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Leonardo Giraudo
Pharmacovigilance Compliance Expert

CBD for Canine Epilepsy – What are the Takeaways from the Epidiolex Experience?

Results from the use of animals during clinical trials to identify an epilepsy treatment for them 

Epilepsy is the most common neurological disorder seen in dogs; scientific literature reports that it has been estimated to affect approximately 0.75% of the canine population. The term epilepsy refers to a heterogeneous disease characterized by the presence of recurrent, unprovoked seizures resulting from an abnormality of an animals’ brain. The condition can be genetic or idiopathic epilepsy, caused by structural problems in the brain (known as structural epilepsy), or can stem from an unknown cause (epilepsy of unknown cause). Epilepsy in dogs can be a challenge for animal owners; in fact, when observing seizures it is important for dog owners to keep a diary of detailed information including:  

1) Affected body parts;  

2) When seizures occur;  

3) How often seizures occur; and  

4) How long they last. 

This information is fundamental for veterinarians to understand how the pathology is generated and how it can be managed/treated by the animal owner. 

Seizures can result from exposure to a specific stimulus, such as an illness, exposure to a toxin, or problems with metabolism (reactive seizures). Any potentially precipitating events should be brought to the attention of the attending veterinarian, such as reactive seizures, which are not generally treated with standard anti-epileptic drugs. Reflex seizures, which are seizures that occur consistently after a particular exposure to, for example, a loud noise, a flashing light, or a more complex movement or behavior, have also been reported in dogs. 

The specific biochemical mechanisms that cause seizures are not yet fully understood in either dogs or humans. It is known that seizures result from dysfunction in the brain’s electrical activity and it is generally believed that they are caused by an imbalance between excitatory and inhibitory activity in specific areas of the brain, leading to either excessive brain activity or activity that is unusually depressed. 

Some evidence suggests that, in a subset of idiopathic epilepsies, abnormal excitatory processes may be caused by functional abnormalities in neurons, specifically mutations in the ion channels that are essential to cells’ electrical function.  

The medical management of seizures in animals can be performed with different medicinal products, used also for the treatment of human seizures. The most used anti-epileptic (AE) is Phenobarbital, which can cause serious side effects, or Potassium Bromide, an anti-convulsant which is also used as a first generation AE. In addition, second generation AEs that are used for seizure treatment include Levetiracetam, which is largely used but its efficacy remains unclear, and Zonisamide, which has  been demonstrated to be effective in a wide range of human seizures but can cause severe adverse events. Third generation AEs such as Lacosamide and Rufinamide are used as treatments for dogs, even if not authorized.  

Dogs, specifically Beagles, are used in pre-clinical trials in order to get safety information on the molecules that are intended to be registered as Medicinal Products. From the experiences acquired during the trials, researchers and pharmaceutical companies can obtain important information for alternative applications for their molecules.  

As we know, there is not a registered veterinary medicinal product that contains as an active substance the Cannabidiol; in humans, the only registered product is called “Epidiolex” and is intended as additional therapy for different kinds of seizures. 

What can we learn from Epidiolex registration and what are the takeaways from these experiences?  

As cited above, the actual treatments for Canine Epilepsy can cause severe adverse events and not all of the more modern AEs are available both for human and animal treatment. A medication using Cannabidiol can be considered a valid alternative or additional therapy to be administered to dogs in the event of seizure. From Epidiolex registration, veterinary pharma can take inspiration for a new approach to seizures in dogs, considering that some safety data is available as Beagles have been used in different studies supporting the registration. 

In the EMA public report, reports have shown that dogs have been used for in vivo evaluation of Epidiolex on the cardiovascular system, showing that the oral administration at dose level of 50 and 100 mg/kg b.w. of CBD exhibited only a biologically significant decrease in heart rate. The document also reported that toxicology studies were performed on dogs, with single dose and repeat dose toxicity studies. As also reported in Epidiolex study literature, it is known that Cannabidiol can cause low severity adverse events, with a small impact on liver functionality and mostly, showing behavioural disorders in animals. 

As similarities have been reported in human and animal epilepsy, the successful use of Cannabidiol for seizure treatment can be investigated by veterinarians and pharma companies in an effort to provide our pets an efficacious treatment with potentially low adverse reactions. 

In conclusion, based on the Epidiolex experience for human epilepsy, we can hope that Cannabidiol will be a valid alternative in animal treatments in the coming years. 

Bibliography

  1. Berendt M, Farquhar RG, Mandigers PJ, Pakzody A, Bhatti SF, De Risio L, Fischer A, Long S, Matsiasek K, Munana K, Patterson EE, Penderis J, Platt S, Podell M, Potschka H, Pumarola MB, Rusbridge C, Stein VM, Tipold A, Volk HA.  International Veterinary Epilepsy Task Force consensus report on epilepsy definition, classification and terminology in companion animals.  2015. BMC Vet Res  11:182. 
  1. Ekenstedt, K.J. and  Oberbauer, A.M. Inherited Epilepsy in Dogs. 2013. Topics in Compan An Med. 28:51-58. 
  1. Heske L, Nodvedt A, Jaderlund KH, Berendt M, Egenvall A.  A cohort study of epilepsy among 665,000 insured dogs: incidence, mortality and survival.  2014.  Vet J; 202:471-6. 
  1. Howbert, J.J., Patterson, E.E., Stead, S.M., Brinkmann, B., Vasoli, V., et al.  2014. Forecasting seizures in dogs with naturally occurring epilepsy. PLOS One. 9: e81920. 
  1. Moore, S.A. 2013. A clinical and diagnostic approach to the patient With seizures. Topics in Compan An Med. 28:46-50. 
  1. Muñana, K.R. 2013. Management of refractory epilepsy. Topics in Compan An Med. 28:67-71. 
  1. Patterson, E. E. 2013. Epileptogenesis and companion animals. Topics in Compan An Med. 28:42-45. 
  1. Podell M. 2013. Antiepileptic drug therapy and monitoring. Topics in Compan An Med. 28:59-66.  
  1. Podell, M, Volk HA, Berendt M, Löscher W, Muñana K, Patterson EE, Platt SR.  2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs.  2016. J Vet Intern Med 30:477-80. 
  1. Potschka, H., Fischer, A., von Rüden, E.-L., Hülsmeyer, V., Baumgärtner, W. 2013. Canine epilepsy as a translational model? Epilepsia. 54:571-579 
  1. EMA/191061/2021 EMEA/H/C/004675 Epidyolex (cannabidiol) An overview of Epidyolex and why it is authorised in the EU 

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