Drug Addiction Part IIKaren 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

Intention tremor Dysdiadochokinesia

Dysmetria on HTS testingDysmetria in UEs

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_______________________________________________________________________________________

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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