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Cannabidiol (CBD) in addition to current treatment for seizure reduction in canine epilepsy 

Clinical Scenario

Bonzo is a 5 year old Staffordshire bull terrier that has been treated for idiopathic epilepsy with phenobarbitone and potassium bromide (KBr). You tried levetiracetam, but the combination of phenobarbital and KBr was more efficacious in Bonzo's case. He is still having more than 2 seizures per month despite achieving therapeutic levels of the drugs in his blood. You and the owner are keen to improve this if possible. There has been lots of news coverage recently about using cannabidiol (CBD) for treating epilepsy in humans. You wonder if, in dogs with idiopathic epilepsy treated with conventional anti-epileptic drugs (AEDs), the addition of CBD would reduce the frequency of Bonzo's seizures....

3-Part Question (PICO)

In [dogs with idiopathic epilepsy] does [cannabidiol in combination with current treatment] compared to [placebo plus current treatment] [decrease seizure frequency]?

Search Strategy and Summary of Evidence

Search Strategy

MEDLINE(R) In-Process & Other Non-Indexed Citations and MEDLINE(R) 1946 to Present using the OVID interface

(dog.mp. OR dogs.mp. OR canine.mp. OR canines.mp. OR canis.mp. OR exp Dogs/)

AND

(epilepsy.mp. OR idiopathic epilepsy.mp. OR idiopathic generalised epilepsy.mp. OR IGE.mp. OR epileptic.mp. OR seizure.mp. OR seizures.mp. OR fit.mp. OR fits.mp. OR exp epilepsy/ OR exp seizures/)

AND

(cannabidiol.mp. OR CBD.mp. OR CBD oil.mp. OR cannabis sativa.mp. OR phytocannabinoids.mp. OR cannabinoid.mp. OR cannabinoids.mp. OR endocannabinoid.mp. OR tetrahydrocannabinol.mp. OR THC.mp. OR cannabis.mp. OR Sativex.mp. OR Epidiolex.mp. OR Epidyolex.mp. OR exp cannabidiol/ OR exp Cannabis sativa/)

CAB Abstracts 1910 to Present using the OVID interface

(dog.mp. OR dogs.mp. OR canine.mp. OR canines.mp. OR canis.mp. OR exp Dogs/)

AND

(epilepsy.mp. OR idiopathic epilepsy.mp. OR idiopathic generalised epilepsy.mp. OR IGE.mp. OR epileptic.mp. OR seizure.mp. OR seizures.mp. OR fit.mp. OR fits.mp. OR exp epilepsy/ OR exp seizures/)

AND

(cannabidiol.mp. OR CBD.mp. OR CBD oil.mp. OR cannabis sativa.mp. OR phytocannabinoids.mp. OR cannabinoid.mp. OR cannabinoids.mp. OR endocannabinoid.mp. OR tetrahydrocannabinol.mp. OR THC.mp. OR cannabis.mp. OR Sativex.mp. OR Epidiolex.mp. OR Epidyolex.mp. OR exp cannabidiol/ OR exp Cannabis sativa/)

Search Outcome

MEDLINE

  • 22 papers found in MEDLINE search
  • 21 papers excluded as they don't meet the PICO question
  • 0 papers excluded as they are in a foreign language
  • 0 papers excluded as they are review articles/in vitro research/conference proceedings
  • 1 total relevant papers from MEDLINE

CAB Abstracts

  • 12 papers found in CAB search
  • 11 papers excluded as they don't meet the PICO question
  • 0 papers excluded as they are in a foreign language
  • 0 papers excluded as they are review articles/in vitro research/conference proceedings
  • 1 total relevant papers from CAB

Total relevant papers

1 relevant papers from both MEDLINE and CAB Abstracts

Summary of Evidence

McGrath et al. 2019, USA

Title:

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

Patient group:

Dogs in Colorado with idiopathic epilepsy which met the International Epilepsy Task Force Tier II criteria and were treated with a minimum of one conventional anti-epileptic drug, yet had continued to experience two or more documented seizures per month for at least 16 weeks. To be included, the dogs needed to have serum therapeutic levels of KBr or phenobarbital or receiving the recommended dose of zonisamide or levetiracetam.

Study Type:

Randomised controlled trial

Outcomes:
  • Mean monthly seizure frequency from 16 weeks before study and the 12 week duration of the study
  • Response to treatment defined as ≥50% reduction in mean monthly seizures
  • Serum AED, biochemistry and CBC at wks 0 and 12
  • Plasma CBD at 4, 8 and 12 weeks
  • Adverse drug effects and change in anxiety-related behaviour using C-BARQ at weeks 0 and 12
Key Results:
  • Eight of the nine dogs in the CBD arm showed a reduction in mean monthly seizure frequency compared to the 16 weeks prior to treatment. Three of the seven dogs receiving placebo treatment also had a reduction in mean monthly seizure frequency. This is also reported as a 33% decrease in group median for mean monthly seizure frequency in CBD group compared to no change in group median in the placebo group.
  • Only two dogs in each of CBD and placebo groups were considered responders (≥50% decrease in mean monthly seizure frequency).
  • No significant adverse clinicopathological events were reported in either group during the study.
  • No behaviour differences were detected by owner assessment using C-BARQ questionnaire.
Study Weaknesses:
  • Very small sample size.
  • If the dogs experienced >1 seizure per 24 hours, this was considered as a single seizure episode. 
  • Data were analysed as mean monthly seizure frequency whereas individual seizure measurement over time would perhaps have been more appropriate.
  • Raw data reported in supplementary materials suggest that the groups were not comparable with respect to their baseline seizure frequency. 
  • These dogs had treatment-unresponsive epilepsy so may not be representative of those commonly seen in general practice.
  • There was a high level (90%) of exclusion on enrollment and only 65% of enrolled subjects completed the study. The impact of these losses is not discussed.
  • Results are only applicable to this product at the dose used as there is no standaridsed product composition or defined dose rate.
Attachment:
Evidence appraisalEvidence appraisal

Comments

In the UK, CBD is considered to be a veterinary medicinal product, but there are currently no soley CBD products authorised for animals or for humans. Veterinary surgeons are advised to follow the prescribing cascade.

In addition, CBD products marketed as supplements are unregulated and not standardised so there is likely to be wide variation in active ingredient concentration. This study tested a very specific product and it is not known whether or how these results can be extrapolated to other products since they may contain different compounds in different concentrations.

More evidence from larger scale studies carried out over a longer time frame is required in order to be confident of the efficay of CBD oil in the treatment of idiopathic epilepsy.

Bottom line

The evidence is inconclusive from a single study focused on whether cannabidiol in combination with current treatment compared to placebo plus current treatment can reduce the seizure frequency in dogs with epilepsy. Larger studies using more sensitive measures of seizure frequency are needed.

Disclaimer

The BETs on this website are a summary of the evidence found on a topic and are not clinical guidelines. It is the responsibility of the individual veterinary surgeon to ensure appropriate decisions are made based on the specific circumstances of patients under their care, taking into account other factors such as local licensing regulations. Read small print

References

McGrath S, Bartner LR, Rao S, Packer RA, Gustafson DL, (2019). 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. J Am Vet Med Assoc 254:1301-08.

About this BET

First author:
Lisa Morrow
Second author:
Zoe Belshaw
Institution:

Centre for Evidence-based Veterinary Medicine, University of Nottingham

Search last performed:
2020-03-06 16:42:05
Original publication date:
2020-03-10 16:42:05
Last updated:
2020-03-10 16:42:05
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