Food intake and feeding behaviour Obesity Nausea and vomiting IBD Stress Cancer Role of EC’s...
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Transcript of Food intake and feeding behaviour Obesity Nausea and vomiting IBD Stress Cancer Role of EC’s...
Food intake and feeding behaviour Obesity Nausea and vomiting IBD Stress Cancer
Role of EC’s in the gut
CB1 receptor agonists including Δ9-THC
“munchies” or craving for high fat diets promote body weight gain
Food intake
Bellocchio et al., 2008 ,Kunos, 2007 Matias and Di Marzo, 2007
CB1 receptors located on vagal afferent neurons may be involved in CB-induced modulation of appetite
anandamide might act as a “hunger signal” in the intestine
OEA -related compound, stimulates appetite
Storr & Sharkey, 2007
Role in obesity
peripherally restricted CB1 receptor antagonist (URB447) effective at suppressing food intake reducing body weight in genetically obese
ob/ob mice.
Role in obesity
Lo Verme et al. ,2009
Food intake and feeding behavior Obesity Stress Nausea and vomiting IBD Cancer
Role of EC’s in the gut
Anandamide (AEA) and 2- AG ↓ anadamide in motion sickness
↓ CB1 receptor activity ↓2-AG in major depression
Effects of endocannabinoids
CBs inhibit emesis in animal models acute cisplatin and delayed emesis morphine radiation-induced emesis anticipatory nausea and vomiting
FAAH inhibitor URB597 suppressed cisplatin nicotine-induced vomiting(in the house musk shrew through CB1 receptors)
Nausea and vomiting
Van Sickle et al., 2001, 2003, 2005; Darmani et al., 2007Ray et al., 2009
CB1 receptor antagonist effective weight loss agent withdrawn from the market in 2008 increased risk of depression and vomiting
Rimonabant : A new Pill To Combat Obesity
Van Gaal et al., 2005 Pi-Sunyer et al., 2006Van Gaal et al.,2008
What is stress?
Role of the ECS in stress
“People are disturbed not by a thing, but by their perception of a
thing.”Epictetus
Difficult to define Hence difficult to
measure Highly subjective First coined in the
1930’s by “Hans Selye”
Stress…
Unpredictable
Uncontrollab
le
Psychological stress induces endocrine, sympathetic, and behavioral responses that allow the individual to cope with stressThe endocannabinoid/CB1 receptor signaling system (ECS) serves to oppose these stress-induced changes
Role of the ECS in stress
Stress produces an increase in circulating endocannabinoids inversely related to stress-induced physiological
effects, including sympathetic activation and circulating glucocorticoid concentrations
Enables the host to adapt to stress and terminates ongoing sympathetic and hypothalamic-pituitary-adrenal (HPA) axis activation
Role in stress
Studies with CB1 receptor antagonists, such as rimonabant used in Europe for obesity support the role of the ECS in stress-related disorders
Rimonabant was associated with significant depression and nausea as a side effect
Role in stress
And so ….
EC’s make you happy , fat and dumb !
Laurel and Hardy
BUT
And so does weed !
Problems with marijuana
http://www.policyalmanac.org/crime/archive/marijuana.shtml