Hi everyone, thanks for joining me on a topic that I'm particularly passionate about, and that's about integrating CBD in particular into to modern evidence-based clinical practise. So, just a little bit about myself, who am I, I'm a veterinary, anesthesiologist, I'm a, board certified specialist with the North American College, I have a PhD in, in pain management. But for this presentation, really, when I'm talking about things that are traditionally considered to be outside of the mainstream, I really need to emphasise that I am an evidence-based clinician.
Just to begin with some of my, current disclosures, so I have research positions at Curtin University. I'm director and founder of VET Pharmacist. I do anaesthesia and analgesia consultancy.
I have a pain clinic here in Perth. I consult to Zoettes, and I'm hospital director for SAS in Perth. So, let's start at the, the beginning.
Where did this, journey, begin for me? Well, I was involved in, in medicinal cannabis in an R&D, context in, in Human Pharma, right from the very beginning of the inception, for, Medicinal cannabis medicines here in Australia. And when many of my colleagues started to recognise that there was a vet working in the medicinal cannabis space, they reached out to me for information.
And usually that information was, trying to answer the questions that they were being presented with in consult. Is this drug applicable for veterinary patients? Where do we find reliable sources, to be able to provide, our, our pets with something that is assured in terms of quality.
And, and is this even legal? And then, of course, at the forefront of all veterinarians' minds is, are we going to do any harm? So, essentially, I started to do many presentations, just like this, to ultimately, present the research when we can be using this drug, when we should avoid using it, and where is the current level of evidence.
So if we go back to the very beginning, the very beginning in terms of cannabis as a medicine is some ways, in the past. So the first documented evidence of cannabis being used as a medicine was over 5000 years ago in the Chinese pharmacopoeia, where it was used as a, as a perioperative analgesic. And then there's more recent times, in as early as the, the 20th century, cannabis preparations were widely prescribed by Western doctors.
You can see here, Queen Victoria, was, widely reported to, to use medical cannabis for, particular ailments. Doctor O'Shaughnessy, here pictured on the bottom left, is one of the, the, the key, people who brought this medicine, back from From the east, to the west. What I like about this particular picture though, if you look at these, these bottles of, of, cannabis medicines here, these tins, the, the, the, the names on the bottle, or should I say, the, the manufacturers on the bottle, are some of the precursors to some of the big pharma groups, of today.
So the Santos, the, the Pfizer groups. Cannabis was very much considered to be a, a mainstream medicine. And it wasn't until the era of prohibition where things really took a turn, where there was a, a, a deceleration, really a curtailment of the use of cannabis, not only recreationally, and medicinally, but regrettably, in the research context as well.
So the era of prohibition was largely about, about control, minority groups in the US used cannabis both recreationally and medicinally and the authorities at the time saw this as a way of being able to control those minority groups. But really the, the final nail in the coffin was the single convention on narcotic drugs in 1961 and 1962, which essentially, Put a ban on the use, or a moratorium on the use of cannabis, both recreationally, medicinally, and in research worldwide, and many countries signed up to this single convention on narcotic drugs. But then, eventually, some research began to, began to occur.
There were some countries that withdrew from the single convention. Interest, particularly in, in Israel, started to rekindle in the 1980s. There was, significant research coming out of that country.
There was also significant patient advocacy that was coming out as well, around the same time. We're a little bit later, in the mid 80s, there was a synthetic THC developed and registered by the FDA for nausea and vomiting due to chemotherapy. Interestingly, it had to be a synthetic, derivative of the naturally occurring molecule, because up to this very day, the, the, the phyto, chemical is considered to be, illegal in, in the US at federal level.
And then various states started to, to, to set up their own systems and, and rebelled a little bit, I guess you could say against the, against the federal system. California, most notably in 1996. And then here in Australia, interestingly, we, we amended the Narcotic Drugs Act in November of, of 2016 to allow medicinal cannabis to be used for human therapeutic purposes.
So what about, veterinary, medicine, what, what about veterinary use for patients? What about the regulations when it comes to the use of, of cannabis as a medicine in, in veterinary, in veterinary circles? We, have different obligations in terms of, of our obligation.
So as veterinarians, we do have the right, particularly in Australia, to recognise that that's not always the case in other jurisdictions, but we do have the right to prescribe human medications off label for veterinary use, where there is no registered, human, veterinary product. So, that's very much the case where, where vets are used to prescribing, medicines that have been manufactured specifically for, for human use. For, for veterinary conditions, in fact, we do that about 30% of, of the time, we, we draw a medication, in veterinary practise, many of those medications have been labelled and registered for, for human therapeutic use.
But there are some exceptions. So one of the main exceptions, in, in Australia is that the formulations of medicinal cannabis that are prescribed can really only be predominantly CBD formulation. Specifically, the formulation needs to comprise 98% or more of the total cannabinoid content as CBD and any other cannabinoid cannot be greater than 2% within that formulation.
So, provided that those conditions are met, that means the drug falls within Schedule 4 of the poison standards here in Australia, veterinarians are permitted to be able to prescribe that product for veterinary patients. And many of the vet surgeons boards, many of the regulatory authorities in Australia have messaged that across various jurisdictions. So where do we get these cannabinoids from these, these ligands?
Well, essentially, there are, there are 3 main sources. So there are, endocannabinoids, meaning endo, meaning from the brain or from the body. There are phyto phytocannabinoids from, from the plant.
And then there are synthetic cannabinoids, which are obviously, derived from, from laboratory sources. We're gonna really focus on the endocannabinoids and phytocannabinoids, today. And how about the system that it all works on, the, the endocannabinoid system or ECS, as, as we call it for short.
It's a biological system composed of endocannabinoids, that bind to cannabinoid receptors. So the ECS system is a system that we have known about for many years, since about the 1950s. It's implicated.
In the regulation of mood, appetite, pain, memory stress, immune response and gastrointestinal function. And like many systems, it contains three main pillars. So we have these receptors, we have these ligands or endocannabinoids, and we have regulatory enzymes that dictate the mode of action of these receptor ligand interactions.
I'm not gonna go into too much detail about the, the receptors, and the, the pharmacology at this level, but, it is important to understand, some basics. So, in terms of the receptors of the endocannabinoid system, they are present on neurons and cells throughout the body. By far, the, the greatest proportion of these receptors are G protein-coupled receptors, and of the gene protein-coupled receptors, CB1 and CB2 are the most well known.
There are also lianggated ion channels, you might remember from, from, from vet school, TRIPV1 implicated with nosyception. There are also serotonin receptors. You start to build up a, an idea about, some of, the, the modes of action of these receptor groups.
And there are also nuclear receptors as well. If we look at the, the CB1 receptor, firstly, it's the most abundant protein-based receptor found in the human brain and CMS, but it's also found in fat cells, liver cells, musculoskeletal tissue, and gastrointestinal tract as well as cardiovascular system, the peripheral nervous system, and the reproductive tract. It mediates inhibitory action on the release of excitatory and inhibitory dopaminergic, GABA, glutaminergic, serotonergic, noradrenaline, and acidylcholine neurotransmitters.
But broadly, it has functionality to do with mood, cognition, reduction of pain and inflammation. It's also responsible for the psychotropic effects of THC, so THC does have a, a relatively strong affinity for CB1 receptor. CB2 receptor, on the other hand, is primarily located in the cells of the immune system.
So it's it's on receptors, such as, on B cells, or T cells, and macrophages, but it's also found in the liver cells, kidney, and the skin. In contrast to CB1 receptor, CB2 receptor, is primarily involved in, in anti-inflammatory effects, but also, in immune modulation as well. Now how about the, the phytocannabinoids itself?
Well, cannabidiol or CBD for short, as we call it, what's its mode of action? Well, it has a low binding affinity for CB1 and CB2 receptors. Of those two, it does have a, a higher binding affinity for CB2.
It's a weak agonist at both of those receptors though, it should be said. It is a potent agonist at TRIV1, so remember, TRV1 being implicated with nosyception. It also limits anantamine degradation through an enzyme called PA.
So nanamine is the, is, is the, is the molecule that's responsible for those euphoric feelings post exercise. It's responsible for that, that post run as high that people, report. So you can build up an idea about how, CBD may have positive effects in terms of, amplifying the amount of anantamine in the body.
It's also an allosteric modulator at opioid receptors, me and Delta. Now THC, while it is not, widely available or or regulated, to be used in in veterinary medicine, it does have some therapeutic indications, and at some point, most jurisdictions will eventually, loosen the laws around the use of THC. So I do think that it's important to have an understanding about its mode of action.
THC is a partial agonist that both CB1 and CB2 receptors, but it does have a stronger affinity, as I mentioned, for, for CB1. It's a phytomimetic of anandamide, that feel good, that feel good molecule, and it also binds FAP, which limits endogenous ananamine degradation, further amplifying the amount of anantamine in the body. Importantly, particularly in veterinary contexts, it's responsible for many of the, the psychotropic effects, that, that many of you who have worked in emergency practise will have recognised for, for toxicities, particularly in dogs.
So, so why are dogs more predisposed to toxicities than than other species, cats, humans, for example, but they have a much higher proportion of CB1 receptors in their cerebellum. So understanding cannabis as a medicine is a different way of thinking, and I say that because there is the potential for one medication to have multiple effects throughout the body. This, this figure here is a, a bit of a graphical representation of the proportion of indications that medicinal cannabis is prescribed in humans in Australia.
So this was taken from the, the human, medicinal regulator in, in Australia. You can see the most, most common reason. Is pain, cancer, symptoms, epilepsy, anorexia, but, but right the way down to, to, things like, you know, psychological effects, movement disorders, appetite and sleep, and, and many others.
And a large part of this ability is because of the, the wide distribution, and mode of action of these receptors. It's also important to understand that that treating with medicinal cannabis, is often not about the cure, it's really about alleviating symptoms and ultimately improving improving quality of life. And I, and I say this because if you get on the internet, you know, you will see, claims that, these, these, these medicines cure, cancer and the like.
They do not. They, they, they are really, effective at certain indications, and limited indications. We'll go into that in a little bit more detail, in, in, in a while.
The other. The thing I would like to say is that, often this area of, of medicine is overcomplicated. You don't have to have a degree in naturopathy, homoeopathy, or alternative medicine.
You certainly don't need to have experienced the drug firsthand to use it in the clinic. And the reason I say that is because there are, in many jurisdictions, particularly, in the In Australia, really tight regulations around the quality of the, the formulations that are available for, for medicinal use. And so what that enables us to be able to do as clinicians, is it enables us to be able to take a medicine off the shelf, be assured of the quality in that bottle, and be able to apply a dose range and get a known effect.
So what is medicinal cannabis used for in veterinary patients? Well, by far the most common indication is analgesia. There are strong anti-inflammatory, properties, particularly with CBD.
In terms of anti-epileptic, predominantly, CBDD is used as an adjunct rather than primary, treatments. So you really use more refractory, cases where first line, options, have, have failed. In terms of antiemetic, CBD is a, is a fairly average antiemetic, so it has been compared to to metoclopramide, in, in, in humans, but we have much more potent antiemetics available as first line treatments in in in veterinary medicine.
THC, on the other hand, is an extremely potent antiemetic, and while that's not available to us, it should be recognised, as, as such. In terms of behavioural therapy, we, we all want a new, Anziolytic, as veterinary, professionals, but, it's, there is still much to know about how we should be applying this in the behavioural context, and I'll touch on that a little bit. This is one of the first surveys that, that went out to really gauge US veterinarians' knowledge, experience and perceptions regarding the use of, of CBD for, for canine, medical conditions in the US.
And this concluded that CBD was most helpful in providing analgesia for chronic and acute pain, relieving anxiety and decreasing seizure frequency and severity. And the most common side effects reported was sedation. So, people often ask me, How, how sedate do do patients get on and how frequently do you see that, that sedation?
Well, I would typically see sedation in a naive patient who, who hadn't tried CBD previously in around 5% of patients, at most. The type of sedation is usually, very transient, so it would be unusual for that sedation to last greater than 24 hours. And I don't see the type of hind limb weakness and prolonged sedation that I would get with gabapentinoids, for example.
But there are definitely some challenges. So it's a rapidly growing interest area in terms of the therapeutic use both across the veterinary, world and across the, the, the human equivalent, which, which also implies and, and may put pressure on, on us from clients, from colleagues. And it's not easy to find the amount of, knowledge that we would feel comfortable with out there.
You know, many of us we're not taught about this at, at that school. Things like the endocannabinoid system, things like the, the, the minor and major cannabinoids are quite foreign to us. How do we know which product to trust?
There are many, products in the unregulated context that are freely available, on the internet, or, on the illicit market. So how do we find a product that we can actually The trust to be able to prescribe, and do no harm to our patients, ultimately. There is a lack of traditional dosing protocols.
So, you know, it's not something that you can just go to, to MIMs or plums and, and, and pull a dose off the shelf. You need to really, search the literature as well. So, to, to really help us get around that, I've created a, a three-step process.
To be able to have confidence in the way we use, cannabinoids in, in clinical practise. Step one is pick the cannabinoid indicated based on the patient's condition. Step 2 is, choose an appropriate product formulation, and then step 3 is, is search literature.
So we'll go through that, now. So step 1, pick the cannabinoid, indicate it on the patient's condition. Well, in many ways, this is kind of a little bit superfluous because in many jurisdictions, CBD is the only product where we are actually legally able to prescribe.
I would also encourage us to stick with CBD because that is where the majority of the evidence in the literature is. But if you look up on the internet, other many minor cannabinoids, there are over 150 other minor cannabinoids that occur naturally within the plant. You'll hear cannabinoid names like CBG, CBDA, CBC, THCV, all of these are naturally found in the plant, but the evidence to support their use at a clinical level is, is almost negligible.
The other area which I spend a little bit of time on is quality, because we're not really taught how to judge, rigorous quality standards in terms of pharmaceutical quality standards, as veterinarians. But there is this, this concept called good manufacturing practise, which is the, the gold standard in terms of pharmaceutical, quality. Standards worldwide.
The products that we prescribe for our patients should ultimately, be good, be manufactured under good manufacturing, practises. So I would encourage anybody who is, who is considering to prescribe, a product to make sure that, that the, the formulation that they do prescribe has been manufactured under good manufacturing practises. So, unfortunately, not all products are the same.
There's also a lot of misinformation, around hemp seed oil, which I find, particularly frustrating. This was a, a picture that I took at a, at a local market, about 6 months ago. And what I want you to focus on is the, the sign there which says, hemp foods, CBD, and then in small print, you see, alternative.
There is no CBD. There is no, cannabinoids in hemp seed oil at all. So what is hemp seed oil?
Hemp seed is actually just derived from the seed, of the, of the cannabis plant. Actually, let's just take a bit of a step back even further. What's the difference between a, a hemp plant and a marijuana plant?
Well, essentially, they are both from the same genus species. They are both cannabis sava plants. The real difference is, is related to the amount of, of THC found in each of those.
So in the, the hemp plant, the, the THC is usually less than, 0.2, 0.3%, wet weight.
And if you look at the, at the marijuana plant, you, you have higher concentrations of THC that naturally occur in that plant. If you look at the anatomy of the plant, the, the leaves, which are the, the, the stereotypical, cannabis leaves, actually contain very few, cannabinoids. If you look at the, the, the, the flower, which is, you know, also called the bud, that contains quite, a high active constituent load.
So, that's what is, is harvested to, to make the, the medicinal formulations, that would be, we would, we would seek. In terms of the, the hemp seed itself, it contains zero cannabinoid content. So essentially, besides, maybe containing some omega 3s, omega 6s, it is an expensive olive oil.
And step 3 is really search the literature, the truth is out there, but it's unlikely to be on Google. It's unlikely to be with human medicinal cannabis companies, or, or other professionals. Trust yourselves.
We're all, veterinary scientists at heart. And what I would all encourage you to do. I to spend some time to do some due diligence and, and search the literature.
So, that's what we're gonna do now. We're going to go through the, the various, indications, and we're going to look at the evidence to support particular doses, for CBD in particular in veterinary medicine. And we're gonna start with, with analgesia, in particular, osteoarthritis.
This is where the bulk of the evidence is to be able to support, clinical use. This was one of the first papers that came out of, out of Cornell University. It looked at the pharmacokinetic safety and clinical efficacy of cannabidiol for the treatment of naturally occurring osteoarthritis in dogs.
And this study found that 2 milligrammes per kilo, Given twice a day of CBD was helpful in improving comfort and activity scores in dogs. This study, using a similar dose, actually it was a dose range of about 1 to 2 milligrammes per kilo administered twice daily, also found similar improvements in mobility and quality of life. What I liked about this study was that it actually, recruited and classified dogs as being in, in chronic maladaptive pain.
So that, that, that pain that has become a disease process unto itself. And I'm often asked, well, where are those higher tier papers, where are those, those rigorous studies? It doesn't get higher than, the, the Journal of Pain in terms of the level of evidence.
And this was a well-designed, randomised double blinded, placebo-controlled study, which looked at CBD for the treatment of canine osteoarthritis. Why was why would canine, patients use this for human journal? Well, dogs are a translational model for, for human osteoarthritis pain.
And this particular work found therapeutic potential of CBD at 1.2 milligrammes per gig a day for the relieving of of arthritis pain. Moving on to other indications, so in terms of seizure reduction.
Interestingly, in its adjunct use, it's, it's never been demonstrated, to, to have been used, in, in research context as a primary. So most of those other studies, if I just go back to, to the pain studies where we looked at, at CBD being used at around 2 milligrammes per kilo, these were used as monotherapy studies where there were no confounding medications on board. If we look at, at research in the, anti-seizure space, we've really only, see research where it is being used, as an adjunct.
This is one of the first studies that came out of Colorado State University, and they found that overall results of this clinical trial reported indicated a significant reduction in seizure frequency, with dogs with intractable epilepsy when CBD was used as an adjunct to conventional, medications. Further, research again out of, Colorado State University, this, study found that at a 9 milligramme per kilo dose, this was actually a, a divided dose of around 4.5 milligrammes per kilo given twice a day.
The decrease in total seizure frequency was significant compared to placebo. So, a 24% decrease in seizure days occurred in dogs that received CBD and a 5.8% increase occurred in dogs that received the placebo.
So one thing I want you to notice here is the significantly higher dose requirement for anti-epileptic, drug use versus what was used for osteoarthritis, about double. So in the, in the, in the dose ranges that we're seeing for osteoarthritis, around 1 to 2 milligrammes per kilo, twice a day, that's, it's almost twice that we're seeing this, efficacy lie, when it's used as an adjunct to conventional anti-epileptic, medications. Interestingly, CBD is registered for use in, in human paediatric patients, particularly for Drave syndrome.
The, the dose recommendation there is, is really quite high, so 10 milligramme per kilo, twice a day. And now behavioural. So, as I said, we all want something to work in the behavioural space, but the evidence in terms of the, the veterary literature is quite scarce in terms of, in terms of CBD's effectiveness.
This was one of the first studies that, that tried to assess whether there was any benefit in terms of, reducing aggressive behaviour in, in shelter dogs, but there was no statistical significance achieved. Most recently, we, we do have, at this paper in, in 2023, which, looked at a single dose of 4 milligramme per kilo, CBD administered two hours prior to exposure to a stressful event. So the, the stressor here was was separation or, or car travel, and they found that that was.
Effective and attenuating markers of, of stress, in, in these canine patients. But if you look again at the dose, we're talking about really, those higher, more neurological doses. So perhaps, that's where we need to be when it comes to, to the anxiolytic properties of, of CBD.
Just to move on to, some of the pharmacokinetics, specifically, and then on to safety. So, the pharmacokinetics are, are interesting. So we know that it's in the body system quite quick.
If we look at the, time to maximum plasma concentration, we see that it, it acts very similar to, to non-steroidal. So it's in the, the body system within a couple of hours in, in both, dogs and cats. This was after a fairly standard 2 milligramme per kg, twice a day, administration.
What I find really interesting about this study is if you look at the maximum plasma concentration after a single dose in dogs, you can see 300 nanograms per mL versus cats at 43 nanograms per mL. It would suggest a, a decrease in bioavailability. And that really flies in the face of what, what we would see clinically.
Most people will dose dogs and cats, equivalently. I think one of the, one of the confounding factors in this study, it could be, could be answered by whether, these patients were in, in the Fed state. So, moving on to, to this study, this was an interesting, study which does somewhat explain those discrepancies that we saw previously in apparent bioavailability.
So this, was a Disposition study after a single dose of, of, cannabidiol given to, to healthy cats. And what this study found that there was that there was a near 11-fold increase in absorption in the fed state versus the fasted state. So that does go to some ways to explain those, discrepancies in the previous study between dogs and cats.
Interestingly, it also found that a 5 milligramme per kg dose of CBD in dogs, was sufficient in terms of plasma concentrations to explore the kinds of plasma concentrations that we would expect to see, anti-epileptic effects for. Now in terms of safety, one of the, the, the, the baseline indicators when we, when we register a drug for use in humans, we first test, that in pre-clinical context to determine how safe it is in other species. Using some of that, safety data, we can leverage, what we call no observable effect limits in dogs.
No observable effects limits are essentially dose escalation studies whereby, a drug is, is ramped up in terms of the concentration administered until, adverse effects are seen. The no observable effects limit in dogs with CBD is 100 milligrammes per kilo per body weight. So for me, that provides, some real reassurance, that there is a very wide safety margin between the types of doses that we would expect to be using clinically, let's say between 1 milligramme to 5 milligrammes per kilo twice a day, compared to where we're going to be seeing significant adverse effects.
Now we don't have any Noel's in cats, but we do have this safety, and tolerability study, which essentially was a dose escalation study, and it found that 30 milligrammes per kilo of CBD in cats was where they first started to see, observable adverse effects, which were mild, transient and resolved without any medical intervention. So still well and truly above what we would be administering, clinically. Now what do we have in terms of long-term safety studies?
Well, this is a real, contribution to our knowledge of the, of the drug. It was a, a, a study that looked, at, at 6 months of administration, at a, a relevant clinical dose, so 4 milligrammes per kilo daily. So it's the type of dose that, a, a dog or a cat would be on for, for long-term treatment of osteoarth.
For example, there was biochemistry, and haematology and, was analysed, and there was no clinical, significant alterations apart from a transient elevation in an ALP. So, interestingly, ALP is one of those, those elevations, enzymes that we often see, within two weeks of administration, of commencing administration of CBD. And we were always historically a little bit cautious about using it in, in, in patients where there was already elevation in, in liver enzymes.
This study does go, some ways to being able to elucidate the origin of that ALP. So, not only did this study look at total, ALP, it, it broke down, into various isomers and origins, and they did find that, that bone ALP was contributing, significantly to the levels of ALP, that were, that were detected. So I just want to finish up on on a couple of practical examples.
This is a a a typical prescribing cascade as to where CBD would fit into clinical practise. So this, if you can imagine, is a an end stage osteoarthritis patient. First line for me, is still non-steroidals or anti nerve growth factor monoclonal antibodies.
So, labrella or Brana in dogs, or a non-steroidal, a COXS2 selective non-steroidal, is still recommended as first line treatment options. What's really changed over the last, 5 to 10 years is that second line space. So essentially, 5 or 10 years ago, I was putting gabapentin in that space.
But we don't have any evidence, for, the use of gabapentin, in, in dogs other than a, a single case series which looked at, at chiari malformation and syringomyelia. But that is really quite different to the type of, of neurogenic type inflammation that we see with osteoarthritis. So, CBD comes in at, at second line, because it's been Used as a second line, adjunct to either non-steroidals or anti nerve growth factor monoclonal antibodies, I'll typically start CBD at, at 1 milligramme per kilo twice a day, and I'll see good therapeutic response in the majority of my patients.
Now, because osteoarthritis is a chronic progressive disease, as that disease progresses, you will inevitably, have to go up to 2 milligrammes per kilo in most patients. But I would recommend starting it at 1 milligramme per kilo. Third line, I'll be recommending, Amano gabapentin.
I start those both at the same time. I'm giving, Amantadine, twice a day. It's gonna take probably around 14 to 20 days to take clinical effect.
So, I'm, I'm citing it at the same time as gabapentin because it's really not confounding my ability to be able to judge dose and, and judge efficacy. And then fourth line, I'm moving, to, to paracetamol, amitripsyline will be my, last drug of choice in this, in this space. So how do, how do cats differ?
So moving on to cats, very similar from first line, so still, non-steroidals, and anti nerve growth effects monoclonal antibodies are, are, are first line in terms of level of evidence and, and my clinical practise. What really changes here is that second line space. So, tramadol, comes in.
Now, if this wasn't, a webinar, often when I present this in front of a live audience, there are, there are some groans in the audience. Yes, I recognise the, the palatability challenges with, with tramadol. But if you can get it into a patient, orally, then it is, it is very well metabolised in cats.
So we know that it's not metabolised in in dogs, but cats produce a, a, a very, significant amount of the active, odours methyl tramadol. And there have been several well established clinical studies to to support the use in terms of efficacy of Tramadol at 2 to 3 milligrammes per kilo orally twice a day. Gabapentin, that comes in, at my second line, 10 milligrammes per kilo orally, twice a day.
A bit of a caveat with, with gabapentin. The studies that have, that have, looked at its, its efficacy in cats have shown positive owner reported outcome measures in terms of, owner reported health related quality of life improvements. But there was significant, decrease in activity scores.
So for me, if I'm looking at an outcome for patients with osteoarthritis, activity is everything. Getting these patients mobile again, getting them, lubricating those joints, getting them, reducing weight loss, getting them building muscle again is really quite critical. So, if I'm seeing, too much sedation with gabapentin, I will, discontinue it because ultimately, I want to increase activity.
Often if there is, Too much decrease in activity, I will move to, to CBD instead, so CBD fits really at the last run of my my second line, Amanoine, so again, similar to gabapentin, The, the, the, the primary issue I have with Amantadine is, is its decrease, in activity. So the study that's been done on Amantadine did show significant decreases in activity scores, with cats. The way I use Amantadine, is often, for a, a, a finite amount of time, typically for around, 2 to 3 months at a time.
To really, decrease central sensitization, try to dampen down the NMDA receptor in some of those patients which, which may, have not been on any treatment for their chronic pain for quite some time. And then, again, amitriptyline is in there. Ketamine, I do use ketamine routinely.
I do like to assess whether it's working effectively. I do go at a higher dose, so most, you know, most recommendations would be around the 0.5 milligrammes per kg to, to 1 milligramme per kilo.
I go that higher dose and it's still, sub-anesthetic. So, no adverse, effects reported. But I do see it effective, in, in some, some patients.
So I think it's, it's, it's a nice little add-on. Just a little, guide to, to really, or at least a bit of a prompt in terms of assessing efficacy in patients with all of these interventions, be it pharmacological or non-pharmacological, we really do need to be making sure that we are assessing for. Efficacy, and the most appropriate way to assess for efficacy, in, in, in chronic disease is to use a, a quality of life measure.
And this particular one here is one of the most rigorous that we have. So Vett Metrica, buy new Metrica. So, thank you everybody, it's been great to be able to present this this evening.
If you have any further questions then please feel free to to reach out to me on the contact details below. Thank you.