Evaluation of an Oral Supplemental Cannabidiol Product for Acceptability and Performance in Mature Horses

Cannabidiol, better known as simply CBD, is one of the non-psychoactive compounds found in hemp. Its supplementation to horses is gaining in popularity as a potential alternative to conventional pharmaceutical treatments for a variety of conditions such as arthritis and anxiety.
 
Despite potential advantages of CBD supplementation, it may have a negative impact on equine health and performance. More scientific research is needed to form recommendations for its use in horses; therefore, this study was designed to investigate supplementation of CBD oil over 28 days in 30 horses.
 
Targeted levels of supplementation were to provide three levels for comparison (0.0 mg/kg, 0.75 mg/kg, or 1.50 mg/kg); however, the supplements collected during the study were analyzed to be substantially lower than targeted levels when tested at a verified testing facility (0.12 mg/kg and 0.13 mg/kg).
 
At this level of supplementation, CBD oil was well-accepted, CBD was not detectible in blood samples, and blood chemistry parameters to assess liver and kidney function were not adversely affected as a result of supplementation. However, more research is needed to describe the discrepancy between formulated levels compared to tested levels of CBD supplements, in order to make recommendations for its application in the horse industry.
 
Abstract

Thirty stock type geldings (15 ± 3 years; 556 ± 63 kg BW) were used in a randomized complete design over 28 days to determine the influence of cannabidiol (CBD) oil supplementation levels on body weight, body condition, and blood chemistry. Horses were randomly assigned to one of three dietary treatments (n = 10 per treatment) formulated with canola oil to provide 1.50 mg CBD/kg BW (TRTA), 0.75 mg CBD/kg BW (TRTB), or 0.00 mg CBD/kg BW (canola oil; CTRL).
 
Treatments were top-dressed onto concentrate and individually administered twice daily. Horses were maintained in adjacent dry lots and received coastal bermudagrass hay ad libitum. Body weight and body condition scores (BCS) were obtained every 14 days.
 
On day 0 and 28, blood was collected via jugular venipuncture and serum was harvested to perform a blood chemistry panel and drugs of abuse screening at the Texas Veterinary Medical Diagnostic Laboratory. Data were analyzed using PROC MIXED of SAS (v9.4), and the model included treatment, time, and the treatment × time interaction, and linear and quadratic orthogonal polynomial contrasts to partition sum of squares.
 
Analysis of composited treatment samples revealed lower CBD concentrations than indicated from initial testing by the manufacturer (0.13 mg CBD/kg in TRTA; 0.12 mg CBD/kg in TRTB). At this level of supplementation, canola-based CBD oil was well-accepted by mature horses, banned substances were not detectable in blood, and blood chemistry parameters were not adversely affected as a result of supplementation. More research is warranted to describe the discrepancy between formulated levels compared to tested levels of CBD in the canola-based supplement.
 
Introduction

The use of cannabidiol (CBD), one of the non-psychoactive compounds found in hemp, is gaining in popularity as a potential alternative to conventional pharmaceutical treatments for a variety of conditions, including but not limited to arthritis and anxiety.
 
Studies conducted in mice and horses have shown that CBD reduces the production of inflammatory cytokines such as tumor necrosis factor-α (TNFα), which may help reduce inflammation in various body tissues or may have a calming effect and lessen anxiety in horses [1,2].
 
Horses receiving 40 g of a pelleted CBD supplement containing 100 mg of CBD over 6 weeks were less reactive to a novel stimulus compared to a control group; however, heart rates were not different and blood serum was not evaluated [3].

Despite the potential advantages of CBD supplementation, dietary CBD may have a negative impact on equine health and performance. Adverse responses reported in mice provided a dose of 615 mg CBD/kg body weight (BW) were lethargy, loss of appetite, and body weight loss [4].
 
It has also been identified in multiple studies that CBD may induce the cytochrome p450 mediated oxidative metabolism in the liver and cause an increase in alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activity, which suggests that liver injury is present.
 
The increase in serum ALP levels were seen in dogs at 2 mg CBD/kg BW and at 2.5 mg CBD/kg BW [5,6]. Increases in ALT serum levels were reported in mice at 615 mg CBD/kg BW and in cats at 2 mg CBD/kg BW [4,7].
 
These studies indicate that CBD may have the potential for dose-dependent liver injury. Another useful indicator of long-term liver damage in horses is gamma-glutamyltransferase (GGT), due to its association with hepatocytes responsible for bile production [8,9].

In addition to the potential of liver injury, CBD may have a positive or negative effect on kidney function depending on the dosing level. Cannabinoid Type 1 (CBR1) and Type 2 (CBR2) receptors are found in the kidneys and interact with G-proteins, which produce several effects including an increase in calcium levels [10]. Elevated blood urea nitrogen (BUN), calcium (Ca), and creatinine are additional indicators of kidney function and signify if the kidneys are under stress [11].
 
Studies in horses have indicated similar concerns to health as those in rodents and companion animals. A pilot pharmacokinetics study evaluating three different dosage levels (50 mg, 100 mg, and 250 mg) of a pelleted CBD supplement given to horses in a single dose was performed by Draeger et al. [12]. Although serum chemistry was within normal ranges, BUN levels increased with CBD supplementation level and creatinine decreased then increased as supplementation level increased.

A study utilizing 2.0 mg/kg was well tolerated (in terms of vital signs, appetite, and attitude) over a period of 7 days [13]. However, when supplemented over 6 weeks, another trial found supplementation at 0.5 mg/kg or 1.5 mg/kg resulted in mild hypocalcemia and elevated liver enzymes in all horses [14].
 
Previous work involving dietary supplementation levels has focused primarily on companion animals, including dogs and cats, with limited information available regarding appropriate CBD oil supplementation levels in mature horses. Previous research in horses utilized 100 mg over 6 weeks, and observed decreased reactivity [3], or a single dose of 50 mg, 100 mg, and 250 mg in a pelleted supplement, and observed increasing levels of BUN indicating possible kidney stress [12].

A single oral dose (suspended in sesame oil) of 0.5, 1, or 2 mg/kg of CBD was utilized in exercising thoroughbreds [15] to evaluate potential anti-inflammatory effects, and was well tolerated by horses with no significant behavioral or gastrointestinal abnormalities observed.
 
Therefore, the objectives of the current study were to (1) determine the influence of CBD oil supplementation levels on the health of mature horses over 28 days by monitoring BW, BCS and grain intake, (2) evaluate factors associated with kidney and liver health by conducting a blood chemistry profile to measure BUN, creatinine, total protein, albumin, Ca, P, glucose, and liver enzymes, and to (3) identify the presence of CBD along with other banned substances ((CBD, 7-carboxycannabidiol, 7-Nor-7-carboxycannabidiol, and tetrahydrocannabinol (THC)) in serum as a result of dietary CBD oil supplementation.
 
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https://www.mdpi.com/2076-2615/13/2/245