Clinical Case
• Patient from last week continues to smoke crack cocaine
• First he smokes only at parties
• Then it becomes a daily habit
• Gets caught stealing money from friends
• Drops out of college
Clinical Case
• His parents make him go to rehab, which he does for 6 weeks
• Patient is doing well, but one day he meets up with friends from college, and smokes crack because he thinks “one time won’t hurt”
• He begins using crack daily again• After a fight one night, he’s taken to the
ER
Clinical Exam in ER
• Hypertension, Tachycardia
• Nystagmus (abnormal eye movement)
• Mild ataxia (unsteady, clumsy limb motion)
• Finger-to-nose dysmetria
• Postural tremor
• Unsteady gait
Cocaine increases synaptic dopamine (DA) levels by blocking the dopamine transporter (DAT)
REVIEW: Neurobiology of Cocaine Euphoria
Courtesy of Charles A. Dackis, MD
Pre-Synaptic Neuron
Post-Synaptic Neuron
Dopamine Receptor
Dopamine Re-uptake Transporter
Dopamine
DSM IV: Substance Dependence
Maladaptive pattern of drug use – Withdrawal– Tolerance– More use than intended (loss of control)– Unsuccessful efforts to quit– Significant time spent in procurement– Functional impairment– Continued use in the face of adverse
effects
Courtesy of Charles A. Dackis, MD
Cocaine EuphoriaPositive ReinforcementActivated Reward Pathways
DA
Cocaine CravingNegative Reinforcement
DA
Cocaine AdministrationDrug-Seeking Behavior
Failed Impulse SuppressionMultiple Risks/Hazards
Reward Dysregulation Cocaine Withdrawal
DA
Cocaine CuesLimbic Activation
DA
Loss of ControlDenial / Poor Decision-Making
Reduced Gray Matter Density
Stress
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+ Dynamic Cycle of Cocaine AddictionDynamic Cycle of Cocaine Addiction
Cocaine
Courtesy of Charles A. Dackis, MD
Brain Pleasure Centers
Addictive drugs initially stimulate and later disrupt natural pleasure centers in the brain
Courtesy of Charles A. Dackis, MD
EXECUTIVE FUNCTION-Decision-making
-Weighing of risks vs. benefits
-Assigning emotional value to stimuli
-Suppressing emotional impulses
-Goal-directed behaviors
-social "control" (the ability to suppress urges that, if not suppressed, could lead to socially unacceptable or illegal outcomes).
Responsible for the rewards of drug use, sex, feeding and drinking.
Cocaine Withdrawal Symptoms_______________________________________________________________________________________
_
Hypersomnia (Lots of sleep)
Depression
Hyperphagia (Lots of eating)
Slow moving and thinking
Poor concentration
Anergia (Lack of energy; inactivity)
Craving?Courtesy of Charles A. Dackis, MD
Elements of the drug environment (people, places, and things) that are associated with cocaine have the remarkable ability to stimulate intense craving.
Patients feel intense craving when they encounter these stimuli, which often leads directly to relapse.
The only treatment that is currently available for cue reactivity is cue avoidance - an objective that is often difficult to attain.
Cue-Induced Cocaine Craving
Courtesy of Charles A. Dackis, MD
Amygdala
Cocaine Video
Anterior Cingulate
1.5
0
.5
1.0
2.0
2.5
Childress, et al. AJP, 1999
Brain Changes During Cocaine Craving
Courtesy of Charles A. Dackis, MD
Neuroimaging Studies of Cue Craving
Robust limbic activation (PET & fMRI) - many studies
Amygdala – plays a primary role in the formation and storage of memories associated with emotional events and is also important in classical conditioning.
Anterior cingulate – Plays a role in rational cognitive functions, such as reward anticipation, error detection, decision-making, empathy and emotion.
Craving intensity correlates with limbic activation
Same regions activated by sexually explicit videos
(Cocaine hijacks sex reward circuits)Courtesy of Charles A. Dackis, MD