PONE-D-21-38974Prevalence and Characteristics of Cannabis-induced Toxicoses in Pets: Results from a Survey of Veterinarians in North AmericaPLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is very interesting, but I am unclear about a few points. I could not see the questionnaire so the information may be there, but it would be useful in the text. I need more information to fully understand the data included int he study.

What is meant by cannabis here? Does it include CBD products and synthetic cannabinoid receptor agonists (SCRAs)? So, both illicit drugs and medical products for human and veterinary use? Mixed exposure cases were included or excluded (e.g. chocolate, xylitol)?

I do not really understand how the numbers were derived. What were respondents asked about the number of cases? Was it the annual cases they saw or the number of cases between a particular period? This is important as you have numbers before and after legalisation in Canada. Were they answering from memory or from their practice case database?

What were the signs seen in the animals other than cats or dogs? Can this be extracted? This could be useful, particularly in animals not previously reported with cannabis exposure. How were these non dog/cat cases diagnosed? Would you suspect cannabis in a drowsy ferret, for example? Or were drug urine tests or owner history available in these cases?

Line 255. Cannabis poisoning has been reported in a ferret

Smith RA. Coma in a ferret after ingestion of cannabis. Vet Hum Toxicol. 1988 Oct;30(5):486.

Figure 3. I do not understand these figures. Over what period are these changes in case numbers? Is the decrease in US cases in 3c an effect of the different timing of legalisation?

Line 412. Were all the fatal cases in dogs?

Line 353. I would say SRACs are ‘known to be potentially lethal in dogs’, as not all cases are fatal and there are hundreds of SCRAs.

Van-de-Velde M, Bates N, Edwards N. Suspected synthetic cannabinoid ingestion in dogs: a case series [abstract]. Clinical Toxicology. 2017;55(5):44-45. https://www.eapcct.org/publicfile.php?folder=congress&file=Abstracts_Basel.pdf

Sioris KM, Keyler D. 2014 K2 and K9s [abstract]. Clin Toxicol 52:710.

https://www.eapcct.org/publicfile.php?folder=congress&file=Abstracts_NewOrleans2.pdf

Line 356. Users may give cannabis products to pets while they are under the influence.

Line 389. Was repeat dose activated charcoal used in these cases or single dose activated charcoal.

Line 398. ’Intra-lipids’ is a trade name (Intralipid®) so would be better to use intravenous lipid emulsion (IVLE).

Figure 4. It is interesting you mention human faeces as a source of exposure. This paper has just been published.

Lauinger CA, Peacock R. Marijuana toxicosis in dogs in Melbourne, Australia, following suspected ingestion of human faeces: 15 cases (2011-2020). Aust Vet J. 2021 Nov 16. doi: 10.1111/avj.13134. Epub ahead of print.

Reviewer #2: This is a very interesting paper concerning a type of intoxication that seems to have some incidence in Canada and USA, with an increase after legalization of cannabis use in these countries. This can be relevant for other countries where this legalization occurs.

The information about clinical signs, products and route of exposure and diagnosis and treatment of the intoxication is also important and well reported and discuss.

The study have some limitation that were identified by the authors.

Only graphs from figure 2 and 3 are not so well done because x-axis is not explicit. Can the authors try to better explain these data?

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Reviewer #1: No

Reviewer #2: No

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Prevalence and Characteristics of Cannabis-induced Toxicoses in Pets: Results from a Survey of Veterinarians in North America

PONE-D-21-38974R1

Dear Dr. Khokhar,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Benito Soto-Blanco, DVM, MSc, PhD

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for addressing the comments and making things clearer. The manuscript is much improved and I am happy to accept it for publication.

Reviewer #2: The information in the graphics was improved. And the information on the supplementary data are necessary and make the diference to the readers understand data presented on graphics.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No