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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 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?
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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