Hiten Soni, MD
Neurobiology Of Addiction
Psychiatrist
Hiten Soni, MD
Hiten Soni, MD
Disclosures
• No financial interests in any
Pharmaceutical Company
• Not endorsing any products or treatment
facilities or modalities
Hiten Soni, MD
Purpose of this presentation
• Learn basic vocabulary
• Become an improved consumer of research literature
• Apply evidence based treatments to improve healthcare outcomes
• Educate your patients
Hiten Soni, MD
What is Neurobiology?
• Study of the neuron and its function
• Neurons are one of the basic cells that makeup the nervous system
Hiten Soni, MD
Brain • Brain is a vital organ and it needs protection.
• Chemical protection = blood brain barrier Keeps some chemicals in the blood from going into the brain
• Wrapped in three layers called meninges.
• Outermost layer is a tough leather like wrapping called “Dura” matter
• Suspended in fluid
• Skull
Hiten Soni, MD
Brain
Hiten Soni, MD
Neurons
• There are primary cells in a organ and
supporting cells.
• Neurons are primary nervous system cells.
• There are supporting cells as well,
including Astrocytes, Glia cells, Schwan
cells etc.
Hiten Soni, MD
Neurons
• Survival of an organism depends on
functional nervous system.
• Communication within and between
neurons is essential for functioning of the
nervous system.
• Communication within the neuron is
electrical.
• Communication between neurons is
chemical.
Hiten Soni, MD
Neurons
• Neurotransmitters are chemical messengers between neurons.
• Neurons’ job is to produce neurotransmitters and process messages.
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
• Neurobiology of addiction
Hiten Soni, MD
Natural Neurotransmitter
Selected Associated Effects
Interacting Psychotropic Drug
Acetylcholine
Learning and Motor functions
Nicotine
Hiten Soni, MD
Natural Neurotransmitter
Selected Associated Effects
Interacting Psychotropic Drug
Acetylcholine
Learning and Motor functions
Nicotine
Amino acids Glutamate GABA
Excitatory responses, Memory Learning, Anxiety/relaxation Coordination, intoxications
Ethanol Benzodiazepines Barbiturates
Hiten Soni, MD
Natural Neurotransmitter
Selected Associated Effects
Interacting Psychotropic Drug
Acetylcholine
Learning and Motor functions
Nicotine
Amino acids Glutamate GABA
Excitatory responses, Memory Learning, Anxiety/relaxation Coordination, intoxications
Ethanol Benzodiazepines Barbiturates
Monoamines Dopamine Norepinephrine Serotonin
Pleasure, Reward, Cravings Stress, Arousal, Learning, Sleep Sleep, Cravings, Mood, Anxiolytics
Cocaine, Amphetamine, Alcohol Cocaine, Amphetamine Alcohol, MDMA, Hallucinogen
Hiten Soni, MD
Natural Neurotransmitter
Selected Associated Effects
Interacting Psychotropic Drug
Acetylcholine
Learning and Motor functions
Nicotine
Amino acids Glutamate GABA
Excitatory responses, Memory Learning, Anxiety/relaxation Coordination, intoxications
Ethanol Benzodiazepines Barbiturates
Monoamines Dopamine Norepinephrine Serotonin
Pleasure, Reward, Cravings Stress, Arousal, Learning, Sleep Sleep, Cravings, Mood, Anxiolytics
Cocaine, Amphetamine, Alcohol Cocaine, Amphetamine Alcohol, MDMA, Hallucinogen
Neuropeptides Enkephalins Beta-endorphins
Pain Response, Learning, Eating Pain Sensitivity, Euphoria, Pleasurable effects
Heroine, Morphine, other opioids
Hiten Soni, MD
Dopamine
Movement
Addiction Reward & well-being
Motivation
Hiten Soni, MD
Drugs can be imposters of brain messengers
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Natural Rewards Elevate
Dopamine Levels
0
50
100
150
200
0 60 120 180
Time (min)
% o
f B
asa
l D
A O
utp
ut NAc shell
Empty
Food
Box Feeding
Di Chiara et al., Neuroscience, 1999.,Fiorino and Phillips, J. Neuroscience, 1997.
Sex
100
150
200
DA
Co
nce
ntr
ati
on
(%
Ba
seli
ne)
Sample
Number
1 2 3 4 5 6 7 8
Female Present
0
100
200
300
400
500
600
700
800
900
1000
1100
0 1 2 3 4 5 hr
% o
f B
asa
l R
elea
se
DA DOPAC HVA
Accumbens
Amphetamine
0
100
200
300
400
0 1 2 3 4 5 hr
% o
f B
asa
l R
elea
se
DA DOPAC HVA
Accumbens
Cocaine
0
100
150
200
250
0 1 2 3 hr
Time After Drug
% o
f B
asa
l R
elea
se Accumbens
Caudate
Nicotine
Di Chiara and Imperato, PNAS, 1988
Effects of Drugs on Dopamine Release
Morphine
Time After Drug
% o
f B
asa
l R
elea
se
0
100
150
200
250
0 1 2 3 4 5 hr
Accumbens
0.5 1.0 2.5 10
Dose
mg/kg mg/kg
mg/kg
mg/kg
But Dopamine is only part of the story
• Scientific research has shown that other
neurotransmitter systems are also affected:
–Serotonin
–Regulates mood, sleep, etc.
–Glutamate
–Regulates learning and memory, etc.
Hiten Soni, MD
But Dopamine is only part of the story
Research has shown that other
neurotransmitter systems are also affected:
Serotonin
Regulates mood, sleep, etc.
Glutamate
Regulates learning and memory, etc.
Hiten Soni, MD
Why Can’t Addicts Just Quit?
Drive Saliency
Memory
Control
Non-Addicted Brain
NO GO
Addicted Brain
Drive
Memory
Control
GO Saliency
Dopamine Transporters in Methamphetamine Abusers
Normal Control
Methamphetamine Abuser
Motor Task Loss of dopamine
transporters in
methamphetamine
abusers may result in
slowing of motor
reactions.
Memory Task Loss of dopamine
transporters in
methamphetamine
abusers may result
in memory impairment.
7 8 9 10 11 12 13 1.0 1.2 1.4 1.6 1.8 2.0
Time Gait (seconds)
4 6 8 10 12 14 16 1.0 1.2 1.4 1.6 1.8 2.0
Delayed Recall (words remembered)
Do
pa
min
e T
ran
spo
rter
Bm
ax
/Kd
Volkow et al., Am. J. Psychiatry, 2001.
Hiten Soni, MD
• Neurobiology of Tolerance
Hiten Soni, MD
Neurobiology of cravings
• Empty receptors “wants” ligands.
• These are perceived as cravings.
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
Hiten Soni, MD
DAT Recovery
with prolonged
abstinence from
methamphetamine
[C-11]d-threo-methylphenidate
Volkow et al., J. Neuroscience, 2001.
low
high
Normal Control
Methamphetamine Abuser
(1 month abstinent)
Methamphetamine Abuser
(14 months abstinent)
Hiten Soni, MD
• Chronic
• Block Dopamine receptors
– Opioid Antagonist
– Methadone
– Naloxone
– Naltrexone
– Acamprosate
– Buprenorphine
Treatment
Hiten Soni, MD
Questions