Medical Marijuana: The “Need for Weed” Movement Might Like Getting High On Some Science

1. Medical Marijuana: The “Need for Weed” Movement Might Like Getting High On Some Science University of Michigan Substance Abuse Center Member Symposium September 16, 2011 Donald R. Vereen, M.D., M.P.H. Director Community Academic Engagement Prevention Research Center of Michigan School of Public Health University of Michigan Former Medical Officer and Special Assistant National Institutes of Health Former “Deputy Drug Czar” White House Office of National Drug Control Policy

2. TIMELINE OF MEDICAL MARIJUANA LEGISLATION California Proposition 215 November 1996 Washington State Ballot Initiative 692 November 1998 Oregon Measure 67 December 1998 Hawaii Senate Bill 862 December 2000 Maine Citizen Initiative Question 2 December 1999 Alaska Ballot Measure 8 March 1999 Colorado General Election Amendment 20 June 2001 Nevada Referendum Question 9 – October 2001 Vermont Senate Bill 76 July 2004 New Mexico Senate Bill 523 July 2007 Rhode Island Senate Bill 70 January 2006 Montana Initiative 148 November 2004

3. Michigan Medical Marihuana Act The Law • Approved by Michigan voters on November 4, 2008 by ballot initiative • TheMichigan Medical Marihuana Program (MMMP) is a state registry program within the Bureau of Health Professions at the Michigan Department of Licensing and Regulatory Affairs.

4. Michigan Medical Marihuana Act The Law • Program Statistics: • 181,303 original and renewal applications received since April 6, 2009. • 105,458 patient registrations issued. Sept 2, 2011 • The number of caregivers will be posted as soon as an accurate number can be obtained. • 19,705 applications denied -- most due to incomplete application or missing documentation.

5. Michigan Medical Marihuana Act The Law • Responsibilities of the MMMP • Review applications submitted by patients and caregivers wishing to participate in the MMMP and issue medical marihuana registration identification cards to those individuals whose applications are approved. • Maintain the confidentiality of program records in accordance with applicable state and federal confidentiality laws. • Collect and disseminate statistics about participation in the MMMP including, but not limited to: • Number of applications filed and approved. • Nature of the debilitating medical conditions of qualified patients. • Number of registration identification cards revoked. • Number of physicians providing written certifications for qualifying patients.

6. Michigan Medical Marihuana Act The Law • The people of the State of Michigan find and declare that: • National Academy of Sciences’ Institute of Medicine (IOM) report of 1999 has “found” / “discovered” beneficial uses of marihuana. • FBI’s Uniform Crime Reports show that nearly 99 out of 100 marihuana arrests occur under “state” law rather than “federal” law. Consequently, changing state law will have the practical effect of protecting from arrest the vast majority of seriously ill people who have a medical need for marihuana. • States are not required to enforce federal law which prohibits the use of marihuana except under very limited circumstances. Michigan joins 12 other states which do not penalize the medical use and cultivation of marihuana.

7. Michigan Medical Marihuana Act The Law • Protections: • A qualifying patient (diagnosed by a licensed physician as having a debilitating medical condition) who has been issued and possesses a registry identification card (a document issued by the MDCH that identifies a person as a registered qualifying patient or registered primary caregiver (a person at least 21 years old who has agreed to assist with a patient’s medical use of marihuana and who has never been convicted of a felony involving illegal drugs)) shall not be subject to arrest, prosecution, or penalty...for the medical use of marihuana in accordance with this act…may possess up to 2.5 ounces of usable marihuana, 12 marihuana plants kept in an enclosed, locked facility, and any incidental amount of seeds, stalks, and unusable roots.

8. Michigan Medical Marihuana Act The Law • Certification: • To be eligible for the Registry Identification Card one must: • Complete an application • Complete information about a ‘primary caregiver” – if applicable • Patient’s physician must complete and sign the Physician Certification Form and indicate the appropriate medical condition(s): CancerGlaucomaCachexia/Wasting Hepatitis CALSSevere/Chronic Pain Agitation of Alzheimer’sNail PatellaSevere nausea HIV/AIDS+Crohn’s DiseaseSeizures Severe Muscle Spasms

9. Institute for Behavior and Health (IBH) – March 18, 2011 • -based on American Society of Addiction Medicine • 1. Only seriously-ill patients who have exhausted other treatment options are permitted access • 2. These patients receive high quality care and supervision from their treating physicians • 3. Marijuana products are tested for quality and potency in licensed labs by qualified individuals • 4. Strict procedures are implemented from physician’s office to point of distribution and use by the intended patient to detect and deter marijuana abuse and diversion to thers in the community

10. CANNABIS KINETICS • Oral use • Psychoactive effects slowed to about one hour • Absorption is erratic • High is less intense, but lasts longer than if smoked • IV use • Water insoluble so cannot be injected

11. CANNABIS KINETICS • SMOKING three cannabis joints will cause you to inhale the same amount of toxic chemicals as one pack of cigarettes. • The French Consumer Institute tested regular Marlboro cigarettes alongside 280 specially rolled joints of cannabis leaves and resin in an artificial smoking machine. • The tests examined the content of the smoke for tar and carbon monoxide, as well as for the toxic chemicals nicotine, benzene and toluene. • Cannabis smoke contains seven times more tar and carbon monoxide. • Someone smoking a joint of cannabis resin rolled with tobacco will inhale twice the amount of benzene and three times as much toluene as if they were smoking a regular cigarette, the study said.

12. Overall problems of use • Mode of administration • No smoking in hospitals • No standard dose of smoked marijuana • Smoke is hazardous in and of itself • Smoking may impair immune system response • Difficulty concentrating on complex tasks • Slowed reaction times • Tolerance develops quickly • Effect is 4 - 6 hrs

13. CANNABINOIDS • There are two main receptors for cannabinoids in humans • CB1(in brain) if stimulated produces • Euphoria • Impaired short term memory and sense of time • CB2 (in spleen, peripheral sites) if stimulated produces • Immunosuppressant activity • Not psychoactive

14. Cannabinoid Receptors: • Cerebellum – body movement and coordination • Cortex – higher cognitive functions • Nucleus accumbens – reward, feeding and other appetitive behaviors • Basal ganglia – movement control • Hypothalamus – body temperature, salt and water balance, reproductive functions, analgesia, feeding behavior • Amygdala – emotional responses, fear • Hippocampus – learning and memory

15. Endocannabinoids (e.g. anandamide) constitute one of the first lines of defense against pain, the anatomical locus and the precise receptor mechanisms underlying cannabinergic modulation of pain are uncertain. Clinical exploitation of the system is severely hindered by the cognitive deficits, memory impairment, motor disturbances and psychotropic effects resulting from the central actions of cannabinoids. Agarwa, N., et al, Neurosci. 2007 Jul;10(7):870-9. Epub 2007 Jun 10.

16. Cannabidiol (CBD) non-psychoactive cannabinoid clinically demonstrated to have analgesic, antispasmodic, anxiolytic, antipsychotic, antinausea, and anti-rheumatoid arthritic properties. R. Mechoulam et al. 2003. Cannabidiol: an overview of some pharmacological aspects. Neuroscience Letters 346: 61-64;

17. The U.S. Food and Drug Administration (FDA) has given the green light to Valeant Pharmaceuticals International to bring the synthetic cannabinoid nabilone (Cesamet) back to market after 17 years. Nabilone, sold in Canada is similar to Marinol - was originally marketed by Eli Lilly and Co. but withdrawn from the market in 1989. It is now approved by the FDA for treatment of vomiting and nausea caused by chemotherapy and is listed as a Schedule II controlled substance.

18. Sativex • Whole plant medicinal cannabis extract • Produced by Bayer and GW pharmaceuticals and approved for use in Canada for multiple sclerosis and neuropathic pain (2005) • Contains THC and nabidiolex, not delta - THC • Phase 3 trials in multiple sclerosis patients showed that sublingual spray was safe and effective for symptom relief

19. Effects of Drugs on Dopamine Levels striatum frontal cortex hippocampus substantia nigra/VTA nucleus accumbens Mounts Intromissions Ejaculations COCAINE AMPHETAMINE Accumbens 1100 Dopamine Pathways Principal “Pleasure” System of the Brain Accumbens 400 1000 900 DA 800 DA 300 700 600 % of Basal Release 500 200 % of Basal Release 400 300 100 200 100 0 0 0 1 2 3 4 5 hr 0 1 2 3 4 5 hr Time After Amphetamine Time After Cocaine Source: Di Chiara and Imperato Natural Rewards Elevate Dopamine Levels FOOD SEX 200 200 NAc shell 150 150 100 100 15 % of Basal DA Output 10 Empty DA Concentration (% Baseline) 50 Copulation Frequency Box Feeding 5 0 0 Scr Scr Scr Scr 0 60 120 180 Bas Female 1 Present Female 2 Present 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Time (min) Sample Number Di Chiara et al. Fiorino and Phillips

20. Hipp NAcc VP Amyg Circuits Involved In Drug Abuse and Addiction CONTROL INHIBITORY CONTROL PFC ACG OFC SCC REWARD MOTIVATION/ DRIVE MEMORY/ LEARNING All of These Must Be Considered In Developing Strategies to Most Effectively Treat Addiction

22. Marijuana brain changes

23. Control Control CG STOP Saliency Saliency Drive Drive Drive OFC GO Saliency NAc Memory Memory Memory Amygdala Non-Addicted Brain Addicted Brain Adapted from: Volkow et al., J Clin Invest 111(10):1444-1451, 2003.

24. ADDICTION IS A DEVELOPMENTAL DISEASE starts in adolescence and childhood 1.6% 1.4% 1.2% 1.0% % in each age group who develop first-time cannabis use disorder 0.8% Brain areas where volumes are smaller in adolescents than young adults. 0.6% 0.4% Sowell, E.R. et al., Nature Neuroscience, 2: 859-861, 1999 0.2% 0.0% 5 10 15 18 25 30 35 40 45 50 55 60 65 70 Age Age at cannabis use disorder as per DSM IV NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003