1. Nicotine Caffeine (it IS a drug!) Cocaine Lesson 17 MDMA (Amphetamines) Antidepressants

2. What is cocaine, why is it used? Activity 2  Euphoria  Arousal  Addiction “Euphoriants” send a signal to the brain that indicates, falsely, the impending arrival of an immense evolutionary benefit.” http://www.tabaccheria21.net/PsicoWeb/cocaina.jpg

3. What are forms of cocaine and how are they administered? Activity 3

4. What is cocaine Dosage? “Line” of cocaine is about 50 mg. Snorted is lethal when over 500 mg. Crack dosage is more like 150 mg. Talk to your neighbor. Why might it be untrue that one can more easily overdose (die) on crack than cocaine?

5. Why might it be false that one can more easily die from crack than cocaine? 1.Because crack is smoked, some potency is lost from burning 2.Because crack is smoked, it gets into the blood faster 3.Because crack is smoked, we are protected from gastrointestinal effects 4.Because cocaine is snorted, it gets into the blood faster 5.Because cocaine is snorted, it has a shorter half life

6. How is cocaine metabolized? Activity 4 Half life approx. 1 hour Benzolecgonine Half life 2-3 days  CYP2A4

7. How does cocaine influence a cell? Activity 5 Dopamine reuptake pump

9. Based on information given, if you radioactively labeled cocaine, where would you see it bind on a PET? 1.Among other places, in the ventral tegmental area (VTA) 2.Among other places, in the nucleus accumbens 3.Among other places, in the prefrontal cortex 4.None of these places

10. How do cocaine forms determine addictiveness? Activity 6 Map for oral, snorted, and smoked Oral < snorted (3 minutes) < smoked (5 seconds) Reward Pathway Tolerance Dependence Some chronic cocaine users choose to snort up to 10 grams of cocaine to achieve euphoria. What does this suggest about tolerance for getting high and tolerance for lethality?

11. Long term change called “kindling”? Limbic system glutamate Long term use =  increased sensitivity (reverse tolerance).

12. http://www.lasersurgery365.com/ http://www.colgate.com.au http://www.squarebirds.org/images/ http://www.uphs.upenn.edu/ Are there benefits associated with cocaine? Activity 7

13. Are there harms associated with cocaine? Activity 8 http://home.att.net/~cdstrickland/restless.jpg

14. What are the long term brain changes? Amygdala (fear) shrinks Blood flow to brain reduced Proteins made by the prefrontal cortex related to impulse control

15. What Genes influence Cocaine Use? Activity 9 DRD2 is known to determine drug craving, generally (not just cocaine) Dopamine transporter gene Cocaine-induced aranoia PMID 16537431 Endogenous cocaine-like substance MicroRNA 212 CYP2A4 gene Philisophicalrabbit.com

16. Are there treatments for cocaine withdrawal? Keep a more limited supply of dopamine in the synapse longer. Can also be used as an antidepressant. Dopamine and Norepinephrine recycling transporter blocker Consider this: Heroin was developed as a safe, non- addictive treatment for opium addiction…….