Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine...
-
Upload
hilda-dickerson -
Category
Documents
-
view
225 -
download
0
Transcript of Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine...
![Page 1: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/1.jpg)
Endocannabinoid signaling and stress in CVSThangam Venkatesan, MD
Associate Professor of MedicineDivision of Gastroenterology and Hepatology
Medical College of WisconsinMilwaukee,WI
![Page 2: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/2.jpg)
Disclosures
Significant relationships
![Page 3: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/3.jpg)
Overview of the endocannabinoid system (ECS) elucidate the role of the ECS in vomiting and stress
Discuss use of marijuana in CVS Future direction
Cannabinoids as potential pharmacotherapy in CVS
Objectives
![Page 4: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/4.jpg)
Pathogenesis of CVS
CVS
Stress
Endocannabinoids
Genetics
Marijuana
![Page 5: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/5.jpg)
Personalized Medicine
“Your DNA test shows you’re predisposed to sue doctors.”
![Page 6: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/6.jpg)
Breaking bad – Viewer discretion advised !
![Page 7: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/7.jpg)
Cannabis and the Gut
![Page 8: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/8.jpg)
Marijuana
Used for centuries as a herbal remedy in the East
Described as the “elixir of the Gods”
Legalized in many states in the US
40% of the CVS population uses marijuana for symptom relief (Choung et al. 2012)
White DG. University of Chicago Press. 1996. (Tara Tantra )
![Page 9: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/9.jpg)
Is Cannabis the panacea of all ills?
Cannabis and the gut
![Page 10: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/10.jpg)
What are cannabinoids ?
![Page 11: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/11.jpg)
What are cannabinoids ?
![Page 12: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/12.jpg)
The endocannabinoid system (ECS)
Phytocannabinoids (derived from the plant) THC , cannabidiol and
other compounds
Synthetic cannabinoids
Endocannabinoids Anandamide (AEA)
Derived from “ananda” or bliss in sanskrit
2- AG(2-arachidonylglycerol)
Receptors ( CB1 and CB2)
Enzymes involved in degradation of endocannabinoids
Devane et al. 1992), Mechoulamet al. 1995; Sugiura et al. 1995
![Page 13: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/13.jpg)
CB1 & CB2 classical receptors for all types of CB agonists
endocannabinoids, phytocannabinoids synthetic CBs
Distributed in many areas in the CNS, enteric neurons, nerve fibers and terminals in the enteric nervous systemCB1 seen throughout the wall of the gutMacrophages & plasma cells are immunoreactive for both CB1 and CB2 receptors
Cannabinoid receptors
Pertwee, 2009
![Page 14: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/14.jpg)
Fatty acid amide hydrolase (FAAH) degradation of AEA and some 2-AG
Monoacylglycerol lipase (MAG lipase) is responsible for the degradation of 2-AG
Causes degradation of 2-AG
Inactivation of AEA and 2-AG
Ahn et al., 2008Duncan et al., 2008
![Page 15: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/15.jpg)
AEA or 2-AG
StressiRmR
FAAH
Precursor
T
↑Ca2
+
Et, AA
+
Postsynaptic neuron
↓Ca2+,K+
Presynaptic neuron
CB1
NT
Endocannabinoid signalling
![Page 16: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/16.jpg)
Tetrahydrocannabinol (THC) , cannabidiolic acid (CBDA), cannabidiol (CBD) and other compounds CBDA and CBD are not psychoactive
Heating the plant cause changes in chemical composition
CBDA CBD THCA THC
Phytocannabinoids(plant derived)
![Page 17: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/17.jpg)
THCA No psychoactive effects in rhesus monkeys up to 5
mg/kg Reduced LiCl induced vomiting in the musk shrew,effect
was reversed with rimonbant pretreatment Reduced conditioned gaping in rats ( a surrogate
marker for nausea) CBDA
Reduced LiCl, motion and cisplatin-induced vomiting in the shrew
Effects of phytocannabinoids
![Page 18: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/18.jpg)
Role of endocannabinoids in health and disease
![Page 19: Endocannabinoid signaling and stress in CVS Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical.](https://reader035.fdocuments.net/reader035/viewer/2022062322/5697bf871a28abf838c88f78/html5/thumbnails/19.jpg)
Food intake and feeding behavior Obesity Nausea and vomiting IBD Stress Cancer
Role of EC’s in the gut