohort.