Prevalence and characteristics of cannabis-induced toxicoses in pets: Results from a survey of veterinarians in North America

Cannabis legalization in North America has coincided with an increase in reports of cannabis-induced toxicosis in pets, but the magnitude of this problem, as well as outcomes of these incidents remain unknown. Therefore, we examined the frequency, diagnostic criteria, clinical signs, and prognoses of cannabis toxicoses in pets in North America. We conducted an online survey between January, 2021 and April, 2021 targeting veterinarians practicing in Canada and the United States (US). Out of the 251 study participants, 191 practiced in Canada. Cannabis toxicosis was most commonly reported in dogs (n = 226 veterinarians), and the number of toxicosis cases increased significantly in Canada (p<0.0001) and the US (p = 0.002) after October, 2018. Frequently reported clinical signs of cannabis toxicosis included: urinary incontinence (n = 195), disorientation (n = 182), ataxia (n = 178), lethargy (n = 150), hyperesthesia (n = 134), and bradycardia (n = 112). Edibles were most commonly suspected to be the cause of toxicosis (n = 116). The most common route of exposure was ingestion (n = 135), while the most cited reason was ingestion while unattended (n = 135). Cannabis toxicosis was mostly diagnosed using supportive clinical signs (n = 229), the most common treatment was outpatient monitoring (n = 182), and pets were most often treated as out-patients (n = 103). The legalization of cannabis use in Canada and the US is likely an important factor associated with the increased cannabis toxicosis cases in pets; however, the legal status may also increase reporting. The medicinal use of cannabis by pet-owners for pets may also contribute to a portion of the reported toxicoses. Most pets that experienced cannabis toxicosis recovered completely, suggesting that most cannabis toxicoses do not result in long-term ill effects. Even though some deaths (n = 16) were reported in association with cannabis toxicosis, the presence of confounders such as toxins, and underlying conditions cannot be ruled out, emphasizing the need for rigorous controlled laboratory studies to investigate this important issue.

177 Commonly observed clinical signs 178 The clinical signs that veterinarians reported to have observed most commonly (in decreasing 179 order) were: urinary incontinence, disorientation, ataxia, lethargy, hyperesthesia, bradycardia, 180 stupor/obtundation, and twitching (Table 1). A small number of veterinarians reported 181 witnessing other signs including head bobbing and hyperthermia. The Chi square Goodness of 182 Fit test and the post-hoc binomial pairwise test revealed that urinary incontinence, 183 disorientation, ataxia, lethargy, hyperesthesia, and bradycardia were the clinical signs that 184 occurred most frequently (Table 1). Interestingly, except for bradycardia, all these clinical signs 185 were reported to be usually severe.  Figure 4A, the products that often led to cannabis toxicosis in pets were edibles 192 and dried cannabis. Other products reported by veterinarians to cause cannabis toxicosis were 212 included: outpatient monitoring and supportive care, administration of intravenous fluids, in-213 hospital monitoring only, administration of activated charcoal, induction of emesis, 214 administration of anti-emetics, thermal support (warming/cooling), and blood pressure 215 monitoring ( Figure 5B). Animals were usually treated either as outpatients or they were 216 hospitalized for less than 24 hours ( Figure 5C). Most participants reported that all clinical signs 217 resolved following cannabis exposure, except for a few pets that reportedly died in association 218 with cannabis toxicosis (n=16 animals). The cost of treatment for majority of the cases was 219 less than CAD$ 500 ( Figure 5D).  245 Diagnosis was frequently based on the presence of supportive clinical signs, and the most 246 common treatment was outpatient monitoring, which lasted for less than 48 hours. Except for 247 a few patients that were reported to have died in association with cannabis exposure, all patients 248 recovered completely after treatment, with a total treatment cost less than CAD $500.
249 Similar to other studies (7), the pets that were treated most often by the veterinarians in our 250 sample were cats and dogs. This is consistent with a recent survey which revealed that there 251 were 7.7 million dogs and 8.1 million cats in Canadian households (8). In our study, cannabis 252 toxicoses were frequently observed in dogs compared to cats, similar to that previously 253 reported (7). Consistent with previous work, participants also reported cannabis toxicoses in 254 other companion animal species such as horses and iguanas (7, 9), and also in previously 255 unreported species such as pet cockatoos and ferrets.
256 Similar to a number of previous studies (5, 10), we observed an overall increase in the number 257 of cannabis toxicosis cases after October 2018, even though our analysis at the participant-258 level revealed that majority of the participants reported equal case numbers pre-and post-259 legalization. This could be because participants did not report the actual case numbers but 260 rather selected among predetermined numeric ranges. As such, small increases that were within 261 the same range, would have been reported as "no change." The increase in case numbers could 262 be due to any combination of the following factors: 1. legalization of cannabis for medical and 263 recreational use in Canada; 2. increased reporting by pet owners due to legalization; and 3.
264 increased awareness of veterinarians about cannabis toxicoses (5, 10). Moreover, it is important 265 to consider the pharmacology of cannabinoids in cannabis, and how they may have contributed 266 to the findings noted above.

331 Products that caused cannabis toxicosis and the routes and reasons for exposure
332 In our study, edibles were the most common cannabis product that resulted in toxicosis, which 333 is not surprising since they are the most common form of cannabis products purchased for dogs 334 (3); however it is difficult to ascertain from our findings whether these edible products were 335 purchased for human or animal consumption. Pets are often exposed to homemade or 336 commercial edible goods, which are typically made using THC butter (5). In our study, and 337 previous studies (9, 18), plant materials, including dried and fresh green cannabis, was another 338 common product that led to cannabis toxicosis. The least common cannabis toxicosis-causing 339 products were topical cannabis products, capsulated cannabis products, and tablets containing 340 cannabinoids. 354 The most commonly stated reason for pet exposure to cannabis was via oral ingestion while 355 unattended, which was also reported in a previous study (42), followed by intentional 356 administration for recreation (given to pets for fun?), or as a medical treatment. Our findings 357 suggest that pet owners would have to put measures in place to prevent pets from accessing 358 cannabis products including restricting cannabis to hard-to-access areas of the house, putting 359 their cannabis products in pet-proof containers, and monitoring pets when cannabis-based 360 products may be accessible. Some pet owners stated that cannabis toxicosis occurred following 361 medical treatment which may be a result of unintended over-administration of these drugs due 362 to the delay in manifestation of their effects. A small number of participants reported that some 363 pets, specifically dogs, were exposed while being walked. 377 The incidence of false-negative results using the human urine drug test kit is also a concern.
378 False negatives may occur if the urine sample is tested too soon after exposure (5), if the urine 379 sample is not handled appropriately leading to the THC binding to the rubber stoppers and 380 glass containers (5), if the patient consumed synthetic cannabinoids (46), or if the patient has 381 diluted urine (47). In dogs, false negatives can also occur since THC is metabolized into 8-OH-382  9 -THC, which may not be detected by the human urine drug test kits (48) since they were not 383 designed to detect this compound.