If there’s one thing generating a buzz in veterinary medicine these days, it’s cannabidiol (CBD). No, not that kind of buzz — CBD derived from hemp containing less than 0.3% tetrahydrocannabinol (THC) is a non-psychoactive agent. Rather, the buzz is coming from clients asking whether the purported human benefits of CBD might help their pets and from veterinary practitioners who are fielding questions, are curious themselves and want to see scientific evidence.
Today’s Veterinary Business spoke with two experts at the forefront of CBD knowledge in the veterinary world. The first was Stephanie McGrath, DVM, Ph.D., assistant professor of neurology at Colorado State University’s College of Veterinary Medicine and Biomedical Sciences, who is researching the use of CBD in animals. The other was Gail Golab, DVM, Ph.D., MANZCVS, DACAW, chief veterinary officer at the American Veterinary Medical Association.
We hope the questions we asked are some of yours. Here’s what they had to say.
The Scientific Evidence
Which CBD animal studies have been conducted?
Dr. McGrath: I’ve done a pharmacokinetic and safety study, and I published my epilepsy pilot study on a small number of dogs as a proof of concept. We also did an osteoarthritis study here at CSU, but it hasn’t been published yet. A study looking at pharmacokinetics and safety as well as osteoarthritis effectiveness in dogs was published out of Cornell with [Dr. Joseph] Wakshlag. And very recently, a pharmacokinetic study in Frontiers came out of a Canadian CBD company called Canopy Growth Corp. The only other one I know about is also from Dr. Wakshlag, also very recent, looking at pharmacokinetics in both dogs and cats. Those are all the studies I know of.
We are still in the infancy of research, which is both the exciting part and the problem. We have just several publications in peer-reviewed journals, which in my opinion is very scarce literature to support the use of CBD at this point.
Is CBD a proven therapy for any pet ailments or diseases?
Dr. McGrath: We have one publication each for epilepsy and osteoarthritis, both involving a small number of dogs and, to be totally honest, fairly equivocal results. These areas show promise, but we still have a long way to go.
Another ailment I hear about on both the human side and the veterinary side is anxiety. I’ve heard anecdotally that CBD might help dogs with noise aversion, separation anxiety or other behavior issues, so I think looking at that would be interesting.
The other fascinating field, which I’m currently working on, is cancer. It looks like CBD might have some anticancer effects as well as the ability to ease the side effects of chemotherapy. Whether it actually works against cancer or helps with side effects of treatment, it might have a role in the oncology field.
I already mentioned osteoarthritis, but I would broaden that to include all pain — whether it’s chronic pain, nerve pain, muscle pain or acute surgical pain. Some of the analgesic and anti-inflammatory effects of CBD might have a role in helping with pain control.
Most of this is anecdotal so far, but there’s definitely promise. I wouldn’t be doing the research if I thought CBD was snake oil. I think it has its place, but we’re far from proving it.
Briefly, how is CBD thought to work physiologically in cats and dogs?
Dr. McGrath: We don’t know, and that’s part of what we’re trying to figure out. We know the body produces receptors that bind to the cannabinoids our body naturally produces as well as to phytocannabinoids, or cannabinoids extracted from plants. But we don’t know what all those receptors are. We hear a lot about CB1 and CB2, but there’s likely a whole host of other receptors that are undiscovered.
There may be other mechanisms of action as well. Cannabinoids might act on different ion channels, which can alter neurotransmission. There’s a lot happening within the body that, unfortunately, we just don’t understand at this point.
Do CBD products have any side effects in pets that veterinarians need to be aware of?
Dr. McGrath: We’re trying to figure this out as well. In a research study, the longest a dog has been given CBD is 12 weeks, at least as far as what I’ve seen. So, we can really only comment right now on the side effects we’ve seen during that period of time. What we’re seeing clinically is very minimal. A couple of dogs have vomited or had some diarrhea, but those are sporadic cases and they seem to be self-limiting. I haven’t seen diarrhea or vomiting last more than one or two episodes.
For laboratory effects, the biggest change we’ve seen is an elevation in some liver enzymes. In my study, we reported an elevation in alkaline phosphatase (ALP) that was consistent across the higher doses of CBD. Dr. Wakshlag also reported an elevation in alanine transaminase (ALT). The big question is, what’s the implication? Does it mean CBD is hurting the liver? Or does it mean it’s being metabolized by the liver, so the liver is secreting a bit more enzyme than it normally would, which is a benign issue? The problem is we don’t know beyond the 12-week period.
We’ve also tested liver function through a bile acids test, and those results have always been normal, so this implies that the liver is functioning normally. But we need a longer-term study where we look at dogs over a year, for example, to make sure CBD is not hepatotoxic.
How does CBD interact with other pet medications?
Dr. McGrath: Again, we’re in our infancy with the research and we have not explored that issue fully. The biggest concerns regarding patients with epilepsy and osteoarthritis are reactions with other antiepileptic drugs and with NSAIDs, which are the mainstay of osteoarthritis treatment right now. But we don’t know.
In all of our studies so far — in Dr. Wakshlag’s work, in the unpublished osteoarthritis study at CSU, and in my epilepsy study — CBD has been given concurrently with other antiepileptic drugs and NSAIDs. And we haven’t seen any clinical side effects or anything in laboratory results that we wouldn’t normally see in dogs receiving those drugs. So far, we haven’t observed any drug-drug interactions, but a true study looking at how these drugs interact with each other has not been done.
So, I would caution pet owners and veterinarians that there are still a lot of question marks in this area. I feel like it’s probably not an issue, but I certainly have not proven that.
Which CBD products are trustworthy?
Dr. McGrath: It’s a real problem right now. I caution pet owners to be as careful as they can be, but there’s still a lot that’s unknown. One of the tips I offer is to look for companies that are readily able to provide a certificate of analysis — a piece of paper, basically, that matches a CBD product to a clear and current description of the ingredients in that product. All of that should be very transparent, meaning the whole profile of cannabinoids should be easy for the pet owner to understand and review. Sometimes there’s also information on whether organisms, heavy metals or pesticides are present — that it’s a “clean” product, if you will.
I’ve heard about instances of forgery in this area, so it’s not a perfect science. But if a company can’t provide that certificate of analysis or they give you one from last year and you’re going to purchase a product today, then they’re obviously not keeping up with their quality assurance.
The other tip I have is for pet owners to use the products the researchers are using. As researchers, we’re not going to give a product we don’t trust to our patients or our clients’ animals. And generally, universities will test the product to ensure it is what it says it is. I feel kind of badly saying this because there are companies that don’t have the funding to support research and they still have good products. So take that with a grain of salt.
But beyond that, honestly, it’s a bit of a tossup. We don’t know what’s in all these products. But at the least, a company should have someone available to answer questions and provide some documentation. When you can’t reach anyone or they can’t provide anything, that’s a red flag.
Are human CBD products safe to use with pets?
Dr. McGrath: I would be cautious only for one reason. The actual CBD or hemp that’s being used to create these products is probably the same. There’s no company I know of that grows different hemp for an animal versus a human. I think the bigger problem is the added ingredients. Hopefully, if the company is making a pet product, it understands what’s safe and what’s not safe for animals, which does not always correlate with humans.
My best example is xylitol, which we commonly find in gum, gummy bears and so on. A lot of companies use it in CBD products, and it’s not safe for pets. So I urge people to be careful. Either review the ingredients or buy a pet-specific product.
The Legal Landscape
Who has legal jurisdiction over the sale and use of CBD pet products — the federal government, my state, city or county?
Dr. Golab: With respect to CBD, but also any therapeutic agent, veterinarians need to understand their obligations at every level. Veterinarians are obligated to comply with federal law where it applies, even if the applicable state or local law is less restrictive. Failure to do so has potential ramifications with respect to both disciplinary action by a licensing board and in malpractice litigation.
In regard to federal law, CBD is covered under at least two statutes: the Food, Drug and Cosmetic Act, which is administered by the U.S. Food and Drug Administration, and the Controlled Substances Act, which is administered by the Drug Enforcement Administration. The 2018 Farm Bill did not remove CBD derived from hemp from regulation under the federal Food, Drug and Cosmetic Act. That legislation descheduled hemp [cannabis with THC of 0.3% or less by dry weight] and its derivatives, but it did not deschedule CBD derived from marijuana. Epidiolex, the approved human drug, is derived from marijuana, and it’s actually scheduled under the Controlled Substances Act. It’s classified in the least restrictive schedule, V, but it is scheduled. So, it’s not correct to say that all CBD is schedule I, but it’s also not correct to say that all CBD is descheduled.
State veterinary medical practice acts may provide direction, as might state pharmacy laws. In the case of hemp-derived products and marijuana-derived products, there are separate laws at the state level that apply specifically to those products as well.
To make sure they understand all their legal obligations, veterinarians are advised to speak with an attorney familiar with drug law at the federal and state levels — one who can interpret all the companion laws as well — and it’s also good to inquire with their state board. Some boards have been more proactive than others about communicating their perspective to veterinarians.
Does the FDA approve CBD products?
Dr. Golab: The FDA has approved one human CBD drug, Epidiolex, which is used to treat two rare and severe forms of epilepsy in people. Currently, under federal law, if a product has not been approved by FDA and is marketed as a therapeutic product, it’s not being marketed legally. If a company is making claims about the ability of a product to prevent, mitigate or cure a disease, or it’s intended to affect the structure or any function of the body, the FDA considers that to be a drug. And therapeutic claims don’t just include label claims; they can include claims made in advertising, such as the sharing of client testimonials and the sharing of research, if those are intended to help sell the product.
Currently, the Food, Drug and Cosmetic Act also prohibits the addition of hemp-based products to animal feed, including pet treats.
What is the legal risk to veterinarians regarding pet CBD use?
Dr. Golab: Under the Food, Drug and Cosmetic Act, the FDA takes actions primarily against drug sponsors when it comes to the manufacture and marketing of unapproved drugs. In fact, the agency has issued 22 warning letters to manufacturers of CBD products, 15 of which included mention of products intended for use in pets. That said, the FDA can and does go after individuals for violations of the Food, Drug and Cosmetic Act. Warning letters may be issued to individuals about the use of the products when that use is deemed unsafe under the statute.
If a veterinarian uses a product and either the product fails to work in the way anticipated or there’s an unintended consequence, such as an adverse effect, the veterinarian has taken a risk in using an unapproved product. If a complaint is filed with the state board or the veterinarian is faced with a malpractice suit, the veterinarian may face some increased risk because of having used an unapproved drug.
Veterinarians can use approved animal or human drugs in an extralabel fashion to treat veterinary patients under the Animal Medicinal Drug Use Clarification Act. Right now, there are no cannabis-derived drugs approved for use in animals. However, there are four FDA-approved cannabis-derived or cannabis-related human drugs [Epidiolex and three other drugs based on synthetic forms of THC] that can be used extralabel to treat veterinary patients.
It becomes more challenging at the state level. There are disconnects between state and federal law as to what products can be manufactured, sold and marketed. In addition, laws covering the medicinal use of cannabis for human patients do not apply to medicinal use in veterinary medicine. Again, it’s best to consult an attorney who’s an expert in drug law in that state and federally, as well as one’s state veterinary board.
If the legal landscape is so complex regarding the use of CBD in pets, should veterinarians just avoid the topic altogether?
Dr. Golab: This is a very difficult issue for veterinarians. They not only have an obligation to follow the law, but they also have an ethical obligation to their patients and clients. They need to be able to speak with their clients and make sure they understand what’s known and not known about cannabis-derived products, including CBD, to best protect the health of the animal and to help their clients make decisions that are well-informed.
For one thing, veterinarians need to let their clients know that not every bottle of CBD is the same — product quality is a serious issue. Often what’s indicated on the container doesn’t match what’s found to be in the product upon testing. It can be more or less, or there may not be any active cannabinoid in the product at all. As a general rule, human products are more concentrated than products for pets. If pet owners are going to use a product for a pet, they need to be able to work with a veterinarian to gather as much information as possible. That includes knowing what is actually in the product and consideration of whether giving the pet CBD or another cannabinoid may impact the effectiveness of other medications the pet may be receiving.
Can a veterinarian talk about CBD with clients?
Dr. Golab: Veterinarians need to be able to advise their clients in the best interest of their patients. There’s a lot of interest out there, and clients are using the products for themselves, so it’s not surprising that they might want to give them to pets. Veterinarians need to be proactive in finding out from clients whether they’re giving CBD to their pets, just like they would ask about other things their client might be doing for their animal.
Providing information is different than actually administering, prescribing or dispensing a cannabis-derived product that has not been approved by FDA. In California, it’s explicit that veterinarians can’t do that and, while some proposals are pending, to date no other state has adopted legislation or regulations that would provide the opportunity for veterinarians to legally do so.
At this point, veterinarians need to think about where the boundary is between providing information to clients and formulating a recommendation. AVMA supports the professional judgment of the veterinarian and advocates for flexibility around that judgment, but veterinarians need to comply with the law. At the point they move from providing information to making a recommendation to use an unapproved CBD product, they’re in dangerous territory and need to decide what risk they’re comfortable with.
Can I sell CBD products in my clinic?
Dr. Golab: The FDA has clearly answered that in one respect: not in treats because you can’t add hemp-based products to animal feed right now. When it comes to CBD oil or other CBD products, it depends on the intended use of the product and how it’s labeled and marketed. The FDA has indicated that selling unapproved products with unsubstantiated therapeutic claims is not only a violation of the law but can also put patients at risk, as these products have not been proven to be safe or effective. And quite honestly, we’re having a difficult time thinking of why veterinarians would be selling such products other than for a therapeutic purpose.
5 CBD STUDIES
Check out these five published studies that explored CBD use in animals.
“Pharmacokinetics of Cannabidiol Administered by 3 Delivery Methods at 2 Different Dosages to Healthy Dogs”: http://bit.ly/2PK4jjJ
“Single-Dose Pharmacokinetics and Preliminary Safety Assessment With Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats”: http://bit.ly/2TzmAkL
“Pharmacokinetics, Safety and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs”: http://bit.ly/32OhnK0
“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”: http://bit.ly/2IgQF3C
“Preliminary Investigation of the Safety of Escalating Cannabinoid Doses in Healthy Dogs”: http://bit.ly/38qdBbi
MORE FROM THE AVMA
The American Veterinary Medical Association is gathering research conducted on the clinical use of cannabinoids in pets and will compile a summary report that also will examine product quality and regulatory matters. The report is expected to be completed early this summer, said Dr. Gail Golab, the AVMA’s chief veterinary officer.
A CBD symposium will be held Aug. 3 and 4 at the AVMA convention in San Diego. In addition to substantive programming on the clinical potential of cannabinoids, Dr. Golab said, organizers hope to present an expert from the human side, where more work has been done, as well as representatives from federal and state regulatory agencies.