Craving

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Craving

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

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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 Dependence

• 3 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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Desire Corresponds With Drug Use
Liking
Wanting
Craving
Non-problematic use
Abuse
Dep
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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
Anterior cingulate
Subcallosal cortex
Nucleus accumbens
Ventral tegmental area
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Prefrontal - Limbic Inhibition
Dorsolateral PFC
Lateral Orbitofrontal cortex
Nucleus accumbens
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Amygdala Limbic Connections
Medial PFC
Nucleus accumbens
Amygdala
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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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Cue-induced Craving Associated ? in BOLD fMRI
Dorsolateral Prefrontal
Ant Cingulate
Medial Prefrontal
Post Cingulate
Garavan et al, 2000
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Amygdala Activation to Ethanol Cues Before and
After Treatment
Amygdala
Before treatment
After treatment
Schneider et al, 2001
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Neural Correlates of Cocaine Cue-induced Craving
Left
Right
insula
-34 mm
34 mm
anterior cingulate
amygdala
-19 mm
19 mm
-9 mm
9 mm
subcallosal cortex
nucleus accumbens area
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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?

24
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