MARIJUANA IN DISCLOSURES PREGNANCY: • No financial disclosures Now that it is legal… June 7, 2018 42nd Annual Antepartum and Intrapartum Management

Lena H. Kim, MD MFM, Sutter Health, California Pacific Medical Center

LEARNING OBJECTIVES AUDIENCE RESPONSE QUESTION #1 What percentage of your pregnant patient population • Current trends in marijuana use uses marijuana? 44% • Marijuana history A. 0% – Marijuana legalization B. <10% • Medicinal use 26% C. 10-20% • Risks in pregnancy & lactation 19% D. >20% • Patient counseling 10% E. I don’t know 2%

% 0% 0 2 <10% 0- >20% 1

I don’t know MARIJUANA USE INCREASING WITH MARIJUANA FACTS LEGALIZATION • Cannabis plant • National Survey on Drug use and Health – Tetrahydrocannabinol (THC) – Trends in marijuana use 2002-2014 • 482 other compounds – Cross-sectional, nationally representative survey • ~65 other cannabinoids • Also known as cannabis, pot, weed… – In-person audio computer-assisted self-interviews • Most commonly used illicit drug • 200,510 reproductive age women – Smoke, vape, edible, extract – 5.3% pregnant (n=10,587) • Self-reported prevalence of use in pregnancy • Adjusted prevalence past-month use in pregnancy – 2-5% – Increased 62% • 15-28% in young, urban, low SES women • 2002 2.37% – 34-60% of users continue in pregnancy • 2014 3.85% Van Gelder et al. Drug Alcohol Depend 2010 Beatty et al. J Addict Res Ther 2012 Brown et al. JAMA 2017

PATIENT VIEWS OF MARIJUANA USE IN AUDIENCE RESPONSE QUESTION #2 PREGNANCY Do you think that marijuana use in pregnancy is • Cross-sectional convenience sample survey harmful? 58% – Women presenting for prenatal care – 306 women A. YES • 35% current use B. NO 23% – 96% reported use for nausea 14% – 34% planned to continue use in pregnancy C. MAYBE 6% • 70% acknowledged risks D. I don’t know – that’s why I am here • 62% cited risk as reason to cut back or quit E B YES NO Y .. A I. M hy w • 10% more likely to use in pregnancy if legalized s t’ ha t – w no k ’t n Mark et al. J Addict Med 2017 o I d MARIJUANA EFFECTS ORIGINS OF MARIJUANA

• CNS effects via cannabinoid receptor type 1 • Cannabis plant Central Asia • Euphoria “high” – Africa – Anxiety, paranoia, fear or panic – Europe • High potency (THC content) increasing • 1990 4% – The Americas • 2014 12% (some as high as 37%) • 500 BC herbal medicine • Heightened sensory perception – Asia – Impaired motor skills (MVA) – Decreased short term memory • 800 AD hashish • Increased appetite – Middle East & Asia

LEGAL STATUS OF MARIJUANA IN THE CRIMINALIZATION OF MARIJUANA UNITED STATES • 16th century cannabis cultivation in America • 1937 Marijuana Tax Act – Hemp fibers: textiles & rope – 1st Federal U.S. law to criminalize marijuana – VA, MA, CT required farmers to grow hemp – Excise tax on sale, possession, transfer of all hemp • Early 1900s recreational use introduced products • Criminalization of all but industrial uses of marijuana • 1931 cannabis outlawed in 29 states – 1st American jailed was a farmer – Prohibition 1920-1933 • Hemp needed throughout WWII • “Evil weed” – 1957 last hemp fields planted in Wisconsin WAR ON DRUGS MEDICAL MARIJUANA LEGALIZATION

• Controlled Substances Act of 1970 • The Compassionate Use Act of 1996 – Marijuana grouped with heroin & LSD – California 1st state to legalize medical marijuana – Schedule I drug • Current count of legal medical use • High potential for abuse – 29 states • 1972 “The Shafer Commission” ignored – District of Columbia – “Marijuana: A Signal of Misunderstanding” – U.S. territories – “Partial prohibition” • Guam – Lower penalties for small amounts of marijuana • Puerto Rico

RECREATIONAL MARIJUANA MEDICINAL MARIJUANA HISTORY

• 2012 Colorado & Washington 1st states to legalize • 1830s cannabis extracts in India recreational marijuana – Decrease abdominal pain/vomiting of cholera • As of January 2018 • Late 1800s in Europe & U.S. – 9 states – “Stomach problems” & other ailments • AK, CA, ME, MA • NV, VT, OR • 1985 FDA approved Marinol – District of Columbia – Cancer: chemotherapy related nausea • U.S. federal law • 2016 FDA approved Syndros – Still illegal – AIDS: appetite loss OTHER MEDICAL USES PREGNANCY & LACTATION

• Chronic pain management • THC small & highly lipophilic – Decrease narcotic dependence • Can’t overdose – Animal models – Neuropathic pain • Crosses the placenta – Migraines • Fetal plasma levels 10% of maternal • Multiple sclerosis muscle spasms – Found in breast milk • Childhood epilepsy (oil CBD >> THC) • 2.5% of maternal dose • Traumatic brain injury? – Long half-life 20-36hr (4-5d if chronic) • Bipolar disease? • Up to 30d to completely excrete • Alzheimer’s disease?

Baker et al. Obstet Gynecol 2018 Moir et al. Chem Res Toxicol 2008

TERATOGEN? ADVERSE PERINATAL OUTCOMES

• No clear association between marijuana and birth • Increased risk of low birth-weight defects – ≥Weekly use of marijuana increased risk – Timing of exposure in pregnancy not always known • 11.2% vs 6.7% • Marijuana exposure 1st month of pregnancy • RR 1.90 (95% CI 1.44-2.45) – Odds of anencephaly increased to 2.5 • Increased risk of IUFD – Possible confounding – RR 1.74 (95% CI 1.03-2.93) • Less folic acid supplementation – Not adjusted for tobacco use

Campolongo et al. Psychopharmacology (Berl) 2011 Warshak et al. J Perinatol 2015 Fergusson et al. BJOG 2002 Conner et al. Obstet Gynecol 2016 Ostrea et al. Pediatrics 1997 SPONTANEOUS PRETERM BIRTH EFFECTS OF FETAL EXPOSURE IN CHILDREN

• Majority of studies – no association • Impaired neurodevelopment • Adverse effects of smoking tobacco – Lower test scores – Possibly synergistic or additive effect • Visual problem solving • Visual-motor coordination • ≥ 1x Weekly use of marijuana increased risk • Visual analysis – 10.4% vs 5.7% • Decreased attention span – RR 2.04 (95% CI 1.32-3.17) • Behavioral problems – Aggression Ko et al. Drug Alcohol Depend 2018 Fried et al. Neurotoxicol Teratol 2003 Warshak et al. J Perinatol 2015 Chandler et al. Alcohol Clin Exp Res 1996 Conner Obstet Gynecol 2016 Goldschmidt et al. Neurotoxicol Teratol 2000 Chabarria et al. Am J Obstet Gynecol 2016

OTHER LONGTERM EFFECTS PROBLEMS WITH THE DATA

• Predictor of marijuana use by age 14 • Limited data • Depression, anxiety – Difficult to study an illegal drug • Many confounding exposures • Controversial effect on school performance – Polysubstance use – Middle SES children age 5-12 • Tobacco, alcohol, other drugs • No difference – Low SES – Urban, low SES • Malnutrition (folic acid) – Intimate partner violence • Poorer reading & spelling scores • Lower teacher-perceived school performance • Reporting & recall bias • Increasing potency over time Fried et al. Neurotoxicol Teratol 1997 Goldschmidt et al. Neurotoxicol Teratol 2004 Alhusen et al. J Pediatr 2013 van Gelder et al. Epidemiology 2009 Mehmedic et al. J Forensic Sci 2010 ACOG COMMITTEE OPINION #722 PATIENT CASE

“Because of concerns regarding impaired neurodevelopment, • 30yo G0 @10 weeks GA with a history of chronic as well as maternal and fetal exposure to the adverse effects of smoking, women who are pregnant or contemplating pain seeing you for a new OB visit. pregnancy should be encouraged to discontinue marijuana use.”

“There are insufficient data to evaluate the effects of marijuana use on infants during lactation and breastfeeding, and in the absence of such data, marijuana use is discouraged.”

Updated 9/22/17 (replaces #637, 7/2015)

PRENATAL CARE PATIENT CASE

• Universal screening for tobacco, alcohol, & drug use • 30yo G0 @10 weeks GA with a history of chronic including marijuana pain seeing you for a new OB visit. – Uses medical marijuana daily to control her pain – In the past, used narcotics • Was not always prescription PROVIDERS’ COUNSELING RESPONSES PATIENT COUNSELING

• Content analysis of audio-recordings • Reassure your patient – 468 patient-health care provider 1st prenatal visits – Screening is NOT to punish or prosecute • 90 (19%) of patients disclosed marijuana use – Screening IS to identify, educate, help – 48% of the time, providers did not counsel • Discuss with your patient • 86% of tobacco use disclosure  counseling – Potential adverse health consequences • 47 counseling results – 33 punitive (urine tox screening, CPS) • Shared decision-making – 34 supportive – Marijuana less risk than illegal narcotics? – 26 medical counseling of risks – Other medical options

Holland et al. Obstet Gynecol 2016

KEY REFERENCES THANK YOU

• ACOG Committee Opinion #722 – Updated 9/22/17, replaces #637 from 7/2015

• Chabarria KC, Racusin DA, Antony KM, Kahr M, Suter MA, Mastrobattista JM, et al. Marijuana use and its effects on pregnancy. Am J Obstet Gynecol 2016;215:506.e1-7

• Conner SN, Bedell V, Lipsey K, Macones GA, Cahill AG, Tuuli MG. Maternal marijuana use and adverse neonatal outcomes: a systematic review and meta-analysis. Obstet Gynecol 2016; 128:713-23

• Metz TD, Stickrath EH. Marijuana use in pregnancy and lactation: a review of the evidence. Am J Obstet Gynecol. 2015 Dec;213(6):761-78.