Petros Levounis, MD, MAProfessor and Chair, Department of Psychiatry
Rutgers New Jersey Medical School
Community Opioid SymposiumWoman’s Foundation & Acadiana Area Human Services District
Lafayette, LouisianaFriday, November 8, 2019
The New Neurobiology of Addiction
I have no competing interests in this presentation.
Disclosures
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1. Identify the origins and current state of the opioid crisis in America.
2. Describe the basic elements of drive and cognition in the neurobiology of addiction.
3. Discuss the clinical use of pharmacotherapy and psychosocial interventions in the treatment of substance use disorders.
Learning Objectives
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4
1. The Basic Model2. Neurobiology3. New Neurobiological Concepts4. Treatments5. New Directions6. Conclusions
Outline
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1The Basic Model
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6
~ 1980
A Biopsychosocial Illness
Biological
Psychological
Social
Use Brain Switch
Addiction
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Olsen and Levounis, Sober Siblings, 2008.
Porter and Jick, N Engl J Med, January 10, 1980.
The Root Cause of the Disaster
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The False Promise
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Money and Influence
Catan and Perez, The Wall Street Journal, December 17, 2012.
Admissions: 1999 Primary non-heroin opioid admission rates (per 100,000)
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Admissions: 2001 Primary non-heroin opioid admission rates (per 100,000)
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Admissions: 2003 Primary non-heroin opioid admission rates (per 100,000)
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Admissions: 2005 Primary non-heroin opioid admission rates (per 100,000)
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Admissions: 2007 Primary non-heroin opioid admission rates (per 100,000)
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Admissions: 2009 Primary non-heroin opioid admission rates (per 100,000)
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Compton, New England Journal of Medicine, 2016.
From Pills to Heroin
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From Heroin to Fentanyl
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From Fentanyl to Carfentanil
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2Neurobiology
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0
50
100
150
200
0 60 120 180
Time (min)
% o
f Bas
al D
A O
utpu
t
Empty
Food Sex
Box Feeding
100
150
200
DA
Con
cent
ratio
n (%
Bas
elin
e)SampleNumber
1 2 3 4 5 6 7 8
Female Present
Natural Rewards
Adapted from: Di Chiara et al, Neuroscience, 1999Adapted from: Fiorino and Phillips, J Neuroscience, 1997
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22
0
100
200
300
400
0 1 2 3 4 5 hr
% o
f Bas
al R
elea
se
COCAINE
0
100
150
200
250
0 1 2 3 hr
% o
f Bas
al R
elea
se
NICOTINE
Adapted from: Di Chiara and Imperato, Proceedings of the National Academy of Sciences USA, 1988; courtesy of Nora D Volkow, MD
Effects of Drugs on Dopamine Levels
100
150
200
250
0 1 2 3 4hr
% o
f Bas
al R
elea
se
0.250.512.5
0
Dose (g/kg ip)
ETHANOL
MORPHINE%
of B
asal
Rel
ease
0
100
150
200
250
0 1 2 3 4 5 hr
0.51.02.510
Dose mg/kg
22
23
0
100
200
300
400
500
600
700
800
900
1000
1100
0 1 2 3 4 5 hr
% o
f Bas
al R
elea
se
DA
Effects of Amphetamines on Dopamine Levels
AMPHETAMINE
Adapted from: Di Chiara and Imperato, Proceedings of the National Academy of Sciences USA, 1988; courtesy of Nora D Volkow, MD.
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Pleasure-Reward Pathways
National Institute on Drug Abuse, www.nida.nih.gov, 2000.
3New Neurobiological
Concepts25
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2019
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Motivational Circuitry
Antireward Pathways
Interoception
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Three Novel Areas
Levounis, Journal of Medical Toxicology, 2016.
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Motivation: The Stinking Thinking Part
Levounis, Arnaout, and Marienfeld, Motivational Interviewing for Clinical Practice, 2017.
GAME 1?
A. A sure gain of $250.
B. 25% chance to gain $1,000,75% chance to gain nothing.
Adapted from: Tversky and Kahneman, Science, 1981.
Reward Systems
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GAME 1?
A. A sure gain of $250. 84%B. 25% chance to gain $1,000, 16%
75% chance to gain nothing.
Reward Systems
Adapted from: Tversky and Kahneman, Science, 1981.
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GAME 2?
A. A sure loss of $750.
B. 25% chance to lose nothing,75% chance to lose $1,000.
Antireward Systems
Adapted from: Tversky and Kahneman, Science, 1981.
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GAME 2?
A. A sure loss of $750. 13%B. 25% chance to lose nothing, 87%
75% chance to lose $1,000.
Adapted from: Tversky and Kahneman, Science, 1981.
Antireward Systems
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People avoid risks to ensure gains (even small gains).
People take risks (even big risks) to avoid definite losses.
Psychology trumps probability.
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Human Nature
Reward and Antireward Systems
Gardner, Chronic Pain and Addiction, 2011.
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4Treatments
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1st Wave: Psychoanalysis
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Levounis, Journal of Medical Toxicology, 2016.37
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2nd Wave: Boot Camps
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Medications
Counseling & Psychotherapy
Mutual Help
3rd Wave: The Current Approach
Nunes, Selzer, Levounis, Davies, Substance Dependence and Co-Occurring Psychiatric Disorders, 2010. Levounis, Arnaout, and Marienfeld, Motivational Interviewing for Clinical Practice, 2017.Renner, Levounis, and LaRose, Office-Based Buprenorphine Treatment of Opioid Use Disorder, 2nd Ed., 2018.
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-10 -9 -8 -7 -6 -5 -40
10
20
30
40
50
60
70
80
90
100
% Efficacy
Log Dose of Opioid
Agonists
Partial Agonists
Antagonists
Medications
Renner, Levounis, LaRose, Office-Based Buprenorphine Treatment of Opioid Use Disorder, APA Publishing, 2018.
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Levounis, Arnaout, and Marienfeld, Motivational Interviewing for Clinical Practice, 2017.
Motivational Interviewing
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Attitudes Towards AA
PATIENTS1. Inner peace2. God3. Medical Services4. AA5. Housing6. Spirituality7. Outpatient Treat.8. Community9. Government10. Trusting People11. Job
What Med Staff Think Patients Think
1. Housing2. Outpatient Treatment3. Medical Services4. Job5. Trusting People6. AA7. Inner Peace8. Community9. Government10. Spirituality11. God
MEDICAL STAFF1. Housing2. Government3. Medical Services4. Outpatient Treat.5. Job6. Community7. Trusting People8. Inner Peace9. God10. Spirituality11. AA
Goldfarb, Am J Drug Alcohol Abuse, 1996.
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5New Directions
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“Between stimulus and response there is a space. In that space is our power to choose our response. In our response lie our growth and our freedom.”
Viktor E. Frankl
4th Wave: Mindfullness
44Frankl V, Man’s Search for Meaning, 1959. Zerbo, Schlechter, Desai, and Levounis, Becoming Mindful, 2017.
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11.4
17.7
24.2 25
9.612.213.2
18.5
5.6
15.7
0
10
20
30
40
Only same-sex Mostly same-sex Equally both sexes Mostly other sex Only other sex
Women Men% re
port
ing
any
subs
tanc
e us
e di
sord
ers
****
*Ref
*p<0.05, ***p<.001 based on logistic regression analysis adjusted for race, age, educational level, personal income, employment status, relationship status, health insurance status, geographic location, MSA, age at alcohol onset, and family history of AOD problems. Reference group was “heterosexual” group.
***
And Back to Psychodynamics…
McCabe SE, Addiction, 2009; courtesy of Sean McCabe, PhD.Levounis, Drescher, and Barber, The LGBT Casebook, 2012.
Ref
6Conclusions
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1. A medical mistake, a greedy industry, and a tricky brain are primarily responsible for the opioid epidemic.
2. Addiction is the war between the hijacked pleasure/reward pathways of the brain and the frontal lobes.
3. Motivational circuitry, the anti-reward pathways, and interoception complete the STOP-GO model of addiction.
4. Partial agonists, Motivational Interviewing, and 12-step work are the first line interventions in 2019.
5. Mindfulness and a renewed consideration for psychodynamic psychotherapy are next frontiers in the psychosocial treatment of addiction.
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Thank youNJMS.Rutgers.edu/Psychiatry
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