MedicalResearch.com Interview with:
Beth A. McCormick, Ph.D.
Professor and Vice Chair | Department of Microbiology & Physiological Systems
Founding Executive Director | University of Massachusetts Center for Microbiome Research
Board of Editors | Gastroenterology
University of Massachusetts Medical School
Worcester, MA 01655
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: There has been extensive, but to date mostly anecdotal, support for a beneficial role for cannabinoids and cannabis-derived agents to provide benefit for symptoms in individuals suffering from intestinal inflammatory disease (IBD).
Our studies have provided one possible rationale for these previous findings: that there is a constitutively active efflux system at the luminal surface of cells that line the intestine that pumps out one class of lipids of the family known as endocannabinoids. In doing so, the intestine floods this surface with these endocannabinoids in a manner that counteracts the actions of a particular potent stimulators of intestinal inflammation that appears to be over-active in certain forms of IBD. This is most significant because a number of cannabinoids and cannabis-derived agents can mimic the actions of this class of endocannabinoids. Moreover, while cannabinoids and endocannabinoids have been shown to provide anti-inflammatory actions, these studies have identified one mechanism used by the body to localize and focus this protective function at a critical site where pro-inflammatory and anti-inflammatory events intersect, providing new insights into how to treat that imbalance in these process that occurs in certain forms of IBD.
Therefore, there is the immediate opportunity to use this research to identify new therapeutic strategies to treat individuals suffering from IBD that could include either agents extracted from marijuana plants or novel molecules selected based upon superior properties made obvious by this newly defined mechanism.
MedicalResearch.com: What should readers take away from your report?
Response: Our studies began with the framework of asking the basic question of how the body protects itself from the actions of pro-inflammatory lipids released from cells that line the intestine to help fight infections but which appear to be over-active in IBD. Through these studies, we identified the efflux pump known as P-glycoprotein (Pgp) as the portal of exit from intestinal cells for this anti-inflammatory agent. We subsequently demonstrated that a specific class endocannabinoids were the agents secreted by Pgp and that these materials had the desired anti-inflammatory activity. We feel this unbiased approach provides a more powerful level of support for the potential clinical implications of our findings. Thus, our research provides support for those individuals who may have felt social pressures or uncertainties about the rationale of using medical marijuana to treat intestinal inflammatory diseases by framing a scientific understanding of how endocannabinoids function to suppress inflammation in the intestine. Our concern is that readers might take this as justification of using excessive amounts of marijuana with the all-to-common practice that if a little is good, a lot is better. Our studies show that these endocannabinoids work locally in the intestine and it will be important to identify best medical practices to restrict the actions of any agent intended to address this opportunity to maximize benefit and minimize side-effects.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: As a secondary aspect of our work involves an improved understanding of Pgp function with regard to endocannabinoids. This information could be directed towards better treatments for solid tumors where the resistance to anti-cancer agents is mediated by the over-expression of Pgp. Additionally, many promising therapeutic to treat conditions such as Alzheimer’s and Parkinson’s diseases are limited by their active exclusion by Pgp expressed in the blood vessels of the brain. Thus, our data provides the potential to improve treatments in oncology and neurology
MedicalResearch.com: Is there anything else you would like to add?
Response: Our studies are the first demonstration of a mechanism used by endocannabinoids for secretion from cells. This is a significant advance to further understanding endocannabinoid biology that can lead to advances in improving medicinal applications of cannabis-derived agents. What may be even more important is the fact that this is the first endogenous substrate identified for Pgp, an efflux pump that initially identified in cancer cells and demonstrated to pump anti-cancer agents out of cancer cells and to limit the uptake of drugs into the brain.
Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis
Rose L. Szabady, … , Randall J. Mrsny, Beth A. McCormick
Published August 13, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI96817.
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