Petros Levounis, MD, MAProfessor and Chair, Department of Psychiatry

Rutgers New Jersey Medical School

Modified by Heather Bell, MDFamily Physician

CHI St. Gabriel's Family Medical Center

The New Neurobiology of

Addiction

2

1. The Basic Model

2. Neurobiology of Addiction

3. New Neurobiological Concepts

4. Addiction Treatments

5. New Directions

Outline

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3

Drugs of Abuse Endogenous Neurotransmitter

Alcohol GABA and Glutamate

Amphetamines and

Cocaine

Dopamine

Benzos and GHB GABA

Cannabis Anandamide

Hallucinogens and

MDMA

Serotonin

Nicotine Acetylcholine

Opioids Endorphins

PCP and Ketamine Glutamate

1The Basic Model

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A Biopsychosocial Illness

Biological

Psychological

Social

UseBrain

Switch

Addiction

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Olsen and Levounis, Sober Siblings, 2008.

6

POLL

A Biopsychosocial Illness

• Biological

– 40-60% of addiction is felt to be “heritable”

– Both parents with alcoholism=7x increased

risk

– 30% of people with psychiatric disorders

also have SUD

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A Biopsychosocial Illness

• Social / Environmental risk factors:

– Low socioeconomic status

– Poor parental support

– Physical and psychological abuse

– Drug availability (access)

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A Biopsychosocial Illness

• Psychological

– Self-medicate to numb or “treat” one’s own

emotional or physical illness

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A Biopsychosocial Illness

• Use begets use

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A Biopsychosocial Illness

• Addiction is its own

disease independent of

the other factors

• BUT modifying the other

factors (biopsychosocial)

can help with relapse

prevention

• Relapse “primer” include

– Stress

– Trigger (cues)

– Exposure

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Brain

Switch

Addiction

2Neurobiology of

Addiction12

13

POLL

0

50

100

150

200

0 60 120 180

Time (min)

% o

f B

asa

l D

A O

utp

ut

Empty

Food Sex

Box Feeding

100

150

200

DA

Con

cen

tra

tio

n (

% B

ase

lin

e)

Sample

Number

1 2 3 4 5 6 7 8

Female Present

Natural Rewards

Adapted from: Di Chiara et al, Neuroscience, 1999

Adapted from: Fiorino and Phillips, J Neuroscience, 1997

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15

0

100

200

300

400

0 1 2 3 4 5 hr

% o

f B

as

al R

ele

as

e

COCAINE

0

100

150

200

250

0 1 2 3 hr

% o

f B

as

al R

ele

as

e

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 B

as

al R

ele

as

e

0.250.512.5

0

Dose (g/kg ip)

ETHANOL

MORPHINE

% o

f B

as

al R

ele

as

e

0

100

150

200

250

0 1 2 3 4 5 hr

0.51.02.510

Dose mg/kg

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16Adapted 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

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Most 200-300% above baseline

“High jacking of pleasure /

reward in nucleus accumbens”

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0

100

200

300

400

500

600

700

800

900

1000

1100

0 1 2 3 4 5 hr

% o

f B

as

al R

ele

as

e

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.

Amphetamines >>> 1000%

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Pleasure-Reward Pathways

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

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• Nucleus accumbens-

reward center

• Hippocampus-

memory center

• Amygdala- emotional

center

* Primitive brain

* Frontal lobe not well

connected until after

age 2219

Limbic System

Levounis, Journal of Medical Toxicology, 2016.

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“Sex is absurd from a

strictly frontal lobe stand

point.”

- Dr. Petros Levounis

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Levounis, Journal of Medical Toxicology, 2016.

3New Neurobiological

Concepts21

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Motivational Circuitry

Anti-reward Pathways

Interoception

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Three Novel Areas

Levounis, Journal of Medical Toxicology, 2016.

2323

Motivation: The Stinking Thinking Part

Reward System

• Activation of dopaminergic pathway

• Emotion over logic

• Over time there is less dopamine uptake in the nucleus

accumbens and the “reward” is less “rewarding”

• Poor inhibitory control and poor executive functioning

mediated by prefrontal cortex (PFC)

• Actions become stereotyped: drug seeking and drug

taking become repetitive and ritualistic

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Reward and Anti-reward Systems

Gardner, Chronic Pain and Addiction, 2011.

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POLL

Anti-Reward (Habenula)

• Activated when expected results do not

materialize

• Activity increased with repetitive drug

exposure causing negative mood with

drug withdrawal

• Using to not get sick rather than using to

get high

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Interoception

• Insula takes sensations and makes

sense of them

• Insula gives the person the “permission”

to feel cravings

* Insula stroke will take away cigarette

cravings. Cravings still actually “there” but

no longer have meaning

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Human Nature

1. People avoid risks to ensure gains

(motivation reward)

2. People take risks to avoid definite loss

(anti-reward)

3. Psychology trumps probability

(interoception)

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4Addiction

Treatments31

Medications

Motivational Interviewing

Mutual Help (12-step)

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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Two Main Strategies

• Agonists

– Nicotine replacement therapies

– Methadone for opioids

• Antagonists

– Naltrexone for opioids

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34

POLL

The New Strategy

• Partial Agonists

– Varenicline for tobacco

– Buprenorphine for opioids

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Motivational Interviewing

• Encourages internally driven change

through a collaborative effect that elicits

the patient’s own recovery-oriented

thoughts and feelings

• Promotes and supports the patient’s

sense of autonomy

• “Rolls with the resistance” toward

treatment engagement

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Mutual Help (12-step)

• Provide patients with the chance to learn

information about addiction, recovery and relapse

• Reduces the stigma associated with addiction

and the humiliation of having lost control over

own behavior

• Patients gain support, encouragement, feedback

and confrontation from peers who understand

– How SUD patients think, feel, and act including

manipulation, schemes and diversions used to

rationalize

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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: Mindfulness

39Frankl V, Man’s Search for Meaning, 1959.

Zerbo, Schlechter, Desai, and Levounis, Becoming Mindful, 2017.

“Trick” the insula to

not give meaning to

cravings/triggers

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