Ultimate Pet Owners Guide for CBD Usage in Dogs - By John Maddigan
The Ultimate Pet Owners Guide for CBD Usage in Dogs – Well Almost
Just a few disclaimers to start:
• Our veterinary hospital doesn’t sell any CBD products.
• I’m not a veterinarian, just the husband of one, who likes to do research on topical questions in veterinary medicine.
• I have no particular axe to grind, just doing the research and giving pet owners the facts without trying to take a point of view.
• I’m a pet owner, a pet lover, and only want the best for my pets and all the pet owners out there.
• This paper is not intended to be “medical advice” but instead to give pet owners more information about CBDs and what they should know before they ask their veterinarian about the use of CBDs for their pet.
Definitions
With that said let’s start with a few definitions so we are all on the same page. Cannabis is a genus (a class of things which have common characteristics) of plants that include both marijuana and hemp, an unfortunate fact for hemp. Because hemp is included in the cannabis genus of plants, it had been classified with marijuana as a Schedule One substance until 2018 with the enactment of the new Farm Act and its subsequent declassification (see below section on legality). Although they are in the same genus of plants, hemp and marijuana have very different compositions of chemicals called “cannabinoids.” Today much of the medical CBD (cannabidiol) oil is sourced from hemp because it has a higher concentration of CBD than marijuana and is legal throughout the country (marijuana is legal in some states but still illegal federally). The big difference between hemp and marijuana is that hemp contains higher concentrations of CBD and relatively lower THC (tetrahydrocannabinol) concentrations (no higher than 0.3 percent THC) compared to marijuana. THC is the psychoactive ingredient which is found in much higher concentrations in marijuana. As a result, it is not possible to get “high” with hemp sourced CBD. So, there it is, cannabis is a class of plants that includes marijuana and hemp and hemp has relatively higher concentrations of CBD and only 0.3 percent of THC, the psychoactive chemical, and marijuana has lower concentrations of CBD and higher levels of THC and that is why marijuana is still a federally regulated Schedule One drug and hemp is not.
Is It Legal?
Yep. In 2014, President Obama signed the Agricultural Act of 2014 (the Farm Bill), which allowed for the study and cultivation of industrial hemp for limited purposes. This led to the Industrial Hemp Farming Act of 2015, which allowed American farmers to produce and cultivate industrial hemp more widely. This legislation removed hemp from the controlled substances list as long as the hemp grown contained no more than 0.3 percent THC. This was reaffirmed in the December 2018 passage of the Agriculture Improvement Act of 2018 by Congress. The bill removed industrial hemp from the Controlled Substances Act, where it had been since 1937.
So Why Does It Work?
As a result of the demand for research on the effects of THC on humans, scientists discovered that every mammal, including us and our dogs, are born with a fully functioning endocannabinoid system (ECS). This is critical as CBD affects the endocannabinoid receptors, which are located in both the central nervous system and the peripheral nervous system. The ECS is a key component to our health and well-being, as it regulates homeostasis (stable equilibrium between systems in the body, in a word balance) in almost every system of mammalian bodies. The ECS controls the rate of production and degradation of the chemicals that our brain and cells use as signals and messengers, known as neurotransmitters. Research revealed that CBD is deeply involved in those endocannabinoid neurotransmissions in that they upregulate and downregulate neural transmissions as needed to maintain homeostasis, helping keep the body in a normal and healthy state (examples in humans would be the downregulation of anxiety, noise phobia, epilepsy, inflammation, and emesis (vomiting)). The really amazing thing about this is that CBD can BOTH upregulate and downregulate neural transmissions and always act to move the body toward a normal state and thus doesn’t shift things in the wrong direction. This is an important characteristic of CBD as most pharmaceuticals either only upregulate or downregulate (think of stimulants or suppressants, they only work in one direction, not necessarily into a homeostatic state). This movement toward homeostasis reduces the likelihood of unwanted side effects and results in CBDs, in theory, having a safe profile for use in our dogs. An interesting factoid is that acupuncture is another treatment known to have the same type of homeostatic action.
Our cats and dogs have the same endocannabinoid system as humans. In addition, humans and mammals have approximately 95 percent similar genetic material so we are susceptible to many of the same illness and diseases i.e. diabetes, obesity, arthritis, etc. Subsequently CBDs act in many of the same ways on us as it does our dogs.
As mentioned above, the endocannabinoid system was only discovered after research into THC led to the discovery of the endocannabinoid receptors and following this, anandamide, a natural cannabinoid receptor agonist, was discovered in 1992 (see below in “What Can CBD Do section). The endocannabinoid system is a complex lipid-signaling (THC and CBD have low solubility in water, but good solubility in most organic solvents, particularly lipids and alcohols) network that modulates central nervous system activity, and its effects can be summarized as “relax, eat, sleep, forget and protect.”
That is why CBD works on us and our pets (we’re all mammals with similar genetic composition) in relatively similar ways (https://cannabis.net/blog/medical/can-your-pet-benefit-from- cannabis). It is VERY important to note that dogs (not certain about research on cats) are much more sensitive to THC than humans are, as dogs have a higher number of brain receptors for cannabinoids than humans. A 2012 study reported a fourfold increase in the number of dogs treated for marijuana intoxication between 2005 and 2010 and I can say with confidence that this trend continues with the legalization of both medical and recreational use of marijuana in many states, and the presence of it in more homes now than ever before.
So, given the fact that CBDs help the body return to a homeostatic state it would seem reasonable to extrapolate that CBDs could be helpful in many ways, but sadly the research to validate these claims are totally absent. While scientists know “how” cannabinoids like CBD effect our endocannabinoid system there is almost no research on animals to validate the numerous claims that are being made every day on the internet.
Is CBD Safe?
The limited research indicates it does no harm but it is best to use hemp derived CBD as it is lower in THC than marijuana derived CBD. The most recent study by Dr. Stephanie McGrath at the Colorado State Veterinary College, found CBD to be harmless, or in other words SAFE. But much more work has to be done to confirm those smaller studies (Dr. McGrath’s study had only 16 dogs over a very short period of time in 2016). Currently there are no long-term studies on the effects of CBD on cats or dogs and to my knowledge and a review of the literature none are in process at the writing of this paper (April 2019). These longitudinal studies need to be done to make everyone feel comfortable about prescribing CBD and other cannabinoids. The only study – done by Dr. Wakshlag – that does look at pharmacokinetics (the branch of pharmacology concerned with the movement of drugs within the body) will be discussed later in this paper.
Studies, Research or Hype?
A quick search on the internet will answer that question – hype. And article after article echo the sentiment in their headlines: Washington Post April 21, 2019: “CBD for pet’s ailments? Many people swear by it, but there’s very little animal research;” “Is the hype about CBD, cannabidiol real?” Still other stories have disclaimers up front stating, “this article is for informational purposes only and does not constitute medical or legal advice...”. This is done because the research is scarce but the hype is everywhere. A USA Today article starts with, “It’s hard to find something CBD can’t treat.”
Currently the marketers for the CBD manufacturer’s claim that CBD is a natural remedy for just about everything – I wonder if it could help with baldness?? But sadly, their therapeutic claims are not backed up with solid scientific research. This is an industry based not on scientific research but mostly built on anecdotal data and testimonials – Montel Williams is a perfect example and there are lots of other celebrities pushing various other products (Gwyneth Paltrow and Willie Nelson).
Despite ALL the claims there is just NO research to back up those claims. Currently there are only two animal studies on the effects of CBDs on dogs. At Colorado State veterinary neurologist Dr. Stephanie McGrath has completed one pilot study on epileptic dogs in 2016.
Her research found that nearly 90 percent of the epileptic dogs experienced fewer seizures when given chicken-flavored CBD, as compared 20 percent on placebo. While the results are encouraging the study only included 16 dogs and even Dr. McGrath acknowledged the limitations of the study. “Although really exciting results, it still has to be taken with a little bit of a grain of salt, because the power of the study is diminished when you don’t have a lot of dogs involved. Dr. McGrath is now conducting two clinical trials with 27 dogs, studying how effectively CBD can treat osteoarthritis and epilepsy. The only concern I have with this study is whether or not 27 dogs is a large enough sample to be scientifically significant.
The second study was conducted by associate professor and veterinarian Dr. Joseph Wakshlag (see study here https://www.frontiersin.org/articles/10.3389/fvets.2018.00165/full) at Cornell University. The participating dogs were suffering from multi-joint pain and osteoarthritis. The eight-month double blind, placebo-controlled study was done in collaboration with ElleVet Sciences and the pets were given ElleVet Mobility Chews (while the study lasted 8 months the drug trial lasted only 4 weeks for the dogs with a 2 week wash-out period between dosages). The primary goal of the Cornell-ElleVet study was to understand how dogs metabolized ElleVet soft chews, which are hemp-based supplements also containing glucosamine and chondroitine, two natural compounds that are already widely used in dogs and humans for arthritis. Although the sponsoring company is touting the results of the study it must be said that this study also only contained 16 dogs and the according to Dr. Wakshlag’s research article the dogs were also allowed to continue taking pain medications and other medications known to help with joint pain: “During the trial, dogs were only allowed to receive NSAIDs, fish oil, and/or glucosamine/chondroitin sulfate without any change in these medications for 4 weeks prior to or during the 10-week study period as standard of care for the disease process.”
While the results from the study were encouraging, with over 80 percent of the dogs showing significant improvement, the study size was small, just 16 dogs. Quoting from ElleVet’s press release here are the reported results of the clinical trial: “The Cornell study found that dogs who took ElleVet's proprietary hemp oil blend showed significant improvement over dogs that received the placebo. The study determined that ElleVet's hemp oil blend is "efficacious for pain in dogs with osteoarthritis, chronic joint pain and geriatric pain and soreness; with dramatic beneficial effects in our more geriatric patients." Over 80% of dogs who have used ElleVet Mobility soft chews have seen a significant or dramatic improvement. Veterinarians have called ElleVet soft chews, "A game changer that will change the face of veterinary medicine." Here's a link to their site and the study: https://ellevetsciences.com/pages/for-vets
Those are the only two studies of the effects of CBD on dogs – one study by Dr. Stephanie McGrath on epileptic dogs too small to be significant and the other by Dr. Joseph Wakshlag, with the same number of subjects as Dr. McGrath, that is being touted by the sponsor of the study to be “efficacious...a game changer.” You decide, but keep in mind that most nutraceutical products do NOT go through even this rigorous a study so kudos to ElleVet for doing it.
US based human trials are also very limited. Dr. Arnold Abrams, an oncologist and professor of clinical medicine at the University of California at San Francisco and a member of a National Academies of Sciences, Engineering and Medicine committee that issued the most comprehensive report to date on the evidence related to the health benefits of cannabis and cannabinoids says, “we really don’t know anything” about CBDs. Here is a link to the study: http://nationalacademies.org/hmd/Reports/2017/health-effects-of-cannabis-and- cannabinoids.aspx
Dr. Abrams reported that there have only been five randomized clinical trials that have looked at CBD, until the Epidiolex studies (used to treat two rare kinds of epilepsy). The amazing fact is that the largest of those studies was a 24-person trial – THAT’S SMALL!
What Can CBD Do?
Good question. Clearly ElleVet believes that their hemp oil blend products help with osteoarthritis but what about the claims about anxiety, epilepsy and seizure disorders, and decreased appetite. Other than the two studies cited above on epilepsy and osteoarthritis there is no scientific data to support any of the claims made every day by multiple manufacturers, regarding other treatment claims, but there IS LOTS of anecdotal evidence that seem to corroborate almost any claim. Here’s an example: today my veterinarian wife had a client tell her that she gave her dog CBD to help stop it from eating its own feces and it worked. She then recommended it to a friend with the same problem and it worked for her dog as well – go figure.
But a colleague also saw an older pet whose parent rubbed CBD on it to make it feel better – arthritic – the pet got very “high” vomited, aspirated (inhaled) some of the vomit and got aspiration pneumonia and ended up with a $1,000.00 vet bill. So you never know.
I personally wouldn’t trust any claim made on the internet as marketers of these products will make any claim BUT everyday feedback is almost overwhelmingly positive, so ask a friend if their pet is using a CBD product.
But if there is no scientific data to support the claims of benefits, how then do some of these marketing claims begin? The answer is mostly from human studies. Remember at the beginning of this article we discussed that the endocannabinoid system (ECS) is common to ALL mammals – us and our dogs. We humans have been using various forms of CBD (both hemp but mostly marijuana based) for many years and three synthetic cannabinoids - sold under the drug names Marinol, Syndros (both use the active ingredient dronabinol), and Cesamet (using the active ingredient nabilone) - for a variety of conditions including the treatment of anorexia in AIDS patients, and nausea and vomiting associated with cancer chemotherapy. So currently we are using very expensive man-made drugs that occur naturally in cannabis plants to treat patients where conventional drugs regimes have failed. For more information on these synthetic drugs you can visit this web page:
https://www.medicaljane.com/2017/05/01/the-3-cannabis-based-medicines-approved-by-the- fda/
So that’s where CBD manufacturers are making the leap from humans to our pets – we have a common endocannabinoid system that works similarly in all mammals. So, if it works in us why wouldn’t it work for our pets? Not an unreasonable assumption, however, veterinarians still don’t have any research to support that assumption. But there is a lot of science that can help us. Scientists know that the CB1 receptor in our brain and the CB2 receptors in the body that are stimulated by the synthetic cannabinoids listed above work basically the same in humans and dogs, the basic difference is that the message (the natural messenger cannabinoid in our dogs is called anandamide) sends a louder, stronger and longer message in dogs. That is why our dogs are much more impacted than humans by the THC in marijuana when they ingest or are given some. Drugs that can hang on longer to the natural messenger receptors are called an agonist – ergo why anandamide is called a cannabinoid receptor agonist. The chief agonist cannabinoids in marijuana are THC and CBD which is why of the hundreds of chemicals in hemp CBD is the one generating the most interest – it’s an agonist.
So what conditions are the pharmaceutical industry looking to treat with cannabinoids? As mentions above anorexia in AIDS patients (we all had heard of the funny stories about getting the “munchies” after smoking some marijuana, and it’s true). Synthetic cannabinoids have also been approved for use in treating nausea and vomiting in patients receiving chemotherapy. This is not a huge issue in dogs as they deal very well with chemotherapy but it could be used in parvo cases where fluid loss is critical. Cannabinoids are effective in the control of both acute and chronic pain. THC has also been shown to be effective in treating inappetence (a lack of appetite). So these are the areas where CBD manufacturers of pet products are making their most claims – pain control, osteoarthritis, epilepsy and seizure disorders and appetite stimulation.
And more progress is being made. On April 2, 2019 the FDA approved the use of one cannabidiol drug, Epidiolex, to treat seizures in young children from Lennox-Gastaut syndrome and Dravet syndrome two rare kinds of epilepsy. This is hopefully the first of a long list drugs developed from the cannabis plant.
So Why is Progress So Slow and Why Isn’t My Veterinarian Telling Me About CBDs?
This is still a very new industry with lots of issues to work out. Questions like: Where does your hemp come from? China, Eastern Europe or domestically as Chinese sources have high concentrations of heavy metals and pesticides. How is your product manufactured? CBDs are not water soluble so making certain it is bioavailable in the finished product is important. Smaller manufacturers may have poor or no quality control procedures in place, may be unable to test raw product (hemp) for concentration of CBD and THC. The result may be a product with a high degree of variability in the finished product from baTHC to baTHC.
But the biggest hurdle to date arises because marijuana is still a Schedule One drug, like heroine, according to the federal government. That makes it very difficult or almost impossible for researchers to get approval and access to marijuana to conduct research. The Schedule One designation also makes it more difficult to get funding (none from the feds) to conduct research. And even though marijuana is legal in many states it is still illegal for your veterinarian to carry or recommend cannabinoid products as the laws legalizing use in people do not apply to cannabis use in animals.
Yes, I mentioned that most of the CBDs come from hemp, but Congress only approved the use of hemp-based CBDs in December 2018 in the Agriculture Improvement Act, so there hasn’t been much time to conduct research, get it peer reviewed and develop drugs. Things are moving more quickly now, but access to marijuana and hemp have been the biggest hurdles in the past.
While marijuana research will still be slow and very limited because of its Schedule One classification, hemp derived CBD research will start to accelerate. The problem now is the lack of regulation of hemp based CBD products. Although CBD products fall under the jurisdiction of the FDA, the FDA really doesn’t regulate the industry, and that causes a myriad of problems for researchers and veterinarians. The FDA regulates CBD products much like it regulates nutritional supplements (i.e. vitamin C or B). Under the federal Food, Drug and Cosmetic Act, products for which therapeutic claims (i.e. helps reduce pain caused by osteoarthritis) must be approved by the FDA in order to be legally manufactured and marketed. The FDA approval process is the means by which the safety and efficacy of such products is demonstrated. Companies like ElleVet have done clinical trials BUT they have not received FDA approval for their products, but let’s give credit for serious clinical trials.
It is this lack of FDA approval that causes all sorts of other problems. Because non-FDA approved products cannot make therapeutic claims, the FDA won’t allow CBD producers to make marketing claims (that’s not working well) – which includes recommended doses. Although today some CBD products do have dosing instructions on the label, little is known about what doses are most effective or safe because it is unlikely that any serious clinical trials were conducted and certainly the product has not been FDA approved.
The dosing problem is further exacerbated by the fact that most products are mislabeled. In a 2017 study, Marcel Bonn-Miller, an adjunct assistant professor in the psychiatry department at the university of Pennsylvania’s Perelman School of Medicine, found that nearly 70 percent of the CBD products they analyzed were mislabeled. Some items were “over-labeled,” others “under-labeled,” and still others contained THC in amounts that could make you intoxicated or impaired. A big problem. But keep in mind this study was done on marijuana-based CBD which is now not how CBD pet products are manufactured. The issue is the inaccuracy of the labeling, not the presence of THC. This study was validated when the FDA also did some testing on CBD products and found that label claims rarely maTHCed the actual content. In fact, some products they tested had NO CBD in them at all. This is what the FDA has posted on its site, however, I could not locate the results of the FDA testing. https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm484109.htm
But I did find a site that did report on the FDA testing and here is the link: https://www.newhope.com/botanicals/fda-finds-only-2-24-CBD-products-have-what-they-say- they-have-them The headline says it all: “FDA finds only 2 of 24 CBD products have what they say have in them” although some of the misses were very close.
To overcome this labeling problem manufacturers can go to a third-party laboratory and obtain a “Certificate of Analysis” which checks for contaminants such as heavy metals. This is important because both China and Eastern Europe are providing raw product (hemp) to manufacturers and much of those products contain heavy metals and other contaminants. The sourcing problem should soon be eliminated as hemp production is increasing rapidly in the USA, especially in Oregon(500 acres in 2016 and 7,808 acres in 2018 and still growing). If the company you are buying your pet products from don’t have a Certificate of Analysis on their web site find a company that does.
Although I’m placing all of the responsibility on the manufacturers they too have issues with raw product – hemp. In particular manufacturers are having difficult creating “clinically reproducible standards” because there’s so much variation with the quality and strength of ingredients (hemp). Here in Central Oregon numerous farmers have now just swiTHCed to hemp production but they are just learning how to best grow and harvest this new crop. They do not have a track record of production yet which may lead to variability in quality and consistency but it is likely this issue will be resolved soon with good old American “know-how.”
Currently dosing really is a problem as even the researchers don’t know how much CBD to give a dog in order to reach a therapeutic dose that achieves the desired effect that is also safe. For example, Dr. McGrath’s is now nearly doubling the dose in her second trial. In her first trial she used a dose of 2.5mg per kilogram administered twice daily. So, if you are using a CBD product start low and increase gradually.
So why doesn’t your veterinarian recommend CBD for your dog? Well first they are not allowed to, and second let me restate the numerous reasons why they are not prepared to do so:
• Not one scientifically reviewed research paper on the use of CBD in dogs or cats.
• No idea of the therapeutic dosage required for any illness.
• No certainty in the quality and efficacy of the products on the market.
• No idea what conditions/illnesses that can be treated with CBD.
• Uncertainty regarding both labeling (is it reliable) and dosage (is it accurate) to obtain a therapeutic dose that is both effective and safe.
• While some studies state that CBDs are harmless to pets (Dr. McGrath study showed CBD cause no harm) there are no scientific papers or research clearly stating that CBDs have no long-term serious side effects (note Dr. Wahshlag’s call for such research in his paper) and if so at what dosage/duration of treatment.
Side Effects – Pharmacokinetics 101
As mentioned above it is believed that hemp derived CBD is safe in pets – according to a study by Dr. Stephanie McGrath at Colorado State University of Veterinary Medicine. Besides Dr. McGrath’s study there is only one study that actually looks at the pharmacokinetic impact of CBD on dogs. This is the study performed by Dr. Joseph Wakshlag at Cornell University. This study showed that CBD is very bioavailable (the ability of a drug to have an active effect), eliminated from the body in approximately 3.8-6.8 hours (for a half-life of 4.2 hours) with no observable side effects. The short half-life is a positive as this means that the drug leaves the body quickly as it is quickly metabolized by the liver. The study showed that there was a slight increase in the alkaline phosphatase (ALP) levels but the increases were still within normal levels. However, the study does recommend that “it may be prudent to monitor liver enzyme values (especially ALP) while dogs are receiving industrial hemp products until controlled long- term safety studies are published.” The study also gives us some clues as to the best products to use: “When examining prior oral CBD bioavailability, it was determined to be low and highly variable (0-19% of dose) with three dogs showing no absorption. This may be due to first pass effect in the liver, and the product as not in an oil base, but a powder within a gelatin capsule being a different delivery vehicle.” As noted earlier in this paper oil is the best delivery system as it provides the most bioavailability, which is what you need for a drug to be effective. As Dr. Wakshlag concludes in his paper, this was a short-term (4 weeks only) study with no observable side effects (at the 2 and 8mg/kg dosing), but “further long-term studies with larger populations are needed to identify long-term effects of CBD rich industrial hemp treatment, however short- term effects appear to be positive.” Here is a link to Dr. Wakshlag’s study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065210/#__ffn_sectitle
In a nutshell hemp derived CBD appears to be safe in the short-term but long-term studies need to be done to determine the long-term effects of CBD usage. So, if you are using CBD have your dog’s liver enzymes checked two weeks after starting (we do this with all dogs when they are first put on NASAIDS).
What’s Next?
For our pets there are lots of new products and new claims, but very little, if any, scientific proof. Sadly the status quo of buyer’s beware will continue. Our hope lies in the research being done on the human side on a number of fronts.
In a story in the Washington Post by Steven Petrow he states that, “Ziva Cooper, an associate professor of clinical neurobiology at Columbia University’s Irving Medical Center, who is doing research with CBD, says “based on animal studies, there seems to be a lot of promise for a number of disease states,” including its potential effects on inflammation...autoimmune disorders and addiction.” Cannabinoids’ effects are also being studied on the following conditions in people:
• Cancer – malignant tissues tend to express higher number of cannabinoid receptors than nonmalignant tumors and binding to those receptors can trigger cancer cell death.
• Nausea and vomiting – as mentioned previously synthetic cannabinoids are already approved to treat these issues in patients receiving chemotherapy.
• Pain – cannabinoids are effective in the control of both acute and chronic pain – ergo the Cornell study by Dr. Wakshlag to confirm these results in dogs.
• Inflammatory bowel disease, diabetes mellitus, glaucoma and infection with methicillin- resistant staphylococcus aureus.
So, there’s lots going on and the results of those studies will undoubtedly result in products being marketed as solving the same problems in our pets, likely without animal studies to affirm the results achieved in human studies.
Summary and Tips
• Because the accuracy of labeling is an issue, make sure your manufacturer has a “Certificate of Analysis” performed by a third-party laboratory.
• Oils are safer than edibles (and likely more bioavailable) because you have more control over dosage (edibles have the oil dissolved in butter so it may not be spread evenly in the product). Add the appropriate number of drops to your pet’s food to ensure that it is eaten immediately.
• Be patient, not all effects will be seen immediately, such as relief from chronic pain. Start with a low dose and increase gradually. If you still aren’t seeing results you may need to change products (the CBD levels listed may not be accurate). Have your veterinarian check your dog’s liver enzymes two weeks after starting treatment.
• Use hemp-based CBD as it has much lower levels of THC, which can impact your dog significantly.
• Oils are more bioavailable than powders so stay away from powder products.
• Oils and treats should be kept at room temperature sway from bright light or sunlight as cannabinoids are susceptible to degradation. If the oil has changed color, discard.
I hope this helps all pet owners looking to use CBD for their pet’s ailments. If you are using CBDs please tell me your story so we can use it to help other pet owners with the same condition.
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