Good evening everybody and welcome to tonight's webinar. We have a proud sponsors of Elevans tonight and I'm sure that as many of you attended the original talk that we had, you will be just as excited and interesting, interested to hear what is going to be told to us tonight about the practical tips for clinical use. So, we have a slightly different format tonight because we have many, many presenters.

What we've done is we've pre-recorded the first part, and then we will have a live presentation for the last part. It just would have been technically too difficult to have everybody on live. So, I'm sure you will still thoroughly enjoy it.

For those of you that haven't been on a webinar with us before, if you have any questions, please just move your mouse over the screen. Little control bar will pop up. There's a Q&A box.

Click on that, type your questions in. And I can't promise you we will get to all of them because we do have a lot of people on. And there's often a lot of questions, but we will get through as many as we possibly can.

Also a reminder that if there is part of the webinar or something that you feel you've missed, these are all recorded and they will be up on the webinar vet website within the next 24 or 48 hours. And you'll be able to go back because you have registered for this and watch them over and over again. So let me introduce our speakers.

There are quite a few of them, so please bear with me. The first person I'd like to introduce is German Graff, who qualified as a veterinary surgeon in Argentina. He was awarded a postgraduate degree in bovine reproduction and Business Administration in Argentina and a master's degree in business consultancy in France.

He has spent the last decade working in the animal health industry, first at a global veterinary product development consultancy, then as the res responsible for IDEX pre-clinical and clinical study services. But most recently, he's been managing Elivan product development and regulatory affairs. Also joining us tonight is Doctor Joseph Waxlach, who started his academic career receiving a BS and an MS from Montclair State University.

He then attended Cornell College of Veterinary Medicine, graduating in 1998. He continued his residency training in both pathology and nutrition, as well as receiving his PhD in pharmacology in 2005. He became a diplomat in the College of Veterinary Nutrition in 2008 and furthered his board certification as a diplomat in the College of Veterinary Sports Medicine and rehabilitation.

He's currently professor of Cornell University College of Veterinary Medicine. And recently joined EIET team as the chief medical officer to oversee their research and clinical trial programme. Dave Tittle qualified from the RVC in London in 2000.

He has spent most of his veterinary career in private practise in coastal North Devon. In 2010, he passed his RCVS certificate examinations in veterinary anaesthesia and was awarded an RCVS Advanced practitioner status in 2015. He has also obtained his GP cert in 2018.

And as well as his anaesthesia and analgesia commitments in his first opinion and referral services at Charter Veterinary Hospital, he also runs referral chronic pain clinics, utilising a variety of techniques. He is thrilled to be asked to join the EEE board advisory board in 2019. And last but not least, Doctor Fred Metzger is a 1986 graduate of Purdue University Veterinary Medicine and a diplomat of the American Board of Veterinary Practitioners.

He is an adjunct professor at Pennsylvania State University and co-authored the clinical pathology interpretation in geriatric veterinary patients, as well as a guide to haematology in dogs and cats with Doctor Alan Riba. Doctor Metzke is the medical director of the VCA Metzke Animal Hospital, and 11 AAHA certified general referral and 24 hour emergency hospital in the State College of Pennsylvania. So as you can see, we have people who are more than qualified to talk to us about this tonight.

So let's go over to the presentation and we'll come back live afterwards. Phil, if you will start the recording for us, please. Well, thank you very much for the introduction and for the opportunity to share these updates with our professional audience.

Now, CBD has been trending as a Subjects for quite some time now and we are pleased to say that elephants and elevate have been leading a scientific approach to the use of cannabinoids in veterinary medicine. The publications, the case reports, and the firsthand experience we will be discussing during this webinar are a solid proof of that. So I want to take a couple of minutes to set the frame for the presentations to come.

First of all, what people know as CBD products, are not a generic type of product. There is no such thing as as one molecule made by different manufacturers that in principle will have the same safety and efficacy profile. There is a vast range of CBD products that goes from purified cannabidiol or CBD isolates to full spectrum hemp extracts.

Isolates are, as the term implies. Just one molecule isolated from an extract, while the full spectrum extracts contain all the compounds extracted from the hemp plant. This will include CBD THC, minor cannabinoids, tins, flavonoids, and so on.

Now, different cultivars, as well as different extraction methods will result in a diverse mix and proportions of the molecules in the extract and therefore in the product. We now know that each cannabinoid has its own pharmacological effect and its safety profile, meaning that the extras from one plant. Obtained using a specific extracting method.

Are not going to deliver the same therapeutical outcomes as the extracts from a different plant or obtained using a different manufacturing method. At Elevans, we control the entire cycle cycle, sorry, of our products from the growth of our proprietary hemp cultivar in Colorado in our own farm to the commercialization and the technical support of the finished products across the UK. We also design, monitor, and fund.

The research on our products so that we can confidently discuss their pharmacokinetics, their pharmacodynamics, their safety, and their efficacy. So because each product is unique, please bear in mind that the results we will be discussing along this webinar do not apply to any CBD product. On the market, but only to vans or elevate CBD plus CBDA completed spectrum products.

So let's briefly review the science of the endocannabinoid system and how phytocannabinoids like those in the hemp extracts help regulating it. So the endocannabinoid system is is thought to be the largest and probably the oldest receptor systems in the body. Some authors even call it the meta system as it works with other systems in the body as well, like the opioid system for instance.

The endocannabinoid system, ECS or endocannabinoid dome. It's actually a plethora of established or putative mediators. Chemically similar to or derived from anandamide and AG2.

Which are the two main endocannabinoids. Together with the metabolic enzymes. And The known or yet to be fully characterised receptors that they interact with.

The existence of an endocannabinoid dome. Has important implications for drug development too. Historically, We would be looking at synthesising a molecule to act directly on a receptor or on an enzyme pathway to have a direct effect or the direct effect that we are after.

However, in the case of the endocannabinoid system, It has been proven that when That was tried. Because of the complexity of the system. We ended up having unwanted effects or even reduced efficacy in comparison to utilising the complete or the comprehensive botanical extract.

So just to recap, We're going to be talking throughout this slide deck about an endomide and AG2 as the main mediators, CB1 and CB2 as the two main endocannabino system receptors and their associated enzymes. Now together this system will have an autocrine, paracrine, neurological, and even neuromuscular regulation function. That will allow us to have an control and effect over pain perception, inflammation, sleep, mood, appetite, emotions, and so on.

Now the endo endocannabinoid system tone is the tone that keeps our bodies static, in a in a normalstatic situation or state. So the, the roles that the ECS plays in maintaining this homeostatic state allow us to open to us a number of opportunities to modulate it pharmacologically to achieve a desired effect. So we can do this by either increasing or reducing the half, the half life of the of the mediators.

Administering a direct agonist or antagonist of the receptors or modulating the enzymes responsible for responsible for the hydrolysis of these mediators. By doing this, we can achieve the alleviation of pain, reduce inflammation, or even improve the mood, modulate the mood to to control depression or anxiety. As we've just said, we're not just talking about one.

Mediator or one compound and its receptor, we're talking about a complexity of chemical entities and receptors that work together to achieve an effect. This is what's been coined as the. Entourage effect and this is similar in a way to what we would do in in clinical practise when we use multimodal analgesia when we're combining different molecules with different mechanisms of action to achieve the similar goal.

Same happens when we combine molecules such as CBD, CBDA and terpines to achieve, for instance, the alleviation of pain. This again supports the fact that When we, when it comes to the endocannabinoid system. A comprehensive or holistic approach is much more effective than that of a single molecule, such as for instance a CBD isolate.

So we're not gonna go into this slide in in detail, but it's just to give you an under a general idea that when we are utilising a hemp extract in the in this case, In to try and modulate pain perception, where we're gonna be acting is actually in every single step from the transaction all the way through to the modulation. Our products have non detectable levels of THC, so we are not going to be able to have an impact on pain perception and some human CBD plus THC products can deliver. So now I can.

We're gonna be modulating the signal all the way through to the central nervous system and then the modulation of that pain perception down from the CNS to for instance the limbs. There is more information about how this works in the previous webinar we did, and if you still have any questions, please do not hesitate to contact us so we can. Go through the mechanisms of each of these molecules, but now I think it's much more interesting to take the time to go through the scientific studies that we are conducting or have better reason to publish and there then the the case report.

So over to Joe, thank you. Thanks, Herman. I'd like to go over some of the studies that we've been doing over at Elevet Sciences, which is similar to Elevans in terms of the product.

And as you can see, we've done a fair number of studies. We've really initiated this with an osteoarthritis and pain study that we'll go over briefly, as well as a handful of other pharmacokinetic and pharmacodynamic type of studies, as well as safety studies. In light of that, we actually did another study to look at the actual quality control of over the counter pet products and so we'll go through all of that and then maybe summarise at the very end about some of the ongoing studies that LAET is doing right now, to help really prove in principle whether the CBD and CDA product can actually mitigate certain clinical diseases to some extent.

So I'd like to start off with the study that we did almost 3 years ago now and was published 2 years ago on osteoarthritis and pain in dogs. And this was a clinical trial where we actually enrolled 22 dogs, 16 of which completed the study. We had a number of dropouts due to other disease processes and then, non-compliance issues.

But we first started off by looking at the pharmacokinetics and pharmacodynamics at 2 milligrammes and 8 milligrammes per kilogramme body weight. That really showed us that we could actually at the 2 mg per kilogramme of an equal amount of CBD and CBDA, we could actually get CBD at about 100 nanograms in the bloodstream over about a 6 to 8 hour period of time. That led us to use that dose in this actual osteoarthritis study.

Our inclusion criteria, of course, were dogs that had radiographically confirmed multi-joint osteoarthritis, many of them being geriatrics, with other pain control measures that really weren't working for them. We allowed them to be on NSAIDs, so 9 of the dogs were on non-steroidal anti-inflammatories. We didn't allow any dog to enrol that had concurrent organ failure other than things like small hepatomas that were leading to elevations in, in some of the liver enzymes.

And basically, if we actually look at the data, you can see that it was a 4 week crossover design and a 2 week washout where it was a double blinded protocol where the veterinarian nor the owner really knew what was being given to their dog. And what you can see here on these graphs on the right hand side is the canine brief pain inventory scale. What you can notice here is that between 0 and 4 weeks we had over a 20 point drop in their overall pain inventory scales, and then we also did a Hudson activity.

Scoring system which has basically been confirmed to be correlated to radiographic signs of arthritis, and you can see the activity went up nearly 20 points as well. While in the placebo group, we saw no changes in the CBI nor the Hudson activity scores. We did CBCs and chemistries and noted no real, adverse events, due to the adverse findings on those CBC or chemistries over the four week period of time and neither the placebo or the actual treatment group.

Our vet pain indices actually also showed a drop in pain scores while gait, as well as crepitus and things like that did not change, but the actual pain indices appeared to change over time. This led us to the publication that was the first publication on CBD use, and CBDA use in osteoarthritis and After that, we figured, well, maybe it's worth doing some longer term pharmacokinetic and safety data. And so we basically chose to use dogs and cats in the study at that 2 milligramme per kilogramme total cannabinoid dose, and we gave it twice a day for 12 weeks.

And we had dogs on what was considered the elevate mobility chew versus the last study, which was in oil, and we found similar, if not better, actual absorption of CBD in this chew format. So we got to a range of around 301 nanograms per mL at the peak in a nice area under the curve of about 1300 nanograms per hour per mL. This concentration peaked at about 1.5 to 2 hours, and then the cats actually we found something.

Strange and a little bit different. We used an elevate blended infused fish oil in those cats, and we found that the absorption was actually about half of what we could get in the absorption at about 43 nanograms per mL in the cats versus the dogs when we use oil in the prior study got to about 100. Our area under the curve of 164 nanograms per hour per mL, and the peak to that actual high concentration was about 2 hours.

So it's obvious we still need to do some work with cats in terms of improving the overall absorption and we're currently doing things in that nature. We then actually went on to see if we could actually get CBD or CBDA into actual dogs, when we actually applied it in a transdermal route. So we actually put the elevant oil into ape cream base, and we actually had 6 female dogs that we treated with 4 milligrammes per kg of total cannabinoids orally along the inner pinna of the ear twice a day for 2 weeks.

And you can see on the graph on the right that our actual CBD and our CBDA concentrations were actually appreciable at about 10 nanograms per mL in the as a peak after two weeks of treatment in the actual dogs, and then we also had CBDA which was about 35 or so nanograms per mL in the serum, showing that actual CBDA absorption from a transdermal approach was actually better than CBD. We also found that THC was non-appreciable in the serum, while THCA, which is sort of the precursor to THC that's found in our product, actually increased to about 5 to 10 nanograms per mL in the serum. So these acidic precursors to CBD and THC actually are absorbed better and are non-psychotropic.

Therefore, we think these, these may have better anti-inflammatory functions than even CBD alone. Similarly, we actually took those same dogs and we did a 2 milligramme per kilogramme dose of the cannabinoid CBD and CBDA in three different forms from an oral approach. So we gave an elevate extract in a medium and long chain triglyceride form, and then we gave another.

2 weeks on a less than in sesame oil base orally, and then lastly we use the same chew that we used in the prior study. And much like the prior study where we found it to be extremely safe and no real problems with CBCs and chemistries, we really wanted to study the actual pharmacokinetics and pharmacodynamics of CBD and CBDA. And what you can see here is that on the graphs on the right hand side, the CBD concentrations reach about 75 to about 125 nanograms per mL as a steady as a steady state in the bloodstream about 6 hours after their last dose after 2 weeks.

And so what we can see here is that CBDA is very similarly absorbed orally, while if you provide the lecithin base, you can see that the lecithin base actually drastically improves the CBDA absorption overall. Once again, we're showing that this CBDA as well as even THCA actually absorbed far better orally and also transdermally providing anitis for us to deliver better dosing overall. This then led us to actually look at the quality control of the actual products that are on the market today.

So we actually chose 30 products off the internet that we actually ordered and then we sent to a third party laboratory. One of those products actually was mislabeled as a CBD product and it was actually only hemp seed, which took 30 products down to 29 because 29 were actually true hemp extracts. We actually used a certified laboratory.

To actually do all the analysis as the third party laboratory. And you can see right here on this graph that all of the products tend to have what I would call fairly subpar concentrations per mL of the actual oils or capsule in the dry form that we used. And what we can see here is that elevates the only one that has a CBD and CBDA mixture, and that is one of the reasons that we feel our proprietary blend tends to work better than others is because of the acidic form being highly efficacious as well.

That said, you can see that many of the products are well below 20 milligrammes per mL, which actually makes dosing very difficult if we're gonna use that 2 milligramme per kilogramme dosing scheme where many of these products, the dog would go through an entire bottle if we were to say a Labrador would actually go through an entire bottle within a week versus the Levt product which you can see is well above many of the other products out there. Therefore, the dosing would have to be far lower for an elevate product. And then once again you can see that we have this red line in that graph and that's actually the terpines and so we measured the terpine concentrations in those products as well.

And you can see we know terpines have some modest medicinal values potentially as well, and you can see very few products have high levels of terpines as well. Once again saying that every product is definitely a little bit different in terms of their overall constituents and what's in them. And that this leads to different pharmacologic effects.

Therefore, what we can say is that our product has these cannabinoids and we can say that our product has some efficacy, particularly in osteoarthritis at this point. We can see that some of these products also on the right hand side had no detectable level of CBD, so these people were actually selling products that had none. So that's actually an egregious, you know, it's violation of, of any, any true company's ethics.

And then we also found that. Some of these products have heavy metals in them, so 4 of the 29. And so that's kind of problematic because things like lead and cadmium toxicity, can be found in some of these products and so if you were to use that egregiously, you know, quite a bit of it, you may, it may lead to problems in your dog.

And so we found that about 10 of the 27 were within the 10% cannabinoids that are on the label and that only about 18 of the 29 were properly labelled according to the United States laws in terms of how you can label a product. So that said, we at elevator are very committed to the scientific portion, and this is how we drive our product forward and prove its efficacy is by doing a number of studies. So currently you can see we have a lot of studies going on.

In acute pain, we now have an acute pain versus a chronic OA pain study going on at the tibial plateau levelling osteotomy for dogs that have stifle disease. We also have a current study going on with intervertebral disc disease, so, surgical pain as well as recovery from IVDD. We also have an anxiety study looking at noise aversion, primarily thunderstorm phobia.

And then we've had a study going on for some time now that should be completed by the 1st quarter of next year on seizures, looking at idiopathic refractory seizures in dogs who are being treated with a variety of other pharmacologic agents to see if we can better control their seizures. There's an oncology study that's currently undergoing clinical enrollment at both the University of Florida and SAGE in San Francisco looking at quality of life during chemotherapy, during weeks 4 through 8. Of chemotherapy and we've got an atopic dermatitis study that's slowly about to actually finish, so we should actually have data on that early next year.

We're looking at immune cell regulation because we know that we have receptors on the immune cells that actually are will be receptors that will have efficacy in terms of the CBD and CBDA on the inflammatory response in the immune cells, looking at the regulation of those immune cells. We also have safety data and PK going on in in horses which appears to be slightly different than. In the pharmacokinetics that we would see in in in dogs, and from a preliminary perspective, we also have aitizeine study ongoing that's just started looking at safety and the PK of these molecules in birds.

We also have an IBD study going on in non-human primates because there's a specific model that's been shown to be a good model of inflammatory bowel disease and we're looking at the pharmacokinetics which again appear to be different. On preliminary examination from dogs and cats. These are all things that we really need to know.

And then lastly, we also have absorption and PK data going on in cats because we know we need to be able to deliver actually more cannabinoid than what we could deliver through the oil, so we're actually looking into different forms to to make cats better target or a better model to do further clinical studies. So with that said, those are the scientific things that are happening. You see we have a number of research partners.

And thanks for letting me have the time to share this with you. And quickly before we actually hand this over to Doctor Dave Tittle who's done a tremendous amount of clinical work, using the Eev and Evans products, we do want to briefly talk about possible drug interactions. Right now we really find that there seem to be no true drug interactions, with things like non-steroidals that we found in our original OA study.

And that there are animals that are things like gabapentin, tramadol, and as well as buprenorphine or other things, they may actually exhibit a little bit of lethargy the first couple of days, but we found no real interactions and actually it's been found in a in a in a very recent study that you may actually be able to decrease gabapentin dose while on CBD products. So that is actually something that may be of interest to the clinicians out there. From a seizure perspective, there is some thought that it would actually interact with the SIP 3A.

Even though we really don't understand the metabolism in dogs quite yet. But right now, as of, you know, let's say today, a lot of the studies that are are starting to come out of some of the preliminary data is really showing that there is no interaction between some of the other seizure meds and that the seizure meds don't end up going up in the bloodstream or down when on a CBD product, which is actually quite encouraging. And then if you're gonna have an anaesthetic episode where you need to put your dog under for anaesthesia for whatever reason, particularly if you're using things like the benzodiazepines, there may be actually a little bit more lethargy and potentially ataxia surrounding some of these anaesthetic protocols that we have to be a little bit .

Conservative about. And then of course animals on certain SSRIs or TCAs you know, may have some some interactions and so I think we have to be a little bit judicious and careful at this juncture, before we say that it's completely safe when giving these things, but I think we'll learn a lot more in the next couple of years about how this interacts with other drugs. Good evening everyone, and also thanks to Elevans for inviting me to speak at this webinar.

And I wanted to start by offering my interpretation of the UK prescribing cascade and how I work through this regulation in clinical practise. So in September 2018, the VMD issued the statement that you see on the screen at the top, and as CBD is considered by the VMD to be a medicine, and that there are no current products available in the UK that are federally authorised, vets are able to scribe a legally obtained human product under the prescribing cascade. They also stated that administration of CBD without of any prescription is considered an offence.

So, in my opinion, as vets, this puts us in a great position in that we're able to control and oversee the use of CBD products in animals. . We're now able to prescribe good quality, proven products with a robust certificate of analysis, with compelling data emerging with regards to their safety and efficacy.

And also, we're able to offer our patients and their owners additional treatment options whilst adhering to the prescribing cascade. My interpretation of the prescribing cascade and how I utilise this in justifying the prescription of Elevanse products in my clinic is that I will always use a veterinary licence product initially. And this is usually some form of non-steroidal, or, or similar, followed by another veterinary licence medicine, such as tramadol or paracetamol and codeine.

As you'll all be aware, some animals will often require additional drugs or combinations or maybe even utilising an off-license method of delivery, such as infusion therapy to aid the condition as it progresses. Now, by this stage, we'll be likely reaching for a licenced human drugs such as gabapentin or romantadine, etc. Some of these drugs or combinations of drugs may have deleterious effects on animals or again, may not meet their analgesic requirements.

So although there are two human licenced CBD products available in the UK, these medicines contain THC and are specifically licenced for the control of signs associated with multiple sclerosis or for the treatment of seizures. In addition, prescribing these drugs is limited to specific Home Office authorised human medics in the UK, so really considered unsuitable for veterinary applications. They're also very costly.

So I think this brings us then to the unique position whereby I'll also now offer my clients elevans where it's clinically indicated and justified on the cascade. And as you'll see in a moment when I present a few case studies, these animals are often in need of just something more to maintain their quality of life. I'll offer Elevanse in addition to the current treatment regimes, unless there's a medical reason to withdraw these other medications.

And in my opinion, and following advice from the VMD this whole, this use is wholly justified and appropriate, but obviously naturally, I'll always obtain informed client consent before prescribing. So next, I want to talk about a few more unique cases that I've used Elevan in as part of their treatment protocol. And both these cases had additional needs outwith the more conventional applications of the product.

So, dear Milly. Milnie's one of the loveliest dogs and is owned by the nicest, most dedicated client that you could wish to have as a clinician. Mills has quite a few comorbidities, as you'll see from the slide.

Diabetes mellitus, she's got ocular disease, progressive osteoarthritis with a degree of, of non-steroidal intolerance. She's got skin disease, IBD signs, and travel sickness, so that certainly made her visits to the vet, more interesting for her owner, at least, . Her owner is is very dedicated to her, and really understands her ongoing requirements and follows a very strict routine, which includes the home cooked diet.

As you can see, she's on a number of pharmaceuticals and nutraceuticals to aid her conditions, in addition to fortnightly acupuncture sessions. And over time we found that she could tolerate rubenacoccib well, although we do have to be cautious when she has an IBD flu to manage her her using extended duration metronidazole therapy. We found that the tramadol made her unacceptably sedate and ataxic even at low doses, although she does tolerate low dose gabapentin well.

We do use paracetamol on occasion to aid her mobility, although due to her ongoing diabetes associated hepatopathy, we avoid where possible. And following discussion with their owner, we did an opt to starter on elevans twice a day at 2 makes per gig. So, you can see from these images, her owner's dedication to her needs is second to none.

She keeps a very detailed diary, a medication chart and a spreadsheet, and she emails this to me, once a month for review. So although at the time that we instigated Elavanse as an adjunctive therapy to aid her osteoarthritis, there's some evidence from human literature that CBD may have benefits in the control of diabetes. And during a period of inhapetence, approximately 6 months into her Elevan therapy, her owners struggled to administer her oil in her food.

As such, she had a period of approximately 4 weeks where she didn't receive her Elevanse and during this time, the majority of her other meds were given with varying success. And at the same time that she became an appetent, she developed signs of bilateral Horness syndrome, which was confirmed by a referral ophthalmologist. As her sight was already compromised, phenylephrine was used when necessary to resolve her clinical signs, and this appeared to improve her vision and therefore her confidence to mobilise.

There is some human data as you can see, to suggest that an autonomic neuropathy, often seen in diabetic patients, contributes to this. A short time after this diagnosis, Millie restarted her relevance, using gelatin capsules to aid administration. And interestingly, at this point, her owners noticed an improvement in her Horner's signs and documented a recurrence of her Horner's signs on those days where they struggled to administer her relevance.

And over time, we've now got a comprehensive data shared set of clinical observations and owner-led observations and pain scoring, which details the improvement in clinical signs and pain scores and quality of life assessment and owner satisfaction utilising her treatment regime. Elevance has helped her osteoarthritis, it's controlled her appetite, which in turn has helped her diabetes regime and has had a positive effect on her IBD signs. And in advance of her car journeys, she no longer requires antiemetics or frequent stops on the way home.

Over more than 2 years, we've got regular blood and urine monitoring, which naturally highlights her diabetic state and the influence of this on her organ function. But to date, I haven't observed any negative influence from Elevans or any of her other concurrent medications on her medical state. These are her before and after images which detail the improvement in a horner signs which would deteriorate within 24 hours of any missed doses.

Her owners have kindly agreed to record a testimonial for Relevance. I, I wasn't present for the recording of this and had no influence in what they chose to say, so this is a, a real owner led assessment. Milly's a cross retriever and poodle, and she's nearly 13 years old, and for 4 years she's been suffering from diabetes, so she has to have insulin twice a day.

The other complication with Milly is that she has problems with her stomach, so that's a major issue with a dog that's got diabetes because you have to feed the dog before you can give the insulin. She also has problems with her arthritis in her limbs, in her joints, and we were having problems with her because she would. Suddenly want to lie down, we would walk her down the road and she would have to lie down, and then we'd get her up again and off she would go.

Then we heard about Elevance. And we had the opportunity to try it with her. She's been on it for a year and we've seen a marked improvement.

In fact, she's in a lot better condition now than other younger dogs who are suffering from the same condition. Not only has it affected her movement, but it's also settled her stomach. So now she eats with such enthusiasm that we can know that we can give her her food and not have to try and tempt her and tempt her, and so we can give her her insulin.

The other problem that we've always had with Milly is that she gets car sick, but since she's been on the elevans. She's no longer car sick and we don't have to give her tablets to prevent the car sickness. On the whole, in the last year, we have found a great improvement in Millie's well-being.

She's pain free. She gets about very well considering her age and her condition. She eats well because her stomach is no longer giving her problems.

We don't have problems with her bowels. And generally, she's doing much better than other dogs. With far less problems that she has.

I would recommend elephants to other people. So my second case is Chloe, and she was diagnosed with carry malformation at a young age, and its progression was documented at 3 years of age, requiring initiation of treatment. Her owners have repeatedly declined referral for surgical intervention and the rapid development of her signs of distress were really quite marked, which was ultimately affecting both her and her owner's quality of life.

Over the last few years, we've progressively added additional drugs to a cocktail in an attempt to control her developing signs. Finding a paper, suggesting some response and improvement in clinical signs in a dog in Germany, who appeared to benefit from the use of olaintib. We chose to start this almost as a last resort.

Her owners were nearing the point of euthanasia when they decided we had nothing to lose in trying elevans. Adding Elevance to a cocktail has had a a remarkable effect so far. Her quality of life has improved markedly, whereby she now plays for the first time in years.

I've usually had to sedate her to collect bloods as touching her forimbs or her neck would result in a frantic scratch response. Collecting a jugular sample with normal restraint was a pivotal moment for us. I wanted to finish by showing two videos.

The first video is Chloe before instigating Elevans as part of her protocol. And this is the video that her owners showed me when they were agonising over euthanizing her and how like highlights how frantic she could be when stimulated. And the second video shows her a few months after adding elevanse to her regime.

I don't think there's any doubt that she appears to be a different happy dog. And I've asked Professor Rusbridge if she has any comment on the use of CBD in these cases, and she agrees that most people using CBD are probably not utilising the correct doses. So a positive response is unusual.

However, although phantom scratching isn't neuro neuropathic pain, the widespread distribution of cannabinoid receptors makes this this scenario perfectly feasible. We So I don't think there's any doubt there that she appears to be a different dog, currently. So in summary, yes, I do feel that Elevans offers us an additional tool in our armoury to offer to our patients and clients within the guidelines of the prescribing cascade.

There are exciting times ahead as more research, data and evidence emerges on the use of cannabinoids and their associated molecules. Thanks again for listening. Right, folks, that brings us to the end of the first part, the recording.

We're now back on live and I'm going to hand back over for the last section and then we will get into the questions. So over to you. Good evening everybody.

Actually, it's the afternoon here in the United States, and I am live in Pennsylvania, in fact, you might hear some construction equipment beeping. They picked the perfect time to do construction during the webinar. But I wanted to take, whenever, whenever a new product comes out.

Like elevator elevants, there's always gonna be caution and there should be. For me, this is not a new product. So I've been using Eevat, obviously Eevvans in the UK for over 3 years, and I wanted to just fill you in on why and what I'm seeing.

Because we have over 300 dogs on it, we might have more, more dogs on this product than anyone, and I wanted to just give you from a practitioner to practitioner, what my observations have been. And they are not, you know, Millie and Chloe don't surprise me. I have a lot of Millie and Chloe's like Dave has.

Which is really fun. It's fun to have something new to do. So anyway, I just want to tell you real quickly why I even got involved in this.

I am not a holistic veterinarian. I don't usually use products that, I mean, I use the, the drugs that we were taught in veterinary school, and I've been in practise 34 years. I'm a board certified vet.

So I had someone talked to me about this literally a little over 3 years ago, and I was not interested until I met Joe Watchlog and Joe, Who spoke earlier, Joe is the world expert on cannabinoids in pets. He's the chief medical officer of EAAT, but that's not why I listened to him. I listened to him because he's a professor of veterinary medicine at Cornell, and I actually visited him at Cornell before he ever became the chief medical officer of EAE, cause I wanted to know the real deal, how this stuff worked, why we thought it worked.

So I actually Fred, we seem to be dropping your sound, I'm afraid, . Could I, could I ask you if you would dial in for us just so we are losing your message. So Joe, one of the things that I wanted to ask you was, while we're trying to get Fred back on the line again, so bear with us folks, while we try.

It was very interesting for me to see that there were so many products that were analysed and they, they didn't meet up to the standards. Hello, Bruce, yes. That, that project was was run, late last year with, the number of, of products that, as you well said did not meet the to begin with they don't, they didn't meet what the the what they said on the label and, and there is a number of reasons for that.

One is that it's the the nutraceutical space is not necessarily as regulated as the pharmaceutical space to begin with. And secondly, most of the manufacturers of this type of products with containing CBD will source their their active ingredient, the either the CBD isolate or the hemp extract from, from a wholesaler and, and then they will just go on and include that in the formulations is another ingredient. Now the problem is if, if you don't really know what's in that active ingredient you you are using, you know, you may be doing it trusting that what you were sold is what you were you were told it was but it in many cases it's not, it's not exactly like that, so.

There there is a wide variety of of products out there that have something or say something on the label and don't necessarily reflect that on on the actual product and then that's why and it's exactly the same for CBD products in humans or for human beings. So it's, that's why the companies that do control the whole process and do the assessments during the manufacturing process can really guarantee what's on, what's on the product at the end. Yeah, German, I, I, I think this goes back to that age-old saying of it's not what's in the product that counts, but what gets into the animal at the end of the day, that's important.

That is correct, yes. Yeah, so when you start getting a quality product like Evans and it it's shown in the research that you know, what what you're promising is kind of in the product. I think that's something that's really important for people to consider.

And exactly and with like with any other compound, any other pharmaceutical, you know, the same molecule in a different carrier in a different set of excipients will have a different absorption and therefore a different half life and therefore a different effect set aside a safety profile. So as I, as I was saying at the beginning, you know, not every probe is the same and how it is formulating how where it comes from and. And you know what the portions are are of each of the ingredients.

Has a lot to do with what the the end result is. I did use and I'm sure for colleagues listening that they were familiar with this when, when there is a generic product of a drug, one of the, of a pioneer drug, one of the key. Of fundamental things that the regulators will look at to approve that generic is to ensure that the whole manufacturing process is exactly the same, the same formulation, the same manufacturing process so that we can achieve or you feel that the pharmacological effect of that product will be the same as that of the pioneer product.

That is not so easy if not even impossible to do with a botanical product. So every single product should have, you know, some research done on on it to support whatever sort of claims they're they're making. Yeah, yeah.

I think that that that's really important and I, I mean, certainly the work that that Elivans is is putting in behind the scenes on this is certainly showing up the quality of, of the products. And I think especially when we discuss it with the colleagues is the fact that Because we have the research, we can't answer the questions and, and that's, you know, it's, it's kind of, kind of key as a vet myself, you know, when you're taking on something new as Fred said, you want to know that there's something backing it up and it's just, it's not just, you know, fancy marketing material, or a nice price. So I think that's, that's definitely so important to have, to have the right data behind the product.

Yeah, absolutely, absolutely. Another set of questions that we've been coming through, and I don't think we can go into each specific drug. I think that'll just take too long.

But is this idea of interactions with other drugs and You know, how you regulate that and what you do if you feel that you've introduced a patient, or the product into a patient and we've got somebody who is possibly a little bit drowsy for a few days. I mean, how, how long do we give it before we start saying, hang on, we need to be concerned? Dave, would you like to comment on that?

Yeah, I think, so far, in my clinical experience, we might see some sedation, initially. I think these patients tend to emerge from that, with continued use, usually after about sort of 7 days, maybe as far as long as 3 weeks. I've not got any real hesitation with using it concurrently with other meds.

There is a a question come through about using it with antidepressants and axiolytics, and although there isn't a huge amount of work out there, comparing different drugs, you would expect a degree of sedation and drowsiness, perhaps some loss of motor function, perhaps even a mild tachycardia with, with certain, SSRIs and things like that, and TCAs. At the moment that that wouldn't stop me using them. Perhaps I might be a bit judicious with my dose initially and just assess clinical response ongoing.

Yeah, that that's really interesting. And you you were talking about seeing an effect, possibly a mild effect with some of the benzodiazepines. I mean, if you were, had an animal that was on Elevans and you were going to do some anaesthesia, would you automatically adjust your pre-med doses or, or not specifically?

Personally, I would avoid using a benzodiazepine as part of my anaesthetic protocol unless there was a real. Indication to do so, and if that was the case, then I would avoid perhaps using it in advance on the day of anaesthesia, but then continue it from the next day. Oh, OK.

So that, that's interesting that you could get that that quick and effect. That's fantastic to know. Certainly that would, that would be my experience today.

Yeah. Excellent. I don't think that we've managed to get Fred back on again.

I, I know we were battling because he was in the US, . I don't see him on there. Have either of you heard from him?

If he's, if he can get into us again. I'm afraid no. Hello.

Hello, guys. I'm here if anybody. Alfredo, are you back with us?

I'm here if you can hear me, Bruce. Fantastic. Yes, please go ahead, Fred.

I'm sorry. I apologise for that, but at least you can tell I really am live. So here's what I wanted to say because whenever you have a new product like this, there's a lot of confusion.

The real and there should be. I'm 3 years into this, so for me this is not a new product anymore. So that's where I thought maybe I could take a few minutes and help people out.

And we were part of the original studies, we were part of the safety data, we're part of some of the other studies. And what's interesting, and I, we lecture at a lot of the conferences in the US and sometimes in the, the UK and it's the people that are lecturing on using hemp, it's very interesting. They talk about the dogs they're using on and you ask them how many dogs they've used it on and it's 3.

I mean, it's not large numbers. So, we, we use, elevants, obviously, elevants in the UK routinely. So I wanted to just, if you can, I don't know which slot on it doesn't really matter at this point, but I wanted to say the, the, what you do when you get a new product is you use it on the worst cases where if something goes wrong, you have nothing to lose.

And I was not a fan. I'm not a homoeopathic vet. I'm not very, I'm not trained in it.

And I was very sceptical when I first learned about Eeved and they asked me to try it. We were one of the few early people to use it. And the only reason I agreed to is after meeting Dr.

Joe Washlag, Joe, who was on earlier, the professor at Cornell, Joe really is the world expert on CBD and pets, and has nothing, and he became the chief medical officer at Elaett, which I think is so good for Ellevet. But Joe was a professor at Cornell that did all the initial studies and he still does a lot of studies, and I got to know Joe really well. You won't find a more ethical person.

And a more knowledgeable person. Not only is he a double board certified veterinarian, he's a veterinary pharmacologist, and he's just a good guy. So he is the world expert.

So when I, after I met him, I became much more interested, and he told me that he really thought this would replace 50% of the non-steroidal anti-inflammatory use in dogs specifically, and I believe him. We're not there yet because this is a new product for most veterinarians, but I think this is going to replace the majority of NSAIDs because of its efficacy and safety. So the first dog I ever used to Ellevat on or elevant for you was Jen Lawson.

She's, we have 75 people that work at Metsre Animal Hospital. She was my first veterinary nurse and she's still there, which was 25 years ago. I cannot afford to do something wrong to her dog.

That that would be very bad for everyone. She had a farm dog, Sammy. She, they have a dairy farmer family as a dairy.

Sammy was a like a shelty mix that ran around the dairy farm. She was 15 years old, she was severely arthritic, hip dysplasia, shoulder problems, multiple problems. She was on every medication you can think of, including gabapentin, trazodone, you know, carprofen.

And others, and others, everything you can think of. So I asked Elive to give me a sample and I asked her if she wanted to use it. I said, I don't know if this is gonna kill your dog, help your dog.

I have no idea, but you're ready to euthanize her anyway. And just like David said with Milly, really, she really reminded me of Milly, Sammy went on to live another 2.5 years.

And I know that's an end of one that's only one dog, but that clearly made me go, there's something to this. I also visited Doctor Watlag at Cornell vet school. After this happened, and I spoke to the veterinarians nurse, I can't remember her name.

Her first name is Ursula. She's a board certified vet. I believe she's had a surgery at Cornhill, so pretty reputable person, and she had a very similar story on her own dog.

So that really got me going and thinking, wow, this, there might be something to this. I mean, we need to study it more, but that was 3 years ago and stories like Millie are everyday to me. Do I think Elavet or Elevance is going to save every dog's life?

Of course not. But what I like about it is it's another alternative, and for me it's becoming the first line for pain in dogs. And I'll give you at the very end here in 5 minutes, I'll tell you other things I've used it for, which I think could even be more interesting.

So we know it works for pain. In my experience, it works best on multi, joint problems. The dog has multiple joint problems.

We do about 150 TPLO procedures at our hospital a year. We, we do a lot of orthopaedics. We have a rehabilitation centre, underwater treadmill physical therapist, and really all of that has become a large part of what we're doing for most of the dogs.

What I noticed it was very interesting. I'm a lab person. I lecture on lab medicine, so the changes, if we're going to bring a new drug or a new medication to market for me, it's got to be safety.

It's got to be number one. So we were involved in the initial safety studies and what I liked about Ela that is they actually did studies. The first thing they did was safety and pharmacokinetics.

You should know what the dose of it is and if it's safe. So the first thing that was reported, which I find interesting, which I really have not seen much since, is dogs that were placed on elaba. Evans to you had some mild increases in the liver enzyme ALT.

Well, we did see that in a few dogs, but it was so small and we didn't have baseline on those dogs. I really considered that a fairly insignificant finding. So when I talk to people about using CBD products, a lot of them will ask me, aren't you worried about the liver?

And I am all about running lab work. That is what I do. So I think it's a good idea to run a profile before you start a dog in any of these medications.

And then monitor them. But I will tell you, I, I, I think you should do routine blood work, but I'm going to tell you my I've seen in 3 years. I think there are very minimal changes.

You might see an ALT or perhaps an alkaline phosphatase. Alkaline phosphatase is the one that we normally see go up a little bit with CBD, but I would ask you, since the dog has the corticosteroid isoenzyme, almost everything makes that that enzyme go up, and I'm not saying to ignore it, but I'm saying for me and the majority of dogs, I, it doesn't stop me from using Elavan. What stops me from using non-steroidals is a different deal.

I mean, if we can get these dogs off non-steroidals and on the elevate or even perhaps a lower dose, then I think that's a much more important finding, and that's what I have seen. So I monitor CBC chemistry urinalysis, and I'm gonna be absolutely honest with you. I have a lot of people that are like, I'm just gonna keep going with thee of that.

I don't want to do any more drug monitoring. I already know it's OK. So here's what I'm saying.

I do think you should do routine drug monitoring. I've had this product for 3 years now. I'm very comfortable with it.

I'm not very worried about it causing a problem, but you know what, I always think it's judicious to do a blood profile at least every year. And if an animal's on a long-term medication, which a lot of these dogs, once they start elevances, they're going to be on it forever, absolutely do routine monitoring maybe every. Maybe 2 weeks after you start, obviously I would do it before you start and then maybe 2 weeks afterwards and then 2 months and then.

Keep increasing the interval. So, the thing that has worried me, when you talk about CBD there's much confusion, and you look at all the products. If you saw the slide Do watchlog showed about 30 different products, it was funny, 18 out of 29 of them were properly labelled.

There's so much confusion and so much, that's why I said unethical people doing things with this product. The when people say CBD they're completely different. There's, you know, 150 different compounds.

You have to know what you're getting. And I think the recent studies are going to show that the CBDA, which is 50% of what EevET is, Eevvan is. It's going to be the real deal.

That might become the more important cannabidiol that really does the work, which is what I'm starting to believe. So my point is, don't let clients buy this in the United States right now. I can go to the grocery store, the gas station, and I can buy a CBD product.

There's no testing. It's very worrisome to me. And when a client asks me about this, I tell him that, you know, I would not go on anything other than Eevat or Eevant for you.

It's the only product that's been tested. And what I like is it's tested at Cornell and University of Florida and some other pretty reputable places. So, and they know the dose.

The one thing I wanted to end with my own dogs are on it, there's a slide that has two pictures of a lab and my white dog Sophie. I've had them on it forever. Sophie's been on it for over 3 years.

She has hip dysplasia. That really good results that don't need to use carprofen anymore on her, which makes me very happy. So I think what I'm trying to say is be very careful with what products you use.

I usually with the L to chew is what I prefer in the dog. I think you get better bioavailability. That's been proven.

The one thing I'm gonna leave you with is some of the other things, those are my dogs. The other thing I wanted to leave you with some of the things that I'm playing around with right now that I think could have huge impact in veterinary medicine. We know osteoarthritis is certainly a use, especially chronic pain, but Joe is doing some things with TPLO and acute pain.

I think the anxiety angle is huge. When you look at how many diseases are related to anxiety, and for me, are you getting ready? This is going to be exciting to you.

I'll tell you the good and the bad. The number one thing I would love to use this for and have some studies would be feline interstitial cystitis. I don't know what you're calling it in the UK, you know, Pandora syndrome, feline lower urinary tract, the blocked cat.

Because we know that has a real anxiety component, but, you know, trying to do something for anxiety in the cat is a nightmare in itself, and it would be nice to have some anti-inflammatory. So, I've used Eevat, the liquid in cats. I've had some that's worked great on, I've had some, not much.

The hardest part is getting the cats to take it because obviously, with CBD they can smell it. The transdermal really has me interested. Especially when Doctor Walker like said the CBDA.

Which is 50% elevate, might work well transdermal or perhaps a food with CBD with with Elavan at some point. Just think about how many cats that you and I see with lower urinary tract, and I'm just tired of not having a great medication. So I'm not saying to use it for those cats, but I'm saying, I think it would be very interesting and I would love to see some good studies.

Clearly, with seizures, we know we're we're using some dogs with seizures. And once again, anxiety, thunderstorm phobia. And I'm really interested in the oncology angle, the atopic dermatitis and IBD.

Now, you know, it worries me if some product works on all these, could it be that good? I think we're at the very early stages. And that's what makes it exciting and, and scary at the same point.

So I just wanted to put my two cents in and say, That I think this is something big. I think this is going to change veterinary medicine, and you know, I want more, more studies too, and we're involved in some of those. So thank you for your time and I'm sorry about the audio problems earlier.

I hope everybody has a great evening. Fred, thank you so much for coming back on and persevering. It's always one of the challenges and joys of, doing these live broadcasts.

So, but it's really good to hear from somebody that is at the coalface as it were, who has experience with using these products and have that put on top of the fantastic presentations that German and Joe and them have done for us in both the Webinar and the previous one as well. So thank you for your time and folks, once again, apologies for the technical difficulties, but I, I think you will agree with me that it was really worth the wait and the perseverance to get Fred back on to, to hear what he, he has to say. Jer, would you like to come back in and just talk us through that last slide because we have run out of time, but I think this, this offer is an important one.

Yeah, thank you. Thank you, thank you to everybody for for this. Well, 1 hour and 10 minutes we got this, running already.

So, yeah, I know the, the. The promotion here, the offer is for all veterinarians, wanting to, to give it a go, they can register through, through our website. Or contacting us to the email address there and then any orders utilise the the discount code webinar 20 would get a 20%.

Of, of the wholesale prices for veterinarians because we have done the studies and we know it works, we offer a guarantee and efficacy guarantee for osteoarthritis, osteoarthritis pain management. So basically if you tried it when a patient and you don't get the results you expected within the. The first couple of weeks, we will reimburse you the products, just give you the product back so you can, can have it for another, another patient.

And I don't know, Bruce, we do, do we have a couple of minutes to address any of the other questions we have? I think we've run a little bit too far over now. I'm really sorry about this and those technical difficulties just ate into things for us.

So, but if you want to grab one more, go ahead. No, that's fine. I think I'll just take this few minutes, if you, if you see the email address there on the screen, please, by all means, even if it's, the commercial address, send us your questions, we'll make sure to reply to you via email.

Likewise, visit the website, there is information there and there is our, our telephone number there. If you have any questions, please do reach out. Fantastic.

And I think folks, the, the guarantee of, you know, 20% off is a great, of the offers of 20% off is a great start, but a guarantee on a product is, is really just putting their money where their mouth is. So, those of you that want to try it, please go ahead. The email address is up there.

Remember, these sessions are recorded, so if you want to go back and watch any of this again, it will be up on the webinar vet website within the next 24 or 48 hours. And it's just up to me to thank every. For attending.

Thank, Fred for his perseverance to come on German for you and your colleagues for the fantastic recorded presentation and for helping us with the slides at the end in these technical difficulties. Thank you very much. And folks from my side, good night.