Use of cannabidiol (CBD) is currently a popular treatment option in small animals and is being used in horses despite the lack of empirical evidence for dosage, efficacy or side effects. For now, the FDA has only approved CBD use in humans for treatment of epilepsy in patients older than a year of age.
In this Research Spotlight, we will cover several research studies using CBD in a variety of equine cases.
Oral Cannabidiol Safety
Alicia Yocum, DVM, of Colorado State University, spoke about safety issues of CBD at the AAEP 2021 Convention. While THC is the psychotropic compound in marijuana or hemp weed, CBD extract has to contain <0.3% of THC to be allowed to the market.
A study used 12 mixed-breed horses given two different doses of CBD for six weeks. The CBD source for this study was added to 5 ml of sunflower lecithin oil. Dosing followed 30 minutes after consumption of one pound of grain. (Human studies have found that bioavailability of CBD increases four- to five-fold when they eat a high-fat meal.) The horses received the full does split into two administrations:
- Low dose Group 1 received 1 mg/kg/day
- High dose Group 2 received 3 mg/kg/day
The results from plasma and blood chemistries and synovial fluid analysis were obtained over many time points:
- No adverse effects were seen with daily monitoring, physical exam or behavior.
- Liver values increased in eight/12 horses, but by 10 days after the last dose, all horses’ liver enzyme values were within normal limits, and some returned to below where they had started.
- Calcium decreased in all 12 horses, but ionized calcium was normal.
- The time to maximum plasma concentration of CBD was the same for both groups—a mean of four to five hours.
- Low-dose CBD was detectable at 24 hours and high-dose at 48 and 96 hours, but half-life values normalized by six weeks in both groups.
- CBD was identified in synovial fluid for 12 hours in six/12 horses, but at 24 hours was only detectable in one/six.
- Plasma concentrations were dose dependent, and this was reflected in the synovial fluid.
The study authors recommended dosing four hours before a desired peak effect.
More information is needed to determine appropriate withdrawal recommendations for competition. At this time, neither the FEI nor the USEF allows any detectable levels of CBD. The other notable point was the expense—$30/day for the low dose and $90/day for the high dose used in the study.
That said, current recommended doses vary between 0.1-1.0 mg/kg/day, which is well below the doses used in this study.
CBD Effects on Sedation and Ataxia
At the AAEP 2021 Convention, Michael St Blanc, DVM, of Louisiana State University, presented results from a study looking at effects of CBD on equine mentation, coordination, and hepatic and renal function.
The 22 Thoroughbred geldings in the study were stall confined and fed 150 mg CBD (0.3 mg/kg) once a day for 56 days. Control horses were only fed the inactive ingredients of alfalfa meal and sunflower lecithin and meal. Blood values, physical exam findings, plasma concentrations, sedation and ataxia scores were collected on Days 0, 28 and 56.
In summary, the CBD was relatively palatable when top dressed on food. Horse body weight did not differ between treated and control groups. No significant changes occurred in blood chemistry parameters, and there was a slight increase in plasma CBD concentrations from 40% to 78%. Both sedation and ataxia scores showed no significant differences throughout the study—all were scored as 0. No adverse effects were seen throughout the study.
Effects of CBD on Heart Rate and Reactivity
The increasing popularity of using CBD to modify horse behavior and to address musculoskeletal pain has stimulated a number of studies looking into various effects of CBD. One study at Murray State University in Kentucky looked at heart rate and reactivity after a six-week period of CBD administration [Draeger, A.; Thomas, E.; Jones, K.; et al. The effects of pelleted cannabidiol supplementation on heart rate and reaction scores in horses. Journal of Veterinary Behavior 2021; doi.org/10.1016/j. jveb.2021.09.003].
The researchers observed the effect of CBD on horse anxiety and reactivity. Studies have previously reported: “The alteration of neurotransmitter release from the brain by cannabinoids could result in pain reduction and muscle relaxation, as well as antioxidant and anti-inflammatory action.”
In the Kentucky study, 17 horses were separated into either a treatment group or control group. All horses received the same management and diet with the exception that the treatment group was supplemented with 40 grams of pelleted CBD that contained 100 mg of CBD. This was fed once daily for six weeks. Testing of reactivity relied on a novel object reaction test (NOT) given before and after six weeks of CBD supplementation. The novel object tested involved a person standing around the corner of the barn holding and opening an umbrella as the horse passed by.
Study results did not identify any change in heart rate between treated and control horses, although the horses treated with CBD were less reactive than the control horses.
Cannabinoid-Related Receptors in the Ileum
Recent mitigation efforts have focused on the use of therapeutic molecules directed against visceral and somatic pain such as experienced with a colic episode. CBD is a potentially useful new therapeutic agent that might be used for this purpose.
An Italian study delved into the pathophysiology of receptors within the ileum of six healthy 1.5-year-old horses slaughtered for food purposes [Galiazzo, G.; Tagliavia, C.; Giancola, F.; et al. Localization of Cannabinoid and Cannabinoid-Related Receptors in the Horse Ileum. Journal of Equine Veterinary Science 2021, vol 104; https://doi.org/10.1016/j. jevs.2021.103688].
Two receptors—CB1R and CB2R—play a protective role in inflammatory bowel disease in humans, and these were examined in equine ileum for their potential use as a target using pharmacological agents. These receptors are widely distributed in equine ileum. CB1R has a role in regulating intestinal permeability, cell regeneration, wound healing and inflammation. CB2R was also identified in enterocytes with the role of preserving intestinal mucosal integrity and immunomodulatory effects in immune cells, such as reduction of lymphokine production.
Other CBD-related receptors in the intestinal tract regulate lipid metabolism and have anti-inflammatory effects.
All of these receptors were identified in the ileum; no other portions of the bowel were examined.
The authors summarized, “Various cell types (epithelial cells, immune cells, neurons, glial cells and muscular cells) showed immunoreactivity for the receptors studied, highlighting the important role of the endo-cannabinoid system in gut homeostasis. It is possible that trials could identify therapeutic uses against visceral pain, inflammation and improvements in intestinal motility using CBD.”
Treatment of Mechanical Allodynia Using CBD
Mechanical allodynia is a syndrome that involves a painful response elicited from a non-painful stimulus, such as hypersensitivity to touch. A study at Colorado State University (CSU) evaluated the effect of CBD on alleviating a 4-year-old Quarter Horse mare’s hypersensitivity to touch around the withers and shoulders [Ellis, K.; and Contino, E. Treatment using cannabidiol in a horse with mechanical allodynia. Equine Veterinary Education2019; doi: 10.1111/eve.13168].
No abnormalities were found on the hypersensitive mare following diagnostic imaging or physical examination. A neurological exam was normal, and there was no lameness. A hormonal panel revealed no abnormalities.
With a touch of her withers or shoulder region, she would twitch uncontrollably, kick and strike out to the point of being dangerous. Only very mild improvement was noted after two 20 mg daily doses of dexamethasone and 5000 IU vitamin E daily given before her presentation to CSU.
Treatments following a thorough exam and imaging then included gabapentin, systemic prednisolone, magnesium and continued vitamin E to no avail over a three-month period.
Other diagnostic testing and treatment with Regumate or reserpine were offered to the client, but she elected to try the mare on CBD.
In only 36 hours of 250 mg (o.5 mg/kg) CBD treatment given twice daily, the mare showed significant improvement in nociception and neuropathic pain with CBD.
An attempt to drop the mare’s dose to half did not work as her clinical signs immediately resurfaced. She went back on the 250 mg bid dose, which was then tapered gradually over two months without any recurrence of clinical signs.
Her maintenance dose is 150 mg (0.33 mg/kg) CBD orally once a day. The owner reports an overall improvement of 90%.
The authors noted that cannabinoid type 2 receptors are present in the central nervous system and lymphoid tissue. CBD mediates release of cytokines from immune cells to reduce inflammation and pain. Cannabinoid type 1 receptors in the brain affect neurotransmitter release to help in calming and reduction of anixiety.
Cannabinoid use might be helpful to modulate equine pain and behavior difficulties, but the authors recommended more research to “establish safety, bioavailability, dosage and drug interactions.”
