The Latest on CBD in Veterinary Medicine

Before we get too far into the weeds—pun intended—let’s recap the important terminology and the endogenous system compounds from the cannabis plant. For clarity’s sake, this article will focus only on plant-derived products.

Research, Legislative, and Dosing Updates

In 2018, veterinary medicine saw the first clinically relevant cannabidiol/cannabidiolic acid (CBD/CBDA) peer-reviewed study showing safety and efficacy in reducing pain in client-owned dogs with osteoarthritis. Prior to this we had several studies looking at the physiological impacts, absorption, metabolism, and postulations as to the therapeutic use of cannabinoids in several lab animal models. Even before this sort of research began in the 1960s, ancient and modern cultures have been using the Cannabis sativa plant for thousands of years in humans and animals for medicine, rituals, and fun.

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Despite no FDA-approved veterinary product being currently available, there are at least ten published pharmacokinetic studies in dogs in addition to three safety studies evaluating clinical presentation of CBD-dominant products at various doses.

Before we get too far into the weeds—pun intended—let’s recap the important terminology and the endogenous system compounds from the cannabis plant. For clarity’s sake, this article will focus only on plant-derived products.

Cannabinoids or “phytocannabinoids” are compounds like CBD or THC, along with hundreds of others, that work on a system of receptors in the body called the endocannabinoid system. There are, for now, two primary receptors known as endocannabinoid system receptor one (CB1) and endocannabinoid system receptor two (CB2). What is the endocannabinoid system (ECS), you might ask? This is one of the oldest homeostatic regulating systems we see across vertebrate species in evolution. The ECS consists of the CB1 and CB2 receptors as well as at least five endogenous ligands known as endocannabinoids. The two most commonly studied are anandamide and 2-arachidonoylglycerol (2-AG). More recently it has been found that cannabinoids, both endogenous and plant based, can be quite promiscuous and have an affinity for other receptors we are more familiar with, such as opioid and serotonin, among others.

Researchers have also found ancient precursors of ECS receptors in nonvertebrate species known as orthologs. In some modern nonvertebrate species, there are only parts of what we consider the evolved ECS, such as endocannabinoids found in insects despite their lack of CB1 and CB2 receptors. Terpenes are another set of chemical compounds found in cannabis plants that add to the aroma of the plant and also have their own set of therapeutic impacts and synergy with cannabinoids.

Research Updates

Clinical research is still ongoing, but compared with other medications such as gabapentin, trazodone, and tramadol, we have a similar amount of data regarding the safety of the most common cannabinoids (CBD and THC), while most of the terpenes found in over-the-counter products are already FDA approved. It should be noted that a majority of the clinical data utilized individual cannabinoids or hemp-based products. Hemp-based products are those containing 0.3% THC or less.

Safety and efficacy are always of concern. Despite no FDA-approved veterinary product being currently available, there are at least ten published pharmacokinetic (PK) studies in dogs in addition to three safety studies evaluating clinical presentation of CBD-dominant products at various doses. For felines, there are two PK studies and two safety studies at various doses. There are two (soon to be three) PK studies in horses in addition to clinical use reports, one PK study for dairy calves, multiple PK studies for lab animal species, and a host of other species with studies that are still in process. Notably, given the vastly different formulations and ratios of various cannabinoids (more than 120 described so far) and terpenes, we cannot and should not assume all products will have the same bioavailability or efficacy when compared with those used in the published studies. Alkaline phosphatase (ALP) elevations in a small percentage of dogs and a transient alanine transaminase (ALT) elevation in one cat in one of the studies appear to be the most concerning side effects, but the clinical relevance is still uncertain. Most human and veterinary experts do not consider this a very serious concern unless the patient is already in some form of hepatic compromise. In general, a good quality product is considered incredibly safe when properly manufactured, tested, and appropriately dosed.

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Acute pain management studies with cannabinoids like CBD are lacking, though anecdotal evidence suggests promise.

Acute pain management studies with cannabinoids like CBD are lacking, though anecdotal evidence suggests promise. However, there are five peer-reviewed veterinary studies showing moderate to good efficacy in decreasing pain scores in dogs for chronic pain from osteoarthritis. Seizure management is another area of interest for owners and practitioners alike. One published study showed around a 33% decrease in seizure frequency and severity for dogs with intractable idiopathic epilepsy with the addition of what is considered, compared with CBD dosing for epilepsy in people, a low dose of a CBD-dominant product. A longer-term study utilizing a higher dose is currently underway. Some questions were rightfully raised about drug interactions or possible cytochrome P450 change with CBD and traditional antiepileptic drugs like phenobarbital. We can now have some comfort in administering drugs like phenobarbital with a CBD product without major concern for drug-to-drug interaction.

Anxiety and behavior modification are areas where better-designed clinical studies are warranted. There are two published studies that show no change and some change in the temperament of shelter dogs when exposed to loud auditory triggers and animal caretakers. Several press releases or abstracts have also been released, giving a glimpse of what’s next for other conditions like atopic dermatitis in dogs, stomatitis in cats, quality of life in canine cancer patients, acute pain in dogs, and anxiety in cats, and it’s all very promising.

Legislative Updates

Products derived from hemp (defined as any cannabis plant with less than 0.3% THC on a dry-weight basis) remain legal at the federal level and in all but four states, while the legality of products derived from marijuana varies from state to state. In states where all forms and uses of cannabis (hemp or marijuana) have been decriminalized or legalized, guidance from State Boards of Veterinary Medicine ranges from no guidance to legislation and regulations around veterinarians’ ability to recommend to or even discuss with clients the use of cannabinoids in veterinary patients.

More and more products derived from hemp are being accepted as no different than other nutraceuticals or supplements that veterinarians recommend every day, often with less scientific backing and data than exists for cannabinoid-containing products. CBD even has its own monograph in Plumb’s Veterinary Drugs, plumbs.com/features/drug-monographs, although the author has some concerns with the write-up. The author also has concerns about recommending marijuana-derived products even in states where it is legal, particularly for those that hold a DEA license given the legal status of marijuana at the federal level. However, Congress does seem poised to pass sweeping federal legislation changes on marijuana. For information on the legal status of all forms of cannabis in your state, visit norml.org/laws.

But keep in mind that regardless of marijuana’s legal status, there is a significant chance of adverse effects, such as intoxication, with higher-THC-containing products. The most current research in humans and animals also suggests beneficial therapeutic use can be achieved without the higher levels found in marijuana, begging the question of true clinical relevance.

Dosing

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Several press releases or abstracts have also been released, giving a glimpse of what’s next for other conditions like atopic dermatitis in dogs, stomatitis in cats, quality of life in canine cancer patients, acute pain in dogs, and anxiety in cats, and it’s all very promising.

Dosing can be quite nuanced as every product seems to have a different cannabinoid or terpene profile. Thus far, several studies show safety and efficacy with wide ranges in dosing and with short- and long-term use. Cannabinoid containing products are not a one-sizefits-all option. Depending on the specific condition and makeup of a product, recommendations can vary greatly. Understanding what is in the product will be an asset for successful and safe use. More information can be found on this via the textbook Cannabis Therapy in Veterinary Medicine.

As with any supplement, harm reduction and education are two key conversations that must be had with clients when recommending cannabinoid-containing products, including recommending monitoring of liver enzymes and tracking the patient’s response to administration. Please visit vetcannacademy.com for more information on cannabis harm reduction education.

Emerging Product Trends

Delta-8 THC

Delta-8 THC is a molecule that can be synthesized from CBD. This opened up a legal loophole for cannabinoid producers, who often market this version of THC as “legal THC.” This compound is unregulated and requires the heavy use of industrial solvents and other questionable chemicals to force the conversion of CBD to Delta-8 THC, some of which may remain in any final product. This compound is intoxicating and can produce similar negative effects seen with typical marijuana ingestion. At this time, it is not recommended to use this compound in animals. For further information, visit fda.gov/consumers/consumer-updates/5-thingsknow-aboutdelta-8tetrahydrocannabinol-delta8-thc.

Nepetalactone

This terpene is an active ingredient in catnip and silvervine that leads to the fun euphoric or intoxicating effect seen in cats. Many veterinary cannabinoid companies are looking to capitalize on the use of this terpene from cannabis in feline products. The intent is to help aid in administration as well as harness its therapeutic effects of mild sedation and euphoria. Similar to Delta-8 THC, the mass production of this terpene brings concerns, but utilization of plant-derived nepetalactone appears benign. 

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Stephen Cital, RVT, SRA, RLAT, CVPP, VTS-LAM (Res. Anesthesia) is an educator, author, researcher, and veterinary anesthesia/analgesia and cannabis expert. Cital works at the Howard Hughes Medical Institute at Stanford University School of Medicine in the Department of Neurobiology. In addition to conducting research, Stephen is an award-winning international lecturer on anesthesia, pain management, cannabis, and best practices.

 

Photo credits: GeorgePeters/DigitalVision Vectors via Getty Images

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