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Research Article
Fighting the storm: novel anti- TNFα and anti-IL-6 C. sativa lines to tame cytokine storm in COVID-19
Igor Kovalchuk
Pathway Research Inc., Lethbridge, AB, T1K7X8, Canada; University of Lethbridge, Lethbridge, AB, T1K3M4, Canada
Corresponding Author
Olga Kovalchuk
Pathway Research Inc., Lethbridge, AB, T1K7X8, Canada; University of Lethbridge, Lethbridge, AB, T1K3M4, Canada
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The main aspects of severe COVID-19 disease pathogenesis include the increasing hyper-induction of proinflammatory cytokines, also known as ‘cytokine storm’, that precedes acute respiratory distress syndrome (ARDS) and often leads to death. COVID-19 patients often suffer from lung fibrosis, a serious and untreatable condition. There remains no effective treatment for these complications. Out of the cytokines, TNFα and IL-6 play crucial roles in cytokine storm pathogenesis and are likely responsible for the escalation in disease severity. These cytokines also partake in the molecular pathogenesis of fibrosis. Therefore, new approaches are urgently needed that can efficiently and swiftly block TNFα, IL-6, and the inflammatory cytokine cascade in order to curb inflammation and prevent fibrosis, and lead to disease remission.
Cannabis sativa has been proposed to modulate gene expression and inflammation and is under investigation for several potential therapeutic applications against autoinflammatory diseases and cancer. Here, we hypothesized that the extracts of our novel C. sativa lines may be used to modulate the expression of pro-inflammatory cytokines and pathways involved in inflammation and fibrosis.
To analyze the anti-inflammatory effects of novel C. sativa lines, we used a well-established full thickness human 3D skin artificial EpiDermFTTM tissue model, whereby tissues were exposed to UV to induce inflammation and then treated with extracts of seven new cannabis lines.
We noted that out of seven studied extracts of novel C. sativa lines, three (#4, #8 and #14) were the most effective, causing profound and concerted down-regulation of TNFα, IL-6, CCL2, and other cytokines and pathways related to inflammation and fibrosis. Most importantly, one of the tested extracts had no effects at all, and one exerted effects that may be deleterious, signifying that cannabis is not generic and cultivar selection must be based on thorough pre-clinical studies.
The observed pronounced inhibition of TNFα and IL-6 is the most important finding, as these molecules are currently considered to be the main actionable targets in COVID-19 cytokine storm and ARDS pathogenesis.
Many currently trialed agents, such as anti-TNFα and anti-IL-6 biologics are expensive and cause an arrays of side effects. On the other hand, anti-TNFα and anti-IL-6 cannabis extracts that are generally regarded as safe (GRAS) modalities can be a useful addition to the current anti-inflammatory regimens to treat COVID-19, as well as various rheumatological diseases and conditions, and ‘inflammaging’ - the inflammatory underpinning of aging and frailty.
Keywords
COVID-19, SARS-CoV2, cytokine storm, TNFα, IL-6, fibrosis, medical cannabis
Figure 1
Figure 2
Figure 3
Kaj KJ Hulsebosch
commented on 22 May, 2020
Dear PathwayRX, I wondered: I live in the Netherlands , under what exact names can i find these C. Sativa lines #4, #8 and #14, or are they novel in the sense that they are new crossings? Kind regards, Kaj Hulsebosch
View 2 replies
Joy King
commented on 25 May, 2020
Has the team considered combinding the Sativa with Pycnogenol? I believe that this Pycnogenol helped me survive the virus.
View 2 replies
ulla singapuri
replied on 12 June, 2020
Dear Joy, pycnogenol or hydrolysed lignin is well known to protect you and your cells. Have a look at meabco and BP-C2 and BP-C1....... helps balance your immune system and have good results also for cancer. No doubt you will see pycnogenol with various cannabinoids in the future. biggest issue is bio availability at the moment.
View 1 reply
Andrew
replied on 12 July, 2020
InMed Pharmaceuticals currently scaling up their cannabinoid production system with Almac. They should be at commercial scale this year. Maybe you contact them as a possible supplier of your cannabinoids.
Olga
replied on 19 January, 2021
Deat Joy, Thank you for your interest. We continue our research in this field and have tried various combinations (sorry, I can't be more specific as the data have not been published yet). We hope to be able to submit our new data for publication soon, Sincerely, Olga
Miguel neumann
commented on 06 June, 2020
is there any specific on the percentage thc-cbd-cbd, etc????
View 2 replies
Olga
replied on 19 January, 2021
Dear Miguel, the paper has undergone a peer review and has been revised and accepted for publication in Aging. The revised version has CBD, THC, CBGA and CBN data in table 3. Best regards, Olga https://www.aging-us.com/article/202500/text
Olga
replied on 19 January, 2021
Dear Miguel. The paper has undergone peer-review and has been published. You can find CBD, THC, CBN percentage in table 3. https://www.aging-us.com/article/202500/text Thank you! Olga
Tim Davies
commented on 11 July, 2020
I am curious to know if the gene sequences are known for the tufa and inl6 ? Also is the metabolic pathway known, as you seem to mention that bio availability might be an issue ?
MDeCicco
commented on 13 July, 2020
Hello, Thank you for your research, and in the testing of Cannabis for Health Care. It was mentioned that all strains were grown and processed at U of Lethbridge. In the CTV report (Video) titled: “Are new cannabis strains key to fighting COVID-19? These Alta. researchers think so“ there were company specific products and lab coat used. Can you confirm that there is a connection between this suggestion and the few successful strains? Appreciated
Shannon hopkins
commented on 05 September, 2020
Are these strains available yet ?
View 1 reply
Olga
replied on 19 January, 2021
Not yet. We are working towards this goal. Regards, Olga
Rob
commented on 13 January, 2021
Hi there all, I am very interested in the products discussed. I am a user and grower of High quality Canadian bud(flower). I have been diagnosed with the virus two days ago and have been Ingesting large amounts of THC gummy‘s and CBD extracts, seem to be feeling OK that being said I am very interested in hopefully purchasing/being a guinea pig for your Controlled product please let me know how I can help.
View 2 replies
noemie
replied on 19 January, 2021
Hello Rob (and all); Just for information, Herbalist Stephen Buhner recommends the use of a nebulizer(with essential oils) for helping with the covid (I recommend his protocol that can be found on his facebook page). I haven't read everything of this study but I am thinking maybe taking thc/cbd through a nebulizer (needs to be oily -or could be watery- extract -- ) . Just to stress that this is not very well known way of administering oneself cbd, and at least for me, it works well, and it goes directly into the lungs (and brain). (I just use the same number of drops I would use sublingually but I put them in the chamber of the nebulizer - cbd oil extract)
Olga
replied on 19 January, 2021
Dear Rob, so sorry to hear that you have contracted COVID. We wish you a speedy and complete recovery. At this stage, we cannot provide any extracts as they have to undergo further clinical trials. We are looking for partnerships to bring this research further. Again - thank you for your interest in our research. With the best wishes and kindest regards, Olga
View 1 reply
David
replied on 24 February, 2021
Hi Pathway RX, Great research being done here! Are you guys familiar with the work done by Grapefruit USA in developing a cannabis cream that can be absorbed through the skin? Seems like it would go together great with these medicinal strains that you guys are developing. Check it out... https://grapefruitblvd.com/hourglass/
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Research Article
Fighting the storm: novel anti- TNFα and anti-IL-6 C. sativa lines to tame cytokine storm in COVID-19
Igor Kovalchuk
Pathway Research Inc., Lethbridge, AB, T1K7X8, Canada; University of Lethbridge, Lethbridge, AB, T1K3M4, Canada
Corresponding Author
Olga Kovalchuk
Pathway Research Inc., Lethbridge, AB, T1K7X8, Canada; University of Lethbridge, Lethbridge, AB, T1K3M4, Canada
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 22 May, 2020
Community comments: 18
Metrics
Comments: 18
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The main aspects of severe COVID-19 disease pathogenesis include the increasing hyper-induction of proinflammatory cytokines, also known as ‘cytokine storm’, that precedes acute respiratory distress syndrome (ARDS) and often leads to death. COVID-19 patients often suffer from lung fibrosis, a serious and untreatable condition. There remains no effective treatment for these complications. Out of the cytokines, TNFα and IL-6 play crucial roles in cytokine storm pathogenesis and are likely responsible for the escalation in disease severity. These cytokines also partake in the molecular pathogenesis of fibrosis. Therefore, new approaches are urgently needed that can efficiently and swiftly block TNFα, IL-6, and the inflammatory cytokine cascade in order to curb inflammation and prevent fibrosis, and lead to disease remission.
Cannabis sativa has been proposed to modulate gene expression and inflammation and is under investigation for several potential therapeutic applications against autoinflammatory diseases and cancer. Here, we hypothesized that the extracts of our novel C. sativa lines may be used to modulate the expression of pro-inflammatory cytokines and pathways involved in inflammation and fibrosis.
To analyze the anti-inflammatory effects of novel C. sativa lines, we used a well-established full thickness human 3D skin artificial EpiDermFTTM tissue model, whereby tissues were exposed to UV to induce inflammation and then treated with extracts of seven new cannabis lines.
We noted that out of seven studied extracts of novel C. sativa lines, three (#4, #8 and #14) were the most effective, causing profound and concerted down-regulation of TNFα, IL-6, CCL2, and other cytokines and pathways related to inflammation and fibrosis. Most importantly, one of the tested extracts had no effects at all, and one exerted effects that may be deleterious, signifying that cannabis is not generic and cultivar selection must be based on thorough pre-clinical studies.
The observed pronounced inhibition of TNFα and IL-6 is the most important finding, as these molecules are currently considered to be the main actionable targets in COVID-19 cytokine storm and ARDS pathogenesis.
Many currently trialed agents, such as anti-TNFα and anti-IL-6 biologics are expensive and cause an arrays of side effects. On the other hand, anti-TNFα and anti-IL-6 cannabis extracts that are generally regarded as safe (GRAS) modalities can be a useful addition to the current anti-inflammatory regimens to treat COVID-19, as well as various rheumatological diseases and conditions, and ‘inflammaging’ - the inflammatory underpinning of aging and frailty.
Figure 1
Figure 2
Figure 3
Kaj KJ Hulsebosch
commented on 22 May, 2020
Dear PathwayRX, I wondered: I live in the Netherlands , under what exact names can i find these C. Sativa lines #4, #8 and #14, or are they novel in the sense that they are new crossings? Kind regards, Kaj Hulsebosch
View 2 replies
Olga Kovalchuk
replied on 22 May, 2020
Dear Kaj, thank you for your interest. These are unique brand new lines that have been developed by us. We hope to bring them to clinical trials soon. Best regards, Olga and the PathwayRX team.
Olga
replied on 19 January, 2021
Dear Kaj, thank you for your interest in our research! These are new cultivars that have been bred by us. We very much hope to be able to run clinical trials and find collaborations that will help bring them to the broader public. Sincerely, Olga
Joy King
commented on 25 May, 2020
Has the team considered combinding the Sativa with Pycnogenol? I believe that this Pycnogenol helped me survive the virus.
View 2 replies
ulla singapuri
replied on 12 June, 2020
Dear Joy, pycnogenol or hydrolysed lignin is well known to protect you and your cells. Have a look at meabco and BP-C2 and BP-C1....... helps balance your immune system and have good results also for cancer. No doubt you will see pycnogenol with various cannabinoids in the future. biggest issue is bio availability at the moment.
View 1 reply
Andrew
replied on 12 July, 2020
InMed Pharmaceuticals currently scaling up their cannabinoid production system with Almac. They should be at commercial scale this year. Maybe you contact them as a possible supplier of your cannabinoids.
Olga
replied on 19 January, 2021
Deat Joy, Thank you for your interest. We continue our research in this field and have tried various combinations (sorry, I can't be more specific as the data have not been published yet). We hope to be able to submit our new data for publication soon, Sincerely, Olga
Miguel neumann
commented on 06 June, 2020
is there any specific on the percentage thc-cbd-cbd, etc????
View 2 replies
Olga
replied on 19 January, 2021
Dear Miguel, the paper has undergone a peer review and has been revised and accepted for publication in Aging. The revised version has CBD, THC, CBGA and CBN data in table 3. Best regards, Olga https://www.aging-us.com/article/202500/text
Olga
replied on 19 January, 2021
Dear Miguel. The paper has undergone peer-review and has been published. You can find CBD, THC, CBN percentage in table 3. https://www.aging-us.com/article/202500/text Thank you! Olga
Tim Davies
commented on 11 July, 2020
I am curious to know if the gene sequences are known for the tufa and inl6 ? Also is the metabolic pathway known, as you seem to mention that bio availability might be an issue ?
MDeCicco
commented on 13 July, 2020
Hello, Thank you for your research, and in the testing of Cannabis for Health Care. It was mentioned that all strains were grown and processed at U of Lethbridge. In the CTV report (Video) titled: “Are new cannabis strains key to fighting COVID-19? These Alta. researchers think so“ there were company specific products and lab coat used. Can you confirm that there is a connection between this suggestion and the few successful strains? Appreciated
Shannon hopkins
commented on 05 September, 2020
Are these strains available yet ?
View 1 reply
Olga
replied on 19 January, 2021
Not yet. We are working towards this goal. Regards, Olga
Rob
commented on 13 January, 2021
Hi there all, I am very interested in the products discussed. I am a user and grower of High quality Canadian bud(flower). I have been diagnosed with the virus two days ago and have been Ingesting large amounts of THC gummy‘s and CBD extracts, seem to be feeling OK that being said I am very interested in hopefully purchasing/being a guinea pig for your Controlled product please let me know how I can help.
View 2 replies
noemie
replied on 19 January, 2021
Hello Rob (and all); Just for information, Herbalist Stephen Buhner recommends the use of a nebulizer(with essential oils) for helping with the covid (I recommend his protocol that can be found on his facebook page). I haven't read everything of this study but I am thinking maybe taking thc/cbd through a nebulizer (needs to be oily -or could be watery- extract -- ) . Just to stress that this is not very well known way of administering oneself cbd, and at least for me, it works well, and it goes directly into the lungs (and brain). (I just use the same number of drops I would use sublingually but I put them in the chamber of the nebulizer - cbd oil extract)
Olga
replied on 19 January, 2021
Dear Rob, so sorry to hear that you have contracted COVID. We wish you a speedy and complete recovery. At this stage, we cannot provide any extracts as they have to undergo further clinical trials. We are looking for partnerships to bring this research further. Again - thank you for your interest in our research. With the best wishes and kindest regards, Olga
View 1 reply
David
replied on 24 February, 2021
Hi Pathway RX, Great research being done here! Are you guys familiar with the work done by Grapefruit USA in developing a cannabis cream that can be absorbed through the skin? Seems like it would go together great with these medicinal strains that you guys are developing. Check it out... https://grapefruitblvd.com/hourglass/
Olga Kovalchuk
replied on 22 May, 2020
Dear Kaj, thank you for your interest. These are unique brand new lines that have been developed by us. We hope to bring them to clinical trials soon. Best regards, Olga and the PathwayRX team.
Olga
replied on 19 January, 2021
Dear Kaj, thank you for your interest in our research! These are new cultivars that have been bred by us. We very much hope to be able to run clinical trials and find collaborations that will help bring them to the broader public. Sincerely, Olga