Debate continues over CBD therapy

A lot has happened since 2018 when published results of the first clinically relevant peer-reviewed study showed safety and efficacy of cannabidiol (CBD) in reducing pain in dogs with osteoarthritis.¹

Despite being used for thousands of years in both humans and animals, cannabinoids—the therapeutic molecules found in Cannabis sativa Linnaeus—have been stigmatized or considered an illegitimate or illegal therapeutic tool for veterinary patients since the 1930s. This largely stemmed from legal prohibition at the federal level, which still exists today.² There is much to be done to educate clinicians about the therapeutic indications for cannabinoids, as well as dosing ranges and harm reduction.

For clinical application, data from preclinical studies and veterinary specific clinical trials show the legitimacy and usefulness of these compounds in veterinary populations. This is especially true when comparing cannabinoid use with other novel or integrative techniques already well adopted by veterinary practitioners despite limited or conflicting evidence. However, the data on how these compounds work still need further research and dissemination to practitioners, in addition to larger powered studies and diversity in clinical use.

RESEARCH UPDATES

Although there is no FDA-approved veterinary CBD product currently available, at least 10 pharmacokinetic (PK) studies on CBD in dogs have been published, in addition to 3 safety studies evaluating clinical presentation of CBD-dominant products at various doses.^1,3-12 For cats, there are 2 PK studies and 2 safety studies at various doses.^12,13

In addition, there have been 2 published PK studies on horses, and 1 PK study on dairy calves, and multiple PK studies are underway on various species.^14-19 It should be noted, given the vastly different formulations and ratios of various cannabinoids (there are more than 120 described so far), that it cannot be assumed all products will have the same bioavailability or efficacy when compared with those used in the published studies. Despite alkaline phosphatase elevations in a small percentage of dogs and a transient alanine aminotransferase elevation in 1 cat in 1 of the studies, the therapeutic index appears to be very high, meaning these products are safe when properly manufactured and tested.

Studies on pain management with cannabinoids such as CBD have not addressed effectiveness on acute pain, although anecdotes suggest effectiveness. However, 5 peer-reviewed studies show moderate to good efficacy in decreasing pain scores in dogs with chronic pain from osteoarthritis.^1,20-23 Another possible use of cannabinoids is for epilepsy. One published study showed an approximate 33% decrease in seizure frequency and severity with the addition of what is considered a low dose of a CBD-dominant product for dogs with intractable idiopathic epilepsy when comparing dosing of CBD for epilepsy in people.²⁴ A longer-term study using a higher dose is underway.

Results of a randomized PK study showed that administering phenobarbital with a CBD product led to no major concerns for drug-to-drug interaction.²⁵ In addition, anxiety and behavior modification warrant better-designed clinical studies. Two published studies show some or no change in the temperament of shelter dogs given CBD when exposed to loud auditory triggers and animal caretakers.^26,27 Other studies are investigating CBD use for conditions such as atopic dermatitis in dogs, stomatitis in cats, epilepsy in dogs, quality of life in canine patients with cancer, acute pain in dogs, and anxiety in cats.

LEGISLATIVE UPDATES

Products derived from hemp—defined as any cannabis plant with less than 0.3% Δ-9-tetrahydrocannabinol (THC)—remain legal at the federal level, whereas the legality of products derived from marijuana (defined as any cannabis plant with more than 0.3% THC) varies from state to state. Even in states where all forms and uses of cannabis have been decriminalized, guidance from state boards of veterinary medicine ranges from no guidance to legislation and regulations around veterinarians’ ability to recommend or even discuss the use of cannabis in their patients. In Nebraska and Idaho, any cannabis-derived product is illegal, regardless of whether it comes from marijuana or hemp.

The authors reached out to 48 states’ veterinary medicine boards and received responses from 19 (Table^28-33). The authors believe that products derived from hemp belong in the same category as other nutraceuticals or supplements that veterinarians recommend every day, often with less scientific backing and data than what exists for cannabinoid-containing products. To that end, CBD has a monograph in Plumb’s Veterinary Drug Handbook.³⁴

EMERGING PRODUCT TRENDS

Cannabigerol (CBG)

Research on this cannabinoid is limited but growing.³⁵ CBG is a precursor molecule for many of the cannabinoids produced by the cannabis plant, including both CBD and TCH. It is noninebriating and demonstrates effects on the neurological system, making it a potential therapeutic in epilepsy and other neurological conditions. Human studies are underway for its use in Huntington disease, Parkinson disease, irritable bowel syndrome, and inflammatory bowel disease. It has high affinity for both α2 and serotonin receptors.

Cannabinol (CBN)

This cannabinoid is a product of oxidation or aging of THC and is often found in products that have been stored for long periods or those exposed to heat during storage. It binds to CB1 receptors in the endocannabinoid system, just as THC does, but is approximately 75% less potent at these receptors than THC. In historic studies, CBN has shown sedative and anticonvulsant effects, which has led to its use as a sleep aid in humans. Recent human-based research has not demonstrated clear evidence of CBN as a sleep aid, though it may work in this way as part of the entourage effect when combined with other cannabinoids and terpenes in full- and broad-spectrum products.³⁶

Nepetalactone
This terpene has been isolated as the primary active ingredient in catnip and silvervine and is 1 of the hundreds of terpenes found in cannabis. At least 1 veterinary cannabis company is looking to develop nepetalactone in feline products to harness its therapeutic effects of mild sedation and euphoria.

∆-8 THC

The “new kid” on the block, ∆-8 THC is a molecule that can be synthesized from CBD, including CBD that is derived from hemp. In this way, it is marketed as legal THC. It is completely unregulated and requires the heavy use of industrial solvents and other chemicals to force the conversion of CBD to ∆-8 THC, some of which may remain in any final product. ProVerde Laboratories has tested hundreds of such products with a wide variation in cannabinoids and other molecules found, some of which have no safety data whatsoever. ∆-8 THC is reported to be anywhere from 20% to 80% less potent than ∆-9 THC (the naturally occurring isomer of THC found in cannabis), requiring much higher doses for similar effects. There is no veterinary indication for its use, and safety concerns, as well as lack of consistency, make it questionable for human use as well.³⁷

For information on the legal status of all forms of cannabis in your state, visit https://www.norml.org/laws/

Liz Hughston, MEd, RVT, CVT, LVT, LMVT, VTS (SAIM) (ECC); and Stephen Cital, RVT, SRA, RLAT, CVPP, VTS-LAM, co-authored the textbook Cannabis Therapy in Veterinary Medicine: A Complete Guide, with fellow co-authors Katherine Kramer and James S. Gaynor. The book was released in 2021.

References

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