Drug Addiction
Part II
Karen Revere
Kian Eftekhari
Will Hiesinger
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
Ataxia
Poor tandem gait from gait ataxia
Appendicular Ataxia
Dysmetria in UEs
Intention tremor
Dysmetria on HTS testing
Dysdiadochokinesia
REVIEW: Neurobiology of Cocaine Euphoria
Pre-Synaptic Neuron
Dopamine Re-uptake Transporter
Dopamine
Dopamine Receptor
Post-Synaptic Neuron
Cocaine increases synaptic dopamine (DA) levels by
blocking the dopamine transporter (DAT)
Courtesy of Charles A. Dackis, MD
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
Dynamic Cycle of Cocaine Addiction
+
Cocaine
Cocaine Euphoria
Positive Reinforcement
Activated Reward Pathways
DA
Cocaine Administration
Reward Dysregulation
Drug-Seeking Behavior
Failed Impulse Suppression
Multiple Risks/Hazards
Cocaine Withdrawal
DA
-
Cocaine Craving
Negative Reinforcement
DA
Loss of Control
Denial / Poor Decision-Making
Reduced Gray Matter Density
Cocaine Cues
Stress
Limbic Activation
DA
Courtesy of Charles A. Dackis, MD
Brain Pleasure Centers
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.
Addictive drugs initially stimulate and later disrupt
natural pleasure centers in the brain
Courtesy of Charles A. Dackis, MD
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
Cue-Induced Cocaine Craving
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.
Courtesy of Charles A. Dackis, MD
Brain Changes During Cocaine Craving
Amygdala
2.5
2.0
Cocaine Video
Anterior
Cingulate
1.5
1.0
.5
0
Childress, et al. AJP, 1999
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