9/30/2016

Debate Disclosures I did not inhale !! Medical Marijuana

Research Support: Gilead, Tobira Pro: Bilal Hameed , MD Con: Rupal Shah, MD

Debating “You have to learn the rules of the game. Then you have to play better than anyone else.”

Albert Einstein

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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 dependence- inducing effects.”

Brazilian psychopharmacologist E. A. Carlini Toxicon 2004;44:461–7.

Marijuana History smoke, vapor, ingestion, oil: Global Cannabis Use? 60 active ingredients known as cannabinoids

• 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

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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 , Washington, Alaska, & DC • Medical Marijuana is legal in 23 states & DC

Green – medical and recreational use legal Light green – medical use legal Yellow – decriminalized Red - Illegal

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The Facts Scope of the Issue Many of our Founding Fathers grew • Marijuana was the most prevalently used illegal substance cannabis and smoked it regularly in the US in 2010 ( US Dept of HHS ) • 190 million people consumed cannabis in 2007 worldwide (United Nations estimate) 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 • 40% of teenagers have tried marijuana / 20% are current Washington, Benjamin Franklin, Thomas Jefferson, Abraham Lincoln, James Madison, John F users (CDC) Kennedy, Jimmy Carter, , , 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, , Barack Obama… Many Queen Victoria used cannabis for childbirth pain

Queen Elizabeth II used cannabis for menstrual cramps

Middle-aged parents are now more likely to Public Opinion About Marijuana smoke weed than their teenage kids

Regular Marijuana Use in 2014

Age 12-17 yrs: 7% Age 35-44 yrs: 8 %

Source: SAMHSA/CDC

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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.

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Studies on Medicinal Cannabis Effects: Meta-Analysis Whiting et al (2015) meta-analysis • # RCTs # Reports # Patients Moderate-quality evidence to support the use of 28Chronic Pain 63 2454 cannabinoids in: – 28Nausea and vomiting due to chemotherapy 37 1772 chronic pain – 14Spasticity due to multiple sclerosis/paraplegia 33 2280 spasticity 4HIV/AIDS 4 255 • Low-quality evidence suggesting that 2Sleep Disorder 5 54 cannabinoids were associated with 2Psychosis 9 91 improvements in: – 2Tourette syndrome 7 36 nausea and vomiting due to chemotherapy – 1Anxiety disorder 1 24 weight gain in HIV infection – 1Glaucoma 1 6 sleep disorders Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Metaanalysis. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic Review and Metaanalysis. JAMA. 313:2456-2473, 2015 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

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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 34% of Canadian centers consider marijuana as a some states? contraindication to transplantation, compared with 70% of US centers 30

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Marijuana users have similar Marijuana Policy for Liver Transplant 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

Ranney et al 31

Marijuana Use Is Not Associated With Progression Marijuana Use Does Not Predict Outcomes to Advanced Liver Fibrosis in HIV/HCV coinfected On The Liver Transplant Waitlist Women • Retrospective cohort of adults evaluated for

575 women 1.00 Median of 11 years transplant from 1/2012 to 12/2013 at UCSF

56% no THC use 0.80 25% < weekly use • 884 adults evaluated and 585 (66%) were 12% weekly use 0.60 7% daily use listed 0.40 • Median follow up of 1.4 years 0.20 Probability of Advanced Fibrosis Advanced of Probability

0.00 • Prevalence of marijuana use was 48% 0 2 4 6 8 10 12 14 16 18 Time since study entry (years) Number at risk • 7% being current users and 41% prior users potcat_aprigte15xxxxxxxxxxxxxxx = Non-User 142 93 70 54 39 31 24 16 14 1 potcat_aprigte15xxxxxxxxxxxxxxx = < Weekly 54 45 33 27 20 17 11 9 7 0 potcat_aprigte15xxxxxxxxxxxxxx = >= Weekly 87 72 64 56 40 31 22 17 14 1 Non-User < Weekly >= Weekly

Slide provided by Dr. Kelly Kelly, EM et al. Clin Infect Dis 2016. Kotwani et al. AASLD abstract accpeted 2016.

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Marijuana Use Does Not Predict Outcomes Recreational Marijuana Use Is Not On The Liver Transplant Waitlist Associated With Worse Outcomes After Renal Transplantation

KM survival estimate for time to death/delisting on the liver transplant waitlist (N=585) Greenan G et al. Clinic Transplant 2016. Kotwani et al. AASLD abstract accepted 2016.

What Should be Your Transplant Center UCSF Liver Transplant Policy in 2015 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!

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Lets Clear the Smoke How We Do We Move Forward?

• Seven states prohibit denying transplant to • Need separate policies on medicinal use versus medical marijuana users solely based on their use recreational of the drug • Large scale clinical trials, administered via several • Very little evidence shows that marijuana predicts routes worse transplant outcomes • Need to re-schedule class of marijuana , need • Transplant professionals should attempt to regulated dispensaries and pharmacies determine whether marijuana use negatively • We cannot make decisions about transplant on case impacts a patient’s life and how it may influence reports behavior or mask mental health issues

Future Studies Thank You

• , San Diego - Center “ Learn from yesterday, live for today, hope for for Medicinal Cannabis Research (CMCR) tomorrow. The important thing is not to stop questioning.” • 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

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