Cannabis: Edibles Cannabinoids and the Adolescent Brain Cookies, - - PDF document

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Cannabinoids and the Adolescent Brain

Susan F. Tapert, Ph.D. University of California, San Diego

Overview

• Rates of marijuana use and disorders
• Does cannabis use affect the adolescent brain
• Education, prevention, and treatment

Cannabis: Smoking Joints, Bowls, Pipes

• Measure in grams per occasion
• 1 joint= .5 grams
• 1 blunt= 1-2 grams.
• 1 bowl=.25-.5 grams.

Bowl Joints Bong Blunts (+/- tobacco)

Cannabis: Edibles

• Cookies, brownies, candies…
• Measure in times used and mg of THC
• Standard “serving size” in Colorado is 10 mg

Hash & Concentrates

• Concentrated marijuana with high THC content
• Hash: purified cannabis resin
• ¼ ounce (7 grams) flowers=1 gram hash or oil.
• Typically sell in 1 gram units for around $35-70.
• Wax/Dabs: ~40mg; 1 gram has 25 40mg doses
• Kief: dry concentrate
• Water hash: bubble hash, solventless wax, ice wax
• C02 Oil: BHO (solvent extracted): wax, shatter, crumble, oil, honeycomb

Honeycomb Budder Wax Shatter Bubble hash

Synthetic Cannabinoids

• Fake weed, synthetics, herbal incense, Spice, K2

1 Gram K2

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Past Month Use of Intoxicants

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

8th grade 12th grade College Students

Monitoring the Future, 2017

Cannabis: Prevalence

• 34% of young adults (18-28) used in past year

– 28% of 10th graders – 13% of 8th graders – Little change in recent years for youth

• Dependence in ~9% of users
• 2nd highest reason for SUD treatment (1=alcohol)
• 12% users drove high in past 2 weeks

SAMHSA, National Surveys on Drug Use and Health, 2013 and 2014. Johnston et al., 2017. Monitoring the Future.

Perceived Risk of Harm

Monitoring the Future, 2017

% say regular MJ use is a “great risk”

20 40 60 80 100 1975 1982 1991 2002 2012 2016 Percentage Saying Great Risk

2016: 31%

Quick Brain Review!

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Gray & White Matter

Top view Side view

Adolescent Brain Development

Somerville, 2016, Neuron

Trajectories of cortical volume adjusting for total brain volume

(schematized from data in Ostby et al., 2009).

Age of asymptote for connectivity

(Dosenbach et al., 2010) and structural (Tamnes et al., 2010) development.

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Overview

• Rates of marijuana use and disorders
• Does cannabis use affect the adolescent brain
• Education, prevention, and treatment

Design of 3-Year Study

Baseline Year 3

NP Assessment MRI SCAN #1 (age ~17) Substance Use Mental Heath NP Assessment NP Assessment MRI SCAN #3 (age ~20) Substance Use Mental Heath NP Assessment 1. Groups defined by substance use patterns

• 2. All participants followed for 3 years

MRI SCAN #2 NP Assessment MRI SCAN #2 (age ~19) Substance Use Mental Heath NP Assessment

Year 1.5

R01 DA021182 (PI: Tapert)

Inclusion Criteria

• Age 15-18
• Right-handed
• Lifetime marijuana use:

– > 200 for “MJ Users” – < 5 for “Controls”

• < 150 lifetime drinks
• < 10 cigs/day
• < 30 lifetime other drugs

Participants (N=108)

IQ No FH of alcoholism Cigarettes/day Female Age (15-19)

*p<.05

Drinks/month <1 111 46% 35% 17.2 Light Drinkers 4 1 Lifetime MJ use 2 113 42% 37% 16.8 Heavy Drinkers 42* 11 2 109 45% 29% 17.7 MJ+Alc Users 44* 541*

Cognition in Abstinent Users (Age ~17)

17

• 1.0
• 0.5

0.0 0.5 1.0

z-score Controls (n=34) MJ+Alc Users (n=31)

Medina, Hanson, Schweinsburg, Cohen-Zion, Nagel, & Tapert, 2007

Neurocognitive Performance over 3 Years

2 4 6 8 10 12 14 Scaled Score

Logical Memory I

CON MJ

* *

20 22 24 26 28 30 Raw Score

Logical Memory Recognition

* * *

2 4 6 8 10 Scaled Score

Digit Span Backwards

* * *

*p<.05 Jacobus et al., 2015, Neuropsychology

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Neurocognition & Age of Onset

4 6 8 10 12 14 16 18 8 10 12 14 16 18 20

Scaled Scores MJ Age of Onset

TMT Number Sequencing

4 6 8 10 12 14 16 18 8 10 12 14 16 18 20

Scaled Scores MJ Age of Onset

TMT Letter Sequencing

4 6 8 10 12 14 16 18 8 10 12 14 16 18 20

Scaled Scores MJ Age of Onset

TMT Switching

4 6 8 10 12 14 16 18 8 10 12 14 16 18 20

Scaled Scores MJ Age of Onset

WAIS-III Digit Symbol Coding

r = .33-.44

Jacobus et al., 2015, Neuropsychology

MRI

• Safe

– Non-invasive – No radioactivity

• Issues

– Motion – Artifact

White Matter, Marijuana, & Alcohol (~Age 20)

0.47

0.3 0.4 0.5 0.6

Age 20

R Sup. Longitudinal Fasciculus

CON

BG BGMJ

*

MJ+ALC

0.3 0.4 0.5 0.6

Age 20

R Superior Corona Radiata

*

*p<.01

0.3 0.4 0.5 0.6

*

0.3 0.4 0.5 0.6

*

17yrs 19yrs 20 yrs 17yrs 19yrs 20 yrs

ALC

Fractional Anisotropy Jacobus et al., 2013, Psychiatry Research

• 1. Groups defined by substance use patterns
• 2. All were asked to stop all substance use

Design of 4-Week Study

Day 1 Day 28

SCAN #1 (age ~17) Substance Use Mental Heath NP Assessment SCAN #1 (age ~17) Substance Use Mental Heath NP Assessment SCAN #2 (age ~17) Substance Use Mental Heath NP Assessment SCAN #2 (age ~17) Substance Use Mental Heath NP Assessment

2x Weekly Urine Toxicology

P20 DA024194; Center PI: Mason, Subcontract PI: Tapert

Jacobus, Goldenberg, Wierenga, Tolentino, Liu, & Tapert, 2012, Psychopharm

50 55 60 65 70 75 80 85 Marijuana Users Controls 50 60 70 80 Baseline 28 Days

*

* Left Insula Medial Frontal Gyrus Brain blood flow after 28 days

• f monitored abstinence

Mean CBF (ml/100g/min)

*p<.01 ~Age 17 N=46

*

Arterial Spin Labeling Recovery with Abstinence

19 users 21 non-users

24

Verbal Memory Working Memory Attention

Hanson et al., 2010, Addict Behav

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Mood

Beck Depression Inventory-II

2 4 6 8 10 Day 1 Day 7 Day 14 Day 21 Day 28

Controls MJ Users

Jacobus et al., in preparation

Overview

• Rates of marijuana use and disorders
• Does cannabis use affect the adolescent brain
• Education, prevention, and treatment

Treatment

• Motivational Enhancement Therapy (MET) with

Cognitive Behavioral Therapy (CBT)

– Kaminer, Sampl, Kadden – https://store.samhsa.gov

• 5 45-75-minute sessions:

1. Motivation building 2. Goal setting 3. Marijuana refusal skills 4. Enhancing social support and pleasant activities 5. Planning for emergencies and coping

Funding Support: NIDA & NIAAA

• Youth at Risk: R01 AA013419 (Tapert)
• NCANDA:
• U01 AA021692 (Tapert)
• U01 AA021695 (Brown/Tapert)
• ABCD:
• U01 DA041089 (Tapert/Paulus)
• U24 DA041147 (Jernigan/Brown)

Tapert lab: Joanna Jacobus, PhD, Asst Prof Sonja Eberson, MA, Lab Manager MJ Meloy, PhD, Lead MR Techologist Norma Castro, MA, Project Coordinator Silvia Escobar, Project Coordinator Sarah Dowling, Project Coordinator Kara Bagot, MD, Asst Prof Postdoctoral fellows: Drs. Ty Brumback, Kelly Courtney, Alejandra Infante. Resident: Alejandro Meruelo, MD PhD Grad students: Tam Nguyen-Louie MA, April May, MS. RAs: Alyssa Lopez, Nadia Dorosti, Claudia Cota, Irene Li, Caroline Barnet, Evan Winiger, Vanessa Diaz. Lab alumni and collaborators: Alecia Dager, PhD, Yale Krista Lisdahl, PhD, UWM Bonnie Nagel, PhD, OHSU Lindsay Squeglia, PhD, MUSC Key UCSD collaborators: Sandra Brown PhD, Anders Dale PhD Terry Jernigan PhD, Martin Paulus MD Marc Schuckit MD, Alan Simmons PhD

THANK YOU!