The New Neurobiology

of Addiction
Petros Levounis, MD, MA
Professor and Chair, Department of Psychiatry
Rutgers New Jersey Medical School

National Press Foundation

Paris Accords of Science Communication
Paris, France
Monday, October 21, 2019
 Outline
1. The Basic Model
2. Neurobiology
3. New Neurobiological Concepts
4. Treatments
5. New Directions
6. Conclusions
2
 1
The Basic Model

3
~ 1980
4
 A Biopsychosocial Illness

Biological
Addiction
Psychological

Social

Use Brain
Switch
5

Olsen and Levounis, Sober Siblings, 2008.

 The Root Cause of the Disaster

Porter and Jick, N Engl J Med, January 10, 1980.

The False Promise

7
 Money and Influence

Catan and Perez, The Wall Street Journal, December 17, 2012.
 Admissions: 1999
Primary non-heroin opioid admission rates (per 100,000)

9
 Admissions: 2001
Primary non-heroin opioid admission rates (per 100,000)

10
 Admissions: 2003
Primary non-heroin opioid admission rates (per 100,000)

11
 Admissions: 2005
Primary non-heroin opioid admission rates (per 100,000)

12
 Admissions: 2007
Primary non-heroin opioid admission rates (per 100,000)

13
 Admissions: 2009
Primary non-heroin opioid admission rates (per 100,000)

14
 From Pills to Heroin

15

Compton, New England Journal of Medicine, 2016.

From Heroin to Fentanyl

16
From Fentanyl to Carfentanil

17
 2
Neurobiology

18
 Natural Rewards

Food Sex

DA Concentration (% Baseline)
200 200
% of Basal DA Output

150 150

100 100

Empty
50
Box Feeding
Female Present
0
0 60 120 180 Sample 1 2 3 4 5 6 7 8
Time (min) Number

19
Adapted from: Di Chiara et al, Neuroscience, 1999
Adapted from: Fiorino and Phillips, J Neuroscience, 1997
 Effects of Drugs on Dopamine Levels
MORPHINE COCAINE
400
250

% of Basal Release
Dose mg/kg
200 0.5 300
% of Basal Release

1.0
2.5
150 10
200
100
100

0
0 1 2 3 4 5 hr 0
0 1 2 3 4 5 hr
250

250
NICOTINE ETHANOL
% of Basal Release

Dose (g/kg ip)

% of Basal Release
200
200 0.25
0.5
1
150 150 2.5

100
100

0
0 0 1 2 3 4hr
0 1 2 3 hr
20
Adapted from: Di Chiara and Imperato, Proceedings of the National Academy of Sciences USA, 1988; courtesy of
Nora D Volkow, MD
Effects of Amphetamines on Dopamine Levels
1100

1000
AMPHETAMINE
900
% of Basal Release

800
DA
700

600

500

400

300

200

100

0 1 2 3 4 5 hr

21
Adapted from: Di Chiara and Imperato, Proceedings of the National Academy of Sciences USA, 1988; courtesy of
Nora D Volkow, MD.
 Pleasure-Reward Pathways

22

National Institute on Drug Abuse, www.nida.nih.gov, 2000.

 3
New Neurobiological
Concepts
23
2019
24
 Three Novel Areas

 Motivational Circuitry
 Antireward Pathways
 Interoception

25

Levounis, Journal of Medical Toxicology, 2016.

 Motivation: The Stinking Thinking Part

26

Levounis, Arnaout, and Marienfeld, Motivational Interviewing for Clinical Practice, 2017.
 Reward Systems

GAME 1
?
A. A sure gain of $250.

B. 25% chance to gain $1,000,

75% chance to gain nothing.

27

Adapted from: Tversky and Kahneman, Science, 1981.

 Reward Systems

GAME 1
?
A. A sure gain of $250. 84%
B. 25% chance to gain $1,000, 16%
75% chance to gain nothing.

28

Adapted from: Tversky and Kahneman, Science, 1981.

 Antireward Systems

GAME 2
?
A. A sure loss of $750.

B. 25% chance to lose nothing,

75% chance to lose $1,000.

29

Adapted from: Tversky and Kahneman, Science, 1981.

 Antireward Systems

GAME 2
?
A. A sure loss of $750. 13%
B. 25% chance to lose nothing, 87%
75% chance to lose $1,000.

30

Adapted from: Tversky and Kahneman, Science, 1981.

 Human Nature

 People avoid risks to ensure gains

(even small gains).

 People take risks (even big risks) to

avoid definite losses.

 Psychology trumps probability.

31
 Reward and Antireward Systems

32

Gardner, Chronic Pain and Addiction, 2011.

33
 4
Treatments

34
 1st Wave: Psychoanalysis

35
35
Levounis, Journal of Medical Toxicology, 2016.
2nd Wave: Boot Camps

36
36
 3rd Wave: The Current Approach

 Medications
 Counseling & Psychotherapy
 Mutual Help

Nunes, Selzer, Levounis, Davies, Substance Dependence and Co-Occurring Psychiatric Disorders, 2010. 37
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.
 5
New Directions

38
 4th Wave: Mindfullness

“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

39
Frankl V, Man’s Search for Meaning, 1959.
Zerbo, Schlechter, Desai, and Levounis, Becoming Mindful, 2017.
 And Back to Psychodynamics…
% reporting any substance use disorders

Only same-sex Mostly same-sex Equally both sexes Mostly other sex Only other sex

40

30
*** 25
24.2

20 17.7 18.5 Ref

*** 15.7
* 13.2
11.4 12.2
*
9.6
10 Ref
5.6

0
Women Men
*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.

McCabe SE, Addiction, 2009; courtesy of Sean McCabe, PhD. 40

Levounis, Drescher, and Barber, The LGBT Casebook, 2012.
 6
Conclusions

41
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.

42
 Thank you
NJMS.Rutgers.edu/Psychiatry

43
APPENDIX

44
 Medications
Agonists
100

90

80

70
% Efficacy 60

50

40
Partial Agonists
30

20

10

0
Antagonists
-10 -9 -8 -7 -6 -5 -4
45
Log Dose of Opioid
Renner, Levounis, LaRose, Office-Based Buprenorphine Treatment of Opioid Use Disorder, APA Publishing, 2018.
 Motivational Interviewing

46

Levounis, Arnaout, and Marienfeld, Motivational Interviewing for Clinical Practice, 2017.
 Attitudes Towards AA
What Med Staff Think
MEDICAL STAFF PATIENTS Patients Think
1. Housing 1. Inner peace 1. Housing
2. Government 2. God 2. Outpatient Treatment
3. Medical Services 3. Medical Services 3. Medical Services
4. Outpatient Treat. 4. AA 4. Job
5. Job 5. Housing 5. Trusting People
6. Community 6. Spirituality 6. AA
7. Trusting People 7. Outpatient Treat. 7. Inner Peace
8. Inner Peace 8. Community 8. Community
9. God 9. Government 9. Government
10. Spirituality 10. Trusting People 10. Spirituality
11. AA 11. Job 11. God

47

Goldfarb, Am J Drug Alcohol Abuse, 1996.