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

4.  Marijuana use in adolescence and adulthood  Risk factor for schizophrenia  Worse outcomes  frequent and longer periods of hospitalization  higher relapse rates even in first-episode patients  elevated rates of extrapyramidal motor symptoms (EPS),  lower medication compliance  higher rates of unemployment, violence,  higher rate of criminality  increased risk of suicide Side effects of heavy marijuana use Barnett et al. 2007 Verdoux and Tournier 2004 Stefanis et al. 2004

5.  Patients with cannabis abuse/dependence  smaller fronto-temporal WM volumes  Significant CNR1 (rs12720071) genotype-by- marijuana-use  effects on WM volumes  neurocognitive impairment Side effects of heavy marijuana use Agarwal et al,2009

6. Marijuana use in CVS  > 40% of adult CVS patients use marijuana  More likely to be male and young

7. CVS ( n=82)Functional vomiting (n=62) Odds ratio for CVS( 95% CI) P value Age (mean±SD) 30±1136±130.7(0.5-0.9)0.005 Gender Female ( n=71) Male (n=73) 33 (40%) 49 (60%) 38 (61%) 24 (39%) 0.4(.2-0.9)0.02 Cannabis use30 (37%)8 (13%)2.9(1.2-7.2)0.02 Retching55 (67%)25 (40%)4.4(2-9.7)0.0003 Depression2 (2%)4 (6%)0.4(1.2-2.6)0.35 Anxiety1 (1%)2 (3%)0.3(.03-4.5)0.41 Other psychiatric disorders 11 (13%)21 (34%)0.3(0.1-0.7)0.006 Marijuana use in CVS Choung R.S.et al, Neurogastroenterology and Motility, 2012

8.  Retrospective chart reviews  Review of 31 published case reports  Case series of 98 patients  Association with chronic, daily marijuana use  Long duration of use preceding onset of symptoms (2-10 years)  Duration of follow up ( variable) Cannabinoid hyperemesis syndrome Wallace E.A. et al, S Med Journal, 2011 Simonetto DA et al, Mayo Clinic Proceedings, 2012

9.  Total of 437 patients with CVS  Mean age was 34 ± 12  Mostly Caucasian (92%)  Eighty-one % of patients reported use of marijuana to treat their symptoms  Marijuana users were more likely to be male and have associated anxiety An Internet survey of marijuana use in CVS Experimental Brain research,2014

10. This patient like several CVS patients took hot showers that soothed her Janet Leigh in “Psycho”

11. Self reported effects of marijuana in patients with CVS Venkatesan et al, International Conference of Nausea & Vomiting,Pittsburgh,2013

12. Hypothesis The activity of the endocannabinoid system (ECS) is significantly altered with an associated increase in salivary cortisol and alpha amylase.

13. CVS patients n=22 Controls n=12 P value Age40±1137±12NS Gender Female Male 17 (77%) 5 (23%) 10 (83%) 2 (17%) NS BMI29.728.6NS Marijuana use8 (40%)0 (0%)0.002 * Pittsburgh Sleep Quality Index (PSQI) scores 12 ± 16 ± 10.0008 * Anxiety10 ± 15 ± 10.002 * Depression7 ± 0.41.6 ± 10.002 * Baseline characteristics

14. Serum 2-AG and NAE concentrations in CVS patients and controls Data were analyzed using one way ANOVA and comparisons between groups were carried out using Bonferroni’s t-tests. * p<0.05; **p<0.01. Data analyzed using one way ANOVA,comparisons between groups were carried out using Bonferroni’s t-tests. * p<0.05; **p<0.01. Venkatesan et al,DDW2013

15. Variable Patients – well phase Patients - sick phase Controls P value (Sick vs well phase in patients) Salivary cortisol (s cort) 6.7 (4.0-19.5)16 (2.6-51.4) 10.5 (3.4- 11.3) 0.09 Salivary alpha amylase 214 (13.5- 272.2) 285 (11.5- 586.0) 138 (44.2- 322.0) NS Salivary cortisol (nmol/L; median [range]), and salivary alpha amylase (U/ml; median [range]) in the well phase and during an episode in CVS patients and controls Venkatesan et al,DDW2013

16. Future direction

17.  Novel therapy  New drugs-manipulation of the ECS and HPA axis Future direction

18. Thank you Kathleen Adams & Mollie Sharon Coffie with GI nurses B Li Regal team of royal retchers! Cecilia Hillard Hershel Raff Reza Shaker Megan Yelena Melanie Shanika Cindy Sam