JHanson 2019

Reefer Madness 1936 American propaganda film

Extolling risks of marijuana use in high school students Suicide, hallucinations, attempted rape, manslaughter

Film “rediscovered” in early 1970s and gained new life as an unintentional satire among advocates of cannabis reform.

“Turn on, tune out, don’t worry be happy.”

Marijuana in Pregnancy Mother Fetus Neonate Infant

Maternal Comments “It must be safe, it is legal.” “It is natural, not a drug.” “The internet says it is safe and can improve

developmental outcomes.” “Pot shops say it is safe and effective for treating

morning sickness.” “Better than methamphetamines, cocaine, or heroin.” “I will take the chance.”

Marijuana, the New Panacea Morning sickness Intractable childhood seizure disorders Autism spectrum disorders. “Good for what ails you, modern day equivalent of

epsom salts.” Pure mineral compound: magnesium and sulfate.

“A wonder drug in search of a disease!” JHanson

THC and Autism Spectrum Disorder Pediatrics, Vol 143, No 2, Feb 2019 Broad Diagnostic Category Complementary Health Approaches (CHA)

An array of modalities developed outside of or parallel to mainstream medicine

Specific vitamins, herbal supplements, mind/body practices (yoga), chelation therapy.

THC is newest CHA

THC, Autism, Questions Define exactly what child is receiving.

How much THC or CBD in current product? May be efficacious in a few selected cases of refractory

seizures What is the safety profile of THC and CBD? Recommendation for use of benzodiazepine (valium,

ativan) before THC. (behavioral health/psychiatry) Is the state legislature now determining who has

autism and appropriate treatment modalities based on a few testimonials?

Full Disclosure Never had prescriptive authority for medical

marijuana.

Do not own a pot shot or grow house.

Discussion not a comment on general use of marijuana.

Main Concern What is the effect on the developing brain?

Fetus

Neonate

Infant

Thinking About Cannabis Joseph P Cannavo, MD

Regional Service Chief, Addiction Treatment Services Divisional Value Advisor, Specialty Psychiatry Colorado Permanente Medical Group.

Marijuana Source: dried leaves/flowers of hemp plant: Cannabis

sativa. Active agreement: Tetrahydrocannabinol: THC Medical marijuana same as street marijuana. Back in the day

Pot, Hash, Hash Oil Getting up to date

Edibles, Waxes, Tinctures Increased potency

Mechanism of Action Interacts with all parts of the brain, a vast modulatory

network.

Endocannabinoid System: CNS, PNS, other physiological processes. Memory, Mood, Appetite and Energy, Balance, Pain

Sensation, Vision, Stress Responses, Reproduction, Sleep, Thermoregulation, Inflammatory/Immune Response.

Hazardous Cannabis Use Miracle Plant of Evil Weed?

Polarized debate.

Unlike alcohol: Use thresholds not well-defined.

Problematic pharmacokinetics

Is Cannabis Addictive? Chemical Reward>Pathology of

drive/reward>Addiction.

9% cannabis users become addicted.

16% when use begins in teens.

50% with daily use.

Cognition Divergent literature. Acute: Impaired learning, memory, attention and

executive function. Pharmacokinetics: Cannabinoids accumulate with

regular use. Heavy users: Impairment for days to weeks after

cessation.

Cognition: Children/Adolescents Not neurotoxic like alcohol.

Dunedin Cohort: 1037 New Zealanders: Birth to 38 yrs. Adolescents with heavy use: decrease 8 IQ points @ 38

yr. Hazard: Irreversible cognitive loss. Insidious life trajectory effect.

Role of genetics, environment?

Withdrawal Severity: Think nicotine

Common: Irritability, dysphoria, sleep difficulty, decreased appetite, restlessness. Dysphoria: anxiety, depression, restlessness

Less Common: physical symptoms: GI, tremors, sweating, fever, chills, headache.

Hazard: Sustained daily use: likely withdrawal.

Safety and Side Effects of THC in Children Pediatrics, Vol 143, N02, Feb 2019

Short Term Decrease in working memory, IQ, executive function,

sustained attention, motor coordination.

Long Term Altered brain development, addiction, poor educational

outcomes, diminished life achievement, increased risk for chronic psychosis disorder.

How Marijuana Harms a Developing Baby’s Brain Dana Smith; Scientific American: Nov 7, 2018 Previous research: infants exposed to cannabis inutero

50% likely to be low birth weight and premature. Society for Neuroscience: Nov 2018, 3 new studies

suggest prenatal cannabis exposure: serious consequences for fetal brain development.

Washington State University Study Newborn rat pups exposed to THC, similar to 2

joints/day took longer to learn new rule (pushing a lever for food).

Finally press correct lever x 2 then press wrong lever.

Auburn University THC exposed rat pups impaired on several different

memory tasks involving mazes.

University of Maryland School of Medicine Finding of impairments of memory and changes of

glutamate in brains of rats exposed to THC. Increased levels of kynurenic acid, decreased

glutamate levels with THC exposure. Kynurenic acid regulates glutamate and other

important neurochemicals. Glutamate: important neurochemical for brain growth

and neuronal electrical transmission.

Medicinal Effects? Clear “medicinal beneficial effects”, great potential for

cannabinoid therapeutics.

Chronic pain, nausea, wasting syndromes, spasticity, seizures, cancers, psychiatric.

Money Talks

By The Numbers: DP: Jan 2019CO Marijuana Sales Steamboat Marijuana tax

revenue 2014: $618 million 2015: $995 million 2016: $1.3 billion 2017: $1.5 billion 2018: $1.4 billion Total: $6 billion Total: $1 billion in marijuana

tax, licensing, and fee revenue

2015: $366,456 2016: $431,112 2017: $489,885 2018: $534,753 Total: $1,822,206

Magnitude of Problem Bob Troyer; former US Attorney Colorado: Denver Post

Commentary, 10/2018. CO youth use marijuana 85% higher than national av. Marijuana-related traffic fatalities: up 151%. Increased alcohol consumption, not decreased.

Denver Health Study 70% of 400 licensed pot shops surveyed recommend

pregnant women use marijuana to treat morning sickness, 35% state safe for baby.

Pediatrics: S.Ryan, 9/2018 Marijuana: most common recreational drug used by

pregnant and lactating women. Up to 36% of women report having used marijuana at

some point in pregnancy. 18% report using it while breastfeeding. Level of THC metabolites in breast milk was 8 times

higher than in mother’s plasma level.

Colorado Birth Statistics 2015 Total Births: 66,566 Potential neonates exposed to THC

36%: 23,963 (~24,000) Mothers that smoked during pregnancy:

6.4%: 4,217 6 times as many babies exposed to THC than nicotine.

THC Highly lipophilic Accumulates in fat-rich organs: brain. Accumulation of THC in brain tissue when growth is

greatest: 1st 2 yrs of life. Brain grows for 1st 20 years of life. THC can disrupt normal axonal growth and

development in growing human brain.

Most Important Question What are the short term and long term effects of

marijuana exposure in the developing fetus, newborn, and infant?

Note: there are no associated physical findings.

Questions asked in NICU Will my baby survive?

How long will my baby be in the hospital?

Will my baby be normal?

“What is normal?” JHanson

Factors that determine outcome Genes

Environment

Developmental Outcome Motor

Verbal

Cognition

THC use during pregnancy and while breastfeeding. Safety:

No known safe level of use. Increased risk of premature birth, low birth weight Increased risk of behavioral and learning complications. Neonates exposed to THC: may manifest:

Tremors in arms, legs, Poor eating coordination. Difficulty with weight gain. Delays in motor growth. Visual complications.

Is Marijuana safe while breastfeeding. No known safe level of use during breastfeeding. Benefits of breastfeeding

Maternal infant bonding Less obesity Decreased incidence of reactive airway disease (asthma) Improved developmental outcomes.

Value judgment: Breastfeeding with or without THC “Just say no.

Studied Outcomes No long term prospective studies regarding outcomes. Confounding variables.

Simultaneous exposure to other drugs: Methamphetamines Cocaine Opioids Cigarettes Ethanol

Dose effects

THC and morning sickness Morning sickness

Occurs: week 4-16 weeks Peak incidence 8-12 weeks Critical time for brain development.

Question Once morning sickness abates, does THC use persist?

Remember Thalidomide? Immunomodulatory drug 1957 marketed in West Germany Indications:

Anxiety, insomnia, gastritis, tension, morning sickness Teratogen

Phocomelia: malformed limbs 40% survival Deformed eyes, hearts, GI, GU tracts, blindness, deafness.

“The road to Hell is paved with good intentions.”

Admonition What long term effects do today’s therapies portend?

Denver Post: 1/24/2019. Use of TCH for autism spectrum disorder.

Pervasive Developmental Disorders and Autism Spectrum Disorders Autism Asperger’s Syndrome Rett’s Syndrome Childhood Disintegrative Disorder Pervasive Developmental Disorder

Value of anecdotal evidence History of medicine replete with anecdotal

testimonials.

Need to be tested in a prospective, randomized double-blinded cohort study as to efficacy, safety.

Long-term consequences Not known May take years to become apparent.

RMHC/PSL Experience ~10% - 12% THC exposure in premies admitted to

NICU. NICU

85 bed NICU, ~ 830 admissions/yr, 5 state referral region.

4% “opioid babies” Captive population: all neonates encouraged to use

breast milk. Donor premie milk if maternal THC use documented. 3 weeks off THC, before maternal milk used (pump and

dump).

Question What is the number of term neonates who are exposed

to THC?

Unknown.

Observation THC use crosses all socioeconomic classes.

Law Marijuana now legal for recreational use in Colorado. Child welfare laws are set by federal government. THC is a scheduled 1 substance (www.dea.gov). Exposing child to marijuana during pregnancy is

considered a reportable offense to county child welfare agencies.

Reality: These agencies overwhelmed with cases, THC is low priority.

Recommendations AAP

ACOG

CDC

All counsel against use of THC during pregnancy or breastfeeding.

Questions? Money talks, reason walks?

Effect on critical thinking ability?

Fact There is no benefit from marijuana exposure to the

developing brain of the fetus, newborn, or infant.

Anyone that says otherwise is either ignorant or not truthful.

Question Would any of you want your baby or grandbaby

exposed to marijuana?

Observation The marijuana dollars are addictive.

Future Actions Mandate that all pots shops have visible, accessible

information regarding risks of marijuana to pregnant mothers, babies, children.

Not a safe treatment for morning sickness.

Require this for state licensure for business.

Information is power.

Tell Your Children Alex Berenson: NYTimes reporter, author Tell Your Children The Truth About Marijuana, Mental

Illness, and Violence; Free Press, 2019 Wife, a psychiatrist who specializes in examining

mentally ill criminals.

Quote: The loveliest trick of the Devil is to persuade you that he does not exist. –C.P.Baudelaire, The Generous Gambler