Veterinary Vertex

Marijuana Toxicity in Dogs: Risks, Diagnosis, and Emerging Biomarkers

June 11, 2024 AVMA Journals
Marijuana Toxicity in Dogs: Risks, Diagnosis, and Emerging Biomarkers
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Veterinary Vertex
Marijuana Toxicity in Dogs: Risks, Diagnosis, and Emerging Biomarkers
Jun 11, 2024
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Join us on this episode of Veterinary Vertex as we welcome Erin Binagia to shed light on marijuana toxicity in dogs. Erin shares findings from her recent study, revealing unexpected electrolyte abnormalities such as hyperkalemia and hypercalcemia in these cases. Discover the diagnostic hurdles veterinarians face, including pet owners often denying exposure and the limitations of current urine drug screens. Don’t miss out on this eye-opening episode that offers vital insights for both veterinarians and pet owners.

JAVMA article: https://doi.org/10.2460/javma.24.02.0092

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Join us on this episode of Veterinary Vertex as we welcome Erin Binagia to shed light on marijuana toxicity in dogs. Erin shares findings from her recent study, revealing unexpected electrolyte abnormalities such as hyperkalemia and hypercalcemia in these cases. Discover the diagnostic hurdles veterinarians face, including pet owners often denying exposure and the limitations of current urine drug screens. Don’t miss out on this eye-opening episode that offers vital insights for both veterinarians and pet owners.

JAVMA article: https://doi.org/10.2460/javma.24.02.0092

INTERESTED IN SUBMITTING YOUR MANUSCRIPT TO JAVMA ® OR AJVR ® ?

JAVMA ® : https://avma.org/JAVMAAuthors

AJVR ® : https://avma.org/AJVRAuthors

FOLLOW US:

JAVMA ® :

Facebook: Journal of the American Veterinary Medical Association - JAVMA | Facebook

Instagram: JAVMA (@avma_javma) • Instagram photos and videos

Twitter: JAVMA (@AVMAJAVMA) / Twitter

AJVR ® :

Facebook: American Journal of Veterinary Research - AJVR | Facebook

Instagram: AJVR (@ajvroa) • Instagram photos and videos

Twitter: AJVR (@AJVROA) / Twitter

JAVMA ® and AJVR ® LinkedIn: https://linkedin.com/company/avma-journals

Speaker 1:

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Speaker 2:

Dogs should be tested for existing heartworm infection prior to starting a preventive. To learn more, visit nextguardpluscliniccom. You're listening to Veterinary Vertex, a podcast of the AVMA Journals. In this episode we chat about clinical examination findings and electrolyte abnormalities of dogs with marijuana tetrahydrocannabinol toxicity with our guest Erin Banaja.

Speaker 3:

Welcome to Veterinary Vertex. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today we have Erin joining us for a very exciting topic. I know I'm going to learn a lot, so, erin, thank you so much for being here with us today.

Speaker 4:

Yeah, thank you so much for having me. I'm really excited.

Speaker 2:

Let's discover the clinical exam and blood work findings of dogs with marijuana toxicity. So, erin, we were talking a little bit earlier just kind of sharing our own clinical stories of patients that unfortunately have had this toxicity. That I've presented to us, and your article discusses the clinical examination findings and electrolyte abnormalities of dogs with marijuana toxicity. Please share with our listeners the background on the study.

Speaker 4:

Okay, yeah, so marijuana, as we all know, is a recreational drug that's now legalized in what I think it's almost about 24 states, so almost half the country legalized in what I think is almost about 24 states, so almost half the country. And our pets, mainly dogs, can actually ingest these products and develop acute neurologic signs. And these signs can look severe and really scary to owners, especially if the pet unknowingly got into a stash or found it randomly on the ground. And most ER doctors will suspect marijuana as soon as they come into the ER. But often owners will deny that possibility of exposure, and especially, probably in states in which it's not legalized yet. But whether it's a truth or a lie doesn't really matter, because in my experience I think if a dog can smell it they'll find it.

Speaker 4:

And we do have a point of care human urine drug test available, but dogs don't seem to produce a large amount of the metabolite that the test tests for. So negative test doesn't really rule out marijuana. And the problem is that these dogs can look like they have severe neurologic disease. So without possibility of proof of marijuana, as an ER doctor we have to also consider it could be a severe neurologic disease. So we often recommend further testing. So my question is what else can help us get to the diagnosis of marijuana without having to send out a drug test that's going to come back many days later, or perform advanced blood tests or imaging of the brain to prove it's not serious? So this study was just the beginning and hopefully the foundation to get us to an answer.

Speaker 2:

Yeah, I think this will be a really important article for our clinicians, and also for our pet owners too, to know what to look out for because, like you said, advanced imaging such as MRI, that's very expensive, especially if you're just because you're having challenges with client communication or something to get the diagnosis of marijuana toxicity Absolutely. What were some of the pivotal findings from this study?

Speaker 4:

Yeah. So ultimately I had found 223 dogs that had a definitive diagnosis for marijuana, so 194 positive urine drug screens and 37 known ingestions. And the earliest positive drug test occurred three and a half hours after known ingestion of marijuana and the sensitivity I got for the urine drug screen was about 72% if it was interpreted based on the package insert. Instructions and a very common history for these dogs was becoming acutely neurologic after going outside or to a public place. That was a very common story that people reported. So either they went outside on a walk or they were out like at a neighbor's house, or they had visitors or workers at the house that was a very common story or workers at the house that was a very common story. However, about 70% of the owners denied even a possibility of exposure. 10% of that subset said that it was in the house but locked up. Absolutely zero way the dog could have gotten it. The rest said zero possibility.

Speaker 4:

The vitals were usually normal, but if they're abnormal these dogs are actually stimulatory. So they are hyperthermic, tachycardic and hypertensive rather than what we think of, like Dullin of Tun did, and bradycardic and hypothermic. Clinical signs usually develop within one to four hours of ingestion and the top signs were ataxia was absolutely most common. About almost 90% of cases had ataxia. About 75% of cases were hyperesthetic, so they had a dramatic menace whenever you had a menacing movement towards their eyes.

Speaker 4:

About half had urinary incontinence and about 30% had vomiting, and the most common combination of neurologic signs was a combination of ataxia and hyperesthesia. So about 70% of cases, and then almost 40%, had a combination of ataxia, hyperesthesia and urinary incontinence. Sometimes these signs were misidentified as seizures by the owner and even sometimes by a referring veterinarian. They were misidentified as seizures and then a really important finding, I think, is that most of it was normal, except for potassium and ionized calcium. In fact, about 50% of cases had a mild hyperkalemia and 80% of cases had a mild hyperkalemia and 80% of cases had a mild hypercalcemia, and survival was 100% in my cases.

Speaker 3:

That's great that survival was so high. Absolutely, really really tough conversations to have with owners. You've obviously seen a lot of these cases. Do you have any advice for people who don't see this very often? How do you approach this with the owners? You don't really believe that they started having signs when they were on the walk. You don't really believe that there's no way they got to it. They got to it, right, right.

Speaker 4:

So I I do, I discuss with owners. Like you know, best case scenario is this is marijuana, toxicity, and even if they think that there's absolutely no way, you know, I think dogs find it, whether it's on their walk or in the house. They've got good noses, they smell it and best case scenario it is marijuana and toxicity, and it's very possible wherever we are.

Speaker 3:

That's a great way to put it. Put spin a positive. Hey, that would be great. If that's what it is. No blame game, right, right, subjectively, do you think there's any breed predisposition Like, ooh, the labs eat everything, but my poodle didn't eat its lunch? Yeah, so my highest.

Speaker 4:

I think my highest population was mixed breed but then, like, labs and goldens were up there in terms of like the number Pit bulls actually, yeah, let's see Pit bulls, german shepherds and huskies and labs and doodles those are my top, top breeds, yeah, so I and um I did look into um. You know how many were repeat offenders for, like, getting into other other things and the re-presenting for like either getting into foreign bodies or getting into other medications, and there was. It wasn't like a high number, but like maybe 20 of the cases had been repeat offenders. So I definitely think that there's a subset of dogs that are probably more likely to get into it because they're likely to get into anything I also, erin, think it's interesting what you said about how they don't.

Speaker 3:

Dogs don't excrete as much as whatever is tested in the in the urine test that you can buy at least over the counter. Is there anything in the works to look for a different metabolite, like a dog-specific metabolite?

Speaker 4:

Yeah, so the dogs do make the metabolite that is measured. They just make, according to the most recent paper, a lot lower concentration of it and it's the THC-COOH is what it's measured. There are other tests that have lower cutoff levels, so those do exist and you know you could use them there's. I know that there is a lab that is kind of working on is there a dog-specific metabolite to use? They don't have anything published yet but they are working on it. So I do think there are people going to that route and looking for that. We just haven't come up with a consensus, yet Fantastic, thank you.

Speaker 3:

What sparked your research interest in marijuana toxicity in dogs and maybe even in cats or anything in the ER? Was it a case a recurring theme?

Speaker 4:

Yeah, a recurring theme, I would say. My interest definitely started as a small animal rotating intern. I worked in a five hospital system. That was really. It was an ER based small animal rotating internship. So my mentors are all criticalists and emergency veterinarians.

Speaker 4:

I probably saw a marijuana toxicity case every night and you know I could start identifying them across the hospital. You know a dog comes in sitting on a table and I'm like across in my office I'm like, oh, yeah, that's marijuana. And I always heard similar stories from the owner like, oh, we went outside for a walk and the dog became clinical when I got home. But they always denied possibility of exposure to marijuana. And then I was always told by my mentors that the urine drug screen is not reliable in dogs. But when I looked into the literature I couldn't find, you know, an actual specificity or subjectivity of the test in dogs. So I never really knew how to explain that to owners. I was also told that marijuana doesn't cause vomiting. So you know, but I had no scientific evidence for that that corroborated what I was being told. And so I was often, you know, recommending additional blood work and abdominal rads to these owners.

Speaker 4:

And the final spark for my study. What really made me want to do this was I was noticing a trend of a mild hyperkalemia in a lot of my cases and I couldn't find anything in the literature to explain that and I was starting to kind of use it as my own personal biomarker. If I saw it to me internally, it strengthened the likelihood it was marijuana, but I, you know, I had no scientific evidence to back me up. So I mainly wanted to do this study to A see if we could find some commonalities, some common signs or combination of signs that can help us, you know, become more confident in our diagnosis, and then, B see if this mild hyperkalemia was a true prevalent finding in marijuana toxicity, do a prospective study based on these results and maybe come up with a diagnostic criteria system to help strengthen the diagnosis of marijuana toxicity, especially when we get negative urine drug screen results.

Speaker 3:

Fantastic, a really great story. Thank you. I always feel a little guilty asking this question, but it's a little self-serving. Why did you choose to share this really important manuscript with JAVMA? It's a little self-serving.

Speaker 4:

Why did you choose to share this really important manuscript with Javma? Yeah, so two specific reasons. The first reason was just the ease and the speed of the submission process For the time I click submit to being available online. To now. Today I'm talking about on a podcast, which I really was not expecting but I'm so grateful for because it's going to reach a larger audience and ultimately it's just a very efficient process. And then the second reason is I did want these results to reach a larger, more generalized population of veterinarians rather than a specialty journal that only criticalists are going to read, because I think this is important information for any veterinarian that's going to see dogs in their hospital. I think marijuana toxicity is a common presentation and will likely only become more prevalent as marijuana is legalized and more readily available across the nation.

Speaker 3:

Well, the great news is I like again what you said it would be great if it's marijuana toxicity and your animals live, so that's even better news. Yes, exactly. Sarah asked you a little bit earlier what were some of the pivotal findings. What were some of the most surprising findings from your study? Like you mentioned, you were told dogs didn't vomit, but yet you found, would you say, 30%.

Speaker 4:

Yeah, 30% of dogs were present with vomiting. Yeah, so that one just helped corroborate what I was seeing. So it confirmed to me that, yes, it could definitely cause vomiting. Also, I really think the most surprising finding that I was not expecting was that about 80% of the cases had an ionized hypercalcemia, which was that was not on my radar at all. I never noticed it and I really just didn't foresee that result.

Speaker 4:

And after some background research I found that it's actually something that does occur in humans and it seems to be related to the activation of the cannabinoid CB1 receptor. And when I first looked it up it seemed to be transient. They found it in labs in humans and they didn't really do anything except for note it. But I just read today that in heavy, chronic use it may be associated with poor bone health and that the CB1 receptors may play an important role in regulating bone density, bone turnover and bone cell activity. So to me the really interesting thing is that this ionized hypercalcemia may potentially be an even better biomarker than that mild hyperkalemia I was noticing for marijuana toxicity in dogs.

Speaker 3:

Oh, fascinating. So you talked about kalemia and calcemia. What are your other next steps? You sound so passionate about this. What are your other next steps for research for marijuana toxicity in dogs?

Speaker 4:

So I have a lot of ideas and I'm hoping to pursue all of them at some point in my lifetime. I'd like to try and get a true sensitivity and specificity of the available drug tests we have right now. I also want to come up with a diagnostic scoring system that I previously mentioned and then compare or like test that against a population of marijuana dogs versus like other neurotoxicity dogs and potentially other other brain you know disease dogs that may come in and see if we can come up with a combination of signs that say it's more likely marijuana than those other diseases. I also have a theory about fecal testing for marijuana in dogs, because dogs do excrete much more of the metabolites in their feces. So I may want to explore that at some point. And lastly, I want to look into what's the best way to approach and communicate with owners to convince them to tell the truth rather than just flat out deny any possibility of marijuana exposure.

Speaker 3:

Yeah, all really really important topics and you know, the fessing up to what the truth is could really be the first step to getting your study done. For the other, the non marijuana neurotoxicity, because if nobody's telling the truth, how do you know? If I mean, you need the test, obviously, but it's gonna be tough to do yeah. Do you ever see a role for AI in this area of research?

Speaker 4:

So I'm not an AI expert or really read on the subject currently, but I do think there's probably a role for AI in every part of medicine. I absolutely could see it helpful in that goals I just discussed and trying to develop a diagnostics criteria set and identifying marijuana cases versus more severe neurologic disease. So I do think that could be helpful, especially while we don't have a sensitive point of care drug test right now. But of course the simplest thing would be to find a more sensitive urine drug screen test with a lower cutoff or try to increase the sensitivity of the test we already have. So meaning, take the test at least four hours after possible exposure, because usually they're not going to come up positive until that four-hour mark.

Speaker 3:

Erin any insight into cat or I'm an equine surgeon, so do horses eat marijuana?

Speaker 4:

I don't know about horses. I definitely have had a few cases of marijuana toxicity in cats, but I want to say maybe two to three cases and I did get positive urine drug screens in maybe one or two of them. So I've definitely seen it in cats and they present similarly, just it's. I think it's much more rare, because you know it's much more rare that cats get into medications and general that I think they're a little bit more finicky in what they put into their mouths compared to dogs. So yes, I've seen it in cats. I don't know about horses.

Speaker 2:

I wish my cats were more finicky. They will be like a piece of plastic on the floor next to a cat treat. And then choose the plastic every time.

Speaker 4:

And I'm always like why there are those few cats that they're going to do anything as well.

Speaker 2:

Yes, but I definitely echo a lot of what you said. My intermates and I, if we would see a dog that we suspected was a marijuana toxicity case, the first thing we do as part of our physical exam is do the menace and if they're hyperesthetic, you're like this is probably a marijuana toxicity case, absolutely yeah.

Speaker 4:

I think the dribbling urine is just the icing on the cake If the dribbling urine on top of all that you're like yeah, no way, it's nothing else.

Speaker 2:

It's great to see the evidence behind that, though, with your manuscript. So I'm really excited to share this with our readership and our listenership too, because it's really important information, and I look forward to your future manuscripts too, especially when writing client communication. Right, exactly, yeah, yeah, it's no fun to deal with the finger pointing game. No, it's not. And for those of you just joining us, we're discussing marijuana toxicity in dogs with our guest, erin Banaja. So, erin, how did your advanced?

Speaker 4:

training prepare you to write this manuscript. Yeah, so I've been coming up with ideas and working on projects research projects since I was a master's student in biology back in like 2011. I did a summer research program as a veterinary student and as an intern resident. I've presented a few abstracts at our major emergency care conference. I've also published two case reports, one in my residency and one since, and I'm also the co-editor of a small animal veterinary textbook that's to be published soon. So, yeah, all of that's helped me understand what data I need to be looking for, how to document it to be interpreted statistically, and prepped me for how to write up my results in a paper. So, ultimately, scientific writing has been a passion of mine and I hope to continue it.

Speaker 2:

Congratulations on the textbook. That's exciting, thank you. Can you share the title of it, if you're able to?

Speaker 4:

It's Pace Studies in Small Animal Point-of-Care Ultrasound. Thank you, Can you share the title of it If you're able to? It's a pace studies and small animal point of care ultrasound.

Speaker 2:

Ooh, very cool. You know, we actually have a really cool new manuscript category. She was going to say they're called technical tutorial videos. They are peer reviewed clinical teaching tool. So things like, yeah, pointing care, ultrasound like a fast T, fast yeah.

Speaker 4:

Yeah.

Speaker 2:

I will send you the instructions for authors if you're interested. We are waiving the open access fee for our first 50 submissions.

Speaker 4:

Okay, awesome yeah.

Speaker 2:

Yeah, yeah, of course. So, going back to your manuscript, what is one piece of information the veterinarian should know before discussing marijuana toxicity and dogs with the client?

Speaker 4:

So this is a tough question to pick just one piece of information. But I think maybe the most important thing to know before talking to a client is that a negative urine drug screen does not rule out the possibility that this dog has marijuana intoxication. Even if the owner is adamantly denying it, it's still possible. So don't rule out marijuana despite those things, and then communicate that with the owner as well, because and just don't believe the owners when they say it's not a possibility. Or maybe not don't believe them.

Speaker 3:

Maybe they truly believe that, but like it's always a possibility, Erin, if I were that client I'd be like, well, why'd you waste my money running that test then?

Speaker 4:

Yeah. So the reason to run it would be if you get a positive result. It's very likely positive. There are a few drug interactions, but it has to be like the dog has to be on another drug. So if they're coming up just positive on that THC strip, it's marijuana.

Speaker 2:

And then what's one thing clients should consider around marijuana toxicity.

Speaker 4:

Yeah. So I think the most important thing would be that it's okay to admit the possibility of marijuana exposure. Even if it's in the cabinet and locked up. Most of the time, dogs seem to sniff it out from anywhere. I think either the owner or even a random stranger, probably unknowingly dropped it somewhere, and whether it's in the house or in public, I think those dogs find it.

Speaker 4:

It's smelly, you know. They get into it and then about one to four hours later they're going to develop neurologic signs. So it helps us out as a veterinarian if the owner admits that the dog has even been in close contact or in an area with it, because it makes us more confident in our diagnosis and we will be much less likely to recommend any further testing. Otherwise, you know, as an ER doctor, I don't want to miss anything more serious, so I'm going to recommend other testing if there's absolutely no possibility of marijuana. And then a marijuana diagnosis has such a better prognosis compared to any other disease that it could be. So just if it's possible, let us know, because it's going to make us all feel better.

Speaker 2:

Thanks for sharing such valuable information, erin. So, for clinicians that are suspecting marijuana toxicity, what are some good talking points for the owners, since there is ultimately usually a successful outcome for these cases?

Speaker 4:

Right, yeah. So in terms of like treatments and prognosis, you know survival, at least in my study, was 100% taken to the fact that was only our definitive cases. You know we had to have a positive known drug screen. Only 22% of those sorry, only 22 out of the 223 cases were even hospitalized. Everyone else just went home. Mostly. Most went home with zero treatments. Some went home with some sub-Q fluids and like an anti-vomiting medication, but ultimately the prognosis is good. Their signs will resolve within 12 to 24 hours and they really don't need any critical care. So that's why you know we'd like them to A like. Tell us the truth. Was it a possibility? Because prognosis is great and they can. Usually their symptoms will resolve within 12 to 24 hours.

Speaker 3:

Thank you so much, erin. As we wind down, we like to ask a it's not really personal, but just a fun question when you begin a puzzle, do you start with the inside pieces or the exterior border pieces?

Speaker 4:

Okay, so I don't do puzzles often, but as a true ER veterinarian, when I start a puzzle I'll take what I get and work with it. Obviously I want to try to find the corner pieces, but otherwise I'll look at the whole thing and match what comes to me, because that's just how I am.

Speaker 3:

Yeah, we're pretty sure we're going to be able to just phenotype people based on how they do puzzles.

Speaker 2:

Yeah, that's a great answer as an ER clinician because really that's how it works you have to take what you're given from the client and the pet and figure out what it could be. You never know what you're going to get. No appointments, you know the great investigators or detectives Well, thank you so much, erin. It's been a pleasure to have you on the podcast.

Speaker 4:

We appreciate you submitting your manuscript to JAVMA.

Speaker 2:

Yeah, thank you so much, I'm so happy that I was able to do it and to our listeners. You can read Erin's article and print JAVMA or online using your favorite search engine. I'm Sarah Wright with Lisa Fortier. I want to thank each of you for joining us on this episode of the Top Rated Veterinary Vertex Podcast. We love sharing cutting-edge veterinary research with you and we want to hear from you. Be sure to leave us a rating and review on Apple podcasts or whatever platform you listen to.

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