COGNITIVE RAMIFICATIONS OF ADOLESCENT CANNABIS USE Randi Schuster

COGNITIVE RAMIFICATIONS OF ADOLESCENT CANNABIS USE Randi Schuster, Ph. D. Massachusetts General Hospital Harvard Medical School © AMSP 2016 1

Before we get started, a disclaimer… © AMSP 2016 2

JM: Background • Demographics: – 18 yo, Male • Academic: – 2 nd yr college student – “A” student in high school – “B/C” student in college – “…nothing sticks anymore” • Psychiatric: – No hx of tx – Current major depressive episode © AMSP 2016 3

JM: Substance Use • No illegal drugs, but cannabis (MJ) • Drank ≤ 1 day/week, ≤ 3 drinks/occasion • MJ use – Regular use (>1 x/wk) age 15 – Currently smokes 2 x/day; ~1 -2 grams/day – MJ Dx (DSM-IV dependence) – THCCOOH levels >500 ng/m. L – “I don’t like to think. MJ quiets my brain. ” © AMSP 2016 4

JM: Δ After 30 d of Abstinence • Substance use – No change in alcohol use – THC levels undetectable THCCOOH (ng/m. L) 600 500 400 300 200 100 0 Baseline 30 Days © AMSP 2016 5

JM: Δ After 30 d of Abstinence • Psychiatric – Improvement in mood – “Doc! I had such a #$&%#$ day. I wanted to burn one so bad. You would be proud--I mowed my backyard instead! It kind of made me feel better. ” © AMSP 2016 6

JM: Δ With Abstinence, contd. • Cognitive – ↑ attention – ↑ executive functions 450 200 Reaction Time 430 190 410 180 390 170 370 160 350 150 Baseline Reaction Time Variability Baseline 30 Days © AMSP 2016 30 Days 7

Lecture: Adolescent MJ Use • MJ background • Rates of adolescent MJ use • Psychosocial consequences of use • Brain development and relevance to MJ use • Cognitive consequences of early MJ use © AMSP 2016 8

Lecture: Adolescent MJ Use • MJ background • Rates of adolescent MJ use • Psychosocial consequences of use • Brain development and relevance to MJ use • Cognitive consequences of early MJ use © AMSP 2016 9

MJ • Cannabis sativa or Cannabis indica – Subspecies of hemp plant – Common throughout world • Dry, shredded leaves, flowers, stems, and seeds • >400 chemical compounds © AMSP 2016 10

How is MJ Used? SMOKED VAPORIZED EATEN/DRUNK Smoked in a pipe, bowl, cigarette Inhaled through machine that converts active compounds into inhalable form Consumed as ingredient in baked goods, candies, sodas Rapid effects Takes time to reach brain, so effects are delayed Rapid effects © AMSP 2016 11

Changing Tide on MJ • 4 states legalized MJ – Oregon – Washington – Alaska – Colorado – + D. C. • More expected in 2016 • Potential to: – ↓ barriers to access – ↑use further © AMSP 2016 12

Past vs. Present © AMSP 2016 13

Lecture: Adolescent MJ Use • MJ background • Rates of adolescent MJ use • Psychosocial consequences of use • Brain development and relevance to MJ use • Cognitive consequences of early MJ use © AMSP 2016 14

Rates of MJ Use Among Youth • Most likely drug tried by 8 th grade – After alcohol and cigarettes – 22 M people >12 yo past 30 d MJ users © AMSP 2016 15

Rates ↑ Across Adolescence • Ever tried – ~17% 8 th graders – ~50%12 th graders • Past year use – 12% 8 th graders – 35% 12 th graders • Current use (past month) – 7% 8 th graders – 21% 12 th graders – Surpasses current alcohol and tobacco use © AMSP 2016 16

↑ Potencies • In 1960 s-70 s potency ~1 -2% THC • Today, up to 20 -25% THC Tetrahydrocannabinol (THC) Active Ingredient in Marijuana © AMSP 2016 17

↓ Harm Perception • 36% of teens think MJ harmless • 43% favor legalization – 80 s: 15% – 90 s-00 s: 30% • Harm perception lowest in 40 yrs – Often precedes ↑ prevalence © AMSP 2016 18

Lecture: Adolescent MJ Use • MJ background • Rates of adolescent MJ use • Psychosocial consequences of use • Brain development and relevance to MJ use • Cognitive consequences of early MJ use © AMSP 2016 19

MJ Use Despite Consequences • 2. 5 M adolescents with MJ use disorder – ~11 x> cocaine – ~13 x> heroin • 355 k adolescents in tx for MJ – ~4 x > for cocaine – ~2 x > heroin 20 © AMSP 2016

↓Age of Onset → ↑ Dependence © AMSP 2016 21 Source: Substance Abuse and Mental Health Services Administration. (2010). Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of National Findings (Office of Applied Studies, NSDUH Series H-38 A, HHS Publication No. SMA 10 -4586 Findings). Rockville, MD.

Withdrawal Syndrome • Irritability • Appetite change • Sleeping difficulties • Physical symptoms • Craving • Anxiety – Fever – Headache – Shakiness – Muscle pain © AMSP 2016 22

“Consequences” of Use • Academic – High school dropout ~2 x > non-users – 4 x ↑ use if non-college-bound • Substance Use – Weekly use → 2 -3 x ↑ use drugs later – Daily use → ↓ cessation of other drugs • Psychiatric – ↑ Psychoses – ↑ Risk for anxiety or depressive disorder – ↑ Severity and duration of mood sxs © AMSP 2016 23

Lecture: Adolescent MJ Use • MJ background • Rates of adolescent MJ use • Psychosocial consequences of use • Brain development and relevance to MJ use • Cognitive consequences of early MJ use © AMSP 2016 24

Δ 9 -tetrahydrocannabinol (THC) • 1°psychoactive constituent • Endocannabinoid system – Brain development • Mimics anandamide – Dial down neuron activity – THC longer and stronger © AMSP 2016 25

THC Binding Sites © AMSP 2016 26

Adolescent Brain • CB 1 ↑↑↑ from infancy to age 30 • Most and latest change in areas of: – Reward and motivation – Cognition © AMSP 2016 27

Brain Differences with Early MJ • Size, shape and function of brain regions – Important for: • Reward and motivation • Cognition • Efficiency of inter-region connectivity © AMSP 2016 28

Lecture: Adolescent MJ Use • MJ background • Rates of adolescent MJ use • Psychosocial consequences of use • Brain development and relevance to MJ use • Cognitive consequences of early MJ use © AMSP 2016 29

Acute Cognitive Effects of MJ • Well-profiled – Paranoia – Attention and processing speed – Memory – Motivation • Increases with THC content © AMSP 2016 30

Last Beyond Acute Intoxication? • Weekend MJ → ↓ academics next week? • Withdrawal syndrome: ~2 wks • MJ alters receptors in brain: ~4 wks © AMSP 2016 31

Residual Cognitive Effects of MJ • Memory – Learning & retaining new information • Attention and concentration – Response speed & variability • Executive functioning – Working memory – Verbal fluency – Decision-making, risk-taking & inhibition © AMSP 2016 32

Earlier Use Is Worse • ↓ age of initiation → worse cognition – Attention – Executive functioning – Memory • ↑ abnormal brain structure and function © AMSP 2016 33

Learning among Early and Late Onset MJ Users Compared to Controls (CON) Schuster et al. , 2016 © AMSP 2016 34

But Likely Reversible with Abstinence • Biological markers normalize ~4 wks – CB receptor density in brain – Cortical blood volumes • Especially in areas important for cognition © AMSP 2016 35

Cognitive Deficit Resolution in Adults • Apparent after a few days of abstinence • Complete return-to-baseline by 30 days © AMSP 2016 36

Similar Recovery in Adolescents? • Contradictory and controversial findings – Some suggest no lasting deficits – Others find persistent deficits in 1+ domains – Most show at least partial recovery by 30 d • Recovery likely, though longer than adults © AMSP 2016 37

Preliminary Findings © AMSP 2016 38

Unanswered Questions • Pre-existing or consequences of use? • Time course of cognitive recovery? • Cause adverse functional outcomes? • Who is most affected? – Co-morbidities – Potency – Genetics © AMSP 2016 39

Conclusions • Rates of MJ use ↑ among adolescents • Brain development → ↑ vulnerability • Cognitive effects – Clear pattern of acute effects – Residual effects less clear, but concerning • Several areas for needed inquiry © AMSP 2016 40