Evidence Update: What’s New with Cannabis for Pets?

It’s been ten years since my first post on the use of cannabis in dogs and cats. For a while, I regularly covered new research studies, but the number of those has become great enough that keeping up with individual papers is not feasible. Fortunately, the principles of evidence-based have an answer- literature reviews!

There are two main types of review articles of use to clinicians: narrative reviews and systematic reviews. Narrative reviews are far more common in veterinary medicine. These involve individuals or small groups reviewing the research on a given subject and writing a summary from their perspective. These reviews can be very useful, and I have written several myself. But of course they are subject to significant bias. Authors can choose which studies to include and which to ignore, and they can interpret the results through the lens of their existing beliefs on the subject. This doesn’t mean narrative reviews are not useful, but it is a reason for caution in the level of confidence we place in their conclusions.

Systematic reviews are more formal projects, with clear and explicit standards to encourage a comprehensive assessment of the research on a given subject and an objective summary of the strength of the evidence. These are less subject to bias, but they have the weaknesses of often being inconclusive. When there are few studies or most research has significant limitations, no confident conclusion is justified, and most systematic reviews end with the conclusion that more research is needed. This is especially the case in veterinary medicine, where having only a few small studies with significant methodological limitations is the rule.

In the case of veterinary cannabis, there are only a few systematic reviews. One has looked specifically at the literature for cannabidiol (CBD) use in dogs with osteoarthritis (OA).

Patikorn C, Nerapusee O, Soontornvipart K, Lawonyawut K, Musikpodok K, Waleethanaphan K, Anantachoti P. Efficacy and safety of cannabidiol for the treatment of canine osteoarthritis: a systematic review and meta-analysis of animal intervention studies. Front Vet Sci. 2023 Sep 15;10:1248417. doi: 10.3389/fvets.2023.1248417. PMID: 37781283; PMCID: PMC10540436.

As expected, this review had to rely on only a few studies (five), and “All studies were rated as having a high risk of bias.” The conclusion was that CBD “may reduce pain…but the certainty of evidence was very low.” Fortunately, “CBD is generally considered safe and well-tolerated in the short-run, with few mild adverse events observed, such as vomiting and asymptomatic increase in alkaline phosphatase level.” However, as usual the bottom line is that more and better research is needed to allow any confident conclusions about the utility of CBD in arthritis dogs.

A slightly older review looks at all uses of cannabis in dogs.

Lima TM, Santiago NR, Alves ECR, Chaves DSA, Visacri MB. Use of cannabis in the treatment of animals: a systematic review of randomized clinical trials. Anim Health Res Rev. 2022 Jun;23(1):25-38. doi: 10.1017/S1466252321000189. Epub 2022 Jun 15. PMID: 35703023.

Only six studies met the criteria for quality to be included, all in dogs “with osteoarthritis (n = 4), with epilepsy (n = 1), and with behavioral disorders (n = 1)” and all using CBD as the test treatment. All studies showed improvement in the conditions being treated, but “studies were heterogeneous and presented risks of bias that required caution in the interpretation of findings.” As in the more recent study, “CBD was well tolerated with mild adverse effects,” but “More RCTs with high quality of evidence are needed, including greater numbers of animal subjects, additional species, and clear readout measures to confirm these findings.”  

A few narrative reviews have also appeared in the last couple of years that provide a good overview of the uses and evidence for cannabis-based remedies in veterinary medicine. The most comprehensive looks at dogs and cats.

Corsato Alvarenga I, Panickar KS, Hess H, McGrath S. Scientific Validation of Cannabidiol for Management of Dog and Cat Diseases. Annu Rev Anim Biosci. 2023 Feb 15;11:227-246. doi: 10.1146/annurev-animal-081122-070236. PMID: 36790884.

One interesting lesson from this review is that despite severely limited evidence and great uncertainty about what cannabis products might be useful for at what doses with what risks, people are using them all the time for everything. The perception appears to be that cannabis is a safe and effective panacea for companion animals, which of course isn’t substantiated by the actual evidence.

“The cannabidiol (CBD) pet market is expected to increase by $3.05 billion during 2021–2025, with a compound annual growth forecast to reach nearly 30%…A survey conducted online in the United States reported that nearly 60% of pet owners give or were giving CBD to their dogs, and 12% to their cats, most commonly for treating conditions like osteoarthritis (OA), seizures, cancer, or anxiety. From these, 64% found it helps with pain reduction, 50% that it aids with sleep, 49% that it reduces anxiety, and 30% that it reduces convulsions.”

The evidence is generally encouraging for some conditions, particularly pain, but it certainly is nowhere near the level needed to justify this kind of confidence among pet owners. Here are some of the main results reviewed for use of cannabis in various conditions.

• In canines, recent studies have shown mixed results regarding CBD’s efficacy as an adjunct therapy for managing inflammatory conditions like OA. 
• Mejia et al. found that CBD administered at 2.5 mg/kg twice daily, either in conjunction with non-steroidal anti-inflammatory drugs or not, did not improve objective measures of pain in client-owned dogs that suffered from OA compared to the placebo. The authors found some improvement in both the placebo and treatment groups, which was attributed to either caregiver’s placebo effect …This was the only study to use objective outcome parameters. 
• Verrico et al. found a significant reduction in pain (perceived by the owner) combined with increased mobility in large dogs with OA when given CBD for 4 weeks at doses ranging from 0.5 to 1.2 mg/kg. 
• Similarly, Gamble et al. reported decreased pain and increased activity in client-owned dogs administered 2 mg/kg CBD twice daily for 4 weeks. 
• Brioschi et al. also found that CBD administered for 12 weeks at 2 mg/kg twice daily significantly reduced the Pain Severity Score in OA dogs when compared to OA dogs not administered CBD. However, all dogs in Brioschi et al.’s study and most dogs in Gamble et al.’s study were administered anti-inflammatory drugs during the clinical trial, indicating a beneficial effect of CBD when combined with anti-inflammatory drugs.
  
• Whether CBD is effective in reducing epileptic episodes in dogs with IE [idiopathic epilepsy]  is inconclusive, and to date there are more clinical reports than controlled clinical studies…Two relevant controlled clinical trials explored the effect of CBD in dogs with IE…Additional studies are needed to strengthen the use of CBD or hemp extract in dogs with IE…Despite that, a survey of 297 pet owners with epileptic dogs showed that nearly half of these people were using different supplements to help reduce seizures or control side effects of other medications, and close to 40% of these supplements contained CBD. 
• A 3-month randomized blinded study found that dogs with IE that received whole hemp extract (THC [tetrahydrocannabinol] < 0.3%) infused hemp oil at 2.5 mg/kg CBD twice daily in conjunction with other epilepsy drugs had a reduction of seizure frequency by 33% compared to the control group. Some study limitations included the small sample size of dogs who completed the trial and the fact that the data could have been analyzed as repeated measures over time to detect individual changes.
• Garcia et al. conducted a double-blinded placebo controlled cross-over clinical trial in which dogs with IE received a CBD/CBDA-rich hemp extract at an approximate dose of 2 mg/kg twice a day for 3 months, in addition to 3 other antiepileptic drugs.  
• Similarly, McGrath et al. found a reduction in the total number of seizures (8.0 ± 4.8 placebo versus 5.0 ± 3.6 CBD/CBDA), as well as seizure days (5.8 ± 3.1 placebo versus 4.1 ± 3.4 CBD/CBDA), when dogs were administered the hemp extract. 
  
• Animal studies on anxiolytic effects of CBD have shown mixed results. CBD seems to have a bell-shaped curve for managing anxiety, as it seems to be anxiolytic at moderate but not low or high levels…A meta-analysis on human studies concluded that the evidence on cannabis-based products’ effects on anxiolysis is incomplete, because most studies had a small sample size along with some inconsistencies…In dogs, there is no established dose for treating anxiety and fear disorders. The few studies available have focused mainly on the short-term effects of CBD on aggressiveness and fear.
• A research study on shelter dogs found that CBD (dose calculated to be ?3.75 mg/kg) administered to dogs for 45 days could reduce aggressiveness toward humans but not behaviors related to stress.
• A second study assessed the effect of CBD supplementation on reducing acute fear triggered by fireworks in dogs supplemented with 1.4 mg/kg/day for 7 days and found no effect of CBD alone on reducing fear-induced stress. 
• Although there is a need for more scientific evidence that CBD is a therapeutic option to treat behavioral problems in dogs, like fearfulness and anxiety, pet owners perceive the calming and antianxiety effects of CBD favorably. Approximately half of pet owners who have given CBD to their dogs to reduce fear or anxiety think it is effective, even though doses given are inconsistent.
  
• No in vivo studies assess the antitumor effects of CBD in either dogs or cats.
• Several in vitro studies on canine tumor cell lines have demonstrated cytotoxic effects of CBD on cancer cells. [However, you can run a study showing bleach kills cancer cells in vitro, but that doesn’t make it a safe and effective therapy for cancer patients.]

The authors also touch on one of the persistent problems with veterinary cannabis products– since they are sold over-the-counter with no meaningful regulation (and often with illegal claims), there is poor quality control. “Some reports have noted inconsistencies in pet CBD supplements that are available in the market, such as misleading or untested claims, violations of good manufacturing practices, lower amounts of CBD than what was stated on the label, and/or THC above the allowed limit (0.3%). Unfortunately, many cannabis products are marketed in the United States with unsubstantiated claims of efficacy.”

As with most studies and reviews, the general conclusion is that the safety profile of non-THC cannabis products is pretty good, though adverse effects do occur. In dogs, there is great variability in the absorption and blood levels of CBD and other relevant compounds with different products and forms, so we still have little idea how much of any given product is safe or useful to give. In cats, the research is even sparser, and since cats appear to be more sensitive to the effects of cannabis-derived compounds (as with most other drugs), the safety and effectiveness of existing products in cats is largely unknown. 

Both dogs and cats have show gastrointestinal symptoms (e.g. vomiting and diarrhea0 as well as changes in some laboratory values. Lethargy or sedation and behavioral abnormalities can also occur, especially with products containing THC. It is also recognized that CBD and other compound sin cannabis can build up in fat tissues over time, so even when the short-term risks appear to be low, there is no reliable research identifying what risks might occur with long-term use.

Another narrative review from 2023 focuses on the specific use of cannabis-derived chemicals for treatment of pain.

Miranda-Cortés A, Mota-Rojas D, Crosignani-Outeda N, Casas-Alvarado A, Martínez-Burnes J, Olmos-Hernández A, Mora-Medina P, Verduzco-Mendoza A, Hernández-Ávalos I. The role of cannabinoids in pain modulation in companion animals. Front Vet Sci. 2023 Jan 4;9:1050884. doi: 10.3389/fvets.2022.1050884. PMID: 36686189; PMCID: PMC9848446.

This review mostly addresses the underlying biology of cannabinoids and pain. The few clinical studies mentioned are mostly in dogs with arthritis, and the results are mixed, as discussed in more detail in the previous review. The authors conclude there is some evidence to support use of cannabis-derived chemicals for treatment of both acute and chronic pain, but the evidence is largely extrapolation from lab animal studies (especially rodents), and there is little real-world scientific research in dogs and cats to support this.

Bottom Line

Most other reviews have looked at the same limited set of studies and drawn similar conclusions. What we can currently say about the use of CBD (virtually no evidence related to other compounds in cannabis) is this:

• It is biologically plausible that CBD may be useful in treating pain, inflammation, epilepsy, and possibly some behavioral problems in dogs and cats.
  
• The existing evidence is extremely weak. We can have a low degree of confidence in the short-term use of CBD for OA pain in dogs. All other uses rely on extremely limited, low-quality, and often conflicting evidence.
  
• The short-term negative effects of CBD, and cannabis generally, appear to be mild. The long-term effects are unknown.

Cannabis is the archetype of a “dirty” drug. It contains hundreds of compounds, most not studied in any depth, and it has effects on many body systems. While this means there is a great potential for cannabis-derived compounds to be useful in many different conditions, it also means the potential for unintended effects and interactions with other drugs is very high unless specific co pounds or subsets of compounds are studied and used individually.

Proponents often talk about the “entourage effect.” This is an idea common in herbal medicine that having multiple compounds in a plant-based remedy is a good thing because they will work in harmony to increase beneficial effects and cancel out each other’s adverse effects. There is no reliable evidence that this phenomenon actually occurs, and it is not very biologically plausible. 

The idea originated with the belief that such remedies were purposefully provided to humans by God, and as such were designed to have this benign nature.  Only the “unnatural” isolation of individual compounds to use as drugs is responsible for the phenomenon of drug side-effects. This argument is not scientifically credible, and it is far more plausible that mixing multiple compounds leads to more adverse and unintended effects. 

Certainly, this is the case with use of cannabis in dogs and cats when THC and CBD are both present in significant amounts. Isolating the CBD reduces these negative effects, so we cannot just assume that using products with multiple compounds and only the THC removed is inherently better than using purified CBD or other cannabis chemicals. Such an entourage effect could occur, but there is not yet compelling evidence for it.

The other important lesson to draw from these recent reviews is that the popularity of cannabis products for dogs and cats is not based on real scientific evidence showing these are safe and effective. This is a fad derived from the popularity of cannabis use in humans, which has origins in ideologies around “natural” medicine, reactions against excessive and largely irrational government prohibitions of cannabis, and factors that have little to do with the actual merits of cannabis as a medicine. 

Hopefully, the high level of interest will drive more research, and we will find out what uses it has. I am concerned, however, that the great confidence pet owners already have in cannabis will mean it continues to be profitable to make and sell unregulated and untested products without any motivation for companies doing so to produce meaningful scientific research evidence. Like glucosamine, which has generated billions of dollars for decades despite being almost certainly useless, the cannabis-based supplement market may be just another example of companies seeking profit and consumers seeking panaceas with neither bothering to put in the effort needed to determine what is actually safe and effective treatment for our pets. 

The evidence has certainly grown in the ten years since I began discussing the issue. Unfortunately, it is still weak and limited, and the enthusiasm for cannabis has grown much faster than the scientific evidence.