Reviewer ’s report  
 
Title: Nabilone administration in refractory chronic diarrhea:  a case series  
 
Version: 0 Date: 09 Feb 2019  
 
Reviewer: Raquel Abalo  
 
Reviewer's report:  
 
In this manuscript, a series of 6 case reports are discussed in which nabilone, a synthetic 
cannabinoid ago nist (a THC analog), was used for treatment of chronic diarrhea that was 
refractory to other treatments including loperamide or kaolin.  
 
The manuscript is informative and clearly written. Conclusions are adequate.  
 
 
I have only the following comments:  
 
- Table 3 should be mentioned in the text  
 
- Some recent reviews and original articles on the effects of cannabinoids on the GI system 
should also be mentioned in the manuscript (probably in the introduction, maybe also in the 
discussion) like PMID 30418525, PMID 30407616, PMID 30076849, PMID 27792038, PMID 
29151076, PMID 28276820, PMID 28239924, PMID 27686064, PMID 26935536.  
 
- Discussion: the results obtained with nabilone should be compared with others in which 
natural cannabinoids (marijuana included) were  used  
 
- Discussion: in view of the literature available, what could be the mechanism by which 
nabilone produced its therapeutic effect? What mechanism could underlie the fact that such 
effect was so prolonged?     
Are the methods appropriate and well described?  
If not, please spe cify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data show n? 
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, fund ing, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that  
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, w rite 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing inter ests 
 
I agree to the open peer review policy of the journal. I understand that my name will be include d 
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Nabilone administration in refractory chronic diarrhea:  a case series  
 
Version: 0 Date: 09 Feb 2019  
 
Reviewer: Raquel Abalo  
 
Reviewer's report:  
 
In this manuscript, a series of 6 case reports are discussed in which nabilone, a synthetic 
cannabinoid ago nist (a THC analog), was used for treatment of chronic diarrhea that was 
refractory to other treatments including loperamide or kaolin.  
 
The manuscript is informative and clearly written. Conclusions are adequate.  
 
 
I have only the following comments:  
 
- Table 3 should be mentioned in the text  
 
- Some recent reviews and original articles on the effects of cannabinoids on the GI system 
should also be mentioned in the manuscript (probably in the introduction, maybe also in the 
discussion) like PMID 30418525, PMID 30407616, PMID 30076849, PMID 27792038, PMID 
29151076, PMID 28276820, PMID 28239924, PMID 27686064, PMID 26935536.  
 
- Discussion: the results obtained with nabilone should be compared with others in which 
natural cannabinoids (marijuana included) were  used  
 
- Discussion: in view of the literature available, what could be the mechanism by which 
nabilone produced its therapeutic effect? What mechanism could underlie the fact that such 
effect was so prolonged?     
Are the methods appropriate and well described?  
If not, please spe cify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data show n? 
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, fund ing, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that  
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, w rite 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing inter ests 
 
I agree to the open peer review policy of the journal. I understand that my name will be include d 
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Nabilone administration in refractory chronic diarrhea:  a case series  
 
Version: 0 Date: 09 Feb 2019  
 
Reviewer: Raquel Abalo  
 
Reviewer's report:  
 
In this manuscript, a series of 6 case reports are discussed in which nabilone, a synthetic 
cannabinoid ago nist (a THC analog), was used for treatment of chronic diarrhea that was 
refractory to other treatments including loperamide or kaolin.  
 
The manuscript is informative and clearly written. Conclusions are adequate.  
 
 
I have only the following comments:  
 
- Table 3 should be mentioned in the text  
 
- Some recent reviews and original articles on the effects of cannabinoids on the GI system 
should also be mentioned in the manuscript (probably in the introduction, maybe also in the 
discussion) like PMID 30418525, PMID 30407616, PMID 30076849, PMID 27792038, PMID 
29151076, PMID 28276820, PMID 28239924, PMID 27686064, PMID 26935536.  
 
- Discussion: the results obtained with nabilone should be compared with others in which 
natural cannabinoids (marijuana included) were  used  
 
- Discussion: in view of the literature available, what could be the mechanism by which 
nabilone produced its therapeutic effect? What mechanism could underlie the fact that such 
effect was so prolonged?     
Are the methods appropriate and well described?  
If not, please spe cify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data show n? 
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, fund ing, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that  
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, w rite 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing inter ests 
 
I agree to the open peer review policy of the journal. I understand that my name will be include d 
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant