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Endocannabinoid signaling and stress in CVS. Thangam Venkatesan, MD Associate Professor of Medicine Division of Gastroenterology and Hepatology Medical College of Wisconsin Milwaukee,WI. Disclosures. Significant relationships. Objectives. Overview of the endocannabinoid system (ECS) - PowerPoint PPT Presentation
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Endocannabinoid signaling and stress in CVSThangam Venkatesan, MD
Associate Professor of MedicineDivision of Gastroenterology and Hepatology
Medical College of WisconsinMilwaukee,WI
Disclosures
Significant relationships
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
Pathogenesis of CVS
CVS
Stress
Endocannabinoids
Genetics
Marijuana
Personalized Medicine
“Your DNA test shows you’re predisposed to sue doctors.”
Breaking bad – Viewer discretion advised !
Cannabis and the Gut
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 )
Is Cannabis the panacea of all ills?
Cannabis and the gut
What are cannabinoids ?
What are cannabinoids ?
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
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
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
AEA or 2-AG
StressiRmR
FAAH
Precursor
T
↑Ca2
+
Et, AA
+
Postsynaptic neuron
↓Ca2+,K+
Presynaptic neuron
CB1
NT
Endocannabinoid signalling
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)
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
Role of endocannabinoids in health and disease
Food intake and feeding behavior Obesity Nausea and vomiting IBD Stress Cancer
Role of EC’s in the gut