Reviewer ’s report  
 
Title: Nabilone administration in refractory chronic diarrhea:  a case series  
 
Version: 0 Date: 25 Feb 2019  
 
Reviewer: Rudolf Schicho  
 
Reviewer's report : 
 
The manuscript titled „Nabilone administration in refractory chronic diarrhea: a case series" 
describes 6 cases of diarrhea of different etiologies retrospectively who received nabilone, a 
THC a nalogue and cannabinoid receptor agonist, to manage symptoms not controlable with other 
drugs. As a result, a mean of the daily bowel movements and body weights is presented 
indicating an improvement in weight loss and stool frequency by nabilone.  
 
It is we ll known that THC improves quality of life in Crohns disease patients. So the current 
reports come to no surprise. The paper summarizes cases that were given the synthetic THC 
analogue nabilone. In general, there is little clinical data data on cannabinoid  effects in GI 
disorders so new information is welcome even though the present study is only observational and 
very limited. If a mean was calculated from stool frequencies and body weights a statistical test 
should be applied whether differences are signi ficant.  
 
What is not clear is whether loperamide was already given before nabilone therapy or 
simultaneously? Was it unsuccessful in ameliorating diarrhea? Please explain. If it was given 
simultaneously discuss the anti -diarrheal effect of loperamide and i ts role in the study.  
 
 
Minor:  
 
page 4 line 1:  
In the past, Cannabis played a strong role, not position  
 
line 36: ….They are able to interact with the endocannabinoid system…….  
You need to be careful with this statement: not all ingredients of C. sativa act  via cannabinoid 
receptors; cannabidiol doesn't  
 
line 48: outside the brain, components of the ECS can be detected in GI tract and immune cells 
and also other organs;  see Maccarrone et al.. Trends Pharmacol Sci. 2015;36(5):277 -96. 
Pharmacokinetic properti es of nabilone are given in Table 2: are these own observations? If not, 
please provide reference(s)  
 
 
 
 
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.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
 
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 interests  
 
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: 25 Feb 2019  
 
Reviewer: Rudolf Schicho  
 
Reviewer's report : 
 
The manuscript titled „Nabilone administration in refractory chronic diarrhea: a case series" 
describes 6 cases of diarrhea of different etiologies retrospectively who received nabilone, a 
THC a nalogue and cannabinoid receptor agonist, to manage symptoms not controlable with other 
drugs. As a result, a mean of the daily bowel movements and body weights is presented 
indicating an improvement in weight loss and stool frequency by nabilone.  
 
It is we ll known that THC improves quality of life in Crohns disease patients. So the current 
reports come to no surprise. The paper summarizes cases that were given the synthetic THC 
analogue nabilone. In general, there is little clinical data data on cannabinoid  effects in GI 
disorders so new information is welcome even though the present study is only observational and 
very limited. If a mean was calculated from stool frequencies and body weights a statistical test 
should be applied whether differences are signi ficant.  
 
What is not clear is whether loperamide was already given before nabilone therapy or 
simultaneously? Was it unsuccessful in ameliorating diarrhea? Please explain. If it was given 
simultaneously discuss the anti -diarrheal effect of loperamide and i ts role in the study.  
 
 
Minor:  
 
page 4 line 1:  
In the past, Cannabis played a strong role, not position  
 
line 36: ….They are able to interact with the endocannabinoid system…….  
You need to be careful with this statement: not all ingredients of C. sativa act  via cannabinoid 
receptors; cannabidiol doesn't  
 
line 48: outside the brain, components of the ECS can be detected in GI tract and immune cells 
and also other organs;  see Maccarrone et al.. Trends Pharmacol Sci. 2015;36(5):277 -96. 
Pharmacokinetic properti es of nabilone are given in Table 2: are these own observations? If not, 
please provide reference(s)  
 
 
 
 
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.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
 
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 interests  
 
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: 25 Feb 2019  
 
Reviewer: Rudolf Schicho  
 
Reviewer's report : 
 
The manuscript titled „Nabilone administration in refractory chronic diarrhea: a case series" 
describes 6 cases of diarrhea of different etiologies retrospectively who received nabilone, a 
THC a nalogue and cannabinoid receptor agonist, to manage symptoms not controlable with other 
drugs. As a result, a mean of the daily bowel movements and body weights is presented 
indicating an improvement in weight loss and stool frequency by nabilone.  
 
It is we ll known that THC improves quality of life in Crohns disease patients. So the current 
reports come to no surprise. The paper summarizes cases that were given the synthetic THC 
analogue nabilone. In general, there is little clinical data data on cannabinoid  effects in GI 
disorders so new information is welcome even though the present study is only observational and 
very limited. If a mean was calculated from stool frequencies and body weights a statistical test 
should be applied whether differences are signi ficant.  
 
What is not clear is whether loperamide was already given before nabilone therapy or 
simultaneously? Was it unsuccessful in ameliorating diarrhea? Please explain. If it was given 
simultaneously discuss the anti -diarrheal effect of loperamide and i ts role in the study.  
 
 
Minor:  
 
page 4 line 1:  
In the past, Cannabis played a strong role, not position  
 
line 36: ….They are able to interact with the endocannabinoid system…….  
You need to be careful with this statement: not all ingredients of C. sativa act  via cannabinoid 
receptors; cannabidiol doesn't  
 
line 48: outside the brain, components of the ECS can be detected in GI tract and immune cells 
and also other organs;  see Maccarrone et al.. Trends Pharmacol Sci. 2015;36(5):277 -96. 
Pharmacokinetic properti es of nabilone are given in Table 2: are these own observations? If not, 
please provide reference(s)  
 
 
 
 
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.  
 
Unable to assess  
 
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.  
 
Not relevant to this manuscript  
 
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 interests  
 
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