The medical use of cannabis has become a hot topic in recent years, particularly in human medicine; many people claim that certain molecules derived from the plant, particularly CBD, can help alleviate a number of conditions. We in the veterinary world are also curious, and a number of trials as well as anecdotal evidence have shown that products containing these molecules may be useful in treating certain diseases in pets. Today we will be explaining how these molecules interact with the body, look at the evidence from studies that tested their use, and briefly discuss the issues with CBD use in veterinary medicine. We should also preface that we will not be discussing the contentious issue of recreational cannabis use, and instead stick to the science of medical cannabis in veterinary medicine.
What’s the Science?
The Endocannabinoid System
Animal bodies are not a single complex machine, they are many different complex machines all tied together in an intricate web. One of the ways animals tie each part together is via signalling molecules. Signalling molecules are released into the body when something needs to happen. These molecules the bind to a receptor like a key into a lock, and cause a change – like increasing the production of a substance or turning production of another off. One of the largest receptor systems, found in all animals’ bodies (except insects), is the endocannabinoid system (ECS).
The endocannabinoid system releases molecules called endocannabinoids that bind to cannabinoid receptors (mainly CB1 and CB2) to cause an effect. The ECS is a relatively new discovery and we are still figuring out exactly how it works. What we do know is that the ECS is widespread in animal bodies, and is involved in homeostasis (keeping things like temperature regular), communication between the central and peripheral nervous systems, pain perception, inflammation, sleep, the immune system, appetite, emotions and many more processes.
Phytocannabinoids and Terpenes
For thousands of years, we have known that the cannabis plant has varying effects on the body. Thanks to decades of research, we now can better explain how.
Cannabis contains molecules called phytocannabinoids – when they enter the body, phytocannabinoids interact with the ECS similar to how endocannabinoids work. The most well known of these phytocannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD). Hemp is the term for varieties of cannabis grown for legal industrial use, which usually have very low levels of THC.
The psychoactive agents…
THC is the psychoactive compound in cannabis that makes users of recreational cannabis ‘high’, as well as causing other effects, both positive and negative. (It is also responsible for the toxicity of the more potent cannabis products in dogs – Ed.)
This is mainly because it binds to CB1 receptors in the brain. To be legally sold in the UK, all cannabis products must contain concentrations of THC below a certain level. The use of THC in medicine has not been thoroughly investigated.
…and the more subtle ones
More relevant to today’s article is CBD. CBD also binds to cannabinoid receptors, but in a different way to THC. It is not psychoactive and does not cause a ‘high’. As we previously mentioned, it has been in the news because many people claim it helps them cope with chronic diseases. Investigation into its use is ongoing, but we do know that one of its effects involves slowing down the conversion of endocannabinoids to arachidonic acid – arachidonic acid is a molecule involved in the inflammatory cascade. In other words, CBD seems to have an anti-inflammatory effect, and so should be able to reduce chronic pain. It may also increase activation of the ECS, leading to improvements in all the body processes the ECS controls. In the UK, it is legal for humans to be prescribed and purchase CBD-products, and there is a lot of evidence that CBD helps many people.
Cannabis also contain molecules called terpenes that give the plant its strong taste and smell. In fact, almost all plants contain terpenes – the smell and taste of pine, lemon and lavender are all caused by terpenes. We have known for years that many terpenes have medical benefits, such as anti-inflammation, relaxation and bronchodilation – the smell of lavender is widely considered to cause relaxation, for example. Terpenes isolated from cannabis are now being investigated for their medical benefits, and some are being combined with CBD-products.
What Evidence Do We Have?
As inquisitive vets, we want to know if any of the chatter surrounding medical cannabis has relevance to veterinary medicine. A number of studies have been performed in recent years, looking at the potential use of CBD-products in animals. THC has also been investigated, as it can be ingested accidentally by pets and is present in some CBD-products in low levels.
Knowing if these molecules are dangerous to our pets is crucial information. Various studies have investigated the effects of THC and CBD in both cats and dogs, the longest study being 12 weeks. In dogs, very few adverse effects were reported, even at high doses of CBD. However, diarrhoea, vomiting and lethargy were reported, and one study did note that products containing THC tended to cause more severe side effects, such as lethargy, hypothermia and difficulty walking, versus those with just CBD. In severe overdose, THC can also cause more serious signs such as collapse, coma or seizures, which may be fatal, but this is very unlikely at therapeutic levels – it is more of an issue with consumption of strong recreational strains or of resin.
Cats also appeared to show few side effects, though head shaking and excessive licking have been seen. Studies that tested the animals’ blood regularly found that the only significant change was an increase in liver enzymes, indicating the liver was under some stress from breaking down the molecules. Importantly, one study used doses of CBD higher than a commonly ‘recommended’ dose (recommended in quotation marks, as there is no official dose yet), showing that a large overdose with CBD is not harmful. Earlier studies showed no lethality and the current LD50 (the amount of a substance that is lethal in 50% of animals) is well in excess of any practical dose. All studies concluded that CBD is not inherently harmful to most pets.
Many animals with chronic pain are on multiple long-term medications; each drug interacts with the body and each other differently, so knowing how CBD fits into all this is important. One of the most common classes of pain relief drugs are NSAIDs – we know that CBD should not interact with NSAIDs, as it interacts with receptors in a different way. The exception is paracetamol, which may interact with the same receptors – the dose level for paracetamol in dogs is relatively low, and so interactions are a risk. Of course, paracetamol should never be used in cats.
In most of the studies looking at pain, the dogs were already on multiple drugs, and no significant side effects were noted. In fact, using CBD may allow animals to stop taking other pain relief drugs. There is some evidence that using drugs like gabapentin, tramadol, buprenorphine or benzodiazepines alongside CBD can cause lethargy and ataxia. Furthermore, as CBD is probably broken down by the liver, other drugs broken down by the liver may not be eliminated as quickly if CBD is present – this could affect how we give drugs in a clinical setting. In general, however, the risk of using other drugs with CBD appears to be low.
Investigations also took place into the absorption of CBD. Absorption is how much of a drug ingested actually gets into the body to cause an effect; if absorption is 50%, then 50% of the drug enters the bloodstream to be used. Earlier studies found that there was poor oral absorption of CBD and most of it did not enter the blood. However, later studies have shown that if swallowed with something fatty (such as oil), a lot more CBD is absorbed in dogs, perhaps 3-5x more. Cats appear to have worse absorption overall however. All of this has relevance for future dosing protocols, if and when more products are legalised.
Two studies looked at the effect on chronic pain when using CBD-products in dogs. A study of 16 dogs with osteoarthritis found that after being on oral CBD, there was a significant reduction in owner perceived pain, veterinary pain-scoring, and dog activity. There was no change in their physical mobility (as pain relief cannot treat physical arthritis), but comfort was increased. A similar study showed similar results with transmucosal CBD given to 9 dogs. One preliminary study led to 20 out of 24 anxious dogs showing reduced anxiety after taking CBD-products.
Other studies have shown positive initial results when CBD was used to treat dermatological conditions and even cancer. Further investigations are ongoing into the effects of CBD on acute pain, seizures, anxiety, skin diseases and even its effects in horses, parrots and primates.
In addition, there is a lot of anecdotal evidence from both owners and vets who use CBD-products. Many claim it has given their animals a new lease of life, alleviated chronic pain, helped treat anxiety and epilepsy, and a myriad of other things.
Why We Shouldn’t Get Too Excited
From the selected above studies, there appears to be a lot of good evidence that CBD is safe, can be absorbed into the body easily, can reduce chronic pain from osteoarthritis, can help anxiety, has limited drug interactions, and may help animals with other conditions.
So, why isn’t every vet using CBD?
The main issue is that we have such limited evidence. Although the above studies have shown promising results, they have all been small-scale with few animals involved, and have only lasted a few weeks – this is unreflective of a general UK pet population using CBD for months and years. Although there has been more evidence from individual owners and vets showing animals doing well on CBD for many years, it is all anecdotal evidence that has not been tested in a rigorous scientific way. We do not want to cast doubt on people’s findings, and many of these animals may have been helped by CBD-products, but this evidence may feature confirmation bias (testers want CBD to work, so will only focus on the positive effects), the placebo effect, a lack of reporting unsuccessful use, and other problems that can only be eliminated via proper scientific testing.
In short, we need a lot more peer-reviewed data proving CBD is safe and effective, before there can be widespread legalisation, manufacture and use.
Problems with Products
The other issue with CBD-products is that the market is vast yet unregulated; it is not difficult for someone to produce and sell CBD-products legally. These could end up being used on pets, despite being untested. Each product contains different phytocannabinoids, terpenes and other substances, which makes collecting data on what works and what doesn’t difficult. To make it more complicated, not every product contains what it says it does; in fact, a 2020 study of 29 products available to purchase in the USA showed that only 18 were appropriately labelled, and 4 contained contamination with toxic heavy metals.
This creates a minefield for a vet who wants to use CBD in a patient. One study recommended “…veterinarians should become versed on products available before using them clinically.” Some companies do perform more rigorous testing, so options are out there if you and your vet do your research. However, until there is proper research into the correct formulation, controlled testing and manufacture, many products will be simply unproven.
Problems with Legality
As we have discussed in a previous blog, the use of CBD in pets in the UK is complicated. In short, vets can use CBD products in animals, but only via a complex process called ‘the cascade’. Generally, vets will have to have tried multiple different drugs before being allowed to try CBD-products. In the UK, only CBD-products licensed to be used in humans are available, and permission is needed from you as an owner – there are no CBD-products licensed for animals.
It is illegal to administer any cannabis-derived products to an animal without a prescription from your vet. You must not purchase CBD-products and use them on your pet without a prescription.
What is in Store for the Future?
As you can see, there is a lot of promising information surrounding the use of CBD in animals. It appears to help with chronic pain and anxiety, and may be used in future to help treat other diseases. However, we need more evidence from large-scale tests before CBD will become widespread; it can take years for a drug to become licensed, so a little patience may be needed.
We should reiterate that CBD is legal to use in animals, under certain conditions, and has proven to be effective in some patients. If your pet has a chronic disease and you have tried other products with no success, it may be worth asking your vet about CBD-products. Remember that any treatment of this kind may be untested, and your results may be variable.
Watch this space, as CBD and other cannabis-derived products could very well become hugely important drugs in both human and veterinary medicine.