25 Feb CBD for Canine Epilepsy: A Natural Solution?

Exploring the Use of CBD in Managing Epilepsy in Dogs: Current Research and Future Directions

Epilepsy is one of the most common neurological conditions in veterinary practice, affecting a significant number of dogs. Traditional first-line treatments can have limitations, particularly in refractory cases where up to 30% of epileptic dogs do not respond adequately to these drugs. This has driven the search for alternative treatments, including the growing interest in cannabidiol (CBD) for managing epilepsy. CBD, a non-psychotropic component of cannabis, has shown promise in both human and veterinary medicine as a potential adjunct to conventional anticonvulsant therapy.

Historical Context and Rising Interest in CBD for Epilepsy Cannabis has a long history in treating various neurological disorders, with reports of its use dating back to 1800 BC. Despite early success, the introduction of phenobarbital and the legal restrictions on cannabis reduced its use for medicinal purposes. However, the recent surge in CBD usage, particularly for childhood refractory seizures, has revived interest in its potential applications, including for canine epilepsy. With increased public awareness, and reduced stigma, pet owners and veterinary professionals alike are exploring CBD as a potential treatment.

In 1980, Cunha et al. reported anticonvulsant effects in 7 out of 8 patients with medically uncontrolled epilepsy, marking the beginning of significant research into cannabis-based treatments. Today, CBD is being studied for a range of neurological conditions, including malignant brain tumors, Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis in humans. Its use is also being explored for mood disorders like anxiety, depression, addiction, and PTSD. As human research expands, veterinary professionals are increasingly considering CBD for canine seizure management.  In fact, a recent US survey revealed vets considered seizures amongst the top 3 conditions where CBD could possibly be used.

Mechanisms of Action of CBD in Epilepsy CBD’s mechanism of action in epilepsy is complex, multifaceted and not yet fully understood.

The endocannabinoid system (ECS), which plays a vital role in regulating neurological functions, is implicated in epilepsy pathophysiology. Research suggests that dysfunction in the ECS, such as low levels of anandamide and CB1 receptors, may contribute to refractory seizure disorders. CBD is thought to reduce neuronal hyperactivity, partly by interacting with presynaptic CB1 receptors. Activation of these receptors inhibits neurotransmission between neurons, which in turn reduces excitability in the brain.

CBD also affects intracellular calcium concentrations and modulates receptors such as GPR55 and TRPV1, both of which influence synaptic activity and neuronal excitability.

Intracellular calcium concentration has a major impact on neurotransmitter release from presynaptic vesicles and influence excitability. CBD has been shown to act as a GPR55 antagonist and a TRPV1 agonist, helping to reduce calcium influx, lower intracellular calcium concentrations and thus dampening neuronal activity. 

Additionally, understanding that a reduction in extracellular concentrations of adenosine can contribute to development of epilepsy, CBD can inhibit adenosine reuptake, increasing the extracellular concentrations of adenosine and in turn have anticonvulsant effects.   

Clinical Research on CBD for Epilepsy in Dogs Several studies have investigated the use of CBD in dogs with epilepsy. Oral administration of CBD oil at doses ranging from 2 to 10 mg/kg has been found to be generally safe. CBD oil is better absorbed when administered in oil based formulations and when given with food. Whilst many indications respond at doses between 1 and 2mg/kg BID, generally higher doses and frequency alongside other antiseizure medications (ASMs) are required to help control seizure activity. While mild sedation has been reported, it appears to be more common in human patients than in dogs. 

One of the key concerns when prescribing CBD alongside conventional antiseizure medications (ASMs) is the potential for drug interactions. CBD is known to inhibit cytochrome P450 enzymes, which play a role in metabolizing many ASMs. Despite this, studies have shown that CBD administration does not significantly alter the serum concentrations of phenobarbital or potassium bromide. This suggests that, while clinical and laboratory monitoring is recommended, dose adjustments for these medications may not be necessary.

Experiments with THC have demonstrated rebound hyperexcitability with enhanced neuronal excitability and increased sensitivity to convulsions and so is generally not used for trials studying effects in epilepsy.  Current consensus is that “Based on the current state of knowledge and the described contradictory proconvulsant / anticonvulsant effects, the clinical use of THC in patients with epilepsy is not recommended”. CBD on the other hand has shown to produce antiepileptiform and anticonvulsant effects in both in vitro and in vivo models.  

In a study evaluating CBD at 2 mg/kg twice daily, a significant reduction in seizure frequency was observed in dogs when used in conjunction with other ASMs. Approximately 43% of dogs showed a 50% or greater reduction in seizure activity. Another study found that CBD treatment resulted in a 33% reduction in seizure days in dogs that were only partially responsive to their current medication regimen. Importantly, other than mild increase in serum AlkPhos, there were no significant changes in routine bloodwork or ASM serum levels, suggesting that CBD can be safely integrated into multimodal seizure management strategies.

Challenges and Future Directions Despite promising findings, the use of CBD for epilepsy in dogs is still in its early stages. Further research is needed to determine the most effective dosages, identify potential long-term side effects, and assess how CBD can be best integrated with other treatments. Studies with larger sample sizes and higher doses are particularly needed to clarify the full potential of CBD. Additionally, there is growing interest in exploring how CBD may impact comorbid conditions, such as cognitive dysfunction syndrome (CCD), which can co-occur with epilepsy in older dogs.

CBD is emerging as a promising treatment for epilepsy in dogs, with early studies suggesting that it can significantly reduce seizure frequency when used alongside conventional medications. The mechanisms underlying CBD’s anticonvulsant effects are complex and multifactorial, involving the endocannabinoid system, calcium signalling, and adenosine modulation. While current evidence is promising, additional research is essential to refine dosing strategies, assess long-term safety, and further investigate potential drug interactions. As our understanding of CBD’s role in epilepsy expands, it may offer a valuable addition to the armamentarium of treatments for canine epilepsy, particularly in cases that are refractory to traditional therapies.

References

1. The efficacy and safety of cannabidiol as adjunct treatment for drug-resistant idiopathic epilepsy in 51 dogs: A double-blinded crossover study – PubMed (nih.gov)
2. Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs
3. Cannabidiol in canine epilepsy – ScienceDirect
4. Drug-drug interaction between cannabidiol and phenobarbital in healthy dogs
5. Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy
6. Review of the neurological benefits of phytocannabinoids – PMC

See you next month!

Jen and the team at PetCann