The endocannabinoid system (ECS) has been evolving since the beginning of vertebrate species, but why did veterinary practitioners never learn about it in school? Just like our human counterparts’ veterinary practitioners have no or only a cursory understanding of the ECS and cannabis therapy. Veterinary practitioners have also been echoing that there “is no evidence” in animals. To the contrary, we have numerous studies utilizing cannabinoids and other cannabis molecules for therapeutic relief and translational studies that could be considered for any vertebrate creature. Here we review the current and pertinent literature in utilizing cannabis derivatives in animals and discuss the future forecast of cannabis in veterinary medicine.
Veterinary Cannabis Studies
To date, we have an ever-growing list of relevant studies for practical use of cannabis in companion animals. Most notably, we now have the results from two studies, one conducted at Colorado State University (CSU) and one from Cornell University, to help shed light on effective and safe dosing of CBD dominant cannabis products in dogs. In the Colorado State University study, conducted by Dr. Stephanie McGrath, we see dogs given three different dosing strategies. A group of 30 healthy beagle dogs were randomly assigned to receive a cannabidiol dominant product in the form of a capsule, oil, and CBD transdermal cream at a dose of 10 mg/kg/day or 20 mg/kg/day for 6 weeks. In the study, the dogs had complete blood counts, chemistry panels, urinalysis, and bile acids performed at 0, 2, 4, and 6 weeks. The most notable effect was elevations in serum alkaline phosphatase (ALP) that occurred in some dogs. All of the dogs in the study also experienced diarrhea, while the dogs that received the transdermal formula had reddened skin after application that was not of clinical concern. Because the products used in the study were plant-based, the variability between batches were measured. Variability was <10% for the CBD-infused transdermal cream and CBD-infused oil. There was considerable variation, 28–31%, between the CBD concentration in the capsules and the amount stated on the label. Higher systemic exposures were observed with the oral CBD-infused oil formulation, and the half-life after a 75 mg and 150 mg dose was 199.7 ±55.9 min and 127.5 ±-32.2 min, respectively. Exposure was dose-proportional, and the oral CBD-infused oil provided the most favorable pharmacokinetic profile. While the study mentions that the diarrhea was not related to the formula, it should be noted that this assertion cannot be made with certainty. The study concluded that this particular CBD dominant product, with no terpenes, appeared to be well tolerated in dogs (9).
Also at CSU, there are two continuing studies: one on osteoarthritis (OA) and the other on canine epilepsy. The OA study at CSU is using a 5 mg/kg daily dose for 6 weeks (the manuscript is currently under review). In the pilot epilepsy study utilizing a hemp-based product, preliminary results show eight out of nine dogs had a reduction in the frequency of seizures at 5 mg/kg once a day. A long-term study over three years will follow this study. A similar study is also being conducted at the University of Florida (10).
In a canine study conducted at Cornell University under the direction of Dr. Joseph Wakshlag, we see similar, yet more favorable results with no diarrhea, utilizing a product made by ElleVet Sciences. A single dose pharmacokinetic study was performed using two different doses of CBD enriched oil. The industrial hemp used in this study has ~10 mg/mL CBD and an equal mix of ~10 mg/mL cannabidiolic acid (CBDA), 0.24 mg/mL THC, 0.27 mg/mL cannabichromene (CBC), and 0.11 mg/mL cannabigerol (CBG). All other cannabinoids were less than 0.01 mg/mL with a robust terpene profile. The initial investigation into single-dose oral pharmacokinetics was performed with four beagles. Each dog received a 2 mg/kg and an 8 mg/kg oral dosage of CBD oil. The dogs were fed 2 h after dosing. Blood was collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 h after oil administration. Pharmacokinetics demonstrated that CBD half-life of elimination median was 4.2 h (3.8–6.8 h) for the 2 mg/kg dose, and 4.2 h (3.8–4.8 h) for the 8 mg/kg dose. These results led to dosing during the clinical trial at 2 mg/kg body weight every 12 h. For the clinical efficacy study, which assessed the use for dogs with radiographically confirmed OA, a randomized placebo-controlled, veterinarian and owner blinded, cross-over study was used. Dogs received CBD oil (2 mg/kg) or placebo oil every 12 h. Hematology, serum chemistry, and physical examinations were performed on every visit. A canine brief pain inventory and Hudson activity scores showed a significant decrease in pain and an increase in activity with CBD oil. Veterinary assessment showed decreased pain during CBD treatment. Owners reported no adverse side effects; however, serum chemistry showed an increase in alkaline phosphatase (ALP) similarly to the CSU study during CBD treatment which normalized over time. Conclusions of the clinical study suggest that 2 mg/kg of ElleVet Sciences CBD product twice daily can help increase comfort and activity in dogs with OA. It should also be noted that some dogs in the study were also on traditional nonsteroidal anti-inflammatory drugs with no adverse effects (11).
Data has shown in both studies that the other nonpsychotropic cannabinoids, primarily CBD, has a wide safety margin with only minimal side effects. In both studies, the elevated ALP was notable. Interestingly, the increase in liver values was not associated with any other elevated liver values (gamma-glutamyl transferase, bile acids, or alanine aminotransferase) and may be a response to cannabinoid metabolism through the cytochrome P450 (CYP450) pathway (12,13).
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Stephen Cital, RVT, SRA, RLAT, VCC, VTS-LAM (Res. Anesthesia) is the co-founder of the Veterinary Cannabis Academy and consultant and research librarian for Veterinary Cannabis Education and Consulting in Wheat Ridge, Colorado. Direct correspondence to: [email protected]
How to Cite This Article
S Cital, Cannabis Science and Technology 2(2), 56-60 (2019).