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|Nexvet - A New Approach To Pain Control In Dogs & Cats|
Before the Texas veterinary boards and the AVMA put a stop to it, (ref) pet owners corresponded with me when they faced painful health problems in their older pets. The most common issue they dealt with was severe arthritis - it made it difficult for their pets to get around. There were others who were forced to deal with inoperable or terminal cancer in their dogs and cats.
Some were faced with debilitating conditions in which their pets wasted away due to their reluctance to eat. In all those situations, the owner's choices in medications to make their pet’s life as comfortable as possible were limited.
Typical veterinary NSAIDs like Rimadyl occasionally cause side effects as serious as the problem for which they were given. Medications like Tramadol were sometimes less effective than one wished (3.8 pain relief versus 10 for a fentanyl patch). Veterinarians often shy away from fentanyl patches (the strongest medication) because of liability issues, fear of the DEA and pet constipation issues.
Corticosteroids used to improve appetite and well being in situations like cancer and FIP in cats brought their own set of side effects.
Many of those emails ask me what I thought about giving their pets marijuana.
Relaxation of the laws prohibiting cannabis use in humans is at the root of this increased interest. Pets have become family members. People have begun thinking: “If there are legitimate medical uses for marijuana for my human family members, why not for my furry family members too ?” Veterinarians are not immune from that line of reasoning either; they are being asked that question more and more by the owners of the pets they treat.
So about a year ago, a popular veterinary newsletter published this article. It was followed by an article on the subject in the AVMA Journal, which you can read here , a letter to their editor by a Florida vet (ref) and a note of very cautious optimism by a distinguished veterinary pain specialist. (ref) Many more articles in the popular press followed.
But building a knowledge base for the safe use of cannabis products in dogs and cats today presents many problems. The greatest are legal and political issues. No one wants to upset the Feds. No one wants to sully his or her reputation.
The second problem is animal experimentation. The kind of experiments that are required to determine safe and effective doses for pain control in dogs and cats are now quite difficult to perform in the United States because of our heightened sensitivity to humane issues. Besides, getting a government grant today to do that research would be quite a challenge.
At one time, gruesome techniques were commonly used to measure the effect of medications on pain sensation (such as timing how long it took a rat to get off a hotplate). Thankfully, experiments like that can no longer be performed in the civilized world. Today, we would be limited to things like activity monitors that might measure an old dog or cat 's inclination to move about after receiving one drug or another. Performed scientifically, those experiments are expensive.
Because of those issues, using cannabinoids (marijuana,Hashish, etc.) in pets today relies on word of mouth, subjective opinion and assuming that dogs and cats will react to these medications the same way that we do. None of that makes for good medicine.
Marijuana (cannabis) does what it does because it mimics (copies) natural messenger compounds in your body and in your pet’s body that have a similar function. It just delivers those messages louder, stronger and for a longer period.
Your pet’s natural messenger cannabinoids are anandamide
and (2-AG). They stimulate receptors present in your pet’s brain (CB1 receptors) and throughout its body (CB2 receptors). The cannabinoids in marihuana attach to those same receptors. However, they resist letting go of those receptors so their effect is more powerful and longer lasting. Drugs that hang on to receptors longer than the natural messengers are called an agonist. The chief agonist cannabinoids in marijuana are Δ9-tetrahydrocannabinol (aka THC or delta-9) and cannabidiol (aka CBD). Echinacea has a few similar compounds. When the effects of cannabinoids wear off, it is because they were processed (metabolized) by the pet’s liver into compounds that left through the bile and urine or were stored in the pet’s body fat.
We do not know much about its effects on pain in dogs and cats. It can be very hard to objectively evaluate pain in our pets. They are so attune to us - the stroke of your hand, a calm optimistic voice, your body language, all make your pet feel better and make it hard to decide what affect the medications you gave actually had.
When it comes to our pets, we have to rely on the feedback we get from humans that take cannabinoids to deal with chronic pain and other health issues. Most do feel some benefit. I have read many of the articles published on that subject. Most describe the benefit as “modest” (ref)- about the same as topical capsaicin liniments. (ref)
Other studies found more benefit. (ref) The pain-relieving benefits never approach that of the powerful opiate narcotics like fentanyl patches nor did they match the pills dentists commonly prescribe for a toothache (ref). (However, it is hard to separate pain from mood and cannabis certainly makes one leave their worries behind.)
Marijuana-based oral sprays seemed to help alleviate some of the pain of one form of arthritis, rheumatoid arthritis, in humans. (ref) That is an autoimmune disease, not the wear-and-tear osteoarthritis common in dogs and cats. But even osteoarthritis may generate neuropathic pain, a type of pain marijuana seemed to help. (ref) Studies in mice seemed to confirm that. (ref)
Pain studies are still allowed to be performed in rodents. Arthritic rats did seem to benefit from the (delta 9) THC that is present in marijuana. (ref)
Not all pain is the same and it may well be that cannabinoids/marijuana deal better with some forms than with others. Again, when we rely on human feedback, it can be hard to separate how much benefit is due to pain relief and how much is due to mood elevation (the high). Perhaps cannabis can elevate your pet’s mood - I do not know..
The optimistic studies I mentioned were small in size. But they were enough to get the NIAAA to fund human trials with standardized amounts of cannabinoids to see how they might affect osteoarthritis pain (knee joint arthritis). These trials were halted due to an unacceptable number of heart and circulatory problems as well as undesirable changes in liver function >in the patients that received the medications. (ref)
In humans, marijuana might have the potential to lessen inflammation occurring at various points in the body through its action on CB2 receptors. The cannabidiol portion of the plant, rather than the TCH portion is thought to be more potent in doing that. (ref) But I know of no studies that examined that effect in animals.
The same goes for appetite. We all know that marijuana stimulates appetite in people. We could assume it has a similar effect in pets or allows them to regain lost weight but no veterinary studies have ever been done. What we have for the moment is folks telling us that the appetite of their sick pets improved on edible cannabis butter or liquid marijuana extract. With time, it should become more apparent if that is really true.
Veterinarians know the signs of marijuana overdose in pets considerably better than they know the drug's benefits to pets. When overdoses have occurred, 96% have been in dogs and only 3% in cats (perhaps because cats are less attracted to sweets).
It has been very rare for pets, consuming a single dose, to die.
What veterinarians see instead is often a staggering pet (ataxic) with a slow heart rate and low blood pressure. Drooling and salivation are common. Many have dilated pupils (mydriasis). A few develop eye twitches (nystagmus).
Some pets develop diarrhea and/or vomit – although it is common that they ate multiple things (including stem fiber) they found when their owners were not looking. Some loose bladder control, others show muscle twitching or tremors.
In more serious cases, the pets come in fearful, anxious, disoriented or in a state of collapse. Anxiety seems worse in dogs that had a prior tendency to fearfulness. You would expect that in a pet with an altered mental state that it did not understand. Those tense pets are more likely to react in an exaggerated way to sudden movement or noises.
Because chocolate often forms part of what the pet consumed, it is hard to tell which signs were due to the stimulants in the cocoa (Theobromine, caffeine) and which were due to the marijuana.
Most cases of marijuana intoxication in pets from a single ingestion incident resolve over a period of 3 - 12 hours with no lasting damage.
Test kits designed to detect marijuana in the urine of humans have been used to detect cannabis exposure in pets. But those tests may miss some cases. The test only measures an end product of cannabis (11-nor-9-Carboxy-THC, aka 11-nor-9-carboxy-delta-9-tetrahydrocannabinol, 11-COOH-THC, THC-COOH) that occurs in urine and it is known that dogs do not produce those same end products in the quantities that humans do. (ref)
Once your veterinarian determines that your pet is not in immediate danger, he/she often gives an oral dose of activated charcoal. Even if marijuana is not high on the list of possible causes for your visit, it is often give because it is thought to prevent the absorption of many toxic products. If ingestion (eating it) was observed or thought to be recent and the pet was lucid (knows what's going on and has normal body strength), they would probably induced the pet to vomit. If more time had passed, a laxative (e.g. Sorbitol ) might be given to flush out the contents of the pet's digestive tract.
If the pets blood pressure was low or if it has become dehydrated due to vomiting , diarrhea or inability to drink, IV fluids might be given as well.
Pets with subnormal temperature will get heat – perhaps a hot water bottle or a controlled environment cage.
Depending on severity, the pet might also get round-the-clock observation. When symptoms are mild, all that may be required is a quite environment without noise or other sensory stimuli such as barking dogs and strangers.
Anxious dogs might receive sedatives.
Because cannabinoids attach to fatty substances in the pet’s blood stream and body, vets have attempted to treat severe marijuana overdoses with an intravenous fat emulsion (intralipid) that might “sop up” some of the drug. (ref) We do not yet know if this is helpful.
You can read more about how pet overdoses are handled here.
It is either as Dr. Kellogg, senior veterinary adviser to the Humane Society, is quoted as having said: "Sometimes public sentiment and activity gets ahead of the scientific background and that can be dangerous." or is it as “safe and nontoxic” as cannabis advocates believe. (ref) , or...... , more likely, it's somewhere in between.
Veterinarians and others that recommend marijuana in a carefree manner have disregarded some important points:
They are assuming that marijuana/cannabis is metabolism in dogs and cats the same way that it is in humans or the rats, mice and monkeys it was tested in. That is untrue
They say that the ingredients in cannabis (chiefly THC and cannabidiol) are “practically harmless” because its LD50 (toxic dose) is very high (greater than 3,000 to 9,000 mg/kg). Those were one-time dose experiments - not the effects of long term use.
You can eat all the raisins or chocolate you like – your dog can’t. You can eat all the onions you like, your cat and dog can’t. You can take an extra strength Tylenol tablet, your cat can’t. Our bodies handle (metabolize) things differently.
I want to tell you a story – please bear with me :
It began a long time ago and has been pretty much forgotten. The medicinal (beneficial) properties of cannabis have been known since antiquity (ref)
But that particular group was not the only one interested in the ingredients in cannabis. The United States chemical warfare program (ref), had a keen interest in those chemicals as well. They were located in Edgewood, Maryland, a short distance from the Baltimore NIH lab where I was working at at the time. Those folks were busy funding all sorts of research around the US designed to make “useful” derivatives of marijuana and judge their effects on the body. As luck would have it their chief experimental “volunteers” were stray dogs.
That interest did not end until 1975 when President Ford sign the UN Geneva Protocol banning chemical weapons.
One of the ECBC contracts was given to the department of Pharmacy at the University of Michigan to study several cannabinoids , DMHP, NAP and MOP. The first thing they noticed was that dogs were more sensitive to the effects of cannabinoid compounds than monkeys. Two of the four dogs in one experiment died by the end of the 4th day of cannabinoid (DMHP) administration. Other ECBC-funded studies conducted elsewhere found that any stimulant in the dog’s system (caffeine, amphetamine, cocaine) or nalorphine concurrent with that cannabinoid, greatly increased the cannabinoid’s toxicity. (That has relevance today. If one was uncertain what recreational drug a pet ate, nalorphine, might be given as well.) They also noticed that there was a great deal of variability in how a given dose would affect a single animal. You can read their report here.
In the following years, many toxicity studies were performed on experimental animals. All found that dogs, mice, cats and monkeys behaved similarly when given cannabinoids. The problem was, these were one time doses. Rarely if ever were multiple doses given to see what occurred over time. You can read a typical study of that type here.
Lets move on to 1975. New chemotherapy medications for cancer are coming on the market and drug companies are looking for ways to control the nausea they cause. One of them is Eli Lilly Laboratories whose research center was in Indianapolis.
But there was a major problem. This was the time of reefer madness. The chemists knew that the garden variety Delta 9 THC in marijuana worked quite well in controlling nausea. But there was fat chance of getting FDA and DEA approval to market a standardized pot pill. It was just too foreign to the thinking of the times. Besides, they would not have had a patentable product – one that could produce a revenue stream sufficient to justify their efforts. They were also hoping (mistakenly) that they could split off the anti-nausea effect of THC from the elation effect – even though a bit of elation in folks facing chemo might not have been such a bad thing.
So they zeroed in on an alternative THC structure previously synthesized. It is called Nabilone. Presented to the FDA and the DEA in correct fashion, that could give the Federal Agencies the fig leaf they needed to approve a cannabinoid anti-nausea medication while still keeping marijuana illegal. The feds finally sent a letter accepted that ruse in 1986. (ref) Nabilone is marketed today as Cesamet.
In 1975, Lilly rounded up six male volunteers who were more than happy to get paid to get high and gave them nabilone. They pronounced the drug safe and its addictive potential minimal. You can read the study here.
However, a study like that one was unlikely to meet the demands of the FDA and the DEA - they like voluminous studies to assure safety (a good thing). One of those demands is usually to know the effects of a particular drug's long term use. So in 1976, Lilly began another study that included the long term effects of nabilone. At the time, it was common to do those studies in stray dogs (euphemistically call “random source dogs”.That is no longer allowed because those dogs were often sick and stressed to a point where the experimental results were inaccurate.)
Here is what they found: Dogs and monkeys absorbed nabilone at about the same rate. However, once in the body, the cannabinoid transformed (metabolized) in very different ways in dogs than in monkeys. Not only were different compounds formed, but these compounds (carbinol metabolites) accumulated in the brains of the dogs at levels 5-6 times higher than in the dog's blood. None accumulated in the brains of monkeys. The dogs appeared OK on the three-months study. But on the one-year study, a considerable number of dogs died ; showing violent convulsions shortly before death. So many had died by the 7th months that the experiment was called off. Just as worrisome, dogs died at all dose levels, that is, it didn’t seem to matter much how large or small the daily drug dose was. That is quite unusual in medicine; most problems are dose-dependent. None of the dogs still had high nabilone levels – it appeared to be the high carbinol metabolites that accumulated in their brains that killed them. It did appear that whatever eventually occurred took longer to occur when the daily dose was small but it eventually occurred just the same. You can read the results of those studies here , here and here.
I know of another 1977 study that looked at the way dogs process the THC in marijuana. But I do not know if its authors were aware how differently the process occurs in dogs versus humans. You can read that study here.
So the Lilly tests had to be repeated – this time in monkeys that appear to react to cannabinoids (in the way they break them down) more similar to the way we humans do. In dogs, it appeared that nabilone was metabolized in the dog's liver similar to the way it was in other species- but something farther down the line, perhaps the dog’s ability to eliminate the carbinol metabolites through its kidneys and liver were different in dogs than in humans and primates.
In addition, we now know that even cannabis receptors differ between dogs and humans. (ref)
What the Lilly researches saw in the dogs receiving cannabinoids – convulsions occurring without warning just before death, deaths not dependent on the size of the dose and nothing significant found at autopsy has many similarities to a syndrome seen in humans called serotonin syndrome. It has been seen on other occasions when cannabis was given to dogs over extended periods. (ref)
(When you see warnings on TV commercials about using their particular drug product when you take or recently took MAOIs - the fear of serotonin syndrome is the reason.)
Lilly’s dog results were unusual enough to be communicated to Dr. Mechoulam in Jerusalem. He assigned one of his grad students, Emil Samara, to figure out what was going on in those dogs. (Dr. Samara is now CEO at Pharma Polaris. I was a PhD student at the same University but in a different department, commuting back and forth from my animal hospital in the Galilee.)
What Dr. Samara found was that unlike in people, dogs combine large portions of the cannabinoids they ingest with glucose to form glucose conjugates. They did not find these “unusual glucoside conjugates” in rats given the same cannabinoid. You can read those studies here, here and here.
This is probably one reason why the human urine drug tests are inaccurate in dogs.
Now that you know how little we veterinarians know about how marijuana/cannabis might affect your dog, you should know that veterinarians know practically nothing as to how it might affect your cat. (ref) So you can’t blame most vets for being hesitant about recommending it.
Perhaps your pet is not expected to live long enough to experience the possible side effects of cannabis that concern me. Even then, its immediate comfort could be more important than the length of its life. Maybe you will be using what is basically a homeopathic amount of cannabis – too little to do much one way or the other. The world is full of those products. Maybe something similar to serotonin syndrome won’t occur in your pet - only a few seem to develop it. It could also be that I am just wrong - Time will tell.
I live on the Texas border where anything to do with marijuana is dealt with severely. So I know very little about the products found in more progressive states. For that, consult your local cannabis connoisseurs.
I do know that the cannabinoids in marijuana dissolve best in fatty substances (they are called lipotrophic). I also know that the overdoses veterinarians see are often associated with something called "cannabis butter". That may be because the milk fat in butter serves as an efficient way to accumulate the active ingredients in marijuana, the butter fat aids in absorption through the pet's digestive system or both - I do not know.
I also know that there is great variation in plant potency (strength) and that heating and drying apparently increases the availability of the cannabinoids in marijuana. There are also differences in the THC to CBD content and ratio between various strains of Indicas marijuana and Sativas marijuana. (ref1 , ref2)
You would probably be reluctant to take a medicine that you thought might cause side effects when you didn’t know how much you were taking. The same should be true for your pets.
The primary advantage of these products is that their strength is known precisely and published studies have been performed to determine their toxic doses (but not in dogs or cats). That at least allows an actual known dose to be calculated.
I wrote a great deal about Lilly’s nabilone (Cesamet) earlier in this article. It is currently a DEA Schedule II controlled substance. It is approved by the FDA for treating nausea and vomiting associated with chemotherapy when ordinary anti-emetics are not effective.
Off label uses in humans include treatment for fibromyalgia, multiple sclerosis (MS), chronic pain, and inflammatory bowel disease.
Dronabinol, sold as Marinol by the Solvay Pharmaceutical Company. It is often called synthetic THC and appears to be no different that the THC found in marijuana (with the same effects and side effects). It is used in humans as an appetite stimulant, to prevent vomiting, as a treatment for the general decline of AIDs and to relieve pain. The DEA put it in Class III for now – until some sort of national marijuana policy is established.
Marketed as Sativex, it is a mouth spray used to treat pain, multiple sclerosis and overactive bladder. It really belongs with the natural products because it is simply an extract of natural cannabis. It is in an alcohol base that some people (and probably pets-not that I suggest you give it) find objectionable. It can be purchased in many countries - but not in the USA at the time I write this article (2011). It is currently undergoing phase III human clinical trials here in the US. (ref) You can read one published study here.
I can't be of much help to you here. Dr. Robinson of the Center for Comparative and Integrative Pain Medicine at the Colorado State Veterinary School had some advice for me when I inquired as to who in the USA might be a good source of that information. She suggested contacting a member of the IVAPM , The International Veterinary Academy of Pain Management . I think that was excellent advice - certainly better than trusting what you read online, in the popular press or the advice you get at your local medical marijuana outlet.
Topically applied cannabis seems to be the current rage. We know very little about the ability of these products to penetrate through the skin or if they enter the blood once they do. If, for instance, they did penetrate the skin and if they only worked locally on local CB1 receptors, perhaps the brain effects that appeared to occur in dogs receiving cannabinoids orally might be avoided. I do not know. Even if those medications did not reach the pet's brain, side effects could occur as they have in humans (ref). You can read the little we know about those topical products when used in people here. (ref) >
The answer to both questions is probably yes.
Your pet’s, age, concurrent medications and breed might affect its reaction to cannabinoids. Its current stress level might also. Cannabinoids are metabolized in your pet’s liver and excreted through its kidneys as well. So any decline in the function of those organs will likely affect how it handles cannabinoids.
Cannabinoids are most soluble in fat and lipids. So obese pets might experience different effects from the same dose given to a lean pet.
Cannabinoids appears to decreases tear production. So breeds of dogs with bulging eyes (brachycephalic breeds) might be more susceptible to dry eye problems when on those medications. (the potential for eye problems is another good reason not to blow marihuana smoke at your pet).
Some pets are prescribed tramadol for pain. We know that humans are more at risk of serotonin syndrome when they take tramadol along with other medications. (ref). Perhaps the same effect occurs in pets.
Older pets often suffer mental decline as they age just as we do (CCDS) . Veterinarians frequently prescribe selegiline (Anipryl, Deprenyl) for those pets. How that stimulant would interplay with the effects of THC within the brain is unknown.
Based on the Astra Zenica studies I referenced earlier (repeat ref) it could be wise to monitor heart function, liver function and kidney function in pets receiving cannabis products in meaningful amounts. Since hepatic seatosis was one side effect that was noted in people, hepatic lipidosis in cats would be another problem that might cross my mind.
According to the attorneys at Norml, no.