C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of...
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![Page 1: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/1.jpg)
c2004 Alcohol Medical Scholars Program
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Craving
Karen Drexler, M.D.Emory University School of Medicine
![Page 2: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/2.jpg)
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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?
![Page 3: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/3.jpg)
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Features
• Intense desire • Many components• 3 types
– Withdrawal-induced– Drug-induced– Cue-induced
• Compels drug-seeking in dependent individuals
![Page 4: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/4.jpg)
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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
![Page 5: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/5.jpg)
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Non-problematic use
Liking Wanting
Abuse
Craving
Dep
Desire Corresponds With Drug Use
![Page 6: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/6.jpg)
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Overview
• What is craving?
• Why is it so compelling?
![Page 7: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/7.jpg)
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Why is Craving So Compelling?
• Correlates with other measures of substance dependence
• Better understanding may lead to better treatment
![Page 8: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/8.jpg)
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Overview
• What is craving?
• Why is it so compelling?
• What are the neural mechanisms that drive craving?
![Page 9: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/9.jpg)
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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)
![Page 10: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/10.jpg)
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Mesocorticolimbic Pathway
Ventral tegmental area
Nucleus accumbens
Anterior cingulate
Subcallosal cortex
![Page 11: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/11.jpg)
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Prefrontal - Limbic Inhibition
Nucleus accumbens
Lateral Orbitofrontal cortex
Dorsolateral PFC
![Page 12: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/12.jpg)
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Amygdala – Limbic Connections
Nucleus accumbens
Amygdala
Medial PFC
![Page 13: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/13.jpg)
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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
![Page 14: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/14.jpg)
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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
![Page 16: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/16.jpg)
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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
![Page 18: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/18.jpg)
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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
![Page 19: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/19.jpg)
c2004 Alcohol Medical Scholars Program
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
![Page 22: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/22.jpg)
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Drug-induced vs Cue-induced Craving
Drug-induced Cue-induced
Mesocorticolimbic pathway
Mesocorticolimbic pathway
(+/-) Amygdala Amygdala
Prefrontal cortex
![Page 23: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/23.jpg)
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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?
![Page 24: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/24.jpg)
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Implications for Treatment
• Appreciation that substance dependence is a brain disease
• Cognitive behavioral therapy
• Medications
![Page 25: C2004 Alcohol Medical Scholars Program1 Craving Karen Drexler, M.D. Emory University School of Medicine.](https://reader030.fdocuments.us/reader030/viewer/2022032705/56649dac5503460f94a9c1e7/html5/thumbnails/25.jpg)
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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