the new neurobiology of addiction · the new neurobiology of addiction. 2 1. the basic model 2....
TRANSCRIPT
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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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.
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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
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POLL
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0 60 120 180
Time (min)
% o
f B
asa
l D
A O
utp
ut
Empty
Food Sex
Box Feeding
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150
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DA
Con
cen
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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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0
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0 1 2 3 4 5 hr
% o
f B
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al R
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COCAINE
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200
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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
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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
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1000
1100
0 1 2 3 4 5 hr
% o
f B
as
al R
ele
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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.
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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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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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