Marijuana as Medicine: Unintended Consequences and Concerns David - PowerPoint PPT Presentation

Marijuana as Medicine: Unintended Consequences and Concerns David R. Reagan, MD PhD | Chief Medical Officer | September 13, 2017 Michael D. Warren, MD MPH | Deputy Commissioner for Population Health | September 13, 2017

Disclosures • David Reagan, MD PhD, has disclosed no actual, potential, or perceived conflicts of interest. • Michael Warren, MD MPH, has disclosed no actual, potential, or perceived conflicts of interest.

Objectives • Describe the current policy landscape related to the use of marijuana as medicine. • Identify the individual benefits associated with use of marijuana as medicine. • Outline the population harms associated with use of marijuana as medicine.

Background

Marijuana: The Basics • Produced from Cannabis sativa • DEA Schedule I Drug – No currently accepted use of whole plant • (There are FDA-approved meds) – High potential for abuse • Available (non-pharmaceutical grade) forms: – Cigarette/blunt/pipe/bong – Edibles – Tea/brew Image sources: 1. Cannabis plant: https://www.dea.gov/druginfo/ds.shtml 2. Cannabis and joint: NIDA, https://www.drugabuse.gov/publications/drugfacts/marijuana 3. Marijuana Cookie: By Subvertc - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=18683918

Marijuana: The Basics • Three main “types” • Determined by enzyme concentration • 0.5-15% THC • “Drug” type THC Type • 0.05-0.7% THC • Fiber / hemp / oil type CBD Type • 0.5-5% THC Hybrid type Source: National Academy of Sciences. https://www.nap.edu/catalog/24625/the-health-effects-of-cannabis-and-cannabinoids-the- current-state

Marijuana: The Basics Delta-9-tetrahydrocannabinol (  -9-THC) • – Compound responsible for psychoactive effects – Time to onset of effect and duration of effect depends on method of ingestion • Typical effects – Euphoria – Disinhibition, increased sociability – Enhanced sensory perception – Time distortion • Adverse effects – Typical: Impaired judgment, reduced coordination, dry mouth, anxiety, fear, distrust, panic – Others: cyclic vomiting, stress cardiomyopathy

Marijuana: The Basics • Even with approved medications, one person’s “desired effects” may be another person’s “adverse effects” Elation Some patients Adverse event experience “high” Laughing among 24% at Heightened anti-emetic dose Awareness and 8% at appetite stimulant dose Source: US Food and Drug Administration. Available at: https://www.fda.gov/ohrms/dockets/dockets/05n0479/05N-0479-emc0004-04.pdf

From opium poppy to oxycodone… Source for images: Drug Enforcement Administration Museum and Visitors Center. Available at: https://www.deamuseum.org/ccp/opium/history.html. Last accessed 04/13/2017.

From mold to penicillin tablets and liquid… Image sources: 1. Penicillin mold: https://commons.wikimedia.org/wiki/File:Penicillium_notatum.jpg. 2. Penicillin tablets: https://www.drugs.com/pro/penicillin-vk.html 3. Penicillin oral solution label: https://www.drugs.com/pro/penicillin-v.html

From foxglove to digitalis… Image sources: 1. Foxglove botanical print: By Walther Otto Müller - http://caliban.mpiz-koeln.mpg.de/koehler/DIGITALIS.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=1815791 2. Dioxin label: https://www.drugs.com/pro/digox-tablets.html 3. Digoxin tablets: https://www.drugs.com/digoxin.html

From marijuana to medicine… • Current FDA-approved cannabinoid- based medications – Dronabinol (Marinol) — synthetic THC • Nausea/vomiting in chemotherapy patients • Appetite stimulation in AIDS patients – Nabilone (Cesamet) — synthetic THC • Multiple sclerosis • Adjunctive analgesic in cancer patients • Pending approval – Epidiolex (>98% CBD) – Nabiximol (Sativex, 1:1 THC/CBD) • FDA approval and pharmaceutical-grade manufacturing process assures safety , efficacy , quality , and consistency

Marijuana Intoxication & Use Disorder Use/Intoxication Substance Use Disorder Mild: 2-3 Symptoms Moderate: 4-5 symptoms Severe: 6+ symptoms Withdrawal can occur after heavy/prolonged use Reversible Self-Harm Source: American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric Association, 2013.

A Common Pathway: Dopamine Many Drugs Lead to Dopamine Release • Amphetamines, Cocaine, Opioids, Nicotine, Sedatives, Marijuana, Ethanol With increased dopamine: • Dopamine receptors are decreased • Equilibrium is re-established • When dopamine decreases, the number of receptors remains less • Normal dopamine levels feel low • Takes months or years to restore normal balance MAO – Monoamine oxidase (inactivates DA) VMAT2 – Vesicular monoamine transporter 2 DAT – Dopamine uptake transporter D1 – D5 – Dopamine receptors

Current Policy Landscape

State Marijuana Laws: Current Landscape Source: National Conference of State Legislatures. Deep Dive: Marijuana. Available at: http://www.ncsl.org/bookstore/state- legislatures-magazine/marijuana-deep-dive.aspx. Last accessed 08/13/2017.

Current TN Laws • Tennessee Code Annotated § 39-17-402 – Defines “marijuana” – Does not include industrial hemp – Allowances for cannabidiol products as approved by FDA or in case of intractable seizures

Medical Marijuana: Public Health Concerns The population The individual harms of Medical benefits of marijuana as marijuana is not marijuana as medicine have a solution to the medicine have opioid crisis. been been overstated. understated.

Individual Benefits of Marijuana as Medicine

Marijuana: Individual Benefits OVERstated • Most comprehensive review to date by National Academy of Sciences in 2017 – 22 conclusions re: therapeutic benefits, only 3 with “substantial or conclusive evidence” of benefit • Spasticity due to multiple sclerosis • Chemotherapy-induced nausea/vomiting • Chronic [neuropathic] pain – 4 conclusions with substantial evidence of harm: • Worsening respiratory symptoms and frequent chronic bronchitis •  risk of motor vehicle crashes • Lower birth weight of offspring • Development of schizophrenia or other psychoses Image source: National Academy of Sciences. https://www.nap.edu/catalog/24625/the-health-effects-of-cannabis-and-cannabinoids- the-current-state

Marijuana: Individual Benefits OVERstated • Not a lack of information on this topic – What can be trusted? – Who benefits? • Quality of available information varies widely – Study type – Publication source – Peer review status Image source: Wake Forest School of Medicine. Available at: http://libguides.wakehealth.edu/EBP/Study. Last accessed 02/08/2017

Marijuana: Individual Benefits OVERstated Helen of Troy “The Face That Launched 1,000 Ships” Article: Porter J, Jick H. Addiction rare in patients treated with narcotics. New England Journal of Medicine. 1980; 302:123 Image: By Evelyn de Morgan - Secondary source: http://en.wikipedia.org/wiki/Image:Helen_of_Troy.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=160766

Marijuana: Individual Benefits OVERstated • Study funded by pharmaceutical company • “ Open- label”  not blinded, large potential for placebo effect • Patients had treatment-resistant epilepsy (e.g. Lennox-Gastaut and Dravet syndromes) • 12% of patients had adverse events related to cannabidiol • Conclusion: Need randomized controlled trial Devinski O et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurology. 2016; 15: 270-78.

Population Harms of Marijuana as Medicine

Marijuana: Population Harms UNDERstated Average Delta-9-THC concentration of DEA Specimens by Year, 1995-2014 Source: ElSohly MA, Mehmedic Z, Foster S, Gon C, Chandra S, Church JC. Changes in Cannabis Potency over the Last Two Decades (1995-2014) - Analysis of Current Data in the United States. Biological Psychiatry. 2016. April 1; 79(7): 613 – 619.

WA: Marijuana-related impaired driving Source: WA data and image: Washington State Marijuana Impact Report. Available at: https://hidtanmi.org/2016/07/01/northwest-hidta- washington-impact-report/. Last accessed 04/12/2017.

CO: Marijuana-related impaired driving Source: Rocky Mountain High Intensity Drug Trafficking Area. The Legalization of Marijuana in Colorado: The Impact. Volume 4, September 2016. Available at: http://www.rmhidta.org/html/2016 FINAL Legalization of Marijuana in Colorado The Impact.pdf. Last accessed 04/20/2017.

Marijuana: Population Harms UNDERstated Image sources: https://www.childrenscolorado.org/conditions-and-advice/marijuana-what-parents-need-to-know/resources/

Marijuana: Population Harms UNDERstated Sources: 1. Wang GS, Le Lait MC, Deakyne SJ, Bronstein AC, Bajaja L, Roosevelt G. Unintentional Pediatric Exposures to Marijuana in Colorado, 2009-2015. JAMA Pediatrics. 2016;170(9):e160971. 2. Wang GS, Roosevelt G, Heard K. Pediatric Marijuana Exposures in a Medical Marijuana State. JAMA Pediatrics. 2013;167(7):630-633.