Drug Addiction Part II

1. Drug AddictionPart II Karen Revere Kian Eftekhari Will Hiesinger

2. 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

3. 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

4. Clinical Exam in ER • Hypertension, Tachycardia • Nystagmus (abnormal eye movement) • Mild ataxia (unsteady, clumsy limb motion) • Finger-to-nose dysmetria • Postural tremor • Unsteady gait

5. Ataxia Poor tandem gait from gait ataxia

6. Dysmetria on HTS testing Appendicular Ataxia Dysmetria in UEs Intention tremor Dysdiadochokinesia

7. 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

8. 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

9. Dynamic Cycle of Cocaine Addiction + Cocaine Cocaine Euphoria Positive Reinforcement Activated Reward Pathways DA Cocaine Administration Drug-Seeking Behavior Failed Impulse Suppression Multiple Risks/Hazards Reward Dysregulation Cocaine Withdrawal DA - Cocaine Craving Negative Reinforcement DA Loss of Control Denial / Poor Decision-Making Reduced Gray Matter Density Cocaine Cues Limbic Activation DA Stress Courtesy of Charles A. Dackis, MD

10. 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

11. 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

12. 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 thesestimuli, 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

13. Brain Changes During Cocaine Craving Amygdala 2.5 2.0 Cocaine Video 1.5 Anterior Cingulate 1.0 .5 0 Childress, et al. AJP, 1999 Courtesy of Charles A. Dackis, MD

14. 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