Therapeutic applications
As the medical community takes leaps into exploring the therapeutic applications of CBD, it's only natural for the veterinary world to be interested.
CBD has been at the forefront of numerous human clinical trials, revealing potential benefits across a spectrum of ailments. Similarly, preliminary studies in the veterinary domain have begun to shed light on its prospective advantages for animals.
While cannabis has been used medicinally for thousands of years, CBD is still an emergent medical intervention. It's important not to get caught up in the hype. The body of evidence for CBD's use in veterinary medicine is still in its infancy. Early results are promising but comprehensive conclusions require further rigorous research and clinical trials.
In this section, we'll cover some of the clinical conditions for which there are studies showing CBD may be useful.
Osteoarthritis, pain and inflammation
As the search for alternative therapeutic options for osteoarthritis (OA), pain and inflammation continues, medicinal cannabis is increasingly being considered for its potential anti-inflammatory and analgesic properties.
It may be used in conjunction with other anti-inflammatory/analgesic medications or as stand-alone therapy in pets with concurrent diseases (eg chronic kidney disease), especially when traditional anti-inflammatory drugs aren’t suitable.
Mechanism of action
Medicinal cannabis acts via receptors (CB1 and CB2) of the endocannabinoid system CB1 receptors are primarily found in the nervous system and are involved in pain modulation. CB2 receptors, prevalent in immune cells, play a role in controlling inflammation.
Studies into CBD have shown that:
it can reduce the production of pro-inflammatory cytokines and chemokines, as well as increase production of anti-inflammatory cytokines
it may affect the pain signaling pathways, including the descending inhibitory pain pathway, offering analgesic effects.
Dose
Commonly used dose: 2-2.5mg/kg bid
Dose range: 1–8mg/kg bid to tid.
Practical considerations
Product selection: There are lots of CBD products available – we recommend choosing one with third-party lab testing, ensuring purity and consistent cannabinoid content (you don’t want your clients paying for expensive hemp oil). Also, consider how the different components of medicinal cannabis work together – it may be worth prescribing full spectrum or broad spectrum CBD to get additional ant-inflammatory effects from terpenes and flavanoids.
Dosing: There is no formulary dose. Studies so far have suggested 2-2.5mg/kg bid appears to be effective, but every patient is different. It's advised to start with a low dose (0.5–1mg/kg) and titrate upwards, monitoring the pet's response. With full spectrum and broad spectrum CBD patients often need less.
Adverse effects: Although generally considered safe, potential side effects include lethargy, diarrhea, or changes in appetite.
Drug interactions: Cannabinoids can interact with other medications, especially those metabolised by the liver's cytochrome P450 system. Always review a pet's current medications before introducing medicinal cannabis.
Resources
Gamble, L. J., Boesch, J. M., Frye, C. W., Schwark, W. S., Mann, S., Wolfe, L., ... & Brown, H. (2018). Pharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs. Frontiers in veterinary science, 5, 165.
Bartner, L. R., McGrath, S., Rao, S., Hyatt, L. K., & Wittenburg, L. A. (2018). Pharmacokinetics and preliminary assessment of safety, and efficacy of cannabidiol in healthy dogs. Veterinarni Medicina, 63(No. 08), 373-378.
Silver, R. J. (2019). The Endocannabinoid System of Animals. Animals, 9(9), 686.
Cancer
Given the established anticancer properties of certain cannabinoids, there is a growing interest in understanding how CBD might aid in the management of cancer-related symptoms or even in the modulation of cancer growth.
Mechanism of action
CBD interacts with the endocannabinoid system, primarily through CB1 and CB2 receptors. The anticancer properties of CBD encompass a broad spectrum of actions:
Inhibition of tumour development: Consistent findings from both in vitro and in vivo studies suggest CBD's potential in deterring cancer growth, with some in vivo tests noting reductions in tumour size and, in certain cases, a decrease in metastasis.(1)
Promotion of cell death and reduced proliferation: CBD shows both pro-apoptotic and anti-proliferative actions, with its impact on apoptosis primarily via CB2 receptors. Elevated CB2 receptor levels in certain tumours like human leukaemias and lymphomas indicate potential sensitivity to CBD's CB2-mediated effects. As a standalone agent, CBD has been documented to decrease cell viability and instigate apoptosis in canine urothelial carcinoma cells.(2)
Anti-metastatic properties: CBD appears to have effects beyond direct influence on tumour cells. It exhibits anti-migrative, anti-invasive and anti-angiogenic characteristics. It shows potential as a comprehensive inhibitor of cancer progression and spread.
Reactive oxygen species (ROS) production: A notable anticancer mechanism of CBD is boosting ROS production. Increased ROS levels facilitate induction of both autophagy and apoptosis, critical processes in restraining cancer cell proliferation.(3)
CBD in combination therapies
Studies have indicated:
vincristine combined with CBD can lead to a significant decline in cancer cell viability, marking a synergistic effect.
mitoxantrone and vinblastine combined with CBD resulted in a pronounced reduction in cell viability in canine urothelial carcinoma cells.
carboplatin combined with CBD did not enhance the anticancer effects as compared to standalone carboplatin treatments.
doxorubicin combined with CBD yielded varying results - both synergistic and antagonistic outcomes, depending on the concentrations utilised.
Dose
Commonly used dose: 3–5mg/kg bid.
Dose range: 3–10mg/kg bid to tid.
Practical considerations
Product selection: The market is flooded with numerous CBD products. It's crucial to select one backed by third-party lab testing, which ensures both purity and consistency in cannabinoid content. Given the synergistic effect of various cannabis compounds, consider recommending full-spectrum or broad-spectrum CBD products.
Dosing: There is no formulary dose. When it comes to cancer, it’s also hard to base dose on clinical effects, however, the evidence so far suggests a dose of 3–5mg/kg bid may be appropriate. Always initiate with a lower dose, around 0.5-1mg/kg, and titrate up.
Adverse effects: CBD is generally deemed safe, but potential side effects, such as lethargy, diarrhea, or appetite changes, might occur.
Drug interactions: CBD's influence on the cytochrome P450 system might modify chemotherapy dosing due to potential alterations in drug metabolism.(4) The exact manner in which CBD impacts the serum concentrations of chemotherapeutic agents warrants further exploration.
Alternative to chemotherapy: CBD could be considered as a therapeutic alternative when chemotherapy isn't feasible.
Chemotherapy-resistant cases: For non-responders to conventional chemotherapy, CBD presents an alternative route.
Post-chemotherapy treatment: Following the conclusion of chemotherapy sessions, CBD may be a valuable adjunct therapy.
Synergistic effects with chemotherapy: Human studies have shown that CBD has enhancing effects on certain chemotherapy drugs.(5)
References
Seltzer, E. S., Watters, A. K., MacKenzie Jr, D., Granat, L. M., & Zhang, D. (2020). Cannabidiol (CBD) as a Promising Anti-Cancer Drug. Cancers (Basel), 12(11), 3203.
Inkol, J. M., Hocker, S. E., & Mutsaers, A. J. (Date of Publication: August 5th). Combination therapy with cannabidiol and chemotherapeutics in canine urothelial carcinoma cells. PLOS ONE.
Solinas, M., Cinquina, V., & Parolaro, D. (2015). Cannabidiol and Cancer — An Overview of the Preclinical Data. Molecular Considerations and Evolving Surgical Management Issues in the Treatment of Patients with a Brain Tumor, Date of Publication: March 25th.
Henry, J. G., Shoemaker, G., Prieto, J. M., Hannon, M. B., & Wakshlag, J. J. (2021). The effect of cannabidiol on canine neoplastic cell proliferation and mitogen-activated protein kinase activation during autophagy and apoptosis. Veterinary and Comparative Oncology, 19, 253-265.
Griffiths, C., Aikins, J., Warshal, D., & Ostrovsky, O. (2021). Can Cannabidiol Affect the Efficacy of Chemotherapy and Epigenetic Treatments in Cancer? Biomolecules, 11, 766.
Anxiety and related issues
Medicinal cannabis, particularly CBD, is rapidly gaining attention for its therapeutic potential in the field of veterinary behavioural medicine.
Mechanism of action
Neurotransmitter regulation: CBD works by interacting with the body's endocannabinoid receptors, predominantly CB1 and CB2. This interaction plays a crucial role in regulating neurotransmitter release, ensuring the maintenance of homeostasis in the nervous system.
Anxiety and fear: Through its interaction with the serotonin 5-HT receptor, CBD has been demonstrated to effectively reduce anxiety and fear in both human and animal studies.(1)
Sleep-wake regulation: CBD's anxiolytic effects have also been shown to have a positive impact on sleep-wake cycles.(2) This becomes particularly relevant for conditions like cognitive dysfunction.
CBD use
General anxiety: Studies in both human and animal models indicate that CBD exhibits both anxiolytic and paniolytic (panic-reducing) properties.
Compulsive behaviours: Some findings suggest that CBD may help in moderating compulsive behaviors and reduce autonomic arousal in subjects.
Fear and phobias: Observations have noted that CBD lessens conditioned fear expression and enhances fear extinction. This may be useful for pets with phobias or distressing memories.
Neuroprotective properties: CBD possesses anti-inflammatory and antioxidant properties that have shown promising results in studies involving various neurodegenerative disorders (eg Alzheimer’s, Parkinson’s, Huntington’s and Multiple Sclerosis). Animal models suggest that CBD might offer therapeutic benefits in addressing and even reversing neural alterations associated with conditions such as Alzheimer’s Disease.(3)
Behavioural disorders: Whether arising from anxiety, phobias or past traumatic experiences, behavioural issues may benefit from CBD as a supplementary or alternative treatment.
Neurological disorders: Given its neuroprotective attributes, CBD is being examined as a potential support for pets with neurodegenerative challenges.(4)
Dose
Dose range: 0.5–8mg/kg bid to tid.
For situational stress/phobias: 5–10mg/kg one hour before the event or PRN dosing once an event has started.
Practical considerations
Product selection: With the plethora of CBD products in the market, always opt for those with third-party lab testing. This ensures both purity and consistent cannabinoid content. A full spectrum or broad spectrum CBD can provide added therapeutic advantages due to the entourage effect of other cannabis components.
Dosing: The lack of a standardised dose necessitates individualised titration. Initiate therapy with a low dose (0.5–1mg/kg) and progressively adjust according to the pet's response. It's important to note that full spectrum and broad spectrum CBD may require lesser doses.
Adverse effects: In general, CBD is considered safe. However, side effects like lethargy, changes in appetite, or gastrointestinal disturbances can occasionally occur.
Drug interactions: Be cautious with other medications, especially those metabolised by the liver's cytochrome P450 system.
References
Blessing, E. M., Steenkamp, M. M., & Manzanares, J. (2015). Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics, 12(4), 825-836.
Hsiao, Y.-T., Yi, P.-L., Li, C.-L., & Chang, F.-C. (2012). Effect of cannabidiol on sleep disruption induced by the repeated combination tests consisting of open field and elevated plus-maze in rats. Neuropharmacology, 62(1), 373-384.
Fernandez-Ruiz, J., Sagredo, O., Pazos, M. R., Garcia, C., Pertwee, R., Mechoulam, R., & Martinez-Orgado, J. (2013). Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid. British Journal of Clinical Pharmacology, 75(2), 323-333.
Zadik-Weiss, L., Ritter, S., Hermush, V., Asher, N., Avital, A., & Or, R. (2020). Feline cognitive dysfunction as a model for Alzheimer’s disease in the research of CBD as a potential treatment- a narrative review. Journal of Cannabis Research, 2(1), 43.
Resources
Shannon, S., Lewis, N., Lee, H., & Hughes, S. (2019). Cannabidiol in Anxiety and Sleep: A Large Case Series. The Permanente Journal, 23, 18-041.
Silver, R. J. (2019). The Endocannabinoid System of Animals. Animals, 9(9), 686.
Ibeas Bih, C., Chen, T., Nunn, A. V., Bazelot, M., Dallas, M., & Whalley, B. J. (2015). Molecular Targets of Cannabidiol in Neurological Disorders. Neurotherapeutics, 12(4), 699-730.
Cognitive dysfunction
Cognitive dysfunction in pets is akin to the dementia seen in humans. Signs of cognitive decline can be distressing for both owner and pet.
Signs of cognitive decline that concern pet owners
Restlessness and pacing: Especially pronounced during the late evening hours, causing both pet and owner distress.
Sleep-wake cycle disruption: Pets might awaken frequently, interrupting their own and their owner’s rest.
Increased anxiety levels: This may be evident in heightened separation anxiety and general unease.
Unexplained vocalisation: Pets might vocalise without discernible triggers.
Disorientation and confusion: Signs include aimless staring and difficulty navigating familiar terrains.
Altered interaction: Pets might either withdraw or become overly attached to their owners.
Compulsive behaviors: Excessive actions, like licking, could lead to secondary issues such as skin complications.
Physical pain: Cognitive decline can be further complicated by physical issues like osteoarthritis
Mechanism of action
CBD interacts with the endocannabinoid system present in all mammals, influencing a variety of physiological processes. This interaction may help modulate neurotransmitter activity, reduce inflammation, and combat oxidative stress—factors that play a role in cognitive dysfunction.
CBD use
The therapeutic potential of CBD in treating cognitive dysfunction in pets revolves around its ability to:
alleviate anxiety and restlessness
regulate the sleep-wake cycle and improve sleep quality
reduce compulsive behaviors
offer pain relief, especially when cognitive issues are accompanied by other ailments like osteoarthritis.
While CBD can't reverse cognitive dysfunction, it offers a means to manage the symptoms, enhancing the quality of life for both pets and their owners.
Dose
Dose range 0.5–8mg/kg bid to tid
Practical considerations
Product selection: With the plethora of CBD products in the market, always opt for those with third-party lab testing. This ensures both purity and consistent cannabinoid content. A full spectrum or broad spectrum CBD can provide added therapeutic advantages due to the entourage effect of other cannabis components.
Dosing: The lack of a standardised dose necessitates individualised titration. Initiate therapy with a low dose (0.5–1mg/kg) and progressively adjust according to the pet's response. It's important to note that full spectrum and broad spectrum CBD may require lesser doses. For sleep-wake cycle disturbance, it can be beneficial to give the last dose just before bedtime (as late as possible)
Adverse effects: In general, CBD is considered safe. However, side effects like lethargy, changes in appetite, or gastrointestinal disturbances can occasionally occur.
Drug interactions: Be cautious with other medications, especially those metabolised by the liver's cytochrome P450 system.
Resources
Zadik-Weiss, L., Ritter, S., Hermush, V., Asher, N., Avital, A., & Or, R. (2020). Feline cognitive dysfunction as a model for Alzheimer’s disease in the research of CBD as a potential treatment- a narrative review. Journal of Cannabis Research, 2(1), 43.
Seizures
The role of CBD in treating seizures in both human and veterinary medicine has garnered significant interest.
Mechanism of action
CBD's anticonvulsant property isn't fully understood yet. However, it does not appear to primarily work via CB1 receptors.
CBD may work via the regulation of calcium and potassium channels. By modulating the activity of these channels, CBD may stabilise erratic neuronal firing, thus helping reduce seizures.
Additionally, CBD's effect on seizures may also be attributed to its action on GP5RR and serotonin receptors, which play a role in various neurological pathways.
CBD use
Reduction in seizure frequency: Studies have shown that CBD can significantly reduce the frequency of seizures in pets, providing relief and improved quality of life.
Safety: CBD is known for its safety profile, especially when compared to traditional antiepileptic drugs. While certain side effects, such as drowsiness, can manifest, they are typically mild and transient.
Co-treatment potential: Preliminary findings suggest that CBD can effectively complement standard antiepileptic medications, potentially enhancing their therapeutic outcomes.
Dose
Dose range: 2.5–10mg/kg bid
Higher end of dose range generally used for shorter term.
Practical considerations
Dosing: Starting dose can be higher (1mg/kg BID) and increases can occur quickly (every 24hours by 1mg/kg) if needed.
Drug Interactions: CBD is a known inhibitor of the cytochrome P450 enzyme system. Veterinarians and pet owners should be aware of this when considering concurrent administration of CBD with traditional antiseizure medications. Proper monitoring and dose adjustments might be necessary to ensure optimal therapeutic benefits and minimal side effects.
Resources
Devinsky, O., Marsh, E., Friedman, D., Thiele, E., Laux, L., Sullivan, J., ... & Cilio, M. R. (2016). Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. The Lancet Neurology, 15(3), 270-278.
McGrath, S., Bartner, L. R., Rao, S., Packer, R. A., & Gustafson, D. L. (2019). Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy. Journal of the American Veterinary Medical Association, 254(11), 1301-1308.
Kaplan, J. S., Stella, N., Catterall, W. A., & Westenbroek, R. E. (2017). Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. Proceedings of the National Academy of Sciences, 114(42), 11229-11234.
Patra, P. H., Barker-Haliski, M., White, H. S., Whalley, B. J., Glyn, S., Sandhu, H., ... & Jones, N. (2019). Cannabidiol reduces seizures and associated behavioral comorbidities in a range of animal seizure and epilepsy models. Epilepsia, 60(2), 303-314.
Kogan, L. R., Hellyer, P. W., Robinson, N. G., & Downing, R. (2020). Consumers’ perceptions of hemp products for animals. Journal of the American Holistic Veterinary Medical Association, 58, 23-32.
Silver, R. J. (2019). The Endocannabinoid System of Animals. Animals, 9(9), 686.
Jones, N. A., Hill, A. J., Smith, I., Bevan, S. A., Williams, C. M., Whalley, B. J., & Stephens, G. J. (2010). Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. Journal of Pharmacology and Experimental Therapeutics, 332(2), 569-577.