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CB1 receptor antagonist effective weight loss agent withdrawn from the market in 2008 increased risk of depression and vomiting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