Veterinary medicine has historically lagged behind human medicine since its inception. Veterinarians and veterinary technicians are cautious creatures that often have not only a human as the owner to deal with but a patient that cannot speak and tell you how treatment is or isn’t working. We also see less uniformity in regulations and practice acts in veterinary medicine compared to our human counterparts. What veterinary medicine and human medicine do have in common is the lack of education on the topic of cannabis as a legitimate medical therapy in veterinary school. Yet, the bias persists. However, the use and demand for cannabis products in veterinary medicine is growing rapidly, mainly by pet owner demand.2,3 Unfortunately, it is growing faster than most practitioners can educate themselves on. Another confounding factor feeding a negative bias in veterinary medicine is the all too often THC toxicity in companion animals. Since the legalization of medical marijuana in the United States began the Animal Poison Control and Pet Poison Hotline has seen a 330% increase in THC toxicities.4 There is no question to the risk and occurrence of THC toxicity in animals, yet it should be noted there are no reported deaths that can be definitively attributed to THC or other phytocannabinoids without other factoring chemicals also present in the system. The suspected lethal dose of THC in dogs is >9 g/kg, a nearly impossible dose to achieve. The most common route of exposure to THC in companion animals is via ingestion. Approximately 66% of exposures involve pets ingesting homemade or commercial edible goods. The second most common source of cannabis exposures involves ingestion of plant material, followed by cannabis oils/tinctures. Symptoms of THC toxicity include lethargy, central nervous system depression, ataxia, vomiting, urinary incontinence/dribbling, increased sensitivity to motion or sound, dilated pupils, hypersalivation, and bradycardia. Less common symptoms include aggression, agitation, low blood pressure, low respiratory rates, elevated heart rates, and nystagmus (continuous abnormal movements of the eyes).
There are some fundamental distinctions one must make on the topic of medical cannabis, and even specific terminology used when approaching medical cannabis as a valid medical therapy. The first distinction is between a “marijuana” plant versus a “hemp” plant.
The hemp plant has much lower levels of THC (less than 0.3% by dry weight) and has found favor among veterinary professionals since there is a reduced risk of THC toxicity.7 This distinction is particularly important for recommendations made by veterinary professionals.
At the time this article was written, there are no states that allow for medical marijuana prescriptions with many states also denying veterinarians the ability to even “recommend” an over the counter hemp-based product. California was the first state to pass legislation at the end of 2018 with AB2215 that allows veterinarians to discuss cannabis as a therapeutic option. The legislation still prohibits veterinarians from prescribing, dispensing or recommending marijuana or hemp products to animals.
To date, we have an ever-growing list of relevant studies for practical use of cannabis in companion animals. Most notably we now have the results from two studies, one conducted at Colorado State University (CSU) and one from Cornell University to help shed light on effective and safe dosing of CBD dominant cannabis products in dogs. In the Colorado State University study conducted by Dr. Stephanie McGrath, we see dogs give three different dosing strategies. A group of 30 healthy beagle dogs was randomly assigned to receive a cannabidiol dominant product in the form of a capsule, oil, and CBD transdermal cream at a dose of 10 mg/kg/day or 20 mg/kg/day for 6 weeks. In the study, the dogs had complete blood counts, chemistry panels, urinalysis, and bile acids were performed at 0, 2, 4, and 6 weeks. The most notable effect was elevations in serum alkaline phosphatase (ALP) occurred in some dogs. All of the dogs in the study also experienced diarrhea, while the dogs that received the transdermal formula had reddened skin after application that was not of clinical concern. Because the products used in the study were plant-based the variability between batches were measured. Variability was <10% for the CBD-infused transdermal cream and CBD-infused oil. There was considerable variation, 28–31% between the CBD concentration in the capsules and the amount stated on the label. Higher systemic exposures were observed with the oral CBD-infused oil formulation, and the half-life after a 75 mg and 150 mg dose was 199.7±55.9 and 127.5±32.2 min. Exposure was dose-proportional, and the oral CBD-infused oil provides the most favorable pharmacokinetic profile.
While the study mentions the diarrhea was not related to the formula, it should be noted that this assertion cannot be made with certainty. The study concluded that this particular CBD dominant product, with no terpenes, appeared to be well tolerated in dogs.9
Also, at CSU are two continuing studies. One on osteoarthritis (OA), the other on canine epilepsy. The OA study at CSU is using a 5 mg/kg daily dose for six weeks. The manuscript is currently under review. In the pilot epilepsy study utilizing a hemp-based product, preliminary results show 8 out of 9 dogs had a reduction in the frequency of seizures at 5 mg/kg once a day. A long-term study over 3 years will follow this study. A similar study is also being conducted at the University of Florida.10
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 initial investigation into single-dose oral pharmacokinetics was performed with 4 beagles. Each dog received a 2 mg/kg and an 8 mg/kg oral dosage of CBD oil. The dogs were fed 2 hours after dosing. Blood was collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after oil administration. Pharmacokinetics demonstrated that CBD half-life of elimination median was 4.2 hours for the 2 mg/kg dose 8 mg/kg dose. These results led to dosing during the clinical trial at 2 mg/kg body weight every 12 hours.
For the clinical efficacy study which assessed the use for dogs with radiographically confirmed osteoarthritis (OA) was a randomized placebo-controlled, veterinarian- and owner-blinded, cross-over study. Dogs received CBD oil (2 mg/kg) or placebo oil every 12 hours. 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 non-steroidal anti-inflammatory drugs with no adverse effects.11
Data has shown in both studies that the other non-psychotropic cannabinoids, primarily CBD, has a wide safety margin with only minimal side effects. In both studies conducted the elevated ALP was notable. Interestingly, the increase in liver values was not associated with any other elevated liver values (GGT, bile acids or ALT) and maybe a response to cannabinoid metabolism through the CYP450 pathway.12,13
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.14 Canopy Growth has announced the completion of their anxiety study in companion animals that are currently awaiting publication. The author is aware of other anxiety-related research being conducted in cats and birds with hopeful publication in the next year.
Aside from pharmacokinetic, pain, seizure and anxiety studies, we have seen scientific articles looking at cannabinoid receptor proliferation in feline and canine epidermal tissues suggesting the efficacy of topical and systemic applications for atopic dermatitis in dogs and hypersensitivity dermatitis in cats.19,20
Just like in human medical cannabis circles the veterinary side of things will continue to evolve, looking for specific cannabinoid and terpene profiles for various ailments or ECS support. As scientists, consumers and animal lovers we must pressure cannabis manufacturers to produce products following good manufacturing guidelines, use safe ingredients for animals and be transparent with what is in their products. To that end, manufacturers should suggest dosing regiments based on science instead of anecdotes. Lastly, we must encourage the veterinary profession to educate themselves on this topic.