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
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38 32
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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.
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QUESTIONS
DISCLAIMER
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Most illicit drug use starts in adolescence
Alcohol
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