1.  Food intake and feeding behaviour  Obesity  Nausea and vomiting  IBD  Stress  Cancer Role of EC’s in the gut

2.  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

3.  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

4.  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

5.  Food intake and feeding behavior  Obesity  Stress  Nausea and vomiting  IBD  Cancer Role of EC’s in the gut

6.  Anandamide (AEA) and 2- AG  ↓ anadamide in motion sickness  ↓ CB1 receptor activity  ↓ 2-AG in major depression Effects of endocannabinoids

7.  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., 2007 Ray et al., 2009

8.  CB1 receptor antagonist  effective weight loss agent  withdrawn from the market in 2008  increased risk of depression and vomiting Rimonabant : A new Pill To Combat Obesity Van Gaal et al., 2005 Pi-Sunyer et al., 2006 Van Gaal et al.,2008

9. What is stress? Role of the ECS in stress

11. “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”

12. Stress… Unpredictable Uncontrollable

13. 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 of the ECS in stress

14.  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

15.  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

16. And so …. EC’s make you happy, fat and dumb ! Laurel and Hardy

17. BUT And so does weed !

18. Problems with marijuana

19. http://www.policyalmanac.org/crime/archive/marijuana.shtml