c2004 alcohol medical scholars program1 craving karen drexler, m.d. emory university school of...

c2004 Alcohol Medical Scholars Program

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Craving

Karen Drexler, M.D.Emory University School of Medicine

c2004 Alcohol Medical Scholars Program

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Overview

• What is craving?

• Why is it so compelling?

• What are the neural mechanisms that drive craving?

• How does knowing neurobiology inform my clinical practice?

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Features

• Intense desire • Many components• 3 types

– Withdrawal-induced– Drug-induced– Cue-induced

• Compels drug-seeking in dependent individuals

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DSM-IV Dependence3 or more of the following:• Tolerance• Withdrawal• Larger amounts than intended• Persistent efforts to cut down or control• A great deal of time spent getting the

substance, taking it, or recovering• Important activities given up• Continued use despite psychological or

physical problem exacerbated by use

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Non-problematic use

Liking Wanting

Abuse

Craving

Dep

Desire Corresponds With Drug Use

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Overview

• What is craving?

• Why is it so compelling?

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Why is Craving So Compelling?

• Correlates with other measures of substance dependence

• Better understanding may lead to better treatment

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Overview

• What is craving?

• Why is it so compelling?

• What are the neural mechanisms that drive craving?

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Neural Mechanisms

Feature Neural substrate

Sensitization of motivation

Mesocorticolimbic dopamine pathway

Inhibition of behavior

Prefrontal cortex (PFC)- lateral

Associative learning Amygdala (medial temporal lobe)

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Mesocorticolimbic Pathway

Ventral tegmental area

Nucleus accumbens

Anterior cingulate

Subcallosal cortex

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Prefrontal - Limbic Inhibition

Nucleus accumbens

Lateral Orbitofrontal cortex

Dorsolateral PFC

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Amygdala – Limbic Connections

Nucleus accumbens

Amygdala

Medial PFC

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Neural Mechanisms

Feature Neural substrate

Sensitization of motivation

Mesocorticolimbic dopamine pathway

Inhibition of behavior

Prefrontal cortex (PFC)- lateral

Associative learning Amygdala

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Neuroimaging in Humans

• Confirm these hypotheses

• Two types of provocation– Drug-induced– Cue-induced

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Drug-induced Craving

High

Craving

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Drug-induced Craving

Structure Possible function

Mesocorticolimbic pathway

(NAcc, SCC, medial OFC)

Reward / Motivation

+/- Amygdala Memory / Learning

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Cue-induced Craving

• Widely distributed cortical activations– Temporal lobe (Amygdala)– Frontal cortex (DLPFC, OFC)

• Less often mesolimbic pathway

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Cue-induced Craving

Structure Possible function

Prefrontal cortex Executive function

Lateral OFC Inhibition / planning

Amygdala Associative learning

Mesocorticolimbic pathway

Reward / motivation

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19Garavan et al, 2000

Cue-induced Craving Associated in BOLD fMRI

Dorsolateral Prefrontal Medial Prefrontal

Ant Cingulate

Post Cingulate

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Amygdala Activation to Ethanol Cues Before and After Treatment

Before treatment After treatment

Schneider et al, 2001

Amygdala

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Left Right-34 mm

-19 mm

-9 mm

+34 mm

+19 mm

+9 mm

insula

anteriorcingulate

amygdala

subcallosalcortex

nucleusaccumbensarea

Neural Correlates of Cocaine Cue-induced Craving

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Drug-induced vs Cue-induced Craving

Drug-induced Cue-induced

Mesocorticolimbic pathway

Mesocorticolimbic pathway

(+/-) Amygdala Amygdala

Prefrontal cortex

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Overview

• What is craving?

• Why is it so compelling?

• What are the neural mechanisms associated with craving?

• How does this affect my clinical practice?

c2004 Alcohol Medical Scholars Program

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Implications for Treatment

• Appreciation that substance dependence is a brain disease

• Cognitive behavioral therapy

• Medications

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Craving Summary

• Intense desire that compels use in dependent individuals

• Associated neural circuits involved in:– Reward– Cognitive control– Learning

• Treatment targeting craving may improve outcome