Treatment with CBD

The effect of CBD for dogs with seizures

McGrath and colleagues recently conducted the first randomized controlled clinical trial ever to assess the anticonvulsant effect of CBD for dogs with seizures. This article reports on their study, and discusses the following:

Seizures in dogs

About 1-6% of dogs suffer from idiopathic epileptic seizures (meaning: seizures with unknown cause). As such, epilepsy is the most frequent neurological condition in dogs. Currently, the most commonly used pharmaceutical treatment in epileptic dogs is phenobarbital or potassium bromide.

Anti-epilepsy medications, however, are ineffective in about 20-30% of epileptic dogs. In addition, many dogs experience side effects of these medications. Therefore, many dog owners have sought out other treatment methods, including cannabis products, such as CBD.

The FDA has approved the oral administration of pure CBD to treat epilepsy in humans.  Additionally, the FDA rescheduled the approved drug as a Schedule V substance. So far, however, nobody has conducted any rigorous research to assess the effectiveness of CBD in treating epilepsy in dogs. This study that we are presenting is the first randomized controlled clinical trial to assess CBD for dogs with seizures.

The goals of the study

McGrath and colleagues evaluated the following:

  1. What is the effect on seizures of giving CBD short-term to dogs in addition to standard anticonvulsive medications?
  2. What is the effect of CBD on the concentration of phenobarbital and bromide in the blood of these dog after 12 weeks?
  3. Are there any adverse side effects of CBD administration?

The researchers advertised the study, and dog owners brought in their dogs who:

  • had at least two seizures a month for at last 16 weeks,
  • took at least one conventional antiepileptic medication,
  • had no obvious brain damage as reason for their seizures,
  • had no infectious diseases that might explain their seizures,
  • had blood levels of phenobarbital and bromide within therapeutic range, or were receiving labeled doses of zonisamide or levetiracetam, and
  • had no additional serious illness.

Owners brought in 248 dogs, but only 26 met the eligibility criteria. These eligible dogs then participated in a randomized controlled double-blind study, which means that:

  • a computer program randomly assigned the dogs into two groups
  • one group was getting CBD and the other group was the control group getting placebo
  • neither the veterinarian nor the owners knew whether the dogs were getting CBD or placebo (double-blind)

CBD for dogs with seizures

Dog owners supplemented their dog’s prescribed medication with:

  • either 2.5 mg/kg CBD in oil form orally two times a day for 12 weeks
  • or placebo oil twice a day for 12 weeks

The cold-pressed hemp oil had a concentration of 100 mg of CBD/mL, and only trace amounts of other cannabinoids, such as THC, cannabinol, cannabigerol, and cannabichromene. Chicken flavoring was added to enhance taste. The placebo was chicken flavored hemp oil with no cannabinoids, so nobody could sense the difference between CBD oil and placebo.

Dog owners brought their dogs back for blood checkups and physical examinations every 4 weeks. In addition, they had to keep a diary about seizures, regarding their:

  • number
  • type 
  • duration

Owners also had to complete a behavioral assessment of their dogs, which evaluated the potential side effects of the treatment and the anxiety of the dogs.

Findings of the study

Scientists compared the average monthly number of seizures for:

  • before and after the study, for each dog
  • dogs that received CBD versus dogs that received placebo

Altogether 16 dogs successfully completed the study. Dogs treated with CBD had a significant reduction in the number of monthly seizures (from 4.0 before to 2.7 after, a 33% reduction in seizures). As a comparison, dogs in the placebo group had no reduction whatsoever in the number of seizures.

Dogs treated with CBD had increased serum alkaline phosphatase (ALP) activity. However, serum bromide and phenobarbital concentrations were the same in the CBD and in the placebo group, or before vs. after the treatment.

In terms of aggression, anxiety, fear, trainability, excitability, and rivalry, there was no difference between the dogs that received CBD vs those that received placebo. The researchers also noted no adverse psychoactive effects in any of the dogs that received CBD oil.

What do the findings mean?

Since this was the first randomized controlled double-blind experimental study ever to assess the effect of CBD for epileptic dogs, the authors were unable to compare their results to prior studies. They noted that no established data exists in veterinary medicine to advise about effective doses, appropriate dosing intervals, and CBD blood concentrations. 

In addition, no established therapeutic regimen about how to give CBD for epileptic dogs exists either. The authors decided to give CBD for epileptic dogs twice a day, because that is what they consider as customary in human therapy. Furthermore, the half-life of CBD in dogs is roughly between 120 to 200 minutes, so that also suggested at least twice a day dosing.

They also used a sophisticated formula involving the ratio of body weight to body surface and converted the customary 1.5 mg/kg CBD human dose to 2.5 mg/kg CBD for dogs. However, the daily recommended starting dose for Epidiolex is 2.5 mg/kg every 12 hours, with a maximum limit of 10 mg/kg every 12 hours.

Therefore, the authors wonder if their conservative approach to dosing might have resulted in doses that were too low for the dogs. They recommend future studies that evaluate different (higher and lower) doses as well.

Adverse side effects

One quarter (3 of 12) of the epileptic dogs in the study that received CBD developed adverse effects. One of the dogs had severe epilepsy to begin with, so its worsened conditions was most probably not due to CBD.  The other two dogs developed ataxia. The authors concluded that this ataxia was probably an adverse side effect of CBD treatment.

As we saw, there was no difference in the blood serum levels of the anticonvulsive medications in the CBD treated vs placebo treated dogs. This suggests that CBD does not influence the breakdown of these two medications in dogs.

The authors are unsure what the clinical importance of increased serum ALP activity is, which they observed in the CBD treated group but not in the placebo group.

Reference

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