Neurobiology of ADOLESCENT SUBSTANCE USE
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Neurobiology for Non-NeurobiologistsMedical Director Akron
Children’s Hospital Addiction Service Program
Medical Director Silver Maple Recovery in Lorain, Oh
Medical Director Prosperity Haven in Chardon, Oh
Medical Director Footprints to Recovery in Elgin, Il
Acknowledgements
Julie Lunstead, MPH, Boston Children’s Hospital
Lily Rabinow, MS, University of Massachusetts School of
Medicine
Louise Breen, BA, Boston Children’s Hospital
Aria Wiseblatt, BA, Boston Children’s Hospital
The creation of these curriculum materials was supported in part by
the Substance Abuse and Mental Health Services Administration
(SAMHSA), Grant #TI025389
Acknowledgements
PARTNER is a member of CO*RE, a collaboration of 13 organizations
representing more than 730,000 clinicians. CO*RE is dedicated to
providing effective clinical education in the areas of opioids,
substance use, pain and addiction. www.core-rems.org
The Hilton Foundation was created in 1944 by international business
pioneer Conrad N. Hilton, who founded Hilton Hotels and left his
fortune to help the world’s disadvantaged and vulnerable people.
The Foundation currently conducts strategic initiatives in six
priority areas including preventing substance use.
www.hiltonfoundation.org
Acknowledgements David Bazzo, MD Professor of Family Medicine,
University of California San Diego
School of Medicine Marc Fishman, MD Medical Director, Maryland
Treatment Centers Assistant Professor,
Johns Hopkins University Department of Psychiatry, Clinical Expert
Nancy Campbell-Heider, PhD, FNP, NP-C, CARN-AP, FAANP
Associate Professor of Nursing, SUNY Buffalo, Clinical Expert,
International Academy of Addiction Nurses Fellow
Marla Kushner, DO, FASAM, FSAHM
Medical Director of New Hope Recovery Center, Chicago, Clinical
Expert
Karen Sweeney, PA-C, MHSJFK Community Behavioral Health Center,
Philadelphia, Clinical Expert
Cynthia Kear, CHCP, MDiv Senior Vice President, California Academy
of Family Physicians Anne Norman, DNP, APRN, FNP-BC
Associate Vice President of Education, American Association of
Nurse Practitioners
Marie-Michèle Léger, MPH, PA-C
Director, Clinical Education, American Academy of Physician
Assistants
Robin Heyden Heyden Ty, LLC Jerri Davis, CHCP Director, Continuing
Professional Development, California Academy
of Family Physicians Penny Mills, MBA Executive Vice President and
CEO, American Society of Addiction
Medicine Arlene Deverman, CAE, CFRE
Chief Learning Officer, American Society of Addiction
Medicine
Jennifer Butchart Coordinator, Professional Development, American
Society of Addiction Medicine
Stephanie Townsell, MPH Public Health Director, Department of
Research and Development, American Osteopathic Association
Thomas McKeithen, Jr, BS, MBA and Chris Larrison
Partners, Healthcare Performance Consulting, Inc.
All staff from Partners (AANP, AAPA, AOA, CAFP, ASAM, HPC) have no
relevant financial
Learning Objectives
To gain a comprehensive understanding general neurobiology and
neurobiology of adolescent brain development
Short Definition of Addiction:
Addiction is a primary, chronic disease of brain reward,
motivation, memory and related circuitry. Dysfunction in these
circuits leads to characteristic biological, psychological, social
and spiritual manifestations. This is reflected in an individual
pathologically pursuing reward and/or relief by substance use and
other behaviors.
Addiction is characterized by inability to consistently abstain,
impairment in behavioral control, craving, diminished recognition
of significant problems with one’s behaviors and interpersonal
relationships, and a dysfunctional emotional response. Like other
chronic diseases, addiction often involves cycles of relapse and
remission. Without treatment or engagement in recovery activities,
addiction is progressive and can result in disability or premature
death.
Relapse 1. Stress 2. Trigger (CUE) 3. Exposure (primer)
Click to add text
Alcohol GABA Glutamate*
Amphetamine &Cocaine Dopamine
Benzodiazepines & GHB GABA
PCP and Ketamine Glutamate*
*Drug of abuse acts on antagonist at NMDA subtype of
glutamate
DUMB LOVE
marijuana nucleus accumbens
Stages of the Addiction
Cycle.During intoxication, drug-induced activation of the brain’s
reward regions (in blue) is enhanced by conditioned cues in areas
of increased sensitization (in green). During withdrawal, the
activation of brain regions involved in emotions (in pink) results
in negative mood and enhanced sensitivity to stress. During
preoccupation, the decreased function of the prefrontal cortex
leads to an inability to balance the strong desire for the drug
with the will to abstain, which triggers relapse and reinitiates
the cycle of addiction. The compromised neurocircuitry reflects the
disruption of the dopamine and glutamate systems and the
stress-control systems of the brain, which are affected by
corticotropin- releasing factor and dynorphin. The behaviors during
the three stages of addiction change as a person transitions from
drug experimentation to addiction as a function of the progressive
neuroadaptations that occur in the brain.
Neurobiologic Advances from the Brain Disease Model of Addiction
Volkow ND et al, N Engl J Med 2016; 374:363-371
Source: US News & World Report, 2005
“Adolescents Are Not Little Adults”
Cerebellum Occipital
Toddler milestones: balance, walking, coordination Preschool
milestones:
emotional regulation School age milestones: achievement
Adolescent milestones: impulse control
Brain Weight by Age
Source: Dekaban AS, Sadowsky D. Changes in brain weights during the
span of human life: Relation of brain weights to body heights and
body weights. Ann Neurol. 1978;4(4):345- 356.
N ew
bo rn
Synaptic Pruning
Drawing supplied by H.T. Chugani. In: Shore R. Rethinking the
Brain: New Insights into Early Development. New York, NY: Families
and Work Institute; 1997.
Myelination
Brain Maturation
Source: Gogtay N, Giedd JN, Lusk L, et al. Dynamic mapping of human
cortical development during childhood through early adulthood. Proc
Natl Acad Sci U S A. 2004;101(21):8174-8179.
Casey BJ, et al., Development Reviews. 2008; 28: 62-77.
Nucleus Accumbens
Prefrontal Cortex
Children, ages 7-11 Teens, ages 13-17 Adults, ages 23-29
Source: Galvan A, Hare TA, Parra CE, et al. Earlier development of
the accumbens relative to orbitofrontal cortex might underlie
risk-taking behavior in adolescents. J Neurosci.
2006;26(25):6885-6892.
Adolescents are developmentally primed to seek big rewards
3.2%
7.4%
4.4%
0.5%
0%
2%
4%
6%
8%
10%
12%
Age
Percentage of Past Year Initiates (among persons at risk for
initiation)
12-13
14-15
Source: Sircar R, Sircar D. Adolescent Rats Exposed to Repeated
Ethanol Treatment Show Lingering Behavioral Impairments. Alcohol
Clin Exp Res. 2005;29(8):1402- 1410.
Intoxicated Adult Rat Swimming Speed
Time to Platform
Source: Sircar R, Sircar D. Adolescent Rats Exposed to Repeated
Ethanol Treatment Show Lingering Behavioral Impairments. Alcohol
Clin Exp Res. 2005;29(8):1402-1410.
Intoxicated Adolescent Rat
Source: Sircar R, Sircar D. Adolescent Rats Exposed to Repeated
Ethanol Treatment Show Lingering Behavioral Impairments. Alcohol
Clin Exp Res. 2005;29(8):1402-1410.
Hippocampal Size by MRI
Source: Nagel BJ, Schweinsburg AD, Phan V, Tapert SF. Reduced
hippocampal volume among adolescents with alcohol use disorders
without psychiatric comorbidity. Psychiatry Res.
2005;139(3):181-190.
P<.05
THC reduces hippocampal neuron activation
With chronic THC exposure, neurons are gradually lost due to
continual suppression
• THC users have smaller hippocampuses, and poorer memory
Source: Iversen L. How cannabis works in the brain. In: Castle D,
Murray R, eds. Marijuana and Madness: Psychiatry and Neurobiology.
Cambridge, United Kingdom: Cambridge University Press;
2004:19-40.
Impact of chronic THC exposure
Never used
• 99.8 to 100.6
•“Mj dependent 3+ yrs” • 99.7 to 93.9
Source: Meier MH, Caspi A, Ambler A, et al. Persistent cannabis
users show neuropsychological decline from childhood to midlife.
Proc Natl Acad Sci U S A. 2012;109(40):E2657-64.
Source: Arnone D, Barrick TR, Chengappa S et al. (2008). Corpus
callosum damage in heavy marijuana use: Preliminary evidence from
diffusion tensor tractography and tract-based spatial statistics.
Neuro Image 41:1067-1074.
Healthy non-user Daily MJ user
Psychosis
Albaugh MD, Ottino-Gonzalez J, Sidwell A, et al. Association of
Cannabis Use During Adolescence With Neurodevelopment. JAMA
Psychiatry. 2021;78(9):1031–1040.
doi:10.1001/jamapsychiatry.2021.1258
Regular marijuana use during adolescence found to increase risk 2
to 5 times of developing psychosis, schizophrenia, anxiety, and
depression in adulthood.
1. Griffith-Lendering, M. F., Wigman, J. T., Prince van Leeuwen,
A., Huijbregts, S. C., Huizink, A. C., Ormel, J.ollebergh, W. A.
(2013). Cannabis use and vulnerability for psychosis in early
adolescence-a TRAILS study. Addiction, 108(4), 733-740.
2. Manrique-Garcia, E., Zammit, S., Dalman, C., Hemmingsson, T.,
& Allebeck, P. (2012). Cannabis use and depression: a
longitudinal study of a national cohort of Swedish conscripts.
[Research Support, Non-U.S. Gov't]. BMC Psychiatry, 12, 112.
3.
3. Fairman, B. J., & Anthony, J. C. (2012). Are early-onset
cannabis smokers at an increased risk of depression spells? J
Affect Disord, 138(1-2), 54-62. 4. Patton GC, Coffey C, Carlin JB,
Degenhardt L, Lynskey M, Hall W. Cannabis use and mental health in
young people: cohort study. BMJ 2002;325:1195-1198
Adolescents Are Vulnerable
Early substance use = high risk addiction Adolescent immaturity
during critical development period
= vulnerability • Impulsiveness and excitement seeking • Difficulty
delaying
gratification • Poor executive
function and inhibitory control
Image Source: PNAS 101:8174–8179, ©2004 National Academy of
Sciences, U.S.A.
National Survey on Drug Use and Health
0
10
20
30
40
50
60
47 45
38 32
er
Sources: Hingson RW, Heeren T, Winter MR. Age at drinking onset and
alcohol dependence: Age at onset, duration, and severity. Arch
Pediatr Adolesc Med. 2006;160(7):739-746. Winters KC, Lee C-YS.
Likelihood of developing an alcohol and cannabis use disorder
during youth: association with recent use and age. Drug Alcohol
Depend. 2008;92(1-3):239-247.
0
5
10
15
20
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11 8
QUESTIONS
DISCLAIMER
Acknowledgements
Acknowledgements
Acknowledgements
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Most illicit drug use starts in adolescence
Alcohol
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