We make it our business to bring you topical science-backed equine insight, so following some questions from our members into the efficacy of feeding horses CBD (Cannabidiol), Dr Kirstie Pickles has written this incredibly thorough guide covering everything from the definitions to the side effects of CBD, as well as her concluding thoughts and advice.
By Kirstie Pickles BVMS MSc PhD CertEIM DipECEIM MRCVS FHEA – European Specialist in Equine Medicine
CBD – What is it exactly?
To answer this question, first let’s make sure we are all talking about the same thing by starting with some definitions!
Colloquially, people often talk about cannabis and marijuana as the same thing. Cannabis refers to the Asian herb of the hemp plant family. Marijuana, however, is the psychoactive dried flower buds and leaves of the cannabis plant, although the term can refer to any part of the cannabis plant containing greater than 0.3% of delta-9-transtetrahydrocannabinol (THC) on a dry weight basis.
Hemp, meanwhile, is any part of the cannabis plant containing less than or equal to 0.3% (THC). THC is one of the many naturally occurring, biologically active cannabinoid compounds produced by the cannabis plant, and is the main psychoactive (affecting how the brain works) constituent for which marijuana is used as a recreational drug.
Cannabidiol (CBD) is a non-psychoactive lipid cannabinoid, therefore CBD products refer to substances containing cannabidiol. These cannabinoids bind to cannabinoid receptors which are found in many mammalian tissues. A multitude of CBD products, from CBD chocolate, oils, capsules and equine supplements are commercially available in the UK.
Why use CBD?
The activation of cannabinoid receptors by endogenous (produced by the body), plant-derived or synthetic cannabinoids reduces pain sensation by decreasing the transmission of pain signals along nerves and, also, by reducing inflammation. CBD shows numerous health-related benefits, including anti-inflammatory, anti-spasmodic and anti-anxiety properties and has been used in human medicine for pain management, anxiety, multiple sclerosis, relief from nausea, and control of certain types of seizures.
For CBD to have a therapeutic effect in the horse, several conditions must be met. Firstly, CBD must be present in the administered product at a sufficient concentration, and in a form well absorbed by the horse. It must then be taken up by the relevant tissue at a useful concentration and that tissue must contain cannabinoid receptors for the CBD to bind to and exert an effect. Lastly, CBD is most likely to have a therapeutic effect in tissues where these receptors are upregulated in the targeted disease state. There should also be no adverse side effects caused by the administration of CBD for it to be a useful therapy.
Next we will look at the evidence for each of these conditions in the horse.
What are the doses and efficacy?
Several studies have investigated the oral bioavailability (amount of active substance in the blood following administration by mouth) of CBD in horses. When doses of 1-3mg/kg CBD are administered orally, approximately 10% is absorbed and available to the horse. Whilst this may seem low, it is comparable to CBD bioavailability in human and dogs. CBD was detectable in equine blood after 1mg/kg oral administration to healthy horses but was only detectable in joint fluid at doses of 3mg/kg indicating that, in healthy horses at least, higher dosages are required to reach joint tissue. Micellar formulations are absorbed faster and obtain a higher concentration peak, while the oil formulations result in lower levels but maintained more consistently over time. CBD penetrates tissues well, especially tissues with a high proportion of fat.
Dosages of 10mg/kg orally are required to achieve blood concentrations equivalent to those following 1mg/kg intravenous administration of CBD showing the large amount lost in the absorption process. Oral CBD doses of 10mg/kg every 12 h were enough to reach concentrations in the blood up to 40 ng/ml, where doses every 24 h reached concentrations above 10 ng/ml during the dosing interval. The therapeutic dose required in horses is currently unknown but reported clinical therapeutic concentrations of CBD in humans are reported as ranging from 5–10 and 15–30 ng/ml, whereas in dogs, 2 mg/kg every 12 h have been described as beneficial for 4 weeks. Recommended dosages of many commercial supplements are far below likely therapeutic dosages and often equate to well below 0.5mg/mg.
Cannabidiol receptors have recently been identified in a number of equine tissues, including nerve roots in the neck and head, small intestine, skin, and joint tissue. Furthermore, greater numbers of receptors were identified in inflamed joint tissue suggesting that they may play a role in joint pain. This is the best evidence to date that CBD could be useful in the management of pain associated with equine joint disease.
What are the side effects?
CBD administration appears to be well tolerated by healthy horses, including older animals, without any adverse effects, even in prolonged administration of up to 3 months. Some studies have reported mild elevations in liver enzymes although these were not of clinical significance and levels returned to normal shortly after stopping administration. However, it is important to realise that, to date, studies have mainly been conducted on healthy animals, and so the use of CBD in horses with pre-existing liver or kidney disease, or other systemic conditions, may be different. Additionally, dosages used in some studies that reported a lack of adverse effects have been lower than those likely to produce a therapeutic effect.
CBD is well absorbed by fat leading to prolonged tissue retention and slow elimination from the body. This slow elimination has competition implications as CBD is on the FEI’s list of controlled medications, and there is limited information available concerning CBD detection times in blood or urine. Additionally, as many of the available CBD products marketed to horse owners contain some quantity of THC, this may also result in a positive drug test. Previous research has indicated that a single dose of THC may result in detectable metabolites of THC in urine or plasma for up to 8 to 12 days in humans and dogs.
When would you use CBD in horses?
An anti-inflammatory role for CBD was recently evidenced in an in vitro (test tube) study in which a CBD concentration of 4 µg/mL significantly decreased production of inflammatory chemicals by white blood cells taken from older horses. A subsequent in vivo (animal) experiment administering 2mg/kg oral CBD once daily for 90 days to older horses (average age 24 years) showed a similar reduction in inflammatory proteins. Importantly, however, CBD did not significantly affect any other metabolic or immune factors, including response to influenza vaccination. Despite the reduction in blood cell derived inflammatory proteins, lameness scores taken before and after 90 days of CBD did not show any reduction, or difference from placebo-treated animals. As the therapeutic dose of CBD is currently speculative, it may be that this study simply did not use a high enough dose to reduce lameness scores, or a larger study is required to see a significant effect.
A case report has described the successful use of oral CBD at 0.5 mg/kg twice daily for four weeks to reduce chronic crib-biting and wind-sucking in a 22-year-old mare. Treatment resulted in a rapid decrease from 15 to 6 hours per day spent performing stereotypic behaviours within 24 hours of initiating therapy, which further decreased to less than 1h/d by 4 weeks. A parallel increase in weight gain occurred over the 4 weeks as stereotypical behaviour decreased, despite no change in feed or management practices. The effect was maintained for 4 weeks after cessation of therapy before the horse was unfortunately euthanised due to a fractured limb.
Again, a single case report details the use of CBD to treat marked sensitivity to touch near the withers/shoulder region of 5 weeks duration in a 4-year-old mare, which had previously failed to respond to gabapentin (used to treat nerve pain), acupuncture, steroids, magnesium and vitamin E. A CBD dose of approximately 0.5mg/kg twice daily by mouth resolved the sensitivity within 2 days. However, cessation of therapy after 60 days led to a recurrence of clinical signs within 24 hours, which, again, was resolved following re-instigation of CBD.
As CBD has been reported to decrease heart rate and to show anxiolytic effects in humans, this effect has been investigated in horses using a single oral administration of CBD paste at dosages of 0.2 mg/kg, 1 mg/kg, 3 mg/kg to healthy horses. Stress parameters, including behavioural observations and heart rate monitoring did not identify any significant differences when compared to a control group. It is possible that higher doses, or administration over longer time periods, may affect behaviour or, as horses in the current study were healthy and displayed calm behaviour throughout, a different effect would have been seen in stressed or anxious horses. The same research group then investigated the effect of oral CBD at 3 mg/kg twice daily for 15 days but, again, found it had no significant effect on behavioural observations, including during a novel object test, or cortisol levels, heart rate and heart rate variability in horses.
What’s my conclusion?
Oral CBD products can be absorbed by horses and are distributed to tissues where cannabidiol receptors are present. Some evidence exists that oral administration can lead to improvement in stereotypical behaviour or skin hypersensitivity. However, these are limited to single case reports.
As yet, there is no evidence that CBD reduces lameness or anxiety, although more research is needed into therapeutic dosages. It is possible that different dosages of CBD are necessary for different therapeutic effects, and it is likely that more studies will be forthcoming to shed further light on this subject.
Many CBD products are available, but it is important to calculate the actual dose given to the horse. Based on the limited data available, dosages less than 0.5mg/kg are extremely unlikely to exert any effect. For a 500kg horse, a dose of 0.5mg/kg would equate to giving 250mg CBD.
Caution should be taken if using CBD in a competition horse as it is likely to remain detectable in urine and blood samples for a considerable period of time following the last dose.