Legalized Marijuana in Oregon: A Primer for Clinicians

Katrina Hedberg, MD, MPH Health Officer & State Epidemiologist History • Originated Central Asia • 3000 BC: Chinese Emperor Shen Nung • Ancient Greeks and Romans familiar with cannabis • 1840’s: Dr. WB O’Shaughnessy, a surgeon working for the British East India Company • 1800’s: Hemp grown in US by President Washington • 1937: US marijuana tax law making it illegal

Oregon Public Health Division 2 Marijuana: US Legal Status

US DEA Controlled Substances Act Schedule 1 • High potential for abuse • No currently accepted medical use in US (federal level); clinical trials lacking

2018: State Laws • 30 States Medical MJ • 9 recreational

Oregon Public Health Division 3 Oregon Medical Marijuana Act

• December 1998: Oregon voters approved Ballot Measure 67 • Allows medical use of marijuana (for specific conditions) • Established a state-controlled permit system (the OMMP) • Protects patients and doctors from penalties

Oregon Public Health Division 4 Marijuana Sales in Oregon

• Jan 2014: Oregon Legislature approved Medical Marijuana Dispensaries (OHA regulates) • July 2015: recreational marijuana became legal • Oct 2015: early sales of retail marijuana allowed at medical dispensaries • Oct 2016: retail marijuana stores open (OLCC regulates)

Oregon Public Health Division 5 Objectives

• Be familiar with cannabis, cannabinoids, and medical conditions for which scientific evidence supports effectiveness.

• Describe elements of Oregon’s clinical guidelines for physicians when recommending use of medical marijuana.

• Understand data on current marijuana use, attitudes and adverse health effects in Oregon.

Oregon Public Health Division 6 Overview • Marijuana – Plant, active compounds, health effects • Health effects – Therapeutic & adverse • Oregon Medical Marijuana Program • Oregon clinical guidelines • Public Health role – Monitoring use and adverse health effects – Protecting health: youth prevention; serving size, packaging, labeling; testing

Oregon Public Health Division 7 MARIJUANA: THE PLANT What is Marijuana? • Cannabis (genus) sativa, indica (species) • Primary active compounds: – Delta-9-tetrahydrocannabinol (THC): psychoactive – Cannabidiol (CBD): pain, neurologic effects • Other cannabinoids: unclear effects • Strains contain differing amts of THC, CBD • FDA-approved medications – Marinol® (dronabinol): pharmaceutical THC – Epidiolex® (cannabidiol): CBD

Oregon Public Health Division 9 Endo-cannabinoid system • Humans and animals naturally synthesize endo-cannabinoids • Lipid structure • Local action: cell-to-cell signaling • Receptors: • CB1 primarily on presynaptic neurons to inhibit neurotransmitter release

• CB2 primarily on immune cells, periphery and microglia

Oregon Public Health Division 10 J Pharmacol Exp Ther 358:580–587, September 2016 Opioid and Cannabinoid receptors

Endogenous opioid and cannabinoid systems are located in the brain, spinal cord & periphery (all levels of pain control)

Oregon Public Health Division 11 Why do people use cannabis? • Different effects, depending on strain, and concentrations of THC & CBD • Recreational: psychoactive, euphoria, “high”, relaxation • Treat symptoms / health conditions: pain, nausea, insomnia, anxiety

• Retail patients may want the “high” OR the medicinal effects • Medical marijuana patients may want medicinal effects but ALSO psychoactive properties

Oregon Public Health Division 12 How used? • Key components: seeds, stem, flowers, leaves • Smoked (cigarettes, pipes, water pipes) • Ingested (cookies, brownies, tea) • Vaporized, or heated (e-cigs, dab) • Trans-dermal (lotions, balms, patches) • Other…

Oregon Public Health Division 13 THERAPEUTIC EFFECTS Scientific Evidence Review National Academies of Sciences, Engineering & Medicine (1982, 1999) 2017 • “The Health Effects of Cannabis and Cannabinoids”

Note: Most studies observational since cannabis is Schedule 1 substance & no clinical trials allowed in US.

Oregon Public Health Division 15 NAS Report of Effectiveness • Conclusive evidence: • Chronic pain in adults • Antiemetic for chemotherapy induced nausea • Spasticity symptoms in multiple sclerosis • Moderate evidence: • Short-term sleep disturbance associated with pain, MS • Limited evidence: • Increasing appetite assoc with HIV • Improving anxiety • Improving PTSD symptoms

Oregon Public Health Division 16 NAS Report of Effectiveness

• No evidence to support or refute treatment of: • Cancer • Cancer-induced anorexia • Irritable bowel syndrome • Epilepsy • Spinal cord injury, ALS • Huntington’s chorea, Parkinson’s disease • Substance use disorders • Mental health outcomes in patients with schizophrenia

Oregon Public Health Division 17 Limitations to Scientific Evidence • Most studies observational, not clinical trials • Lack scientific rigor: patient and control selection; variability in strains & active compounds (CBD, THC); unclear dosing; control for other treatments, etc • Manner of use varies (e.g. smoking, vaping, topical): bioavailability may vary, and side effects may be linked to “by-products” (e.g. particulate matter from smoke)

Oregon Public Health Division 18 ADVERSE HEALTH EFFECTS Acute Adverse Health Effects: Physical symptoms

• Increased heart rate • Increased blood pressure • Vasodilation • Red eyes • Hyperemesis

Oregon Public Health Division 20 Acute Adverse Effects: Cognitive

• Impaired short-term memory – difficulty with attention, learning and retaining information • Impaired motor co-ordination – e.g. driving skills • Altered judgment and perceptions of safety • High doses – paranoia and psychosis

Predicted by cannabis as a neuromodulator of CNS signaling largely reversible upon abstinence

Oregon Public Health Division 21 Chronic Adverse Health Effects: Physical • Lung damage: • Symptoms of bronchitis in habitual smokers similar to cigarette smokers • Increase in cough, sputum production, wheezing • Cardiovascular, cancer: unclear evidence • Developing brain: • Infants, youth, teens

Oregon Public Health Division 22 Chronic Adverse Effects: Psychiatric • Frequent use increases the likelihood of problematic use (1:10 develop cannabis use disorder) • Negative effect on pre-existing psychiatric illness risk • Dependency, withdrawal symptoms

Oregon Public Health Division 23 OREGON MEDICAL MARIJUANA PROGRAM Oregon Medical Marijuana Program

• Administer medical marijuana program – $20-$200 card application fee; $200 grow site fee – Fees reduced to SNAP, Medicaid, Supplemental Security Income (SSI), veterans • Administer facility program (dispensaries, processors, grow sites)

Oregon Public Health Division 25 Qualifying Medical Conditions

• Cancer • Glaucoma • A degenerative/pervasive neurological condition • HIV/AIDS • Post-traumatic stress disorder (PTSD) • A medical condition with: – Severe pain – Severe nausea – Seizures – Persistent muscle spasms (e.g. caused by multiple sclerosis)

Oregon Public Health Division 26 Medical marijuana applications by year 80000

70000

60000

50000

40000

30000

20000

10000

0 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Oregon Public Health Division 27 Medical Marijuana Conditions

100 90 80 70 60 50 40

Percent 30 20 10 0

Oregon Public Health Division 28 OREGON CLINICAL GUIDELINES Medical Marijuana Recommendation Guidelines (I)

• Ongoing evaluation & treatment annually – Change in condition – Response to therapy • Medical record documentation – Evaluation, history, physical, diagnosis, treatment – Presence of qualifying condition – Response to therapy

Oregon Public Health Division 30 Medical Marijuana Recommendation Guidelines (II)

• Patient evaluation – Health history, co-morbidities, substance use, medications, PDMP – Physical examination (done in person) • Treatment plan – Advice about all treatment options – Review risks and benefits of cannabis – Assess contraindications

Oregon Public Health Division 31 Medical Marijuana Recommendation Guidelines (III)

• Considerations for pediatric patients (informed consent) • Continuing education • Financial prohibitions • Concurrent use of marijuana and opioids – Focus on improving functional status and patient safety – Assess contraindications • Mechanism of delivery (no smoking!!!) & dosing

Oregon Public Health Division 32 Opioid guidelines & marijuana

• Marijuana use prevalent • Limited data on opioid–marijuana interactions • Clinicians: discuss / document use, reasons, amount • Follow emerging evidence for marijuana use to treat pain and best practices (prescribing guidelines) • Consideration of marijuana + opioids: focus on improving functional status, quality of life, safety • Assess for contraindications to concurrent use • Safe disposal of all controlled substances

Oregon Public Health Division 33 DATA ON USE & HEALTH EFFECTS Past month marijuana use among Oregon & US youth, 2012-2017

30%

25% 24% Oregon 11th Graders 21% 20% 20% 19% US 11th Graders 15%

Oregon 8th Graders 10% 9%

7% 7% 5% US 8th Graders 6%

0% 2012 2013 2014 2015 2016 2017

Sources: Oregon Student Wellness Survey; Oregon Healthy Teens Survey; Monitoring the Future Survey

Oregon Public Health Division 35 Marijuana use among adults by age group, 2002–2015

30%

26% 25% 22% 18-25 years Oregon

20% 18-25 years US 20%

15% 17%

11% 10% 7% >25 years Oregon 7% 5%

4% >25 years US 0% 2002–03 2006–07 2010–11 2014-15

Year Oregon Public Health Division 36 Method of Marijuana Use Oregon, 2016 90%

80%

70%

60%

50%

40%

30%

20%

10%

0% Smoked Ate Vaped Dabbed Multiple

Oregon Public Health Division 37 Marijuana-related calls to Oregon Poison Center

140 Early retail sales begin (October 2015)) 116 120

100

80 Measure 91 passed (November 2014) 66 60

40

20 15 0 2013-Q1 2013-Q3 2014-Q1 2014-Q3 2015-Q1 2015-Q3 2016-Q1 2016-Q3 2017-Q1 2017-Q3

Oregon Public Health Division 38 PUBLIC HEALTH ROLE: PROTECTION Protecting the Public’s Health

– Health messaging / public education – Protecting children / vulnerable populations from accidental exposures and adverse effects – Preventing youth initiation and use – Minimizing risks of marijuana products on market

Oregon Public Health Division 40 Limiting accidental exposures/ adverse effects

• Concentration/ Serving Size (potency) • Packaging (OLCC) • Labeling (OLCC) • Advertising • Testing rules re: potency, contaminants

Oregon Public Health Division 41 Warning Labels On All Products

• For use only by adults 21 and older. Keep out of reach of children. • Medical grade if applicable • Product not approved by FDA to treat, cure, or prevent any disease. • It is illegal to drive a motor vehicle while under the influence of marijuana. • Handout for breast feeding / pregnant women

Oregon Public Health Division 42 Marijuana as medicine… general considerations

• Advances in endocannabinoid research for medical uses of cannabis are “dampened” by psychoactive effects of THC • Evidence (controlled, randomized clinical trials) to support therapeutic efficacy and safety of medical marijuana is mostly lacking (2018: four drugs FDA- approved)

Oregon Public Health Division 43 …continued

• Oregonians are using non-pharmaceutical grade products (e.g. lack quality control, batch variation, unclear dosing, patient counseling from “bud tenders” without medical training) • Adequate bioavailability may be difficult with herbal products on retail market

Oregon Public Health Division 44 Conclusion As societal discussions around health effects of marijuana evolve, it is important to ground these discussions in facts: what is known, and what gaps exist in knowledge of potential benefits and risks.

Oregon Public Health Division 45 Questions?

Oregon Public Health Division 46