IMAGING

By Paul Basilio

As cannabidiol (CBD) continues its ubiquitous spread from pharmacies to gas stations to pet stores, it’s natural that owners are considering it for their horses. The products are marketed to reduce anxiety and pain, but human data about the safety, efficacy and pharmacokinetics of these treatments are limited, and there are even fewer data about its use in horses.

CBD is also banned by most horse shows and equine governing bodies, but clients continue to use it in their horses.

Alicia F. Yocom, DVM, and colleagues at the Colorado State University are helping the science catch up with the hype.

“When we started, there were no published scientific studies looking at the use of CBD in the horse, except for a single case report of mechanical allodynia in a horse,” Dr. Yocom said during a presentation at the 67th Annual AAEP Convention in Nashville. “CBD is heavily marketed to our clients and to veterinarians at various doses and in various formulations, but we do not know what a clinically effective dose is at this point.”

CBD and tetrahydrocannabinol (THC) are 2 of more than 120 compounds found in the Cannabis sativa plant. THC is the psychotropic compound responsible for marijuana’s well-known effects at getting people high, but CBD products must contain less than 0.3% THC—and it must be made from hemp.

Currently, there is only 1 FDA-approved CBD product, which is indicated for epilepsy and seizure disorders in children 12 months of age or older.

“Studies that have looked at behavior and arthritis are inconclusive at this point,” she added. “There are some studies that have looked at dogs with osteoarthritis that have shown reduced subjective pain scores, but there was no improvement in objective lameness scores.”

To gauge the plasma pharmacokinetics, shortterm safety and middle carpal joint synovial fluid levels of CBD, the team enrolled 12 adult horses— split evenly into 2 groups.

The low-dose group received 1 mg/kg/day of CBD, and the high-dose group received 3 mg/kg/day for 6 weeks. The CBD used in the study was an oil product in a sunflower-lecithin oil base, and it was analyzed by a commercial lab before the study and again at 2, 4, and 6 weeks to test for purity.

For 24-hour pharmacokinetics, the horses were given a full dose and blood was taken at 8 times in the first 24 hours. After that, the doses were divided into a twice-daily schedule.

Each horse was fed 2% of its body weight in hay and was given 1 lb of grain approximately 30 minutes prior to CBD administration.

“We gave the CBD in a fed state because there is a study in humans that showed an increase in oral bioavailability of 4- to 5-fold after humans were given a high-fat meal,” she explained.

CBD plasma concentrations were found to be dose-dependent in both groups and time to maximum concentration was similar in both groups, with a mean of around 4-to-5 hours. There were no adverse effects noted on daily monitoring or physical exams in any of the horses after 6 weeks, but there were some abnormalities in the clinicopathological parameters.

“We saw elevated liver enzymes in 8 of 12 horses, and hypocalcemia in all horses,” Dr. Yocom said. “Because of the hypocalcemia we checked the ionized calcium levels, which were normal in all horses.”

There were some spikes in liver values in all horses, but they decreased or returned to normal by 10 days after the last dose. Two of the horses had elevated liver enzymes before the study, but they returned to normal levels after CBD was discontinued.

After discontinuation of CBD, calcium levels improved or returned to normal in all horses.

Elimination data showed that after discontinuation, CBD was still detectable in blood in both groups at 24 hours and in the higher dose group at 48 and 96 hours. CBD values were detectable in synovial fluid in 6 of 12 horses at 12 hours (1 in the low-dose group; 5 in the high-dose group). After 5 weeks of twice-daily administration, CBD was detectable in synovial fluid in 8 of the 12 horses.

Plasma concentrations are markedly variable among individual horses, which is similar to results in dogs and humans. However, the total plasma concentrations of CBD for horses were significantly lower than in dogs and humans.

“The low plasma concentrations found in horses is actually similar to guinea pigs,” Dr. Yocom added. “We don’t know if that’s because of the herbivore diet or that they’re both hindgut fermenters, but those are possible theories.”

Average time to maximum concentration was also similar between groups, but the individual ranges were still quite large. It took anywhere from 30 minutes to 12 hours for horses to reach maximum plasma concentrations.

“We would recommend dosing about 4 hours before your desired peak effect,” she said.

In the synovial fluid, CBD was only reliably detected in the high-dose group, and the plasma levels correlated with increases in synovial levels.

“We don’t know if there may be a cumulative effect since we did see CBD in synovial fluid more frequently after 5 weeks when compared with 12 and 24 hours,” Dr. Yocom explained.

While the study was the first step in evidencebased analysis of CBD in horses, the doses used in the study were much higher than are typically present in commercially available supplements so that the team could provide a measure of safety data for future studies.

Yocom AF, O’Fallon ES, Gustafson DL, et al. Pharmacokinetics, safety, and synovial fluid concentrations of single- and multiple-dose oral administration of 1 and 3 mg/kg cannabidiol in horses. J Equine Vet Sci. 2022;(18)113:103933. https://www.sciencedirect.com/science/article/abs/pii/S0737080622000715?via%3Dihub