Cannabis holds great promise for treating many disease states in dogs and cats. It’s important for veterinarians to educate clients by staying informed about the growing number of cannabis products appearing on the market.
The legalization of cannabis in the United States is expanding every year. Many pet guardians are turning to their veterinarians for counsel about the medicinal benefits and appropriate use of cannabis for their dogs and cats. As the market becomes flooded with products labeled for pets, it has become critical that veterinarians are able to have open and informed discussions with clients about cannabis.
Cannabis nomenclature
Many common misconceptions about cannabis products can be eliminated by understanding the terminology associated with the industry.
• Cannabis is the plant’s genus classification – hemp and marijuana are varieties of cannabis sativa L.1
• Cannabis plants that contain high levels of delta-9-tetrahydrocannabinol (THC) are termed marijuana. THC is the psychoactive cannabinoid that causes a “high”.
• Cannabis plants with low levels of THC (less than 0.3%) are termed hemp plants. Hemp plants can be used for medicinal or industrial purposes.
• Medicinal hemp plants are rich in cannabinoids like cannabidiol (CBD). While CBD is receiving most of the attention, medicinal hemp plants contain other therapeutic compounds such as terpenes and flavonoids.2
The endocannabinoid system
The endocannabinoid system is made up of cannabinoid receptors and endogenous lipid ligands called endocannabinoids. These receptors are located in the central and peripheral nervous system as well as other tissues such as immune cells. These receptors can be bound by cannabinoids made by the body called endocannabinoids. Cannabinoids from plant sources, phytocannabinoids, can also bind these receptors.
The endocannabinoid system regulates and influences many physiologic processes involved in homeostasis in the body, including pain, mood, and immune function.3 Several endocannabinoid receptors have been identified. The most studied receptors are CBD1 and CBD2. CBD1 receptors are bound by THC and are concentrated in the nervous system including the cerebellum. This is why our canine patients present with static ataxia after the ingestion of cannabis containing THC.3 CBD is a CBD1 antagonist and can therefore lessen the effects of THC. CBD2 receptors are found primarily in immune cells and the central nervous system. CBD’s anti-inflammatory properties are a result of its inverse agonist action on CBD2.4 CBD has been shown to have antioxidant properties and reduces pain.2 These properties make CBD and other therapeutic phytocannabinoids of great interest for treatment of common disease in dogs and cats.
Toxicity concerns
Medicinal and recreational marijuana is becoming more prevalent in households due to its increasing availability. As cultivation technology advances, the concentration of THC in available products has risen significantly over the last few decades. As a result, the number and severity of marijuana toxicosis cases seen in veterinary practice has increased.5
Dogs are the most common species seen for marijuana toxicosis. Dogs have a higher concentration of THC (CBD1) receptors than other species. A dose of THC causing a
comfortable dysphoria in a human would cause severe static ataxia and other clinical signs in a dog. The onset of clinical presentations varies greatly, depending on the route of exposure (inhalation vs. ingestion), dose and type of product (cannabis products mixed with THC-infused butter maybe more dangerous).5 Symptoms can include hypersalivation, urinary incontinence, static ataxia, vomiting, depression, hyperactivity, and bradycardia. Rarely, death caused by marijuana toxicity has been reported. Most dogs recover with supportive care, including intravenous fluids, judicious induction of emesis and activated charcoal, benzodiazepines if indicated, and monitoring of vital signs.6
Product selection
Due to the legal limitations of products with THC, this author recommends using products with less than 0.3% THC and high levels of CBD. There is currently no federal regulation of these products (the U.S. Farm Bill is still pending at the time of writing), so when selecting a product to recommend, or researching a product found by a client, it is important to consider several factors:
1. Plant cultivation
Organic farming practices are important to avoid unnecessary chemical exposure. While hemp can be sourced from China and Europe, hemp grown in the United States is regulated at the state level. This allows for better quality control and a safer substrate.
2. Extraction method
Two predominant types of extraction method exist in the cannabis industry – alcohol extraction and CO2 extraction. While each method has benefits, most large companies use CO2 extraction to ensure that the highest levels of medicinal components are preserved.
3. Guaranteed analysis (GA)
The manufacturer should be able to provide a GA that shows the concentration of THC, CBD and terpenes present in the hemp extract. The GA should also include testing of heavy metals, solvents and pesticides.
4. Delivery method
Hemp extract can be added to oil or made into a chewable form. It is important to take note of the other ingredients for patients with food sensitivities.
5. Concentration
To keep consumer costs low, many manufacturers create products with very low CBD concentrations. As a result, pets may be getting subtherapeutic doses. In this author’s experience, a minimum of 15 mg of CBD per 1 ml of oil is necessary to administer a therapeutic dose at a reasonable volume.
A recent pharmacokinetic study done at Colorado State University revealed that oral absorption of oil with hemp extract was superior to transdermal application.8 More studies are needed to investigate transdermal administration to local lesions.
CBD isolate is available in most states and has anecdotally been less effective compared to full spectrum hemp extracts.
What conditions is CBD most effective for?
In this author’s clinical experience, full spectrum CBD products have been most effective in cases of anxiety, osteoarthritis and seizure disorders in both dogs and cats. For the purposes of these case studies, HempRx Forte was used.
Anxiety
CBD-rich cannabis is the most effective natural method for treating anxiety in both dogs and cats, in this author’s practice.
Start at a dose of 0.5 mg/kg by mouth every 12 hours with food, and increase every three days to the desired effect. Most guardians notice improvement within 12 to 24 hours. In
refractory cases, this author has administered CBD with SSRIs. However, there are no studies proving their combined safety.
Osteoarthritis
A recent study at Colorado State University demonstrated that dogs with osteoarthritis had improved pain scores with 2 mg/kg of CBD every 12 hours.7 It’s this author’s clinical experience that CBD improves the mobility and comfort of dogs and cats experiencing pain from osteoarthritis and neurogenic causes. Many traditional pharmaceuticals such as gabapentin, tramadol and amantadine have questionable efficacy and undesirable side effects. While non-steroidal anti-inflammatories are effective, many of the side effects
make their long-term use prohibitive.
Epilepsy
CBD-rich hemp extracts have gained popularity for treating children’s seizure disorders. Due to the lack of THC, these children can enjoy life without the sedative effects of traditional anticonvulsants. Many pet guardians are hesitant to use drugs like potassium bromide and phenobarbital long-term due to their undesirable side effects. Other drugs like levetiracetam have questionable efficacy and dosing schedules that make compliance difficult. CBD may provide a safe and efficacious alternative for some animals. It may also help reduce dosage in conventional pharmaceuticals.
In this author’s experience, many animals with refractory seizures may require doses of up to 2 mg/kg to 4 mg/kg of CBD every 12 hours. CBD is metabolized by the icytochrome P450 system and may therefore alter metabolism of anticonvulsants such as phenobarbital.7
Dose/ administration/ side effects
Very few studies have been published that explore the pharmacokinetics and optimum dosing schedule for CBD in cats and dogs. One pilot study investigating the pharmacokinetics of CBD found that the half-life of the particular oil used was around four hours.7 In the author’s clinical practice, starting with a dose of 0.2 mg/kg to 0.5 mg/kg twice daily, and increasing to efficacy, has been generally successful. For long-term treatment, higher doses (2 mg/kg to 4 mg/kg) for large dogs can be cost prohibitive. Finding the lowest dose that gives the desired effect can increase compliance.
In this author’s experience, adverse effects are rare and may include vomiting and diarrhea (more common in cats) and mild sedation.
Legal questions
Marijuana is legal in several states for medicinal and recreational use, but remains illegal at the federal level. At this time, it is illegal for veterinarians to prescribe or dispense products derived from marijuana plants. The legality of hemp products containing CBD varies by state. To find the current legislation in a specific state, visit http://norml.org/states.
Additional applications for CBD
CBD has proven efficacious (anecdotally) in the following disease processes:
• Chronic upper respiratory infections in cats
• Poor appetite in cats
• Atopy
• Feline asthma
• Chronic pancreatitis
• Inflammatory bowel disease (IBD)
Cannabis in Canada
By Katherine Kramer, DVM
Although cannabis has recently been legalized for people in Canada, Canadian veterinarians are still not allowed to recommend or prescribe any cannabis products. The Canadian Veterinary Medical Association and the Canadian Association for Veterinary Cannabinoid Medicine are working with Health Canada to provide a legal pathway for veterinarians but it still may be several years before there are any veterinary approved products.
One benefit of legalization is that we should begin to see many more companion animal studies as the legal barriers have been removed. Anecdotal evidence is certainly mounting
as veterinarians across Canada are reporting that seeing benefits in their patients for a wide range of issues: arthritis and chronic pain, cancer and chemotherapy, inflammatory
bowel disease, asthma, allergies, diabetes, seizure disorders, anxiety, etc.
Unfortunately the rate of accidental toxicity is increasing due to easy access to cannabis products and pet guardians hoping to see the same therapeutic benefits in their pets as seen in people. Cannabis pet products are readily available online, in dispensaries and pet stores. These products are illegal and not regulated so finding a safe, quality controlled product can be challenging. Dosing is experimental and widely variable depending on the patient, medical condition, concurrent medications and product being used. Starting with a low dose and titrating slowly is the best option.
Cannabis therapy has tremendous potential for our patients. Education will be key in helping pet guardians find and use pet products safely and effectively until veterinarians are allowed to prescribe cannabis.
Conclusion
Cannabis holds great promise for the safe and effective treatment of many disease states caused by inflammation, immune dysfunction and neurotransmitter imbalance in dogs and cats. It’s the author’s hope that the ever-changing legal landscape will allow for further investigation into the use of phytocannabinoids for dog- and cat-specific disease processes.
References
1https://plants.usda.gov/java/Classifi cationServlet?source=display&classid=CASA3,(accessed on 9/22/18).
2Podell M. “Highs and lows of medical marijuana in the treatment of epilepsy”. Proc Am Coll Vet Intern Med Forum, 2015.
3Murillo-Rodriguez, Eric. The Endocannabinoid System. 1st ed. London: Academic Press; c2017. Chapter 2, “Cannabinoid Receptors and Their Signaling Mechanisms”, p26-28.
4Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. Cannabidiol displays unexpectedly high potency as an antogonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. (2007) Mar;150(5):613-23
5Meola SD, Tearney CC, Haas SA, Hackett TB, Mazzaferro EM. “Evaluation of trends in marijuana toxicosis in dogs living in a state with legalized medical marijuana: 125 dogs (2005-2010)”. J Vet Emerg Crit Care. (2012) 6:690-696.
6Fitzgerald KT, Bronstein, AC, Newquist, KL. “Marijuana Poisoning”. Topics in Compan An Med. (2013) 28(8-12).
7Bornheim LM, Everhart ET, Li J, Correia MA. “Induction and genetic regulation of mouse hepatic cytochrome P450 by cannabidiol”. Biochemical Pharacol. (1994) 48:1(161-171).
8Gamble LJ, Boesch JM, Frye CW, Schwark WS, Mann S, Wolfe L, Brown H, Berthelsen ES, WakShlag JJ. “Pharmacokinetics, safety and clinical effi cacy of Cannabidiol treatment in osteoarthritic dogs”. Front Vet Sci. (2018) 5:165.