VETgirl Q1 2020 Beat e-Newsletter

MEDICAL CANNABINOIDS: A REVIEW STEPHEN CITAL RVT, SRA, RLAT, VCC, CVPP, VTS-LAM Director of Education and Development, ElleVet Sciences, Portland ME

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4 CBD STUDIES FOR OSTEOARTHRITIS (OA) AND CANINE EPILEPSY Also, at CSU there are two continuing studies: one on osteoarthritis (OA) and the other with a longer-term study focused on the utility for canine epilepsy. The pilot study for epilepsy published in the summer of 2019 used a 5 mg/kg daily dose for 6 weeks. More subjective clinical differences were seen between the placebo group and treatment group using a product form Applied Basic Sciences. However, these differences were not of statistical difference from the placebo group in the conclusion. The author suspects the dose in this study is too low compared to human extrapolation of dosing. A long-term study over three years will follow with higher dosing. A similar study is also being conducted at the University of Florida with ElleVet Sciences product. 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. 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. 5 CBD STUDIES FOR ANXIETY/PANIC ATTACKS Animal models of CBD utility for anxiety or panic attacks are supported by studies placing a prey species in front of a predator species and conditioned escape responses in mice and rats. According to these studies, anxiety or panic attacks would be related to the flight and freezing defensive responses elicited by threats which expression was decreased in both models. (continued)

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