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

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Brain

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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.

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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.

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Neurons

• Neurotransmitters are chemical messengers between neurons.

• Neurons’ job is to produce neurotransmitters and process messages.

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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

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Dopamine

Movement

Addiction Reward & well-being

Motivation

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Drugs can be imposters of brain messengers

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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.

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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

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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)

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• Chronic

• Block Dopamine receptors

– Opioid Antagonist

– Methadone

– Naloxone

– Naltrexone

– Acamprosate

– Buprenorphine

Treatment

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Questions