Debate Medical Marijuana Disclosures I did not inhale!! Pro: Bilal Hameed, MD Con: Rupal Shah, MD Research Support: Gilead, Tobira Debating You have to learn the rules of the game. Then you have to play better than anyone else. Albert Einstein 1
Marijuana Very few drugs, if at all, have such a tangled history as a medicine. In fact, prejudice, superstition, emotionalism, and even ideology have managed to lead cannabis to ups and downs concerning both its therapeutic properties and its toxicological and dependenceinducing effects. Brazilian psychopharmacologist E. A. Carlini Toxicon 2004;44:461 7. Marijuana History smoke, vapor, ingestion, oil: 60 active ingredients known as cannabinoids Global Cannabis Use? 2737 BC Sheng Neng, Emperor of China, touted cannabis tea for Rx of gout, rheumatism, malaria and poor memory Use spread in Asia, Middle East, Africa and India, for pain and stress relief W. B. O Shaughnessy, an Irish physician working in Calcutta in the 1830s recommended cannabis pain, vomiting, convulsions, and spasticity 2
Marijuana History is US Use of cannabis received official legitimacy by its listing in the US Dispensatory in 1854 Federal Bureau of Narcotics pushed for the congressional passage of the 1937 Marihuana Tax Act In 1942, it was removed from the US Dispensatory In 1970 US Congress finally declare it to have no medical value Recreational Marijuana is now legal in Oregon, Washington, Alaska, Colorado & DC Medical Marijuana is legal in 23 states & DC Green medical and recreational use legal Light green medical use legal Yellow decriminalized Red - Illegal 3
Scope of the Issue Marijuana was the most prevalently used illegal substance in the US in 2010 (US Dept of HHS) 190 million people consumed cannabis in 2007 worldwide (United Nations estimate) 40% of teenagers have tried marijuana / 20% are current users (CDC) The Facts Many of our Founding Fathers grew cannabis and smoked it regularly US Politicians who have admitted to using or were known to use marijuana include mayors, governors, members of the House of Representatives, and Presidents (list not complete): George Washington, Benjamin Franklin, Thomas Jefferson, Abraham Lincoln, James Madison, John F Kennedy, Jimmy Carter, Bill Clinton, Al Gore, George W. Bush, Jeb Bush, Newt Gingcrich, Joseph P. Kennedy II, Ed Koch, Andrew Como, Bruce Babbitt, Michael Bloomberg, Bill Bradely, Paul Cellucci, Richard Lamm, John Edwards, John Kerry, Sarah Palin, Arnold Schwarzenegger, Jesse Ventura, Barack Obama Many Queen Victoria used cannabis for childbirth pain Queen Elizabeth II used cannabis for menstrual cramps Public Opinion About Marijuana Middle-aged parents are now more likely to smoke weed than their teenage kids Regular Marijuana Use in 2014 Age 12-17 yrs: 7% Age 35-44 yrs: 8 % Source: SAMHSA/CDC 4
Where Candidates Stands on Marijuana? Lifetime Dependence of Marijuana Cannabis: Not a New medicine Lifetime dependence risk Marijuana: 9% Nicotine: 32% Heroin: 23% Cocaine: 17% Alcohol: 15% Robson P. Expert Opin Drug Saf 2011. 5
Studies on Medicinal Cannabis Effects: Whiting et al (2015) meta-analysis # RCTs # Reports # Patients 28Chronic Pain 63 2454 28Nausea and vomiting due to chemotherapy 37 1772 14Spasticity due to multiple sclerosis/paraplegia 33 2280 4HIV/AIDS 4 255 2Sleep Disorder 5 54 2Psychosis 9 91 2Tourette syndrome 7 36 1Anxiety disorder 1 24 1Glaucoma 1 6 Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Metaanalysis. JAMA. 313:2456-2473, 2015 Meta-Analysis Moderate-quality evidence to support the use of cannabinoids in: chronic pain spasticity Low-quality evidence suggesting that cannabinoids were associated with improvements in: nausea and vomiting due to chemotherapy weight gain in HIV infection sleep disorders Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Metaanalysis. JAMA. 313:2456-2473, 2015 No Increase in Lung Cancer in Marijuana Smokers Pooled analyses 6 case-controlled studies US, Canada, UK, New Zealand - 2,100 lung cancer cases and 3,000 controls Provided little evidence for an increased risk of lung cancer among habitual or long-term cannabis smokers Even when data was analyzed based on intensity, duration, consumption and age of initiation, no significant association was found Zhang et al. International Journal of Cancer; 136, (4): 894 903, Feb 2015. 6
Blurred Boundaries Recreational vs medical use Benefit vs harm of use Lab research and pharmacologic application vs federal restrictions State vs federal law Rules are not based on scientific evidence but on political ideology and gamesmanship Marijuana and Transplant Marijuana Policy for Liver Transplant What to do now that Marijuana is legal in some states? 34% of Canadian centers consider marijuana as a contraindication to transplantation, compared with 70% of US centers 30 7
Marijuana Policy for Liver Transplant Marijuana users have similar survival rates to non-users 56% responded from 102 active adult liver transplant centers 70% of transplant centers have an existing policy 47% identified marijuana use as a controversial characteristic 46% consider current recreational use as absolute contraindication 11% consider medicinal use as absolute contraindication 31 Ranney et al Marijuana Use Is Not Associated With Progression to Advanced Liver Fibrosis in HIV/HCV coinfected Women 575 women Median of 11 years 56% no THC use 25% < weekly use 12% weekly use 7% daily use Probability of Advanced Fibrosis 0.00 0.20 0.40 0.60 0.80 1.00 0 2 4 6 8 10 12 14 16 18 Time since study entry (years) Number at risk potcat_aprigte15 xxxxxxxxxxxxxxx = Non-User 142 93 70 54 39 31 24 16 14 1 potcat_aprigte15 xxxxxxxxxxxxxxx = < Weekly 54 45 33 27 20 17 11 9 7 0 potcat_aprigte15 xxxxxxxxxxxxxx = >= Weekly 87 72 64 56 40 31 22 17 14 1 Non-User < Weekly >= Weekly Marijuana Use Does Not Predict Outcomes On The Liver Transplant Waitlist Retrospective cohort of adults evaluated for transplant from 1/2012 to 12/2013 at UCSF 884 adults evaluated and 585 (66%) were listed Median follow up of 1.4 years Prevalence of marijuana use was 48% 7% being current users and 41% prior users Slide provided by Dr. Kelly Kelly, EM et al. Clin Infect Dis 2016. Kotwani et al. AASLD abstract accpeted 2016. 8
Marijuana Use Does Not Predict Outcomes On The Liver Transplant Waitlist Recreational Marijuana Use Is Not Associated With Worse Outcomes After Renal Transplantation KM survival estimate for time to death/delisting on the liver transplant waitlist (N=585) Kotwani et al. AASLD abstract accepted 2016. Greenan G et al. Clinic Transplant 2016. What Should be Your Transplant Center Policy? Don t ask, don t tell Ask, and if yes for medical marijuana allow use attempt enforcement of not smoking- use other routes Ask, and if yes, for medical or recreational - propose abstinence for a defined period of time (eg. 6 mo.) Don t list anyone who currently uses or historically used marijuana Very harsh! UCSF Liver Transplant Policy in 2015 9
Lets Clear the Smoke Seven states prohibit denying transplant to medical marijuana users solely based on their use of the drug Very little evidence shows that marijuana predicts worse transplant outcomes Transplant professionals should attempt to determine whether marijuana use negatively impacts a patient s life and how it may influence behavior or mask mental health issues How We Do We Move Forward? Need separate policies on medicinal use versus recreational Large scale clinical trials, administered via several routes Need to re-schedule class of marijuana, need regulated dispensaries and pharmacies We cannot make decisions about transplant on case reports Future Studies University of California, San Diego - Center for Medicinal Cannabis Research (CMCR) Established in 2012 as a program to oversee an objective, high quality medical research that will enhance understanding of the efficacy and adverse effects of marijuana as a pharmacological agent Thank You Learn from yesterday, live for today, hope for tomorrow. The important thing is not to stop questioning. 10