Role of EC’s in the gut
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Food intake and feeding behaviour
Obesity
Nausea and vomiting
IBD
Stress
Cancer
Food intake
 CB1 receptor agonists including Δ9-THC
 “munchies” or craving for high fat diets
 promote body weight gain
Bellocchio et al., 2008 ,Kunos, 2007
Matias and Di Marzo, 2007
Role in obesity
 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.
Lo Verme et al. ,2009
Role of EC’s in the gut
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Food intake and feeding behavior
Obesity
Stress
Nausea and vomiting
IBD
Cancer
Effects of endocannabinoids
 Anandamide (AEA) and 2- AG
 ↓ anadamide in motion sickness
 ↓ CB1 receptor activity
 ↓2-AG in major depression
Nausea and vomiting
 CBs inhibit emesis in animal models
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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)
Van Sickle et al., 2001, 2003, 2005; Darmani et al., 2007
Ray et al., 2009
Rimonabant : A new Pill To Combat
Obesity
CB1 receptor antagonist
 effective weight loss agent
 withdrawn from the market in 2008
 increased risk of depression and vomiting
Van Gaal et al., 2005
Pi-Sunyer et al., 2006
Van Gaal et al.,2008
Role of the ECS in stress
What is 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
Role of the ECS in stress
Psychological stress induces endocrine, sympathetic,
and behavioral responses that allow the individual to
cope with stress
The endocannabinoid/CB1 receptor signaling system
(ECS) serves to oppose these stress-induced changes
Role 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-pituitaryadrenal (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
And so ….
EC’s make you
happy , fat and
dumb !
Laurel and Hardy
And so does weed !
BUT
Problems with marijuana
Tetrahyrocannabinol content in a joint
9.00%
8.00%
7.00%
6.00%
5.00%
4.00%
8.02%
3.00%
2.00%
3.80%
3.96%
1990
1995
4.60%
1.00%
0.00%
2000
2005
http://www.policyalmanac.org/crime/archive/marijuana.shtml