The Neurobiology of Addiction and

Implications for Treatment

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

National Press Foundation

The American Society of Addiction Medicine Annual Conference
San Diego, California
Wednesday, April 11, 2018 1
 Outline

1. The Basic Model

2. Neurobiology of Addiction
3. Addiction Treatments
4. New Directions
5. Conclusions

2
 1
The Basic Model

3
 A Biopsychosocial Illness

Biological
Addiction
Psychological

Social

Use Brain
Switch
4

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

6
 Money and Influence

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

8
 Admissions: 2001
Primary non-heroin opioid admission rates (per 100,000)

9
 Admissions: 2003
Primary non-heroin opioid admission rates (per 100,000)

10
 Admissions: 2005
Primary non-heroin opioid admission rates (per 100,000)

11
 Admissions: 2007
Primary non-heroin opioid admission rates (per 100,000)

12
 Admissions: 2009
Primary non-heroin opioid admission rates (per 100,000)

13
From Pills to Heroin to Fentanyl

14
 2
Neurobiology of
Addiction
15
 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

16
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
17
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

18
Adapted from: Di Chiara and Imperato, Proceedings of the National Academy of Sciences USA, 1988; courtesy of
Nora D Volkow, MD.
 Pleasure-Reward Pathways

19

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

 3
Addiction
Treatments
20
 1st Wave: Psychoanalysis

21
21
Levounis, Journal of Medical Toxicology, 2016.
2nd Wave: Boot Camps

22
22
 3rd Wave: The Current Approach

1.Mutual Help (12-step)

2.Motivational Interviewing
3.Medications

Nunes, Selzer, Levounis, Davies, Substance Dependence and Co-Occurring Psychiatric Disorders, 2010. 23
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.
 Mutual Help
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

24

Goldfarb, Am J Drug Alcohol Abuse, 1996.

Motivational Interviewing

25
 Medications
Agonists
100

90

80

70
% Efficacy 60

50

40
Partial Agonists
30

20

10

0
Antagonists
-10 -9 -8 -7 -6 -5 -4
26
Log Dose of Opioid
Renner, Levounis, LaRose, Office-Based Buprenorphine Treatment of Opioid Use Disorder, APA Publishing, 2018.
 4
New Directions

27
 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

28
Frankl V, Man’s Search for Meaning, 1959.
Zerbo, Schlechter, Desai, and Levounis, Becoming Mindful, 2017.
 … and Back to Psychodynamics
Only same-sex Mostly same-sex Equally both sexes Mostly other sex Only other sex

% reporting any substance use disorders

40

30 ***
24.2 25

20 17.7 18.5
*** 15.7
* 13.2 12.2
11.4 *
9.6
10 Ref
5.6

0
Women Men
* p<0.05, *** p<.001, Ref = Reference Group
29
McCabe, Addiction, 2009, Courtesy of Sean E. McCabe, PhD; Levounis, Drescher, and Barber, The
LGBT Casebook, APA Publishing, 2012.
 5
Conclusions

30
1. A medical mistake, an over-aggressive industry, and a tricky
brain are primarily responsible for the opioid epidemic.
2. Addiction hijacks the pleasure/reward pathways of the brain
and weakens the frontal lobes.
3. Partial agonists, Motivational Interviewing, and Mutual Help
are the first line addiction treatments in 2018.
4. Mindfulness may be the next frontier in the psychosocial
treatment of addiction—and Freud is not dead.

31
 Thank you
NJMS.Rutgers.edu/Psychiatry

32
APPENDIX

33
 The Stop-Go Model

34

Volkow ND and Baler RD, Neuropharmacology, 2013.

 Three Novel Areas

1.Motivational Circuitry
2.Antireward Pathways
3.Interoception

35

Levounis, Journal of Medical Toxicology, 2016.

Motivation: Medial Orbito-Frontal Cortex

36
 Reward Systems

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

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

75% chance to gain nothing.

37

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.

38

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.

39

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.

40

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.

41
42
 The Stop-Go Model Revisited

43

Volkow ND and Baler RD, Neuropharmacology, 2013.